Abstract: A common requirement of statistical methods, critical to the interpretation of the data, is that the analyzed observations are independent. This is not always the case in experiments and clinical studies, a mistake which can be expected to lead to erroneous study results. The phenomenon is explained, its consequences described, and suggestions to avoid the problems presented.
Abstract: An increasing number of young patients are undergoing knee arthroplasties. Thus, the long-term risks of having a knee prosthesis must be evaluated. This study focuses on the potential carcinogenic effects of the prosthesis; it is a long-term follow-up of all patients in Sweden between 1975 and 2006.
Abstract: The Nepi ANtidiabetes StudY (NANSY) is a 5-year randomized, double-blind, placebo-controlled trial in Swedish primary care, examining whether the development of type 2 diabetes (T2D) and retinopathy (separately reported) would be delayed in 40- to 70-year-old subjects with impaired fasting glucose (IFG) who, in addition to lifestyle changes, were treated with either placebo or low-dosage sulphonylurea (SU) (1-mg glimepiride; Amaryl(®) ). Of 274 subjects (163 men, 111 women), 138 were allocated to placebo (46.0% men, 56.8% women) and 136 to glimepiride (54.0% men, 43.2% women). The primary endpoint was conversion to diabetes. Average follow-up time was 3.71 years; 96 subjects converted to diabetes, 55 allocated to placebo and 41 to glimepiride (absolute difference 9.8%; p = 0.072). In conclusion, the study failed to support the notion that low-dose SU added to lifestyle changes in IFG subjects would help to delay the conversion to diabetes.
Abstract: Vertebral fractures are often painful and lead to reduced quality of life and disability. We compared the efficacy and safety of balloon kyphoplasty to nonsurgical therapy over 24 months in patients with acute painful fractures. Adults with one to three vertebral fractures were randomized within 3 months from onset of pain to undergo kyphoplasty (n = 149) or nonsurgical therapy (n = 151). Quality of life, function, disability, and pain were assessed over 24 months. Kyphoplasty was associated with greater improvements in Short-Form 36 (SF-36) Physical Component Summary (PCS) scores when averaged across the 24-month follow-up period compared with nonsurgical therapy [overall treatment effect 3.24 points, 95% confidence interval (CI) 1.47-5.01, p = .0004]; the treatment difference remained statistically significant at 6 months (3.39 points, 95% CI 1.13-5.64, p = .003) but not at 12 months (1.70 points, 95% CI -0.59 to 3.98, p = .15) or 24 months (1.68 points, 95% CI -0.63 to 3.99, p = .15). Greater improvement in back pain was observed over 24 months for kyphoplasty (overall treatment effect -1.49 points, 95% CI -1.88 to -1.10, p < .0001); the difference between groups remained statistically significant at 24 months (-0.80 points, 95% CI -1.39 to -0.20, p = .009). There were two device-related serious adverse events in the second year that occurred at index vertebrae (a spondylitis and an anterior cement migration). There was no statistically significant difference between groups in the number of patients (47.5% for kyphoplasty, 44.1% for control) with new radiographic vertebral fractures; fewer fractures occurred (~18%) within the second year. Compared with nonsurgical management, kyphoplasty rapidly reduces pain and improves function, disability, and quality of life without increasing the risk of additional vertebral fractures. The differences from nonsurgical management are statistically significant when averaged across 24 months. Most outcomes are not statistically different at 24 months, but the reduction in back pain remains statistically significant at all time points.
Abstract: The aim of this paper was to compare selected indication parameters for patients scheduled for hip and knee replacement at orthopaedic units in Sweden.
Abstract: Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously.
Abstract: Data from arthroplasty registers are often analyzed using survival methods. Several methodological problems exist, for example relating to competing events, non-random censoring, non-proportional hazards and dependent observations. League tables and ranking of specific survival results leds to further methodological difficulties. Most of these problems are, however, well known and a number of methods for dealing successfully with the problems have been developed. These methods are usually accessible in commercially available statistical software packages. The statistical analysis and reporting of data from arthroplasty registers can thus be improved. Development of arthroplasty register guidelines for statistical analysis could play an important role in making these registers even more useful.
Abstract: BACKGROUND: The optimal management of a torn anterior cruciate ligament (ACL) of the knee is unknown. METHODS: We conducted a randomized, controlled trial involving 121 young, active adults with acute ACL injury in which we compared two strategies: structured rehabilitation plus early ACL reconstruction and structured rehabilitation with the option of later ACL reconstruction if needed. The primary outcome was the change from baseline to 2 years in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS)--pain, symptoms, function in sports and recreation, and knee-related quality of life (KOOS(4); range of scores, 0 [worst] to 100 [best]). Secondary outcomes included results on all five KOOS subscales, the Medical Outcomes Study 36-Item Short-Form Health Survey, and the score on the Tegner Activity Scale. RESULTS: Of 62 subjects assigned to rehabilitation plus early ACL reconstruction, 1 did not undergo surgery. Of 59 assigned to rehabilitation plus optional delayed ACL reconstruction, 23 underwent delayed ACL reconstruction; the other 36 underwent rehabilitation alone. The absolute change in the mean KOOS(4) score from baseline to 2 years was 39.2 points for those assigned to rehabilitation plus early ACL reconstruction and 39.4 for those assigned to rehabilitation plus optional delayed reconstruction (absolute between-group difference, 0.2 points; 95% confidence interval, -6.5 to 6.8; P=0.96 after adjustment for the baseline score). There were no significant differences between the two treatment groups with respect to secondary outcomes. Adverse events were common in both groups. The results were similar when the data were analyzed according to the treatment actually received. CONCLUSIONS: In young, active adults with acute ACL tears, a strategy of rehabilitation plus early ACL reconstruction was not superior to a strategy of rehabilitation plus optional delayed ACL reconstruction. The latter strategy substantially reduced the frequency of surgical reconstructions. (Funded by the Swedish Research Council and the Medical Faculty of Lund University and others; Current Controlled Trials number, ISRCTN84752559.)
Abstract: We identified 1305 femoral impaction bone grafting revisions using the Exeter stem performed between 1989 and 2002 in 30 hospitals throughout Sweden. There were 1188 patients with a mean age of 71 years (29 to 94) followed up for between five and 18 years. The participating departments reported 70 further revisions in total, of which 57 could also be identified on the Swedish National Arthroplasty Registry. Kaplan-Meier survivorship for all causes of failure was 94.0% (95% confidence interval (CI) 92 to 96) for women and 94.7% (95% CI, 92 to 96) for men at 15 years. Survivorship at 15 years for aseptic loosening was 99.1% (95% CI 98.4 to 99.5), for infection 98.6% (95% CI 97.6 to 99.2), for subsidence 99.0% (95% CI 98.2 to 99.4) and for fracture 98.7% (95% CI 97.9 to 99.2) Statistically significant predictors of failure were the year in which revision was conducted (p < 0.001). The number of previous revisions was slightly above the level of significance (p = 0.056). Age, gender, the length of the stem and previous septic loosening were not predictors of failure (p = 0.213, p = 0.399, p = 0.337, p = 0.687, respectively). The difference in survivorship between high- and low-volume departments was only 3% at ten years. We conclude that impaction bone grafting with the Exeter stem has an excellent long-term survivorship following revision arthroplasty. The technique of impaction grafting appears to be reliable, can be learned rapidly and produces a predictably low incidence of aseptic loosening.
Abstract: Objective: Statistical analysis is ubiquitous in medical research, but fundamental statistical principles are not always well understood, which has negative effects for both authors and readers of scientific papers. The purpose of this brief review is to provide a methodological overview on populations, samples, analysis units and sampling uncertainty to facilitate an increased understanding of statistical concepts.
Abstract: PURPOSE: The purpose of this investigation was to extend the previously reported short-term randomized trial of open and endoscopic carpal tunnel release in patients with carpal tunnel syndrome (CTS) to compare outcomes 5 years after surgery. METHODS: In a single-center randomized controlled trial, 128 patients (25 to 60 years) with clinically diagnosed and electrophysiologically confirmed idiopathic CTS were randomized immediately before surgery to open or 2-portal endoscopic release. The outcome measures included the validated CTS questionnaire's symptom severity and functional status scales (scored from 1 to 5) completed at baseline and 1 year postoperatively. At the extended follow-up of the trial 5 years after surgery, 2 patients had died and the other 126 participants (63 patients in each group) completed the CTS questionnaire. RESULTS: At the 5-year follow-up no difference between the groups was found in the CTS symptom severity score. The mean (SD) score in the open group was 1.42 (0.7) and in the endoscopic group was 1.45 (0.7), and the mean difference in score change from baseline was 0.03 (95% confidence interval, -0.21 to 0.27). Between 1 year and 5 years postoperatively, the CTS symptom severity score had deteriorated by at least 0.4 point in 9 patients in the open group and in 10 patients in the endoscopic group. The mean (SD) CTS functional status score was 1.29 (0.5) in the open group and 1.30 (0.5) in the endoscopic group. At 5 years, 11 patients in the open group and 10 patients in the endoscopic group reported persistent pain in the scar or proximal palm. Three patients in each group had repeat surgery on the operated hand because of persistent or recurrent symptoms. CONCLUSIONS: The improvements in symptoms of CTS and hand-related disability 5 years after open and 2-portal endoscopic carpal tunnel release were equivalent. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic I.
Abstract: The results of a treatment method on adenocarcinoma corpus uteri stage I-II based upon cytometrically measured DNA ploidy are presented. All patients had a simple hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given only to those patients with non-diploid tumours regardless of stage and grade. A total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were included where 1,396 patients were followed-up for at least 5 years or until death and the remaining 238 patients were followed-up 3.5-5 years or until death. By using cytometry only, we identified a low-risk group comprising 83% of the patients (with 5.2% dead from their disease) and a high-risk group of 17% (with 15.7% dead from their disease). By using grade only (well- and moderately differentiated vs poorly differentiated), the low-risk group comprised 87% of the patients (with 4.6% dead from their disease) and the high-risk group 13% (with 13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic and II), the low-risk group comprised 78% of the patients (with 3.6% dead from their disease) and the high risk group 22% (with 14.5% dead from their disease). By combining these prognostic parameters, we were able to identify small subgroups with increased mortality rates in need of adjuvant therapy. As ploidy still had a strong prognostic strength regardless of given adjuvant radiotherapy, we do not believe that this treatment was effective. We therefore recommend future research to be directed toward cytostatics as an alternative adjuvant treatment.
Abstract: BACKGROUND: Despite a decreasing incidence of peptic ulcer disease, most previous studies report a stabile incidence of ulcer complications. We wanted to investigate the incidence of peptic ulcer complications in Sweden before and after the introduction of the proton pump inhibitors (PPI) in 1988 and compare these data to the sales of non-steroid anti-inflammatory drugs (NSAID) and acetylsalicylic acid (ASA). METHODS: All cases of gastric and duodenal ulcer complications diagnosed in Sweden from 1974 to 2002 were identified using the National hospital discharge register. Information on sales of ASA/NSAID was obtained from the National prescription survey. RESULTS: When comparing the time-periods before and after 1988 we found a significantly lower incidence of peptic ulcer complications during the later period for both sexes (p < 0.001). Incidence rates varied from 1.5 to 7.8/100000 inhabitants/year regarding perforated peptic ulcers and from 5.2 to 40.2 regarding peptic ulcer bleeding. The number of sold daily dosages of prescribed NSAID/ASA tripled from 1975 to 2002. The number of prescribed sales to women was higher than to males. Sales of low-dose ASA also increased. The total volume of NSAID and ASA, i.e. over the counter sale and sold on prescription, increased by 28% during the same period. CONCLUSION: When comparing the periods before and after the introduction of the proton pump inhibitors we found a significant decrease in the incidence of peptic ulcer complications in the Swedish population after 1988 when PPI were introduced on the market. The cause of this decrease is most likely multifactorial, including smoking habits, NSAID consumption, prevalence of Helicobacter pylori and the introduction of PPI. Sales of prescribed NSAID/ASA increased, especially in middle-aged and elderly women. This fact seems to have had little effect on the incidence of peptic ulcer complications.
Abstract: BACKGROUND: Balloon kyphoplasty is a minimally invasive procedure for the treatment of painful vertebral fractures, which is intended to reduce pain and improve quality of life. We assessed the efficacy and safety of the procedure. METHODS: Adults with one to three acute vertebral fractures were eligible for enrolment in this randomised controlled trial at 21 sites in eight countries. We randomly assigned 300 patients by a computer-generated sequence to receive kyphoplasty treatment (n=149) or non-surgical care (n=151). The primary outcome was the difference in change from baseline to 1 month in the short-form (SF)-36 physical component summary (PCS) score (scale 0-100) between the kyphoplasty and control groups. Quality of life and other efficacy measurements and safety were assessed up to 12 months. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00211211. FINDINGS: 138 participants in the kyphoplasty group and 128 controls completed follow-up at 1 month. By use of repeated measures mixed effects modelling, all 300 randomised participants were included in the analysis. Mean SF-36 PCS score improved by 7.2 points (95% CI 5.7-8.8), from 26.0 at baseline to 33.4 at 1 month, in the kyphoplasty group, and by 2.0 points (0.4-3.6), from 25.5 to 27.4, in the non-surgical group (difference between groups 5.2 points, 2.9-7.4; p<0.0001). The frequency of adverse events did not differ between groups. There were two serious adverse events related to kyphoplasty (haematoma and urinary tract infection); other serious adverse events (such as myocardial infarction and pulmonary embolism) did not occur perioperatively and were not related to procedure. INTERPRETATION: Our findings suggest that balloon kyphoplasty is an effective and safe procedure for patients with acute vertebral fractures and will help to inform decisions regarding its use as an early treatment option.
Abstract: Public disclosure of outcome-orientated ranking of hospitals is becoming increasingly popular and is routinely used by Swedish health-care authorities. Whereas uncertainty about an outcome is usually presented with 95% confidence intervals, ranking's based on the same outcome are typically presented without any concern for bias or statistical precision. In order to study the effect of incomplete registration of re-operation on hospital ranking we performed a simulation study using published data on the two-year risk of re-operation after total hip replacement. This showed that whereas minor registration incompleteness has little effect on the observed risk of revision, it can lead to major errors in the ranking of hospitals. We doubt whether a level of data entry sufficient to generate a correct ranking can be achieved, and recommend that when ranking hospitals, the uncertainties about data quality and random events should be clearly described as an integral part of the results.
Abstract: BACKGROUND AND PURPOSE: Roentgen stereometric analysis (RSA) cannot discern whether a single prosthesis is fixed or migrating below the detection level. Samples of patients usually show migration values that appear to be continuously distributed. Is there such continuity, or is there a dichotomy between stable and migrating prostheses? The hypothesis of a dichotomy has, to our knowledge, not been tested. We present an exploratory evaluation of such a dichotomy using a mixture distribution algorithm. METHODS: We analyzed the migration (as determined by RSA) of 147 cemented acetabular cups of 7 different designs by using a new set of algorithms for frequency distribution analysis called Rmix. RESULTS: We first analyzed a migration vector, regardless of direction. After 2 years there was a significant dichotomy between 2 lognormal subgroups within the sample. Although some types of cups were over-represented in one of the subgroups, neither cup design, sex, nor operating department could explain the dichotomy into two groups, which appears to reflect the existence of two basically different types of behavior of the cups. We next analyzed the migration along the 3 axes in space, and found a similar dichotomy. During the second year, around 80% of the patients belonged to a distinct, normally distributed subgroup with a mean not different from 0 mm and a small variation. The remainder differed significantly from this subgroup and showed migration. INTERPRETATION: There is a dichotomy in migration pattern. During the second postoperative year, most cups belonged to a subpopulation that appeared stable. The remainder is probably at risk of loosening. For a single type of prosthesis, the relative size of the stable subgroup may be a good index of the expected performance. The possibility of detecting subgroups within a seemingly continuous sample might be useful in many fields of medicine.
Abstract: Tamoxifen is the most used adjuvant drug in breast cancer treatment. Its main action is as an anti-oestrogen, but in the endometrium of some patients it acts as an oestrogen. Some investigators have even reported an increased risk of developing endometrial carcinoma. The question of how to follow-up these patients and how to identify patients at risk of developing endometrial premalignant changes was investigated by the noninvasive ultrasound method. The follow-up of 292 patients from before the start of adjuvant treatment with tamoxifen and 94 without tamoxifen treatment was conducted at regular intervals. The changes in endometrial thickness as measured by ultrasound and histopathological changes are reported. A thicker endometrium was found in patients with receptor positive breast cancer even before the treatment with tamoxifen started. Cumulative increasing thickness was found during treatment and this thicker endometrium remained until almost 3 years after the end of treatment. If the endometrium was <3 mm after 3 months of treatment the probability that it would be thin after 5 years was high. An increased risk of developing endometrial carcinoma was found, however due to this regular follow-up the cancer was identified at an early stage.
Abstract: OBJECTIVE: To investigate the relationship between carpal tunnel syndrome (CTS) and keyboard use at work in a general population. METHODS: A health status questionnaire was mailed to 2,465 persons of working age (25-65 years) who were randomly selected from the general population of a representative region of Sweden. The questionnaire required the subjects to provide information about the presence and severity of pain, numbness and tingling in each body region, employment history, and work activities, including average time spent using a keyboard during a usual working day. Those reporting recurrent hand numbness or tingling in the median nerve distribution were asked to undergo a physical examination and nerve conduction testing. The prevalence of CTS, defined as symptoms plus abnormal results on nerve conduction tests, was compared between groups of subjects that differed in their intensity of keyboard use, adjusting for age, sex, body mass index, and smoking status. RESULTS: Eighty-two percent responded to the questionnaire, and 80% of all symptomatic persons attended the examinations. Persons who had reported intensive keyboard use on the questionnaire were significantly less likely to be diagnosed as having CTS than were those who had reported little keyboard use, with a prevalence that increased from 2.6% in the highest keyboard use group (> or = 4 hours/day), to 2.9% in the moderate use group (1 to <4 hours/day), 4.9% in the low use group (<1 hour/day), and 5.2% in the no keyboard use at work group (P for trend = 0.032). Using > or = 1 hour/day to designate high keyboard use and <1 hour/day to designate low keyboard use, the prevalence ratio of CTS in the groups with high to low keyboard use was 0.55 (95% confidence interval 0.32, 0.96). CONCLUSION: Intensive keyboard use appears to be associated with a lower risk of CTS.
Abstract: Patients with osteoarthritis undergoing knee replacement have been reported to have an overall reduced mortality compared with that of the general population. This has been attributed to the selection of healthier patients for surgery. However, previous studies have had a maximum follow-up time of ten years. We have used information from the Swedish Knee Arthroplasty Register to study the mortality of a large national series of patients with total knee replacement for up to 28 years after surgery and compared their mortality with that of the normal population. In addition, for a subgroup of patients operated on between 1980 and 2002 we analysed their registered causes of death to determine if they differed from those expected. We found a reduced overall mortality during the first 12 post-operative years after which it increased and became significantly higher than that of the general population. Age-specific analysis indicated an inverse correlation between age and mortality, where the younger the patients were, the higher their mortality. The shift at 12 years was caused by a relative over-representation of younger patients with a longer follow-up. Analysis of specific causes of death showed a higher mortality for cardiovascular, gastrointestinal and urogenital diseases. The observation that early onset of osteoarthritis of the knee which has been treated by total knee replacement is linked to an increased mortality should be a reason for increased general awareness of health problems in these patients.
Abstract: We aimed to study trends in gender-related differences in incidence, and prevalence for long-term oxygen therapy due to chronic obstructive pulmonary disease. Another aim was to study survival after onset of oxygen therapy. Prospectively followed were 5689 Swedish patients, who were prescribed oxygen therapy because of chronic obstructive pulmonary disease from 1987 to 2000. The annual incidence of women starting oxygen therapy increased more rapidly than that in men. In 2000, 7.6 per 100,000 women started treatment compared with 7.1 in men. The frequency of ever smoking in Sweden in the age group receiving oxygen, i.e. age 65-84 years, was 36.4% in women and 65.0% in men, indicating that women ran a higher risk of developing an oxygen-requiring chronic hypoxaemia. An increase in women requiring oxygen therapy is predicted due to the increase in smoking frequency in young and middle-aged women and it is estimated that about 70% of Swedish patients on oxygen in 2026 will be women, with an estimated prevalence of 61 per 100,000. In conclusion, the incidence and prevalence for long-term oxygen therapy increases more rapidly among women than in men. This is probably due to the increased frequency of smoking in women compared with men and a higher susceptibility to develop severe hypoxaemia in women. The survival is better in women with long-term oxygen therapy than in men.
Abstract: A multifactorial grading score (MGS) for invasive squamous cell carcinoma of the uterine cervix has demonstrated its capacity to predict survival in a 5-10 year perspective and metastasis frequencies, and is a valuable tool for treatment schedules. In this study it was shown that the power of prognosis is valid even up to 20 years. In this material from 619 cervical carcinoma patients the MGS scores turned out to remain as strong as earlier proven. Earlier studies have shown that MGS is superior to other mono- and multifactorial grading systems, histological differentiation into cell types, age, clinical stage, irradiation and DNA-analysis. Treatment of cervical squamous cell carcinoma is more specific today to meet the patients' need for instance to preserve fertility or to minimize operation and eventually radiotherapy. The MGS score is a strong prognostic tool in patients with cervical carcinoma.
Abstract: BACKGROUND: Staging of osteoarthritis (OA) of the knee is commonly based on the Ahlbäck classification. Its value has been questioned, however. We therefore evaluated the reproducibility and validity of this classification of knee osteoarthritis. PATIENTS AND METHODS: 48 patients (48 knees) (medial OA: n = 30; lateral OA: n = 8) operated with total knee prostheses were studied. Weight-bearing radiographs were evaluated twice by 4 observers. Presence of bone attrition on radiographs was compared with observations of the resected parts of the distal femur and proximal tibia. RESULTS: When the same observer classified the radio-graphs twice according to Ahlbäck, the repeatability was fair in both medial OA (kappa values = 0.15-0.65) and lateral OA (0.59-0.76), and between different observers it was poor (kappa: 0.1). Comparison between radiographic classification and classification based on visual inspection of the bone pieces removed during arthroplasty revealed an acceptable sensitivity in both medial (67-95%) and lateral OA (43-86%), but the specificity was low (medial: 11-67%; lateral: 25-75%). INTERPRETATION: The main problem with the Ahlbäck classification was that a joint space could often be seen radiographically despite the presence of bone attrition on the preparations. According to our study, conventional radiographs do not give sufficient information for correct grading.
Abstract: BACKGROUND: Syndesmotic injuries of the ankle without fractures can result from external rotation, abduction and dorsiflexion injuries. Kinematic studies of these trauma mechanisms have not been performed. We attempted to describe the kinematics of the tibiofibular joint in cadaveric specimens using radiostereometry after sequential ligament sectioning, and resulting from different trauma mechanisms and axial loading, in order to put forward treatment guidelines for the different types of syndesmotic injuries. METHODS: We assessed the kinematics of the distal tibiofibular joint in fresh-frozen cadaveric specimens using radiostereometry in the intact situation, and after alternating and sequential sectioning of the distal tibiofibular and anterior deltoid ligaments. To assess which of the known trauma mechanisms would create the largest displacements at the syndesmosis, the ankle was brought into the following positions under an axial load that was comparable to body weight (750 N): neutral, dorsiflexion, external rotation, abduction, and a combination of external rotation and abduction. RESULTS: In the neutral position, the largest displacements of the fibula consisted of external rotation and posterior translation. Loading of the ankle with 750 N did not apparently increase or decrease the displacements of the fibula, but gave a larger variety of displacements. In every position, sectioning of a ligament resulted in some fibular displacement. Sectioning of the anterior tibiofibular ligament (ATiFL) invariably resulted in external rotation of the fibula. Additional sectioning of the anterior part of the deltoid ligament (AD) gave a larger variety of displacements. In general, sectioning of the posterior tibiofibular ligament (PTiFL) gave the smallest displacements. Combined sectioning of the ATiFL and the PTiFL resulted in a larger variety of displacements in the neutral position. Sectioning of the AD together with the ATiFL and PTiFL resulted in tibiofibular displacements in the neutral situation exceeding the maximum values found in the intact situation, the most important being fibular external rotation. INTERPRETATION: Sectioning of the ATiFL results in mechanical instability of the syndesmosis. Of all trauma mechanisms, external rotation of the ankle resulted in the largest and most consistent displacements of the fibula relative to the tibia found at the syndesmosis. Based on our findings and the current literature, we recommend that patients with isolated PTiFL or AD injuries should be treated functionally when no other injuries are present. Patients with acute complete ATiFL ruptures, or combined ATiFL and AD ruptures should be treated with immobilization in a plaster. Patients with combined ruptures of the ATiFL, AD and PTiFL need to be treated with a syndesmotic screw.
Abstract: BACKGROUND: Hospital-specific variation in outcome is generally considered to be an important source of information for clinical improvement. We have measured the magnitude of this variation. METHODS: We determined the revision risk in 37,642 cemented primary total knee arthroplasties inserted as a result of osteoarthritis from 1993 through 2002 at 93 hospitals in Sweden. We used 2 essentially different methods to estimate risk of revision: a fixed-effects model (Cox's proportional hazards model) and a random-effects model (shared gamma frailty model). RESULTS: The 2 models ranked hospitals differently. As expected, the fixed-effects model provided more dispersed estimates of hospital-specific revision rates. In contrast to the random-effects model, chance events can easily cause overly optimistic or pessimistic outcomes in the fixed-effects model. Although the revision risk varied significantly between hospitals, the overall revision risk was still low. INTERPRETATION: Assessment of variation in outcome is an important instrument in the continuing effort to improve clinical care. However, regarding revision rate after knee arthroplasty, we do not believe that such analyses necessarily provide valid information on the current quality of care. We question their value as information source for seeking personal healthcare.
Abstract: OBJECTIVES: To compare endoscopic and open carpal tunnel release surgery among employed patients with carpal tunnel syndrome. DESIGN AND SETTING: Randomised controlled trial at a single orthopaedic department. PARTICIPANTS: 128 employed patients aged 25-60 years with clinically diagnosed and electrophysiologically confirmed idiopathic carpal tunnel syndrome. MAIN OUTCOME MEASURES: The primary outcome was severity of postoperative pain in the scar or proximal palm and the degree to which pain or tenderness limits activities, each rated on a 4 point scale, transformed into a combined score of 0 (none) to 100 (severe pain or tenderness causing severe activity limitation). The secondary outcomes were length of postoperative work absence, severity of symptoms of carpal tunnel syndrome and functional status scores, SF-12 quality of life score, and hand sensation and strength (blinded examiner); follow-up at three and six weeks and three and 12 months. RESULTS: 63 patients were allocated to endoscopic surgery and 65 patients to open surgery, with no withdrawals or dropouts. Pain in the scar or proximal palm was less prevalent or severe after endoscopic surgery than after open surgery but the differences were generally small. At three months, pain in the scar or palm was reported by 33 patients (52%) in the endoscopic group and 53 patients (82%) in the open group (number needed to treat 3.4, 95% confidence interval 2.3 to 7.7) and the mean score difference for severity of pain in scar or palm and limitation of activity was 13.3 (5.3 to 21.3). No differences between the groups were found in the other outcomes. The median length of work absence after surgery was 28 days in both groups. Quality of life measures improved substantially. CONCLUSIONS: In carpal tunnel syndrome, endoscopic surgery was associated with less postoperative pain than open surgery, but the small size of the benefit and similarity in other outcomes make its cost effectiveness uncertain.
Abstract: BACKGROUND: Home mechanical ventilation (HMV) and long-term oxygen therapy (LTOT) are the two treatment alternatives when treating respiratory insufficiency in patients with kyphoscoliosis. We aimed to study the effect on survival with regard to HMV or LTOT alone in patients with respiratory insufficiency due to kyphoscoliosis. METHODS: Swedish patients with nonparalytic kyphoscoliosis (ie, scoliosis not related to neuromuscular disorders) who started LTOT or HMV between 1996 and 2004 were followed up prospectively until February 14, 2006, with death as the primary outcome. Treatment modality, arterial blood gas levels, the presence of concomitant respiratory diseases, and age were recorded at the onset of treatment. No patient was lost to follow-up. RESULTS: One hundred patients received HMV, and 144 patients received oxygen therapy alone. Patients treated with HMV experienced better survival, even when adjusting for age, gender, concomitant respiratory diseases, and blood gas levels, with a hazard ratio of 0.30 (95% confidence interval, 0.18 to 0.51). CONCLUSION: The survival of patients with kyphoscoliosis receiving HMV was better than that of patients treated with LTOT alone. We suggest HMV and not oxygen therapy alone as the primary therapy for patients with respiratory failure due to kyphoscoliosis, regardless of gender, age, and the occurrence of concomitant respiratory diseases.
Abstract: STUDY OBJECTIVES: In 1996, researchers in Sweden initiated a collaborative randomized study comparing lung volume reduction surgery (LVRS) and physical training with physical training alone. The primary end point was health status; secondary end points included survival and physiologic measurements. DESIGN: After an initial 6-week physical training program, researchers' patients were randomized to either LVRS (surgical group [SG]) with continued training for 3 months, or to continued training alone (training group [TG]) for 1 year. SETTING: All seven thoracic surgery centers in Sweden. PATIENTS: All patients in Sweden with severe emphysema fulfilling inclusion criteria for LVRS. INTERVENTIONS: Patients randomized to surgery underwent a median sternotomy, except for a few patients in whom thoracotomy or video-assisted thoracoscopy were performed. In the TG, supervised physical training continued for 1 year; in the SG, supervised physical training continued for 3 months postoperatively. MEASUREMENTS AND RESULTS: Fifty-three patients were included in each group. Six in-hospital deaths occurred after surgery (12%), and one more death occurred during follow-up. Two deaths occurred in the TG. The difference in death rates between the groups was not statistically significant. Health status, as measured by St. George Respiratory Questionnaire (SGRQ) [total scale score mean difference at 1 year, 14.7; 95% confidence interval (CI), 9.8 to 19.7] as well as by the Medical Outcomes Study Short-Form General Health Survey (physical function scale score mean difference at 1 year, 19.7; 95% CI, 12.1 to 27.3) was improved from baseline in the SG compared with the TG. FEV(1), residual volume, and shuttle walking test values also improved in the SG but not in the TG after 6 months and 12 months. CONCLUSIONS: In severe emphysema, LVRS can improve health status in survivors but is associated with mortality risk. The effects are stable for at least 1 year. Physical training alone failed to achieve a similar improvement.
Abstract: BACKGROUND: We have previously shown that patients with instability of the anterior syndesmosis benefit from an anatomical reconstruction. It is not known whether this is because of restored kinematics. METHODS: In a prospective study of 5 patients, we assessed clinical findings and tibiofibular kinematics, evaluated by radiostereometry, before and after reconstruction of a chronic syndesmotic injury. RESULTS: We found no statistically significant differences in tibiofibular kinematics before and after reconstruction. The kinematics of the fibula relative to the tibia during external rotation stress differed from that known in asymptomatic volunteers, but the differences were not typical enough to differentiate between patients and healthy subjects. Clinical examination and ankle scores, however, showed that all patients benefited from reconstruction of the anterior syndesmosis. INTERPRETATION: Radiostereometry is not an adequate technique to diagnose chronic syndesmotic instability or to demonstrate restoration of the kinematics of the ankle as a cause of the beneficial effect of anatomical reconstruction of the syndesmosis.
Abstract: OBJECTIVE: Liraglutide is a long-acting glucagon-like peptide 1 analog designed for once daily injection. This study assessed the efficacy and safety of liraglutide after 12 weeks of treatment in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A double-blind, randomized, parallel-group, placebo-controlled trial with an open-label comparator arm was conducted among 193 outpatients with type 2 diabetes. The mean age was 56.6 years and the mean HbA(1c) was 7.6% across the treatment groups. Patients were randomly assigned to one of five fixed-dosage groups of liraglutide (0.045, 0.225, 0.45, 0.60, or 0.75 mg), placebo, or open-label sulfonylurea (glimepiride, 1-4 mg). The primary end point was HbA(1c) after 12 weeks; secondary end points were fasting serum glucose, fasting C-peptide, fasting glucagon, fasting insulin, beta-cell function, body weight, adverse events, and hypoglycemic episodes. RESULTS: A total of 190 patients were included in the intention-to-treat (ITT) analysis. HbA(1c) decreased in all but the lowest liraglutide dosage group. In the 0.75-mg liraglutide group, HbA(1c) decreased by 0.75 percentage points (P < 0.0001) and fasting glucose decreased by 1.8 mmol/l (P = 0.0003) compared with placebo. Improvement in glycemic control was evident after 1 week. Body weight decreased by 1.2 kg in the 0.45-mg liraglutide group (P = 0.0184) compared with placebo. The proinsulin-to-insulin ratio decreased in the 0.75-mg liraglutide group (-0.18; P = 0.0244) compared with placebo. Patients treated with glimepiride had decreased HbA(1c) and fasting glucose, but slightly increased body weight. No safety issues were raised for liraglutide; observed adverse events were mild and transient. CONCLUSIONS: A once-daily dose of liraglutide provides efficacious glycemic control and is not associated with weight gain. Adverse events with the drug are mild and transient, and the risk of hypoglycemia is negligible.
Abstract: BACKGROUND: The current practice of the Swedish Knee Register is not to take into consideration if one or both knees in a patient are subject to surgery when evaluating risk of revision after arthroplasty. Risk calculations are typically done by statistical methods, such as Kaplan-Meier analyses and Cox's proportional hazards models, that are based on the assumption that observed events are independent, and this is rarely appreciated. The purpose of this study was to investigate if ignoring bilateral operations when using these methods biases the results. METHODS: The bias of not taking bilateral operations into account was investigated by statistically analysing 55 298 prostheses in 44 590 patients, undergoing knee arthroplasty surgery in Sweden during 1985-1999, using traditional proportional hazards analysis, which assumes that all observations are independent, and a shared gamma frailty model, which allows patients to contribute repeated observations. RESULTS: The effect of neglecting bilateral prostheses is minute, possibly because bilateral prosthesis failure is a rare event. CONCLUSION: We conclude that the revision risk of knee prostheses in general can be analysed without consideration for subject dependency, at least in study populations with a relatively low proportion of subjects having experienced bilateral revisions.
Abstract: We compared the value of 7.5 Nm external rotation stress in diagnosing tibiofibular syndesmotic injuries of the ankle on lateral radiographs with radiostereometric analysis (RSA) in 10 cadaveric legs. After sectioning 2 ligaments, RSA showed an increase in posterior translation and external rotation of the fibula. This increase in posterior translation was smaller than the posterior displacement of the fibula on the lateral radiograph, and RSA showed mainly an increase in external rotation of the fibula that can not be measured on conventional radiographs. We conclude that instability of the syndesmosis in cadaveric ankles can be detected with 7.5 Nm external rotation stress RSA, but that external rotation stress lateral radiography is unreliable.
Abstract: In 11 healthy volunteers, the normal kinematics of the tibiofibular syndesmosis of the ankle during weight bearing and external rotation stress were compared to a nonweight-bearing neutral position by radiostereometry. We found very small rotations and displacements in this "normal" group, which indicated that the fibula is closely attached to the tibia, thereby preventing larger movements at the level of the ankle. We found no common kinematic pattern during weight bearing in the neutral position. Application of a 75 Nm external rotation moment on the foot caused external rotation of the fibula between 2 and 5 degrees, medial translation between 0 and 2.5 mm and posterior displacement between 1.0 and 3.1 mm. These data can be used as normal reference values for studies of patients with suspected syndesmotic injuries.
Abstract: The aim of this study was to describe some of the factors that might play a role in influencing attitude to xenotransplantation: first, the consideration of receiving cells and tissue from xenotransplants in relation to whole xeno-organs; secondly, the fact that there is greater uncertainty regarding the result and risk of infection associated with xenotransplantation than with allotransplantation. We also describe the attitude to research on xenotransplantation, and the relationship between the attitude to receiving a xenotransplant and an allotransplant. Finally, we describe the attitude to xenotransplantation in relation to treatment for renal failure and waiting-time for allotransplantation. A questionnaire was sent to randomly selected members of the public aged 18 to 75 (n=1,000) and to all patients in the same age range who were waiting for kidney transplants in Sweden in the spring of 1998 (n=460). The response rate was 60% among the public and 87% among the patients. Both study groups were positive to a greater extent in their attitude to receiving cells and tissue than to receiving a whole organ such as a kidney. The response 'rather positive' to receiving organs was generally favored by the public, whereas the most generally favored response to receiving cells and tissue was 'very positive'. When there was suggested to be a greater uncertainty regarding the outcome with xenotransplantation compared with allotransplantation, the number of negative and uncertain respondents increased, both among the public and the patients. Eighty percent of the public and about 90% of the patients were in favor of continued research on xenotransplantation. Of those members of the public who responded, the attitude to receiving an organ from a human was positive in 86% of cases, with an emphasis on 'very positive'. There was a moderate relation between the attitude to receiving an organ from a human and to receiving a xenotransplant. Among the patients, there was no systematic or strong relation between the attitude to xenotransplantation and the kind of dialysis treatment they were on. Neither was there any systematic or strong relation to the waiting-time. The overall impression is that the attitude to xenotransplantation seems to be most influenced by whether the xenotransplant would involve whole organs or cells and uncertainty regarding the outcome.
Abstract: PURPOSE: To describe and compare the pattern of antihypertensive drug prescriptions during different time periods. METHODS: Antihypertensive prescriptions were registered in all patients who underwent an annual follow-up during 1998 (n = 984), 1992-1993 (n = 924), and 1981 (n = 689), at the hypertension outpatient clinic in primary health care, Skara, Sweden. RESULTS: From 1981 to 1998 the total prescriptions of thiazides declined from 61 to 10% (p < 0.001), whilst prescriptions of calcium antagonists increased from 4 to 30% (p < 0.001), and ACE inhibitors from zero to 23% (p < 0.001). Prescriptions of calcium antagonists and ACE inhibitors increased during 1990-1995, but during 1996-1998 a significant decrease in primary prescriptions of calcium antagonists was demonstrated (OR: 0.15; 95% CI: 0.06-0.36). During all periods, females were more frequently treated with older types of antihypertensive drugs than males. In the analysis of total prescriptions in 1998 women were prescribed calcium antagonists (OR: 0.59; 95% CI: 0.45-0.78) and ACE inhibitors (OR: 0.43; 95% CI: 0.31-0.58) less frequently than men. CONCLUSION: There were significant changes in type of antihypertensive drugs used, both by time and between genders. Changes during the latest years indicate that the prescription pattern can be greatly influenced by new scientific reports and economic debate.
Abstract: AIMS: To examine determinants for glycaemic control in primary care patients with Type 2 diabetes. METHODS: In a community-based surveillance of primary care patients with Type 2 diabetes, 190 men and 186 women were consecutively identified and examined for cardiovascular risk factors. Insulin resistance and beta-cell function were estimated using homeostasis model assessment (HOMA). Good glycaemic control was defined as HbA(1c) < 6.5%. RESULTS: Following adjustment for age and gender, HbA(1c) > or = 6.5% was associated with duration of diabetes (10.6 vs. 6.4 years, P < 0.001), lower levels of serum insulin (6.3 vs. 8.0 mU/l, P = 0.012), higher serum triglyceride levels (2.0 vs. 1.7 mmol/l, P = 0.002) and impairment of beta-cell function (HOMA index 19.5 vs. 45.8, P < 0.001). The association between HbA(1c) levels and duration remained with adjustment for age, gender, waist-hip ratio (WHR) and serum triglycerides (odds ratio (OR) for HbA(1c) > or = 6.5% by 5 years diabetes duration = 1.7; 95% confidence interval (CI) 1.4--2.1) but was lost following additional adjustment for beta-cell function (OR for HbA(1c) > or = 6.5% = 1.3; 95% CI 0.96-1.7). In a separate linear regression with beta-cell function as the dependent variable there was a significant association with HbA1c after adjustments for differences in age, gender, WHR, serum triglyceride levels and diabetes duration (P < 0.001). CONCLUSIONS: Increasing HbA1c by time was associated with declining beta-cell function.
Abstract: Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver.
Abstract: AIM: NANSY is a randomised, placebo-controlled Swedish-Norwegian study which aims to include 2 x 1112 male and female subjects with impaired fasting glucose (IFG), to assess whether conversion to type 2 diabetes can be delayed by addition of sulphonylurea to dietary regulation and increased exercise. This pilot study was conducted to find the optimum dose of glimepiride in NANSY. METHODS: In a double blind trial in primary care 25 IFG subjects were in random order exposed to single doses and one-week treatments with 0 (placebo), 0.5, 1.0 and 2.0 mg glimepiride once daily. The optimum dose was assessed by measuring blood glucose during oral 75 g glucose tolerance test (OGTT), comparing fasting blood glucose, and the area under the blood glucose curve (AUC), and by monitoring hypoglycaemic events. RESULTS: With single doses, there was a clear dose-response relationship for the reduction in AUC, with a statistically significant difference only between placebo (mean 1981, 95% confidence intervals (CI) 1883-2078) and 2 mg glimepiride (mean 1763, 95% CI 1665-1861). However, following 1-week treatments, the only significant difference was between placebo (mean 1934, 95% CI 1856-2012) and 1 mg glimepiride (mean 1714, 95% CI 1637-1792). Correspondingly, the only statistically significant difference in fasting blood glucose day 7 was between placebo (5.87 mmol/l, 95% CI 5.68-6.05 mmol/l) and 1 mg glimepiride (5.42 mmol/l, 95% CI 5.21-5.62 mmol/l). Chemical hypoglycaemia was common but hypoglycaemic symptoms were rare and similar between the active doses, and easily countered by the subjects. CONCLUSIONS: The sulphonylurea dose-effect curve may be bell-shaped, perhaps due to down regulation of sulphonylurea receptors during chronic exposure. Alternatively, the finding could be a rebound phenomenon, secondary to preceding hypoglycaemia. The optimum dose for NANSY was found to be 1 mg glimepiride.
Abstract: The aim of this study was to investigate whether polymorphisms in the beta(2)-adrenergic receptor gene (5'LC-Arg19Cys, Arg16Gly, Gln27Glu) are associated with hypertension in patients with or without type 2 diabetes and with the blood pressure levels in normotensive sib pairs. The association study included 291 hypertensive patients without type 2 diabetes, 124 hypertensive patients with type 2 diabetes, and 265 healthy control subjects from SWEDEN: In addition, normotensive sib pairs that were discordant for the Arg16Gly (72 pairs) and Gln27Glu (40 pairs) polymorphisms were identified in type 2 diabetes families from FINLAND: Genotyping was performed using polymerase chain reaction-restriction fragment-length polymorphism analysis. Homozygous carriers of the Arg16 allele had a significantly increased odds ratio (OR) for hypertension in patients with type 2 diabetes (OR 2.14; 95% confidence interval [CI], 1.05 to 4.33), particularly among lean (body mass index<27 kg/m(2)) patients (OR 3.47; 95% CI, 1.06 to 11.33). The Gln27 allele showed a weaker association to hypertension (OR 1.55; 95% CI, 1.00 to 2.41) and was found to be in linkage disequilibrium with the Cys19 allele of the 5'LC-Arg19Cys polymorphism. In the paired-sibling analysis, siblings with at least 1 copy of the Arg16 allele had higher systolic blood pressure (P=0.049), and nondiabetic siblings had a higher body mass index (P=0.026) than siblings homozygous for the Gly16 allele. These results indicate that the Arg16 allele of the beta(2)-adrenergic receptor gene confers an increased risk for hypertension in subjects with type 2 diabetes and is associated with higher blood pressure levels and higher body mass index in sib pairs who are discordant for the polymorphism.
Abstract: AIM: To assess the prevalence of borderline isolated systolic hypertension (borderline ISH), and to examine its association with other cardiovascular risk factors. METHODS: A cross-sectional community-based study was carried out in 1993-1994 in Skara, Sweden, including 1109 randomly chosen subjects > or = 40 years old. Normotension (NT) was defined as systolic blood pressure (SBP) < 140 and diastolic blood pressure (DBP) < 90 mmHg, borderline ISH as SBP 140-159 and DBP < 90 mmHg and hypertension (HT) as SBP > or = 160 or DBP > or = 90 mmHg or ongoing treatment. RESULTS: The prevalence of borderline ISH (n = 203) by age was 4% in ages 40-49 years, 15% in ages 50-59 years, 28% in ages 60-69 years and 25% in ages 70-79 years. With borderline ISH as reference, normotensive subjects less often had fasting blood glucose > 5.5 mmol/l (odds ratio (OR): 0.4, 95% CI: 0.26-0.75), BMI > 27 kg/m2 (OR: 0.6, 95% confidence intervals (CI): 0.42-0.85) and known diabetes (OR: 0.4, 95% CI: 0.16-0.95). Hypertensive subjects more often had high density lipoprotein (HDL) cholesterol < 1.0 mmol/l (OR: 2.0, 95% CI: 1.35-2.99), a history of previous cardiovascular disease (CVD) (OR: 1.7, 95% CI: 1.01-2.72), known diabetes (OR: 2.4, 95% CI: 1.29-4.58) and microalbuminuria (men) (OR: 1.9, 95% CI: 1.15-3.11). CONCLUSION: Borderline ISH is a common condition. It is associated with a more unfavourable risk factor profile than that of normotensive subjects concerning primarily glucose metabolism and obesity. The prevalence of known diabetes increased with the degree of hypertension.
Abstract: BACKGROUND: The Arg389 variant of the beta(1)-adrenergic receptor gene mediates a higher isoproterenol-stimulated adenylate cyclase activity than the Gly389 variant in vitro. We investigated whether the Arg389Gly or the Ser49Gly polymorphism is associated with hypertension in Scandinavians. Methods and Results-- A total of 292 unrelated, nondiabetic, hypertensive patients and 265 unrelated healthy control subjects were included in a case-control association study. From 118 families, 102 nondiabetic sibling pairs without antihypertensive medication who were discordant for the Arg389Gly polymorphism were selected for a sibling study. Allele and genotype frequencies of the Arg389Gly and Ser49Gly polymorphisms were compared between hypertensive patients and normotensive control subjects. Blood pressure and heart rate were compared between carriers of the different genotypes. In the case-control study, the age- and body mass index-adjusted odds ratio for hypertension in subjects homozygous for the Arg389 allele was 1.9 (95% confidence interval, 1.3 to 2.7; P=0.0005) when compared with carriers of 1 or 2 copies of the Gly389 allele. The genotype-discordant sibling pair analysis revealed that siblings homozygous for the Arg389 allele had significantly higher diastolic blood pressures (79.4+/-9.9 versus 76.0+/-10.1 mm Hg; P=0.003) and higher heart rates (68.3+/-11.0 versus 65.1+/-9.4 bpm; P=0.02) than siblings carrying 1 or 2 copies of the Gly389 allele. The Ser49Gly polymorphism was not associated with hypertension. CONCLUSION: Our data suggest that individuals homozygous for the Arg389 allele of the beta(1)-adrenergic receptor gene are at increased risk to develop hypertension.
Abstract: OBJECTIVE: To explore a possible temporal association between changes in antidepressant sales and suicide rates in different age groups. METHODS: A time series analysis using a two-slope model to compare suicide rates in Sweden before and after introduction of the selective serotonin reuptake inhibitors, SSRIs. RESULTS: Antidepressant sales increased between 1977-1979 and 1995-1997 in men from 4.2 defined daily doses per 1000 inhabitants and day (DDD/t.i.d) to 21.8 and in women from 8.8 to 42.4. Antidepressant sales were twice as high in the elderly as in the 25-44-year-olds and eight times that in the 15-24-year-olds. During the same time period suicide rates decreased in men from 48.2 to 33.3 per 10(5) inhabitants/year and in women from 20.3 to 13.4. There was significant change in the slope in suicide rates after the introduction of the SSRI, for both men and women, which corresponds to approximately 348 fewer suicides during 1990-1997. Half of these 'saved lives' occurred among young adults. CONCLUSION: We demonstrate a statistically significant change in slope in suicide rates in men and women that coincided with the introduction of the SSRI antidepressants in Sweden. This change preceded the exponential increase in antidepressant sales.
Abstract: The aim of this study was to survey attitudes toward xenotransplantation and to investigate whether there is a difference in attitudes between patients awaiting a kidney transplantation and the general public. A questionnaire was sent to randomly selected members of the public aged 18-75 (n = 1000) and to all patients of the same age group waiting for kidney transplants in Sweden in 1998 (n = 460). Among the public, 60 % expressed a positive attitude toward receiving an animal kidney graft with the same degree of risk as a human kidney graft, compared with 66 % for the patients. The proportion in favour of receiving a heart remained 60 % for the public, but rose to 70 % for the patients. If a human heart was not available, 61 % of the public were for the use of an animal heart, compared with 73 % in the patient group. A majority of the respondents would accept a transplant from an animal, provided the result and risk of infection were the same as with a human transplant. A greater proportion of patients had a positive attitude to receiving a xenotransplant than did the general public. A life threatening situation marginally increased the positive proportions.
Abstract: The characteristics of scientific fraud and its impact on medical research are in general not well known. However, the interest in the phenomenon has increased steadily during the last decade. Biostatisticians routinely work closely with physicians and scientists in many branches of medical research and have therefore unique insight into data. In addition, they have methodological competence to detect fraud and could be expected to have a professional interest in valid results. Biostatisticians therefore are likely to provide reliable information on the characteristics of fraud in medical research. The objective of this survey of biostatisticians, who were members of the International Society for Clinical Biostatistics, was to assess the characteristics of fraud in medical research. The survey was performed between April and July 1998. The participation rate was only 37%. We report the results because a majority (51%) of the participants knew about fraudulent projects, and many did not know whether the organization they work for has a formal system for handling suspected fraud or not. Different forms of fraud (e.g., fabrication and falsification of data, deceptive reporting of results, suppression of data, and deceptive design or analysis) had been observed in fairly similar numbers. We conclude that fraud is not a negligible phenomenon in medical research, and that increased awareness of the forms in which it is expressed seems appropriate. Further research, however, is needed to assess the prevalence of different types of fraud, as well as its impact on the validity of results published in the medical literature.
Abstract: AIMS: An increased risk for Type 2 diabetes in male and female smokers has been associated with insulin resistance. However, this might also be the result of an adverse effect on the beta-cell. The aim of the present study was to examine the association between smoking and beta-cell function. METHODS: A community-based, cross-sectional observation study. In 1994, a randomized age-stratified sample of men and women aged > or = 40 years in the city of Skara, Sweden, were invited to a survey of cardiovascular risk factors. In all, 1,109 subjects participated (80%). After the exclusion of subjects with known hypertension or diabetes mellitus, 874 subjects remained to explore. Samples were drawn after an overnight fast. Lifestyle (smoking, physical activity, alcohol consumption) was assessed using a questionnaire. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment (HOMA). RESULTS: Cigarette smoking men (n = 101) had a lower HOMA beta-cell value (58.1), than never-smokers (n = 158, beta-cell value 90.1, P < 0.001). The difference remained with adjustments for age, body mass index, daily alcohol intake and physical exercise habits: 25.9 (95% confidence interval (CI) 9.7-38.8, P = 0.003). Correspondingly, in men the HOMA beta-cell value was lower in current smokers than in ex-smokers (difference 24.3, 95% CI 11.1-35.2, P < 0.001). In women, no significant difference appeared in beta-cell function vs. different smoking status. There was no association between smoking status and insulin resistance. CONCLUSIONS: At least in men, smoking may interfere with beta-cell function. The prevention of Type 2 diabetes should include strategies to stop smoking.
Abstract: PRIMARY OBJECTIVE: In 1989, a new therapy to reduce intracranial pressure in severely head-injured patients was introduced in Lund. The new treatment reduced mortality significantly. The present study describes the quality of life for the survivors. METHODS AND PROCEDURES: The study includes 53 patients treated during 1989-1994, according to a new treatment protocol for increased intracranial pressure ('Lund concept' group). During 1982-1986, 38 patients were managed according to a protocol including high dose thiopentone ('Thiopentone' group). The two groups are compared regarding neurophysical and psychiatric symptoms as well as aspects regarding the patient's role, performance, interpersonal relationship, frictions, feelings and satisfaction in work, areas of social and leisure activities, and extended family. RESULTS: Mortality was reduced from 47% to 8%, but the number of patients with a persistent vegetative state and/or remaining severe disability did not increase. However, the number of patients with persisting emotional and intellectual deficits increased significantly. CONCLUSION: The new treatment regime has dramatically increased the number of survivors after severe head trauma. Although most patients have a favourable outcome, there are more patients with remaining sequelae and disabilities, and the demand for qualified rehabilitation has increased.
Abstract: OBJECTIVE: Insufficient coping with stress may lead to increased susceptibility for disease and death. Use of anxiolytic-hypnotic drugs has been suggested as a coping strategy, and some opinions have proposed their use as preventive medication. The aim of this study was to estimate if use of anxiolytic-hypnotic drugs counters the increased mortality observed in individuals lacking other coping strategies such as emotional support and social participation. METHODS: A population based cohort study with 10-year (1982/83-1993) survival analysis was performed in 491 men born in 1914, living in the Swedish city of Malmö. RESULTS: Compared with men with a high level of psychosocial coping resources who did not use anxiolytic-hypnotic drugs, men with a low level of psychosocial coping resources had a higher risk of death irrespective whether they used anxiolytic-hypnotic drugs, RR = 1.7 (95% CI 1.1-2.6) or not RR = 1.8 (95%: 1.3-2.5). CONCLUSION: Anxiolytic-hypnotic drugs do not seem to counter increased mortality in elderly men with low psychosocial coping resources.
Abstract: This article summarizes the results of a large-scale population-based study conducted to determine the prevalence of carpal tunnel syndrome in the Swedish general population. The study utilized a health questionnaires as well as clinical and electrophysiological examinations. Population prevalence rates of carpal tunnel syndrome, based on clinical diagnosis and electrophysiological criteria, were calculated. Obesity and specific work-related hand activities were shown to be risk factors for carpal tunnel syndrome.
Abstract: OBJECTIVE: To estimate endometrial thickness by transvaginal ultrasound technique (TVU) in patients treated with tamoxifen; and to compare the results with hysteroscopy and directed biopsy, and to relate the findings to curettage material. METHODS: Fifty-four women, over 50 years of age at the time of their primary breast cancer operation and scheduled for adjuvant treatment of tamoxifen, were investigated. If the endometrium measured 8 mm or more (35 patients) hysteroscopy and directed biopsy was performed. RESULTS: In the 35 patients, hysteroscopy and curretage revealed polyps in 18 cases (51.4%), proliferation in 1 case (2.9%) and atrophy in 16 cases (45.7%). In 54.3% (19 cases) of the patients the histopathological finding was a polyp or benign proliferation of the endometrium in agreement with the thickened endometrium seen with TVU. In the remaining 45.7% (16 cases) of the patients a thickened endometrium by transvaginal ultrasound was false positive as the hysteroscopic and subsequent histopathological diagnosis only showed atrofia of the uterine endometrium. CONCLUSIONS: In almost half of the patients the TVU gave a misleading picture concerning the condition of the endometrium. Changes in the myometrium and related connective tissue could be misinterpreted by the ultrasound technique as changes in the endometrium. These results may confirm the theory that stimulation and changes by antiestrogenic treatment of the uterine tissue is not only restricted to the endometrium. In patients with thickened endometrium measured by TVU, a dilatation and curettage is not sufficient, as TVU has not the ability to differentiate between endometrial polyps and myometrial changes. A hysteroscopy and directed biopsy could therefore be performed.
Abstract: AIM: To examine treatment and glucose control in type 2 diabetes patients with and without hypertension, and to explore differences in markers for insulin resistance and beta cell function. METHODS: A community-based, cross-sectional observational study was carried out at the hypertension and diabetes outpatient clinic in primary health care, Skara, Sweden. The subjects were all the 400 patients with type 2 diabetes (202 men, 198 women) who underwent annual follow-up from May 1992 through September 1993; 204 of these also had hypertension. RESULTS: The patients with both type 2 diabetes and hypertension had a higher b.m.i. (mean; 28.9 kg m(-2) (s.d.; 4.4) vs. 27.4 kg m(-2)(4.6)), higher triglycerides (2.0 mmol l(-1)(1.1) vs. 1.7 mmol l(-1)(1.1)), higher LDL/HDL cholesterol ratio (4.3(1.4) vs. 4.1(1.2)) and higher fasting insulin (8.5 mU l(-1)(1.1) vs. 6.6 mU l(-1)(1.1)). Conversely, glucose levels were lower; HbA1c (6.4%(1.4) vs. 6.8%(1.6)) and fasting blood glucose (8.1 mmol l(-1)(2.3) vs. 8.9 mmol l(-1)(2.7)) than in patients with type 2 diabetes alone. By the homeostasis model assessment (HOMA), patients with type 2 diabetes alone had more impaired beta cell function. They also had a higher frequency of insulin treatment (20% vs. 12%) and were less often treated non-pharmacologically (33% vs. 50%). CONCLUSIONS: Patients with type 2 diabetes and hypertension constitute a high risk category with a more atherogenic risk factor profile related to the insulin resistance syndrome. Patients with type 2 diabetes without hypertension seem to constitute a subgroup of type 2 diabetes with predominately impaired beta cell function.
Abstract: OBJECTIVES: To assess (1) whether the utilisation of codeine or propoxyphene differs among the three major Swedish cities (Stockholm, Göteborg and Malmö) and between urban and semirural areas; (2) if so, whether it co-varies with the utilisation of other potentially dependence-promoting drugs, benzodiazepines; (3) what influence age, gender and socioeconomic factors have on the prescribing of the two narcotic analgesics; and (4) whether different codeine-prescriber categories have different prescribing habits. METHODS: In Sweden, all pharmacies are owned by one corporation, Apoteket AB. This corporation collects, stores and compiles statistics on all drug sales in Sweden, and data are available both on national, regional, county and municipal levels. The employed unit is defined daily dose (DDD) per 1,000 inhabitants per day. Using the pharmacy computer system while dispensing a drug, prescription patterns can be elucidated. This system describes the number of drug items dispensed, drug amounts and age and gender of patients. Furthermore, data from another, ecological study were used to relate codeine and propoxyphene utilisation to that of benzodiazepines and to various socioeconomic data available from records of the city of Malmö. RESULTS: The utilisation of analgesics in Sweden has increased during a 10-year period. The withdrawal of over-the-counter combinations containing aspirin and low-dose codeine in 1990 resulted only in a transient decrease of codeine use. The utilisation of codeine in Malmö and Göteborg was considerably higher than that in Stockholm and in the rest of Sweden, including the surroundings of Malmö. In Malmö and Göteborg, codeine was most often prescribed by private physicians to middle-aged persons, particularly women. Districts in Malmö with a high utilisation of codeine were associated with unfavourable socioeconomic conditions and a high utilisation of benzodiazepines. The utilisation pattern of propoxyphene showed less or no such deviations. CONCLUSION: The results suggest an inappropriate use of codeine in two major cities in Sweden.
Abstract: The aims of this study were to identify risk factors for hip fracture in men aged 50 years or more. We identified 730 men with hip fracture from 14 centers from Portugal, Spain, France, Italy, Greece and Turkey during the course of a prospective study of hip fracture incidence and 1132 age-stratified controls selected from the neighborhood or population registers. The questionnaire examined aspects of work, physical activity past and present, diseases and drugs, height, weight, indices of co-morbidity and consumption of tobacco, alcohol, calcium, coffee and tea. Significant risk factors identified by univariate analysis included low body mass index (BMI), low sunlight exposure, a low degree of recreational physical activity, low consumption of milk and cheese, and a poor mental score. Co-morbidity including sleep disturbances, loss of weight, impaired mental status and poor appetite were also significant risk factors. Previous stroke with hemiplegia, prior fragility fractures, senile dementia, alcoholism and gastrectomy were associated with significant risk, whereas osteoarthrosis, nephrolithiasis and myocardial infarction were associated with lower risks. Taking medications was not associated with a difference in risk apart from a protective effect with the use of analgesics independent of co-existing osteoarthrosis and an increased risk with the use of anti-epileptic agents. Of the potentially 'reversible' risk factors, BMI, leisure exercise, exposure to sunlight and consumption of tea and alcohol and tobacco remained independent risk factors after multivariate analysis, accounting for 54% of hip fractures. Excluding BMI, 46% of fractures could be explained on the basis of the risk factors sought. Of the remaining factors low exposure to sunlight and decreased physical activity accounted for the highest attributable risks (14% and 9% respectively). The use of risk factors to predict hip fractures had relatively low sensitivity and specificity (59.6% and 61.0% respectively). We conclude that lifestyle factors are associated with significant differences in the risk of hip fracture. Potentially remediable factors including a low degree of physical exercise and a low BMI account for a large component of the total risk.
Abstract: AIM: To assess the effect of oral antihyperglycaemic therapy on fasting proinsulin and the relation between proinsulin levels and cardiovascular risk factors in type 2 diabetes. METHODS: One hundred and sixty-five patients with type 2 diabetes, fasting blood glucose concentration (FBG) > or = 6.7 mmol/l, were recruited from five diabetes outpatient clinics in primary health care. Diet and antihyperglycaemic medication, aiming at FBG < 6.7 mmol/l, was maintained for 6 months after completed dose titration in a randomized, double-blind, double-dummy trial with metformin (M), glibenclamide (G) and primary combination of both drugs (MG). The study compared M, G and MG in low dose (MGL) and also different high-dose regimens, i.e. G added to M (M/G), M added to G (G/M) and primary combination (MGH). Outcome measures were fasting proinsulin, glycaemia, body mass index, blood pressure, lipids, insulin and C-peptide. RESULTS: Lower proinsulin levels were found when therapy was initiated with metformin (M vs. G, p = 0.013 and M/G vs. G/M, p = 0.033). M and G were equally effective on glucose levels. In the group as a whole FBG decreased from (mean +/- s.d.) 10.2 +/- 2.7 to 7.0 +/- 1.2 mmol/l with no change in proinsulin. Proinsulin was associated with cardiovascular risk factors, linking high proinsulin to an atherogenic risk marker profile. Mean proinsulin change from baseline was inconsistently associated with markers of insulin resistance. Meal-stimulated glucose (net AUC) decreased after treatment only in those with low baseline proinsulin levels. CONCLUSION: It may be advantageous to initiate oral antihyperglycaemic therapy with metformin rather than with sulphonylurea. High proinsulin levels are associated with an atherogenic-risk marker profile and an impaired therapeutic postprandial glucose response after treatment in patients with type 2 diabetes. Proinsulin change after therapy is inconsistently associated with markers of insulin resistance and unrelated to fasting blood glucose reduction.
Abstract: CONTEXT: Carpal tunnel syndrome (CTS) is a cause of pain, numbness, and tingling in the hands and is an important cause of work disability. Although high prevalence rates of CTS in certain occupations have been reported, little is known about its prevalence in the general population. OBJECTIVE: To estimate the prevalence of CTS in a general population. DESIGN: General health mail survey sent in February 1997, inquiring about symptoms of pain, numbness, and tingling in any part of the body, followed 2 months later by clinical examination and nerve conduction testing of responders reporting symptoms in the median nerve distribution in the hands, as well as of a sample of those not reporting these symptoms (controls). SETTING: A region in southern Sweden with a population of 170000. PARTICIPANTS: A sex- and age-stratified sample of 3000 subjects (age range, 25-74 years) was randomly selected from the general population register and sent the survey, with a response rate of 83% (n = 2466; 46% men). Of the symptomatic responders, 81% underwent clinical examination. MAIN OUTCOME MEASURES: Population prevalence rates, calculated as the number of symptomatic responders diagnosed on examination as having clinically certain CTS and/or electrophysiological median neuropathy divided by the total number of responders. RESULTS: Of the 2466 responders, 354 reported pain, numbness, and/or tingling in the median nerve distribution in the hands (prevalence, 14.4%; 95% confidence interval [CI], 13.0%-15.8%). On clinical examination, 94 symptomatic subjects were diagnosed as having clinically certain CTS (prevalence, 3.8%; 95% CI, 3.1%-4.6%). Nerve conduction testing showed median neuropathy at the carpal tunnel in 120 symptomatic subjects (prevalence, 4.9%; 95% CI, 4.1%-5.8%). Sixty-six symptomatic subjects had clinically and electrophysiologically confirmed CTS (prevalence, 2.7%; 95% CI, 2.1%-3.4%). Of 125 control subjects clinically examined, electrophysiological median neuropathy was found in 23 (18.4%; 95% CI, 12.0%-26.3%). CONCLUSION: Symptoms of pain, numbness, and tingling in the hands are common in the general population. Based on our data, 1 in 5 symptomatic subjects would be expected to have CTS based on clinical examination and electrophysiologic testing.
Abstract: Serum total sialic acid (S-TSA) is a recently identified risk marker for atherosclerosis and cardiovascular mortality. The purpose of this study was to evaluate the influence of three sialic acid rich glycoproteins (orosomucoid, haptoglobin, and alpha1-antitrypsin) on the relationship between S-TSA and carotid atherosclerosis. The mean S-TSA was 0.045 g/l higher among cases than controls (P<0.001) in 310 45-64 year-old male and female pairs of carotid atherosclerosis cases and disease-free controls from the Atherosclerosis Risk in Communities (ARIC) Study. Also mean serum levels of the glycoproteins were significantly higher in cases compared to controls. In a conditional multiple logistic regression model with the glycoproteins as independent variables, orosomucoid was correlated most strongly with case control status. However, when incorporated into the mathematical model, S-TSA not only contributed additional information as to the risk of atherosclerosis; none of the three glycoproteins contributed further once S-TSA had been accounted for. Thus, some other source of serum sialic acid or variations in the degree of sialylation of glycoproteins may be essential for understanding the relation between S-TSA and atherosclerosis.
Abstract: OBJECTIVE: To study the association between polymorphisms in the angiotensin converting enzyme (ACE) gene and angiotensinogen (AGT) gene and hypertension and/or type 2 diabetes in a community population. PATIENTS AND METHODS: The insertion (I)/deletion (D) polymorphism of the ACE gene and the M235T polymorphism of the AGT gene were genotyped in 773 nondiabetic individuals with hypertension, 193 normotensive patients with type 2 diabetes, 243 patients with type 2 diabetes and hypertension, and in 820 normotensive control individuals identified in a community-based study. RESULTS: The DD genotype was associated with hypertension in individuals less than 70 years [odds ratio (OR) = 1.54, confidence interval (CI) = 1.09-2.18] and remained so when patients with type 2 diabetes were excluded from the analysis (OR = 1.45, CI = 1.01-2.09). The strongest association was with the combination of type 2 diabetes and hypertension (OR = 2.19, CI = 1.09-4.38). There was no association with type 2 diabetes without hypertension. No association was observed between the M235T variant or the 3'-microsatellite polymorphism of the AGT gene and hypertension. CONCLUSION: The D-allele of the ACE gene ID polymorphism increases susceptibility to hypertension, particularly when associated with type 2 diabetes. No association was observed between the M235T variant or 3'-microsatellite polymorphism of the AGT gene and hypertension.
Abstract: Recent cases of fraud in clinical trials have attracted considerable media attention, but relatively little reaction from the biostatistical community. In this paper we argue that biostatisticians should be involved in preventing fraud (as well as unintentional errors), detecting it, and quantifying its impact on the outcome of clinical trials. We use the term 'fraud' specifically to refer to data fabrication (making up data values) and falsification (changing data values). Reported cases of such fraud involve cheating on inclusion criteria so that ineligible patients can enter the trial, and fabricating data so that no requested data are missing. Such types of fraud are partially preventable through a simplification of the eligibility criteria and through a reduction in the amount of data requested. These two measures are feasible and desirable in a surprisingly large number of clinical trials, and neither of them in any way jeopardizes the validity of the trial results. With regards to detection of fraud, a brute force approach has traditionally been used, whereby the participating centres undergo extensive monitoring involving up to 100 per cent verification of their case records. The cost-effectiveness of this approach seems highly debatable, since one could implement quality control through random sampling schemes, as is done in fields other than clinical medicine. Moreover, there are statistical techniques available (but insufficiently used) to detect 'strange' patterns in the data including, but no limited to, techniques for studying outliers, inliers, overdispersion, underdispersion and correlations or lack thereof. These techniques all rest upon the premise that it is quite difficult to invent plausible data, particularly highly dimensional multivariate data. The multicentric nature of clinical trials also offers an opportunity to check the plausibility of the data submitted by one centre by comparing them with the data from all other centres. Finally, with fraud detected, it is essential to quantify its likely impact upon the outcome of the clinical trial. Many instances of fraud in clinical trials, although morally reprehensible, have a negligible impact on the trial's scientific conclusions.
Abstract: Pallents with breast cancer exhibit an increased risk of developing cancer from other organs, a risk that might increase due to tamoxifen treatment. This drug has been found to cause activation of oestrogen receptors, leading to oestrogenic effects on the postmenopausal endometrium. We report follow-up of 94 patients with breast cancer without initial symptoms aged more than 50 years at the time of operation. They were followed-up with vaginal ultrasound at regular intervals and endometrial sampling was performed according to treatment after surgery: tamoxifen, tamoxifen in combination with other regimes and without tamoxifen treatment. A large proportion were investigated prior to treatment. We identified endometrial carcinoma, metastasis of breast carcinoma and histopathological changes in 17/67 (25%) of the patients treated with tamoxifen compared to 1/32 in those not treated with tamoxifen.
Abstract: Hip fracture is a major public health problem, but with a potential for prevention. Data from a European multicentre study on hip fracture epidemiology with a case control design, the MEDOS study, were used to describe and analyse circumstances around falls associated with hip fracture. The study includes 2185 fracture cases age > 50 years from 14 centres in southern Europe: Portugal, Spain, France, Italy, Greece and Turkey. Information was collected by a standardized and validated questionnaire translated into six languages and administered by trained interviewers. Circumstances around the fall were categorized according to: (1) place, age group and time of day; (2) functional disability; (3) drug consumption including alcohol; and (4) environmental factors. Possibilities for prevention were also analysed. High risk falls were identified using seven reasonably well-established risk factors, and similarly eight risk factors were used to identify high risk fallers. Selected trains of events were also studied. A pattern of great diversity was found both among the fallers and the environment in which they fell and fractured the hip. Those with more than one factor involved constituted only 14.7% of female and 19.7% of male fractures. A majority of cases were not physically disabled before the fall. A majority (66.5%) fell and fractured their hip indoors and only 4.3% outside in darkness. Cardiovascular and cerebrovascular comborbidity were observed with 4.9 and 7.8%, of falls respectively. Falls in a stairway comprised 11% of falls. The correlation between the number of the risk factors of the faller and in the environment was 0.07 and there was no difference between males and females. The pattern of causality behind falls that cause hip fracture and therefore of prevention comprises many sometimes small groups and intricate time sequence. The results suggest that global preventive strategies could presently not be implemented. Instead, the pattern of prevention should include different target groups and be country and site specific. For the high risk group of institutionalized patients prevention can be implemented without delay.
Abstract: The objective of the study was to investigate the accuracy of using preoperative data for the prediction of bile duct calculi in patients operated on for acute cholecystitis. 279 consecutive patients underwent cholecystectomy with peroperative cholangiography for acute calculous cholecystitis in the Department of Surgery, Lund University Hospital, between 1985 and 1991. The correlation between 13 preoperative clinical and laboratory variables, and the incidence of bile duct calculi was studied. Among the 13 variables tested, serum bilirubin concentration and serum gamma-glutamyltransferase activity were independent factors of predictive significance. These two factors were used for constructing an additive prognostic index for the presence of bile duct stones. Thus, three groups of patients could be identified having a 3, 7-9 or 59% risk of harboring bile duct stones, corresponding to a sensitivity of 61% and a specificity of 93% in predicting the presence of bile duct stones in the 'high-risk' group. Logistic regression analysis permits accurate preoperative identification of bile duct stones in patients with acute calculous cholecystitis.
Abstract: OBJECTIVE: The aim of this study was to investigate the intra-urban variation of antibiotic utilization in children in Malmö and to evaluate the influence of socio-economic factors on this variation. METHODS: In an ecological analysis, the variations in antibiotic utilization in children, expressed as defined daily dose (DDD) or as the number of prescriptions per 1000 inhabitants per day, were compared with variations in socio-economic and demographic factors in the 17 administrative districts of the Swedish city of Malmö (235000 inhabitants). RESULTS: There were large between-area differences in antibiotic utilization, especially in children aged 0-6 years. Socio-economic factors reflecting a privileged situation correlated positively with antibiotic utilization. Thus, in districts with a high median family income and a high employment rate, the utilization of antibiotics was higher than in other districts. Conversely, in districts with a high proportion of blue-collar workers, people with foreign backgrounds and recipients of social benefit, antibiotic utilization was comparatively low. In contrast, the utilization of penicillin V relative to other antibiotics showed an opposite pattern, including positive correlations with the proportion of social benefit, immigrants and blue-collar workers and a negative correlation with employment rate. Conversely, the utilization of macrolides in relation to other antibiotics in children aged 0-6 years was highest in districts inhabited by those who were socio-economically privileged. INTERPRETATION: The findings suggest that utilization of antibiotics in children may vary considerably within a city, that it may increase with the degree of parental affluence, and that such affluence may reduce the utilization of penicillin V relative to other antibiotics.
Abstract: The aim of the present study was to elucidate the relations between demographic and socioeconomic factors, morbidity and the utilization of major drug groups in an urban Swedish population. The study was performed as an ecological analysis during November 1991 in the 17 different districts of Malmö, the third largest Swedish city (235,000 inhabitants).The material comprised 86,228 ACT-coded drug items which corresponded to 76% of all prescriptions dispensed during the study month. Of these, 43,032, dispensed to patients aged 15-64 years, were analysed in the present work. Age standardized drug utilization was expressed as the number of dispensed Defined Daily Doses per 1000 inhabitants per day. Morbidity was measured in terms of reimbursed days on sick leave. The sociodemographic parameters used were socioeconomic status (SES), employment rate, median income per family, households on social allowance, and ethnicity.For four of the five major pharmacological groups (ATC-groups A, C, J, N and R, i.e. alimentation, circulation, infectious diseases, nervous system and respiration), most pronouncedly group N and least so group R, utilization correlated positively with not only the extent of morbidity but also with an unfavourable socioeconomic situation, high proportion of immigrants, and households on social allowance or with low income and/or with a low employment rate. The utilization of antibiotics (group J), however, instead correlated negatively with these parameters. For all five drug groups, these trends were similar among men and women, albeit with varying strength.In conclusion, socioeconomic factors may have a profound influence on the utilization of several major drug groups. At least in the case of antibiotics, the consequence of this influence is irrational drug use.
Abstract: OBJECTIVES: To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. DESIGN: A community-based, cross-sectional, observational study. SETTING: Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. SUBJECTS: All patients (n = 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September 1993. MAIN OUTCOME MEASURES: Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). RESULTS: Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmHg, women 165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82 mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension. HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. CONCLUSIONS: A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate.
Abstract: Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA). Immunosuppressive treatment has dramatically improved outcome for these patients, but today we have to deal with the problems of relapses, cases refractory to treatment, and long-term side effects of therapy. This study comprises a consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy-confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to 273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of patients. Nearly half of the patients (46%) relapsed. There was no statistically significant difference in overall relapse rate according to type of ANCA. Renal survival was 78% in patients alive at the end of follow-up. Three variables seemed important for renal survival: serum creatinine, the titer of proteinase 3-ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte count, at time of referral. Cancer incidence data were obtained from the population-based South Swedish Regional Tumor Registry. Standardized morbidity ratio was calculated using expected values from the health care region. We found an 11-fold increase in risk for bladder cancer in patients treated with cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest relationship with azathioprine use for at least 12 mo and with corticosteroid therapy for at least 48 mo. In addition, four patients developed myelodysplastic syndrome and five had carcinoma in situ of the skin. Because the therapeutic regimen used today is not efficient enough to prevent relapses and is associated with a host of side effects, of which the risk for cancer is by far the most important, improved therapy and medical care are needed for patients with WG and MPA.
Abstract: PURPOSE: Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS: The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS: No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION: The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.
Abstract: OBJECTIVE: To investigate possible associations between use of cardiovascular drugs and suicide. DESIGN: Cross sectional ecological study based on rates of use of eight cardiovascular drug groups by outpatients. A population based cohort study including users of drugs to control hypertension. SUBJECTS: The ecological study included 152 of Sweden's 284 municipalities. The cohort study included all inhabitants of one Swedish municipality who during 1988 or 1989 had purchased cardiovascular agents from pharmacies within the municipality. Six hundred and seventeen subjects (18.2%) were classified as users of calcium channel blockers and 2780 (81.8%) as non-users. MAIN OUTCOME MEASURES: Partial correlations (least squares method) between rates of use of cardiovascular drugs and age standardised mortality from suicide in Swedish municipalities. Hazard ratios for risk of suicide with adjustments for difference in age and sex in users of calcium channel blockers compared with users of other hypertensive drugs. RESULTS: Among the Swedish municipalities the use of each cardiovascular drug group except angiotensin converting enzyme inhibitors correlated significantly and positively with suicide rates. After adjustment for the use of other cardiovascular drug groups, as a substitute for the prevalence of cardiovascular morbidity, only the correlation with calcium channel blockers remained significant (r = 0.29, P < 0.001). In the cohort study, five users and four non-users of calcium channel blockers committed suicide during the follow up until the end of 1994. The absolute risk associated with use of calcium channel blockers was 1.1 suicides per 1000 person years. The relative risk, adjusted for differences in age and sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5). CONCLUSIONS: Use of calcium channel blockers may increase the risk of suicide.
Abstract: Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.
Abstract: A growing empirical literature has investigated attitudes towards discounting of health benefits with regard to social choices of life-saving and health-improving measures and individuals' time preferences for the management of their own health. In this study, the authors elicited the time preferences of vascular surgeons in the context of management of small abdominal aortic aneurysms, for which the choice between early elective surgery and watchful waiting is not straightforward. They interviewed 25 of a random sample of 30 Swedish vascular surgeons. Considerable variation in the time preferences was found in the choices between watchful waiting and surgical intervention among the otherwise very homogeneous group of surgeons. The discount rates derived ranged from 5.3% to 19.4%. The median discount rate (10.4%) is similar to those usually reported for social choices concerning life-saving measures. The surgeons who were employed in university hospitals had higher discount rates than did their colleagues in county and district hospitals.
Abstract: The reliability and validity of methods to assess social networks, social support and control were investigated in a population of 12,009 females and males born between 1926 and 1945 (the "Malmö Shoulder and Neck Study"). This study demonstrated an overall reliability with kappa coefficients between 0.70 and 0.47, but the reliability was more varying among females and lower in the youngest age group. The analysis of the construct validity indicated that the different indices measure different aspects of the psychosocial environment, but both theoretical and methodological problems were identified, when the validity of multidimensional concepts are to be determined. The validity of such indices can best be judged by combining quantitative and qualitative methods. Potential validity problems must be kept in mind when these indices are used in epidemiological research. The results from the reliability analysis call for repeated assessments and the sample size must be adjusted vis-a-vis the reliability.
Abstract: Endometrial thickness as measured by ultrasound during tamoxifen treatment has previously been reported. However, there has not been any study investigating endometrial thickness before treatment and following it at regular intervals during treatment. 90 patients with breast cancer without any gynecological symptoms were followed (aged more than 50 years at the operation of their breast cancer). They were investigated by vaginal ultrasound and a common clinical investigation at our out-care patient department. Adjuvant breast cancer therapy consisted of tamoxifen, tamoxifen after radiotherapy and/or in a few cases cytostatics, cytostatics with or without the addition of radiotherapy, radiotherapy or no further therapy. Patients with receptor positive tumours were given tamoxifen. Their endometrium was already thicker before the start of adjuvant treatment as measured by ultrasound. After 3 months and 12 months we found the endometrium to be significantly thicker in those treated with tamoxifen compared to other treatment groups. After 12 months of tamoxifen treatment 22/32 women had an endometrial thickness of 5 mm or more. The frequency of ovarian cysts also seemed to be affected by therapy. In patients treated with tamoxifen alone or in combination, the frequency of cysts was 5/35 before treatment, 6/37 after 3 months, and 0/32 after one year. The corresponding frequencies for those not treated with tamoxifen were 2/20, 3/11 and 3/23 respectively.
Abstract: The aim of the present investigation was to see if alternative histopathological parameters could identify a smaller high risk group than commonly seen using routine histopathological parameters. The material consisted of 150 primary resected patients of FIGO Ia-Ic diagnosed as endometrial carcinoma and 12 cases of atypical hyperplasias which were suspected to contain small areas of carcinoma. The patients were treated from December 1979 to April 1993 at the Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. Those with deep myometrial invasion (> 50%) were given external radiotherapy (20-30 Gy) postoperatively. The follow-up period ranged from 2.5 to 5 years with 116 patients followed-up for more than 5 years. As no therapy was given before surgery we could investigate histopathologic variables such as degree of differentiation and cytology, number of mitoses per high power field (x 40), nuclear polymorphism, mode of invasion, the extension of myometrial invasion, vessel invasion as well as grade of lymphocyte reaction around the tumour cells. We found the degree of differentiation, vessel invasion, number of mitoses, mode of invasion and cytologic abberation to be significant prognostic parameters. The frequency of deep myometrial invasion (> 50%) was extremly high (51/150 = 33%). However, this usually strong parameter was only significant when comparing stage Ia with Ic. Thus the prognostic capacity of myometrial invasion is diminished in primary hysterectomized patients. In the regression analyses only vascular invasion remained significant. By combining vascular invasion with the degree of differentiation we diminished the high-risk group consisting of candidates for further investigation and treatment. Thus a high risk group consisting of poorly differentiated carcinomas with vascular invasion was constructed comprising 24 of 139 patients with a mortality rate of 60%.
Abstract: BACKGROUND: The incidence of breast carcinoma is increasing in most populations, whereas mortality caused by this disease is fairly constant. The authors analyzed the incidence of and mortality from invasive breast carcinoma in a population with access to good medical care, into which mammographic screening was introduced in 1976 and adjuvant therapy in 1978. METHODS: In a consecutive series of patients with invasive breast carcinoma from Malmö, 1961-1991, changes in age-adjusted incidence were analyzed and compared with incidence of the disease in the rest of Sweden. Age-adjusted breast carcinoma mortality was studied for the period 1964-1992. RESULTS: The introduction of mammographic screening was associated with an increase in breast carcinoma incidence. This was restricted to the age group that was eligible for screening (age 45-69 years) and to Stage I disease. Between 1977 and 1992, age-adjusted breast carcinoma mortality decreased in Malmö by 43% (95% CI, 26-56%) as compared with 12% (95% CI, 8-16%) in the rest of Sweden. The decrease was statistically significant in both populations and significantly greater in Malmö than in the rest of Sweden (P < 0.001). In Malmö the decrease was seen in two age groups, age 45-69 years and age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. There were no changes in incidence or mortality among women younger than 45 years in either population. CONCLUSIONS: Breast carcinoma incidence was strongly related to diagnostic activity, especially mammographic screening. The decrease in mortality occurred in temporal relation to the introduction of screening and adjuvant therapy, making a causal relation likely. The difference in results between Malmö and the rest of Sweden indicates an important role for screening in mortality reduction.
Abstract: BACKGROUND: Obesity has, in a number of studies, been found to correlate to disability and mortality, primarily due to diseases of the circulatory and musculoskeletal systems. In addition, an excess mortality among underweight subjects has been observed in previous studies. METHODS: Five complete birth-year cohorts (1926-1930) of male residents in Malmö (n = 7697) were invited to the survey at the Department of Preventive Medicine, Malmö General Hospital, and 5926 (77%) attended with complete data. Each subject was followed from inclusion, defined by the date of examination, until the end of the calendar year when he turned 58, a total study period of approximately 11 years. Data on about 300 questionnaire items and laboratory tests were determined at the health survey visit. Nationwide Swedish data registers were used for surveillance. RESULTS: Of the participants, 4.7% were underweight, 37.7% overweight, 7.3% obese and 50.3% normal weight; 849 (14.3%) had been granted disability pension at the end of follow-up, 717 after screening. After adjustment for smoking there was a J-shaped relation between body mass index (BMI) and incidence of disability pension, the relative risk ( with the normal group as reference) among underweight men being 1.9. For the overweight subjects it was 1.3 and for the obese 2.8, all differences were significant. Disease of the musculoskeletal and circulatory systems and mental disorders accounted for 67.2% of all main diagnoses resulting in disability pensions during follow-up. A total of 377 (6.4%) men died during follow-up. Diseases of the circulatory system, neoplasms, injury/poisoning and diseases of the respiratory system accounted for 91.8% of the deaths. CONCLUSIONS: Both underweight, overweight and obesity were related to risk of disability pension, with a J-shaped risk relationship.
Abstract: OBJECTIVES: An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (IHD) mortality. METHODS: Multivariate 10-year survival analysis in a population based cohort of 500 men born in 1914. Relative risks (RR) were adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes mellitus, smoking habit, high alcohol consumption, history of previous IHD, cancer, and other diseases). RESULTS: The RR of both all-cause and IHD mortality were significantly increased among those using both AHD and analgesics compared to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and RR = 2.7 for IHD mortality. CONCLUSION: Although the number of cases was small, warranting interpretative caution, the current study suggests that the combined use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an increase in all-cause and IHD mortality in elderly men.
Abstract: The Mediterranean Osteoporosis Study (MEDOS), a multicentre study on incidence, risk factors, and means of prevention of hip fracture in the Mediterranean region, started in 1986 and involved 14 centres, in Portugal, Spain, France, Italy, Greece, and Turkey. The design includes a case-control study comparing 8,185 individuals in age groups above 50 (2,816 cases and 5,369 controls; two controls per case). Information on falls was only collected for a small fraction of the controls. In a questionnaire including 160 main questions eleven referred to circumstances around the fall. Falls were classified according to a) high risk environment, e.g. occurred in darkness and b) high risk fallers, e.g. confusion, reduced functional ability. There was great variation between centra for a majority of the results. However, 2/3 of fractures happened during daylight. 9% of fractures, same for both males and females, took place in darkness. Females have more indoor fractures than males. Around 15% of fractures took place in connection with going to the toilet. Mental factors play a minor role as reported immediate cause to the fall. Before the fall that caused the hip fracture between 28-84% could get up from a chair without any difficulties. Of the males 0-26% lived alone as against 0-37% or females. Conclusion: The data on circumstances around the fall shows a complex pattern with substantial variation between different cultures, but where a, however, minority took place under risk circumstances that have a clear preventive potential.
Abstract: STUDY OBJECTIVE: To test the stress hypothesis by characterising women during their first pregnancy who continue to smoke in early pregnancy in comparison with women who quit smoking, with special reference to psychosocial factors like social network, social support, demands, and control in work and daily life. DESIGN: The study is based on a cohort of primigravidas followed during pregnancy. Data were collected by self administered questionnaires during the pregnant womens' first antenatal visit at about 12 weeks. SETTING: The study was performed in the antenatal clinics in the city of Malmö, Sweden. PARTICIPANTS: The participants were all primigravidas living in the city of Malmö, Sweden, over a one year period, 1991-92. A total of 872 (87.7%) of the 994 invited women agreed to participate. The population of this study on smoking includes all primigravidas who at the time of conception were smoking (n = 404, 46.3%). MAIN RESULTS: At the first antenatal visit (63.6% (n = 257) of the prepregnancy smokers were still smoking (a total smoking prevalence of 29.5%). The pregnant smokers were on average younger and had a lower educational level. The highest relative risk (RR) of continued smoking was found among unmarried women RR 2.7 (95% confidence interval) (1.5, 4.8), women having unplanned pregnancies RR 2.2 (1.2, 4.0) and those with a low social participation RR 1.6 (1.0, 2.7), low instrumental support RR 2.6 (1.2, 6.0), low support from the child's father RR 2.1 (1.0, 4.2) and those exposed to job strain RR = 2.3 (1.1, 4.8). The associations were independent of potential confounders such as age, educational level, nationality, cohabiting status, passive smoking, and previous years of smoking. CONCLUSIONS: This study supports the stress hypothesis. Smoking can be one way women handle stress when demands become too great. In order to reduce smoking among pregnant women, maternity centre resources need to be focused more on women with low psychosocial resources who are at highest risk for continued smoking. It is also important to involve actively the woman's partner or other important people in the woman's social network.
Abstract: We examined the apparent value of questions of functional status and mental score in determining the risk of hip fracture from a large retrospective case--control study undertaken in six countries. Of nine questions utilized in 75% of the MEDOS study population, four questions were found to be statistically significant and independently related to the risk of hip fracture. From this an additive score was devised with three points for not being able to wash or dress, six points for not knowing one's age, and ten points for not knowing the day of the week, which gave a gradient of risk of 5.7 when categorized into quartiles. Similar gradients of risk were observed in all countries. A less than perfect score was associated with a specificity of 79% and sensitivity of 46%, comparable to the power of bone mineral density measurements. The risk factor score accounted only partially for the increase in risk associated with dementia, cardiovascular accidents and parkinsonism. We conclude that the steep gradient of risk associated with this simple score should be evaluated prospectively.
Abstract: OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: MalmÅ, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in MalmÅ during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.
Abstract: The role of vitamin D in the prevention of hip fracture is controversial and protective effects appear to be confined to the institutionalized and elderly population. The aim of this study was to assess the interaction of age and body mass index (BMI) on the effects of vitamin D on the risk of hip fracture in the community. We studied 1634 women with low-energy fractures of the hip aged 50 years or older, and 3532 age-matched controls from 14 centres in six Mediterranean countries (the MEDOS study), with a structured retrospective questionnaire. The use of vitamin D supplements was associated with a modest and non-significant decrease in the risk of hip fracture (RR = 0.74; 95% confidence interval (CI) 0.53-1.03; p = 0.07). The risk reduction was influenced by age and body mass. Women aged above 80 years had a significant decrease in the relative risk of hip fracture (RR = 0.63; 95% CI 0.40-0.98) as did women with a BMI below 20 kg/m2 (RR = 0.45; 95% CI 0.24-0.84). Elderly women were more likely to have a low BMI but the elderly did not appear to benefit from vitamin D where their BMI was 20 kg/m2 or higher. The findings could not be explained by differences in sun exposure or in physical exercise. We conclude that the use of vitamin D for the prevention of hip fracture might usefully be targeted to the frail and elderly.
Abstract: A case-control study of 177 premenopausal and 216 postmenopausal breast cancer patients diagnosed in the southern Swedish Health Care Region between 1981 and 1984, and 195 premenopausal and 254 postmenopausal controls randomly chosen during 1984 from the same population by means of a computerized population register was used to estimate the relations among alcohol consumption, cigarette smoking, and the risk of cancer. Cigarette smoking did not seem to be related to the risk for breast cancer among pre- or postmenopausal women. Beer consumption did not show any consistent relation to the risk of breast cancer. An occasional (less frequent than once a week) or a weekly consumption of wine and spirits appeared to be protective compared with abstaining (RRadj = 0.4, 95% CI = 0.3-0.7 for weekly wine consumption, and RRadj = 0.6, 95% CI = 0.4-0.9 for occasional consumption of spirits) among postmenopausal but not among premenopausal women (RRadj = 0.8, 95% CI = 0.7-2.3 and RRadj = 1.0, 95% CI = 0.7-1.8 respectively). The risk estimates were adjusted for differences between cases and controls in age at menarche, age at first full-term pregnancy, age at diagnosis, smoking, and use of exogenous hormones, and for postmenopausal women, age at menopause. The study was based on observations of women with a relatively low exposure to cigarette smoking and alcohol. More frequent exposure or exposure to greater quantities of alcohol and smoking may exhibit different relationships with breast cancer risk.
Abstract: In this study we investigated the importance of social network and social support systems outside the workplace and workload and psychological job strain in former work for the prevalence of daily neck and low back pain. The study population (n = 621) comprised a random half of all male residents in Malmö, Sweden, born in 1914, of whom 500 (80.5%) participated. Two of the social network and social support indices (social anchorage and availability of material and informational support) were independent of life-style factors (leisure time physical activity, smoking and alcohol consumption) related to daily neck and back pain after retirement (OR = 2.0, 95% CI 1.2-3.4 and OR = 1.7, 95% CI 1.0-2.7, respectively), while the psycho-social and physical factors in former work were not. As no conclusion about the direction of the association can be drawn, prospective studies are needed to further explore these findings.
Abstract: BACKGROUND: Treatment of endometrial carcinoma has not improved during the last decades, due to the already good results. Such therapy has been a compromise, strong enough to cure some of those in need of harder treatment, but weak enough not to cause too severe side-effects. One way of solving the problem of overtreatment is to identify those in real need of a harder regimen. Generally, the histopathologic picture and the depth of myometrial invasion of the tumour have been used. However, this often means a too large high-risk group, often exceeding 50% of the patients. METHODS: Steroid receptor concentrations and later DNA-measurements have been increasingly used to identify high-risk groups not, however, in combination. In 156 patients with endometrial carcinoma, both estradiol receptor concentration and flow cytometrically estimated DNA content were measured on all patients and the patients were followed-up for over five years. RESULTS: By using the number of DNA-populations (ploidy) we could identify a small high-risk group (28%) with a death frequency of 35%. This small group could be further divided, by using the estradiol receptor concentration, into an extremely small high-high-risk group (11%) consisting of 17 patients of whom 9 died from the disease within 5 years, almost all of the deaths occurring within 2 years. CONCLUSION: Thus histopathology was reduced to merely identifying cancer but DNA- and estradiol receptor measurements in combination could identify an extremely small high-risk group, with almost all deaths occurring within 2 years.
Abstract: This study describes the operation of an in-home alarm system in seven Swedish municipalities. Statistics on the diffusion of this technology, its costs, and the characteristics of its use are reported. Alarms were triggered by 60% of the users. Mean annual costs per recipient varied from SEK 1,985 to SEK 8,215, mainly reflecting different patterns of use.
Abstract: Patients with clinically node negative resectable breast cancer were randomized to either mastectomy only or radical mastectomy and radiotherapy, and followed for 15-20 years. During follow-up axillary metastases occurred with the same frequency after mastectomy as was initially observed in the group that underwent axillary dissection. There was no significant survival difference between the two groups. When adjusting the treatment effect for differences in age, tumour size, lymph node metastases, and histology, the outcome after radical mastectomy plus irradiation was significantly inferior. Comedo carcinoma proved also in this study to carry a poor prognosis.
Abstract: BACKGROUND. In a study of 2290 cases of invasive breast cancer in Malmö, the prognostic value of histologic typing and axillary nodal status was examined. Two periods were studied: Period 1, 1961-1970, and Period 2, 1981-1988. METHODS. All primarily unilateral invasive breast cancers were included in the study and classified according to the histologic classification proposed by Linell et al. and Linell and Ljungberg (the Linell-Ljungberg classification), which includes a histologic grading of ductal carcinoma based on content of tubular structures. From Period 1, the tumors were reclassified. In Period 2, the Linell-Ljungberg classification was used as a clinical routine. Median follow-up in Period 1 was 23 years, and in Period 2, 5 years. Survival was calculated in relation to histologic type and axillary nodal status. RESULTS. The Linell-Ljungberg classification divides invasive ductal carcinoma (IDC) into two groups of approximately equal size: IDC of comedo type, 40% of total; and IDC of tubuloductal type, 30% of total. There was a significantly better survival rate in the tubuloductal group than in the comedo group. In a multivariate analysis, this difference was shown to be independent of axillary nodal status and tumor size. By combining histologic classification with axillary nodal status, one group of patients could be identified containing 90% of patients dying from breast cancer within 5 years of diagnosis and another group with less than 10% risk of dying from breast cancer within 5 years. CONCLUSIONS. Valuable prognostic information can be obtained in a clinical setting from routinely obtained primary prognostic factors in breast cancer: pTNM stage, histologic type, and histologic malignancy grade. This information should be considered the baseline in the clinical evaluation of other more elaborate prognostic factors.
Abstract: In drug utilisation studies, the units of defined daily doses (DDD) and DDD/1000 inhabitants per day standardise for differences in dosage and population size, but not for age-related differences in drug utilisation. There is no consensus as to how age standardisation of DDD data should be carried out. Using cardiovascular drug utilisation data from Sweden and Spain, the current study compared the outcome of different methods of age standardisation. Both indirect methods (based on a comparison of observed and expected drug usage) and direct methods (using different weighting for the age categories) were used. The largest impact of standardisation was seen for diuretics. The crude rate for men and women combined was 26 DDD/1000 inhabitants per day in Costa de Ponent and 98 DDD/1000 inhabitants per day in Värmland. The corresponding figures when standardising the Costa de Ponent population were 26 and 58, respectively. Using the equivalent average rate (EAR) method, the rate for Värmland was 129 DDD/1000 inhabitants per day. Lesser but still important differences were found for beta-adrenoceptor and antihypertensives. Thus, the results of standardisation differ depending on which method is used and which drugs are evaluated. EAR is recommended for direct standardisation because of its ease of use and because it does not require the choice of a standard population.
Abstract: OBJECTIVE--To analyse the relation between treated blood pressure and concomitant risk factor and morbidity from acute myocardial infarction. DESIGN--Prospective longitudinal study. Treated blood pressures and other variables were used to predict acute myocardial infarction. SETTING--Primary health care in Skaraborg, Sweden. SUBJECTS--1121 men and 1453 women aged 40-69 years at registration at outpatient clinics, 1977-81, with no evidence of previous myocardial infarction were followed up for an average of 7.4 years. Subjects were undergoing treatment with drugs to lower blood pressure or had blood pressure that exceeded the systolic or diastolic limits, or both, for diagnosis (> 170/> 105 mm Hg (patients aged 40-60 years) and > 180/> 110 mm Hg (older than 60 years)) on three different occasions, or both. MAIN OUTCOME MEASURES--First validated event of fatal or non-fatal acute myocardial infarction. RESULTS--In men but not in women there was a negative relation between treated diastolic blood pressure and risk of acute myocardial infarction. Left ventricular hypertrophy and smoking were contributory risk factors in both sexes, as was serum cholesterol concentration in men. In men with normal electrocardiograms (n = 345) risk increased with increasing diastolic blood pressure (P = 0.047), whereas the opposite was found in men with electrocardiograms suggesting ischaemia or hypertrophy, or both (n = 499, P = 0.009). In those with a reading of 95-99 mm Hg the relative risk was 0.30 (P = 0.034); at > or = 100 mm Hg it was 0.37 (P = 0.027). No similar relations were seen in women or for systolic blood pressure. CONCLUSION--It may be hazardous to lower diastolic blood pressure below 95 mm Hg in hypertensive men with possible ischaemia or hypertrophy, or both. Electrocardiographic findings should be considered when treatment goals are decided for men with hypertension.
Abstract: OBJECTIVE: To compare the prognostic capability of clinical stage, tumour differentiation, myometrial invasion, age and DNA content in endometrial carcinoma. Then to use the results to identify a small, high risk group suitable for more intensive adjuvant therapy. DESIGN: A prospective five year follow up between June 1980 and June 1987. SETTING: Department of Oncology, gynaecological section, University Hospital, Lund, Sweden. Endometrial tissue was obtained immediately prior to treatment for flow cytometric DNA analysis. SUBJECTS: Two hundred and fifty-one patients referred for treatment. INTERVENTIONS: None. RESULTS: Age, myometrial invasion of greater than 50%, and number of DNA populations (ploidy) were the only significant parameters related to survival. By combining myometrial invasion and number of DNA populations, we divided the patients into four groups. A very small high risk group was identified (7%) with a low survival rate (61%). Two intermediate groups with either myometrial invasion exceeding 50% or with more than one DNA population present constituted 34% of the patients and these had an overall survival rate of 75% and a relatively large low risk group of 59% of the patients (with a survival rate of 95%) was constructed out of those without deep myometrial invasion and demonstrating only one DNA population. CONCLUSIONS: These data suggest that number of DNA populations and depth of myometrial invasion could be combined to identify a small high risk group (7%) with a low survival rate (61%) suitable for adjuvant therapy.
Abstract: STUDY OBJECTIVE--The aim was to survey oral contraceptive usage among women under 25 years of age. DESIGN--This was a cross sectional population study based on information collected by questionnaire mailed to randomly selected individuals. SETTING--The study population consisted of Swedish women born between 1960 and 1964 and living in the southern Swedish health care region which has about one and a half million inhabitants. PARTICIPANTS--The sample consisted of 3477 women, of whom 2573 or 74% agreed to participate in the study and were interviewed between November 1990 and April 1991. MAIN RESULTS--Of the 2573 women participating, 2254 (88%) reported having used oral contraceptives at some time, 77% of them having started during their teens. Teenage start of oral contraceptive use was found to be related to a lower age at menarche, a higher marriage/cohabitation rate, a lower rate of teenage full term pregnancy, a higher rate of spontaneous abortion, a lower frequency of teetotalism, and a higher frequency of smoking. Longterm use of antipsychotic drugs appeared to be less common among women who started oral contraceptive use early, but no relationship with other pharmaceutical drug usage was found. No relationship was found between oral contraceptive use and the presence of a first degree relative with cancer. CONCLUSIONS--A large proportion of Swedish women start using oral contraceptives during their teens, and report long duration of usage both before their first full term pregnancy and before the age of 25 years. The few women who have never used oral contraceptives do not appear to be representative of the general population.
Abstract: Stroke incidence was analysed in a Swedish cohort of male (n = 1428) and female (n = 1812) hypertensive patients in comparison with age- and sex-matched population controls (1:1) and with normotensive untreated subjects (1249 men and 1247 women). Mean follow-up was 8.3 years. Patients were aged 40-69 at the start of follow-up in 1977-1981. Relative risks (95% confidence interval [CI]) for stroke morbidity were 1.63 (1.16, 2.29) for men and 1.40 (0.94, 2.09) for women compared to population controls. Corresponding figures for stroke mortality were 1.96 (1.01-3.82) and 1.48 (0.71-3.06). Compared to the normotensive sample with adjustment for smoking and body mass index relative risks for stroke morbidity were 3.07 (1.96-4.80) for men and 2.56 (1.46-4.51) for women. The prognosis of treated hypertension with respect to stroke is better than anticipated from previous studies, a fact that should be considered when treatment guidelines are developed.
Abstract: The risk of hip fracture is higher among persons living in long-term care than among persons living at home. The aim of this study was to explain the difference in risk between the two types of residence by identifying differences in the respective risk factor profiles. Information from the Mediterranean osteoporosis (MEDOS) study questionnaire was used for statistical analyses of 107 non-demented female cases and 225 neighbourhood controls matched for age, sex, and residential area. The statistical analyses incorporated adjustments of the risk estimates by unconditional multivariate logistic regression. Urban background, activity, and morbidity were found to differ between the two types of residence. The detected differences in risk factor profiles were, however, not considered to be sufficient as an explanation for the difference in risk of fracture.
Abstract: The Skaraborg Hypertension Project was undertaken in 1977-1981, and 1428 male and 1812 female hypertensives aged 40-69 years were involved at hypertension out-patient clinics in primary health care. Their long-term risk of acute myocardial infarction during a follow-up of 8.3 years was compared to that of age- and sex-matched controls drawn from the census register at the beginning of surveillance and to normotensive untreated controls identified in a population survey in 1977. Relative risks (with a 95% confidence interval) for acute myocardial infarction morbidity compared to the population was 0.99 (0.78, 1.25) in men and 1.36 (0.95, 1.94) in women. Corresponding figures for acute myocardial infarction mortality were 0.97 (0.68, 1.38) and 1.15 (0.67, 1.99). With normotensive controls used as reference and adjusting for smoking habits and body mass index, the relative risks for acute myocardial infarction morbidity were 1.48 (1.12, 1.98) in men and 2.34 (1.43, 3.85) in women, and for acute myocardial infarction mortality 1.66 (1.07, 2.57) and 1.71 (0.84, 3.48), respectively. Treated hypertension is a weak risk factor for acute myocardial infarction in unselected hypertensive patients.
Abstract: In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA-IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities.
Abstract: In the evaluation of a hypertension treatment program, the end-point surveillance included incidence of acute myocardial infarction and acute stroke identified from hospital in-patient registers and the national mortality register. To ascertain the validity, in-patient records containing the ICD-codes 410-411 and 430-438 were validated. First event of acute myocardial infarction and acute stroke suggested in the in-patient register could be confirmed in 96% and 94%, respectively. In-patient diagnoses of suspected acute myocardial infarction or other acute or subacute ischemic heart diseases, transient ischemic attack and unspecified heart diseases, transient ischemic attack and unspecified cerebrovascular disease revealed high proportions of what in fact turned out to be definite events (11%, 24% and 53% respectively). It is concluded that disease ascertainment for this cohort study claims validation of register data with hospital records.
Abstract: OBJECTIVE: To analyse the outcome of selective management of patients with abdominal aortic aneurysms, the expansion patterns of the aneurysms, and the factors that influenced the rate of rupture. DESIGN: Retrospective study. SETTING: Malmö General Hospital, Lund University, Malmö, Sweden. SUBJECTS: 155 patients (96 men and 59 women) with abdominal aortic aneurysms who were not selected for operation for whatever reason were included in the study immediately after their first ultrasound scan. MAIN OUTCOME MEASURES: Mortality, expansion rate (mm/year) measured on ultrasound scan, and rate of rupture of aneurysm. RESULTS: Median aneurysmal diameter was 40 mm (range 20-80), and length (n = 106) 70 (range 28-140). The patients were followed up for a median of 3.4 years (range 0-10.2). A total of 107 patients died and in 21 the aneurysms ruptured (4 were operated on and survived). Thirteen patients were re-evaluated and operated on electively. Ultrasonography was repeated in 98 patients, the median expansion rates (mm/year) were 3.1 (diameter) and 1.9 (length). There was a significant linear relationship between initial size (diameter and length) and rate of expansion of diameter. The risk of rupture was greater in larger aneurysms that were expanding more quickly. The cumulative mortality was not affected by the 21 aneurysms that ruptured. CONCLUSION: Selective management of patients with aortic aneurysms is justified.
Abstract: The tumor growth phenotype was characterized in relation to concentration of circulating estradiol, estradiol receptor (ER) activation and progesterone receptor (PgR) induction. Ten tumor pieces from an ER and PgR positive human endometrial adenocarcinoma grown in non-oophorectomized nude mice for one year were randomly selected to grow during a preparation phase of 4 weeks either in oophorectomized nude mice - to adapt tumor growth to the absence of estradiol (group A), or in non-oophorectomized nude mice (group B). For the experimental phase, tumor pieces from each group were again randomly assigned to either of two subgroups (i.e., 4 subgroups in all): with estradiol treatment (subgroups A+ and B+), or without (subgroups A- and B-) as control subgroups. There were no differences in take rate or tumor growth rate between the control subgroups (A- vs. B-), indicating tumor growth to be estradiol-independent. The tumor was estradiol-sensitive, however, as tumor growth could be stimulated by estradiol. Despite its estradiol-independence of growth, the tumor's estradiol-binding capacity varied according to whether the host animals were oophorectomized or not; and despite the similar growth patterns during the experimental phase, the values of high affinty bound ER (ER activation) were greater for tumors grown in non-oophorectomized mice during the preparation phase than for those grown in oophorectomized mice. Thus, our findings show that an ovarain (estradiol) independent but responsive phenotype of tumor growth is present in human endometrial adenocarcinomas growing in nude mice. This growth phenotype may represent an intermediate state of tumor progression to hormone independence and resistance, which has hitherto been observed only in rodent tumors.
Abstract: During a 9-year period, 92 women with squamous cell carcinoma of the cervix, FIGO stages IA1-IIA, were subjected to primary surgery according to Wertheim Meigs. Grading according to a malignancy grading score (MGS) and evaluation of tumor size before surgery together with surgical findings of positive nodes or insufficient surgical margin at the primary site were used to identify persons prospectively at high risk for relapse. Twenty-five women thus received postoperative treatment. Results among node-positive patients were good; only 2 out of 12 patients relapsed. Among 67 node-negative patients in stages IA2-IIA, 4 relapses occurred. These 4 patients had greater than or equal to 16 risk points according to MGS, but small tumors. Instead of tumor size, supplementary risk factor is therefore needed. Among the few patients in stage IA1, no high-point patients relapsed. These patients would probably have done just as well with less-extensive surgery.
Abstract: In general, findings in studies on oral contraceptives (OCs) and breast cancer have not indicated prognosis to be worse among users of OCs. In few studies, however, has age at the start of OC usage been considered as a prognostic factor. In the present study, prognosis in breast cancer is compared with OC usage, particularly with age at the start of OC usage, among 193 consecutive patients at the Department of Oncology, University Hospital, Lund. An earlier series of 193 breast cancer patients at Malmö General Hospital is included for comparisons. In the Lund series, five-year survival was 62% among women who started to use OCs before the age of 20.78% among those who started to use OCs between the ages of 20 and 25, and 86% among non-users and those who started to use OCs after the age of 25 (p = 0.009, test for homogeneity). Although age was found to be a prognostic factor in the Lund series (RR = 0.90, p = 0.001), this was not so in the earlier (older) Malmö series. The relationship with age differed significantly between the two series (p = 0.003), suggesting the apparent effect of age at diagnosis to be a cohort effect due to the introduction of OCs during the 'sixties. The age-specific relationship between survival and OC usage would seem to indicate the presence of a biological mechanism in which OCs may participate during precancerous and early stages of breast cancer.
Abstract: In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at less than or equal to 20 years of age) than among nonusers or late users (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1-5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3-51.7; and OR, 18.6; 95% CI, 2.2-165.8, respectively). No significant relationships were found between proto-oncogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible.
Abstract: To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.
Abstract: The rate of lead elimination in blood by occupationally exposed individuals has been studies using a compartment model with three exponential terms. The analysis of data by exponential regression leads to numerical problems. It is often a difficult task to decide how many measurements should be performed, the length of the observation period, and how the observations should be distributed to get high accuracy. In a simulation study, the sensitivity of the parameter estimates was investigated as a function of these three factors. The effects of missing observations in some interval was also studied. It is shown that a too short observation time leads to a relatively high frequency of outliers in the estimated values of all three half-times. It is also shown that missing values in one compartment affect the parameter estimates of that and faster compartments. The results obtained can be used as a help to decide what experimental accuracy is needed for a given accuracy of compartment model parameters for a variety of medical and biological problems.
Abstract: In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.
Abstract: We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.
Abstract: The combination of cisplatin (90-120 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/day in continuous infusion for five days) was given for 2-3 cycles, prior to combined radiotherapy and surgery, to 73 patients with esophageal squamous cell carcinoma, 60 with limited disease (LD), and 13 with extensive disease (ED) (i.e. with metastasis) of whom 3 had recurrent disease. Before preoperative radiotherapy among 60 LD patients, 12 (20%) had complete response, 21 (35%) partial response, 25 (42%) had stable disease, and 2 (3%) progressive disease. Swallowing was improved in 35/73 (48%) of the cases. In the resected specimens, no tumor was found in 8/53 (15%) of the cases, microscopic tumor in 18/53 (34%) and macroscopic tumor in 27/53 (51%). In the ED group, complete response of distant metastases was obtained in 6/13 (48%) of the patients, one of whom is still alive with no evidence of disease 62 months after the start of treatment.
Abstract: The ciliated epithelium of the rabbit trachea was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose: 2, 6, 10, 16, or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-diamminedichloroplatinum (cis-DDP) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of ciliary damage, from blebs on the cilia to swollen tips, broken and bent cilia and finally an epithelial injury with areas free from cilia, and a surface covered with microvilli-like structures. SEM also showed cell loss, and remnants of dead cells on the surface together with detritus. By transmission electron microscopy (TEM), ciliary damage, cell death and cell loss of the ciliated cell layer, as well as exfoliation of portions of goblet-like cells on the surface, could be confirmed. Scoring of SEM and TEM micrographs showed that for the tracheal part treated with cis-DDP and radiation, the maximal damage was expressed in the dose group 10 Gy, and above this no further increase in the average reaction occurred. For the part of the trachea only exposed to cis-DDP, the damage increased with the dose. The difference observed speaks for an accelerated proliferation exerted by the radiation.
Abstract: The Mediterranean osteoporosis study (MEDOS) questionnaire was designed by a group of specialists in bone disease from Southern Europe (MAB Group) and the WHO Collaborating Centre for the Epidemiology of Rheumatic Conditions, assisted by experts from WHO in Geneva and from the European Foundation for Osteoporosis and Bone Disease. The purpose of the questionnaire was to identify putative risk factors for hip fracture in a retrospective case control study applied during a prospective study of the incidence of hip fracture in 14 regions of Europe.
Abstract: In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively). The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors. Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03). Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF. Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis. Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy. For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening. The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.
Abstract: Using the Cox proportional hazards model, and considering tumour necrosis and vascular invasion by tumour as additional factors in assessment, a series of 88 patients with primary Grade III and IV soft tissue sarcomas of the locomotor system was analysed for factors associated with death due to the tumour. Grade IV malignancy, a tumour size larger than 10 cm., tumour necrosis, and vascular invasion by tumour cells were significant risk factors. Patients with 0 or 1 risk factor, one half of the cases, had a 3 year survival rate of more than 90%, whereas the figure was 65% for those with 2 risk factors and 20% for those with 3 or 4 risk factors.
Abstract: The national Swedish cancer registry was used to analyse the age-specific time trends in breast cancer incidence in Sweden from 1970 to 1984. The analysis included both a calendar year and a birth cohort approach to estimate time trends in disease occurrence. According to the birth cohort approach there was a statistically significant increase in the incidence with an average annual increase of the incidence of 3.2% (P = 0.0114), 3.4% (P = 0.0002) and 2.2% (P = 0.0264) in the age groups 25-29, 30-34 and 35-39, respectively. Possible causes of the observed increasing incidence are discussed.
Abstract: The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.
Abstract: Women with malignant lymphoma, non-Hodgkin's lymphoma and Hodgkin's disease were of a significantly later age at first full-term pregnancy (AFFP) than controls without malignant disorders. The odds ratio (OR) of having the first pregnancy at 30 years of fertility was 6.4 for women with malignant lymphoma. This ratio was higher than the ratio of 3.9 in a group of breast cancer patients. A low parity in the lymphoma group enhanced the risk associated with a late AFFP.
Abstract: The Skaraborg Hypertension Project is a 5-year trial testing the impact of structured hypertension care implemented in half of the country, the other half serving as control. Population investigations revealed improved blood pressure control in all treated hypertensives in the study area, blood pressure reduction averaging 2-5 mmHg. The primary trial hypothesis of a possible impact on stroke incidence in the community was tested in this study. Cases of fatal and non-fatal stroke were identified from local and national mortality and morbidity registers, and diagnoses were validated against medical records. Of an initial 1169 reported cases, 1097 proved to be true stroke after validation. A statistically significant difference in stroke incidence trends (fatal and non-fatal) between the study and control populations was identified (P = 0.0251). Improved hypertension control in the study area seems the most plausible explanation for the relative decline in stroke incidence in the study area.
Abstract: Gonadal and hypophyseal hormones were investigated in 15 males with breast cancer and 15 tumour referents, on average 1 month postoperatively. Plasma prolactin was found to be significantly more often elevated in men with breast cancer compared with referents (p less than 0.005). Another group of men with breast cancer disclosed a tendency for lower S-FSH levels compared with the referents (p less than 0.01). No significant difference was seen between cases and referents regarding S-LH, p-estradiol or p-testosterone. The size of the primary breast tumour was correlated with a higher prolactin level. The findings lend support to a theory implicating prolactin and possibly prolactinomas as a risk factor for the disease in males.
Abstract: Total gastrectomy and oesophagojejunostomy with linear stapling devices were performed on 22 pigs to evaluate whether intersecting staple lines reduce the blood flow with an increased risk of anastomotic leakage. The blood flow at intersecting staple lines and single row staple lines of the anastomosis was studied with the reference organ method 24 h after the first operation. The mean blood flow in intersecting staple lines was 0.305 ml min-1 g-1 tissue and 0.307 ml min-1 g-1 tissue for single row staple lines. The confidence interval for the reduction in blood flow for intersecting staple lines compared with non-crossing staple lines was from -16 to +17 per cent. In one animal the reduction in blood flow was 37 per cent; in all other animals there was no reduction in blood flow or a reduction less than 25 per cent. An equivalence test shows that if a reduction in blood flow exists it is most likely to be less than 30 per cent (P less than 0.001). Our data confirm that intersecting staple lines in oesophagojejunal anastomoses do not reduce mean anastomotic blood flow to a dangerous level.
Abstract: The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
Abstract: Two-hundred and forty adult patients with a high-grade soft tissue sarcoma were treated surgically in 18 hospitals participating in the Scandinavian Sarcoma Group Protocol I. The patients were randomized to either postoperative doxorubicin or control; patients whose surgical margin was judged marginal also received radiotherapy. The outcome after different surgical margins was analyzed in 185 tumors of Grades III or IV in the extremities. The total cumulative local tumor control was 91 percent (168 of 185) after a median of 47 months. The cumulative local control rates in the surgical groups were: compartmental or wide amputation--37/37 (100 percent), compartmental local excision--23/24 (96 percent), wide local excision--77/84 (92 percent), marginal excision and radiotherapy--19/21 (90 percent), and marginal excision alone (reevaluated margin)--12/19 (63 percent, significantly lower than others). The risk of local recurrence was 13 times higher after marginal than after compartmental surgery (P = 0.02) and 3 times higher if the tumor was larger than 10 cm (P = 0.05). The treatment with doxorubicin did not influence the risk of local recurrence. The survival rates did not differ significantly in the groups.
Abstract: During six years 188 consecutive patients with gastric carcinoma admitted to the Department of Surgery, University Hospital, Lund, were followed up to evaluate clinical as well as histopathologic factors which might be important to predict postoperative survival. We also introduced a new histopathologic scoring system based on nine different parameters. Radicality estimated by the surgeon, resection line margin, score at histologic grading and TNM were factors which in a multivariate analysis strongly correlated to survival.
Abstract: 149 patients with carcinoma of the esophagus treated with radiotherapy were evaluated. Eighty-one patients had treatment with palliative intent and 68 with curative intent. The 4-year actuarial survival was 1 and 5% respectively. The tumor size, Karnofsky index (KI) and radiation dose were prognostic factors. The duration of palliation of the patients dysphagia was dose-dependent.
Abstract: The interaction between estradiol and its receptor in human endometrial adenocarcinoma was investigated in a human tumor-nude mice model. Estradiol treatment was found to activate estrogen receptor (ER), estimated through the measurement of ER in the nuclear fraction. The receptor activation in the tumors was significantly higher in tumors previously treated with estradiol than in previously non-treated tumors. The activation seems also to be dependent on the estrogen dose. We concluded, that previous influence of estradiol may change the sensitivity of estrogen receptor positive tumors for its hormone, and therefore the measurement of the receptor content alone does not seem to be a sufficient marker for the prediction of the receptor activation process.
Abstract: In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.
Abstract: From 1981 to 1986, 240 patients with primary, malignancy grade III or IV soft-tissue sarcoma were entered into a randomized adjuvant chemotherapy multicenter trial, conducted by the Scandinavian Sarcoma Group. After a median follow-up time of 46 (2-97) months, a multivariate analysis of risk factors for metastases was performed in 138 radically operated on patients with tumors of the extremities. Adjuvant single-agent doxorubicin did not improve the metastasis-free survival. Histologic malignancy grade IV, tumor size greater than 10 cm, vascular invasion by tumor, and male sex were identified as risk factors. Patients with no or one risk factor had a 5-year metastasis-free survival of 0.7, with two risk factors 0.5, and with three or four risk factors 0.2. The combination of different risk factors provides a prognostic model for soft tissue sarcomas, which could be a basis for therapeutic trials.
Abstract: Eighty-seven workers exposed to asbestos in a railroad car repair shop, with characteristic asbestos-induced pleural plaques, underwent extensive lung-function examination. Vital capacity (VC) showed the greatest reduction among the static lung volumes, with an asymmetrical distribution of one-fourth of the subjects below 80% of the predicted value. Logistic regression demonstrated VC to be sufficient for optimal discrimination of asbestos-exposed subjects from a group of matched controls. No further discriminatory power was gained by additional spirometric measures, lung mechanics, blood gas analysis, or diffusing capacity. Smoking had an influence on dynamic but not on static lung volumes. In conclusion, reduced static lung volumes among smoking asbestos-exposed workers with pleural plaques should, in the absence of other lung diseases, be mainly attributed to the asbestos exposure.
Abstract: Increased volume of trapped gas (VTG) was found in 87 asbestos-exposed railroad repair shop workers, divided into three subgroups according to smoking habits. All the examined subjects had pleural plaques. Determination of VTG was used to study function of small airways. Increased VTG was found among asbestos-exposed smokers as well as nonsmokers. In both groups the VTG:TLC ratio was elevated compared with controls. Increased VTG is a sign of small airways dysfunction. In asbestos-exposed subjects, it might be caused by an early peribronchial reaction to inhaled asbestos fibers.
Abstract: Sixty-six patients with squamous cell carcinoma of the esophagus were treated with combined surgery and radiotherapy, mostly in a sandwich fashion. Fourteen patients received misonidazole during preoperative radiotherapy. Prospective cumulative survival at 1, 2, and 5 years was 60%, 35%, and 17%, respectively. Original biopsy specimens and operation specimens were evaluated according to a histopathologic grading system based on an evaluation of the tumor cell population in terms of cell differentiation, structure, nuclear polymorphism, and the frequency of mitotic figures. The tumor-host relationship was also estimated by the mode of invasion, stage of invasion, vascular invasion, and degree of lymphocytic infiltration. A multivariate regression analysis according to Cox and actuarial survival were used to determine the relative contributions of the clinical and histopathologic parameters to patient outcome. The major results were as follows: (1) patients who were old (70 to 80 years) fared as well as younger patients (P = 0.9198); (2) tumor site did not influence therapeutic outcome (P = 0.1100); (3) there was an insignificant difference in survival between patients with M0 and M1 disease (P = 0.7130); (4) radical surgery gave better survival; (5) misonidazole administered preoperatively was associated with worse survival (P = 0.0147); and (6) the histopathologic malignancy grading score system was very useful for prognostication--the tumor-host score in the operative specimen was the strongest of all analyzed predictive parameters. Since palliation was excellent in all patients treated in the combined fashion, selection criteria should be wide for such a program, not the least since long-term survival is possible also for patients with very advanced tumors.
Abstract: STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.
Abstract: The survival of 193 premenopausal breast cancer patients was investigated in relation to their history of early use of oral contraceptives. The women were born in 1939 or later and diagnosed in the southern health care region of Sweden. Women, who had started their oral contraceptive use (OC-use) before 20 years of age had a significantly lower survival rate as compared with those who had never used OC and late users (p = 0.02 and = 0.04 respectively, generalized Wilcoxon test). For women who started OC-use between 20 to 25 years of age, a tendency for a shorter survival was seen in comparison with women who had never used OC (p = 0.18). For all patients simultaneously, the relative risk adjusted for age at diagnosis increased for earlier OC-start. When only stages II and III were considered in a stratified multivariate model, a significantly elevated risk was seen for early users of OC irrespective of age or of adjuvant treatment given. The estrogen and progesterone receptor concentrations of the primary tumor were significantly lower among early users (p = 0.001 and p = 0.05 respectively).
Abstract: On the basis of information obtained from a population-based cancer registry in Sweden, male patients with breast cancer (n = 95) were found to have experienced significantly more brain concussions and skull fractures than male patients with lung cancer (n = 383) or malignant lymphoma (n = 69). Other risk factors significantly associated with breast cancer among men were drug treatment associated with prolactin elevations, radiation treatment, family history of breast cancer among first-degree relatives, a history of gynecomastia, gonadal injury, and treatment for inguinal hernias. The results confirm some previously described risk factors for male breast cancer and suggest that events elevating plasma prolactin (e.g., drugs, brain concussions, and skull fractures) and events predisposing for inguinal hernias may be new risk factors for the disease. Using hospital charts is likely to underestimate exposure for different risk factors; therefore, the results need to be confirmed in studies that directly retrieve information. However, such studies are difficult or impossible to undertake in most countries because the disease is so rare.
Abstract: The cytogenetic findings in samples from 106 patients with non-Hodgkin lymphomas (NHL), histopathologically classified according to the Kiel classification, have been correlated with survival time. Clonal chromosomal abnormalities were found in 60 patients, and only normal karyotypes in ten. The chromosome analysis of the remaining samples failed. The failures did not differ in survival compared with the cytogenetically successful cases, indicating that this group is not a prognostic entity within NHL. The cytogenetic findings were classified in six ways in order to evaluate the prognostic value of the cytogenetic pattern. Multivariate analysis demonstrated that presence of clonal chromosome abnormalities and the number of aberrations both were important prognostic factors independent of histopathology, whereas, the modal chromosome number, presence of translocations, or unidentified marker chromosomes were not. Some characteristic chromosome abnormalities were correlated with survival time: Patients with a 1p+ marker or +7 had a significantly shorter survival time than patients with normal karyotypes only (NN). Patients with +3, +12, 6q-, i(17q), and t(14;18)(q32;q21) did not differ significantly from the NN group.
Abstract: Flow cytometry was used for the investigation of the DNA distribution in biopsy specimens from 72 patients with squamous cell carcinoma of the uterine cervix. A prospective grading score system using tumor cell parameters and tumor host parameters was also applied. 50% of the tumors were aneuploid with up to 4 different tumor populations. The definition of DI +/- 8% was applied. The median age of the patients was 61 years with FIGO median value of 2B. Significant correlations were observed between ploidy and MGS-scores and stage stadium according to FIGO. Increasing MGS score was noted with increasingly distorted ploidy. No significant difference was found between DI below and above 1.5 for MGS, FIGO stage stadium, histology according to Ackerman, tumor parameters and tumor host parameters for the total material. However, for aneuploid tumors MGS and tumor cell parameters were related with DI below and above 1.5 (P = 0.05 and P = 0.02, respectively). No correlation between clinical stage according to FIGO and S-phase % was noted. It remains to be settled to what extent DNA flow cytometry and MGS-scoring in our ongoing prospective series of invasive squamous cell carcinoma of the uterine cervix can take their place in the multifactorial prognostic index suggested by Jacobsen et al (Am. J. Clin. Oncol. 8: 39, 1985).
Abstract: Measurements were performed at 37 degrees C on 49 fresh samples excised from cancerous (n = 16) or non-malignant (n = 33) thyroid tissues of 23 patients. They were carried out for protons at a frequency of 10.7 MHz with pulse sequences (90 degrees-t-90 degrees) and (90 degrees-t-180 degrees-t) for T1 and T2 respectively. The estimates were correlated to histopathology with quantitative measurements of the proportions of colloid, thyroid epithelium, fibrosis, and haemorrhage tissue. Discriminant analysis of malignant and non-malignant tissues using T1 and T2 values, was not successful. T1 and T2 values were correlated to each other. Both were correlated to the proportions of water, thyroid epithelium and haemorrhage and inversely correlated to the amount of colloid. Multiple regression analysis revealed that T2 values were more tissue-specific than T1 values. The analyses indicate possibilities to identify different thyroid tissues by magnetic resonance imaging, especially by T2 weighted MR images.
Abstract: Six hundred and forty-four patients with primary malignant tumours of the female genital tract were subject to a two-stage screening program on admission, with clinical examination in all and mammography in 380. Clinical examination alone revealed 4 cancers, while supplementary mammography screening of 369 patients with normal clinical examination revealed an additional 6 tumours, of which 5 were invasive. The prevalence rate was about three times that found in two mass-screening programs in different parts of Sweden. Thus, it could be concluded that there is an increased risk for mammary carcinoma in patients with gynaecologic malignancies. It seems reasonable therefore, to recommend mammography routinely in this group of patients.
Abstract: The sum of two exponential functions was fitted to the decay of blood lead (PbB) level after the end of lead exposure. For two subjects who had not formerly been occupationally exposed to lead but who had been exposed to a single short heavy dose, the fast compartment (probably soft tissues) had a biological half-time of 27 and 44 d, respectively. For 20 lead workers after the end of occupational exposure, the corresponding median was 29 (range 7-63) d. For 21 ex-lead workers, the median biological half-time of the slow compartment was 5.6 (range 2.3-27) years. There was significant interindividual variation in both the fast and the slow half-time. This finding probably means a considerable variation in risk at a certain exposure level. In the lead workers, the PbB fraction corresponding to the slow compartment had a median as high as 1.8 (range 0.7-2.7) mumol/l, which constituted more than half of the total PbB. This fraction was associated with exposure history, and with the lead level in the skeleton, the latter determined in vivo by an X-ray fluorescence method. The data thus indicate a rather rapid turnover of the skeletal lead pool, a phenomenon which may affect the PbB level considerably.
Abstract: In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.
Abstract: Histological slides from the lungs of 89 dead asbestos cement workers have been examined with respect to ferruginous bodies and fibrosis. The results have been compared with individually matched controls with no known exposure to asbestos, and related to asbestos exposure, expressed as duration of exposure and cumulative asbestos dose, and smoking habits. The asbestos cement workers studied had been employed for on average 15 years, with a mean cumulative dose of 26 fibre-years per ml (f-y/ml). Clear dose-response relations between exposure (duration of exposure and cumulative asbestos dose) and level of ferruginous bodies were found. An association was evident already at a low cumulative dose (1-10 f-y/ml). Fibrosis was more common and more pronounced among the exposed workers than among controls. An association between ferruginous bodies and fibrosis was also found. Among the controls, but not among exposed workers, there was an association between smoking history and fibrosis.
Abstract: Multicenter clinical trials are often large and complex, involving many institutions and investigators. The organizational structure is of vital importance in conducting and coordinating such trials. The present article describes the organization of a multicenter trial of adjuvant therapy of breast cancer. The trial is conducted since 1978 and involves all 15 hospitals in the Southern Swedish Health Care Region. The paper also describes methods of determining patient accrual rate, compliance with entrance criteria, diagnostic procedures, treatment, and follow-up. Comparison of data obtained from a population-based regional tumor registry revealed an accrual rate of more than 80%. Compliance with entrance criteria varied between the treatment groups from 85% to 97%. No patients were lost to follow-up. Compliance with diagnostic procedures and treatment was generally good. Reporting of recurrences was in accordance with data from patients' records in 98% of patients. One hundred thirteen patients died during the first 5 years of study. Twenty-one of these deaths were not reported to the secretariat. This strongly illustrates the necessity of matching to a population register before presenting data of such trials.
Abstract: A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. No rise in death rates was observed for asthma, bronchitis or emphysema, in spite of other evidence of a high risk of occupational asthma, due to exposure to piperazine. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time of at least 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time of at least 15 years was used. A case-referent study within the cohort did not reveal any significant association between any specific chemical exposure and cancer morbidity.
Abstract: Blood-lead levels were determined, each summer during the period 1978-1984, in children from Scania in Southern Sweden. A total of 1395 determinations were made. The average blood-lead concentration was 55 (range 14-250) micrograms 1(-1). There was a statistically significant decrease over time, both in rural and urban areas, averaging about 4 micrograms 1(-1) per year. Lead exposure has thus decreased remarkably. One possible explanation is the contemporary, considerable reduction of the alkyl lead content of petrol.
Abstract: All 72 resections for colorectal liver secondaries during the period 1971-1984 were analysed retrospectively. Liver tumours were single in 35 (49 per cent), unilateral in 55 (76 per cent) and associated with extrahepatic disease in 12 (18 per cent) patients. Operative mortality was 5.6 per cent. With respect to the disease in the liver, the presence or absence of four or more metastases was the predominant prognostic determinant with a 5 year survival rate of 20 per cent in patients with less than four liver tumours, and no 3 year survivor among patients with four or more tumours. When the number of liver tumours was less than four, the prognosis in patients with unilateral disease was not significantly better than in patients with bilateral disease (P = 0.19). No other liver disease variable seemed to play any role in the prognosis. Extrahepatic disease was associated with a poor prognosis and no 5 year survivor. The length of the tumour-free resection margin was the only treatment variable that varied with the outcome: a resection margin of less than 10 mm was followed by a poor survival. Variables that did not influence survival included uni- or bilateral disease, liver tumour volume, tumour size, type of liver resection, Dukes' classification, differentiation of the primary tumour and synchronous or metachronous disease. It is concluded that resection for liver colorectal secondaries is indicated when there are less than four liver tumours, even if bilateral, no extrahepatic disease is present, and a resection margin of at least 10 mm can be obtained. It should not be performed unless all of these requirements are met.
Abstract: The European Organization for Research on Treatment of Cancer (EORTC) Thyroid Cancer Cooperative Group presented a prognostic index in 1979 that included all histologic groups of thyroid carcinomas, and was based on a multivariate analysis of 507 patients with a median follow-up of 40 months. The current report not only uses a multivariate analysis to study the clinical validity and reproducibility of this index on case material consisting of 226 differentiated thyroid carcinomas with a considerably long follow-up (11 years), but also it investigates possible prognostic factors, other than those proposed by the EORTC. Three EORTC variables could be reproduced as important: age at diagnosis, locally advanced disease, and distant metastases. Of the additional histopathologic variables tested, microscopic tumor invasion beyond thyroid capsule (pT4) and marked cellular atypia (MCA) proved to be significant. When the effect of the age-correlated tumor factors pT4 and MCA of differentiated thyroid carcinomas were taken into consideration, age alone lost its prognostic importance as a guide for treatment.
Abstract: In a prospective study, 270 women who gave birth to infants weighing greater than or equal to 4500 g (large baby, LB) underwent an oral glucose tolerance test (OGTT) within the first week of the puerperium. Of these women, 179 (66.3%) were retested 3-10 yr later, and 236 (87.4%) were also evaluated 20-27 yr later. The frequency of pathologic OGTTs increased with time, but the tests were of little prognostic significance for the individual patient. Women who had borne LBs developed non-insulin-dependent diabetes mellitus (NIDDM) six times more often than did a control group of women matched for age and parity and with the same period of follow-up. However, patients who developed NIDDM were also very obese, of high parity, and had a positive family history for diabetes mellitus in a high percentage of cases. Women with LBs as the only risk factor did not develop NIDDM in our study. We conclude that the birth of one LB is of minor, if any, importance in the subsequent development of NIDDM.
Abstract: In a population-based group of women, consecutively diagnosed, with premenopausal breast cancer there was a significant correlation between tumour size and plasma prolactin (r = 0.30; P less than 0.004). The concentration of estrogen receptor was negatively correlated to tumour size (r = 0.17; P less than 0.09). There were no substantial correlations between tumour size and progesterone receptor, plasma progesterone or estradiol. Adjustments for menstrual cycle day and age did not alter the above findings. The ratio of plasma prolactin and estrogen receptor was significantly greater (P less than 0.037) for the group of the patients that had started using oral contraceptives before the age of 20 as compared with the other patients. Consequently, the tumour size was significantly greater in the group of early users (P less than 0.003). The findings indicate that breast tumours developing in previous early users of oral contraceptives have a low estrogen receptor concentration, while these patients have higher plasma prolactin. The tumour size is greater in early users indicating a poorer prognosis than other women with breast cancer. As early use of oral contraceptives increases breast cancer risk and a high ratio of plasma prolactin and estrogen receptor concentration of the primary tumour characterize early oral contraceptive users the ratio may be a valuable marker for the breast cancer risk.
Abstract: A consecutive series of 73 patients treated with intraarterial infusion of 5-fluorouracil (5-FU) for liver metastases from colorectal primary was studied retrospectively using multivariate analysis in order to find determinants of survival. Nontreatment factors had a great impact on variation in survival with liver tumor volume and metastases to lymph glands in the liver hilum as major prognostic determinants. In addition, survival from onset of treatment varied with the interval between the primary operation and the diagnosis of liver metastases. Treatment with intraarterial 5-FU was more effective when administered at long-term (3 months every 6 months) than at short-term (5 days every 6 weeks). Single temporary dearterialization, used as an adjunct to infusion of 5-FU, had a negative impact on length of survival and was followed by a high frequency of complications. The occurrence of hepatic arterial thrombosis was associated with comparatively good prognosis.
Abstract: Nicotinamide is an inhibitor of adenosine diphosphate ribosyl transferase (ADPRT) which is involved in the mechanism of DNA repair after high doses of ionizing radiation. C3H mice with transplanted mammary adenocarcinomas were treated with low doses of nicotinamide, 10 mg/kg, 5 days a week, and in combination with ionizing radiation, 30 Gy, using different drug dose schedules. Mice given nicotinamide in combination with irradiation took a longer time to reach a tumor volume of 1,000 mm3 and a higher complete response rate (i.e. defined as total disappearance of the tumor for at least 7 days) than those given radiation alone. This was true whether nicotinamide was given daily from one week before tumor transplantation until the animal was killed or from transplantation day until day of irradiation. In addition, nicotinamide given per os at a dose between the recommended maximum daily allowance for human subjects (20 mg/70 kg), and the therapeutic allowance (1 g-12 g daily) 5 days a week for 9 weeks, showed a radiosensitizing effect without any histologically detectable damage to the normal tissues of the mouse, including bone marrow, intestine and the liver.
Abstract: We report 60 synovectomies of the knee in 51 children with juvenile chronic arthritis. Synovitis had been present for an average of 5 years and the average age at operation was 13 years. Results were evaluated in terms of pain, knee movement, relapse of synovitis and radiological change during a follow-up averaging 7.5 years. The relief of pain was rewarding and there was a slight postoperative gain in range of knee movement in most cases. The older the patient at onset of disease, the greater the risk of pain during follow-up. Progressive joint destruction was more common in younger patients, those with systemic or polyarticular disease, and those with highly active disease at the time of operation. Recurrence of synovitis was more frequent in patients who had their operation in a phase of high disease activity; this occurred most often in patients with polyarticular disease.
Abstract: A prospective longitudinal investigation of spontaneous cephalic version from breech presentation in the last trimester is reported. All pregnancies were assessed with ultrasound in the 32nd week of gestation, and were thereafter checked weekly. Of the 310 singleton breech presentations identified at 32 weeks, spontaneous cephalic version occurred in 177 (57%) while breech presentation persisted in 133 patients (43%). Of 140 patients with a breech presentation at delivery 95% were already presenting by the breech in the 32nd week. Spontaneous cephalic version was less likely in pregnancies with extended fetal legs, low birth-weight, short umbilical cord and primiparity.
Abstract: In thirty-one premenopausal patients with carcinoma of the breast the plasma prolactin was measured after mastectomy. A highly significant correlation between tumour size and plasma prolactin levels (p less than 0.002) was observed after adjustment for age at diagnosis and parity. At the time of the prolactin determination no clinical signs of metastatic disease were evident, suggesting that the prolactin levels were unrelated to the tumour burden.
Abstract: Various prognostic factors have been tested in multivariate analyses of 216 patients with papillary, follicular or medullary thyroid carcinomas without initial distant metastases. The median follow-up time was 11 years. The patient's sex was not found to be a significant predictor. Age at diagnosis seemed to be an important predictor for papillary as well as for follicular carcinomas, but when deaths in intercurrent disease were estimated, marked cellular atypia and tumour invasion beyond the thyroid capsule proved to be more important predictors. For medullary carcinomas tumour invasion beyond the thyroid capsule was the only significant predictor.
Abstract: One hundred-eighty-five consecutive spermiograms from men of infertile couples in 1980-1981 were compared with as many spermiograms of age-matched controls from 1960-1961. The semen parameters analyzed were: volume, sperm density, and sperm morphology. The following significant changes were noted over the time period: the mean seminal volume decreased from 3.79 ml to 3.42 ml (p less than 0.05), the mean sperm count decreased from 125.4 mill/ml to 78.0 mill/ml (p less than 0.001) and the proportion of double sperm heads increased from 0.52% to 1.51% (p less than 0.001). Further analysis showed even more pronounced changes in these parameters for men living in the urban area compared those from the surrounding rural areas.
Abstract: The heterocyclic secondary amine piperazine is known to cause asthma. In a cohort of 602 workers, employed during the period 1942-1979, at a chemical industry where piperazine is handled, a study conducted by means of a mailed questionnaire showed a strong exposure-response relationship as to frequency of work-related airway symptoms indicating asthma. In the most exposed group about a third of the workers had experienced such symptoms. Age, length of employment, smoking habits, and previous work-related asthmatic symptoms, but not atopy, modified the response. Further, there was an association between piperazine exposure and chronic bronchitis. In the most exposed group every fourth subject had chronic bronchitis. The frequency was modified by smoking habits; atopy was a confounder. Although many subjects, especially high-exposed ones, left work because of airway symptoms, there was no difference in occurrence of airway symptoms between former and present employees, ie, no "healthy worker selection" ("survivor population effect").
Abstract: Eighty-six patients with invasive squamous cell carcinoma of the vulva stage I were followed for 2 to 20 years after surgical treatment varying from local excision to radical vulvectomy with inguinal lymph node dissection. The results are presented and the prognosis discussed in relation to the radicality of the surgical intervention, the degree of tumour differentiation, the morphologic properties of tumour cell population, and the tumour host relationship. The most important prognostic factor seemed to be the radicality of the surgical intervention. To reduce patient morbidity in radical surgery while still achieving a comparable survival rate an operative approach with less than radical vulvectomy, inguinal dissections or pelvic lymphadenectomy, or both, is proposed for selected patients.
Abstract: A visually increased uptake of 201Tl chloride corresponding to a 'cold' (131I or 99Tcm ) thyroid nodule is mostly seen in well-differentiated carcinomas but also often in follicular adenomas. Since a visually increased uptake of 201Tl can be due to an increased initial uptake and/or a delayed elimination, an extended dynamic investigation was performed in patients with well-differentiated carcinomas or with follicular adenomas. Data were collected in a dynamic simultaneous double isotope ( 99Tcm + 201Tl) study up to 50 min after intravenous administration. Adenomas could be significantly separated from carcinomas by the elimination (p = 0.0001), but not by the initial uptake.
Abstract: The spermiograms of 63 fertile men (whose female partners were pregnant at the time of examination) were evaluated. A wide Gaussian distribution of the different semen parameters was found. Both parametric and nonparametric statistical tests were applied and gave almost identical results. In a subgroup of 34 men, a second semen sample was analysed, but a significant difference (p less than or equal to 0.05) between the two samples was found only regarding the proportion of abnormal forms. Between various semen parameters significant correlations were found. There was no association between follicle stimulating hormone (FSH) and sperm density with sperm counts greater than 20 mill/ml.
