Abstract: PURPOSE: The aim of this study was to describe the use of palliative sedation (PS) its indications and outcomes in patients followed up till death by an inpatient palliative care consult team (PCCT) at a tertiary cancer center. METHODS: All patients referred for 5 years to the PCCT and followed up till death were eligible for the study. Both PCCT recordings and hospital charts were reviewed and a codified assessment was performed. RESULTS: Over a total of 2,033 consecutive consults, 129 patients died during admission and were eligible. Eighty-three had the indication to PS, 4% of all consults (95% confidence interval [95%CI], 3% to 5%) and 64% of eligible patients (95%CI, 56% to 73%). PS was more frequently indicated in males and in patients with recurrent dyspnea and recurrent agitation, while it was less frequently indicated in older people and in patients with cerebral metastases and recurrent drowsiness. The most frequent indications to PS were dyspnea (37%) and delirium (31%) alone or combined with other symptoms. PS was successfully achieved in 69 patients; the drugs most frequently used for PS were midazolam (46%), haloperidol (35%), and chlorpromazine (32%) and opioid dose escalation was higher in sedated patients (P < 0.01). CONCLUSIONS: PS is an important intervention in the management of terminal disease by a consulting palliative care team. Improved collaboration and communication between the hospital staff and the PCCT should be offered to meet patients' needs when PS is required.
Abstract: This study is part of a research program to reach consensus on an international cancer pain classification system. A confirmative and explorative approach was applied to investigate which of the variables identified in the literature, by experts and patients that are associated with pain.
Abstract: Patients treated with opioid drugs for cancer pain experience different relief responses, raising the possibility that genetic factors play a role in opioid therapy outcome. In this study, we tested the hypothesis that genetic variations may control individual response to opioid drugs in cancer patients.
Abstract: The aim of this systematic review was to evaluate the evidence that oral morphine can be recommended as the first choice opioid in the treatment of moderate to severe cancer pain in updating the European Association for Palliative Care opioid recommendations. A systematic literature review was performed to update the 2007 Cochrane review 'Oral morphine for cancer pain'. The literature search was conducted on MedLine, EMBASE and Cochrane Central Register of Controlled Trials databases. The search strategy, limited in time (from 1 July 2006 to 31 October 2009), was aimed to be as extensive as possible using both text words and MeSH/EMTREE terms; a hand search of the reference lists of identified papers was also performed. Randomized clinical trials, containing data on efficacy and/or side effects of morphine, were identified. Among the papers retrieved from the cited databases and the Cochrane review, 17 eligible studies, for a total of 2053 patients, and a meta-analysis were selected. These studies do not add significant information to the previous Cochrane review confirming the limitation of efficacy and tolerability data on opioid-naïve and non-selected populations of cancer patients treated with morphine and suggesting that oral morphine, oxycodone and hydromorphone have similar efficacy and toxicity in this patient population.
Abstract: The aim of this systematic review is to evaluate the scientific evidence for the efficacy and side effects of hydromorphone in the management of moderate to severe cancer pain. Randomized and non-randomized clinical trials, reporting data on efficacy and/or side effects of hydromorphone, were identified. Thirteen eligible studies, involving 1208 patients, were selected. Seven studies compared hydromorphone with other opioids (five with morphine, one with oxycodone and one with fentanyl and buprenorphine) and five of them were randomized controlled trials (RCTs). Most of the studies were conducted on patients already receiving opioid treatment, often at stabilized doses, and most had methodological limitations. The RCTs comparing hydromorphone with morphine and oxycodone showed similar analgesic results, while the comparison of side effects showed minor differences, not consistent across studies. Due to clinical and methodological heterogeneity of the studies, a meta-analysis was not performed. In conclusion there is evidence to support the efficacy and tolerability of hydromorphone for moderate to severe cancer pain as an alternative to morphine and oxycodone, while there is no evidence to demonstrate its superiority or inferiority in comparison with morphine as the first choice opioid for the same indication.
Abstract: Aim of this study was to validate the use of subjective average pain assessment over an 8-h time period to evaluate cancer pain intensity. A sample of 95 consecutive cancer inpatients were asked to score on 0-10 numerical scales the intensity of their pain at hourly intervals, and then, at the 8th hour, to rate their average pain intensity over the last 8h. Agreement between the average of the 8 hourly measures (8hA) and the single patient-rated average (PA8h) was examined with the intraclass correlation coefficient (ICC) and the absolute difference (AD) between the two measurements. Associations between AD, gender, age older than 70, somatic pain, visceral pain, neuropathic pain, pain on movement and the presence of pain exacerbations during the 8-h period, were also examined. Average pain intensity scores were very similar with the two measurement schedules: 3.4 for 8hA and 3.7 for PA8h, with a median AD of 0.44 points. Only six patients (6.3%) showed ADs higher than 2 points. Also the ICC (0.85) showed a substantial agreement between the two schedules. Among the examined variables, gender, age over 70years and presence of pain exacerbations showed a significant association with the agreement level. Overall, our results support the validity of a subjective average pain measurement over 8-h period in cancer patients.
Abstract: Numerical rating scales (NRS), and verbal rating scales (VRS) showed to be reliable and valid tools for subjective cancer pain measurement, but no one of them consistently proved to be superior to the other. Aim of the present study is to compare NRS and VRS performance in assessing breakthrough or episodic pain (BP-EP) exacerbations.
Abstract: Workpackage 3.1 (WP 3.1), within the European Palliative Research Collaborative (EPCRC), was aimed at critically revising and updating the European Association for Palliative Care recommendations on cancer pain management. The aim of this paper is to report the results of the first phase in the revision process which consists of a literature review and an expert consensus about the contents to be considered relevant in the development of the new guidelines. A systematic literature search was carried out from 2001 to 2008 through various databases including Medline, Cinahl, Cochrane Database of Systematic Reviews, Embase and Google. Through this process, guideline quality was evaluated, content was compared with EAPC recommendations and a first set of key-points was developed. A modified two-round Delphi method was applied to choose the most relevant topics for future systematic literature reviews. Fourteen guidelines on cancer pain management, published or updated after 2000, were retrieved. A comparison of these guidelines with the EAPC recommendations led to the formulation of 37 key-points, which were submitted to a panel of experts through a Delphi method. Through the responses given by the experts (25 after the first round and 19 after the second) and after a revision by the WP 3.1 local and steering committees, a final list of 22 topics was generated to answer all identified key-points. Each of these topics will be the object of systematic literature reviews. The final version of the "Evidence-based guidelines for the use of opioid analgesics in the treatment of cancer pain: the EAPC recommendations" will be based on the results of the 22 systematic literature reviews.
Abstract: To evaluate whether the current European Association for Palliative Care recommendation regarding the starting dose of 5 mg of normal-release morphine (NRM) sulfate oral solution every 4 hours in opioid naive patients or 10 mg in patients already being treated with "weak" opioids is effective and could be proposed as starting routine dose in clinical practice. Secondary aims were to estimate the percentage of patients who were high responders to NRM and to study the association of baseline patient characteristics with both high analgesic responsivity and the need of opioid dose escalation.
Abstract: To compare quality of life and bladder, intestinal, and sexual dysfunctions in 2 groups of patients undergoing different types of radical hysterectomies (RHs).
Abstract: Screening of the oral cavity and dental care was suggested as mandatory preventive measures of osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs). We investigated the occurrence of ONJ before and after implementation of dental preventive measures when starting BP therapy.
Abstract: Adequate and rapid pain control is one of the main goals of cancer pain treatment. The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain. Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase (first 5 days), depending on previous analgesic therapy. Pain intensity was assessed using an 11-point Numerical Rating Scale (0-10), and data were recorded in a patient-compiled diary. The primary endpoint was the proportion of time with pain control (a reduction of at least 50% with respect to the baseline pain score) during the titration phase. A total of 159 consecutive patients (102 men; mean age 65 years) with cancer-related pain were enrolled. Pain control was observed for 75% (95% CI 70-80) of the follow-up period in the intent-to-treat population. Overall, 50% and 75% of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively. The mean pain score was 7.63 points at baseline, and decreased to 2.43 and 1.67 points (both P<0.001) at days 3 and 5 respectively. The most commonly reported adverse events were somnolence (24% of patients), constipation (22%), vomiting (13%), nausea (10%) and confusion (7%). Normal-release morphine results in rapid and satisfactory pain control, and is well tolerated, during the strong-opioid titration phase in patients with moderate-to-severe cancer pain.
Abstract: The capability to make decisions about one's own dying and death is commonly considered a necessary component of a good death, but difficulties in communicating about imminent death have been documented. This paper attempts to describe the process of constructing an instrument to elicit individual preferences concerning dying, while respecting the patient's awareness, and to verify its applicability in a palliative care setting. The development of the End-of-Life Preferences Interview (ELPI) was performed through (a) a literature search aimed at identifying relevant issues; (b) examination by a panel of experts in the field of palliative care of the items generated; and (c) pretesting of feasibility on all eligible consecutive patients referred to three centers of palliative care during a two-month period. The final version of the ELPI consisted of two parts: The first level explores preferences about issues regarding the caregiving process, and the second level focuses on preparation for death. Each of the two parts is introduced by key questions aimed at allowing the patient to decide whether and when to stop exploring such sensitive matters. Among the 49 eligible patients (41%), the interview was proposed to only 13 of them (27%), and only one of them refused. The reasons for such a low compliance of physicians in proposing the ELPI were evaluated by a semi-structured interview and are herein discussed. The use of the ELPI in clinical practice can favor the passage to a greater consideration of the self-determination of the patient at the end of life, with due consideration of his or her cultural and emotional needs.
Abstract: The aim of this study is to describe the last month of life of severely demented elders in long-term care institutions, and the clinical decisions in the management of their end-of-life events.
Abstract: Few studies have focused on neuropsychiatric symptoms like hallucinations or delusions occurring in the early posttransplant period. The aim of this study was to estimate the percentage of patients reporting neuropsychiatric symptoms in the immediate postoperative phase, to describe the phenomenology, and to evaluate the emotional impact of such disorders.
Abstract: In patients with bone metastases, pain may be absent or moderate at rest, but may be exacerbated by different movements or positions. No study has evaluated separately pain at rest and on movement in patients with bone metastases undergoing treatment with zoledronic acid (ZA).
Abstract: In the palliative care setting, the Edmonton Symptom Assessment Scale (ESAS) was developed for use in daily symptom assessment of palliative care patients. ESAS considers the presence and severity of nine symptoms common in cancer patients: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being and shortness of breath plus an optional tenth symptom, which can be added by the patient. The aim of this study was to validate the Italian version of ESAS and to evaluate an easy quality of life monitoring system that uses a patient's self-rating symptom assessment in two different palliative care settings: in-patients and home patients. Eighty-three in-patients and 158 home care patients were enrolled. In the latter group, the Italian validated version of the Symptom Distress Scale (SDS) was also administered at the admission of the patients. The two groups of patients have similar median survival, demographic and clinical characteristics, symptom prevalence and overall distress score at baseline. ESAS shows a good concurrent validity with respect to SDS. The correlation between the physical items of ESAS and SDS was shown to be higher than the correlation between the psychological items. The association of ESAS scores and performance status (PS) showed a trend: the higher the symptom score was, the worse was the PS level. Test-retest evaluation, applied in the in-patient group, showed good agreement for depression, well-being and overall distress and a moderate agreement for all the other items. In conclusion, ESAS can be considered a valid, reliable and feasible instrument for physical symptom assessment in routine "palliative care" clinical practice with a potentially different responsiveness in different situations or care settings.
Abstract: World Health Organization (WHO) guidelines, Agency for Health Care Policy and Research (AHCPR) clinical practice guidelines, and EAPC recommendations indicate oral route of opioid administration as the preferred route. Transdermal administration of opioids is considered an alternative when patients cannot take medications orally. Moreover, WHO and EAPC indicate orally administered morphine as the first-choice drug for the treatment of moderate to severe cancer-related pain. However, we can see that in Italy there is an increasing use of transdermal fentanyl (TF) as first-choice strong opioid (and route) even when oral administration of opioids is possible.
Abstract: In clinical practice the major role of opioid drugs is the management of malignant and nonmalignant pain. The primary aim of this study is to evaluate the trend in sales of four opioid analgesic drugs (codeine, tramadol, morphine, fentanyl), from wholesalers to community pharmacies, as an indicator of opioid consumption in nine European countries in 2001, 2002 and 2003. Secondary aims are to compare: (a) the amount of each drug purchased by different countries in 2003; (b) the average price for each drug in the different countries in 2003; and (c) the total expenditure for each opioid from 2001 to 2003.
Abstract: The aim of this review was to evaluate the methods of pain measurement in controlled clinical trials in oncology published between 1999 and 2002. An electronic literature search strategy was used according to established criteria applied to the Medline database and PubMed search engine. Articles were selected to include only studies that had chronic cancer pain as the primary or secondary objective of a controlled clinical trial. A specific evaluation scheme was used to examine how pain measurement methods were chosen and implemented in the study procedures. The search strategy identified 613 articles, and 68 were selected for evaluation. Most articles (69%) chose unidimensional pain measurement tools, such as visual analogue scales, numerical rating scales and verbal rating scales, whereas others used questionnaires. The implementation of the pain assessment method was problematic in many studies, especially as far as time frame of pain assessment (70%), administration modalities (46%), and use of non-validated measurement methods (10%). Design of study and data analysis were often unclear about the definition of pain outcome measure (40%), patient compliance with pain assessment (98%), and impact of missing data (56%). Statistical techniques were seldom appropriate to the type of data collected and often inadequate to describe the pain variable under study. It is clear from this review that most authors were aware of the need of valid pain measurement tools to be used in clinical trials. However, too often these tools were not appropriately used in the trial, or at least their use was not described with sufficient accuracy in the trial methods.
Abstract: This study compares the relative prognostic power of clinical variables and quality-of-life (QoL) measures in a population of terminal cancer patients.
Abstract: To describe how patients die in hospital, 370 patients (age >18 years; in hospital for>24 hours) who died on the general wards of 40 Italian hospitals were assessed. Differences between patients whose death was expected and patients whose death was unexpected were evaluated. Data on treatments and care in proximity of death were collected after interviewing the nurse responsible for the patient within 72 hours of the patient's death, and from clinical and nursing records. For 58% of patients, death was highly expected. Symptom control was inadequate for the most severely ill patients: 75% experienced at least one "severe" symptom (42% pain and 45% dyspnea). Nurses tended to judge patients' global care as "good" or "very good" (76%), in spite of the persistence of symptoms and the scant use of analgesics. Despite some encouraging signs of sensitivity to end-of-life problems, acute inpatient institutions in Italy still deal inadequately with the needs of dying persons.
Abstract: Accurate pain assessment is considered essential for effective management of cancer pain. The aim of this study was to evaluate the compliance of hospitalized patients with chronic cancer pain, referred to an inpatient palliative care consultation service, with self-assessment of pain intensity by means of a daily pain form. The form was distributed daily by the pain consult nurse and required three daily pain intensity measurements on 0 to 10 numerical scales, separately for pain at rest and pain on movement. Of 174 consecutive patients, 106 (61%) participated in the study and were followed up for a median of 10.6 days (range 1-32 days). Compliance was defined as the number of assessment forms completed over the number of evaluation days available for each patient. Mean compliance was 58%. The main reasons for not completing the form were related to subjective psychological variables (44%), physical distress (26%), and absence of pain (16%). Lack of understanding of the method was reported as the main reason for non-compliance by only 1% of patients.
Abstract: In the second half of the nineties, a scientific debate about the usefulness of qualitative research in medicine began in the main medical journals as well as the amount of "qualitative" papers published on peer reviewed journals has noticeably increased during these last years. Nevertheless the label of qualitative methodology has been assigned to an heterogeneous collection of studies. Some of them show a complete awareness of the specificity of this kind of research, while others are still largely influenced by the quantitative paradigm prevailing in the medical field. The concern with the rigour and credibility of qualitative methods has lead to the development of a number of checklist for assessing qualitative research. The purposes of this review were to describe the quality of the development of qualitative research in the medical field, focusing on oncology and palliative care, and to discuss the applicability of a descriptive checklist.
Abstract: Health-Related Quality of Life assessment is widely used in clinical research, but rarely in clinical practice. Barriers including practical difficulties administering printed questionnaires have limited their use. Telehealth technology could reduce these barriers and encourage better doctor-patient interaction regarding patient symptoms and quality-of-life monitoring. The aim of this study was to develop a new system for transmitting patients' self-reported outcomes using mobile phones or the internet, and to test whether patients can and will use the system via a mobile phone.
Abstract: Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.
Abstract: In the last few years, palliative care for advanced and terminal cancer patients has undergone considerable evolution. We determined the characteristics of patients admitted to the 4-bed Palliative Care Unit (PCU) of the National Cancer Institute (NCI) of Milan in 1987, 1993 and 2000 to evaluate how our diagnostic and therapeutic approaches have changed over the years. We reviewed the charts of every patient admitted to the PCU in 1987, 1993, and the first ten months of 2000. We recorded demographic data; the primary tumor sites; the main reason for admission; the types of therapies administered (oncologic, analgesic, surgical, neurosurgical analgesic procedures, and supportive therapy); the type and number of cardiological, radiological and endoscopic examinations, as well as specialist consultations; the duration of stay and eventual death on the Unit. There were no significant differences regarding gender, age, primary tumor site and death in hospital of the patients admitted during these years. The time spent in hospital increased over time (P = 0.006). A significant increase was observed in the percentage of patients admitted for supportive therapy (P < 0.001) and investigation concerning the stage of the disease (P < 0.001). There was a significant decrease in admission for invasive analgesic procedures (P < 0.001), as well as for pain diagnosis and/or uncontrolled pain. Uncontrolled pain remained the most frequent reason for admission. Over the years, during hospitalization, 7% to 12% of the patients underwent radiotherapy,1% to 9% had computerized tomography, and 4% to 8% had palliative surgery. More than 50% of the patients received intravenous hydration; a few patients received hypodermoclysis in 1987. Over time, there was a significant increase in "as needed" administration of nonsteroidal anti-inflammatory drugs and a significant reduction in their regular administration (from 24% in 1987 and 1993 to 3% in 2000) (P < 0.001). The use of codeine, tramadol and methadone increased (P < 0.001), whereas the use of oral morphine, buprenorphine and oxycodone decreased in 2000 (P < 0.001). There was a reduction in the use of antidepressants (no significant constant trend) and a significant increase in the use of anticonvulsants, laxatives and pamidronate (P < 0.001). Regularly administered hypnotics decreased in 1993 and increased in 2000 (P < 0.001). Over these years, no significant differences were found in the routes of opioid administration, in route switching and in the mean maximum oral opioid dose (ranging from 108 to 126 mg/day). The percentage of patients undergoing percutaneous cordotomy significantly decreased in 1993 and 2000 (P < 0.001). Over time, there was an increase in requests for specialist consultations, which was significant for neurological, cardiological and oncological consults (P < 0.001). Although the characteristics of the patients admitted to the PCU did not change over these years, there have been significant modifications in our therapeutic approaches, above all in the use of supportive therapy, adjuvant drugs, opioids and neurosurgical invasive procedures. Moreover, a major collaborative interaction with other specialists of the NCI took place with the aim to tailor treatment for each single patient.
Abstract: The evaluation of cancer patients needs, especially during that delicate period when they are hospitalized, allows the identification of those areas of care that require to be improved. Aims of the study were to evaluate the needs in cancer inpatients and to improve the understanding of the meanings of the needs expressed.
Abstract: 4.5S RNA is the bacterial homolog of the mammalian signal recognition particle (SRP) RNA that targets ribosome-bound nascent peptides to the endoplasmic reticulum. To explore the interaction of bacterial SRP with the ribosome, we have isolated rRNA suppressor mutations in Escherichia coli that decrease the requirement for 4.5S RNA. Mutations at C732 in 16S rRNA and at A1668 and G1423 in 23S rRNA altered the cellular responses to decreases in both Ffh (the bacterial homolog of SRP54) and 4.5S RNA levels, while the C1066U mutation in 16S rRNA and G424A mutation in 23S rRNA affected the requirement for 4.5S RNA only. These data are consistent with a dual role for 4.5S RNA, one involving co-translational protein secretion by a 4.5S-Ffh complex, the other involving free 4.5S RNA.
Abstract: Aims: The aim of the study was to investigate possible differences in access to the service, symptomatology and therapy in relation to age among terminal cancer patients admitted to a home care program. We examined prospectively all 116 terminal cancer patients enrolled in a home care program in 1998, comparing those up to 70 years of age (48 patients) with those above 70 (68 patients). We also compared the age-related characteristics of this population with those of all 348 patients enrolled in the program in 1989-1991. There were no significant differences between the two age groups of the 1998 population in terms of symptoms, tumor site or medication, although NSAID use tended to be greater in older patients, and opioid and anti-emetic use greater in younger patients. Patients up to 70 years of age had significantly shorter survival from admission to home care than those over 70, and a greater proportion had metastases. There were no such significant age-related differences as regards survival and the presence of metastases in patients enrolled 10 years before. In conclusion, among terminally ill cancer patients referred to a palliative home care service in Milan, mostly treated at the National Cancer Institute, the 10-year admission trend showed that palliative care is made available increasingly later, particularly to those up to 70 years of age, in contrast to current recommendations.
Abstract: There is little knowledge of the psychological and social conditions of candidates for liver transplantation and the meaning that these patients attribute to those conditions.
Abstract: Quality of life (QoL) assessment is crucial for the evaluation of palliative care outcome. In this paper, our methodological approach was based on the creation of summary measures. Fifty-eight Palliative Care Units (PCUs) in Italy participated in the study. Each PCU randomly selected patients to be 'evaluated' among the consecutively 'registered' patients. At baseline (first visit) and each week the patient was asked to fill in a QoL questionnaire, the Therapy Impact Questionnaire (TIQ). Short-survivors (<7 days) were not included in the QoL study. The random sample of patients (n = 601) was highly representative of the general patient population cared for by the PCUs in Italy. The median survival was 37.9 days. We collected 3546 TIQ, 71.4 % completed by the patients. A Summary Measure Outcome score was calculated for 409 patients (81% of the patients included in the QoL study). The results of this national study showed that cooperative clinical research in palliative care is possible and QoL measures can be used to assess the outcome.
Abstract: To evaluate the anatomic characteristics and intraocular pressure (IOP) lowering mechanisms of deep sclerectomy with reticulated hyaluronic acid implant (DS with RHAI) using ultrasound biomicroscopy (UBM).
Abstract: A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T0 after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies.
Abstract: Sulfonylureas block the activation of vascular potassium-dependent ATP channels and impair the vasodilating response to ischcmia in nondiabetic individuals, but it is not know whether this occurs in type 2 diabetic patients under chronic treatment with these drugs. Glimepiride, a new sulfonylurea, apparently has no cardiovascular interactions. The aim of our study was to compare the effect of the widely used compound glibenclamide, the pancreas-specific glimepiride, and diet treatment alone on brachial artery response to acute forearm ischemia.
Abstract: At present, abdominoperineal resection remains the most diffuse method of treatment of very low rectal cancer. Today, we can avoid this method in some patients by using a sphincter-saving procedure.
Abstract: The aims of this study were: to assess the attitude of non-small-cell lung cancer (NSCLC) patients to being treated with chemotherapy, determining whether and how much it differs from that expressed by patients with benign diseases or by healthy people; and to investigate how the information received about the treatment may influence the patients' decisions. A three-item self-assessment questionnaire measuring willingness to be treated with chemotherapy and presented according to three different scenarios (with an optimistic, neutral, and pessimistic physician's presentation) was administered to 104 NSCLC patients, 129 other patients with respiratory diseases (RDP), 140 health care providers (HCP) and 120 students (STU). Guttman's coefficient of reproducibility confirms the hierarchical structure of the three scenarios ranging from an optimistic to a pessimistic view. Relative to the other groups, cancer patients showed: (a) a consistently higher degree of uncertainty about whether to accept or reject chemotherapy; (b) the lowest acceptance rate in the optimistic and neutral scenario and, in contrast, the highest in the pessimistic scenario; (c) the highest percentage of constant answers, independently of the scenario presented, particularly as regards the answers "I don't know" (NSCLC = 25%, RDP = 9%, HCP = 2%, STU = 5%) and "Yes, I accept" (NSCLC = 29%, RDP = 31%, HCP = 19%, STU = 16%). Answer patterns differed markedly between cancer patients, the HCP, and the STU group, and in most cases the difference was statistically significant at a confidence level of 0.001. The differences between NSCLC and RDP patients were less marked, and not always statistically significant. The choice between accepting and rejecting chemotherapy is very difficult for patients with NSCLC, much more so than for healthy people, and it is often independent of the way the information is provided.
Abstract: In the last 10 years of clinical research there has been increasing interest in the evaluation of quality of life. Several generic and specific instruments have been developed for this purpose. EORTC QLQ C-30 is a cancer-specific questionnaire translated into various languages and validated in several European countries including Italy, where the impact of malignant disease on different areas of quality of life is poorly documented.
Abstract: According to the data of the literature, the prevalence of pain in cancer patients at various stages of the disease and the settings of care range from 38 to 51%, with an increase of up to 74% in the advanced and terminal stages. Despite published World Health Organization (WHO) guidelines for pain management, 42 to 51% of cancer patients receive inadequate analgesia and 30% receive no analgesics at all. A 3-year Research Project "Towards a Pain-free Hospital", which began one year ago, is ongoing at the National Cancer Institute of Milan. The research is organized in three subsequent steps. In the 1st one, a series of patient- and staff-oriented evaluation tools are used to assess the level of appropriateness of pain communication, assessment, management and control of the in-patients. The 2nd step will implement a number of continuing educational interventions aimed at improving patient awareness and staff knowledge of the appropriate pain assessment and management in order to respond to the patient's pain problem. In the 3rd step, all the assessment tools used in step one will be applied again to establish the prevalence of pain, the causes and intensity and patient satisfaction with pain management and to evaluate the impact of the interventions performed during the 2nd step regarding the overall ability of our hospital to tackle pain emergency in the hospitalized cancer population. The results relative to the 1st step are herein reported, in particular as regards the study on prevalence, causes, severity of pain, the interference of pain with sleep, mood and concentration, the use of pain medications and the relief obtained, the structural validity and internal consistency of the assessment tool used. A total of 258 patients hospitalized for at least 24 h were interviewed by 9 physicians using a brief structured questionnaire prepared ad hoc: 51.5% of the patients presented pain during the previous 24 h caused by surgery (49.6%) or by the tumor mass itself (29.3%). Out of the 133 patients with pain, a high degree (much or very much) of pain at rest was present in 27.1% and pain on movement in 30.8%; 31.6% did not take any analgesic treatment, and 14.3% of the latter reported a high degree of pain at rest and 21.4% on movement. Pain interfered with sleep from much to very much in 28.8% and with irritability and nervousness in 15.9% of the patients. In the 91 patients taking analgesics, 57.2% reported a high degree of pain relief. A high degree of pain and interference, however, was associated with low relief levels. The assessment tool used was shown to have a good structural validity and internal consistency (Chrombach alpha index of interference scale = 0.73). Although the Milan Cancer Institute has the longest tradition in Italy of pain assessment by means of validated tools and pain management according to the WHO guidelines and educational efforts in this field, the results of the study clearly show that it is necessary to persevere with continuing educational and informative programs in order to reduce the frequency and severity of pain and thus improve the quality of life of in-patients.
Abstract: Cancer disease modifies the order and the nature of needs connected with the state of health. The aim of this study was to evaluate the informative, psychological, social and practical needs of hospitalised cancer patients by means of the Needs Evaluation Questionnaire (NEQ), an instrument designed concisely for the convenience of patients and medical staff.
Abstract: Multi-gated acquisition (equilibrium-gated radionuclide ventriculography) (MUGA) is considered the gold standard for measuring left ventricular ejection fraction (LVEF) because it is accurate, machine interpreted, and reproducible. Echocardiographic LVEF measurements are subject to variability in image acquisition and interpretation and to the limitations of 2-dimensional (2D) versus 3-dimensional imaging.
Abstract: As part of a large multicentre study on palliative care units in Italy, carried out between 1 January and 30 June 1995, we describe the place, circumstances and 'quality of death' of patients admitted to home palliative care. Data presented refer to 401 patients (67% of the 601 patients randomly selected for evaluation). Of these 401 patients 303 (76%) died at home. According to the Support Team Assessment Schedule (STAS) pain was fairly well controlled during the final week of life, while the control of other symptoms appeared to be less satisfactory. Invasive procedures were undertaken on 56% of patients, while in hospital the percentage increased to 75%. Twenty-five per cent of patients were totally pharmacologically sedated during the final 12 h of life. Neither the number of symptoms nor other factors were apparently associated with the decision to sedate the patient. The wide variations in the frequency of sedation among centres suggest that the choice to sedate the patient may reflect the provider's behaviour or services' policy rather than the patients' preference or needs. The definition of common criteria and guidelines for sedation of patients should be one of the topics for discussion among palliative care teams.
Abstract: Outcome in palliative care can be defined as patients' quality of life, quality of death and satisfaction with care. In an Italian multicentre prospectic study ('Staging') the quality of life of 571 palliative care patients with advanced cancer disease was assessed since the beginning of palliative care till the end of the study. We analyzed the tissue of quality of life missing data and the possibility to input the missing quality of life evaluation through the quality of life evaluation made by a proxy (doctor, nurse). The greatest functional impairment and an increasing level of some symptoms (fatigue, general malaise, emotional status) were observed during the last two weeks of life, whereas for other symptoms (gastro-intestinal, pain) some degree of control was possible. The quality of life analysis for palliative care patients should consider the different response of different quality of life components to the palliative care intervention.
Abstract: A multicenter study involving six palliative care units in Italy was carried out on 159 terminal cancer patients seen at home or in hospital. The physician or the nurse completed independently from the patient the Therapy Impact Questionnaire (TIQ), a questionnaire devised for quality-of-life evaluation in terminal cancer patients. The patient's assessment was used as the valid reference measurement to compare with the health-care workers' evaluation to assess the validity of the latter. The results showed that percentages of agreement were higher for physical than for psychological and cognitive symptoms, and that there was a greater agreement on the absence rather than on the presence of a problem. None of the characteristics of the patient nor of the proxy showed any statistically significant relationship with the two disagreement indexes. The results suggest that caution is needed in the use of health-care workers as alternative sources of information regarding patients' quality of life.
Abstract: In uncontrolled clinical trials, the administration of oral zinc sulfate has been reported both to prevent and correct taste abnormalities in cancer patients receiving external radiotherapy (ERT) to the head and neck region.
Abstract: The objective of this study was to evaluate the neurologic and quality of life impact of low dose adjuvant interferon (IFN)-alpha immunotherapy in patients with malignant melanoma metastatic to regional lymph nodes after radical surgery.
Abstract: To define the dose ratio between morphine and methadone in relation to the previous morphine dose and the number of days needed to achieve the same level of analgesia in a group of patients with advanced cancer with pain who switched from morphine to oral methadone.
Abstract: A multicenter cross-sectional study of 115 terminal cancer patients in eight home-care units assessed the prognostic value of quality of life scores, as measured by the Therapy Impact Questionnaire (TIQ). The analysis of the questionnaires completed by 100 patients revealed an association between survival and many of the scales: fatigue, gastrointestinal symptoms, global health status, functional impairment, emotional status, and cognitive status. This association was also observed for some specific physical symptoms, such as confusion, weakness, and loss of appetite, and the overall number of symptoms reported by the patient. Adjusting for some possible confounding factors, only confusion (among the physical symptoms), cognitive status, and global health status (among TIQ primary scales) showed independent prognostic value. As regards the latter two scales, median survival time was distributed differently for patients with no impairment of either (137 days), with impairment of one scale (50 days) and with impairment of both scales (17 days). The judgment expressed by the patient about subjective perception of general malaise and cognitive difficulties can give the clinician important prognostic information.
Abstract: This study presents a prospective evaluation of the home care programme for patients with advanced cancer at the National Cancer Institute of Milan. Demographic, psychosocial and physical variables were evaluated. The Therapy Impact Questionnaire was used for symptom and quality of life assessment. The association of clinical and demographic variables with the place of death was investigated, considering that the aim of the home care programme is to follow up patients until death in their houses. Eighty-six per cent (86%) of patients died at home and 14% in hospitals. Multivariate analysis showed that only a higher degree of family support was associated with home death. Several changes in symptoms and quality of life items scores were seen, pain improved while physical debility and cognitive functions worsened throughout the home care duration to death. High intensity pain and dyspnoea were still present in, respectively, 23.8 and 15.3% of patients in the last week of life. Psychological distress was high at the end of life and did not seem to be affected by treatment. Home care is a feasible alternative for implementing palliative care in a selected population of patients with advanced cancer. Palliation of physical symptoms is more easily achieved than the control of psychological suffering. Family and economical issues implied by home care models should be part of the discussion in implementing palliative care for advanced cancer patients.
Abstract: The aims of this study were to describe the analgesia, side effects, and dosage and the causes of suspension of treatment in a large sample of advanced cancer patients with pain after treatment with oral methadone from 7 to 90 days.
Abstract: The problems related to requests for euthanasia by terminal patients; the variations in attitude of palliative care physicians and the possibility that availability of the best palliative care might obviate the problem by eliminating requests for euthanasia, are under discussion.
Abstract: Only 5-10% of patients with lung cancer (LC) can be expected to be cured by radical treatments. In the remaining subjects the potential survival benefit of treatment must be weighed, taking into consideration the possible deterioration of quality of life (QL). Indeed, studies dealing with different aspects of QL are being increasingly reported in LC. In a few of them, the interesting observation was made that the patient-rated QL correlated well with the subsequent clinical outcome. In the present study we analyse 11 items of the Therapy Impact Questionnaire (a new instrument of QL), assessing both disease and therapy impact on physical condition, functional status, concomitant emotional and cognitive factors and social interactions. Questionnaires were completed by 128 consecutive LC patients, who had been seen, in the years 1990 through 1993, either for a newly diagnosed cancer (40 patients), or after a successful operation (15 patients), or during active and/or symptomatic treatment (73 patients). At the time of the QL assessment, a minimal set of demographic and clinical variables was recorded. Univariate tests of survival showed that stage of disease, difficulty at work or doing the housework, weight loss, performance status, difficulty relaxing, having been felt unsure, and tumor cell type were all associated, in decreasing order of significance, with prognosis. QL variables correlated well with each other, but poorly with clinical and demographic variables (an expected exception was the good correlation existing between working capacity/physical autonomy and the corresponding observer evaluation of performance status). This lack of correlations explains how QL variables maintained their significance in multivariate survival analyses. In the best multivariate model, the self-estimated difficulty at work or doing the housework followed the stage of disease, but preceded weight loss as a significant, independent, prognostic determinant. Further studies evaluating several other additional prognostic indicators are needed to better clarify the relative prognostic importance of quality of life.
Abstract: Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone.
Abstract: We have used a genetic approach to uncover the functional roles of rRNA in protein synthesis. Mutations were constructed in a cloned rrn operon by site-directed mutagenesis or isolated by genetic selections following random mutagenesis. We have identified mutations that affect each step in the process of translation. The data are consistent with the results of biochemical and phylogenetic analyses but, in addition, have provided novel information on regions of rRNA not previously investigated.
Abstract: Thirty eyes affected by angle-closure glaucoma that had undergone YAG-laser iridotomy were studied to evaluate variations of central anterior chamber depth, width of the angle, and loss of endothelial cells after laser treatment.
Abstract: A consecutive sample of 53 chronic cancer pain patients were administered 5 different pain intensity scales: a visual analogue scale (VAS), a numerical rating scale from 0 to 10 (NRS), a verbal rating scale (VRS), the Italian Pain Questionnaire (Italian version of the McGill Pain Questionnaire) (PRI), and the Integrated Pain Score (IPS) which is an instrument designed at the Pain Therapy and Palliative Care Division of the National Cancer Institute of Milan to integrate pain intensity and duration in a single measure. These scales were administered before and after a definite therapy change. At the time of the second evaluation the patients were also administered a pain relief scale (IRS). A factor analysis of the scoring properties of these instruments revealed a high degree of association between the variables. A single factor clearly emerged explaining most of the different scales variability. A logistic regression analysis showed that VAS, NRS, VRS were more strongly associated with IRS than PRI and IPS.
Abstract: The effect of L-propionylcarnitine on patients with left ventricular dysfunction (EF < 45%) NYHA class II, symptomatic despite therapy with digitalis and diuretics was evaluated in a phase II parallel, double-blind, randomized, placebo-controlled study. Fifty patients (28 men and 22 women) aged 37-70 years received 1.5 g of L-propionylcarnitine or placebo on a random basis as oral treatment for 6 months. At baseline, during a 7 day placebo run-in period, and during the 6-month treatment bicycle exercise test, M-B mode and Doppler echocardiography, and clinical evaluation (clinical score) were repeatedly performed. The analysis of variance for repeated measurements showed a statistically significant difference (P < 0.01) in the mean value of exercise time between the treatments over the period of the study. There was a final increase of 0.36 min in the placebo group, 1.4 min in the treated group and a minor production of lactate during exercise in the treated group. Left ventricular shortening fraction and left ventricular ejection fraction showed a significant increase in the L-propionylcarnitine group (respectively P < 0.01 and P < 0.0001) whereas no difference was apparent in the placebo group. Stroke volume index and cardiac index showed significant increments in the treated group (P < 0.05) and systemic vascular resistance was lowered (P < 0.05). No haemodynamic variations were observed in the placebo group, and the clinical score showed a significant improvement in the L-propionylcarnitine treated group. In conclusion, L-propionylcarnitine treatment was shown to improve patient symptomatology and effort tolerance.
