Abstract: AIM: To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), were anonymously tested for HBV and HCV infections. MATERIAL AND METHODS: Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs. RESULTS: The overall prevalence of anti-HCV was 2.6%, with a bimodal distribution characterized by the highest prevalence (12%) in subjects over 75 years old. None of the subjects under 25 years old was anti-HCV positive. Anti-HCV positivity was similar in males and females (2.4% vs. 2.7%). HCV-RNA was positive in 40% of cases and genotype 1 was the most common. The HBsAg prevalence was 1%, with a significant difference according to country of origin (0.8% in Italian subjects vs. 6.4% in immigrants, P=0.01). HBsAg positivity increased significantly with age (R=0.57, P<0.02). The overall percentages for the prevalence of isolated anti-HBs, anti-HBs+/anti-HBc+, and isolated anti-HBc were 23.8%, 8.4%, and 4.2%, respectively. CONCLUSIONS: Our study provides a new picture of HCV and HBV epidemiology in Northern Italy, with these features: (1) a cohort effect showing a reduction of HCV infection in the elderly, possible due to age-related mortality; (2) an unchanged overall prevalence of HBV infection, despite continuing immigration of subjects from endemic countries.
Abstract: ABSTRACT: BACKGROUND: This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands. METHODS: We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices. RESULTS: Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of euro167,200 compared to euro145,400 for the CPI/r regimen. This results in an incremental cost of euro21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs) are euro41,600 per LYG and euro42,500 per QALY. CONCLUSION: We estimated the iCER for TPV/r compared to CPI/r at approximately euro40,000 in treatment experienced HIV-1 infected patients in the Netherlands. This ratio may well be in range of what is acceptable and warrants reimbursement for new drug treatments in the Netherlands, in particular in therapeutic areas as end-stage oncology and HIV and other last-resort health-care interventions.
Abstract: OBJECTIVE: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). METHODS: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n approximately =100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step. RESULTS: The internal consistence reliability (Cronbach's alpha) was >or=0.70 for all domains. Most domains had Cronbach's coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood. CONCLUSION: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work.
Abstract: BACKGROUND: Amphotericin B is a widely used broad-spectrum antifungal agent, despite being associated with significant adverse events, including nephrotoxicity. METHODS: The present prospective study collected data on outcomes for 418 adult patients treated consecutively with polyenes in hematology and oncology wards in 20 hospitals in Europe. RESULTS: Patients initially received amphotericin B deoxycholate (62% of patients), liposomal amphotericin B (27%), or other lipid formulations of amphotericin B (11%). Of the patients initially treated with amphotericin B deoxycholate, 36% had therapy switched to lipid formulations of amphotericin B, primarily because of increased serum creatinine levels (in 45.7% of patients) or other amphotericin B-attributable adverse events (in 41.3% of patients). Nephrotoxicity, which was defined as a > or = 50% increase in the serum creatinine level, developed in 57% of patients with normal kidney function at baseline. Predictors of nephrotoxicity included formulation type and duration of treatment. Compared with patients without nephrotoxicity, patients with nephrotoxicity had a higher mortality rate (24%), and their mean length of stay in the hospital was prolonged by 8.6 days. Slight increases in the serum creatinine level (i.e., > or = 50%) were associated with a significantly longer stay in the hospital. Severe nephrotoxicity (i.e., a > or = 200% increase in the serum creatinine level) was a significant predictor of death, as were severe underlying medical conditions and documented fungal infection. CONCLUSION: This prospective study confirmed that, in European hospitals, amphotericin B formulations have a major influence on the length of stay in the hospital and nephrotoxicity-associated mortality.
Abstract: BACKGROUND: Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion. AIM: To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naive patients treated with pegylated interferon alpha-2b plus ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus-related in most cases) has no impact on virological response.
Abstract: OBJECTIVE: To describe the changes in costs of care for HIV-positive patients in Italy after the spread of antiretroviral combination therapies (HAART). METHODS: Five thousand four hundred and twenty-two patients from the I.CO.N.A. (Italian Cohort Naive Antiretrovirals) study were followed between 1997 and 2002. Costs included antiretroviral therapies (ART), hospital admissions, prophylaxis, and main laboratory examinations. The perspective was that of the National Health Service. RESULTS: Admission costs per person-year decreased from 2148 euro in 1997 to 256 in 2002, while the average annual costs of ART increased from 2145 to 3149 euro (1997 prices). From 1997 to 1999, ART costs increased from 42.3 to 85.9% of the total, while admission costs decreased from 42.3 to 7.0% and prophylaxis from 7.3 to 1.7%. The breakdown of ART costs shows how dual therapies decreased over time in favor of HAART, falling from 26.8% in 1997 to 5.9% in 2002. Patients with fewer than five treatment switches had the lowest costs distributions over the entire observation period. CONCLUSIONS: From 1997 to 2002 inpatient costs progressively decreased in favor of antiretroviral therapy. Annual average costs per patient decreased, while total direct costs increased over time: health resources, initially concentrated on hospitalized patients were then distributed over a growing number of subjects.
Abstract: OBJECTIVE: To describe the epidemiological, clinical and economic changes that occurred in the HIV epidemic in Italy prior to and after the introduction of highly active antiretroviral therapy (HAART). DESIGN: A prospective, observational, multicentre case-control study was conducted comparing data, collected over 6 months, from an AIDS cohort in 1998 with that of a cohort in 1994. Out of 77 patients with AIDS in the 1998 cohort, 74 survived. These 74 patients were matched for severity of illness with 74 patient survivors from the 1994 cohort to enable valid comparisons of mortality, disability-dependency (DD), health-related QOL (HR-QOL), and direct costs. RESULTS: Overall, a considerable difference was observed in mortality (33.8% in 1994 vs 3.9% in 1998) between unmatched patients of the two cohorts. As for matched patients, the number of hospital admissions was 1.7 in 1994 and 0.8 in 1998; the average length of stay was 28.1 days in 1994 and 12.6 days in 1998. The direct cost per patient per year was euro15 390 and euro11 465 for the 1994 and 1998 cohorts, respectively (1999 values). The 1998 patient cohort had significantly better HR-QOL at 6 months in two domains of the instrument used (emotional reaction and energy) and the percentage of totally dependent patients was significantly lower compared with the 1994 cohort (1.4% vs 6.8%). CONCLUSIONS: This is the first study to present a comprehensive comparison of direct costs, DD and HR-QOL of patients with AIDS between two time periods. The use of a case-control design has enabled changes in costs and outcomes to be linked to the introduction of HAART in Italy in 1997.
Abstract: BACKGROUND/AIMS: Steatosis in patients with chronic hepatitis C (CHC) may be the result of both viral and host factors. To evaluate: (1) the relationship between steatosis and either host or viral factors; (2) the correlation between steatosis and fibrosis in patients with CHC. METHODS: A consecutive series of 349 patients were evaluated for steatosis. At liver biopsy, patients were tested for virological, and laboratory analysis and questioned for alcohol consumption. RESULTS: Logistic regression analysis demonstrated that steatosis was independently associated with genotype 3a (odds ratio, OR 3.5), alcohol intake at the time of biopsy (OR 2.6) and age >35 years (OR 2.7). In multivariate analysis the presence of fibrosis was associated with past alcohol abuse (OR 3.7), and age older than 44 years (OR 2.2). Overall, a weak correlation was found between grade of steatosis and fibrosis score (r=0.861, P=0.05), which disappeared excluding patients without past or current alcohol intake. A direct correlation emerged between grade of steatosis and both 'grading' and 'staging' only in patients with genotypes other than 3a. CONCLUSIONS: Genotype 3a is the main risk factor for steatosis in patients with CHC. The grade of steatosis correlated with both grading and staging only in patients with genotypes other than 3a and this relationship is strictly linked to alcohol consumption.
Abstract: Diarrhea is a common symptom that many HIV patients experience either as a consequence of HIV infection or of highly active antiretroviral therapy (HAART). A multicenter, prospective observational study was conducted in 11 AIDS clinics in Italy to determine the effect of diarrhea on health-related quality of life among patients receiving HAART. The study enrolled 100 consecutive HIV positive patients who had diarrhea while on HAART. For each enrolled patient a control patient with matching disease stage who did not have diarrhea was identified using existing data from another prospective observational study conducted in 34 AIDS clinics (including the 11 in current study). Quality of life was measured by MOS-HIV Health Survey (MOS-HIV). Paired t-test and multiple regression analysis were used to compare the quality of life among patients with and without diarrhea. Mean patient age was 40 +/- 7 years; 69% were male. Mean CD4 cell count was 342 +/- 239 cells/mm3; 59% had AIDS. Of the cases, 49 patients had severe diarrhea (> 5 bowel movements or > 3 watery per day) and 46 patients had moderate diarrhea (3-5 bowel movements). Compared to matched control patients, cases experiencing diarrhea while on HAART had significantly lower MOS-HIV scores in all domains. The significant adverse effect of diarrhea on quality of life should be considered when choosing the appropriate antiretroviral drugs regimen.
Abstract: OBJECTIVE: To assess the impact of highly active antiretroviral therapy (HAART) on health resource utilisation (HRU) and to estimate associated direct costs in a population based setting. DESIGN: Retrospective study of all patients in the Institute of Infectious and Tropical Diseases (Brescia, Northern Italy) during a 4 years period related to the prescription of HAART has been performed: from 1997 (before HAART) to 2000 (after substantial period of HAART prescription). MAIN OUTCOME MEASURES AND RESULTS: HIV inpatient admissions (IA's) decreased from 506.8/1000 patients (pts) in 1997 to 246.3/1000 pts in the year 2000. Day care admissions (DCA's) also decreased from 1658.3/1000 pts to 942/1000 pts, while outpatient consultations (OC's) increased from 2046.9/1000 pts to 2590.6/1000 pts in the same years, respectively. By contrast, a relative increase of IA's and DCA's of patients whose serostatus was HIV-negative or unknown has been found. Cost of antiretroviral therapy increased by 2582 Euro (2272 US Dollars), while cost of HIV care (IA+DCA+OC) decreased by 1546 Euro (1360.4 US Dollars) per patient, resulting in a saving in direct cost equal to 60% of the increase in the expenditure for antiretroviral drugs. CONCLUSIONS: Our results demonstrate the shift of HIV care from inpatient to outpatient services that occurred after HAART had been introduced into clinical practice. Despite persisting clinical benefits, an increase in total direct cost for HIV pts has been seen for the first time during the HAART era in the year 2000, probably due to an over-prescription of HAART, according to actual Guideline for antiretroviral therapy use, to pts who were not at risk of clinical progression in the short term. Pharmacoeconomical surveillance of HAART is necessary while a favourable impact on the saving in cost is expected from the new treatment guidelines that suggest a relative delay in starting HAART.
Abstract: According to economic principles an inappropriate prescription is the choice of an antimicrobial with higher/equivalent cost and lower effectiveness (or higher cost and equivalent/lower efficacy) than an alternative (in this case, the former is specified as a "dominated" drug). To identify cost-effective antibiotics we applied the principles of incremental cost-effectiveness analysis (ICEA) to microbiological data of San Bortolo Hospital. Its 27 wards were grouped in 9 functional areas. The resistance patterns of 8 urinary pathogens in the 1997 microbiology data base were assessed. The measure of antibiotic effectiveness was expressed as the percentage of isolates susceptible to each antibiotic tested. The difference in cost (i.e. the incremental change) between each antibiotic and the next more expensive alternative was calculated, and compared with the incremental change in effectiveness. Calculations were made for each pathogen. The antibiotics remaining after exclusion of all "dominated" antibiotics were pooled on a list defined as "Specific Area Formulary". The implications of the use of economic principles within a general antimicrobial policy are discussed.
Abstract: Treatment of osteomyelitis requires prolonged hospital stay, lengthy antibiotic therapy and adequate surgical debridement. Outpatient parenteral antibiotic therapy (OPAT) is a new approach to reduce patient discomfort and hospital costs. Teicoplanin, a glycopeptide antibiotic with a long half-life (72 hours), is one of the most useful drugs for OPAT. We performed a pilot study to assess the safety and efficacy of three-times weekly teicoplanin in the treatment of methicillin-resistant (MR) acute staphylococcal osteomyelitis. Ten patients with acute post-traumatic osteomyelitis were enrolled. Pathogens were MR Staphylococcus aureus (5 patients) and MR coagulase-negative staphylococci (5 patients). After a loading dose of 400 mg b.i.d. for 3 days, patients were treated with an intravenous dose of 1000 mg on Mondays and Wednesdays and with a 1200 mg dose on Fridays. Teicoplanin trough levels were maintained within a 10 to 20 mg/L range. If hardware removal had been possible at enrollment, treatment was carried out for at least 4 weeks. If, on the contrary, hardware removal had not been possible, teicoplanin was administered as suppressive therapy until hardware removal. Treatment was successfully performed in 9 out of 10 patients, whereas in one patient only improvement was achieved. Side effects were not recorded. Three times weekly teicoplanin seems to be a valuable option in the treatment of acute MR staphylococcal osteomyelitis. Further studies are warranted in order to better define the role of this new administration schedule in this field.
Abstract: The aim of this study was to determine patients' perceptions of antibiotic therapy and the doctor's skill in the management of ambulatory respiratory tract infections. Standardized face-to-face interviews were used with more than 3000 randomized patients or parents from four European countries. Attitudinal dimensions relating to their doctor identified four patient types: Involved (30%), Deferent (23%), Ignored (13%) and Critical (17%). Involved and Deferent patients were the most satisfied by the information received from their doctor (43%/39% compared with 17%/16% for Ignored/Critical, respectively, P < 0.01). They also scored more highly on the accurate use of antibiotics, with 80%/80% vs. 38%/62%, respectively (P < 0.01), understanding dosing intervals and 77%/77% vs. 36%/60% (P < 0.01), understanding the course length. Involved and Deferent patients showed better compliant behaviour, with 91% of both groups vs. 86% of the Ignored and Critical claiming to have taken every dose (P < 0.001) and 92%/87% vs. 84%/85% claiming to have finished the course (P < 0.001 for Involved only). Involved and Deferent patients were less prone to save part of a course of antibiotics than the Ignored and Critical (46%/41% vs. 20%/31%, P < 0.001), and they perceived the antibiotics prescribed to be more effective (36%/31% vs. 21%/15%, P < 0.001). By analysing patient perceptions, this study identifies an important mirror effect, whereby a more sympathetic attitude from the doctor should increase the patient's involvement in disease management, for a more appropriate use of antibiotics in common infections.
Abstract: From January 1991 to June 1997, patients undergoing primary elective monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective, open clinical study on the efficacy and safety of regional prophylaxis with teicoplanin (TEC). Those scheduled for monolateral TKR (115 patients) received 400 mg of TEC in 100 ml of saline as a 5-min infusion into a foot vein of the leg to be operated on immediately after the tourniquet was inflated to 400 mm Hg (ca. 50 kPa). For patients undergoing bilateral surgery (45 patients), regional administration of TEC was also repeated for the second knee operation. Follow-up ranged from a minimum of 2 years to 8 years. None of the patients experienced local or systemic adverse effects following regional administration of TEC. In the immediate postoperative and 2-year follow-up periods, only one superficial infection of the primary site attributable to intraoperative contamination (prophylaxis failure) out of the 205 prostheses implanted was observed. Deep infections involving the prosthesis did not occur. Infectious complications at distant sites were observed in nine cases (urinary tract infection due to Escherichia coli in eight cases, and Salmonella enteritidis gastroenteritis in one case) in the immediate postoperative period; they all were rapidly cured after antibiotic treatment. A delayed prosthetic infection, related to hematogenous spread of the etiological agent and therefore not considered a prophylactic failure, was observed in a patient who had undergone TKR 5 years before. Regional administration of TEC in monolateral and bilateral TKR appears to be a safe and valuable prophylactic technique.
Abstract: Nosocomial infections are a good indicator of the quality of health care provided by hospitals. Despite their cost-effectiveness, nosocomial infection programs are rarely applied in Italy. Epidemiological surveillance is the simplest measure to adopt because it allows us to monitor the baseline endemic rates, identify new epidemics and assess the improvements achieved by interventions provided. The presence of continuous epidemiological surveillance must be considered the exception rather than the rule in Italy. In this paper, the prevention of nosocomial infections was analysed through two economic evaluation techniques (i.e. cost-benefit and cost effectiveness). A hierarchy of intervention based on cost effectiveness, hospital size and organisational setting was also provided. The main conclusions are the following: 1. Benefits associated to prevention of nosocomial infections are considered small because of the uncertainty associated to the future. Therefore a discount factor must be applied. 2. Local factors and specific reasons are usually advocated to explain the simple fact that infection control programs are only formally implemented and usually limited to the constitution of a nosocomial infections committee. 3. The prevention of nosocomial infections must be provided for under specific laws which take into account the various organisations and structures found in different hospitals.
Abstract: Among mental disorders associated with HIV infection, dementia is the one most likely to have a major impact on public health, both as a result of the high levels of individual disability, and the greater demand of health care resource utilization. Epidemiologic and economic impact of HIV-associated dementia needs to be estimated, in order to provide policy makers and health managers with the information required for decision making and resource allocation. An increase in HIV encephalopathy prevalence rates may be expected as a consequence of longer survival time in dementia patients and in patients with other AIDS defining disease (longer survival increases the risk of developing HIV encephalopathy). A resource utilization study shows that, in the chronic stage of the disease, in-patient days per person-year are almost double in AIDS subjects with neurological complications as compared with those without neurological complications; no major difference appears when considering out-patients consultations and day-care treatments. In conclusion, a significant rise in resource utilization and in related costs may be anticipated as a consequence of the increasing prevalence of HIV encephalopathy. Further studies seem necessary to compare different approaches in the management of this debilitating disease, in view of a more rational utilization and allocation of resources.
Abstract: OBJECTIVE: To demonstrate the application of an approach for assessing efficiency and rationality in the use of resources for the care of patients with AIDS (PWA), using data for north-east Italy. DESIGN: An economic methodology, the balance of care (BoC) approach, enabled identification of scenarios for the current, planned and recommended provision of care in the study region. METHODS: Data on the supply and utilization of care by PWA across four locations (inpatient care, day care, home care and sheltered accommodation) was collected for a 6-month period during 1994. The current BoC measured in care contacts across the locations was compared with a planned BoC scenario, derived from the Italian AIDS Health Plan, and a recommended BoC scenario based on a delphi expert panel judgement of the appropriate care location according to sets of hypothetical clinical and social characteristics of PWA. The cost consequences of reallocating patient contacts between the current BoC to the recommended BoC was assessed for inpatient and day care contacts. RESULTS: There is an overprovision of home care in the planned BoC scenario if applied to the study region. The cost consequences of a shift of care contacts according to the recommended scenario results in a potential cost reduction of 9.2% compared with the current scenario, and hence an expected efficiency improvement. CONCLUSION: The BoC approach can be applied to improve the efficiency and rationality of resource use in planning care provision for PWA.
Abstract: Evidence for an association between socioeconomic status (SES) and health service utilisation (HSU) by patients with AIDS is examined using data for an Italian AIDS study population. A composite measure of SES which takes into account several key variables was developed using Multiple Correspondence Analysis. A classification of SES categories (high, medium-high, medium-low, low) was constructed and resource utilisation across the categories compared. The study population were patients with AIDS referred to 10 AIDS clinics in the study area in North-East Italy. A questionnaire survey was undertaken over the period January to June 1994, and was completed by 555 patients. Statistical analysis was conducted, using log-linear modelling, of health service utilisation (covering inpatient and day care) by SES categories, illness severity and HIV transmission route group. The analysis demonstrated that SES has a statistically significant association with variation in HSU, secondary in importance to severity of illness. This finding has important implications for future care planning for HIV/ AIDS in Italy, and potentially to other countries. Further research is needed to examine the relationship between SES and health service utilisation and costs in Italy and in other European countries.
Abstract: This study estimates the current and future hospital resources for AIDS patients in the European Union (EU), using multinational scenario analysis (EU Concerted Action BMH1-CT-941723). In collaboration with another EU-project ('Managing the Costs of HIV Infection'), six national European studies on the utilization of hospital care for AIDS have been selected to provide the data for our analysis. The selection criteria involve recentness, quality, comparability, accessibility and representativeness. Baseline hospital resource utilization is estimated for hospital inpatient days and outpatient contracts, using a standardized approach controlling for two severity stages of AIDS (chronic stage and late stage). The epidemiological part of the study is based on standard models for backcalculating HIV incidence and projecting AIDS incidence, prevalence and mortality. In the next step, baseline resource utilization is linked to epidemiological information in a mixed prevalence and mortality-based approach. Several scenarios render different future epidemiological developments and hospital resource needs. For the year 1999, hospital bed needs of 10,000-12,700 in the EU are indicated, representing an increase of 20-60% compared to the estimated current (1995) level. The projected range for 1999 corresponds to a maximum of 0.65% of all hospital beds available in the EU. The growth in the number of outpatient hospital contacts is projected to possibly exceed that of inpatient days up to 1.82 million in 1999. Our methodology illustrates that estimation of current and future hospital care for AIDS has to be controlled for severity stages, to prevent biases. Further application of the multinational approach is demonstrated through a 'what-if' analysis of the potential impact of combination triple therapy for HIV/AIDS. Estimation of the economic impact of other diseases could as well benefit from the severity-stages approach.
Abstract: OBJECTIVES: A study was conducted to evaluate the extent of a Q-fever epidemic through active case finding in the area of Vicenza (north-eastern Italy), and to identify risk factors for Q-fever in this outbreak. METHODS: 1) Descriptive epidemiology; 2) Seroepidemiological survey; 3) Case-control study. 1) Epidemic curve and maps with the location of cases. Identification of the road followed by the flocks of sheep. 2) Cross-sectional study on humans and flocks of sheep tested for anti-Coxiella burnetii antibodies. 3) Cases were defined by the presence of fever > 38 degrees C plus serological confirmation. Controls were 94 apparently healthy individuals attending outpatient facilities for control visits or certification, group-matched by geographical area, age and gender. A standardized questionnaire was administered by trained interviewers. Odds ratio and 95% confidence intervals (CI) were used to evaluate risk factors for Q-fever. RESULTS: A total 58 cases were identified in a 5-month period. Male to female ratio was 2.8:1; mean age was 42 years (range: 20-65 years). Twenty-eight patients (48%) were hospitalized. Fever was accompanied by asthenia (81%), headache (76%), chills (72%), and myalgia and arthralgia (53%); cough was present in 47% of patients. Rx abnormalities were found in 81% of the patients undergoing chest X-ray. Among 111 apparently healthy family members who underwent serological testing, four (3.6%) had antibodies to Coxiella burnetii. Three flocks which passed through the outbreak area between late May and early June were shown to be infected, with prevalence of antibodies ranging between 45 and 53%. The case-control study showed a significant association with exposure to flocks of sheep (Odds ratio = 6.1; 95% CI 2.5, 16.3). Other potential risk factors were not more commonly reported by cases with respect to controls. CONCLUSIONS: Indirect exposure to flocks of sheep was a determinant of this outbreak of Q-fever. This finding suggests that transmission occurred through inhalation of contaminated airborne particles. The importance of control measures should be stressed in areas traversed by flocks of sheep.
Abstract: Teicoplanin is a glycopeptide antibiotic whose activity is selectively oriented against Gram-positive aerobic and anaerobic bacteria, including Staphylococcus aureus, coagulase-negative staphylococci, Clostridium difficile, Peptostreptococcus spp. and Corynebacterium jeikeium; such activity is affected by neither methicillin resistance nor beta-lactamase production. Teicoplanin is not significantly absorbed from the gastrointestinal tract; consequently, it has to be administered intravenously (either by infusion or by rapid injection) or intramuscularly. Its long half-life allows regimens based upon once daily administration. The adverse effects most frequently associated with teicoplanin treatment are local and hypersensitivity reactions, such as itching and drug fever; anaphylactoid reactions (the 'red man syndrome') are seldom observed. Teicoplanin also has less potential than vancomycin to cause nephrotoxicity, especially when administered in combination with an aminoglycoside. Teicoplanin has been proven to be effective in the treatment of microbiologically documented Gram-positive infections, including 'difficult to treat infections' such as endocarditis and prosthetic infections. Furthermore, recent trials in patients with haematological malignancies or other cancers have clearly demonstrated that teicoplanin is at least as efficacious as vancomycin in the empirical initial antibiotic regimen for febrile neutropenic patients, and is associated with fewer adverse effects. Finally, owing to its good tolerability profile and the advantage of once daily administration by both intravenous and intramuscular routes, teicoplanin has proven to be very useful for the outpatient treatment of serious Gram-positive infections. In conclusion, teicoplanin is potentially an effective alternative to vancomycin both in immunocompetent and immunocompromised patients, with the advantage over vancomycin of single daily dose administration and lower toxicity. Further comparative studies with vancomycin are, however, required to better define the therapeutic role of teicoplanin for particular infections (i.e. infective endocarditis).
Abstract: Of 160 travellers from various regions in Italy who had taken part in a five-day organized trip to Phuket, Thailand, and been accommodated in the same luxury hotel, 17 showed either amebic abscess or colitis. A pretested questionnaire that focused on the consumption of foods and beverages well known to be a source of intestinal infection in endemic areas was available from these 17 patients as well as from 41 out of 74 asymptomatic travellers. Stool samples for parasitological examination were also available. In patients affected with amebic abscess, antibodies to Entamoeba histolytica were also determined. Overall, parasitological examinations were negative in eight (13.8%) patients, and 50 out of 58 (86.2%) were found to be positive. The prevalence of Giardia lamblia and E. histolytica infections was 67.2% and 72.4%, respectively, and 28 subjects (48.3%) were stool-positive for both of these protozoa. No other intestinal parasites were found. No particular food or beverage was consumed by all of the parasitized subjects and by none of the stool-negative individuals. However, the consumption of drinks with ice, ice cream and raw fruit in ice was significantly associated with E. histolytica and/or G. lamblia infections (Fisher's exact test, p ranging from 0.03 to 0.003).
Abstract: Three cases of cutaneous anthrax are reported which occurred in a farming family in northern Italy. Epidemiological studies revealed contact with an infected cow (delivery of a stillborn fetus and slaughter). The cow was slaughtered soon after the delivery; cultures of carcass specimens yielded growth of Bacillus anthracis. The origin of the animal infection was not known. Serum samples were obtained from all 11 members of the family group and randomly from 10 of the 75 cows on the farm, which appeared to be in good health. Tests for antibodies against protective antigen and lethal factor using EIA and Western blot techniques were positive in three subjects (in paired sera) with cutaneous anthrax and in one subject who neither had had direct contact with the infected cow nor showed any sign of anthrax.
Abstract: A prospective, randomized study comparing oral teicoplanin with oral vancomycin in the treatment of pseudomembranous colitis (PMC) and Clostridium difficile-associated diarrhea (CDAD) was performed. Teicoplanin was administered at a dosage of 100 mg twice a day for 10 days, and vancomycin was administered at a dosage of 500 mg four times a day for 10 days. CDAD was diagnosed by demonstrating both C. difficile and cytotoxin in the feces of symptomatic patients (more than three loose stools per day). The diagnosis of PMC was also based on colonoscopy. Cytotoxin assay and cultures were checked in all patients 7 to 10 days after discontinuation of therapy and 25 to 30 days thereafter. Of the 51 patients enrolled, 46 were judged to be assessable. Among these, 26 received teicoplanin and 20 received vancomycin. At enrollment, both groups were comparable in terms of age, sex, occurrence of PMC or CDAD, and previous antibiotic treatment. Eighteen of the 20 patients in the vancomycin group and 10 of the 26 patients in the teicoplanin group had previously undergone surgery (P = 0.0004). Treatment resulted in the clinical cure of 20 (100%) vancomycin and 25 (96.2%) teicoplanin patients (P = 0.56). After discontinuation of therapy, clinical symptoms recurred in four (20%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.21). Posttherapy asymptomatic C. difficile carriage (positive follow-up cultures without any clinical symptoms) occurred in five (25%) vancomycin patients and two (7.7%) teicoplanin patients (P = 0.11).Overall, 9 of 20 (45%) vancomycin patients and 5 of 26 (19.2%) teicoplanin patients (P=0.059) appeared not to be cleared of C. difficile after treatment. No adverse effects related to vancomycin or teicoplanin therapy were observed.
Abstract: OBJECTIVE: To evaluate the costs and cost-effectiveness of home-care assistance (HCA) as an alternative to hospital-based care only for patients with AIDS (PWA). DESIGN: A 6-month prospective study. Use of resources by a control group of PWA receiving ordinary hospital-based care (OC group) was compared with that by a random group of PWA who, in addition to hospital care, were also receiving home care (HC group). SETTING: Home- and hospital-based care for PWA in Vicenza, Italy. PATIENTS: HC group selection was based on eligibility criteria for severity of illness, home location and economic and family support. Ten of the PWA satisfying all eligibility criteria were randomly allocated to the HC group. The control group consisted of 32 PWA lacking one or more of the eligibility criteria. INTERVENTION: HCA involved the provision of palliative care for PWA by a multidisciplinary team of caregivers. Hospital-based services covered inpatient and outpatient services. MAIN OUTCOME MEASURE: The health benefits for HC and OC groups using a quantitative quality of life measure (the Quality of Well-Being Scale). RESULTS: Overall health-care cost savings of 6-7%, relative to the OC group, were predicted for the HC group. Costs per well week were estimated at US$482 for the HC group and US$791 for the OC group. CONCLUSION: Home-care assistance appears to be a cost-effective strategy for the treatment and care of PWA if strict eligibility criteria are adhered to.
Abstract: Opioid narcotics are present in seminal plasma, although their physiological effect on spermatozoa is still unknown. This study reports data on metabolic parameters of human spermatozoa in the presence of a met-enkephalin analogue: D-Ala2-Mephe4-Met-(o)-ol-Enkephalin, FK 33824, Sandoz, Basel, Switzerland (DAMME), and its receptor antagonist naloxone hydrochloride, Endo Laboratories, Garden City, New York. Our findings indicate that the metenkephalin analogue reduces sperm motility and cellular O2 consumption without affecting cellular ATP content and viability. The hypothesis that DAMME acts on adenylate-cyclase is briefly discussed.
Abstract: The aim of this study was to ascertain whether there is a correlation between gonadal steroids and opioid control of prolactin (PRL) secretion. Four castrated men, aged 18 to 24 years were submitted to intravenous injection of 250 ug of a met-enkephalin analog (D-Ala2-Mephe4-Met-(o)-ol-Enkephalin, FK 33824) (DAMME). In normal men DAMME injection was also performed on the 6th day after treatment with clomiphene citrate (CC) (200 mg/day for 5 days), a specific nonsteroidal estrogen receptor blocker. In castrated men and in normal men after CC treatment, there was a lower PRL response to DAMME than in controls (P less than 0.0005). These results suggest that gonadal steroid deficiency seems to cause a change in the opioid system and/or dopaminergic control of prolactin secretion.
Abstract: Endogenous opioid peptides exert a tonic inhibition on gonadotropin secretion at the hypothalamic level, but the mechanisms by which they act are still unknown. Previous experimental studies suggest that the endogenous opioid peptides change dopaminergic and serotoninergic tones at the hypothalamic level. We have investigated whether the stimulatory effect of naloxone on luteinizing hormone (LH) secretion is due to its influence on these neurotransmitters. Two experimental models were studied, and two sets of effects on LH secretion induced by intravenous naloxone infusion (20 mg over 2 hours) in 14 normal men 20 to 25 years of age were evaluated: the effect of oral sulpiride (150 mg), a potent dopaminergic antagonist, and the effect of oral fenfluramine (60 mg), a drug that stimulates the serotoninergic receptors by releasing serotonin and inhibiting its reuptake. The study demonstrated that naloxone infusion significantly stimulated the LH secretion throughout the period of observation (P less than 0.01 versus saline). The pretreatment with sulpiride did not change the LH response to naloxone. After fenfluramine pretreatment, naloxone failed to induce any rise in LH secretion. Follicle-stimulating hormone did not show any important variation in either test. The data suggest that in man the stimulatory ability of the opiate receptor antagonist naloxone to elicit a rise in LH plasma levels may involve the serotoninergic, but not the dopaminergic, hypothalamic system. This hypothesis, however, does not exclude the involvement of other hypothalamic neurotransmitters.
