Estimating the prevalence of Parkinson's disease (PD) and proportions of patients with associated dementia and depression among the older adults based on secondary claims data.

OBJECTIVES: While the epidemiology of Parkinson's disease (PD) has been extensively studied, data on the prevalence of PD among the older adults in Germany are scarce, based on small samples, and limited to primary data designs. This study estimated the PD prevalence among the older adults in Germany in 2006 using secondary data. METHODS: We included 815,573 health insurance members aged ≥65 years from all regions in Germany. PD was identified in case of at least one inpatient or outpatient diagnosis. An outpatient diagnosis had to be confirmed by either a subsequent diagnosis or an antiparkinsonian drug within 12 months. PD was also assumed if a first prescription was confirmed by a diagnosis within 12 months. Cases were checked for a diagnosis of dementia or depression. RESULTS: The standardized prevalence of PD was 1680 (95% confidence interval (CI): 1644-1716) cases per 100,000 persons. The prevalence increased with age and peaked in the age group of ≥90 years (4633 cases; 95% CI: 4227-5068) with higher rates in men (1729; 95% CI: 1684-1776) than in women (1644; 95% CI: 1593-1697). Dementia and depression occurred in 26.6% (95% CI: 25.8-27.5) and 32.6 (95% CI: 31.7-33.5) of PD cases, respectively. CONCLUSIONS: The age-related increase of PD prevalence and the age-specific prevalence estimates are in line with other European studies, stressing the public health relevance related to PD. In addition to the minimization of biases that might occur in primary data studies, further strengths of our findings are the large underlying sample size and the coverage of Germany.

Tocilizumab-induced pancreatitis: case report and review of data from the FDA Adverse Event Reporting System.

WHAT IS KNOWN AND OBJECTIVE: Tocilizumab (TCZ) is a humanized monoclonal antibody acting against the IL-6 receptor. It is a drug used in the treatment of rheumatoid arthritis and can be either given intravenously every 4 weeks or subcutaneously once a week. Known adverse events (AE) associated with TCZ include: infections of the upper respiratory tract, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. Here, we present the first well-documented case of TCZ-induced acute pancreatitis (AP) and a systematic review of the literature including data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Patient data collection was performed within the Berlin Case-Control Surveillance Study. A literature search for TCZ-induced AP was conducted. Analysis of the FAERS database concerning TCZ-associated pancreatic AE from the period of 2009 until the first quarter of 2013 was conducted. RESULTS AND DISCUSSION: A 40-year-old man presented with a 2-day history of progressive upper abdominal pain with elevated serum lipase and triglyceride levels. Biliary pancreatitis was ruled out by abdominal sonography and CT scan. Cessation of intravenously administered TCZ resulted in improvement of the patient's condition and a decline in elevated laboratory values, suggesting a probable relationship between TCZ intake and AP. Analysis of the FAERS database retrieved 52 cases of TCZ-associated AP that accounted for 70% of all pancreatic AE in association with TCZ use. Further literature search detected three additional cases in which TCZ use was associated with AP. WHAT IS NEW AND CONCLUSION: Physicians should be aware of the probable association between TCZ use and AP. Targeted post-authorization studies are needed to confirm and quantify the risk of TCZ-induced AP.

[Therapy Goals for Children and Adolescents with ADHD and their Primary Caregivers. A Content Analysis and Examination of Agreement of ADHD Patients and their Primary Caregivers]. / Therapieziele von Kindern und Jugendlichen mit ADHS und ihren Hauptbezugspersonen. Eine inhaltsanalytische Auswertung und Prüfung der Übereinstimmung zwischen Betroffenen und Bezugspersonen.

OBJECTIVE: The aim of this study was to identify individual therapy goals (ITGs) of children and adolescents with ADHD and their primary caregivers. METHODS: Within the evaluation of the selective contract for children and adolescents with ADHD in Bremerhaven, Germany, ITGs of 42 study participants (aged 8-17) and their primary caregivers were collected with the psychotherapy basis documentation for children and adolescents (Psy-BaDo-KJ). ITGs were analysed following the classification of categories for individual therapy goals (KITZ) and their modification for children and adolescents. Analysis focused on the most frequently named ITGs and the agreement of patients and primary caregivers ITGs on the individual level. RESULTS: 235 ITGs were named. The greatest proportion of ADHD patients and their caregivers (47%) focused on interactional, psychosocial conflicts. In 19% of the cases (n=8) patients and their caregivers had the same main goal. 38% of patients and of caregivers (n=16) named the other ones main goal in one of his/her ITGs as well. CONCLUSIONS: ADHD patients and their primary caregivers both pursue ITGs related to ADHD symptoms. Few ITGs address medication related aspects. In case of differences in the ITGs of a patient and his/her primary caregivers, therapists should check whether differing ITGs address the same problem from different perspectives.

[Pharmacovigilance in Germany : It is about time]. / Pharmakovigilanz in Deutschland : Es wird langsam Zeit.

BACKGROUND: Pharmacovigilance is defined as the activities relating to the detection, assessment, and prevention of adverse drug reactions (ADRs). Although its beginnings in Germany date back more than 50 years, a stagnation in this field has been observed lately. OBJECTIVES: Different tools of pharmacovigilance will be illustrated and the reasons for its stagnation in Germany will be elucidated. CURRENT DATA: Spontaneous reporting systems are an important tool in pharmacovigilance and are based on reports of ADRs from treating physicians, other healthcare professionals, or patients. Due to several weaknesses of spontaneous reporting systems such as underreporting, media bias, confounding by comorbidity or comedication, and due to the limited quality of the reports, the development of electronic healthcare databases was publicly funded in recent years so that they can be used for pharmacovigilance research. In the US different electronic healthcare databases were merged in a project sponsored by public means resulting in more than 193 million individuals. In Germany the establishment of large longitudinal databases was never conceived as a public duty and has not been implemented so far. Further attempts to use administrative healthcare data for pharmacovigilance purposes are severely restricted by the Code of Social Law (Section 75, Book 10). This situation has led to a stagnation in pharmacovigilance research in Germany. CONCLUSIONS: Without publicly funded large longitudinal healthcare databases and an amendment of Section 75, Book 10, of the Code of Social Law, the use of healthcare data in pharmacovigilance research in Germany will remain a rarity. This could have negative effects on the medical care of the general population.

Comparison of basal insulin therapies with regard to the risk of acute myocardial infarction in patients with type 2 diabetes: an observational cohort study.

AIMS: To assess the risk of acute myocardial infarction (AMI) in patients with type 2 diabetes mellitus treated with long-acting insulin analogues in comparison with other basal insulin therapy. METHODS: We used German insurance claims data from the years 2004-2009 to conduct a study in a retrospective cohort of patients with type 2 diabetes. Naïve insulin users were defined as patients who had an insulin-free history before the first prescription of long-acting analogue insulin, human NPH insulin or premixed insulin and who were pretreated with oral antidiabetic drugs. Adjusted hazard ratios (HRs) of AMI and corresponding 95% confidence intervals (CIs) were calculated using sex-stratified Cox models. Propensity-score-matched analyses were conducted as sensitivity analyses. RESULTS: We identified 21,501 new insulin users. Patients treated with premixed insulin were older than patients treated with analogue or NPH insulin (mean age 70.7 vs. 64.1 and 61.6 years, respectively) and had more comorbidities. Regarding the risk of AMI, adjusted HRs showed no statistically significant difference between NPH and analogue insulin (HR 0.94, 95% CI 0.74-1.19), but a higher risk for premixed than for analogue insulin (HR 1.27, 95% CI 1.02-1.58). Contrary to the primary analysis, the propensity-score-matched analysis did not show an increased risk for premixed insulin. CONCLUSIONS: In contrast to a former database study, no difference was observed for the risk of AMI between long-acting analogue and NPH insulin in this study. Neither long-acting analogue insulin nor premixed insulin appears to be associated with AMI in patients with type 2 diabetes.

Use of over-the-counter (OTC) drugs and perceptions of OTC drug safety among German adults.

PURPOSE: In Europe, little empirical evidence is available about over-the-counter (OTC) drug consumption and risk perceptions. The objective of this study was to describe consumers' OTC drug use and perceptions of OTC drug safety in Germany. METHODS: An online survey based on a quota sample with combined strata for age, gender, and education of 300 adult German participants was conducted in June and July 2013. The survey questionnaire covered the participants' OTC and prescription drug use, risk perceptions of OTC and prescription drugs, package leaflet reading habits, and OTC drug off-label use. RESULTS: Seven day prevalences of OTC drug use were higher in women (52.0%) than in men (40.8%). The risk perception of specific OTC drugs was impacted by the route of administration, the indication, and the drugs' ingredients. Products for dermal application or plant-based products were considered 'rather not risky' by 82.7-96.6 of the participants, depending on the product. Products for oral use or chemically synthesized substances were considered less safe. While 48.0% of consumers reported always reading the package leaflet of OTC drugs, 44.5% reported not reading it if they knew the drug or believed the drug was very safe. People, 60 years and older, reported significantly lower levels of OTC drug off-label use (9.3%) than younger people (22.0%). CONCLUSIONS: The 7-day prevalence of OTC drug use in Germany is high, especially among women. Consumers generally have balanced perceptions regarding OTC drug safety. Behaviours and knowledge related to OTC drug use should be considered by health care providers and regulators.

[Linkage of statutory health insurance data with those of a hospital information system: feasible, but also "useful"?]. / Verknüpfung von Routinedaten der Gesetzlichen Krankenversicherung mit Daten eines Krankenhausinformationssystems: Machbar, aber auch "nützlich"?

AIM: Administrative data are increasingly being linked with other data sources for research purposes in the field of epidemiology and health services research abroad. In Germany, the direct linkage of routine data of statutory health insurance (SHI) providers with other data sources is complicated due to strict data protection requirements. The aim of this analysis was to evaluate an indirect linkage of SHI routine data with data of a hospital information system (HIS). METHODS: The dataset comprised data from 2004 to 2010 from 2 sickness funds and one HIS. In both data sources, hospitalisations were restricted to admissions into one hospital with at least one diagnosis of heart failure. The 2 data sources were linked, in cases of the agreement of the admission and discharge dates, as well as the agreement of at least a certain percentage of diagnoses in HIS data when compared to SHI data (full coding depth). Based on the direct linkage using the pseudonymised insurance number as gold standard, the proposed linkage approach was evaluated by means of test statistics. Furthermore, the completeness of relevant information of the HIS was described. RESULTS: The dataset contained 3 731 hospitalisations from the HIS and 8 172 hospitalisations from the SHI routine data. The sensitivity of the linkage approach was 86.7% in the case of an agreement of at least 30% of the diagnoses and decreased to 41.7% in the case of 100% agreement in the diagnoses. The specificity was almost 100% at all studied cut-offs of agreement. Anthropometric measures and diagnostic information were available only for a small fraction of cases in the data of the HIS, whereas information on the health status and on laboratory information was comparatively complete. CONCLUSION: For the linkage of SHI routine data with complementary data sources, indirect linkage methods can be a valuable alternative in comparison to direct linkage, which is time-consuming with regard to planning and application. Since the proposed approach was used in a relatively small sample and a restricted patient population, a replication using nation-wide data without respective restrictions would require an extension of the algorithm. Furthermore, the large administrative effort seems questionable considering the comparatively high amount of missing values in interesting information in the HIS.

[Use of routine data from statutory health insurances for federal health monitoring purposes]. / Nutzungsmöglichkeiten von Routinedaten der Gesetzlichen Krankenversicherung in der Gesundheitsberichterstattung des Bundes.

Federal health monitoring deals with the state of health and the health-related behavior of populations and is used to inform politics. To date, the routine data from statutory health insurances (SHI) have rarely been used for federal health monitoring purposes. SHI routine data enable analyses of disease frequency, risk factors, the course of the disease, the utilization of medical services, and mortality rates. The advantages offered by SHI routine data regarding federal health monitoring are the intersectoral perspective and the nearly complete absence of recall and selection bias in the respective population. Further, the large sample sizes and the continuous collection of the data allow reliable descriptions of the state of health of the insurants, even in cases of multiple stratification. These advantages have to be weighed against disadvantages linked to the claims nature of the data and the high administrative hurdles when requesting the use of SHI routine data. Particularly in view of the improved availability of data from all SHI insurants for research institutions in the context of the "health-care structure law", SHI routine data are an interesting data source for federal health monitoring purposes.

High-dimensional versus conventional propensity scores in a comparative effectiveness study of coxibs and reduced upper gastrointestinal complications.

PURPOSE: High-dimensional propensity score (hd-PS) adjustment has been proposed as a tool to improve control for confounding in pharmacoepidemiological studies using longitudinal claims databases. We investigated whether hd-PS matching improved confounding by indication in a study of Cox-2 inhibitors (coxibs) and traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and their association with the risk of upper gastrointestinal complications (UGIC). METHODS: In a cohort study of new users of coxibs and tNSAIDs we compared the effectiveness of these drugs to reduce UGIC using hd-PS matching and conventional propensity score (PS) matching in the German Pharmacoepidemiological Research Database. RESULTS: The unadjusted rate ratio (RR) of UGIC for coxib users versus tNSAID users was 1.21 [95 % confidence interval (CI) 0.91-1.61]. The conventional PS matched cohort based on 79 investigator-identified covariates resulted in a RR of 0.84 (0.56-1.26). The use of the hd-PS algorithm based on 900 empirical covariates further decreased the RR to 0.62 (0.43-0.91). CONCLUSIONS: A comparison of hd-PS matching versus conventional PS matching resulted in improved point estimates for studying an intended treatment effect of coxibs versus tNSAIDs when benchmarked against results from randomized controlled trials.

Evaluation of pregnancy outcome records in the German Pharmacoepidemiological Research Database (GePaRD).

PURPOSE: Routine health care data are a valuable source for the assessment of risks of drugs during pregnancy. Therefore, the aim of the current analysis was the evaluation of pregnancy outcome records in German health insurance data. METHODS: We used the German Pharmacoepidemiologic Research Database including data of more than 15 million insurants (about 18% of the German population). Among 10-49 year-old women, we identified six categories of pregnancy outcomes: term births, preterm births, stillbirths, induced abortions, spontaneous abortions and ectopic pregnancies. In order to assess the validity of these records, we have set our results in relation to representative data for the corresponding outcomes in Germany. We also investigated whether pregnancy markers (diagnoses, procedures or medical services which indicate an existing pregnancy) can be used to identify pregnancies. RESULTS: In total, we identified 94 261 pregnancy outcomes in 2005. The percentage of births outside hospital (1.2%) and of preterm births (11.6%), the rate of stillbirths (3 per 1000 live births) and the rate of ectopic pregnancies (20 per 1000 live births) agreed well with representative data for Germany. Compared to epidemiological data, the occurrence of spontaneous abortions was underestimated (5.4% of all pregnancies). There were 4.1 induced abortions per 100 live births, compared to 18.1 in national data. Positive predictive values and sensitivities of markers varied across marker categories and for different pregnancy outcomes. CONCLUSIONS: Completeness of pregnancy outcomes recorded in the database varied by pregnancy outcome. This should be taken into account in studies of drug safety in pregnancy.

Background paper to the recommendation for routine rotavirus vaccination of infants in Germany.

Two rotavirus (RV) vaccines were introduced to the European market in 2006. To support the decision-making process of the German Standing Committee on Vaccination ("Ständige Impfkommission", STIKO) regarding adoption of routine RV vaccination into the national vaccination schedule in Germany relevant scientific background was reviewed. According to STIKO's Standard Operating Procedures for the development of evidence-based vaccination recommendations, a set of key questions was addressed and systematic reviews were performed with a focus on the efficacy, effectiveness, impact and safety of RV vaccines. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to assess the quality of available evidence. Data from 5 randomized controlled trials demonstrated a high efficacy of RV vaccines in preventing severe RV-associated gastroenteritis (91%) and hospitalization (92%) in settings comparable to Germany. Post-marketing observational studies confirmed these findings. In several countries, impact studies suggest that age groups not eligible for vaccination might also benefit from herd effects and demonstrated a decrease in the number of nosocomial RV infections after RV vaccine introduction. The vaccines were considered safe, except for a slightly increased risk of intussusception shortly after the first dose, corresponding to 1-2 additional cases per 100,000 infants vaccinated (relative risk =1.21, 95% confidence interval [CI] 0.68-2.14). RV case-fatality is extremely low in Germany. However, RV incidence among children aged <5 years is high (reported 8-14 cases per 1000 children annually), and of these almost half require hositalization. In view of the available evidence and expected benefits, STIKO recommends routine rotavirus vaccination of children under the age of 6 months with the main goal of preventing RV-associated hospitalizations in Germany, especially among infants and young children.

Ciprofloxacin-related acute severe myalgia necessitating emergency care treatment: a case report and review of the literature.

OBJECTIVE: To report a case of an uncommon and up to date unpublished peracute and overwhelming muscle pain following administration of ciprofloxacin. CASE SUMMARY: A 58-year-old male developed fulminating musculoskeletal pain associated with third-time exposure to ciprofloxacin administered for treatment of chronic otitis media. Symptoms resolved slowly after intense combined analgetic therapy and cessation of ciprofloxacin therapy. 24 h after ciprofloxacin discontinuation the symptoms had completely disappeared and no more analgetic treatment was needed. Laboratory values, especially muscle enzymes, did not reveal any pathological pattern. The patient's past medical history highlighted reproducible side effects with both systemic and local administration of ciprofloxacin including milder symptoms of the musculoskeletal system. DISCUSSION: Common side effects of fluoroquinolones include gastrointestinal, central nervous and allergic reactions, but also more uncommon reactions such as tendonitis and rhabdomyolysis. In our case, there had been no signs of rhabdomyolysis. Besides an elevated IgE level no clinical signs of a true anaphylactic reaction associated with release of mast cell mediators had been observed. A pharmacokinetic interaction between ciprofloxacin and the patient's comedication carbamazepine is unlikely to be the responsible mechanism, since fluoroquinolones inhibit cytochrome P450 isoenzyme CYP1A2 but not CYP3A4 which metabolizes carbamazepine. CONCLUSION: To our knowledge, this is the first report describing fulminating musculoskeletal pain following administration of ciprofloxacin without any signs of rhabdomyolysis. Physicians should notice that there is a variety of adverse reactions of this usually well-tolerated agent and they should be aware of unusual complaints of their patients who receive fluoroquinolone treatment.

The contribution of comorbidities to mortality in hospitalized patients with heart failure.

BACKGROUND: Heart failure (HF) with reduced ejection fraction (HFrEF) has a worse prognosis than HF with preserved EF (HFpEF). The study aimed to evaluate whether different comorbidity profiles of HFrEF- and HFpEF-patients or HF-specific mechanisms contribute to a greater extent to this difference. METHODS: We linked data from two health insurances to data from a cardiology clinic hospital information system. Patients with a hospitalization with HF in 2005-2011, categorized as HFrEF (EF < 45%) or HFpEF (EF ≥ 45%), were propensity score (PS) matched to controls without HF on comorbidites and medication to assure similar comorbidity profiles of patients and their respective controls. The balance of the covariates in patients and controls was compared via the standardized difference (SDiff). Age-standardized 1-year mortality rates (MR) with 95% confidence intervals (CI) were calculated. RESULTS: 777 HFrEF-patients (1135 HFpEF-patients) were PS-matched to 3446 (4832) controls. Balance between patients and controls was largely achieved with a SDiff < 0.1 on most variables considered. The age-standardized 1-year MRs per 1000 persons in HFrEF-patients and controls were 267.8 (95% CI 175.9-359.8) and 86.1 (95% CI 70.0-102.3). MRs in HFpEF-patients and controls were 166.2 (95% CI 101.5-230.9) and 61.5 (95% CI 52.9-70.1). Thus, differences in MRs between patients and their controls were higher for HFrEF (181.7) than for HFpEF (104.7). CONCLUSIONS: Given the similar comorbidity profiles between HF-patients and controls, the higher difference in mortality rates between HFrEF-patients and controls points more to HF-specific mechanisms for these patients, whereas for HFpEF-patients a higher contribution of comorbidity is suggested by our results.

Selection of controls in database case-control studies: glucocorticoids and the risk of glaucoma.

In case-control studies conducted using computerized databases, controls are often selected as a random sample from the base population. This representative choice of controls is intended to guard against selection bias. We show, using data from a database case-control study, that such a definition of controls may also lead to selection bias under two conditions: (1) if the target disease has a prolonged asymptomatic clinical course with its detection depending on a specific physical examination and (2) if exposed patients have a higher likelihood of having the disease detected than unexposed patients. The extent of the bias that could result from the use of randomly selected controls was investigated in the context of a case-control study of the risk of ocular hypertension or glaucoma associated with the use of glucocorticoids, conducted using the Quebec universal health insurance computerized databases. This article also illustrates that a computerized database can be useful to empirically explore opportunities for bias.

Exposure to allopurinol and the risk of cataract extraction in elderly patients.

OBJECTIVE: To determine whether exposure to allopurinol is associated with an increased risk of cataract extraction in elderly patients. METHODS: We conducted a case-control study using data from the Quebec universal health insurance program for all elderly patients. The 3677 cases were patients with a cataract extraction between 1992 and 1994. The 21,868 controls were randomly selected among patients not diagnosed with cataract and matched to cases on the date of the extraction. We determined the odds ratio of cataract extraction according to the cumulative dose and duration of allopurinol use relative to nonusers, using conditional logistic regression analysis. The analysis was adjusted for the effects of age, sex, diabetes mellitus, hypertension, glaucoma, and ophthalmic and oral corticosteroid exposure. RESULTS: A cumulative dose of allopurinol of more than 400 g or a duration of use of longer than 3 years were associated with an increased risk of cataract extraction, with odds ratios of 1.82 (95% confidence interval [CI], 1.18-2.80) and 1.53 (95% CI, 1.12-2.08), respectively. No increase in risk was observed for lower cumulative doses or shorter exposure periods. CONCLUSION: Long-term administration of allopurinol increases the risk of cataract extraction in elderly patients.

Prevention by aluminium phosphate of gastric lesions induced by ethanol in the rat: role of endogenous prostaglandins and sulfhydryls.

This study was designed to demonstrate the cytoprotective effect of an antacid containing aluminium phosphate (Phosphalugel) against ethanol-induced gastric injury in the rat and to determine whether this cytoprotective effect is mediated by endogenous prostaglandins and sulfhydryls. We have quantitatively evaluated gastric mucosal lesions using macroscopic and histological techniques one hour after ethanol administration. Two ml of aluminium phosphate given orally one hour before administration of 2 ml of 100% ethanol significantly (p less than 0.01) reduced the area of macroscopic lesions induced by ethanol (3.3 +/- 0.9%) when compared to distilled water (20 +/- 4.8%). The histological study showed that aluminium phosphate prevented deep tissue necrosis. However, it did not protect surface epithelial cells against ethanol injury. Pretreatment with indomethacin, 5 mg/kg sc one hour before aluminium phosphate, slightly but significantly (p less than 0.05) reduced the cytoprotective effect of aluminium phosphate. Macroscopic lesions occupied 4.3 +/- 0.94% and 1.88 +/- 0.41% of total mucosal area in indomethacin group and in vehicle group, respectively. On the other hand, the sulfhydryl blocker, N-ethyl-maleimide, 10 mg/kg sc, given one hour before aluminium phosphate, completely abolished the cytoprotective effect of aluminium phosphate (32.92 +/- 4.85% in N-ethyl-maleimide group versus 3.78 +/- 1.41% in vehicle group; p less than 0.01). These results show that aluminium phosphate has a cytoprotective effect against ethanol injury in the rat. This property appears to be mediated by both endogenous prostaglandins and sulfhydryls.

Treatment with potentially hepatotoxic drugs and the risk of hepatocellular carcinoma: results of a european case - control study.

Some toxicological data and case reports have suggested that patients taking potentially hepatotoxic drugs may have an increased risk of benign and malignant liver tumours. Pharmacoepidemiological studies on this issue are sparse, most of them focusing on the association between hepatocellular carcinoma (HCC) and the use of oral contraceptives (OC). The objectives of our study were to examine the risk of HCC in patients taking the drugs mentioned in these case reports and toxicological studies. We used data from an international case - control study which had investigated the risk of HCC in women taking OC including 317 cases of HCC and 1060 frequency age-matched hospital controls. We investigated the risk for oral antidiabetic and immunosuppressive drugs, methyldopa, nitrofurantoin and clofibrate using unconditional logistic regression analysis. The analysis was adjusted for age, hepatitis B, hepatitis C, alcohol abuse and other risk factors of HCC. The adjusted odds ratios for ever-use of the investigated drugs varied between 0.67 and 1.64, none of them being statistically significant. There was equally no significantly increased risk for long-term use of these drugs. Altogether there is no evidence for an increased risk of HCC in patients taking the drugs investigated, however, the relatively small statistical power for certain drugs with a low exposure prevalence has to be taken into account. Copyright (c) 2000 John Wiley & Sons, Ltd.

[Health in the USSR in the era of Perestroika]. / La santé en URSS à l'heure de la Perestroïka.

For years, the Health Service of the USSR was considered a model and a guide. Countries in the Third World were invited to follow its various elements in organizing their own national health systems. But, since August 1987, everybody has known that the Health Service of the USSR is in a very bad situation. Official reports, journals of the Party and declarations of the health authorities all emphasized the catastrophic state of the health care organization in USSR: rising mortality rates, alcohol and drug abuse, extensive pollution, hospitals without hygiene or equipment, lack of professionalism and extended corruption among medical doctors and other health workers, patients' dissatisfaction etc... Of special concern are the cardiovascular and maternal mortality rates which are now much higher than in other countries. In the wake of perestroïka, a plan of reform was initiated by the Party and the Government, and was announced in 1988 by Health Minister E.N. Tchazov. The basic principle of the Health Service in the USSR remains prevention. Nevertheless, a great number of new measures will be implemented. Health information and care will be brought to the people by health workers. Mass screening for the most frequent diseases will be performed. Computers will be used on a large scale for managing high risk groups. Health centers will be strengthened. But the most revolutionary element of the reform will be the extension of the "paying sector", with increased number of facilities having financial autonomy. These facilities provide care and require some payment from the patients. They existed previously, but in the future they will be increased and strengthened. This means that the patients will have to pay more money but the services will be likely improved. The future will show whether the plan will succeed or fail.