Dati preliminari dello studio multicentrico caso-controllo "Grave danno epatico acuto indotto da farmaci"

Il danno epatico indotto dall'assunzione di farmaci viene comunemente indicato con il termine inglese DILI (Drug-Induced Liver Injury). Il paracetamolo rappresenta la causa più comune di DILI, seguito da antibiotici, FANS e farmaci antitubercolari. In particolare, i FANS sono una delle classi di farmaci maggiormente impiegate in terapia. Numerosi case report descrivono pazienti che hanno sviluppato danno epatico fatale durante il trattamento con FANS; molti di questi farmaci sono stati ritirati dal commercio in seguito a gravi reazioni avverse a carico del fegato. L'ultimo segnale di epatotossicità indotto da FANS è associato alla nimesulide; in alcuni paesi europei come la Finlandia, la Spagna e l'Irlanda, la nimesulide è stata sospesa dalla commercializzazione perché associata ad un'alta frequenza di epatotossicità. Sulla base dei dati disponibili fino a questo momento, l'Agenzia Europea dei Medicinali (EMA) ha recentemente concluso che i benefici del farmaco superano i rischi; un possibile aumento del rischio di epatotossicità associato a nimesulide rimane tuttavia una discussione aperta di cui ancora molto si dibatte. Tra le altre classi di farmaci che possono causare danno epatico acuto la cui incidenza tuttavia non è sempre ben definita sono gli antibiotici, quali amoxicillina e macrolidi, le statine e gli antidepressivi.Obiettivo dello studio è stato quello di determinare il rischio relativo di danno epatico indotto da farmaci con una prevalenza d'uso nella popolazione italiana maggiore o uguale al 6%. E’ stato disegnato uno studio caso controllo sviluppato intervistando pazienti ricoverati in reparti di diversi ospedali d’Italia. Il nostro studio ha messo in evidenza che il danno epatico da farmaci riguarda numerose classi farmacologiche e che la segnalazione di tali reazioni risulta essere statisticamente significativa per numerosi principi attivi. I dati preliminari hanno mostrato un valore di odds ratio significativo statisticamente per la nimesulide, i FANS, alcuni antibiotici come i macrolidi e il paracetamolo.

Unione Europea e sanità

La tesi di dottorato "Unione Europea e Sanità" è uno studio sistematico del diritto alla salute e della protezione della sanità pubblica nell'ordinamento giuridico dell'Unione Europea. Il primo capitolo analizza le competenze sanitarie dell'Unione Europea, introdotte per la prima volta dal Trattato di Maastricht e definitivamente sistemate all'art. 168 TFUE. La norma identifica alcuni settori specifici nei quali l'Unione può agire e altri, quali l'organizzazione dei sistemi sanitari e la fornitura di cure mediche, che rimangono in capo agli Stati membri. Il secondo capitolo esamina le deroghe e le esigenze imperative connesse alla salvaguardia della salute nel mercato interno ed è suddiviso in tre sezioni dedicate alla libera circolazione delle merci, al diritto di stabilimento e alla libera prestazione dei servizi. Nella prima ci si è occupati dello sviluppo della legislazione farmaceutica. Nella seconda si sono analizzati il mutuo riconoscimento delle qualifiche professionali e le legislazioni statali che restringono il diritto di stabilimento degli operatori sanitari transfrontalieri. Nella terza si è rivolta l'attenzione alla mobilità dei pazienti che, attraverso la giurisprudenza della Corte di Giustizia, è stata trasfusa in un atto di diritto derivato. Il terzo capitolo si concentra sul ruolo del diritto alla salute nell'ordinamento giuridico dell'Unione Europea in considerazione del valore vincolante della Carta dei diritti fondamentali. Coerentemente, si è scelto di mantenere una struttura tripartita. Nella prima sezione, ci si interroga sull'esistenza di tale diritto alla luce dei pochi casi presenti. Nella seconda, lo si analizza per il tramite delle obbligazioni di proteggere, rispettare ed adempiere, enucleate attraverso alcuni strumenti internazionali e si verifica il ruolo del principio di non discriminazione in relazione all'accesso alle cure. Nella terza, infine, si verifica il ruolo del consenso informato rispetto alla sperimentazione clinica ed alla donazione di materiale biologico.

Medical Malpractice in Public Healthcare Systems: An Empirical Investigation of Scheduled Damages

In the last decades, medical malpractice has been framed as one of the most critical issues for healthcare providers and health policy, holding a central role on both the policy agenda and public debate. The Law and Economics literature has devoted much attention to medical malpractice and to the investigation of the impact of malpractice reforms. Nonetheless, some reforms have been much less empirically studied as in the case of schedules, and their effects remain highly debated. The present work seeks to contribute to the study of medical malpractice and of schedules of noneconomic damages in a civil law country with a public national health system, using Italy as case study. Besides considering schedules and exploiting a quasi-experimental setting, the novelty of our contribution consists in the inclusion of the performance of the judiciary (measured as courts’ civil backlog) in the empirical analysis. The empirical analysis is twofold. First, it investigates how limiting compensations for pain and suffering through schedules impacts on the malpractice insurance market in terms of presence of private insurers and of premiums applied. Second, it examines whether, and to what extent, healthcare providers react to the implementation of this policy in terms of both levels and composition of the medical treatments offered. Our findings show that the introduction of schedules increases the presence of insurers only in inefficient courts, while it does not produce significant effects on paid premiums. Judicial inefficiency is attractive to insurers for average values of schedules penetration of the market, with an increasing positive impact of inefficiency as the territorial coverage of schedules increases. Moreover, the implementation of schedules tends to reduce the use of defensive practices on the part of clinicians, but the magnitude of this impact is ultimately determined by the actual degree of backlog of the court implementing schedules.

Prevention, diagnosis, therapy and follow-up care of sepsis: 1st revision of S-2k guidelines of the German Sepsis Society (Deutsche Sepsis-Gesellschaft e.V. (DSG)) and the German Interdisciplinary Association of Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI))

Practice guidelines are systematically developed statements and recommendations that assist the physicians and patients in making decisions about appropriate health care measures for specific clinical circumstances taking into account specific national health care structures. The 1(st) revision of the S-2k guideline of the German Sepsis Society in collaboration with 17 German medical scientific societies and one self-help group provides state-of-the-art information (results of controlled clinical trials and expert knowledge) on the effective and appropriate medical care (prevention, diagnosis, therapy and follow-up care) of critically ill patients with severe sepsis or septic shock. The guideline had been developed according to the "German Instrument for Methodological Guideline Appraisal" of the Association of the Scientific Medical Societies (AWMF). In view of the inevitable advancements in scientific knowledge and technical expertise, revisions, updates and amendments must be periodically initiated. The guideline recommendations may not be applied under all circumstances. It rests with the clinician to decide whether a certain recommendation should be adopted or not, taking into consideration the unique set of clinical facts presented in connection with each individual patient as well as the available resources.

Rates Of Obesity And Incidence Of Diabetes In Hispanics In The United States: An Examination Of The Epidemiological Paradox

Using pooled data from the 2008-2011 National Health Interview Survey and employing multinomial and binomial logistic regression methods, this research examines disparities in rates of obesity and incidence of diabetes between individual Hispanic subgroups in comparison to non-Hispanic whites and blacks. Immigration status(including nativity, duration in the United States, and citizenship status) is hypothesized to play a central role in rates and obesity and incidence of diabetes. Unlike Cuban-Americans, Mexican-Americans, Puerto Ricans, and other Hispanics were more likely to be overweight as well as obese when compared to non-Hispanic whites. Mexican-Americans had the only significance in prevalence of type 2 diabetes in comparison to non-Hispanic whites. Both of these health outcomes are strongly associated with the various immigration variables.

Trends in the Association Between Socioeconomic Status and Obesity in U.S. Adults: 2002-2012

Since the 1980s, the prevalence of obesity has more than doubled to over 30 percent of the adult population (Thorpe, 2004). Obesity is a key contributing factor to continually rising national healthcare costs. Addressing its negative implications is essential not only from a cost perspective, but also for the betterment of our nation¿s general health and wellbeing. Obesity is reportedly associated with a 35% increase in inpatient and outpatient spending, as well as a 77% increase in related necessary medications (Sturm, 2002). Obesity, which some have argued should be classified as a disease in itself, has roughly the same association with the development of chronic health conditions as does 20 years of aging (Sturm, 2002). Defined as ambulatory care-sensitive conditions, these obesity-related chronic health diagnoses ¿ like diabetes, cardiovascular disease, and hypertension ¿ are in turn the primary drivers of current healthcare spending, as well as future predicted health expenditures. It is well established that lower socioeconomic status (SES) is associated with higher rates of obesity and the subsequent development of aforementioned obesity-related conditions. Socioeconomic status has traditionally been defined by education, income, and occupation (Adler, 2002); however, this study found empirical evidence for education being the most fundamental of these three SES indicators in determining obesity outcomes. For both men and women, as education levels increased, the likelihood of an individual being obese decreased. However, with less education, there was increased disparity between the obesity rates for men and women. Women consistently saw higher rates of obesity and were more impacted in terms of obesity onset by belonging to a lower SES category than men. In addition, this study assessed whether the impact of one¿s socioeconomic status on obesity-related health outcomes (specifically the negative impact low-SES as measured by education level) has changed over time. Results deriving from annual data from the National Health Interview Survey (NHIS) for all years from 2002 to 2012 indicate that the association between low-socioeconomic status and negative health outcomes has not increased in magnitude over the past decade. Instead, obesity rates have increased across the overall U.S. adult population, most likely due to a number of larger external societal factors resulting in increased caloric intake and decreased energy expenditure across every SES group. In addition, while the association between low-SES and obesity has not worsened, a consequence of the Great Recession has been a larger percentage of the U.S. population in lower-SES, which is still consistently subject to the same worse health outcomes.

Healthcare and patient costs of a proactive chlamydia screening programme: the Chlamydia Screening Studies project

BACKGROUND AND OBJECTIVE: Most economic evaluations of chlamydia screening do not include costs incurred by patients. The objective of this study was to estimate both the health service and private costs of patients who participated in proactive chlamydia screening, using mailed home-collected specimens as part of the Chlamydia Screening Studies project. METHODS: Data were collected on the administrative costs of the screening study, laboratory time and motion studies and patient-cost questionnaire surveys were conducted. The cost for each screening invitation and for each accepted offer was estimated. One-way sensitivity analysis was conducted to explore the effects of variations in patient costs and the number of patients accepting the screening offer. RESULTS: The time and costs of processing urine specimens and vulvo-vaginal swabs from women using two nucleic acid amplification tests were similar. The total cost per screening invitation was 20.37 pounds (95% CI 18.94 pounds to 24.83). This included the National Health Service cost per individual screening invitation 13.55 pounds (95% CI 13.15 pounds to 14.33) and average patient costs of 6.82 pounds (95% CI 5.48 pounds to 10.22). Administrative costs accounted for 50% of the overall cost. CONCLUSIONS: The cost of proactive chlamydia screening is comparable to those of opportunistic screening. Results from this study, which is the first to collect private patient costs associated with a chlamydia screening programme, could be used to inform future policy recommendations and provide unique primary cost data for economic evaluations.

Prevalence and associated factors of viral hepatitis and transferrin elevations in 5036 patients admitted to the emergency room of a Swiss university hospital: cross-sectional study

BACKGROUND: The epidemiology of liver disease in patients admitted to emergency rooms is largely unknown. The current study aimed to measure the prevalence of viral hepatitis B and C infection and pathological laboratory values of liver disease in such a population, and to study factors associated with these measurements. METHODS: Cross-sectional study in patients admitted to the emergency room of a university hospital. No formal exclusion criteria. Determination of anti-HBs, anti-HCV, transferrin saturation, alanine aminotransferase, and obtaining answers from a study-specific questionnaire. RESULTS: The study included 5'036 patients, representing a 14.9% sample of the target population during the study period. Prevalence of anti-HBc and anti-HCV was 6.7% (95%CI 6.0% to 7.4%) and 2.7% (2.3% to 3.2%), respectively. Factors independently associated with positive anti-HBc were intravenous drug abuse (OR 18.3; 11.3 to 29.7), foreign country of birth (3.4; 2.6 to 4.4), non-white ethnicity (2.7; 1.9 to 3.8) and age > or =60 (2.0; 1.5 to 2.8). Positive anti-HCV was associated with intravenous drug abuse (78.9; 43.4 to 143.6), blood transfusion (1.7; 1.1 to 2.8) and abdominal pain (2.7; 1.5 to 4.8). 75% of all participants were not vaccinated against hepatitis B or did not know their vaccination status. Among anti-HCV positive patients only 49% knew about their infection and 51% reported regular alcohol consumption. Transferrin saturation was elevated in 3.3% and was associated with fatigue (prevalence ratio 1.9; 1.2 to 2.8). CONCLUSION: Emergency rooms should be considered as targets for public health programs that encourage vaccination, patient education and screening of high-risk patients for liver disease with subsequent referral for treatment if indicated.

Pediatric craniofacial trauma

PURPOSE: Maxillofacial and skull fractures occur with concomitant injuries in pediatric trauma patients. The aim of this study was to determine the causes and distributions of maxillofacial and skull fractures as well as concomitant injuries of pediatric patients in Switzerland. Results were compared with worldwide studies. MATERIALS AND METHODS: A retrospective review was conducted of 291 pediatric patients with maxillofacial and skull fractures presenting to a level-I trauma center over a 3-year span. Data concerning the mechanism of the accident and the topographic location of the injuries were analyzed. RESULTS: The most common causes were falls (64%), followed by traffic (22%) and sports-related accidents (9%). Fifty-four percent of the fractures occurred in the skull vault and 37% in the upper and middle facial third. One third of the patients (n = 95) suffered concomitant injuries, mostly cerebral concussions (n = 94). CONCLUSIONS: The spectrum of craniofacial injuries is related to the specific developmental stage of the craniofacial skeleton. It is probable that national prevention programs will have a positive effect on reducing the incidence of falls. Standardization of studies is needed for international comparison.

Routine vaccination against pertussis and the risk of childhood asthma: a population-based cohort study

BACKGROUND: In industrialized countries vaccination coverage remains suboptimal, partly because of perception of an increased risk of asthma. Epidemiologic studies of the association between childhood vaccinations and asthma have provided conflicting results, possibly for methodologic reasons such as unreliable vaccination data, biased reporting, and reverse causation. A recent review stressed the need for additional, adequately controlled large-scale studies. OBJECTIVE: Our goal was to determine if routine childhood vaccination against pertussis was associated with subsequent development of childhood wheezing disorders and asthma in a large population-based cohort study. METHODS: In 6811 children from the general population born between 1993 and 1997 in Leicestershire, United Kingdom, respiratory symptom data from repeated questionnaire surveys up to 2003 were linked to independently collected vaccination data from the National Health Service database. We compared incident wheeze and asthma between children of different vaccination status (complete, partial, and no vaccination against pertussis) by computing hazard ratios. Analyses were based on 6048 children, 23 201 person-years of follow-up, and 2426 cases of new-onset wheeze. RESULTS: There was no evidence for an increased risk of wheeze or asthma in children vaccinated against pertussis compared with nonvaccinated children. Adjusted hazard ratios comparing fully and partially vaccinated with nonvaccinated children were close to one for both incident wheeze and asthma. CONCLUSION: This study provides no evidence of an association between vaccination against pertussis in infancy and an increased risk of later wheeze or asthma and does not support claims that vaccination against pertussis might significantly increase the risk of childhood asthma.

Culture, risk factors and mortality: can Switzerland add missing pieces to the European puzzle?

BACKGROUND: The aim was to compare cause-specific mortality, self-rated health (SRH) and risk factors in the French and German part of Switzerland and to discuss to what extent variations between these regions reflect differences between France and Germany. METHODS: Data were used from the general population of German and French Switzerland with 2.8 million individuals aged 45-74 years, contributing 176 782 deaths between 1990 and 2000. Adjusted mortality risks were calculated from the Swiss National Cohort, a longitudinal census-based record linkage study. Results were contrasted with cross-sectional analyses of SRH and risk factors (Swiss Health Survey 1992/3) and with cross-sectional national and international mortality rates for 1980, 1990 and 2000. RESULTS: Despite similar all-cause mortality, there were substantial differences in cause-specific mortality between Swiss regions. Deaths from circulatory disease were more common in German Switzerland, while causes related to alcohol consumption were more prevalent in French Switzerland. Many but not all of the mortality differences between the two regions could be explained by variations in risk factors. Similar patterns were found between Germany and France. CONCLUSION: Characteristic mortality and behavioural differentials between the German- and the French-speaking parts of Switzerland could also be found between Germany and France. However, some of the international variations in mortality were not in line with the Swiss regional comparison nor with differences in risk factors. These could relate to peculiarities in assignment of cause of death. With its cultural diversity, Switzerland offers the opportunity to examine cultural determinants of mortality without bias due to different statistical systems or national health policies.

Growth curves for cardio-metabolic risk factors in children and adolescents

OBJECTIVE: This study developed percentile curves for anthropometric (waist circumference) and cardiovascular (lipid profile) risk factors for US children and adolescents. STUDY DESIGN: A representative sample of US children and adolescents from the National Health and Nutrition Examination Survey from 1988 to 1994 (NHANES III) and the current national series (NHANES 1999-2006) were combined. Percentile curves were constructed, nationally weighted, and smoothed using the Lambda, Mu, and Sigma method. The percentile curves included age- and sex-specific percentile values that correspond with and transition into the adult abnormal cut-off values for each of these anthropometric and cardiovascular components. To increase the sample size, a second series of percentile curves was also created from the combination of the 2 NHANES databases, along with cross-sectional data from the Bogalusa Heart Study, the Muscatine Study, the Fels Longitudinal Study and the Princeton Lipid Research Clinics Study. RESULTS: These analyses resulted in a series of growth curves for waist circumference, total cholesterol, LDL cholesterol, triglycerides, and HDL cholesterol from a combination of pediatric data sets. The cut-off for abnormal waist circumference in adult males (102 cm) was equivalent to the 94(th) percentile line in 18-year-olds, and the cut-off in adult females (88 cm) was equivalent to the 84(th) percentile line in 18-year-olds. Triglycerides were found to have a bimodal pattern among females, with an initial peak at age 11 and a second at age 20; the curve for males increased steadily with age. The HDL curve for females was relatively flat, but the male curve declined starting at age 9 years. Similar curves for total and LDL cholesterol were constructed for both males and females. When data from the additional child studies were added to the national data, there was little difference in their patterns or rates of change from year to year. CONCLUSIONS: These curves represent waist and lipid percentiles for US children and adolescents, with identification of values that transition to adult abnormalities. They could be used conditionally for both epidemiological and possibly clinical applications, although they need to be validated against longitudinal data.

Research on Alpine Landscape Development: From Research to Policy

Swiss National Research Programs (NRPs) are usually geared to addressing issues of major societal concern. In so doing these programs produce different kinds of knowledge: analytical knowledge necessary for revealing the driving forces, conflicting interests and institutional settings that govern the processes under scrutiny; target knowledge oriented towards revealing the directions in which the processes should be guided; and action knowledge that informs about the means by which this can best be achieved. Analytical knowledge answers the questions “what is the problem?” and “what causes it?” while target knowledge helps to define “what is our vision for the future?” and action knowledge deals with “how can we solve the problem?” Production of these 3 different types of knowledge is usually linked in an iterative process in the course of the research supported in an NRP.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

THE RELATIONSHIP BETWEEN OBESITY AND PSYCHOLOGICAL GENERAL WELL-BEING IN UNITED STATES WOMEN

While clinical studies have shown a negative relationship between obesity and mental health in women, population studies have not shown a consistent association. However, many of these studies can be criticized regarding fatness level criteria, lack of control variables, and validity of the psychological variables.^ The purpose of this research was to elucidate the relationship between fatness level and mental health in United States women using data from the First National Health and Nutrition Examination Survey (NHANES I), which was conducted on a national probability sample from 1971 to 1974. Mental health was measured by the General Well-Being Schedule (GWB), and fatness level was determined by the sum of the triceps and subscapular skinfolds. Women were categorized as lean (15th percentile or less), normal (16th to 84th percentiles), or obese (85th percentile or greater).^ A conceptual framework was developed which identified the variables of age, race, marital status, socioeconomic status (education), employment status, number of births, physical health, weight history, and perception of body image as important to the fatness level-GWB relationship. Multiple regression analyses were performed separately for whites and blacks with GWB as the response variable, and fatness level, age, education, employment status, number of births, marital status, and health perception as predictor variables. In addition, 2- and 3-way interaction terms for leanness, obesity and age were included as predictor variables. Variables related to weight history and perception of body image were not collected in NHANES I, and thus were not included in this study.^ The results indicated that obesity was a statistically significant predictor of lower GWB in white women even when the other predictor variables were controlled. The full regression model identified the young, more educated, obese female as a subgroup with lower GWB, especially in blacks. These findings were not consistent with the previous non-clinical studies which found that obesity was associated with better mental health. The social stigma of being obese and the preoccupation of women with being lean may have contributed to the lower GWB in these women. ^