Dramatic effect of early clopidogrel administration in reducing mortality and MACE rates in ACS patients. Data from the Swiss registry AMIS-Plus.

BACKGROUND: Patients who have acute coronary syndromes with or without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy of early clopidogrel administration (300 mg) (<24 hours) when given with aspirin in such patients. METHODS: We included 30,243 patients who had an acute coronary syndrome with or without ST segment elevation. Data on early clopidogrel administration were available for 24,463 (81%). Some 15,525 (51%) of the total cohort were administrated clopidogrel within 24h of admission. RESULTS: In-hospital death occurred in 2.9% of the patients in the early clopidogrel group treated with primary PCI and in 11.4% of the patients in the other group without primary percutaneous coronary intervention (PCI) and no early clopidogrel. The unadjusted clopidogrel odds ratio (OR) for mortality was 0.31 (95% confidence interval 0.27-0.34; p <0.001). Incidence of major adverse cardiac death (MACE) was 4.1% in the early clopidogrel group treated with 1°PCI and 13.5% in the other group without primary PCI and no early clopidogrel (OR 0.35, confidence interval 0.32-0.39, p <0.001). Early clopidogrel administration and PCI were the only treatment lowering mortality as shown by mutlivariate analysis. CONCLUSIONS: The early administration of the anti-platelet agent clopidogrel in patients with acute coronary syndromes with or without ST-segment elevation has a beneficial effect on mortality and major adverse cardiac events. The lower mortality rate and incidence of MACE emerged with a combination of primary PCI and early clopidogrel administration.

Biliary atresia: Swiss national study, 1994-2004.

OBJECTIVES: To determine the epidemiology of biliary atresia (BA) in Switzerland, the outcome of the children from diagnosis, and the prognostic factors. PATIENTS AND METHODS: The records of all patients with BA born in Switzerland between January 1994 and December 2004 were analyzed. Survival rates were calculated with the Kaplan-Meier method, and prognostic factors evaluated with the log rank test. Median follow up was 58 months (range, 5-124). RESULTS: BA was diagnosed in 48 children. Incidence was 1 in 17,800 live births (95% confidence interval 1/13,900-1/24,800), without significant regional, annual, or seasonal variation. Forty-three children underwent a Kasai portoenterostomy (PE) in 5 different Swiss pediatric surgery units. Median age at Kasai PE was 68 days (range, 30-126). Four-year survival with native liver after Kasai PE was 37.4%. Liver transplantation (LT) was needed in 31 in 48 children with BA, including 5 patients without previous Kasai PE. Four patients (8%, all born before 2001) died while waiting for LT, and 29 LT were performed in 27 patients (28 in Geneva and 1 in Paris). All of the transplanted patients are alive. Four-year overall BA patient survival was 91.7%. Four-year survival with native liver was 75% in patients who underwent Kasai PE before 46 days, 33% in patients operated on between 46 and 75 days, and 11% in patients operated on after 75 days (P = 0.02). CONCLUSIONS: Overall survival of patients with BA in Switzerland compares favorably with current international standards, whereas results of the Kasai operation could be improved to reduce the need for LTs in infancy and early childhood.

The application of trend surface models to the analysis of time factors in Swiss cancer mortality.

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.

Torasemide is an effective diuretic in the newborn rabbit.

The effect of intravenous (i.v.) torasemide on diuresis and renal function was evaluated in three groups of normoxemic, 5- to 10-day-old, newborn New Zealand White rabbits. The animals of group 1 received 0.2 mg/kg of torasemide i.v., whereas in group 2 an i.v. dose of 1.0 mg/kg was given. The third group of animals received a bolus i.v. dose of 1.0 mg/kg torasemide with continuous i.v. replacement of estimated urinary fluid and electrolyte losses. Torasemide proved to be an effective, potassium-sparing diuretic, without significant effect on glomerular filtration rate (GFR). Renal blood flow (RBF) fell and the renal vascular resistance (RVR) rose in all three groups of animals, although the rise in RVR in group 3 was not significant. These changes in renal hemodynamics were most pronounced in the animals of group 2 and are probably secondary to torasemide-induced hypovolemia (2.8% loss of body weight) and accompanying humoral reactions, such as an increase in angiotensin II (not measured). When the latter is prevented by simultaneous re-infusion of an electrolyte solution (group 3), replacing urinary losses, GFR increases and the changes in RBF and RVR are blunted. We conclude that torasemide is an effective, potassium-sparing diuretic in newborn rabbits. No evidence was found for a vasodilatory action of the drug.

Sex differentials in Swiss cancer mortality.

Swiss national cancer mortality statistics from 1951 to 1984 and survival rates from the Vaud Cancer Registry datafile over the period 1974-1980 were considered in terms of sex ratios. Overall age-standardized cancer mortality for population aged 35-64 showed only a moderate decline in males (from 230 to 221/100,000), but a substantial one in females (from 191 to 152/100,000). Mortality from most cancer sites (except gallbladder and thyroid) was persistently higher in males, the male/female ratio ranging between 1.2 for intestines, skin, brain and lympho-reticular neoplasms to about 2 for stomach or pancreas, up to 7-10 for lung and cancers related to tobacco and alcohol (mouth or pharynx, oesophagus). The sex ratio for lung cancer increased between the early 1950's and the mid 1960's, but noticeably declined thereafter, probably reflecting trends in smoking prevalence among subsequent generations of Swiss males and females. Less obvious is the substantial increase in the sex ratio for liver cancer (from 1.6 to 5.7), which was evident in younger middle age, too. Population-based cancer survival statistics indicated that for most common sites rates were appreciably higher in females than in males. Thus, better survival explains part of the advantage in cancer mortality for women. This can be related to earlier diagnosis, better compliance or responsiveness to treatment, although there is no obvious single interpretation for this generalized more favourable pattern in females.

Hemophilia Registry of the Medical Committee of the Swiss Hemophilia Society: Update and Annual Survey 2008.

The Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society was established in 2000. Primarily it bears epidemiological and basic clinical data (incidence, type and severity of the disease, age groups, centres, mortality). Two thirds of the questions of the WFH Global Survey can be answered, especially those concerning use of concentrates (global, per capita) and treatment modalities (on-demand versus prophylactic regimens). Moreover, the registry is an important tool for quality control of the haemophilia treatment centres. There are no informations about infectious diseases like hepatitis or HIV, due to non-anonymisation of the data. We plan to incorporate the results of the mutation analysis in the future.

Overall and cause-specific mortality in GH-deficient adults on GH replacement.

OBJECTIVE: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. DESIGN: In KIMS (Pfizer International Metabolic Database) 13,983 GH-deficient patients with 69,056 patient-years of follow-up were available. METHODS: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. RESULTS: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). CONCLUSIONS: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.

Circadian and circaseptan patterns of natality and perinatal mortality of infants with different birth weights

OBJECTIVE. Data on human natality, stillbirth and perinatal mortality from Switzerland (1979-1987), available in four birthweight categories, are reexamined to assess any about-weekly (circaseptan) and changes in about-daily (circadian) patterns in central Europe over a century and a halfDESIGN. Retrospective analyses on archived data.SETTING. Federal Office of Statistics for Switzerland.RESULTS. In addition to prominent circadians, weekly patterns are also documented.CONCLUSION. Exogenous variations, prominent in early extrauterine life, such as changes of scheduling in obstetrics, may contribute to circadian and cireaseptan natality patterns. Information on these patterns serves in the optimization of neonatal care. Partly endogenous, partly physical environmental aspects, at least of about-weekly patterns, remain to be elucidated in series consisting exclusively of spontaneous parturitions.

Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies

BACKGROUND: Father's occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well. METHODS: We used pooled data on 18,393 men and 7060 women from the Whitehall II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality. RESULTS: During the 20-y follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes; the age, sex and cohort-adjusted HR for the lowest versus the highest educational group was 1.45 (95% CI 1.24 to 1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality robust to adjustment for the other indicators (HR 1.41, 95% CI 1.03 to 1.93 for those shorter than average and HR 1.36, 95% CI 0.98 to 1.88 for those taller than average for cardiovascular mortality). Greater all-cause and cancer mortality was observed in participants whose father's occupational position was manual rather than non-manual (HR 1.11, 95% CI 1.00 to 1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height. CONCLUSIONS: The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.

Seasonality and cyclic tendency of mortality in a Pyrenean population

Las características de la mortalidad Influyen decisivamente en la estructura demográfica de las poblaciones, regida por diferentes factores: internos (rasgos específicos genéticos y culturales), externos (características del ecosistema) e intermedios (capacidad de la población de autoajustarse al ambiente). El estudio de la distribución estacional de las 3313 defunciones registradas en la Villa de El Pont de Suert (Alta Ribagorça, Cataluña) desde 1664 evidencia la importancia de todos estos factores. Los patrones de distribución muestran el Influjo de las condiciones climáticas, de los ambientes epidemiológicos, así como de las transformaciones socioeconómicas y demográficas. El modelo de tendencia cíclica en la mortalidad, común a muchas poblaciones ibéricas de montaña, no se evidencia en esta población.

The decline in breast cancer mortality in Europe: an update (to 2009).

We updated trends in breast cancer mortality in Europe up to the late 2000's. In the EU, age-adjusted (world standard population) breast cancer mortality rates declined by 6.9% between 2002 and 2006, from 17.9 to 16.7/100,000. The largest falls were in northern European countries, but more recent declines were also observed in central and eastern Europe. In 2007, all major European countries had overall breast cancer rates between 15 and 19/100,000. In relative terms, the declines in mortality were larger at younger age (-11.6% at age 20-49 years between 2002 and 2007 in the EU), and became smaller with advancing age (-6.6% at age 50-69, -5.0% at age 70-79 years). The present report confirms and further quantifies the persisting steady fall in breast cancer mortality in Europe over the last 25-30 years, which is mainly due to advancements in the therapy.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Patterns and trends in esophageal cancer mortality and incidence in Europe (1980-2011) and predictions to 2015

BACKGROUND: Over the last few decades, esophageal cancer incidence and mortality trends varied substantially across Europe, with important differences between sexes and the two main histological subtypes, squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). PATIENTS AND METHODS: To monitor recent esophageal cancer mortality trends and to compute short-term predictions in the European Union (EU) and selected European countries, we analyzed data provided by the World Health Organization (WHO) for 1980-2011. We also analyzed incidence trends and relative weights of ESCC and EAC across Europe using data from Cancer Incidence in Five Continents. RESULTS: Long-term decreasing trends were observed for male esophageal cancer mortality in several southern and western European countries, whereas in central Europe mortality increased until the mid-1990s and started to stabilize or decline over the last years. In some eastern and northern countries, the rates were still increasing. Mortality among European women remained comparatively low and showed stable or decreasing trends in most countries. Between 2000-2004 and 2005-2009, esophageal cancer mortality declined by 7% (from 5.34 to 4.99/100 000) in EU men, and by 3% (from 1.12 to 1.09/100 000) in EU women. Predictions to 2015 show persistent declines in mortality rates for men in the EU overall, and stable rates for EU women, with rates for 2015 of 4.5/100 000 men (about 22 300 deaths) and 1.1/100 000 women (about 7400 deaths). In northern Europe, EAC is now the predominant histological type among men, while for European women ESCC is more common and corresponding rates are still increasing in several countries. CONCLUSION(S): The observed trends reflect the variations in alcohol drinking, tobacco smoking and overweight across European countries.