Coronary Artery Surgery Study (CASS): Comparability of 10 year survival in randomized and randomizable patients

AbstractThe Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction.Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison.Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis ≥70% and an ejection fraction < 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction < 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p < 0.05).After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial

Recommendations for Care of the Asymptomatic Patient

We present a set of reasonable guidelines for the care of healthy, asymptomatic individuals based upon recommendations prepared by an Internal Medicine review committee of Henry Ford Hospital. There recommendations have four goals: to prevent disease, to detect disease in an asymptomatic and potentially curable state, to enhance the patient\u27s quality of life, and to help physicians teach patients good health habits. Recommendations are made for infectious diseases, cancer, metabolic diseases, neurosensory conditions like visual and hearing loss, and general health habits. Some recommendations are at variance with those of well recognized authorities and should be viewed only as a suggested protocol for the care of the asymptomatic patient. Results of ongoing studies may alter our understanding of some areas of controversy and mandate revision of these guidelines periodically

Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host

Schmallenberg virus (SBV) is an emerging orthobunyavirus of ruminants associated with outbreaks of congenital malformations in aborted and stillborn animals. Since its discovery in November 2011, SBV has spread very rapidly to many European countries. Here, we developed molecular and serological tools, and an experimental in vivo model as a platform to study SBV pathogenesis, tropism and virus-host cell interactions. Using a synthetic biology approach, we developed a reverse genetics system for the rapid rescue and genetic manipulation of SBV. We showed that SBV has a wide tropism in cell culture and “synthetic” SBV replicates in vitro as efficiently as wild type virus. We developed an experimental mouse model to study SBV infection and showed that this virus replicates abundantly in neurons where it causes cerebral malacia and vacuolation of the cerebral cortex. These virus-induced acute lesions are useful in understanding the progression from vacuolation to porencephaly and extensive tissue destruction, often observed in aborted lambs and calves in naturally occurring Schmallenberg cases. Indeed, we detected high levels of SBV antigens in the neurons of the gray matter of brain and spinal cord of naturally affected lambs and calves, suggesting that muscular hypoplasia observed in SBV-infected lambs is mostly secondary to central nervous system damage. Finally, we investigated the molecular determinants of SBV virulence. Interestingly, we found a biological SBV clone that after passage in cell culture displays increased virulence in mice. We also found that a SBV deletion mutant of the non-structural NSs protein (SBVΔNSs) is less virulent in mice than wild type SBV. Attenuation of SBV virulence depends on the inability of SBVΔNSs to block IFN synthesis in virus infected cells. In conclusion, this work provides a useful experimental framework to study the biology and pathogenesis of SBV

Heterocellular induction of interferon by negative-sense RNA viruses

The infection of cells by RNA viruses is associated with the recognition of virus PAMPs (pathogen-associated molecular patterns) and the production of type I interferon (IFN). To counter this, most, if not all, RNA viruses encode antagonists of the IFN system. Here we present data on the dynamics of IFN production and response during developing infections by paramyxoviruses, influenza A virus and bunyamwera virus. We show that only a limited number of infected cells are responsible for the production of IFN, and that this heterocellular production is a feature of the infecting virus as opposed to an intrinsic property of the cells

A cluster randomised control trial to evaluate the effectiveness and cost-effectiveness of the Italian medicines use review (I-MUR) for asthma patients

Background The economic burden of asthma, which relates to the degree of control, is €5 billion annually in Italy. Pharmacists could help improve asthma control, reducing this burden. This study aimed to evaluate the effectiveness and cost-effectiveness of Medicines Use Reviews provided by community pharmacists in asthma. Methods This cluster randomised, multi-centre, controlled trial in adult patients with asthma was conducted in 15 of the 20 regions of Italy between September 2014 and July 2015. After stratification by region, community pharmacists were randomly allocated to group A (trained in and delivered the intervention at baseline) or B (training and delivery 3 months later), using computerised random number generation in blocks of 10. Each recruited up to five patients, with both groups followed for 9 months. The intervention consisted of a systematic, structured face-to-face consultation with a pharmacist, covering asthma symptoms, medicines used, attitude towards medicines and adherence, recording pharmacist-identified pharmaceutical care issues (PCIs). The primary outcome was asthma control, assessed using the Asthma-Control-Test (ACT) score (ACT ≥ 20 represents good control). Secondary outcomes were: number of active ingredients, adherence, cost-effectiveness compared with usual care. Although blinding was not possible for either pharmacists or patients, assessment of outcomes was conducted by researchers blind to group allocation. Results Numbers of pharmacists and patients enrolled were 283 (A = 136; B = 147) and 1263 (A = 600; B = 663), numbers completing were 201 (A = 97; B = 104) and 816 (A = 400; B = 416), respectively. Patients were similar in age and gender and 56.13% (458/816) had poor/partial asthma control. Pharmacists identified 1256 PCIs (mean 1.54/patient), mostly need for education, monitoring and potentially ineffective therapy. Median ACT score at baseline differed between groups (A = 19, B = 18; p < 0.01). Odds ratio for improved asthma control was 1.76 (95% CI 1.33–2.33) and number needed to treat 10 (95% CI 6–28). Number of active ingredients reduced by 7.9% post-intervention (p < 0.01). Adherence improved by 35.4% 3 months post-intervention and 40.0% at 6 months (p < 0.01). The probability of the intervention being more cost-effective than usual care was 100% at 9 months. Conclusions This community pharmacist-based intervention demonstrated both effectiveness and cost-effectiveness. It has since been implemented as the first community pharmacy cognitive service in Italy

Determinants of costs and the length of stay in acute coronary syndromes : a real life analysis of more than 10 000 patients

Aims: The aim of this study was to investigate inpatient costs of acute coronary syndromes (ACS) in Switzerland and to assess the main cost drivers associated with this disease. Methods and Results: We used the national multicenter registry AMIS (acute myocardial infarction in Switzerland) which includes a representative number of 65 hospitals and a total of 11.623 patient records. The following cost modules were analyzed: hospital stay, percutaneous coronary interventions (PCI) and thrombolysis. Expenses were assessed using data from official Swiss national statistical sources. Mean total costs per patient were 12.101 Euro (median 10.929 Euro; 95% CI: 1.161–27.722 Euro). The length of stay ranged from one to 129 days with a mean of 9.5 days (median 8.0 days; 95% CI: 1–23). Overall costs were independently influenced by age, gender and existent co-morbidities, e.g. cerebrovascular disease and diabetes (p < 0.0001). Conclusion: Our study determined specific causes for the high costs associated with hospital treatment on a large representative sample. The results should highlight unnecessary expenses and help policy makers to evaluate the base case for a DRG (Diagnosis Related Groups) scenario in Switzerland. Cost weighting of the identified secondary diagnosis should be considered in the calculation and coding of a primary diagnosis for ACS

Nurse-Led Medicines' Monitoring for Patients with Dementia in Care Homes: A Pragmatic Cohort Stepped Wedge Cluster Randomised Trial

People with dementia are susceptible to adverse drug reactions (ADRs). However, they are not always closely monitored for potential problems relating to their medicines: structured nurse-led ADR Profiles have the potential to address this care gap. We aimed to assess the number and nature of clinical problems identified and addressed and changes in prescribing following introduction of nurse-led medicines' monitoring.Pragmatic cohort stepped-wedge cluster Randomised Controlled Trial (RCT) of structured nurse-led medicines' monitoring versus usual care.Five UK private sector care homes.41 service users, taking at least one antipsychotic, antidepressant or anti-epileptic medicine.Nurses completed the West Wales ADR (WWADR) Profile for Mental Health Medicines with each participant according to trial step.Problems addressed and changes in medicines prescribed.Information was collected from participants' notes before randomisation and after each of five monthly trial steps. The impact of the Profile on problems found, actions taken and reduction in mental health medicines was explored in multivariate analyses, accounting for data collection step and site.Five of 10 sites and 43 of 49 service users approached participated. Profile administration increased the number of problems addressed from a mean of 6.02 [SD 2.92] to 9.86 [4.48], effect size 3.84, 95% CI 2.57-4.11, P <0.001. For example, pain was more likely to be treated (adjusted Odds Ratio [aOR] 3.84, 1.78-8.30), and more patients attended dentists and opticians (aOR 52.76 [11.80-235.90] and 5.12 [1.45-18.03] respectively). Profile use was associated with reduction in mental health medicines (aOR 4.45, 1.15-17.22).The WWADR Profile for Mental Health Medicines can improve the quality and safety of care, and warrants further investigation as a strategy to mitigate the known adverse effects of prescribed medicines.ISRCTN 48133332