Results and Outcome Reporting In ClinicalTrials.gov, What Makes it Happen?

At the end of the past century there were multiple concerns regarding lack of transparency in the conduct of clinical trials as well as some ethical and scientific issues affecting the trials' design and reporting. In 2000 ClinicalTrials.gov data repository was developed and deployed to serve public and scientific communities with valid data on clinical trials. Later in order to increase deposited data completeness and transparency of medical research a set of restrains had been imposed making the results deposition compulsory for multiple cases.We investigated efficiency of the results deposition and outcome reporting as well as what factors make positive impact on providing information of interest and what makes it more difficult, whether efficiency depends on what kind of institution was a trial sponsor. Data from the ClinicalTrials.gov repository has been classified based on what kind of institution a trial sponsor was. The odds ratio was calculated for results and outcome reporting by different sponsors' class.As of 01/01/2012 118,602 clinical trials data deposits were made to the depository. They came from 9068 different sources. 35344 (29.8%) of them are assigned as FDA regulated and 25151 (21.2%) as Section 801 controlled substances. Despite multiple regulatory requirements, only about 35% of trials had clinical study results deposited, the maximum 55.56% of trials with the results, was observed for trials completed in 2008.The most positive impact on depositing results, the imposed restrains made for hospitals and clinics. Health care companies showed much higher efficiency than other investigated classes both in higher fraction of trials with results and in providing at least one outcome for their trials. They also more often than others deposit results when it is not strictly required, particularly, in the case of non-interventional studies

Associations between health-related quality of life, physical function and fear of falling in older fallers receiving home care

Falls and injuries in older adults have significant consequences and costs, both personal and to society. Although having a high incidence of falls, high prevalence of fear of falling and a lower quality of life, older adults receiving home care are underrepresented in research on older fallers. The objective of this study is to determine the associations between health-related quality of life (HRQOL), fear of falling and physical function in older fallers receiving home care

Impact of flu on hospital admissions during 4 flu seasons in Spain, 2000–2004

<p>Abstract</p> <p>Background</p> <p>Seasonal flu epidemics in the European region cause high numbers of cases and deaths. Flu-associated mortality has been estimated but morbidity studies are necessary to understand the burden of disease in the population. Our objective was to estimate the excess hospital admissions in Spain of diseases associated with influenza during four epidemic influenza periods (2000 – 2004).</p> <p>Methods</p> <p>Hospital discharge registers containing pneumonia, chronic bronchitis, heart failure and flu from all public hospitals in Spain were reviewed for the years 2000 to 2004. Epidemic periods were defined by data from the Sentinel Surveillance System. Excess hospitalisations were calculated as the difference between the average number of weekly hospitalisations/100,000 in epidemic and non-epidemic periods. Flu epidemics were defined for seasons 2001/2002, 2002/2003, 2003/2004.</p> <p>Results</p> <p>A(H3N2) was the dominant circulating serotype in 2001/2002 and 2003/2004. Negligible excess hospitalisations were observed during the 2002/2003 epidemic where A(H1N1) was circulating. During 2000/2001, flu activity remained below threshold levels and therefore no epidemic period was defined. In two epidemic periods studied a delay between the peak of the influenza epidemic and the peak of hospitalisations was observed. During flu epidemics with A(H3N2), excess hospitalisations were higher in men and in persons <5 and >64 years higher than 10 per 100,000. Pneumonia accounted for 70% of all flu associated hospitalisations followed by chronic bronchitis. No excess flu-specific hospitalisations were recorded during all seasons.</p> <p>Conclusion</p> <p>Flu epidemics have an impact on hospital morbidity in Spain. Further studies that include other variables, such as temperature and humidity, are necessary and will deepen our understanding of the role of each factor during flu epidemics and their relation with morbidity.</p

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

High Distribution of CD40 and TRAF2 in Th40 T Cell Rafts Leads to Preferential Survival of this Auto-Aggressive Population in Autoimmunity

CD40-CD154 interactions have proven critical in autoimmunity, with the identification of CD4(lo)CD40(+) T cells (Th40 cells) as harboring an autoaggressive T cell population shedding new insights into those disease processes. Th40 cells are present at contained levels in non-autoimmune individuals but are significantly expanded in autoimmunity. Th40 cells are necessary and sufficient in transferring type 1 diabetes in mouse models. However, little is known about CD40 signaling in T cells and whether there are differences in that signaling and subsequent outcome depending on disease conditions. When CD40 is engaged, CD40 and TNF-receptor associated factors, TRAFs, become associated with lipid raft microdomains. Dysregulation of T cell homeostasis is emerging as a major contributor to autoimmune disease and thwarted apoptosis is key in breaking homeostasis.Cells were sorted into CD4(hi) and CD4(lo) (Th40 cells) then treated and assayed either as whole or fractionated cell lysates. Protein expression was assayed by western blot and Nf-kappaB DNA-binding activity by electrophoretic mobility shifts. We demonstrate here that autoimmune NOD Th40 cells have drastically exaggerated expression of CD40 on a per-cell-basis compared to non-autoimmune BALB/c. Immediately ex-vivo, untreated Th40 cells from NOD mice have high levels of CD40 and TRAF2 associated with the raft microdomain while Th40 cells from NOR and BALB/c mice do not. CD40 engagement of Th40 cells induces Nf-kappaB DNA-binding activity and anti-apoptotic Bcl-X(L) expression in all three mouse strains. However, only in NOD Th40 cells is anti-apoptotic cFLIP(p43) induced which leads to preferential survival and proliferation. Importantly, CD40 engagement rescues NOD Th40 cells from Fas-induced death.CD40 may act as a switch between life and death promoting signals and NOD Th40 cells are poised for survival via this switch. This may explain how they expand in autoimmunity to thwart T cell homeostasis

NOMA: A Preventable “Scourge” of African Children

Noma is a serious orofacial gangrene originating intraorally in the gingival-oral mucosa complex before spreading extraorally to produce a visibly destructive ulcer. Although cases of noma are now rarely reported in the developed countries, it is still prevalent among children in third world countries, notably in sub-Sahara Africa, where poverty, ignorance, malnutrition, and preventable childhood infections are still common. This review summarizes historical, epidemiological, management, and research updates on noma with suggestions for its prevention and ultimate global eradication. The global annual incidence remains high at about 140,000 cases, with a mortality rate exceeding 90% for untreated diseases. Where the patients survive, noma defects result in unsightly facial disfigurement, intense scarring, trismus, oral incompetence, and social alienation. Although the etiology has long been held to be infectious, a definitive causal role between microorganisms cited, and noma has been difficult to establish. The management of noma with active disease requires antibiotics followed by reconstructive surgery. Current research efforts are focused towards a comprehensive understanding of the epidemiology, and further elucidation of the microbiology and pathogenesis of noma

Regrets Associated with Providing Healthcare: Qualitative Study of Experiences of Hospital-Based Physicians and Nurses

Regret is an unavoidable corollary of clinical practice. Physicians and nurses perform countless clinical decisions and actions, in a context characterised by time pressure, information overload, complexity and uncertainty

Genome-Wide Association between Branch Point Properties and Alternative Splicing

The branch point (BP) is one of the three obligatory signals required for pre-mRNA splicing. In mammals, the degeneracy of the motif combined with the lack of a large set of experimentally verified BPs complicates the task of modeling it in silico, and therefore of predicting the location of natural BPs. Consequently, BPs have been disregarded in a considerable fraction of the genome-wide studies on the regulation of splicing in mammals. We present a new computational approach for mammalian BP prediction. Using sequence conservation and positional bias we obtained a set of motifs with good agreement with U2 snRNA binding stability. Using a Support Vector Machine algorithm, we created a model complemented with polypyrimidine tract features, which considerably improves the prediction accuracy over previously published methods. Applying our algorithm to human introns, we show that BP position is highly dependent on the presence of AG dinucleotides in the 3′ end of introns, with distance to the 3′ splice site and BP strength strongly correlating with alternative splicing. Furthermore, experimental BP mapping for five exons preceded by long AG-dinucleotide exclusion zones revealed that, for a given intron, more than one BP can be chosen throughout the course of splicing. Finally, the comparison between exons of different evolutionary ages and pseudo exons suggests a key role of the BP in the pathway of exon creation in human. Our computational and experimental analyses suggest that BP recognition is more flexible than previously assumed, and it appears highly dependent on the presence of downstream polypyrimidine tracts. The reported association between BP features and the splicing outcome suggests that this, so far disregarded but yet crucial, element buries information that can complement current acceptor site models

International Analysis of Electronic Health Records of Children and Youth Hospitalized With COVID-19 Infection in 6 Countries

Question What are international trends in hospitalizations for children and youth with SARS-CoV-2, and what are the epidemiological and clinical features of these patients? Findings This cohort study of 671 children and youth found discrete surges in hospitalizations with variable trends and timing across countries. Common complications included cardiac arrhythmias and viral pneumonia, and laboratory findings included elevations in markers of inflammation and abnormalities of coagulation; few children and youth were treated with medications directed specifically at SARS-CoV-2. Meaning These findings suggest large-scale informatics-based approaches used to incorporate electronic health record data across health care systems can provide an efficient source of information to monitor disease activity and define epidemiological and clinical features of pediatric patients hospitalized with SARS-CoV-2 infections