Evaluation of subcutaneous proleukin (Interleukin-2) in a randomized international trial (ESPRIT): Geographical and gender differences in the baseline characteristics of participants

Background: ESPRIT, is a phase III, open-label, randomized, international clinical trial evaluating the effects of subcutaneous recombinant interleukin-2 (rIL-2) plus antiretroviral therapy (ART) versus ART alone on HIV-disease progression and death in HIV-1-infected individuals with CD4+ T-cells ≥300 cells/μL. Objectives: To describe the baseline characteristics of participants randomized to ESPRIT overall and by geographic location. Method: Baseline characteristics of randomized participants were summarized by region. Results: 4,150 patients were enrolled in ESPRIT from 254 sites in 25 countries. 41%, 27%, 16%, 11%, and 5% were enrolled in Europe, North America, South America, Asia, and Australia, respectively. The median age was 40 years, 81% were men, and 76%, 11%, and 9% were Caucasian, Asian, and African American or African, respectively. 44% of women enrolled (n = 769) were enrolled in Thailand and Argentina. Overall, 55% and 38% of the cohort acquired HIV through male homosexual and heterosexual contact, respectively. 25% had a prior history of AIDS-defining illness; Pneumocystis jirovecii pneumonia, M. tuberculosis, and esophageal candida were most commonly reported. Median nadir and baseline CD4+ T-cell counts were 199 and 458 cells/μL, respectively. 6% and 13% were hepatitis B or C virus coinfected, respectively. Median duration of antiretroviral therapy (ART) was 4.2 years; the longest median duration was in Australia (5.2 years) and the shortest was in Asia (2.3 years). 17%, 13%, and 69% of participants began ART before 1995, between 1996 and 1997, and from 1998 onward, respectively. 86% used ART from two or more ART classes, with 49% using a protease inhibitor-based regimen and 46% using a nonnucleoside reverse transcriptase inhibitor-based regimen. 78% had plasma HIV RNA below detection (<500 cp/mL). Conclusion: ESPRIT has enrolled a diverse population of HIV-infected individuals including large populations of women and patients of African-American/African and Asian ethnicity often underrepresented in HIV research. As a consequence, the results of the study may have wide global applicability

Expanding the perspective of translational medicine: the value of observational data

In 2003, the Journal of Translational Medicine was launched to foster the publication of high quality research in both "bench-to-bedside" as well as ex vivo human observation. In spite of the success of several large-scale observational studies, e.g. Framingham Heart Study, the opportunity to expand upon the ex vivo human observation has remained limited within the field of translational medicine. We believe that this presents a significant opportunity that merits consideration in both the planning and analysis of large scale observational studies and can contribute greatly to expanding our approaches in translational medicin

Ready or Not, Here They Come: Acting Interns’ Experience and Perceived Competency Performing Basic Medical Procedures

OBJECTIVE: To assess acting interns’ (AI’s) experience with and perceived level of competency performing 6 basic medical procedures. DESIGN: Fourth-year medical students at the University of Cincinnati (UCCOM) are required to complete 2 AI rotations in Internal Medicine. All AIs in 2003–2004 (n = 150) and 2004–2005 (n = 151) were asked to complete a survey about whether during each of their rotations they had performed and felt competent performing the following procedures: phlebotomy, intravenous (IV) catheter insertion, arterial blood gas (ABG), nasogastric (NG) tube insertion, lumbar puncture (LP), and Foley catheter insertion. RESULTS: Four hundred sixty-seven of 601 possible surveys (across both years and both rotations) were completed (78% response rate). During both rotations, relatively few students performed the procedures, ranging from 9% for Foley catheter insertion (24/208) to 50% for both ABG and NG tube insertion (130/259). The two procedures most often performed were ABG (range 46–50%) and NG tube insertion (range 42–50%). Feelings of competency varied from 12% (LP) to 82% (Foley catheter). Except for LP, if students performed a procedure at least once, they reported feeling more competent (range 85% for ABG to 96% for Foley catheter insertion). Among the students who performed LP during a rotation, many still did not feel competent performing LPs: 23 (74%) in rotation 1 and 20 (40%) in rotation 2. CONCLUSION: Many fourth-year students at UCCOM do not perform basic procedures during their acting internship rotations. Procedural performance correlates with feelings of competency. Lumbar puncture competency may be too ambitious a goal for medical students

Factors Influencing the Participation of Older People in Clinical Trials : Data Analysis from the MAVIS Trial

Peer reviewedPostprin

Twelve years of clinical practice guideline development, dissemination and evaluation in Canada (1994 to 2005)

Background - Despite the growing availability of clinical practice guidelines since the early 1990's, little is known about how guideline development and dissemination may have changed over time in Canada. This study compares Canadian guideline development, dissemination, and evaluation in two six year periods from 1994–1999 and 2000–2005. // Methods - Survey of guideline developers who submitted their clinical practice guidelines to the Canadian Medical Association Infobase (a Canadian guideline repository) between 1994 and 2005. Survey items included information about the developers, aspects of guideline development, and dissemination and evaluation activities. // Results - Surveys were sent to the developers of 2341 guidelines in the CMA Infobase over the 12 year period, 1664 surveys were returned (response rate 71%). Of these, 730 unique guidelines were released from 1994–1999, and 630 were released from 2000–2005. Compared to the earlier period, more recent guidelines were being produced in English only. There has been little change in the type of organizations developing guidelines with most developed by provincial and national organizations. In the recent period, developers were more likely to report using computerized search strategies (94% versus 88%), publishing the search strategy (42% versus 34%), reaching consensus using open discussion (95% versus 78%), and evaluating effectiveness of the dissemination strategies (12% versus 6%) and the impact of the CPGs on health outcomes (24% versus 5%). Recent guidelines were less likely to be based on literature reviews (94% versus 99.6%) and were disseminated using fewer strategies (mean 4.78 versus 4.12). // Conclusion - Given that guideline development processes have improved in some areas over the past 12 years yet not in others, ongoing monitoring of guideline quality is required. Guidelines produced more recently in Canada are less likely to be based on a review of the evidence and only about half discuss levels of evidence underlying recommendations. Guideline dissemination and implementation activities have actually decreased. Unfortunately, the potential positive impact on patient health outcomes will not be realized until the recommendations are adopted and acted upon

Prevalence and factors associated with convulsive status epilepticus in Africans with epilepsy

Objective: We conducted a community survey to estimate the prevalence and describe the features, risk factors, and consequences of convulsive status epilepticus (CSE) among people with active convulsive epilepsy (ACE) identified in a multisite survey in Africa. Methods: We obtained clinical histories of CSE and neurologic examination data among 1,196 people with ACE identified from a population of 379,166 people in 3 sites: Agincourt, South Africa; Iganga-Mayuge, Uganda; and Kilifi, Kenya. We performed serologic assessment for the presence of antibodies to parasitic infections and HIV and determined adherence to antiepileptic drugs. Consequences of CSE were assessed using a questionnaire. Logistic regression was used to identify risk factors. Results: The adjusted prevalence of CSE in ACE among the general population across the 3 sites was 2.3 per 1,000, and differed with site (p \u3c 0.0001). Over half (55%) of CSE occurred in febrile illnesses and focal seizures were present in 61%. Risk factors for CSE in ACE were neurologic impairments, acute encephalopathy, previous hospitalization, and presence of antibody titers to falciparum malaria and HIV; these differed across sites. Burns (15%), lack of education (49%), being single (77%), and unemployment (78%) were common in CSE; these differed across the 3 sites. Nine percent with and 10% without CSE died. Conclusions: CSE is common in people with ACE in Africa; most occurs with febrile illnesses, is untreated, and has focal features suggesting preventable risk factors. Effective prevention and the management of infections and neurologic impairments may reduce the burden of CSE in ACE

Designing theoretically-informed implementation interventions: Fine in theory, but evidence of effectiveness in practice is needed

The Improved Clinical Effectiveness through Behavioural Research Group (ICEBeRG) authors assert that a key weakness in implementation research is the unknown applicability of a given intervention outside its original site and problem, and suggest that use of explicit theory offers an effective solution. This assertion is problematic for three primary reasons. First, the presence of an underlying theory does not necessarily ease the task of judging the applicability of a piece of empirical evidence. Second, it is not clear how to translate theory reliably into intervention design, which undoubtedly involves the diluting effect of "common sense." Thirdly, there are many theories, formal and informal, and it is not clear why any one should be given primacy. To determine whether explicitly theory-based interventions are, on average, more effective than those based on implicit theories, pragmatic trials are needed. Until empirical evidence is available showing the superiority of theory-based interventions, the use of theory should not be used as a basis for assessing the value of implementation studies by research funders, ethics committees, editors or policy decision makers

Interventions for behaviour change and self-management in stroke secondary prevention: protocol for an overview of reviews

Abstract Background Stroke secondary prevention guidelines recommend medication prescription and adherence, active education and behavioural counselling regarding lifestyle risk factors. To impact on recurrent vascular events, positive behaviour/s must be adopted and sustained as a lifestyle choice, requiring theoretically informed behaviour change and self-management interventions. A growing number of systematic reviews have addressed complex interventions in stroke secondary prevention. Differing terminology, inclusion criteria and overlap of studies between reviews makes the mechanism/s that affect positive change difficult to identify or replicate clinically. Adopting a two-phase approach, this overview will firstly comprehensively summarise systematic reviews in this area and secondly identify and synthesise primary studies in these reviews which provide person-centred, theoretically informed interventions for stroke secondary prevention. Methods An overview of reviews will be conducted using a systematic search strategy across the Cochrane Database of Systematic Reviews, PubMed and Epistomonikas. Inclusion criteria: systematic reviews where the population comprises individuals post-stroke or TIA and where data relating to person-centred risk reduction are synthesised for evidence of efficacy when compared to standard care or no intervention. Primary outcomes of interest include mortality, recurrent stroke and other cardiovascular events. In phase 1, two reviewers will independently (1) assess the eligibility of identified reviews for inclusion; (2) rate the quality of included reviews using the ROBIS tool; (3) identify unique primary studies and overlap between reviews; (4) summarise the published evidence supporting person-centred behavioural change and self-management interventions in stroke secondary prevention and (5) identify evidence gaps in this field. In phase 2, two independent reviewers will (1) examine person-centred, primary studies in each review using the Template for Intervention Description and Replication (TIDieR checklist), itemising, where present, theoretical frameworks underpinning interventions; (2) group studies employing theoretically informed interventions by the intervention delivered and by the outcomes reported (3) apply GRADE quality of evidence for each intervention by outcome/s identified from theoretically informed primary studies. Disagreement between reviewers at each process stage will be discussed and a third reviewer consulted. Discussion This overview will comprehensively bring together the best available evidence supporting person-centred, stroke secondary prevention strategies in an accessible format, identifying current knowledge gaps

Association of Type 1 Diabetes With Month of Birth Among U.S. Youth: The SEARCH for Diabetes in Youth Study

OBJECTIVE - Seasonal environment at birth may influence diabetes incidence in later life. We sought evidence for this effect in a large sample of diabetic youth residing in the U.S. RESEARCH DESIGN AND METHODS— We compared the distribution of birth months within the SEARCH for Diabetes in Youth Study (SEARCH study) with the monthly distributions in U.S. births tabulated by race for years 1982-2005. SEARCH study participants (9,737 youth with type 1 diabetes and 1,749 with type 2 diabetes) were identified by six collaborating U.S. centers. RESULTS— Among type 1 diabetic youth, the percentage of observed to expected births differed across the months (P = 0.0092; decreased in October-February and increased in March―July). Their smoothed birth-month estimates demonstrated a deficit in November-February births and an excess in April-July births (smoothed May versus January relative risk [RR] = 1.06 [95% CI 1.02―1.11]). Stratifications by sex or by three racial groups showed similar patterns relating type 1 diabetes to month of birth. Stratification by geographic regions showed a peak-to-nadir RR of 1.10 [1.04-1.16] in study regions from the northern latitudes (Colorado, western Washington State, and southern Ohio) but no birth-month effect (P > 0.9) in study regions from more southern locations. Among type 2 diabetic youth, associations with birth month were inconclusive. CONCLUSIONS— Spring births were associated with increased likelihood of type 1 diabetes but possibly not in all U.S. regions. Causal mechanisms may involve factors dependent on geographic latitude such as solar irradiance, but it is unknown whether they influence prenatal or early postnatal development