Are routinely collected NHS administrative records suitable for endpoint identification in clinical trials? Evidence from the West of Scotland coronary prevention study

Background: Routinely collected electronic patient records are already widely used in epidemiological research. In this work we investigated the potential for using them to identify endpoints in clinical trials.<p></p> Methods: The events recorded in the West of Scotland Coronary Prevention Study (WOSCOPS), a large clinical trial of pravastatin in middle-aged hypercholesterolaemic men in the 1990s, were compared with those in the record-linked deaths and hospitalisations records routinely collected in Scotland.<p></p> Results: We matched 99% of fatal study events by date. We showed excellent matching (97%) of the causes of fatal endpoint events and good matching (.80% for first events) of the causes of nonfatal endpoint events with a slightly lower rate of mismatching of record linkage than study events (19% of first study myocardial infarctions (MI) and 4% of first record linkage MIs not matched as MI). We also investigated the matching of non-endpoint events and showed a good level of matching, with .78% of first stroke/TIA events being matched as stroke/TIA. The primary reasons for mismatches were record linkage data recording readmissions for procedures or previous events, differences between the diagnoses in the routinely collected data and the conclusions of the clinical trial expert adjudication committee, events occurring outside Scotland and therefore being missed by record linkage data, miscoding of cardiac events in hospitalisations data as ‘unspecified chest pain’, some general miscoding in the record linkage data and some record linkage errors.<p></p> Conclusions: We conclude that routinely collected data could be used for recording cardiovascular endpoints in clinical trials and would give very similar results to rigorously collected clinical trial data, in countries with unified health systems such as Scotland. The endpoint types would need to be carefully thought through and an expert endpoint adjudication committee should be involved.<p></p&gt

Effects of Community Exercise Therapy on Metabolic, Brain, Physical, and Cognitive Function Following Stroke : A Randomized Controlled Pilot Trial

© The Author(s) 2014.Peer reviewedPostprintPostprin

Optimal CD4 count for initiating HIV treatment: impact of CD4 observation frequency and grace periods, and performance of dynamic marginal structural models.

BACKGROUND: In HIV infection, dynamic marginal structural models have estimated the optimal CD4 for treatment initiation to minimize AIDS/death. The impact of CD4 observation frequency and grace periods (permitted delay to initiation) on the optimal regimen has not been investigated nor has the performance of dynamic marginal structural models in moderately sized data sets-two issues that are relevant to many applications. METHODS: To determine optimal regimens, we simulated 31,000,000 HIV-infected persons randomized at CD4 500-550 cells/mm to regimens "initiate treatment within a grace period following observed CD4 first 0.5% lower AIDS-free survival compared with the true optimal regimen. CONCLUSIONS: The optimal regimen is strongly influenced by CD4 frequency and less by grace period length. Dynamic marginal structural models lack precision at moderate sample sizes

Low False-Positive Rate of Kepler Candidates Estimated From A Combination Of Spitzer And Follow-Up Observations

(Abridged) NASA's Kepler mission has provided several thousand transiting planet candidates, yet only a small subset have been confirmed as true planets. Therefore, the most fundamental question about these candidates is the fraction of bona fide planets. Estimating the rate of false positives of the overall Kepler sample is necessary to derive the planet occurrence rate. We present the results from two large observational campaigns that were conducted with the Spitzer telescope during the the Kepler mission. These observations are dedicated to estimating the false positive rate (FPR) amongst the Kepler candidates. We select a sub-sample of 51 candidates, spanning wide ranges in stellar, orbital and planetary parameter space, and we observe their transits with Spitzer at 4.5 microns. We use these observations to measures the candidate's transit depths and infrared magnitudes. A bandpass-dependent depth alerts us to the potential presence of a blending star that could be the source of the observed eclipse: a false-positive scenario. For most of the candidates (85%), the transit depths measured with Kepler are consistent with the depths measured with Spitzer as expected for planetary objects, while we find that the most discrepant measurements are due to the presence of unresolved stars that dilute the photometry. The Spitzer constraints on their own yield FPRs between 5-40%, depending on the KOIs. By considering the population of the Kepler field stars, and by combining follow-up observations (imaging) when available, we find that the overall FPR of our sample is low. The measured upper limit on the FPR of our sample is 8.8% at a confidence level of 3 sigma. This observational result, which uses the achromatic property of planetary transit signals that is not investigated by the Kepler observations, provides an independent indication that Kepler's false positive rate is low.Comment: 33 pages, 16 figures, 3 tables; accepted for publication in ApJ on February 7, 201

AIDS-associated Kaposi's sarcoma is linked to advanced disease and high mortality in a primary care HIV programme in South Africa

BACKGROUND: AIDS-associated Kaposi's sarcoma is an important, life-threatening opportunistic infection among people living with HIV/AIDS in resource-limited settings. In western countries, the introduction of combination antiretroviral therapy (cART) and new chemotherapeutic agents has resulted in decreased incidence and improved prognosis of AIDS-associated Kaposi's sarcoma. In African cohorts, however, mortality remains high. In this study, we describe disease characteristics and risk factors for mortality in a public sector HIV programme in South Africa. METHODS: We analysed data from an observational cohort study of HIV-infected adults with AIDS-associated Kaposi's sarcoma, enrolled between May 2001 and January 2007 in three primary care clinics. Paper records from primary care and tertiary hospital oncology clinics were reviewed to determine the site of Kaposi's sarcoma lesions, immune reconstitution inflammatory syndrome stage, and treatment. Baseline characteristics, cART use and survival outcomes were extracted from an electronic database maintained for routine monitoring and evaluation. Cox regression was used to model associations with mortality. RESULTS: Of 6292 patients, 215 (3.4%) had AIDS-associated Kaposi's sarcoma. Lesions were most commonly oral (65%) and on the lower extremities (56%). One quarter of patients did not receive cART. The mortality and lost-to-follow-up rates were, respectively, 25 (95% CI 19-32) and eight (95% CI 5-13) per 100 person years for patients who received cART, and 70 (95% CI 42-117) and 119 (80-176) per 100 person years for patients who did not receive cART. Advanced T stage (adjusted HR, AHR = 5.3, p < 0.001), advanced S stage (AHR = 5.1, p = 0.008), and absence of chemotherapy (AHR = 2.4, p = 0.012) were associated with mortality.Patients with AIDS-associated Kaposi's sarcoma presented with advanced disease and high rates of mortality and loss to follow up. Risk factors for mortality included advanced Kaposi's sarcoma disease and lack of chemotherapy use. Contributing factors to the high mortality for patients with AIDS-associated Kaposi's sarcoma likely included late diagnosis of HIV disease, late accessibility to cART, and sub-optimal treatment of advanced Kaposi's sarcoma. CONCLUSIONS: These findings confirm the importance of early access to both cART and chemotherapy for patients with AIDS-associated Kaposi's sarcoma. Early diagnosis and improved treatment protocols in resource-poor settings are essential

Sterilization of granulomas is common in both active and latent tuberculosis despite extensive within-host variability in bacterial killing

Over 30% of the world’s population is infected with Mycobacterium tuberculosis (Mtb), yet only ~5–10% will develop clinical disease1. Despite considerable effort, we understand little about what distinguishes individuals who progress to active tuberculosis (TB) from those who remain latent for decades. The variable course of disease is recapitulated in cynomolgus macaques infected with Mtb2. Active disease in macaques is defined by clinical, microbiologic and immunologic signs and occurs in ~45% of animals, while the remaining are clinically asymptomatic2,3. Here, we use barcoded Mtb isolates and quantitative measures of culturable and cumulative bacterial burden to show that most lesions are likely founded by a single bacterium and reach similar maximum burdens. Despite common origins, the fate of individual lesions varies substantially within the same host. Strikingly, in active disease, the host sterilizes some lesions even while others progress. Our data suggest that lesional heterogeneity arises, in part, through differential killing of bacteria after the onset of adaptive immunity. Thus, individual lesions follow diverse and overlapping trajectories, suggesting critical responses occur at a lesional level to ultimately determine the clinical outcome of infection. Defining the local factors that dictate outcome will be important in developing effective interventions to prevent active TB

Health Profiles of Newly Arriving Refugees in Kentucky, 2016: Data from the University of Louisville Global Health Program

Objectives: Refugees resettling in the United States bring with them a number of health conditions, the majority chronic. These health conditions may impact their ability to be successful with disease self-management and employment, and acculturate and thrive in their new communities. Knowledge of health conditions present in individual refugee populations can be of benefit to healthcare providers in the community and public health. The objective of this manuscript is to describe the state of health among refugees newly arriving in the US and resettling in Kentucky during 2016. Methods: Using data from the domestic health screens, immunization clinics, and the Centers for Disease Control and Prevention Electronic Disease Notification, a database entitled Arriving Refugee Informatics Surveillance and Epidemiology (ARIVE) was developed and the Research Electronic Data Capture (REDCap) system used as the platform. Results: A total of 1495 adult and pediatric refugees were screened during January-June 2016 in Louisville, Lexington, Owensboro, and Bowling Green, Kentucky and data entered into ARIVE. Results from those domestic health screenings identified dental abnormalities (60%), obesity (23%), decreased visual acuity (14%), hyperlipidemia (14%), and elevated blood lead levels in child refugees (12%). Latent tuberculosis infection was identified in 13% and more than 32% had evidence of at least one intestinal parasite. Conditions of social importance included tobacco use among 16%. Mental health issues were evident as 15% had a positive Refugee Health Screener (RHS-15) result and more than 13% indicated they had witnessed or experienced torture. Conclusions: This analysis shows that the main health conditions facing refugees after arriving in the US are chronic conditions that require long‐term medical management and support services. Upon review of these results, a systematic approach to solving the problem of long‐term follow‐up needs to be established for refugees in order to address and decrease the impact of chronic health conditions. Using information from this Kentucky assessment may promote interest in a national refugee health database as a means of developing population-based and population-specific interventions to improve overall health