The use of segmented regression in analysing interrupted time series studies : an example in pre-hospital ambulance care

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Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r²=0.98–1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml⁻¹ of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=−0.06, P-value=2.7 × 10⁻⁴). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections

Trends in the use of coercive measures in Finnish psychiatric hospitals: a register analysis of the past two decades

BackgroundCoercive measures is a topic that has long been discussed in the field of psychiatry. Despite global reports of reductions in the use of restraint episodes due to new regulations, it is still questionable if practices have really changed over time. For this study, we examined the rates of coercive measures in the inpatient population of psychiatric care providers across Finland to identify changing trends as well as variations in such trends by region.MethodsIn this nationwide registry analysis, we extracted patient data from the national database (The Finnish National Care Register for Health Care) over a 20-year period. We included adult patients admitted to psychiatric units (care providers) and focused on patients who had faced coercive measures (seclusion, limb restraints, forced injection and physical restraints) during their hospital stay. Multilevel logistical models (a polynomial model of quadratic form) were used to examine trends in prevalence of any coercive measures as well as the other four specified coercive measures over time, and to investigate variation in such trends among care providers and regions.ResultsBetween 1995 and 2014, the dataset contained 226,948 inpatients who had been admitted during the 20-year time frame (505,169 treatment periods). The overall prevalence of coercive treatment on inpatients was 9.8%, with a small decrease during 2011–2014. The overall prevalence of seclusion, limb restraints, forced injection and physical restraints on inpatients was 6.9, 3.8, 2.6 and 0.8%, respectively. Only the use of limb restraints showed a downward trend over time. Geographic and care provider variations in specific coercive measures used were also observed.ConclusionsDespite the decreasing national level of coercive measures used in Finnish psychiatric hospitals, the overall reduction has been small during the last two decades. These results have implications on the future development of structured guidelines and interventions for preventing and more effectively managing challenging situations. Clinical guidelines and staff education related to the use of coercive measures should be critically assessed to ensure that the staff members working with vulnerable patient populations in psychiatric hospitals are ethically competent.</p

Prenatal exposures and exposomics of asthma

This review examines the causal investigation of preclinical development of childhood asthma using exposomic tools. We examine the current state of knowledge regarding early-life exposure to non-biogenic indoor air pollution and the developmental modulation of the immune system. We examine how metabolomics technologies could aid not only in the biomarker identification of a particular asthma phenotype, but also the mechanisms underlying the immunopathologic process. Within such a framework, we propose alternate components of exposomic investigation of asthma in which, the exposome represents a reiterative investigative process of targeted biomarker identification, validation through computational systems biology and physical sampling of environmental medi

Profiling quality of care for patients with chronic headache in three different German hospitals – a case study

BACKGROUND: Legal requirements for quality assurance in German rehabilitation hospitals include comparisons of providers. Objective is to describe and to compare outcome quality of care offered by three hospitals providing in-patient rehabilitative treatment exemplified for patients with chronic headache. METHODS: We performed a prospective three center observational study on patients suffering from chronic headache. Patients underwent interventions commonly used according to internal guidelines of the hospitals. Measurements were taken at three points in time (at admission, at discharge and 6 months after discharge). Indicators of outcome quality included pain intensity and frequency of pain, functional ability, depression, quality of life and health related behavior. Analyses of differences amongst the hospitals were adjusted by covariates due to case-mix situation. RESULTS: 306 patients from 3 hospitals were included in statistical analysis. Amongst the hospitals, patients differed significantly in age, education, diagnostic subgroups, beliefs, and with respect to some pain-related baseline values (covariates). Patients in all three hospitals benefited from intervention to a clinically relevant degree. At discharge from hospital, outcome quality differed significantly after adjustment according to case-mix only in terms of patients' global assessment of treatment results. Six months after discharge, the only detectable significant differences were for secondary outcomes like improved coping with stress or increased use of self-help. The profiles for satisfaction with the hospital stay showed clear differences amongst patients. CONCLUSION: The results of this case study do not suggest a definite overall ranking of the three hospitals that were compared, but outcome profiles offer a multilayer platform of reliable information which might facilitate decision making

Detection of silent myocardial ischemia in asymptomatic patients with diabetes: results of a randomized trial and meta-analysis assessing the effectiveness of systematic screening

<p>Abstract</p> <p>Background</p> <p>Most guidelines recommend a systematic screening of asymptomatic high risk patients with diabetes for silent ischemia, but the clinical benefit of this strategy has not been demonstrated compared with the simple control of cardiovascular risk factors. We sought to determine whether referring asymptomatic diabetic patients for screening of silent ischemia decreases the risk of cardiovascular events compared with usual care.</p> <p>Methods</p> <p>DYNAMIT was a prospective, randomized, open, blinded end-point multicenter trial run between 2000 and 2005, with a 3.5 year mean follow-up in ambulatory care in 45 French hospitals. The study included 631 male and female with diabetes aged 63.9 ± 5.1 years, with no evidence of coronary artery disease and at least 2 additional cardiovascular risk factors, receiving appropriate medical treatment. The patients were randomized centrally to either screening for silent ischemia using a bicycle exercise test or Dipyridamole Single Photon Emission Computed Tomography (N = 316), or follow-up without screening (N = 315). The main study end point was time to death from all causes, non-fatal myocardial infarction, non-fatal stroke, or heart failure requiring hospitalization or emergency service intervention. The results of a meta-analysis of DYNAMIT and DIAD, a similar study, are also presented.</p> <p>Results</p> <p>The study was discontinued prematurely because of difficulties in recruitment and a lower-than expected event rate. Follow-up was complete for 98.9% patients regarding mortality and for 97.5% regarding the main study end point. Silent ischemia detection procedure was positive or uncertain in 68 (21.5%) patients of the screening group. There was no significant difference between the screening and the usual care group for the main outcome (hazard ratio = 1.00 95%CI 0.59 to 1.71). The meta-analysis of these and DIAD results gave similar results, with narrower confidence intervals for each endpoint.</p> <p>Conclusions</p> <p>These results suggest that the systematic detection of silent ischemia in high-risk asymptomatic patients with diabetes is unlikely to provide any major benefit on hard outcomes in patients whose cardiovascular risk is controlled by an optimal medical treatment.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00627783">NCT00627783</a></p

Improving quality indicator report cards through Bayesian modeling

<p>Abstract</p> <p>Background</p> <p>The National Database for Nursing Quality Indicators^®(NDNQI^®) was established in 1998 to assist hospitals in monitoring indicators of nursing quality (eg, falls and pressure ulcers). Hospitals participating in NDNQI transmit data from nursing units to an NDNQI data repository. Data are summarized and published in reports that allow participating facilities to compare the results for their units with those from other units across the nation. A disadvantage of this reporting scheme is that the sampling variability is not explicit. For example, suppose a small nursing unit that has 2 out of 10 (rate of 20%) patients with pressure ulcers. Should the nursing unit immediately undertake a quality improvement plan because of the rate difference from the national average (7%)?</p> <p>Methods</p> <p>In this paper, we propose approximating 95% credible intervals (CrIs) for unit-level data using statistical models that account for the variability in unit rates for report cards.</p> <p>Results</p> <p>Bayesian CrIs communicate the level of uncertainty of estimates more clearly to decision makers than other significance tests.</p> <p>Conclusion</p> <p>A benefit of this approach is that nursing units would be better able to distinguish problematic or beneficial trends from fluctuations likely due to chance.</p

Meta-analysis of trials comparing anastrozole and tamoxifen for adjuvant treatment of postmenopausal women with early breast cancer

<p>Abstract</p> <p>Objective</p> <p>It was aimed to review the literature and make a meta-analysis of the trials on both upfront, switching, and sequencing anastrozole in the adjuvant treatment of early breast cancer.</p> <p>Methods</p> <p>The PubMed, ClinicalTrials.gov and Cochrane databases were systematically reviewed for randomized-controlled trials comparing anastrozole with tamoxifen in the adjuvant treatment of early breast cancer.</p> <p>Results</p> <p>The combined hazard rate of 4 trials for event-free survival (EFS) was 0.77 (95%CI: 0.70–0.85) (<it>P </it>< 0.0001) for patients treated with anastrozole compared with tamoxifen. In the second analysis in which only ITA, ABCSG 8, and ARNO 95 trials were included and ATAC (upfront trial) was excluded, combined hazard rate for EFS was 0.64 (95%CI: 0.52–0.79) (<it>P </it>< 0.0001). In the third analysis including hazard rate for recurrence-free survival (excluding non-disease related deaths) of estrogen receptor-positive patients for ATAC trial and hazard rate for EFS of all patients for the rest of the trials, combined hazard rate was 0.73 (95%CI: 0.65–0.81) (<it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>Anastrozole appears to have superior efficacy than tamoxifen in the adjuvant hormonal treatment of early breast cancer. Until further clinical evidence comes up, aromatase inhibitors should be the initial hormonal therapy in postmenopausal early breast cancer patients and switching should only be considered for patients who are currently receiving tamoxifen.</p

Design choices made by target users for a pay-for-performance program in primary care: an action research approach

Contains fulltext : 110832.pdf (publisher's version ) (Open Access)BACKGROUND: International interest in pay-for-performance (P4P) initiatives to improve quality of health care is growing. Current programs vary in the methods of performance measurement, appraisal and reimbursement. One may assume that involvement of health care professionals in the goal setting and methods of quality measurement and subsequent payment schemes may enhance their commitment to and motivation for P4P programs and therefore the impact of these programs. We developed a P4P program in which the target users were involved in decisions about the P4P methods. METHODS: For the development of the P4P program a framework was used which distinguished three main components: performance measurement, appraisal and reimbursement. Based on this framework design choices were discussed in two panels of target users using an adapted Delphi procedure. The target users were 65 general practices and two health insurance companies in the South of the Netherlands. RESULTS: Performance measurement was linked to the Dutch accreditation program based on three domains (clinical care, practice management and patient experience). The general practice was chosen as unit of assessment. Relative standards were set at the 25th percentile of group performance. The incentive for clinical care was set twice as high as the one for practice management and patient experience. Quality scores were to be calculated separately for all three domains, and for both the quality level and the improvement of performance. The incentive for quality level was set thrice as high as the one for the improvement of performance. For reimbursement, quality scores were divided into seven levels. A practice with a quality score in the lowest group was not supposed to receive a bonus. The additional payment grew proportionally for each extra group. The bonus aimed at was on average 5% to 10% of the practice income. CONCLUSIONS: Designing a P4P program for primary care with involvement of the target users gave us an insight into their motives, which can help others who need to discuss similar programs. The resulting program is in line with target users' views and assessments of relevance and applicability. This may enhance their commitment to the program as was indicated by the growing number of voluntary participants after a successfully performed field test during the procedure. The elements of our framework can be very helpful for others who are developing or evaluating a P4P program