This study showed that assessment of the complement-binding capacity of donor-specific anti-HLA antibodies may help identify patients at high risk for kidney-allograft loss and may improve risk ...stratification to guide treatment.
Despite considerable advances in transplantation, the induced alloimmune response remains a major determinant of late kidney-allograft loss.
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In the United States and Europe, thousands of kidney transplants fail each year, and kidney-allograft failure is a major cause of end-stage renal disease, leading to increased morbidity, mortality, and costs.
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One of the most important advances in transplantation medicine has been the recognition that anti-HLA antibodies are destructive.
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Various studies over the past decade have indicated that the alloimmune response, mediated by anti-HLA antibodies, plays a key role in the failure of kidney allografts; this concept has been extended . . .
ObjectivesThis study aimed to investigate adherence to Consolidated Standards of Reporting Trials (CONSORT) for abstracts in reports of randomised trials on child and adolescent depression ...prevention. Secondary objective was to examine factors associated with overall reporting quality.DesignMeta-epidemiological study.Data sourcesWe searched MEDLINE, EMBASE, PsycINFO, PsycArticles and CENTRAL.Eligibility criteriaTrials were eligible if the sample consisted of children and adolescents under 18 years with or without an increased risk for depression or subthreshold depression. We included reports published from 1 January 2003 to 8 August 2020 on randomised controlled trials (RCTs) and cluster randomised trials (CRTs) assessing universal, selective and indicated interventions aiming to prevent the onset of depression or reducing depressive symptoms.Data extraction and synthesisAs the primary outcome measure, we assessed for each trial abstract whether information recommended by CONSORT was adequately reported, inadequately reported or not reported. Moreover, we calculated a summative score of overall reporting quality and analysed associations with trial and journal characteristics.ResultsWe identified 169 eligible studies, 103 (61%) RCTs and 66 (39%) CRTs. Adequate reporting varied considerably across CONSORT items: while 9 out of 10 abstracts adequately reported the study objective, no abstract adequately provided information on blinding. Important adverse events or side effects were only adequately reported in one out of 169 abstracts. Summative scores for the abstracts’ overall reporting quality ranged from 17% to 83%, with a median of 40%. Scores were associated with the number of authors, abstract word count, journal impact factor, year of publication and abstract structure.ConclusionsReporting quality for abstracts of trials on child and adolescent depression prevention is suboptimal. To help health professionals make informed judgements, efforts for improving adherence to reporting guidelines for abstracts are needed.
This study developed a novel risk assessment model to predict the occurrence of cardiovascular disease (CVD) events. It uses a Genetic Algorithm (GA) to develop an easy-to-use model with high ...accuracy, calibrated based on the Isfahan Cohort Study (ICS) database. The ICS was a population-based prospective cohort study of 6,504 healthy Iranian adults aged greater than or equal to 35 years followed for incident CVD over ten years, from 2001 to 2010. To develop a risk score, the problem of predicting CVD was solved using a well-designed GA, and finally, the results were compared with classic machine learning (ML) and statistical methods. A number of risk scores such as the WHO, and PARS models were utilized as the baseline for comparison due to their similar chart-based models. The Framingham and PROCAM models were also applied to the dataset, with the area under a Receiver Operating Characteristic curve (AUROC) equal to 0.633 and 0.683, respectively. However, the more complex Deep Learning model using a three-layered Convolutional Neural Network (CNN) performed best among the ML models, with an AUROC of 0.74, and the GA-based eXplanaible Persian Atherosclerotic CVD Risk Stratification (XPARS) showed higher performance compared to the statistical methods. XPARS with eight features showed an AUROC of 0.76, and the XPARS with four features, showed an AUROC of 0.72. A risk model that is extracted using GA substantially improves the prediction of CVD compared to conventional methods. It is clear, interpretable and can be a suitable replacement for conventional statistical methods.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent patent losses for antiretroviral drugs (ARV) have led to the debate of cost-saving through the replacement of patented drugs with generic drugs. The split of recommended single-tablet regimens ...(STR) into their single substance partners is one of the considerations mentioned in said debate. Particularly, generic tenofovir disoproxil/emtricitabine (TDF/FTC) is expected to hold untapped cost-saving potential, which may curb increasing overall expenditures for combined antiretroviral therapy (cART) within the statutory health insurance (SHI) of Germany.
Data of ARV reimbursed by the SHI were used to describe the trends of defined daily doses (DDD) as well as the revenue within the German ARV market. They were also used to determine the cost-savings of moving to generic drugs. The time period observed was between January 2017 and June 2019. The potential cost-savings were determined with following assumption in mind: the maximum possible use of generic ARV, including 1) the split of STR and replacing all substance partners with generic ones, and 2) replacing patented tenofovir alafenamide/emtricitabine (TAF/FTC) with generic TDF/FTC.
Throughout the observation period, the DDD of generic ARV increased nearly five-fold while their revenue increased more than four-fold. Total cost-saving showed a sharp increase over the same period, with generic TDF/FTC accounting for a share of around 70%. The largest potential cost-saving could have been achieved through replacing patented TAF/FTC with generic TDF/FTC, peaking at nearly 10% of total revenue, but showing decreasing trends in general.
The progressive distribution of generic ARV ensured increasing cost-savings
but consequently curbed the potential cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for these effects. In any case, substituting with generic ARV should not fail to adhere to the treatment guidelines and continue to consider the medical requirements for the treatment.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products ...Act.Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions.
Abstract Objective To investigate the validity and reliability of the EuroQol‐5D (EQ-5D), the 12‐item Short‐Form Health Survey (SF-12v2), and the Hospital Anxiety and Depression Scale (HADS) in a ...stable coronary population. Study design Cross-sectional study EUROASPIRE III. Setting Quality of life data (QoL) were available on 8745 patients hospitalized for coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), acute myocardial infarction (AMI), or myocardial ischemia. They were interviewed and examined at least 6 months after their hospital admission. Reliability and validity of the 3 instruments were tested. Internal consistency, and discriminative, convergent, criterion and construct validity were assessed. Results Cronbach's alpha indicated good internal consistency for all measures (0.73 to 0.87). Discriminative validity analyses confirmed significant QoL differences between known groups: age, gender, educational level. In addition, all hypothesized correlations between QoL constructs (convergent validity) and items (criterion validity) were confirmed with significant correlations. Confirmatory factor analyses indicated good construct validity for HADS and SF-12v2. On country-specific level, results were roughly similar. Conclusion The EQ-5D as well as the SF-12v2 and the HADS are reliable and valid instruments for use in a stable coronary population, both on aggregate European level and on country-specific level. However, our results must be generalized with caution, because EUROASPIRE III patients might not be representative for all patients with stable coronary heart disease.
Objectives Depression is a major contributor of young people's burden of disease. In this study we aim to estimate the effect of elevated depressive symptoms on physical health-related quality of ...life. Design We used self-reported information from the prospective BELLA cohort study, which included adolescents selected from the general population in Germany. The baseline assessment (2003–2006) and the 1-, 2-, and 6-year follow-up waves provide the data basis. Participants The baseline study population consisted of 1,460 adolescents between the ages of 12 and 17 who, according to their caregivers, did not suffer from depression. Variables The primary outcome, as measured by the physical component score (PCS) of the SF-36 at a 6-year follow-up (range: 0–100), is physical health-related quality of life. The exposure of interest is depressive symptoms, as measured by the Center for Epidemiological Studies Depression Scale for Children (CES-DC) at baseline, 1-year follow-up and 2-year follow-ups (range: 0–60). We dichotomized the exposure into subthreshold (≤15) and elevated depressive symptoms (>15). For the main analyses we considered a cumulative index for elevated depressive symptoms across the three time points (range: 0–3). Considered confounders are sex, age, socioeconomic status, migrant background, social support, anxiety symptoms, physical activity, chronic diseases, and sleeping problems. Statistical methods We used multiple imputation to account for missing values. Within each imputed dataset, we applied inverse probability weighting (IPW) to estimate the effect of the cumulative index for elevated depressive symptoms at baseline, 1- and 2-year follow-up on physical health-related quality of life at 6-year follow-up. We derived 95% confidence intervals by bootstrapping. Results After adjusting with IPW, the effect of the cumulative index per one unit increase of elevated depressive symptoms on the physical component score was −1.71 (95% CI: −3.51 to −0.04). The adjusted effect estimates of single exposure of elevated depressive symptoms on physical health-related quality of life were −0.83 (95% CI: −3.69 to 1.87) at baseline, −2.96 (95% CI: −4.94 to −0.52) at 1-year follow-up and −1.32 (95% CI: −3.85 to 1.15) at 2-year follow-up. Conclusion Findings suggest that elevated depressive symptoms during adolescence decrease physical health-related quality of life in young adulthood.
The 2021 European Resuscitation Council (ERC) guidelines recommend two automated external defibrillators (AEDs)/km2 and at least 10 first responders/km2. We examined 1) access to AEDs and volunteer ...first responders in line with these guidelines and 2) its associations with socioeconomic factors and income inequality, focusing on small spatial scales.
We considered data on 776 AEDs in February 2022 and 1,173 out-of-hospital cardiac arrests (OHCAs) including 713 OHCA with app-alerted volunteer first responders from February to September 2022 in Berlin. We fit multilevel models to analyse AED area coverage and Poisson models to examine first responder availability across 12 districts and 536 neighbourhoods.
Median AED area coverage according to the 2021 ERC guidelines was 43.1% (interquartile range (IQR) 2.3–87.2) at the neighbourhood level and median number of available first responders per OHCA case was one (IQR 0.0–1.0). AED area coverage showed a positive association with average income tax per capita, with better coverage in the highest compared to the lowest quartile neighbourhoods (coefficient: 0.13, 95% confidence interval (CI): 0.01–0.25). First responder availability was not associated with income tax. AED area coverage and first responder availability were positively associated with income inequality, with better coverage (coefficient: 0.13, 95% CI: 0.04–0.23) and availability (rate ratio: 1.31, 95% CI: 1.03–1.67) in quartiles of highest as compared to lowest inequality.
Access to resuscitation resources is neither equitable nor in accordance with the 2021 ERC guidelines. Ensuring better access necessitates understanding of socioeconomic factors and income inequality at small spatial scales.
Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts ...may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008-11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40-65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective:
Adipocytokines are hormones secreted from adipose tissue that possibly link adiposity and the risk of cardiovascular disease, but limited prospective data exist on plasma adipocytokines ...and ischemic stroke risk. We investigated associations and predictive properties of 4 plasma adipocytokines, namely resistin, adipsin, leptin, and total adiponectin, with regard to incident ischemic stroke in the PRIME Study.
Methods:
A cohort of 9,771 healthy men 50 to 59 years of age at baseline was followed up over a period of 10 years. In a nested case–control study, 95 ischemic stroke cases were matched with 190 controls on age, study center, and date of examination. Hazard ratios (HRs) per standard deviation increase in plasma adipocytokine levels were estimated using conditional logistic regression analysis. The additive value of adipocytokines in stroke risk prediction was evaluated by discrimination and reclassification metrics.
Results:
Resistin (HR, 1.88; 95% confidence interval CI, 1.16–3.03), adipsin (HR, 2.01; 95% CI, 1.33–3.04), and total adiponectin (HR, 1.53; 95% CI, 1.01–2.34), but not leptin, were independent predictors of ischemic stroke. The performance of a traditional risk factor model predicting ischemic stroke was significantly improved by the simultaneous inclusion of resistin, adipsin, and total adiponectin (c‐statistic: 0.673 95% CI, 0.631–0.766 vs 0.826 95% CI, 0.792–0.892, p < 0.001; net reclassification improvement: 38.1%, p < 0.001).
Interpretation:
Higher plasma levels of resistin, adipsin, and total adiponectin were associated with an increased 10‐year risk of ischemic stroke among healthy middle‐aged men. Resistin, adipsin, and total adiponectin provided incremental value over traditional risk factors for the prediction of ischemic stroke risk. ANN NEUROL 2012;
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