Addressing persistent evidence gaps in cardiovascular sex differences research – the potential of clinical care data

Women have historically been underrepresented in cardiovascular clinical trials, resulting in a lack of sex-specific data. This is especially problematic in two situations, namely those where diseases manifest differently in women and men and those where biological differences between the sexes might affect the efficacy and/or safety of medication. There is therefore a pressing need for datasets with proper representation of women to address questions related to these situations. Clinical care data could fit this bill nicely because of their unique broad scope across both patient groups and clinical measures. This perspective piece presents the potential of clinical care data in sex differences research and discusses current challenges clinical care data-based research faces. It also suggests strategies to reduce the effect of these limitations, and explores whether clinical care data alone will be sufficient to close evidence gaps or whether a more comprehensive approach is needed

Addressing persistent evidence gaps in cardiovascular sex differences research – the potential of clinical care data

Women have historically been underrepresented in cardiovascular clinical trials, resulting in a lack of sex-specific data. This is especially problematic in two situations, namely those where diseases manifest differently in women and men and those where biological differences between the sexes might affect the efficacy and/or safety of medication. There is therefore a pressing need for datasets with proper representation of women to address questions related to these situations. Clinical care data could fit this bill nicely because of their unique broad scope across both patient groups and clinical measures. This perspective piece presents the potential of clinical care data in sex differences research and discusses current challenges clinical care data-based research faces. It also suggests strategies to reduce the effect of these limitations, and explores whether clinical care data alone will be sufficient to close evidence gaps or whether a more comprehensive approach is needed

Довідкові регіональні видання з геральдики

Одним з джерел інформації про наявність історичних гербів міст України та новотворів 60-х–80-х рр. ХХ ст. виступає «Алфавитный каталог городов, поселков, сел, губерний и областей России, СНГ, бывших союзных республик СССР, имеющих старые и современные гербы». Автор рецензії проаналізував принципи укладання подібних джерел інформації, зробив свої зауваження та висловив побажання щодо їх вдосконалення.«Alphabetical catalogue of towns, settlements, villages, provinces and regions of Russia, Commonwealth of Independent States, former Soviet Republics of the USSR, which have old and present-day coat of arms» is one of the sources that gives information about historical coat of arms and newly formed emblems of Ukraine during 60th – 80th of XX century. The author of the review analysed the structure of similar sources and made her remarks and suggestion regarding to its improvement

Bayesian evidence synthesis in case of multi-cohort datasets:An illustration by multi-informant differences in self-control

Abstract The trend toward large-scale collaborative studies gives rise to the challenge of combining data from different sources efficiently. Here, we demonstrate how Bayesian evidence synthesis can be used to quantify and compare support for competing hypotheses and to aggregate this support over studies. We applied this method to study the ordering of multi-informant scores on the ASEBA Self Control Scale (ASCS), employing a multi-cohort design with data from four Dutch cohorts. Self-control reports were collected from mothers, fathers, teachers and children themselves. The available set of reporters differed between cohorts, so in each cohort varying components of the overarching hypotheses were evaluated. We found consistent support for the partial hypothesis that parents reported more self-control problems than teachers. Furthermore, the aggregated results indicate most support for the combined hypothesis that children report most problem behaviors, followed by their mothers and fathers, and that teachers report the fewest problems. However, there was considerable inconsistency across cohorts regarding the rank order of children’s reports. This article illustrates Bayesian evidence synthesis as a method when some of the cohorts only have data to evaluate a partial hypothesis. With Bayesian evidence synthesis, these cohorts can still contribute to the aggregated results

Plasma proteomic patterns show sex differences in early concentric left ventricular remodeling

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women. METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM. RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51-2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00-1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women. CONCLUSIONS: cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT001747

Statins are associated with a large reduction in all-cause mortality in women from a cardiac outpatient population

OBJECTIVES: Uncertainty about the benefit of (high-intensity) statins for women remains due to under-representation of women in primary prevention trials and scarcity of sex-stratified data. This study evaluates the sex-specific relation between statin treatment and survival and the additional benefit of high-intensity statins. METHODS: Electronic health record data from 47 801 patients (17 008 statin users and 30 793 non-users) without prior cardiovascular disease were extracted from thirteen Dutch outpatient cardiology clinics. Patients prescribed statins at baseline were propensity-score matched to those eligible for statin therapy (low-density lipoprotein >2.5 mmol/L) without a statin prescription. Statins were divided into low-intensity and high-intensity according to Dutch guidelines. Mortality data were obtained via linkage to the national mortality registry. Cox regression was used to evaluate the relationship between statin prescription and intensity and all-cause and cardiovascular mortality. RESULTS: Propensity score matching created a cohort of 8631 statin users and 8631 non-users. 35% of women and 28% of men received a low-intensity statin. The beneficial effect of statins on both all-cause and cardiovascular mortality was stronger in women (HR 0.66, 95% CI 0.58 to 0.74 and HR 0.55, 95% CI 0.39 to 0.71, respectively) than in men (HR 0.89, 95% CI 0.81 to 0.95 and HR 0.93, 95% CI 0.77 to 1.08, respectively). High-intensity statins conferred modest protection against all-cause mortality (HR 0.94, 95% CI 0.88 to 1.00) and cardiovascular mortality (HR 0.86, 95% CI 0.74 to 0.98) in both sexes. CONCLUSIONS: The protective effect of primary prevention statins was stronger in women than men for both all-cause and cardiovascular mortality. High-intensity statins conferred a modest additional benefit in both sexes. Statins seem to be effective regardless of treatment intensity, especially in women

Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

BACKGROUND: Knowledge about adverse drug reactions (ADRs) in the population is limited because of underreporting, which hampers surveillance and assessment of drug safety. Therefore, gathering accurate information that can be retrieved from clinical notes about the incidence of ADRs is of great relevance. However, manual labeling of these notes is time-consuming, and automatization can improve the use of free-text clinical notes for the identification of ADRs. Furthermore, tools for language processing in languages other than English are not widely available. OBJECTIVE: The aim of this study is to design and evaluate a method for automatic extraction of medication and Adverse Drug Reaction Identification in Clinical Notes (ADRIN). METHODS: Dutch free-text clinical notes (N=277,398) and medication registrations (N=499,435) from the Cardiology Centers of the Netherlands database were used. All clinical notes were used to develop word embedding models. Vector representations of word embedding models and string matching with a medical dictionary (Medical Dictionary for Regulatory Activities [MedDRA]) were used for identification of ADRs and medication in a test set of clinical notes that were manually labeled. Several settings, including search area and punctuation, could be adjusted in the prototype to evaluate the optimal version of the prototype. RESULTS: The ADRIN method was evaluated using a test set of 988 clinical notes written on the stop date of a drug. Multiple versions of the prototype were evaluated for a variety of tasks. Binary classification of ADR presence achieved the highest accuracy of 0.84. Reduced search area and inclusion of punctuation improved performance, whereas incorporation of the MedDRA did not improve the performance of the pipeline. CONCLUSIONS: The ADRIN method and prototype are effective in recognizing ADRs in Dutch clinical notes from cardiac diagnostic screening centers. Surprisingly, incorporation of the MedDRA did not result in improved identification on top of word embedding models. The implementation of the ADRIN tool may help increase the identification of ADRs, resulting in better care and saving substantial health care costs