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Medical Intelligence In Counter-Insurgency (COIN) And Counter-Terrorist (CT) Operations
Medical intelligence (MEDINT) is now regarded as critically important across a broad spectrum of security concerns. Its usual functions are either in force protection, evaluating risks to personnel at the tactical and operational levels, or, at a strategic level, in considering threats to the health and stability of nation-states. The uses of MEDINT in Counter-Terrorism (CT) and Counter-Insurgency (COIN) have received little attention except in so far as they overlap with these concerns; for example, where they involve matters of force-protection or the threat of bioterrorism. But this was not always so. In the past, information relating to health and medicine was considered crucial to the success of COIN operations, if not to domestic terrorism. By adapting some of these techniques to contemporary practice, and utilizing technologies that were not available in former times, we can use MEDINT in innovative ways to exploit the vulnerabilities of hostile groups and to isolate them from surrounding populations. This paper indicates some of the ways in which intelligence from a range of sources can be utilized to engage with communities more effectively; to anticipate the behavior of target groups/individuals; to determine their whereabouts, interactions and supply chains; and ultimately to exploit their weaknesses or dependencies. The paper is not intended as definitive but as a starting point in a conversation as to how MEDINT could or should contribute to CT and COIN operations.
Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts.
BACKGROUND: Little is known about the underlying relationship between mosaic loss of chromosome Y (mLOY), the most common chromosomal alterations in older men, and the risk of age-related lung diseases. METHODS: We included 217 780 participants from the UK Biobank and 42 859 participants from the China Kadoorie Biobank. The mLOY events were detected using the Mosaic Chromosomal Alterations pipeline. Outcomes included all lung diseases, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Cox proportional hazard models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of mLOY with lung diseases in both cohorts. The combined HRs were derived from meta-analysis. RESULTS: Results from two cohorts showed that expanded mLOY was associated with increased risks of all lung diseases [HR (95% CI): 1.19 (1.04, 1.37)], COPD [HR (95% CI): 1.20 (1.13, 1.28)], lung cancer [HR (95% CI): 1.34 (1.21, 1.48)], and IPF [HR (95% CI): 1.34 (1.16, 1.56) in UKB]. There was evidence of positive interactions between mLOY and smoking behavior [relative excess risk due to interaction (97.5%CI)>0]. Additionally, we observed that current smokers with expanded mLOY had the highest risk of incident lung diseases in both cohorts. CONCLUSION: mLOY may be a novel predictor for age-related lung diseases. For current smokers carrying mLOY, adopting quitting smoking behavior may contribute to substantially reduce their risk of incident lung diseases.
Understanding maternal sepsis risk factors and bacterial etiology: A case control study protocol.
INTRODUCTION: Maternal disorders are the third leading cause of sepsis globally, accounting for 5.7 million (12%) cases in 2017. There are increasing concerns about the emergence of antimicrobial resistance (AMR) in bacteria commonly causing maternal sepsis. Our aim is to describe the protocol for a clinical and microbiology laboratory study to understand risk factors for and the bacterial etiology of maternal sepsis in a tertiary Obstetrics and Gynaecology Hospital. METHODS: This case-control study aims to recruit 100 cases and 200 controls at Tu Du Hospital in Ho Chi Minh City, Vietnam, which had approximately 55,000 births in 2022. Women aged ≥ 18 years and ≥ 28 weeks gestation having a singleton birth will be eligible for inclusion as cases or controls, unless they have an uncomplicated localised or chronic infection, or an infection with SARS-CoV-2. Cases will include pregnant or recently pregnant women with sepsis recognised between the onset of labour and/or time of delivery/cessation of pregnancy for up to 42 days post-partum. Sepsis will be defined as suspected or confirmed infection with an obstetrically modified Sequential Organ Failure Assessment score of ≥ 2, treatment with intravenous antimicrobials and requested cultures of any bodily fluid. Controls will be matched by age, location, parity, mode of delivery and gestational age. Primary and secondary outcomes are risk factors associated with the development of maternal sepsis, the frequency of adverse outcomes due to maternal sepsis, bacterial etiology and AMR profiles of cases and controls. DISCUSSION: This study will improve understanding of the epidemiology and clinical implications of maternal sepsis management including the presence of AMR in women giving birth in Vietnam. It will help us to determine whether women in this setting are receiving optimal care and to identify opportunities for improvement.
Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population.
Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection. We conducted a clinical trial (NCT04297436) of 4CMenB (Bexsero, GSK), a licensed Nm vaccine containing OMVs and recombinant antigens, comprising a single arm, open label study of two doses with 50 adults in coastal Kenya who have high exposure to Ng. Data from a Ng antigen microarray established that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 but had declined by 24 weeks. For most reactive OMV-derived antigens, the reverse was the case. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.
Early pregnancy maternal blood pressure and risk of preeclampsia: Does the association differ by parity? Evidence from 14,086 women across 7 countries.
OBJECTIVE: To determine if the relationship between blood pressure (BP) before 16 weeks' gestation and subsequent onset of preeclampsia differs by parity, and by history of hypertensive disorders of pregnancy (HDP) in parous women. STUDY DESIGN: Data from two studies were pooled. First, routinely collected clinical data from three metropolitan hospitals in Sydney, Australia (2017-2020), where BP was measured as part of routine clinical care using validated mercury-free sphygmomanometers. Second, prospectively collected research data from the INTERBIO-21st Study, conducted in six countries, investigating the epidemiology of fetal growth restriction and preterm birth, where BP was measured by dedicated research staff using an automated machine validated for use in pregnancy. MAIN OUTCOME: Adjusted odds ratios (aOR) (95% confidence interval (CI)) for the association of systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) with preeclampsia were obtained from logistic regression models. Models were adjusted for age, smoking, body mass index, previous hypertension, previous diabetes, and previous preeclampsia. Interactions for parity, and history of HDP in parous women were included. RESULTS: There were 14,086 pregnancies (Sydney = 11008, INTERBIO-21st = 3078) in the pooled analyses, 6914 (49 %) were parous, of which 414 (6.0 %) had a history of HDP. Nulliparous women had a higher risk of preeclampsia (2.6 %) compared with parous women (1.5 %): [aOR (95 %CI) 3.61 (2.67, 4.94)], as did parous women with a history of HDP (15.0 %) compared with no history (0.7 %) [12.70 (8.02, 20.16)]. MAP before 16 weeks' gestation (mean [SD] 78.8[8.6] mmHg) was more strongly associated than SBP or DBP with development of preeclampsia in parous women [2.22 (1.81, 2.74)] per SD higher MAP] compared with nulliparous women [1.58 (1.34, 1.87)] (p for interaction 0.013). There were no significant differences on the effect of blood pressure on preeclampsia in parous women by history of HDP (p for interaction 0.5465). CONCLUSION: The risk of preeclampsia differs according to parity and history of HDP in a previous pregnancy. Blood pressure in early pregnancy predicts preeclampsia in all groups, although more strongly associated in parous than nulliparous women, but no different in parous women by history of HDP.
Understanding the physiological and biological response to ambient heat exposure in pregnancy: protocol for a systematic review and meta-analysis.
INTRODUCTION: Climate change increases not only the frequency, intensity and duration of extreme heat events but also annual temperatures globally, resulting in many negative health effects, including harmful effects on pregnancy and pregnancy outcomes. As temperatures continue to increase precipitously, there is a growing need to understand the underlying biological pathways of this association. This systematic review will focus on maternal, placental and fetal changes that occur in pregnancy due to environmental heat stress exposure, in order to identify the evidence-based pathways that play a role in this association. METHODS AND ANALYSIS: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search PubMed and Ovid Embase databases from inception using tested and validated search algorithms. Inclusion of any studies that involve pregnant women and have measured environmental heat stress exposure and either maternal, placental or fetal physiological or biochemical changes and are available in English. Modelling studies or those with only animals will be excluded. The risk of bias will be assessed using the Office of Health Assessment and Translation tool. Abstract screening, data extraction and risk of bias assessment will be conducted by two independent reviewers.Environmental parameters will be reported for each study and where possible these will be combined to calculate a heat stress indicator to allow comparison of exposure between studies. A narrative synthesis will be presented following standard guidelines. Where outcome measures have at least two levels of exposure, we will conduct a dose-response meta-analysis should there be at least three studies with the same outcome. A random effects meta-analysis will be conducted where at least three studies give the same outcome. ETHICS AND DISSEMINATION: This systematic review and meta-analysis does not require ethical approval. Dissemination will be through peer-reviewed journal publication and presentation at international conferences/interest groups. PROSPERO REGISTRATION NUMBER: CRD42024511153.
Elemental composition and potential toxicity of the riverine macrophyte Podostemum ceratophyllum Michx. reflects land use in eastern North America.
Land use influences surface water quality, often alleviating stoichiometric constraints on primary production and altering biogeochemical cycling. However, land use effects on nutrient content and potential trace metal accumulation in aquatic plants remain unclear, and high concentrations of metals and altered nutrient ratios could impact the health of herbivores and detritivores. We tested for land use effects on nutrient and trace metal accumulation in a widespread riverine macrophyte, Podostemum ceratophyllum, collected from 91 locations from Georgia to Maine, USA in 2014-2016. We quantified carbon (C), nitrogen (N), phosphorus (P), their molar and mass ratios, N and C stable isotopes, and 17 additional elements in dried plants collected from each location to estimate relationships between plant tissue content and watershed land use, which we quantified as agriculture, forest, and development. Decreasing forest cover was correlated with increasing δ15N, Mg, Mn, and P in Podostemum tissue. Increasing urban development was correlated with increasing δ15N, Mg and P, while increasing agriculture was correlated with a decrease in C: P and the concentrations of multiple metals, along with increases in P, Mg and δ15N. Decreases in ratios of N: P and C:P with increasing agriculture and urban development in the watershed indicate more rapid P storage relative to C and N in plant tissue, and increased resource quality of the plant to consumers in these watersheds. We also observed potentially toxic dietary concentrations of some trace metals (B, Cd, Tl, Zn) in plant tissue which could be related to the plant's natural herbivory defense system or to land use. We conclude that land use influences the elemental composition of P. ceratophyllum, and potentially the quality and toxicity of the plant to herbivores and detritivores in eastern North American rivers.
Vaccine-induced human monoclonal antibodies to PfRH5 show broadly neutralizing activity against P. falciparum clinical isolates.
Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P. falciparum laboratory strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced anti-PfRH5 mAbs on more genetically diverse P. falciparum clinical isolates. We used mAbs previously isolated from single B cells of UK adult PfRH5 vaccinees and used ex-vivo growth inhibition activity (GIA) assays to assess their efficacy against P. falciparum clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in P. falciparum clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups: high, medium and low. Except for one isolate, our data show no significant differences in the mAb GIA profile between P. falciparum clinical isolates and the 3D7 reference strain, which harbors the vaccine allele. We also observed an additive relationship for mAb combinations, whereby the combination of GIA-low and GIA-medium antibodies resulted in increased GIA, having important implications for the contribution of specific clones within polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the pfrh5 gene, these mutations were predicted to have little or no functional impact on the antigen structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of anti-PfRH5 mAbs and constitute, to our knowledge, the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human mAbs to PfRH5.
A randomised trial of malaria vaccine R21/Matrix-M™ with and without antimalarial drugs in Thai adults.
In preparation for mass vaccinations with R21/Matrix-M™ combined with mass administrations of dihydroartemisinin, piperaquine, and a single low dose primaquine we assessed the tolerability, safety, and potential interactions of this combination affecting immunogenicity or pharmacokinetics. 120 healthy Thai volunteers were randomised to receive either antimalarials combined with vaccinations (n = 50), vaccinations alone (n = 50), or antimalarials only (n = 20). Three rounds of vaccines and antimalarials were administered one month apart. The vaccine was well tolerated alone and in combination with the antimalarials. None of the participants failed completion of the 3-dose vaccine course. There was no significant difference in the vaccine immunogenicity or in the pharmacokinetics of piperaquine given individually or in combination. This study supports proceeding to a large trial of mass vaccinations with R21/Matrix-M™ combined with mass antimalarial administration in Bangladesh.
Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry.
AIMS: We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF). METHODS AND RESULTS: In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [-0.075 (95% confidence interval -0.144, -0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [-0.037 (-0.071, -0.003)], new-onset/worsening heart failure [-0.064 (-0.088, -0.039)], bleeding events [-0.031 (-0.059, -0.003)], thromboembolic events [-0.071 (-0.115, -0.027)], mild symptoms [0.037 (-0.048, -0.026)], or severe/disabling symptoms [-0.090 (-0.108, -0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex. CONCLUSION: Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.
Patients' experience on pain outcomes after hip arthroplasty: insights from an information tool based on registry data.
BACKGROUND: Arthroplasty registries are rarely used to inform encounters between clinician and patient. This study is part of a larger one which aimed to develop an information tool allowing both to benefit from previous patients' experience after total hip arthroplasty (THA). This study focuses on generating the information tool specifically for pain outcomes. METHODS: Data from the Geneva Arthroplasty Registry (GAR) about patients receiving a primary elective THA between 1996 and 2019 was used. Selected outcomes were identified from patient and surgeon surveys: pain walking, climbing stairs, night pain, pain interference, and pain medication. Clusters of patients with homogeneous outcomes at 1, 5, and 10 years postoperatively were generated based on selected predictors evaluated preoperatively using conditional inference trees (CITs). RESULTS: Data from 6,836 THAs were analysed and 14 CITs generated with 17 predictors found significant (p
Association between loop diuretic dose changes and outcomes in chronic heart failure: observations from the ESC-EORP Heart Failure Long-Term Registry.
AIMS: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes. METHODS AND RESULTS: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease. CONCLUSION: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease.
Characteristics, management, and outcomes of patients with left-sided infective endocarditis complicated by heart failure: a substudy of the ESC-EORP EURO-ENDO (European infective endocarditis) registry.
AIMS: To evaluate the current management and survival of patients with left-sided infective endocarditis (IE) complicated by congestive heart failure (CHF) in the ESC-EORP European Endocarditis (EURO-ENDO) registry. METHODS AND RESULTS: Among the 3116 patients enrolled in this prospective registry, 2449 (mean age: 60 years, 69% male) with left-sided (native or prosthetic) IE were included in this study. Patients with CHF (n = 698, 28.5%) were older, with more comorbidity and more severe valvular damage (mitro-aortic involvement, vegetations >10 mm and severe regurgitation/new prosthesis dehiscence) than those without CHF (all p ≤ 0.019). Patients with CHF experienced higher 30-day and 1-year mortality than those without (20.5% vs. 9.0% and 36.1% vs. 19.3%, respectively) and CHF remained strongly associated with 30-day (odds ratio[OR] 2.37, 95% confidence interval [CI] [1.73-3.24; p 10 mm, severe valvular regurgitation and/or new prosthetic dehiscence, perivalvular complication, and prosthetic IE (OR 0.22, 95% CI 0.12-0.38; p
Individualised Estimation of Quality-adjusted Survival Benefit and Cost-effectiveness of Proton Beam Therapy in Intermediate-stage Hodgkin Lymphoma.
AIMS: Radiotherapy for Hodgkin lymphoma leads to the irradiation of organs at risk (OAR), which may confer excess risks of late effects. Comparative dosimetry studies show that proton beam therapy (PBT) may reduce OAR irradiation compared with photon radiotherapy, but PBT is more expensive and treatment capacity is limited. The purpose of this study is to inform the appropriateness of PBT for intermediate-stage Hodgkin lymphoma (ISHL). MATERIALS AND METHODS: A microsimulation model simulating the course of ISHL, background mortality and late effects was used to estimate comparative quality-adjusted life years (QALYs) lived and healthcare costs after consolidative pencil beam scanning PBT or volumetric modulated arc therapy (VMAT), both in deep-inspiration breath-hold. Outcomes were compared for 606 illustrative patients covering a spectrum of clinical presentations, varying by two age strata (20 and 40 years), both sexes, three smoking statuses (never, former and current) and 61 pairs of OAR radiation doses from a comparative planning study. Both undiscounted and discounted outcomes at 3.5% yearly discount were estimated. The maximum excess cost of PBT that might be considered cost-effective by the UK's National Institute for Health and Care Excellence was calculated. RESULTS: OAR doses, smoking status and discount rate had large impacts on QALYs gained with PBT. Current smokers benefited the most, averaging 0.605 undiscounted QALYs (range -0.341 to 2.171) and 0.146 discounted QALYs (range -0.067 to 0.686), whereas never smokers benefited the least, averaging 0.074 undiscounted QALYs (range -0.196 to 0.491) and 0.017 discounted QALYs (range -0.030 to 0.086). For the gain in discounted QALYs to be considered cost-effective, PBT would have to cost at most £4812 more than VMAT for current smokers and £645 more for never smokers. This is below preliminary National Health Service cost estimates of PBT over photon radiotherapy. CONCLUSION: In a UK setting, PBT for ISHL may not be considered cost-effective. However, the degree of unquantifiable uncertainty is substantial.
The ESC-EORP Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry.
AIMS: The European Society of Cardiology (ESC) EURObservational Research Programme (EORP) Chronic Ischaemic Cardiovascular Disease Long Term (CICD LT) registry aims to study the clinical profile, treatment modalities, and outcomes of patients diagnosed with CICD in a contemporary environment in order to assess whether these patients at high cardiovascular (CV) risk are treated according to ESC guidelines on prevention or on stable coronary disease and to determine mid- and long-term outcomes and their determinants in this population. METHODS AND RESULTS: Nine thousand one hundred and seventy-four patients over 18 years with documented CICD defined by a history acute coronary syndrome with/without ST elevation, previous coronary revascularization, or stable coronary artery disease were enrolled between 1 May 2015 and 31 July 2018. Individual patient data on clinical profile, biology, and treatment modalities were collected across 154 centres from 20 ESC countries. Two years of follow-up is scheduled in order to determine the following clinical outcomes: all-cause and CV death, all-cause and CV hospitalizations, changes in medications, and quality of life using the EuroQol5D-5L score. CONCLUSION: The CICD LT is an international registry of care and outcomes of patients hospitalized with CICD which will provide insights into the contemporary profile and management of patients with this common disease.
Association between common cardiovascular risk factors and clinical phenotype in patients with hypertrophic cardiomyopathy from the European Society of Cardiology (ESC) EurObservational Research Programme (EORP) Cardiomyopathy/Myocarditis registry.
AIMS: The interaction between common cardiovascular risk factors (CVRF) and hypertrophic cardiomyopathy (HCM) is poorly studied. We sought to explore the relation between CVRF and the clinical characteristics of patients with HCM enrolled in the EURObservational Research Programme (EORP) Cardiomyopathy registry. METHODS AND RESULTS: 1739 patients with HCM were studied. The relation between hypertension (HT), diabetes (DM), body mass index (BMI), and clinical traits was analysed. Analyses were stratified according to the presence or absence of a pathogenic variant in a sarcomere gene. The prevalence of HT, DM, and obesity (Ob) was 37, 10, and 21%, respectively. HT, DM, and Ob were associated with older age (P<0.001), less family history of HCM (HT and DM P<0.001), higher New York Heart Association (NYHA) class (P<0.001), atrial fibrillation (HT and DM P<0.001; Ob p = 0.03) and LV (left ventricular) diastolic dysfunction (HT and Ob P<0.001; DM P = 0.003). Stroke was more frequent in HT (P<0.001) and mutation-positive patients with DM (P = 0.02). HT and Ob were associated with higher provocable LV outflow tract gradients (HT P<0.001, Ob P = 0.036). LV hypertrophy was more severe in Ob (P = 0.018). HT and Ob were independently associated with NYHA class (OR 1.419, P = 0.017 and OR 1.584, P = 0.004, respectively). Other associations, including a higher proportion of females in HT and of systolic dysfunction in HT and Ob, were observed only in mutation-positive patients. CONCLUSION: Common CVRF are associated with a more severe HCM phenotype, suggesting a proactive management of CVRF should be promoted. An interaction between genotype and CVRF was observed for some traits.
Heart failure in Europe: Guideline-directed medical therapy use and decision making in chronic and acute, pre-existing and de novo, heart failure with reduced, mildly reduced, and preserved ejection fraction - the ESC EORP Heart Failure III Registry.
AIMS: We analysed baseline characteristics and guideline-directed medical therapy (GDMT) use and decisions in the European Society of Cardiology (ESC) Heart Failure (HF) III Registry. METHODS AND RESULTS: Between 1 November 2018 and 31 December 2020, 10 162 patients with acute HF (AHF, 39%, age 70 [62-79], 36% women) or outpatient visit for HF (61%, age 66 [58-75], 33% women), with HF with reduced (HFrEF, 57%), mildly reduced (HFmrEF, 17%) or preserved (HFpEF, 26%) ejection fraction were enrolled from 220 centres in 41 European or ESC-affiliated countries. With AHF, 97% were hospitalized, 2.2% received intravenous treatment in the emergency department, and 0.9% received intravenous treatment in an outpatient clinic. AHF was seen by most by a general cardiologist (51%) and outpatient HF most by a HF specialist (48%). A majority had been hospitalized for HF before, but 26% of AHF and 6.1% of outpatient HF had de novo HF. Baseline use, initiation and discontinuation of GDMT varied according to AHF versus outpatient HF, de novo versus pre-existing HF, and by ejection fraction. After the AHF event or outpatient HF visit, use of any renin-angiotensin system inhibitor, angiotensin receptor-neprilysin inhibitor, beta-blocker, mineralocorticoid receptor antagonist and loop diuretics was 89%, 29%, 92%, 78%, and 85% in HFrEF; 89%, 9.7%, 90%, 64%, and 81% in HFmrEF; and 77%, 3.1%, 80%, 48%, and 80% in HFpEF. CONCLUSION: Use and initiation of GDMT was high in cardiology centres in Europe, compared to previous reports from cohorts and registries including more primary care and general medicine and regions more local or outside of Europe and ESC-affiliated countries.