Use of implantable cardioverter-defibrillators for primary prevention in older patients: A systematic literature review and meta-analysis

Background: Randomized clinical trials (RCTs) have demonstrated the efficacy of implantable cardioverter-defibrillators (ICDs) in reducing sudden cardiac death (SCD) in specific patient populations. However, patients ≥ 65 years were under-represented in these trials and the overall benefit of ICDs may be diminished in older patients due to competing risks for death. We evaluate the published data on ICD efficacy at reducing all-cause mortality in patients ≥ 65 years and in patients ≥ 75 years. Methods: We searched MEDLINE to identify RCTs and observational studies of ICDs that provided age-based outcome data for primary prevention of SCD. The primary endpoint was mortality evaluated by a meta-analysis of the RCTs using a random-effects model. Secondary endpoints included operative mortality, long-term complications and quality of life. Results: The enrollment of patients ≥ 65 years in RCTs was limited (range: 33% in DEFINITE to 56% in MUSTT). Combining data from four RCTs (n = 3,562) revealed that primary prevention ICD therapy is efficacious in reducing all-cause mortality in patients ≥ 65 years (HR 0.66; 95% CI 0.50–0.87; test of heterogeneity: X2 = 5.26; p = 0.15). For patients ≥ 75 years, combining data from four RCTs (n = 579) revealed that primary prevention ICD therapy remains efficacious in reducing all-cause mortality (HR 0.73; 95% CI 0.51–0.974; p = 0.03). There appears to be no difference in ICD-related, operative, in-hospital, or long- -term complications among older patients compared to younger patients, although it remains unclear if older patients have a better quality of life with an ICD than younger patients. Conclusions: Although the overall evidence regarding ICD efficacy in patients ≥ 65 years is limited and divergent, and the evidence available for patients ≥ 75 years is even more sparse, our meta-analysis suggests that primary prevention ICDs may be beneficial in older patients. Our findings need to be validated by future studies, particularly ones examining ICD complications and quality of life. (Cardiol J 2011; 18, 5: 503–514

Systematic review of disease-modifying antirheumatic drugs for juvenile idiopathic arthritis

<p>Abstract</p> <p>Background</p> <p>Treatment of juvenile idiopathic arthritis (JIA) with disease-modifying antirheumatic drugs (DMARDs) may improve outcomes compared to conventional therapy (e.g., non-steroidal anti-inflammatory drugs, intra-articular corticosteroids). The purpose of this systematic review was to evaluate the comparative effectiveness and safety of DMARDs versus conventional therapy and versus other DMARDs.</p> <p>Results</p> <p>A systematic evidence review of 156 reports identified in MEDLINE^®, EMBASE^®, and by hand searches. There is some evidence that methotrexate is superior to conventional therapy. Among children who have responded to a biologic DMARD, randomized discontinuation trials suggest that continued treatment decreases the risk of having a flare. However, these studies evaluated DMARDs with different mechanisms of action (abatacept, adalimumab, anakinra, etanercept, intravenous immunoglobulin, tocilizumab) and used varying comparators and follow-up periods. Rates of serious adverse events are similar between DMARDs and placebo in published trials. This review identified 11 incident cases of cancer among several thousand children treated with one or more DMARD.</p> <p>Conclusions</p> <p>Few data are available to evaluate the comparative effectiveness of either specific DMARDs or general classes of DMARDs. However, based on the overall number, quality, and consistency of studies, there is moderate strength of evidence to support that DMARDs improve JIA-associated symptoms. Limited data suggest that short-term risk of cancer is low.</p

The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961–/– mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood

Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer

This work was supported by the United Kingdom Department of Health under the Pharmacogenetics Research programme (grant number PHGX23A).Background and aims: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. Methods: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. Results: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0-26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300-450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17-2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73-17.61]), body surface area (OR 2.08 [1.36-3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18-9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70-0.86]. Conclusions: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area

Evaluating Human Papillomavirus Vaccination Programs

Human papillomavirus (HPV) has been implicated as the primary etiologic agent of cervical cancer. Potential vaccines against high-risk HPV types are in clinical trials. We evaluated vaccination programs with a vaccine against HPV-16 and HPV-18. We developed disease transmission models that estimated HPV prevalence and infection rates for the population overall, by age group, by level of sexual activity within each age group, and by sex. Data were based on clinical trials and published and unpublished sources. An HPV-16/18 vaccine for 12-year-old girls would reduce cohort cervical cancer cases by 61.8%, with a cost-effectiveness ratio of $14,583 per quality-adjusted life year (QALY). Including male participants in a vaccine rollout would further reduce cervical cancer cases by 2.2$442,039/QALY compared to female-only vaccination. Vaccination against HPV-16 and HPV-18 can be cost-effective, although including male participants in a vaccination program is generally not cost-effective, compared to female-only vaccination

Understanding sexual violence in sex working populations - law, legal consciousness and legal practice in four countries (2021–2023) : study protocol v2.5

Background Globally, the most important human rights and public health issue that sex workers face is their experience of high levels of violence (Kinnell, 2006, Kinnell, 2008, Alexander, 1999). Deering’s systematic review estimated levels of sexual violence in sex working populations as being between 14% and 54% (Deering et al, 2014). Aims This international, robust mixed methods study will explore the frequency of sexual violence against sex workers, barriers in criminal justice and the legal consciousness of sex workers regarding their rights and consent. The hypothesis to be tested is that the safety of sex workers from sexual violence is mediated by the differing legal contexts of sex work environments. We will compare experiences across research sites in the context of legalisation (Nevada USA), client criminalisation (Northern Ireland), decriminalisation (New Zealand) and partial criminalisation (England, Scotland and Wales) [henceforth ESW]. Methods An international survey (n = 1,000) will be translated into several languages, to disaggregate experiences by demographic categories (gender, ethnicity, sexual orientation) and sex work sector (including online, street-based and brothels). Interviews (n = 100) with sex workers, police, prosecutors and service providers will be thematically analysed to explore legal consciousness, why the patterns occur and contextualise the statistical findings. These data will be supplemented with comparative legislative, policy and case analysis. Research study data will be used to compare the social factors and legal norms shaping sex workers experiences of sexual violence, justice and support interventions. Recommendations for a ‘best practice’ review of legal improvements and support interventions will be produced following completion of the study. Given the sensitive nature of the research, robust ethical and data protection mechanisms are in place. The research has ethical approval from each research site, an Advisory Board and trained, paid peer researchers to assist with data gathering, analysis and dissemination. The study will report findings in 2023/2024

An economic evaluation of prolonged mechanical ventilation*

Patients who receive prolonged mechanical ventilation (PMV) have high resource utilization and relatively poor outcomes, especially the elderly, and are increasing in number. The economic implications of PMV provision however are uncertain and would be helpful to providers and policymakers. Therefore, we aimed to determine the lifetime societal value of PMV

Zastosowanie wszczepialnych kardiowerterów- -defibrylatorów w profilaktyce pierwotnej u pacjentów w podeszłym wieku. Systematyczny przegląd piśmiennictwa i metaanaliza

Wstęp: W randomizowanych badaniach klinicznych (RCT) wykazano skuteczność zastosowania wszczepialnych kardiowerterów-defibrylatorów (ICD) w zapobieganiu nagłym zgonom sercowym (SCD) w określonych grupach chorych. Jednak w badaniach tych oceniano niewielkie grupy chorych &ge; 65. roku życia, a całkowite korzyści z wszczepienia ICD wśród starszych pacjentów mogą być ograniczone ze względu na zwiększone ryzyko zgonu. Na podstawie aktualnego piśmiennictwa oceniono, na ile wszczepienie ICD zmniejsza ryzyko zgonu z jakiejkolwiek przyczyny u pacjentów &ge; 65. roku życia oraz w wieku &#8805; 75 lat. Metody: Danych z RCT oraz badań obserwacyjnych oceniających profilaktykę pierwotną SCD, w zależności od wieku, poszukiwano w bazie MEDLINE. Za pierwszorzędowy punkt końcowy przyjęto śmiertelność ocenianą w metaanalizach lub RCT z zastosowaniem modelu &#8243;random-effects&#8243;. Za drugorzędowe punkty końcowe przyjęto śmiertelność związaną z zabiegiem operacyjnym, powikłania odległe oraz jakość życia (QoL). Wyniki: Do RCT nie włączano zbyt licznych grup pacjentów &ge; 65. roku życia (od 33% badanej populacji w badaniu DEFINITE do 56% w badaniu MUSTT). Na podstawie zsumowanych danych z 4 RCT (n = 3562) wykazano, że wszczepienie ICD w profilaktyce pierwotnej skutecznie zapobiega śmiertelności całkowitej u chorych w wieku &ge; 65 lat [współczynnik hazardu (HR): 0,66; 95% przedział ufności (CI): 0,50&#8211;0,87; test niejednorodności X2 = 5,26; p = 0,15). U pacjentów &ge; 75. roku życia zsumowane dane z 4 badań RCT (n = 579) również potwierdziły skuteczność ICD w profilaktyce pierwotnej w zapobieganiu śmiertelności całkowitej (HR: 0,73; 95% CI: 0,51&#8211;0,974; p = 0,03). Wydaje się, że powikłania związane z ICD, z zabiegiem operacyjnym, wewnątrzszpitalne oraz odległe nie różnią się istotnie w grupach pacjentów w podeszłym wieku w porównaniu z młodszymi chorymi, jednak pozostaje niejasne, czy u starszych osób wszczepienie ICD poprawia jakość życia bardziej niż u młodszych chorych. Wnioski: Choć dane dotyczące skuteczności ICD u pacjentów &ge;65. roku życia są ograniczone i rozbieżne, a dostępne informacje na temat chorych w wieku &ge; 75 lat &#8212; jeszcze bardziej niepełne, wyniki niniejszej metaanalizy sugerują, że pacjenci w podeszłym wieku mogą odnieść korzyści z wszczepienia ICD w ramach profilaktyki pierwotnej. Rezultaty autorów metaanalizy powinny zostać zweryfikowane w kolejnych badaniach, zwłaszcza oceniających powikłania związane z ICD oraz jakość życia