RESUMO
BACKGROUND: Cardiovascular events, including heart failure and arrhythmias, following chimeric antigen receptor (CAR) T-cell therapy are increasingly recognized. Although global longitudinal strain (GLS) has demonstrated prognostic utility for other cancer therapy-related cardiac dysfunction, less is known regarding the association of GLS with adverse cardiac events following CAR T-cell therapy. OBJECTIVES: To determine the association of baseline GLS with adverse cardiovascular events in adults receiving CAR-T cell therapy. METHODS: Patients who had an echocardiogram within 6 months prior to receiving CAR T-cell therapy were retrospectively identified. Clinical data and cardiac events were collected via chart review. Echocardiograms were analyzed offline for GLS, left ventricular ejection fraction, and Doppler parameters. Multivariable logistic regression was used to determine the association between adverse cardiovascular events and echocardiographic parameters. RESULTS: Among 75 CAR T-cell therapy patients (mean age 63.9, 34.7% female), nine patients (12%) experienced cardiac events (CEs) including cardiovascular death, new/worsening heart failure, and new/worsening arrhythmia within 1 year of treatment. In univariable models, higher baseline GLS (OR 0.78 [0.63, 0.96], p = .021) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.40 [1.08, 1.81], p = .012) was associated with a higher risk of CE. After adjusting for age and LDH, higher baseline GLS (OR 0.65 [0.48-0.88], p = <.01) was associated with a lower risk of CE and higher baseline mitral E/e' (OR 1.56 [1.06, 2.29], p = .024) was associated with a higher risk of CE. CONCLUSION: Lower GLS and higher mitral E/e' on a baseline echocardiogram were associated with higher risk for CEs in patients receiving CAR T-cell therapy.
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Insuficiência Cardíaca , Receptores de Antígenos Quiméricos , Disfunção Ventricular Esquerda , Adulto , Humanos , Feminino , Masculino , Função Ventricular Esquerda , Volume Sistólico/fisiologia , Estudos Retrospectivos , Imunoterapia Adotiva/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/terapia , Terapia Baseada em Transplante de Células e Tecidos , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapiaRESUMO
BACKGROUND: Regular engagement over time in hypertension care, or retention, is a crucial but understudied step in optimizing patient outcomes. This systematic review leverages a hermeneutic methodology to identify, evaluate, and quantify the effects of interventions and contextual factors for improving retention for patients with hypertension. METHODS: We searched for articles that were published between 2000 and 2022 from multiple electronic databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, clinicaltrials.gov, and WHO International Trials Registry. We followed the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guideline to report the findings for this review. We also synthesized the findings using a hermeneutic methodology for systematic reviews, which used an iterative process to review, integrate, analyze, and interpret evidence. RESULTS: From 4686 screened titles and abstracts, 18 unique studies from 9 countries were identified, including 10 (56%) randomized controlled trials (RCTs), 3 (17%) cluster RCTs, and 5 (28%) non-RCT studies. The number of participants ranged from 76 to 1562. The overall mean age range was 41-67 years, and the proportion of female participants ranged from 0% to 100%. Most (n = 17, 94%) studies used non-physician personnel to implement the proposed interventions. Fourteen studies (78%) implemented multilevel combinations of interventions. Education and training, team-based care, consultation, and Short Message Service reminders were the most common interventions tested. CONCLUSIONS: This review presents the most comprehensive findings on retention in hypertension care to date and fills the gaps in the literature, including the effectiveness of interventions, their components, and contextual factors. Adaptation of and implementing HIV care models, such differentiated service delivery, may be more effective and merit further study. REGISTRATION: CRD42021291368. PROTOCOL REGISTRATION: PROSPERO 2021 CRD42021291368. Available at: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=291368.
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Hipertensão , Atenção Primária à Saúde , Humanos , Hipertensão/terapia , Retenção nos Cuidados , HermenêuticaRESUMO
BACKGROUND: Hypertensive disorders of pregnancy, including hypertension, are a leading cause of maternal mortality in Nigeria. However, there is a paucity of data on pregnant women with hypertension who receive care in primary health care facilities. This study presents the results from a cross-sectional analysis of pregnant women enrolled in the Hypertension Treatment in Nigeria Program which is aimed at integrating and strengthening hypertension care in primary health care centres. METHODS: A descriptive analysis of the baseline results from the Hypertension Treatment in Nigeria Program was performed. Baseline blood pressures, treatment and control rates of pregnant women were analysed and compared to other adult women of reproductive age. A complete case analysis was performed, and a two-sided p value < 0.05 was considered statistically significant. RESULTS: Between January 2020 to October 2022, 5972 women of reproductive age were enrolled in the 60 primary healthcare centres participating in the Hypertension Treatment in Nigeria Program and 112 (2%) were pregnant. Overall mean age (SD) was 39.6 years (6.3). Co-morbidities were rare in both groups, and blood pressures were similar amongst pregnant and non-pregnant women (overall mean (SD) first systolic and diastolic blood pressures were 157.4 (20.6)/100.7 (13.6) mm Hg and overall mean (SD) second systolic and diastolic blood pressures were 151.7 (20.1)/98.4 (13.5) mm Hg). However, compared to non-pregnant women, pregnant women had a higher rate of newly diagnosed hypertension (65.2% versus 54.4% p = 0.02) and lower baseline walk-in treatment (32.1% versus 42.1%, p = 0.03). The control rate was numerically lower among pregnant patients (6.3% versus 10.2%, p = 0.17), but was not statistically significant. Some pregnant patients (8.3%) were on medications contraindicated in pregnancy, and none of the pregnant women were on aspirin for primary prevention of preeclampsia. CONCLUSIONS: These findings indicate significant gaps in care and important areas for future studies to improve the quality of care and outcomes for pregnant women with hypertension in Nigeria, a country with the highest burden of maternal mortality globally.
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Hipertensão , Gestantes , Gravidez , Adulto , Humanos , Feminino , Estudos Transversais , Nigéria/epidemiologia , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Atenção Primária à SaúdeRESUMO
INTRODUCTION: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction and associated with considerable morbidity and mortality. We sought to evaluate the association between change in cardiac mechanics after diagnosis of TTS with 1-year incidence of major adverse cardiovascular events (MACE). METHODS: We retrospectively identified 85 patients with apical TTS based on ICD 9/10 codes and chart adjudication, who had a follow-up echocardiogram within 6 months of diagnosis. Echocardiograms were analyzed for left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), GLS ratio, global circumferential strain (GCS), and global radial strain (GRS). Multivariable logistic regression was performed to identify parameters associated with MACE (all-cause mortality, heart failure, stroke, and coronary artery disease [CAD] requiring percutaneous coronary intervention [PCI]) at 1 year. Event-free survival was assessed in patients with GLS (≤-18% vs. >18%) and LVEF (≥53% vs. <53%). RESULTS: Within 1 year of diagnosis, MACE occurred in 15 (18%) patients. Between baseline and follow-up echocardiogram (median 15 [range 1-151] days), there were significant differences in change in LVEF and GLS in patients with versus without incident MACE. In multivariate analysis, change in LVEF (odds ratio [OR] = .93 [.87, .98], p = .013) and change in GLS (OR = 1.32 [1.04, 1.67], p = .022) were independently associated with MACE; however, the association with change in GLS was attenuated (odds ratio [OR] = 1.13 [.94, 1.36], p = .21) after adjustment for baseline and change in LVEF. Among patients with normalized LVEF at follow-up, there were five (14.7%) MACE; whereas, there were no events among patients with normalized GLS. CONCLUSIONS: In patients with apical TTS, recovery in GLS and LVEF at follow-up was associated with significantly lower MACE at 1 year. Normalization of GLS at follow-up was better able to discriminate event-free survival than normalization of LVEF.
Assuntos
Intervenção Coronária Percutânea , Cardiomiopatia de Takotsubo , Disfunção Ventricular Esquerda , Humanos , Função Ventricular Esquerda , Volume Sistólico , Cardiomiopatia de Takotsubo/complicações , Estudos Retrospectivos , Prognóstico , Ecocardiografia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagemRESUMO
Objective: Consumers in the US make choices within a food supply dominated by processed packaged foods and beverage products. Front-of-package nutrition labels (FOPL) equip consumers to make healthier choices, but further evaluation and regulation regarding FOPL format, scope, and display have been recommended by the World Health Organization. As a leader in consumer FOPL guidance, the American Heart Association's (AHA) Heart Check programme certifies food companies seeking to add an AHA Heart Check logo as a FOPL for qualifying heart healthy products. A cross-sectional assessment of the AHA Heart Check Standard Certification was conducted within the US packaged food and beverage supply to assess the eligibility and prevalence of the programme as a FOPL. Methods: Data were derived from Label Insight's Open Data initiative, which is the largest publicly-available US branded food composition database. The proportions of products that were certified and eligible to be certified for the Standard Certification were reported by nutrient attributes, grocery aisles and food brands. Results: Among 153,453 products examined, fewer than 1% exhibited the Heart Check certification on their label. Among products that were not Heart Check certified,13.8% were eligible for Standard Certification. The most common reason for ineligibility was the saturated fat content (52%), followed by total fat content (47%) and sodium content (47%). Heart Check certification and eligibility differed substantially across grocery aisle categories. Conclusions: The abundance of unhealthy products in the US packaged food and beverage supply and absence of harmonized FOPL policies suggest the need for FOPL like the Heart Check label to promote adherence to healthy diets. There are opportunities for food manufacturers and the AHA to certify more heart healthy foods and beverages. However, more consistent criteria and transparent labelling could enhance Heart Check certification to facilitate consumers' ability to make more informed and healthful purchases.
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American Heart Association , Bebidas , Humanos , Estudos Transversais , Prevalência , Valor NutritivoRESUMO
BACKGROUND: Over half of patients with elevated blood pressure require multi-drug treatment to achieve blood pressure control. However, multi-drug treatment may lead to lower adherence and more adverse drug effects compared with monotherapy. OBJECTIVE: The Quadruple Ultra-low-dose Treatment for Hypertension (QUARTET) USA trial was designed to evaluate whether initiating treatment with ultra-low-dose quadruple-combination therapy will lower office blood pressure more effectively, and with fewer side effects, compared with initiating standard dose monotherapy in treatment naive patients with SBP < 180 and DBP < 110 mm Hg and patients on monotherapy with SBP < 160 and DBP < 100 mm Hg. METHODS/DESIGN: QUARTET USA was a prospective, randomized, double-blind trial (ClinicalTrials.gov NCT03640312) conducted in federally qualified health centers in a large city in the US. Patients were randomly assigned (1:1) to either ultra-low-dose quadruple combination therapy or standard dose monotherapy. The primary outcome was mean change from baseline in office systolic blood pressure at 12-weeks, adjusted for baseline values. Secondary outcomes included measures of blood pressure change and variability, medication adherence, and health related quality of life. Safety outcomes included occurrence of serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. A process evaluation aimed to understand provider experiences of implementation and participant experiences around side effects, adherence, and trust with clinical care. DISCUSSION: QUARTET USA was designed to evaluate whether a novel approach to blood pressure control would lower office blood pressure more effectively, and with fewer side effects, compared with standard dose monotherapy. QUARTET USA was conducted within a network of federally qualified healthcare centers with the aim of generating information on the safety and efficacy of ultra-low-dose quadruple-combination therapy in diverse groups that experience a high burden of hypertension.
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Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , Pressão Sanguínea , Método Duplo-Cego , Resultado do TratamentoRESUMO
PURPOSE: The field of cardio-oncology aims to optimize the cardiac health of cancer patients. The goals of this study are to (1) describe the demographics of a cardio-oncology clinic and (2) apply the American Society of Clinical Oncology (ASCO) cardiac risk stratification guidelines among breast cancer patients to assess the development of cardiovascular events, primarily heart failure (HF). METHODS: We performed a retrospective chart review on 203 consecutive cardio-oncology patients who were seen between January 2019 and March 2020. Mean follow-up for the cohort was 29.2 ± 3.1 months (range 0-113). We applied the ASCO guidelines to the breast cancer subgroup. RESULTS: The plurality of patients 82/203 (40%) referred to clinic had breast cancer. The most common reason for referral was asymptomatic left ventricular (LV) dysfunction or HF (40%). Only 36/203 (18%) of patients were referred for a pre-chemotherapy evaluation. In breast cancer patients, there was a trend toward significance in up-titrating or initiating beta-blockers in the high vs. low risk ASCO groups [46/69 (67%) vs. 5/13 (38%), p = 0.054]. Approximately 13/82 (16%) of breast cancer patients required alterations to their anti-cancer therapy. HF events occurred in 1/36 (3%) of cancer treatment naïve patients and 14/167 (8%) of those with prior therapy, specifically 9% of the breast cancer subset. CONCLUSION: Our study provides insight into referral practices, interventions, and outcomes at a cardio-oncology clinic. Furthermore, breast cancer patients continue to have high rates of HF. These findings suggest a need to shift referral practices upstream for a pre-chemotherapy evaluation to optimize cardiovascular health.
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Neoplasias da Mama , Insuficiência Cardíaca , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Oncologia , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Nigeria faces an increase in the burden of non-communicable diseases (NCDs), including cardiovascular diseases (CVDs), leading to an estimated 29% of all deaths in the country. Nigeria has an estimated hypertension prevalence ranging from 25 to 40% of her adult population. Despite this high burden, awareness (14-30%), treatment (< 20%), and control (9%) rates of hypertension are low in Nigeria. Against this backdrop, we sought to perform capacity and readiness assessments of public Primary Healthcare Centers (PHCs) to inform Nigeria's system-level hypertension control program's implementation and adaptation strategies. METHODS: The study employed a multi-stage sampling to select 60 from the 243 PHCs in the Federal Capital Territory (FCT) of Nigeria. The World Health Organization (WHO) Service Availability and Readiness Assessment was adapted to focus on hypertension diagnosis and treatment and was administered to PHC staff from May 2019 - October 2019. Indicator scores for general and cardiovascular service readiness were calculated based on the proportion of sites with available amenities, equipment, diagnostic tests, and medications. RESULTS: Median (interquartile range [IQR]) number of full-time staff was 5 (3-8), and were predominantly community health extension workers (median = 3 [IQR 2-5]). Few sites (n = 8; 15%) received cardiovascular disease diagnosis and management training within the previous 2 years, though most had sufficient capacity for screening (n = 58; 97%), diagnosis (n = 56; 93%), and confirmation (n = 50; 83%) of hypertension. Few PHCs had guidelines (n = 7; 13%), treatment algorithms (n = 3; 5%), or information materials (n = 1; 2%) for hypertension. Most sites (n = 55; 92%) had one or more functional blood pressure apparatus. All sites relied on paper records, and few had a functional computer (n = 10; 17%) or access to internet (n = 5; 8%). Despite inclusion on Nigeria's essential medicines list, 35 (59%) PHCs had zero 30-day treatment regimens of any blood pressure-lowering medications in stock. CONCLUSIONS: This first systematic assessment of capacity and readiness for a system-level hypertension control program within the FCT of Nigeria demonstrated implementation feasibility based on the workforce, equipment, and paper-based information systems, but a critical need for essential medicine supply strengthening, health-worker training, and protocols for hypertension treatment and control in Nigeria.
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Hipertensão , Atenção Primária à Saúde , Adulto , Estudos Transversais , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , NigériaRESUMO
Importance: There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). Objective: To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. Design, Setting, and Participants: A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Interventions: Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Main Outcomes and Measures: Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Results: Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Conclusions and Relevance: Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03066804.
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Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Valsartana/uso terapêutico , Idoso , Aminobutiratos/efeitos adversos , Aminobutiratos/farmacologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Biomarcadores/sangue , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/farmacologia , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Volume Sistólico , Valsartana/efeitos adversos , Valsartana/farmacologia , Teste de CaminhadaRESUMO
OBJECTIVE: Americans consume Na in excess of daily recommendations. Most dietary Na comes from packaged foods, and bread is a major contributor. In the UK, national Na reduction strategies contributed to lower Na levels in packaged foods and lower population Na intake. Similar initiatives are emerging in the USA and require surveillance to assess effectiveness. We aimed to examine Na levels in bread products in the USA and compare levels with similar UK products. DESIGN: Na data for bread products were obtained from the US Label Insight Open Data Initiative (n 4466) and the FoodSwitch UK database (n 1651). Mean, median and range of Na content, and proportion of products meeting Na targets established by the National Salt Reduction Initiative (NSRI) and the UK Department of Health (DH) were calculated overall, by bread type and by country. RESULTS: Mean (sd) Na content in bread was 455 (170) mg/100 g in the USA and 406 (179) mg/100 g in the UK. In both countries, savoury bread had the highest mean Na (USA=584 mg/100 g, UK=543 mg/100 g) and fruit bread the lowest mean Na (USA=345 mg/100 g, UK=277 mg/100 g). Na content of US bread products was 12 % higher than in the UK, with 21 % of US bread products and 31 % of UK bread products meeting the NSRI and DH targets, respectively. CONCLUSIONS: US bread products have, on average, 12 % more Na than similar products in the UK. Variation in Na content within product categories, and between countries, suggests the feasibility of manufacturing products with lower Na to lower dietary Na intake.
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Pão/análise , Dieta , Política Nutricional , Cloreto de Sódio na Dieta/análise , Sódio/análise , Comércio , Ingestão de Energia , Humanos , Reino Unido , Estados UnidosRESUMO
Importance: Wide heterogeneity exists in acute myocardial infarction treatment and outcomes in India. Objective: To evaluate the effect of a locally adapted quality improvement tool kit on clinical outcomes and process measures in Kerala, a southern Indian state. Design, Setting, and Participants: Cluster randomized, stepped-wedge clinical trial conducted between November 10, 2014, and November 9, 2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December 31, 2016. During 5 predefined steps over the study period, hospitals were randomly selected to move in a 1-way crossover from the control group to the intervention group. Consecutively presenting patients with acute myocardial infarction were offered participation. Interventions: Hospitals provided either usual care (control group; n = 10â¯066 participants [step 0: n = 2915; step 1: n = 2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or care using a quality improvement tool kit (intervention group; n = 11â¯308 participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432; step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback, checklists, patient education materials, and linkage to emergency cardiovascular care and quality improvement training. Main Outcomes and Measures: The primary outcome was the composite of all-cause death, reinfarction, stroke, or major bleeding using standardized definitions at 30 days. Secondary outcomes included the primary outcome's individual components, 30-day cardiovascular death, medication use, and tobacco cessation counseling. Mixed-effects logistic regression models were used to account for clustering and temporal trends. Results: Among 21â¯374 eligible randomized participants (mean age, 60.6 [SD, 12.0] years; n = 16â¯183 men [76%] ; n = 13â¯689 [64%] with ST-segment elevation myocardial infarction), 21â¯079 (99%) completed the trial. The primary composite outcome was observed in 5.3% of the intervention participants and 6.4% of the control participants. The observed difference in 30-day major adverse cardiovascular event rates between the groups was not statistically significant after adjustment (adjusted risk difference, -0.09% [95% CI, -1.32% to 1.14%]; adjusted odds ratio, 0.98 [95% CI, 0.80-1.21]). The intervention group had a higher rate of medication use including reperfusion but no effect on tobacco cessation counseling. There were no unexpected adverse events reported. Conclusions and Relevance: Among patients with acute myocardial infarction in Kerala, India, use of a quality improvement intervention compared with usual care did not decrease a composite of 30-day major adverse cardiovascular events. Further research is needed to understand the lack of efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02256657.
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Infarto do Miocárdio/terapia , Melhoria de Qualidade , Idoso , Feminino , Humanos , Índia , Análise de Intenção de Tratamento , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Guias de Prática Clínica como Assunto , Projetos de Pesquisa , Resultado do TratamentoRESUMO
Ischemic heart disease is the leading cause of death in India, and there are likely more myocardial infarctions in India than in any other country in the world. We have previously reported heterogeneous care for patients with myocardial infarction in Kerala, a state in southern India, including both gaps in optimal care and inappropriate care. Based on that prior work, limitations from previous nonrandomized quality improvement studies and promising gains in process of care measures demonstrated from previous randomized trials, we and the Cardiological Society of India-Kerala chapter sought to develop, implement, and evaluate a quality improvement intervention to improve process of care measures and clinical outcomes for these patients. In this article, we report the rationale and study design for the ACS QUIK cluster-randomized stepped-wedge clinical trial (NCT02256657) in which we aim to enroll 15,750 participants with acute coronary syndromes across 63 hospitals. To date, most participants are men (76%) and have ST-segment elevation myocardial infarction (63%). The primary outcome is 30-day major adverse cardiovascular events defined as death, recurrent infarction, stroke, or major bleeding. Our secondary outcomes include health-related quality of life and individual- and household-level costs. We also describe the principal features and limitations of the stepped-wedge study design, which may be important for other investigators or sponsors considering cluster-randomized stepped-wedge trials.
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Síndrome Coronariana Aguda/terapia , Fidelidade a Diretrizes , Infarto do Miocárdio/terapia , Guias de Prática Clínica como Assunto , Melhoria de Qualidade , Hemorragia/epidemiologia , Humanos , Índia , Mortalidade , Infarto do Miocárdio/epidemiologia , Avaliação de Processos e Resultados em Cuidados de Saúde , Lacunas da Prática Profissional , Recidiva , Acidente Vascular Cerebral/epidemiologiaRESUMO
BACKGROUND: Multiple genetic loci are associated with clinical cardiovascular (CV) disease and individual CV risk factors. Individuals with ideal levels of all major CV risk factors have very low risk for CV disease morbidity or mortality. Ideal levels of risk factors can be attained by lifestyle modifications; however, little is known about gene variants associated with ideal CV health. Our objective was to carry out a genome-wide association study on the trait. METHODS AND RESULTS: We examined 2 dichotomous phenotypes of ideal CV health-clinical (untreated cholesterol <200 mg/dL, untreated blood pressure <120/<80, not diabetic) and clinical+behavioral (clinical plus: not a current smoker, body mass index <25 kg/m(2))-among white participants aged 50±5 years. We performed a meta-analysis of 4 genome-wide association studies (total n=11,708) from the MESA, CARDIA, ARIC, and Framingham Heart Study cohorts. We identified a single-nucleotide polymorphism (rs445925) in the APOC1/APOE region that was associated with clinical ideal CV health at genome-wide level of significance (P<2.0 × 10(-9)). The significance of this region was validated using exome chip genotyping. The association with ideal CV health was attenuated after adjusting for low-density lipoprotein cholesterol. CONCLUSION: A common single-nucleotide polymorphism in the APOC1/APOE region, previously found to be associated with protective levels of cholesterol and lower CV risk, may be associated with ideal health. In future replication studies, larger sample sizes may be needed to detect loci with more modest effects on ideal CV health. In addition to the important impact of lifestyle modifications, we have identified evidence for gene variation that plays a role in ideal CV health.
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Apolipoproteína C-I/genética , Doenças Cardiovasculares/genética , Perfilação da Expressão Gênica/métodos , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Fatores de ProteçãoRESUMO
The obligate intracellular bacterium, Wolbachia pipientis (Rickettsiales), is a widespread, vertically transmitted endosymbiont of filarial nematodes and arthropods. In insects, Wolbachia modifies reproduction, and in mosquitoes, infection interferes with replication of arboviruses, bacteria and plasmodia. Development of Wolbachia as a tool to control pest insects will be facilitated by an understanding of molecular events that underlie genetic exchange between Wolbachia strains. Here, we used nucleotide sequence, transcriptional and proteomic analyses to evaluate expression levels and establish the mosaic nature of genes flanking the T4SS virB8-D4 operon from wStr, a supergroup B-strain from a planthopper (Hemiptera) that maintains a robust, persistent infection in an Aedes albopictus mosquito cell line. Based on protein abundance, ribA, which contains promoter elements at the 5'-end of the operon, is weakly expressed. The 3'-end of the operon encodes an intact wspB, which encodes an outer membrane protein and is co-transcribed with the vir genes. WspB and vir proteins are expressed at similar, above average abundance levels. In wStr, both ribA and wspB are mosaics of conserved sequence motifs from Wolbachia supergroup A- and B-strains, and wspB is nearly identical to its homolog from wCobU4-2, an A-strain from weevils (Coleoptera). We describe conserved repeated sequence elements that map within or near pseudogene lesions and transitions between A- and B-strain motifs. These studies contribute to ongoing efforts to explore interactions between Wolbachia and its host cell in an in vitro system.
Assuntos
Genes Bacterianos/genética , Wolbachia/genética , Animais , Sequência de Bases , Óperon/genética , ProteômicaRESUMO
BACKGROUND: Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common causes of skin and soft tissue infections in the United States, and a variety of genetic host factors are suspected to be risk factors for recurrent infection. Based on the CDC definition, we have developed and validated an electronic health record (EHR) based CA-MRSA phenotype algorithm utilizing both structured and unstructured data. METHODS: The algorithm was validated at three eMERGE consortium sites, and positive predictive value, negative predictive value and sensitivity, were calculated. The algorithm was then run and data collected across seven total sites. The resulting data was used in GWAS analysis. RESULTS: Across seven sites, the CA-MRSA phenotype algorithm identified a total of 349 cases and 7761 controls among the genotyped European and African American biobank populations. PPV ranged from 68 to 100% for cases and 96 to 100% for controls; sensitivity ranged from 94 to 100% for cases and 75 to 100% for controls. Frequency of cases in the populations varied widely by site. There were no plausible GWAS-significant (p < 5 E -8) findings. CONCLUSIONS: Differences in EHR data representation and screening patterns across sites may have affected identification of cases and controls and accounted for varying frequencies across sites. Future work identifying these patterns is necessary.
Assuntos
Algoritmos , Registros Eletrônicos de Saúde , Estudo de Associação Genômica Ampla/métodos , Staphylococcus aureus Resistente à Meticilina , Fenótipo , Infecções Estafilocócicas/diagnóstico , Adulto , Estudos de Casos e Controles , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Fatores de Risco , Sensibilidade e Especificidade , Infecções Estafilocócicas/genética , Estados UnidosRESUMO
We used electronic health record data from 162 patients enrolled in the NUgene Project (2002-2013) to determine demographic factors associated with long-term (from 1 to up to 9.5 (mean = 5.6) years) weight loss following Roux-en-Y gastric bypass surgery. Ninety-nine (61.1%) patients self-reported white, and 63 (38.9%) self-reported black, mixed, or missing race. The average percent weight loss was -33.4% (standard deviation, 9.3) at 1 year after surgery and -30.7% (standard deviation, 12.5) at the last follow-up point. We used linear mixed and semiparametric trajectory models to test the association of surgical and demographic factors (height, surgery age, surgery weight, surgery body mass index, marital status, sex, educational level, site, International Classification of Diseases code, Current Procedural Terminology code, Hispanic ethnicity, and self-reported race) with long-term percent weight loss and pattern of weight loss. We found that black, mixed, and missing races (combined) in comparison with white race were associated with a decreased percent weight loss of -4.31% (95% confidence interval: -7.30, -1.32) and were less likely to have higher and sustained percent weight loss (P = 0.04). We also found that less obese patients were less likely to have higher and sustained percent weight loss (P = 0.01). These findings may be helpful to patients in setting expectations after weight loss surgery.
Assuntos
Derivação Gástrica/estatística & dados numéricos , Modelos Lineares , Obesidade Mórbida/cirurgia , Redução de Peso/etnologia , Análise de Variância , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Autorrelato , Tempo , Resultado do TratamentoRESUMO
Wolbachia pipientis, a widespread vertically transmitted intracellular bacterium, provides a tool for insect control through manipulation of host-microbe interactions. We report proteomic characterization of wStr, a Wolbachia strain associated with a strong cytoplasmic incompatibility phenotype in its native host, Laodelphax striatellus. In the Aedes albopictusâ C/wStr1 mosquito cell line, wStr maintains a robust, persistent infection. MS/MS analyses of gel bands revealed a protein 'footprint' dominated by Wolbachia-encoded chaperones, stress response and cell membrane proteins, including the surface antigen WspA, a peptidoglycan-associated lipoprotein and a 73 kDa outer membrane protein. Functional classifications and estimated abundance levels of 790 identified proteins suggested that expression, stabilization and secretion of proteins predominate over bacterial genome replication and cell division. High relative abundances of cysteine desulphurase, serine/glycine hydroxymethyl transferase, and components of the α-ketoglutarate dehydrogenase complex in conjunction with above average abundances of glutamate dehydrogenase and proline utilization protein A support Wolbachia genome-based predictions for amino acid metabolism as a primary energy source. wStr expresses 15 Vir proteins of a Type IV secretion system and its transcriptional regulator. Proteomic characterization of a robust insect-associated Wolbachia strain provides baseline information that will inform further development of in vitro protocols for Wolbachia manipulation.
Assuntos
Proteínas de Bactérias/análise , Proteoma/análise , Wolbachia/crescimento & desenvolvimento , Aedes , Animais , Linhagem Celular , Eletroforese em Gel Bidimensional , Espectrometria de Massas em TandemRESUMO
For ibrutinib-related atrial fibrillation (IRAF), guidelines for anticoagulation do not exist. We sought to describe stroke, bleeding, and anticoagulation rates among patients with IRAF. We performed a single-center retrospective review of 168 patients treated with ibrutinib followed from 2013 to 2022. Over a median follow-up of 6.4 years, 44 (26.0%) patients developed IRAF of which 38 (86.4%) had a CHA2DS2-VASc ≥2 and 7 (15.9%) had a HAS-BLED ≥3. Anticoagulation was initiated in 20 (45.5%) without a clear pattern in scores, risk factors, or cumulative dose, besides having another reason for anticoagulation. Few patients with IRAF developed non-hemorrhagic CVA (n = 3, 6.8%) or significant bleeding (n = 3, 6.8%). Among those with each adverse outcome, 2 in each group were anticoagulated and all were older than 65 years old. In conclusion, decisions for anticoagulation vary widely and patients who are elderly or with HTN may be most at risk for CVA or significant bleed.
Assuntos
Adenina/análogos & derivados , Fibrilação Atrial , Piperidinas , Acidente Vascular Cerebral , Humanos , Idoso , Fibrilação Atrial/complicações , Anticoagulantes/uso terapêutico , Medição de Risco , Coagulação Sanguínea , Acidente Vascular Cerebral/etiologia , Hemorragia/etiologia , Fatores de RiscoRESUMO
BACKGROUND: This study aims to understand and describe the clinical impact of SARS-CoV-2 (COVID-19) infection in patients with Hypertrophic Cardiomyopathy (HCM). METHODS: A data repository of over 6.6 million patients in a large metropolitan (Chicago IL) healthcare system was queried to identify adults with a history of HCM and COVID-19 infection between 2019 and 2021. Propensity score-matched analysis was performed based on age, sex, BMI, and elements of the cardiovascular history, including tobacco use, hypertension, hyperlipidemia, myocardial injury, and heart failure. RESULTS: Individuals with HCM and COVID-19 infection had more total hospitalizations (41.6 v 23 per 100 persons, p < 0.01), more heart-failure-related hospitalizations (24.2 v 8.7 per 100-persons, p < 0.01), more non-ST elevation myocardial injury (NSTEMI) hospitalizations (8.6 v 4.6 per 100-persons, p < 0.01), and increased mortality (10.8 v 5 per 100-persons, p < 0.01) compared to HCM patients without a history of COVID-19 infection. Patients with HCM and COVID-19 were also noted to have a higher peak CRP when compared to those without prior COVID-19 (Inter-quartile range of 9.0-106.9 v 1.8-21.3, p < 0.01). CONCLUSIONS: In patients with HCM, COVID-19 infection is associated with increased incidence of myocardial injury, increased number of total and heart-failure specific hospitalizations, and increased mortality.