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1.
Lancet ; 402(10409): 1241-1250, 2023 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-37805215

RESUMO

BACKGROUND: In sub-Saharan Africa, health-care provision for chronic conditions is fragmented. The aim of this study was to determine whether integrated management of HIV, diabetes, and hypertension led to improved rates of retention in care for people with diabetes or hypertension without adversely affecting rates of HIV viral suppression among people with HIV when compared to standard vertical care in medium and large health facilities in Uganda and Tanzania. METHODS: In INTE-AFRICA, a pragmatic cluster-randomised, controlled trial, we randomly allocated primary health-care facilities in Uganda and Tanzania to provide either integrated care or standard care for HIV, diabetes, and hypertension. Random allocation (1:1) was stratified by location, infrastructure level, and by country, with a permuted block randomisation method. In the integrated care group, participants with HIV, diabetes, or hypertension were managed by the same health-care workers, used the same pharmacy, had similarly designed medical records, shared the same registration and waiting areas, and had an integrated laboratory service. In the standard care group, these services were delivered vertically for each condition. Patients were eligible to join the trial if they were living with confirmed HIV, diabetes, or hypertension, were aged 18 years or older, were living within the catchment population area of the health facility, and were likely to remain in the catchment population for 6 months. The coprimary outcomes, retention in care (attending a clinic within the last 6 months of study follow-up) for participants with either diabetes or hypertension (tested for superiority) and plasma viral load suppression for those with HIV (>1000 copies per mL; tested for non-inferiority, 10% margin), were analysed using generalised estimating equations in the intention-to-treat population. This trial is registered with ISCRTN 43896688. FINDINGS: Between June 30, 2020, and April 1, 2021 we randomly allocated 32 health facilities (17 in Uganda and 15 in Tanzania) with 7028 eligible participants to the integrated care or the standard care groups. Among participants with diabetes, hypertension, or both, 2298 (75·8%) of 3032 were female and 734 (24·2%) of 3032 were male. Of participants with HIV alone, 2365 (70·3%) of 3365 were female and 1000 (29·7%) of 3365 were male. Follow-up lasted for 12 months. Among participants with diabetes, hypertension, or both, the proportion alive and retained in care at study end was 1254 (89·0%) of 1409 in integrated care and 1457 (89·8%) of 1623 in standard care. The risk differences were -0·65% (95% CI -5·76 to 4·46; p=0·80) unadjusted and -0·60% (-5·46 to 4·26; p=0·81) adjusted. Among participants with HIV, the proportion who had a plasma viral load of less than 1000 copies per mL was 1412 (97·0%) of 1456 in integrated care and 1451 (97·3%) of 1491 in standard care. The differences were -0·37% (one-sided 95% CI -1·99 to 1·26; pnon-inferiority<0·0001 unadjusted) and -0·36% (-1·99 to 1·28; pnon-inferiority<0·0001 adjusted). INTERPRETATION: In sub-Saharan Africa, integrated chronic care services could achieve a high standard of care for people with diabetes or hypertension without adversely affecting outcomes for people with HIV. FUNDING: European Union Horizon 2020 and Global Alliance for Chronic Diseases.


Assuntos
Fármacos Anti-HIV , Diabetes Mellitus , Infecções por HIV , Hipertensão , Feminino , Humanos , Masculino , Fármacos Anti-HIV/uso terapêutico , Diabetes Mellitus/terapia , Diabetes Mellitus/tratamento farmacológico , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Hipertensão/terapia , Hipertensão/tratamento farmacológico , Tanzânia/epidemiologia
2.
J Cardiovasc Electrophysiol ; 34(6): 1405-1414, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37146210

RESUMO

INTRODUCTION: Guidelines indicate primary-prevention implantable cardioverter-defibrillators (ICDs) for most patients with left ventricular ejection fraction (LVEF) ≤ 35%. Some patients' LVEFs improve during the life of their first ICD. In patients with recovered LVEF who never received appropriate ICD therapy, the utility of generator replacement upon battery depletion remains unclear. Here, we evaluate ICD therapy based on LVEF at the time of generator change, to educate shared decision-making regarding whether to replace the depleted ICD. METHODS: We followed patients with a primary-prevention ICD who underwent generator change. Patients who received appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) before generator change were excluded. The primary endpoint was appropriate ICD therapy, adjusted for the competing risk of death. RESULTS: Among 951 generator changes, 423 met inclusion criteria. During 3.4 ± 2.2 years follow-up, 78 (18%) received appropriate therapy for VT/VF. Compared to patients with recovered LVEF > 35% (n = 161 [38%]), those with LVEF ≤ 35% (n = 262 [62%]) were more likely to require ICD therapy (p = .002; Fine-Gray adjusted 5-year event rates: 12.7% vs. 25.0%). Receiver operating characteristic analysis revealed the optimal LVEF cutoff for VT/VF prediction to be 45%, the use of which further improved risk stratification (p < .001), with Fine-Gray adjusted 5-year rates 6.2% versus 25.1%. CONCLUSION: Following ICD generator change, patients with primary-prevention ICDs and recovered LVEF have significantly lower risk of subsequent ventricular arrhythmias compared to those with persistent LVEF depression. Risk stratification at LVEF 45% offers significant additional negative predictive value over a 35% cutoff, without a significant loss in sensitivity. These data may be useful during shared decision-making at the time of ICD generator battery depletion.


Assuntos
Desfibriladores Implantáveis , Taquicardia Ventricular , Humanos , Função Ventricular Esquerda , Volume Sistólico , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/terapia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Fatores de Risco
3.
J Cardiovasc Electrophysiol ; 34(2): 279-290, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36352771

RESUMO

INTRODUCTION: Use of a novel magnetic sensor enabled optical contact force ablation catheter has been established to be safe and effective for treatment of symptomatic drug-refractory paroxysmal atrial fibrillation (AF) but has yet to be demonstrated in the persistent AF (PersAF) population. METHODS: PERSIST-END was a multicenter, prospective, nonrandomized, investigational study designed to demonstrate the safety and effectiveness of TactiCath™ Ablation Catheter, Sensor Enabled™(SE) (TactiCath SE) for use in the treatment of subjects with documented PersAF refractory or intolerant to at least one Class I/III AAD. The ablation strategy included pulmonary vein isolation and additional targets at physician discretion. Follow-up through 15-months, including a 3-month blanking period and 3-month therapy consolidation period, was performed with cardiac event and Holter monitoring. Primary safety, primary effectiveness, clinical success, and quality of life (QOL) endpoints were analyzed. RESULTS: Of 224 subjects enrolled at 21 investigational sites in the United States and Australia, 223 underwent ablation with the investigational catheter. The primary safety event rate was 3.1% (seven events in seven subjects). The Kaplan-Meier estimate of freedom from AF/atrial flutter/atrial tachycardia recurrence at 15-months was 61.6% and clinical success at 15 months was 89.8%. Subject QOL significantly improved following ablation as assessed via AFEQT (31.6 point increase, p < .0001) and EQ-5D-5L (10.7 point increase, p < .0001) and was met with a 53% reduction in all cause cardiovascular healthcare utilization. CONCLUSION: The sensor-enabled force-sensing catheter is safe and effective for the treatment of drug refractory recurrent symptomatic PersAF, reducing arrhythmia recurrence while improving QOL and healthcare utilization.


Assuntos
Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/tratamento farmacológico , Qualidade de Vida , Estudos Prospectivos , Sistema de Condução Cardíaco , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Recidiva
4.
J Cardiovasc Electrophysiol ; 33(11): 2375-2381, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36069136

RESUMO

INTRODUCTION: Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure. METHODS AND RESULTS: We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD. CONCLUSION: This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.


Assuntos
Antiarrítmicos , Insuficiência Cardíaca , Humanos , Antiarrítmicos/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/farmacologia , Neprilisina/uso terapêutico , Tetrazóis/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Volume Sistólico , Valsartana/farmacologia , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/tratamento farmacológico , Resultado do Tratamento
5.
J Cardiovasc Electrophysiol ; 31(3): 607-611, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31912933

RESUMO

BACKGROUND: Class 1C antiarrhythmic drugs (AADs) are effective first-line agents for atrial fibrillation (AF) treatment. However, these agents commonly are avoided in patients with known coronary artery disease (CAD), due to known increased risk in the postmyocardial infarction population. Whether 1C AADs are safe in patients with CAD but without clinical ischemia or infarct is unknown. Reduced coronary flow capacity (CFC) on positron emission tomography (PET) reliably identifies myocardial regions supplied by vessels with CAD causing flow limitation. OBJECTIVE: To assess whether treatment with 1C AADs increases mortality in patients without known CAD but with CFC indicating significantly reduced coronary blood flow. METHODS: In this pilot study, we compared patients with AF and left ventricular ejection fraction ≥50% who were treated with 1C AADs to age-matched AF patients without 1C AAD treatment. No patient had clinically evident CAD (ie, reversible perfusion defect, known ≥70% epicardial lesion, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction). All patients had PET-based quantification of stress myocardial blood flow and CFC. Death was assessed by clinical follow-up and social security death index search. RESULTS: A total of 78 patients with 1C AAD exposure were matched to 78 controls. Over a mean follow-up of 2.0 years, the groups had similar survival (P = .54). Among patients with CFC indicating the presence of occult CAD (ie, reduced CFC involving ≥50% of myocardium), 1C-treated patients had survival similar to (P = .44) those not treated with 1C agents. CONCLUSIONS: In a limited population of AF patients with preserved left ventricle function and PET-CFC indicating occult CAD, treatment with 1C AADs appears not to increase mortality. A larger study would be required to confidently assess the safety of these drugs in this context.


Assuntos
Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/diagnóstico por imagem , Frequência Cardíaca/efeitos dos fármacos , Imagem de Perfusão , Tomografia por Emissão de Pósitrons , Idoso , Antiarrítmicos/efeitos adversos , Antiarrítmicos/classificação , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Função Ventricular Esquerda
6.
J Cardiovasc Electrophysiol ; 31(5): 1137-1146, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32064730

RESUMO

INTRODUCTION: Sudden cardiac death is a substantial cause of mortality in patients with cardiomyopathy, but evidence supporting implantable cardioverter-defibrillator (ICD) implantation is less robust in nonischemic cardiomyopathy (NICM) than in ischemic cardiomyopathy. Improved risk stratification is needed. We assessed whether absolute quantification of stress myocardial blood flow (sMBF) measured by positron emission tomography (PET) predicts ventricular arrhythmias (VA) and/or death in patients with NICM. METHODS: In this pilot study, we prospectively followed patients with NICM (left ventricular ejection fraction ≤ 35%) and an ICD who underwent cardiac PET stress imaging with sMBF quantification. NICM was defined as the absence of angiographic obstructive coronary stenosis, significant relative perfusion defects on imaging, coronary revascularization, or acute coronary syndrome. Endpoints were appropriate device therapy for VA and all-cause mortality. Subgroup analysis was performed in patients who had no prior history of VA (ie, the primary prevention population). RESULTS: We followed 37 patients (60 ± 14 years, 46% male) for 41 ± 23 months. The median sMBF was 1.56 mL/g/min (interquartile range: 1.00-1.82). Lower sMBF predicted VA, both in the whole population (hazard ratio [HR] for each 0.1 mL/g/min increase: 0.84, P = .015) and in the primary prevention subset (n = 27; HR for each 0.1 mL/g/min increase: 0.81, P = .049). Patients with sMBF below the median had significantly more VA than those above the median, both in the whole population (P = .004) and in the primary prevention subset (P = .046). Estimated 3-year VA rates in the whole population were 67% among low-flow patients vs 13% among high-flow patients, and 39% vs 8%, respectively, among primary-prevention patients. sMBF did not predict all-cause mortality. CONCLUSIONS: In patients with NICM, lower sMBF predicts VA. This relationship may be useful for risk stratification for ventricular arrhythmia and decision making regarding ICD implantation.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatias/diagnóstico por imagem , Circulação Coronária , Morte Súbita Cardíaca/etiologia , Imagem de Perfusão do Miocárdio , Tomografia por Emissão de Pósitrons , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/prevenção & controle , Cardiomiopatias/complicações , Cardiomiopatias/mortalidade , Cardiomiopatias/terapia , Tomada de Decisão Clínica , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Intervalo Livre de Progressão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Função Ventricular Esquerda
7.
Europace ; 22(7): 1044-1053, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357207

RESUMO

AIMS: Evidence links markers of systemic inflammation and heart failure (HF) with ventricular arrhythmias (VA) and/or death. Biomarker levels, and the risk they indicate, may vary over time. We evaluated the utility of serial laboratory measurements of inflammatory biomarkers and HF, using time-dependent analysis. METHODS AND RESULTS: We prospectively enrolled ambulatory patients with left ventricular ejection fraction (LVEF) ≤35% and a primary-prevention implanted cardioverter-defibrillator (ICD). Levels of established inflammatory biomarkers [C-reactive protein, erythrocyte sedimentation rate (ESR), suppression of tumourigenicity 2 (ST2), tumour necrosis factor alpha (TNF-α)] and brain natriuretic peptide (BNP) were assessed at 3-month intervals for 1 year. We assessed relationships between biomarkers modelled as time-dependent variables, VA, and death. Among 196 patients (66±14 years, LVEF 23±8%), 33 experienced VA, and 18 died. Using only baseline values, BNP predicted VA, and both BNP and ST2 predicted death. Using serial measurements at 3-month intervals, time-varying BNP independently predicted VA, and time-varying ST2 independently predicted death. C-statistic analysis revealed no significant benefit to repeated testing compared with baseline-only measurement. C-reactive protein, ESR, and TNF-α, either at baseline or over time, did not predict either endpoint. CONCLUSION: In stable ambulatory patients with systolic cardiomyopathy and an ICD, BNP predicts ventricular tachyarrhythmia, and ST2 predicts death. Repeated laboratory measurements over a year's time do not improve risk stratification beyond baseline measurement alone. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01892462 (https://clinicaltrials.gov/ct2/show/NCT01892462).


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Biomarcadores , Humanos , Inflamação/diagnóstico , Peptídeo Natriurético Encefálico , Prognóstico , Volume Sistólico , Função Ventricular Esquerda
8.
Europace ; 20(4): 698-705, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-28339886

RESUMO

Aims: Several published investigations demonstrated that a longer T-peak to T-end interval (Tpe) implies increased risk for ventricular tachyarrhythmia (VT/VF) and mortality. Tpe has been measured using diverse methods. We aimed to determine the optimal Tpe measurement method for screening purposes. Methods and results: We evaluated 305 patients with LVEF ≤ 35% and an implantable cardioverter-defibrillator implanted for primary prevention. Tpe was measured using seven different methods described in the literature, including six manual methods and the automated algorithm '12SL', and was corrected for heart rate. Endpoints were VT/VF and death. To account for differences in the magnitude of Tpe measurements, results are expressed in standard deviation (SD) increments. We evaluated the clinical utility of each measurement method based on predictive ability, fraction of immeasurable tracings, and intra- and interobserver correlation. >Over 31 ± 23 months, 82 (27%) patients had VT/VF, and over 49 ± 21 months, 91 (30%) died. Several rate-corrected Tpe measurement methods predicted VT/VF (HR per SD 1.20-1.34; all P < 0.05), and nearly all methods (both corrected and uncorrected) predicted death (HR per SD 1.19-1.35; all P < 0.05). Optimal predictive ability, readability, and correlation were found in the automated 12SL method and the manual tangent method in lead V2. Conclusion: For the prediction of VT/VF, the utility of Tpe depends upon the measurement method, but for the prediction of mortality, most published Tpe measurement methods are similarly predictive. Heart rate correction improves predictive ability. The automated 12SL method performs as well as any manual measurement, and among manual methods, lead V2 is most useful.


Assuntos
Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica , Eletrocardiografia , Frequência Cardíaca , Prevenção Primária , Taquicardia Ventricular/diagnóstico , Disfunção Ventricular Esquerda/diagnóstico , Fibrilação Ventricular/diagnóstico , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevenção Primária/instrumentação , Medição de Risco , Fatores de Risco , Volume Sistólico , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapia , Fibrilação Ventricular/mortalidade , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapia , Função Ventricular Esquerda
9.
Oecologia ; 188(1): 237-250, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29948315

RESUMO

In temperate deciduous forests of eastern USA, most earthworm communities are dominated by invasive species. Their structure and functional group composition have critical impacts on ecological properties and processes. However, the factors determining their community structure are still poorly understood, and little is known regarding their dynamics during forest succession and the mechanisms leading to these changes. Earthworm communities are usually assumed to be stable and driven by vegetation. In contrast, the importance of dispersal and ecological drift is seldom acknowledged. By analyzing a 19-year dataset collected from forest stands in eastern USA, we demonstrated that on a decadal timescale, earthworm community dynamics are shaped by the interplay of selection, dispersal, and ecological drift. We highlighted that forests at different successional stages have distinct earthworm species and functional groups as a result of environmental filtering through leaf litter quality. Specifically, young forests are characterized by soil-feeding species that rely on relatively fresh soil organic matter derived from fast-decomposing litter, whereas old forests are characterized by those feeding on highly processed soil organic matter derived from slow-decomposing litter. In addition, year-to-year species gains and losses are primarily driven by dispersal from regional to local species pools, and by local extinction resulted from competition and ecological drift. We concluded that with continued dispersal of European species and the recent "second wave" of earthworm invasion by Asian species from the surrounding landscape, earthworms at the investigated forests are well-established, and will remain as the major drivers of soil development for the foreseeable future.


Assuntos
Oligoquetos , Animais , Florestas , Espécies Introduzidas , Folhas de Planta , Solo
10.
Ecology ; 97(1): 160-70, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27008785

RESUMO

The factors regulating soil animal communities are poorly understood. Current theory favors niche complementarity and facilitation over competition as the primary forms of non-trophic interspecific interaction in soil fauna; however, competition has frequently been suggested as an important community-structuring factor in earthworms, ecosystem engineers that influence belowground processes. To date, direct evidence of competition in earthworms is lacking due to the difficulty inherent in identifying a limiting resource for saprophagous animals. In the present study, we offer the first direct evidence of interspecific competition for food in this dominant soil detritivore group by combining field observations with laboratory mesocosm experiments using 13C and 15N double-enriched leaf litter to track consumption patterns. In our experiments, the Asian invasive species Amynthas hilgendorfi was a dominant competitor for leaf litter against two European species currently invading the temperate deciduous forests in North America. This competitive advantage may account for recent invasion success of A. hilgendorfi in forests with established populations of European species, and we hypothesize that specific phenological differences play an important role in determining the outcome of the belowground competition. In contrast, Eisenoides lonnbergi, a common native species in the Eastern United States, occupied a unique trophic position with limited interactions with other species, which may contribute to its persistence in habitats dominated by invasive species. Furthermore, our results supported neither the hypothesis that facilitation occurs between species of different functional groups nor the hypothesis that species in the same group exhibit functional equivalency in C and N translocation in the soil. We propose that species identity is a more powerful approach to understand earthworm invasion and its impacts on belowground processes.


Assuntos
Comportamento Alimentar , Espécies Introduzidas , Oligoquetos/classificação , Oligoquetos/fisiologia , Animais , América do Norte , Solo
11.
J Biol Chem ; 289(20): 14360-9, 2014 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-24692561

RESUMO

The glycoprotein hormones are all structurally related heterodimers consisting of an α-subunit and a ligand-specific ß-subunit that confers their unique biological activity. Crystal structures showed how the ß-subunit surrounds a part of the α-subunit, and we showed the existence of the two mechanisms responsible for that assembly. In human choriogonadotropin, the ß-subunit is folded before the subunits dock, and the α-subunit becomes incorporated into the dimer by a mechanism we termed "threading," passing between parts of the preassembled ß-subunit. Here, we show that the human lutropin ß-subunit is not folded completely prior to its interaction with the α-subunit and show that docking of the subunits enables the α-subunit to serve as a chaperone to the ß-subunit. Based on data described here, we propose that the α-subunit facilitates formation of the human lutropin ß-subunit by two mechanisms. First, the cystine knot of the α-subunit potentiates formation of the ß-subunit cystine knot, and second, contacts between α-subunit loop 2 and a hydrophobic tail in the ß-subunit facilitate formation of the seatbelt latch disulfide, which stabilizes the heterodimer. The primary influence of the α-subunit was seen when the hydrophobic tail was present or absent, but the secondary mechanism was required only when the hydrophobic tail of the ß-subunit was present. During the evolution of human choriogonadotropin, neither of these α-subunit roles was necessary for folding of the ß-subunit. The complex mechanism for lutropin assembly may be required to provide an additional control on its positive feedback function in vertebrate reproduction.


Assuntos
Gonadotropina Coriônica/química , Hormônio Luteinizante/química , Multimerização Proteica , Gonadotropina Coriônica/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Modelos Moleculares , Estrutura Quaternária de Proteína , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo
13.
JAMA Cardiol ; 9(7): 641-648, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776097

RESUMO

Importance: Atrial fibrillation and obesity are common, and both are increasing in prevalence. Obesity is associated with failure of cardioversion of atrial fibrillation using a standard single set of defibrillator pads, even at high output. Objective: To compare the efficacy and safety of dual direct-current cardioversion (DCCV) using 2 sets of pads, with each pair simultaneously delivering 200 J, with traditional single 200-J DCCV using 1 set of pads in patients with obesity and atrial fibrillation. Design, Setting, and Participants: This was a prospective, investigator-initiated, patient-blinded, randomized clinical trial spanning 3 years from August 2020 to 2023. As a multicenter trial, the setting included 3 sites in Louisiana. Eligibility criteria included body mass index (BMI) of 35 or higher (calculated as weight in kilograms divided by height in meters squared), age 18 years or older, and planned nonemergent electrical cardioversion for atrial fibrillation. Patients who met inclusion criteria were randomized 1:1. Exclusions occurred due to spontaneous cardioversion, instability, thrombus, or BMI below threshold. Interventions: Dual DCCV vs single DCCV. Main Outcomes and Measures: Return to sinus rhythm, regardless of duration, immediately after the first cardioversion attempt of atrial fibrillation, adverse cardiovascular events, and chest discomfort after the procedure. Results: Of 2079 sequential patients undergoing cardioversion, 276 met inclusion criteria and were approached for participation. Of these, 210 participants were randomized 1:1. After exclusions, 200 patients (median [IQR] age, 67.6 [60.1-72.4] years; 127 male [63.5%]) completed the study. The mean (SD) BMI was 41.2 (6.5). Cardioversion was successful more often with dual DCCV compared with single DCCV (97 of 99 patients [98%] vs 87 of 101 patients [86%]; P = .002). Dual cardioversion predicted success (odds ratio, 6.7; 95% CI, 3.3-13.6; P = .01). Patients in the single cardioversion cohort whose first attempt failed underwent dual cardioversion with all subsequent attempts (up to 3 total), all of which were successful: 12 of 14 after second cardioversion and 2 of 14 after third cardioversion. There was no difference in the rating of postprocedure chest discomfort (median in both groups = 0 of 10; P = .40). There were no cardiovascular complications. Conclusions and Relevance: In patients with obesity (BMI ≥35) undergoing electrical cardioversion for atrial fibrillation, dual DCCV results in greater cardioversion success compared with single DCCV, without any increase in complications or patient discomfort. Trial Registration: ClinicalTrials.gov Identifier: NCT04539158.


Assuntos
Fibrilação Atrial , Cardioversão Elétrica , Obesidade , Humanos , Fibrilação Atrial/terapia , Masculino , Cardioversão Elétrica/métodos , Feminino , Obesidade/complicações , Obesidade/terapia , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Resultado do Tratamento , Índice de Massa Corporal
14.
Res Sq ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38313290

RESUMO

Background: Adolescents aged 10-19, living with HIV (ALHIV) lag behind in attaining optimal viral load suppression (VLS) rates and retention in care, an important impediment to reaching epidemic control. This study aimed to identify barriers and facilitators to both VLS and retention among in the sub-population who seek care from TASO Mbale and TASO Soroti centers of excellence, to facilitate adaptation of the operation triple zero in the setting. Methods: We used a mixed methods approach, extracting secondary data on ALHIV who were active in care during April-June 2022 quarter to determine one year retention in care. Analysis was done in STATA Corp, 15.0. We used logistic regression to determine associated factors and adjusted odds ratio (aOR) to report level of predictability, using 95% confidence interval (CI) and P<0.05 for statistical significance. For qualitative component, purposive sampling of 59 respondents was done. Focused group discussions, key informant interviews, and in-depth interviews were used to collect data. Thematic content analysis was done using Atlas ti. Results: There were 533 ALHIV, with 12-month retention rate of 95.9% and VLS rate of 74.9%. Predictors for good VLS included good adherence [aOR:95%CI 0.066(0.0115, 0.38) P=0.02], being on first line treatment [aOR:95%CI 0.242 (0.0873,0.6724) P=0.006]. For retention, they include being a school going [aOR:95%CI 0.148(0.024,0.9218) P=0.041], multi month dispensing aOR:95%CI 32.6287(5.1446,206.9404) P<0.001, OVC enrolment aOR:95%CI 0.2625(0.083, 0.83) P=0.023]. Meanwhile key barriers included: individual ones such as internal stigma, lack of transport and treatment/drug fatigue; facility-level such as prolonged waiting time and lack of social activities; community level include stigma and discrimination, inadequate social support and food shortage. In terms of facilitators, individual level ones include good adherence and knowledge of one's HIV status; facility-level such as provision of adolescent friendly services and community-level such as social support and decent nutrition. Conclusions: VLS rate was sub-optimal mainly due to poor adherence. HIV programs could utilize the barriers and facilitators identified to improve VLS. Conversely, retention rate at one year was good, likely due to provision of adolescent friendly health services. ALHIV and their caregivers need to be empowered to sustain retention and improve VLS. Contributions to science: By accentuating the barriers and facilitators to retention and VLS among the ALHIV, we ensure HIV programs continue to prioritize effective interventions and discard others as the epidemic evolves. To this, our findings strategically validate the effectiveness of provision of adolescent friendly services and client-centered care in attaining good retention rate.Secondly, being a mixed-methods study, complementarily adds value to the existing body of knowledge on barriers and facilitators while reminding programmers that VLS remains sub-optimal and more efforts are necessary.Finally, different stakeholders could use our findings to advocate for more resources to address some of the barriers such as food shortage, empowerment of ALHIV and caregivers and strengthening skilling programs for ALHIV, especially the out-of-school.

15.
Urol Nurs ; 32(1): 29-37, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22474863

RESUMO

The use of indwelling urinary catheters in hospitalized patients presents an increased risk of the development of complications, including catheter-associated urinary tract infection (CAUTI). With regard to the risk of developing a CAUTI, the greatest factor is the length of time the catheter is in situ. The aim of this article is to review the evidence on the prevention of CAUTI, particularly ways to ensure timely removal of indwelling catheters. Published studies evaluating interventions to reduce the duration of catheterization and CAUTI in hospitalized patients were retrieved. The research identified two types of strategies to reduce the duration of indwelling urinary catheters and the incidence of CAUTI: nurse-led interventions and informatics-led interventions, which included two subtypes: computerized interventions and chart reminders. Current evidence supports the use of nurse-led and informatics-led interventions to reduce the length of catheterizations and subsequently the incidence of CAUTI.


Assuntos
Infecção Hospitalar , Controle de Infecções/métodos , Cateterismo Urinário , Infecções Urinárias , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/enfermagem , Infecção Hospitalar/prevenção & controle , Humanos , Incidência , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/enfermagem , Cateterismo Urinário/estatística & dados numéricos , Infecções Urinárias/epidemiologia , Infecções Urinárias/enfermagem , Infecções Urinárias/prevenção & controle
16.
Curr Probl Cardiol ; 47(9): 101266, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35644503

RESUMO

Left atrial appendage (LAA) occlusion devices provided an acceptable and valid alternative to anticoagulation among patients with atrial fibrillation who carry high bleeding risk. Watchman device is non-inferior to oral anticoagulation to prevent cerebrovascular accidents. The presence of a longer distal portion of the older generation Watchman led to exclusion of patients with prohibitive anatomy of the LAA such as chicken-wing morphology or shallow LAA. Watchman FLX provides a wider range of sizes and can be implanted with complex anatomy or shallow LAA. In the case series, we discuss 3 patients with challenging LAA anatomy that underwent successful Watchman FLX implantation.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Acidente Vascular Cerebral , Anticoagulantes , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Cateterismo Cardíaco , Humanos , Desenho de Prótese , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
17.
J Interv Card Electrophysiol ; 65(1): 141-151, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35536500

RESUMO

BACKGROUND: The EnSite Precision™ cardiac mapping system (Abbott) is a catheter navigation and mapping system capable of displaying the three-dimensional (3D) position of conventional and sensor-enabled electrophysiology catheters, as well as displaying cardiac electrical activity as waveform traces and dynamic 3D maps of cardiac chambers. The EnSite Precision™ Observational Study (NCT-03260244) was designed to quantify and characterize the use of the EnSite Precision™ cardiac mapping system for mapping and ablation of cardiac arrhythmias in a real-world environment and evaluate procedural outcomes. METHODS: A total of 1065 patients were enrolled at 38 centers in the USA and Canada between 2017 and 2018 and were followed for 12 months post procedure for arrhythmia recurrence, medication use, and quality-of-life changes. Eligible subjects were adults undergoing a cardiac electrophysiology mapping and radiofrequency ablation procedure using the EnSite Precision™ System. RESULTS: A final cohort of 925 patients (64.3 years of age, 30.2% female) were analyzed. The primary procedural indication was atrial flutter in 48.1% (445/925), atrial fibrillation in 46.5% (430/925), and other arrhythmias in 5% (50/925). Electroanatomic mapping was performed in 81.5% (754/925) of patients. Mapping was stable throughout 79.8% (738/925) of procedures with initial mapping time of 8.6 min (IQR 4.7-15.0). Average mapping efficiency created with AutoMap or TurboMap was 164.9 ± 365.7 used points per minute. Median number of mapping points collected and used was 1752.5 and 811.0, respectively. Only 335/925 (36.2%) required editing and 66.0% (221/335) of these patients required editing of less than 10 points. Fluoroscopy was utilized in most cases (n = 811/925, 87.4%) with fluoroscopy time of 11.0 min (IQR 6.0-18.0). Overall median procedure time was 101.0 min (IQR 59.0-152.0). Acute procedural success was high for both atrial fibrillation (n = 422/430, 98.1%) and atrial flutter (n = 434/445, 97.5%). CONCLUSION: In a real-world study analysis, use of the EnSite Precision™ mapping system was associated with high procedural stability, short mapping times, high point density requiring infrequent editing, low fluoroscopy time, and high prevalence of acute procedural success.


Assuntos
Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Adulto , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Flutter Atrial/diagnóstico por imagem , Flutter Atrial/cirurgia , Eletrofisiologia Cardíaca , Ablação por Cateter/métodos , Feminino , Fluoroscopia , Humanos , Masculino , Resultado do Tratamento
18.
Heart Fail Clin ; 7(2): 241-50, ix, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21439502

RESUMO

Use of implantable cardioverter defibrillators (ICDs) and/or cardiac resynchronization therapy reduces mortality among several high-risk cohorts, primarily those with left ventricular systolic dysfunction and heart failure. Since the advent of these technologies, concerns regarding the high initial costs of device implantation have been considered a potential barrier to widespread adoption. Despite such concerns, the use of these devices for primary or secondary prevention of sudden cardiac death seems to be cost-effective when compared with national standards. Moreover, ICDs have been shown to be cost-effective in several health care systems and specialized populations such as those with high-risk long QT syndrome and hypertrophic cardiomyopathy.


Assuntos
Estimulação Cardíaca Artificial/economia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis/economia , Insuficiência Cardíaca/terapia , Análise Custo-Benefício , Progressão da Doença , Insuficiência Cardíaca/economia , Humanos , Prevenção Primária , Anos de Vida Ajustados por Qualidade de Vida , Prevenção Secundária , Estados Unidos
19.
Prog Cardiovasc Dis ; 66: 80-85, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34332663

RESUMO

Atrial Fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF) frequently coexist, resulting in significant morbidity and mortality. Therapeutic options for patients with AF and HFrEF are limited due to few antiarrhythmic drug (AAD) choices and historically equivocal effects of procedural interventions on mortality. However, recent randomized trials examining catheter ablation (CA) in AF patients with HFrEF have shown a beneficial effect on arrhythmic burden and HF symptoms, as well as an improvement in mortality. This review focuses on the role of CA for AF patients with HFrEF.


Assuntos
Fibrilação Atrial/terapia , Ablação por Cateter , Insuficiência Cardíaca/fisiopatologia , Potenciais de Ação , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Frequência Cardíaca , Humanos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
20.
Prog Cardiovasc Dis ; 66: 37-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34332660

RESUMO

Aortic stenosis is the most common valvulopathy requiring replacement by means of the surgical or transcatheter approach. Transcatheter aortic valve replacement (TAVR) has quickly become a viable and often preferred treatment strategy compared to surgical aortic valve replacement. However, transcatheter heart valve system deployment not infrequently injures the specialized electrical system of the heart, leading to new conduction disorders including high-grade atrioventricular block and complete heart block (CHB) necessitating permanent pacemaker implantation (PPI), which may lead to deleterious effects on cardiac function and patient outcomes. Additional conduction disturbances (e.g., new-onset persistent left bundle branch block, PR/QRS prolongation, and transient CHB) currently lack clearly defined management algorithms leading to variable strategies among institutions. This article outlines the current understanding of the pathophysiology, patient and procedural risk factors, means for further risk stratification and monitoring of patients without a clear indication for PPI, our institutional approach, and future directions in the management and evaluation of post-TAVR conduction disturbances.


Assuntos
Estenose da Valva Aórtica/cirurgia , Arritmias Cardíacas/terapia , Estimulação Cardíaca Artificial , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Marca-Passo Artificial , Substituição da Valva Aórtica Transcateter/efeitos adversos , Potenciais de Ação , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/fisiopatologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Humanos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
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