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BACKGROUND: Aortic stenosis (AS) and mitral regurgitation (MR) result in different patterns of left ventricular remodeling and hypertrophy. OBJECTIVES: We characterized left ventricular wall stress (LVWS) profiles in pressure and volume-overloaded systems, examined the relationship between baseline LVWS and cardiac remodeling, and assessed the acute effects of valve intervention on LVWS using invasive pressures combined with cardiac magnetic resonance (CMR) imaging measures of left ventricular volumes/mass. METHODS: A total of 47 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) and 15 patients with severe MR undergoing MitraClip (MC) underwent a 6-minute walk test (6MWT), transthoracic echocardiogram, and CMR before their procedures. Catheters in the left ventricle were used to record hemodynamic changes before and after valve/clip deployment. This was integrated with CMR data to calculate LVWS before and after intervention. RESULTS: The TAVR group demonstrated significant reductions in systolic LVWS post procedure (median 24.7 Pa [IQR: 14 Pa] pre vs median 17.3 Pa [IQR: 12 Pa] post; P < 0.001). The MC group demonstrated significant reductions in diastolic LVWS (median 6.4 Pa [IQR: 5 Pa] pre vs median 4.3 Pa [IQR: 4.1 Pa] post; P = 0.021) with no significant change in systolic LVWS (30.6 ±1.61 pre vs 33 ±2.47 Pa post; P = 0.16). There was an inverse correlation between baseline systolic LVWS and 6MWT in the TAVR group (r = -0.31; P = 0.04). CONCLUSIONS: TAVR results in significant reductions in systolic LVWS acutely. MC results in significant reductions in diastolic LVWS. Higher baseline systolic LVWS in TAVR is associated with shorter 6MWT suggesting that in AS, LVWS may be a useful marker of early decompensation.
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Estenosis de la Válvula Aórtica , Insuficiencia de la Válvula Mitral , Reemplazo de la Válvula Aórtica Transcatéter , Remodelación Ventricular , Humanos , Masculino , Femenino , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Anciano , Remodelación Ventricular/fisiología , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Anciano de 80 o más Años , Imagen por Resonancia Cinemagnética/métodos , Ecocardiografía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatologíaRESUMEN
Objective: To quantify proportions of loss to follow-up in patients presenting with a pregnancy of unknown location and explore patients' perspectives on follow-up for pregnancy of unknown location. A pregnancy of unknown location is a scenario in which a patient has a positive pregnancy test but the pregnancy is not visualized on transvaginal ultrasound. Study Design: We conducted a retrospective cohort study of patients with pregnancy of unknown location who presented to an urban academic emergency department or complex family planning outpatient office. We sought to calculate the proportion of patients lost to follow-up, defined as inability to contact the patient within 2 weeks. We then conducted focus groups of patients diagnosed with a pregnancy of unknown location. We used thematic analysis to identify themes related to follow-up. Results: We reviewed 464 charts of patients diagnosed with pregnancy of unknown location. The median age in this cohort was 27 with most patients identifying as Black (80%, n = 370) and using public insurance (67%, n = 315). When looking at loss to follow-up rates, Black patients experienced loss to follow-up (20%, n = 72) more often than White patients (4%, n = 2; p = 0.003). Focus group participants had a mean age of 31.8+/-4.8, and the majority were of Black race (n = 16, 72.7%). Participants identified barriers to follow-up including the long duration of management, general inconvenience, and poor communication with their health care team. Participants felt a burden of responsibility to learn about their condition and to self-advocate for their follow-up and communication of results. Conclusions: These data indicate that Black patients are more likely to experience loss to follow-up compared with White patients during monitoring for pregnancy of unknown location. Patients identified many barriers to follow-up and felt that successful follow-up required substantial self-efficacy.
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BACKGROUND: Women 18-24 years of age have the highest proportion of unintended pregnancies of any age group, and thus represent a significant population in need of abortion services. Prior research indicated that only half of college student health centers provide appropriate abortion referrals. Our objective was to better understand the referral experience and barriers to abortion referral at college student health centers. PROCEDURES: We conducted a "secret caller" study at all 4-year colleges in Pennsylvania between June 2017 and April 2018, using a structured script requesting abortion referral. Calls were transcribed, coded using an iteratively developed codebook, and analyzed for themes related to barriers and facilitators of abortion referral. MAIN FINDINGS: A total of 202 completed transcripts were reviewed. Themes that emerged were knowledge, experience, and comfort with abortion referral; support, empathy, and reassurance; coercion; misleading language; questioning the caller's autonomy; and institutional policy against referral. Most staff lacked knowledge and comfort with abortion referral. Although some staff members made supportive statements toward the caller, others used coercive language to try to dissuade the caller from an abortion. Many staff cited religious institutional policies against abortion referral and expressed a range of feelings about such policies. CONCLUSIONS: Abortion referrals at student health centers lack consistency. Staff members frequently did not have the knowledge needed to provide appropriate abortion referrals, used coercive language in responding to requests for referrals, and perpetuated abortion stigma. Some health staff used coercive or evasive language that further stigmatized the caller's request for an abortion referral. College health centers should improve training and resources around abortion referral to ensure they are delivering appropriate, high-quality care.
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Aborto Inducido , Embarazo , Humanos , Femenino , Embarazo no Planeado , Derivación y Consulta , Pennsylvania , EstudiantesRESUMEN
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the commonest genetic cardiomyopathy and may result in sudden cardiac death (SCD). Clinical risk stratification scores are utilised to estimate SCD risk and determine potential utility of a primary prevention implantable cardioverter defibrillator (ICD). METHODS: Patients with a confirmed diagnosis of HCM from a quaternary HCM service were defined according to clinical characteristics, genetic profiles and cardiac imaging results. European Risk-SCD score and American Heart Association / American College of Cardiology (AHA/ACC) Score were calculated. The primary outcome was cardiac arrest. RESULTS: 380 patients with HCM were followed up for a median of 6.4 years. 18 patients (4.7%) experienced cardiac arrest, with predictive factors being younger age (37.2 vs 54.4 years, p = 0.0041), unexplained syncope (33.3% vs 9.4%, p = 0.007), non-sustained ventricular tachycardia (50.0% vs 12.7%, p < 0.0001), increased septal thickness (21.5 vs 17.5 mm, p = 0.0003), and presence of a sarcomeric gene mutation (100.0% vs 65.8%, p = 0.038). The Risk-SCD and AHA/ACC scores had poor agreement (kappa coefficient 0.38). Risk-SCD score had poor sensitivity (44.4%), classifying 55.6% of patients with cardiac arrest as low-risk but was highly specific (93.7%). AHA/ACC risk score did not discriminate between groups significantly. 20 patients (5.3%) died, with most >60-year-olds having a non-cardiac cause of death (p = 0.0223). CONCLUSION: This study highlights limited (38%) agreement between the Risk-SCD and AHA/ACC scores. Most cardiac arrests occurred in ostensibly low or medium-risk patients under both scores. Appropriate ICD selection remains challenging. Incorporating newer risk markers such as HCM genotyping and myocardial fibrosis quantification by cardiac MRI may assist future risk refinement.
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Cardiomiopatía Hipertrófica , Desfibriladores Implantables , Humanos , Persona de Mediana Edad , Medición de Riesgo/métodos , Factores de Riesgo , Desfibriladores Implantables/efectos adversos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/genéticaRESUMEN
BACKGROUND: An intramyometrial pregnancy is a rare form of ectopic pregnancy, making up an estimated 1% of all ectopic pregnancies. Previously described management options have included surgical excision in the emergency setting. CASE: A 32-year-old woman, gravida 4 para 0, at 6 0/7 weeks of gestation by last menstrual period, was noted to have a gestational sac implanted entirely within the uterine myometrium. Ultrasonography and magnetic resonance imaging confirmed the presence of an intramyometrial ectopic pregnancy within a septate uterus. The patient's abnormal pregnancy was successfully treated with multidose methotrexate. CONCLUSION: Intramyometrial pregnancy is a rare entity that should be considered when it is suggested by ultrasonography or if an intrauterine pregnancy is surgically inaccessible from the endometrial cavity. In a stable patient, multidose systemic methotrexate may be a feasible management strategy.
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Embarazo Ectópico , Útero Septado , Embarazo , Femenino , Humanos , Adulto , Metotrexato/uso terapéutico , Embarazo Ectópico/diagnóstico por imagen , Embarazo Ectópico/cirugía , Útero/diagnóstico por imagen , Útero/patología , Miometrio/patologíaRESUMEN
OBJECTIVES: This study aimed to evaluate the feasibility and acceptability of virtual group contraceptive counseling in the abortion care setting. STUDY DESIGN: Patients seeking abortion care at an urban university hospital were invited to participate in this cohort study. Prior to their clinical appointments, groups of two to six patients participated in 45-minute virtual contraceptive counseling visits facilitated by study staff. Contraceptive method use, effectiveness, and side effects were reviewed according to group interest. Participant satisfaction scores were collected immediately following the sessions. After their appointments, providers estimated the time spent on contraceptive counseling during the clinical visit. RESULTS: Of 195 patients approached, 86 (44%) were enrolled. Fifty-seven (66%) enrolled patients completed a session. The most common reason for declining enrollment was concern about the time commitment. Most (93%) participants reported being "satisfied" or "very satisfied" overall, and 96% would recommend group contraceptive counseling to a friend. Providers reported that compared to typical counseling, participants required a shorter amount of time during the clinical visit than nonparticipants (time spent <5 minutes: 74% vs 54%). CONCLUSIONS: Virtual group contraceptive counseling for patients seeking abortion was feasible and acceptable in this study. Group virtual visits may reduce provider time burden, add value when virtual care delivery is desired or required, and deserve further study. IMPLICATIONS: Family planning clinics can consider incorporating virtual group counseling as a person-centered and efficient approach to contraceptive counseling at the time of abortion care.
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Aborto Espontáneo , Anticonceptivos , Embarazo , Femenino , Humanos , Anticonceptivos/uso terapéutico , Estudios de Cohortes , Estudios de Factibilidad , Anticoncepción/métodos , Consejo/métodos , Servicios de Planificación FamiliarRESUMEN
BACKGROUND: Worldwide, the cardiology profession has an under-representation of women. We assessed medical students' perceptions of cardiology as a career choice with the aim of identifying barriers to gender diversity. METHOD: An anonymous survey was distributed to medical students studying at three Australian medical universities. Questions pertained to demographics, year and stage of medical training, desire to pursue cardiology, and perceived barriers to a cardiology career. Results were analysed according to identified gender and desire to pursue or not pursue a cardiology career. Multivariable logistic regression evaluated for independent associations. The primary outcome were barriers identified to pursuing a career in cardiology. RESULTS: From 127 medical student respondents (86.6% female, mean age 25.9±4.8 years), 37.0% stated they wanted to pursue a career in cardiology (39.1% of women versus 23.5% of men, p=0.54). The top four perceived barriers to a cardiology career included: poor work-life balance (92/127, 72.4%), physician training process (63/127, 49.6%), on-call requirements (50/127, 39.4%) and lack of flexibility (49/127, 38.6%), with no gender differences. Women were more likely to report gender-related barriers (37.3% versus 5.9%, p=0.01) and less likely to identify procedural aspects as a barrier (5.5% women versus 29.4% men, p=0.001). Students in their pre-clinical years were more likely to want a career in cardiology (odds ratio 3.0, 95% confidence interval 1.2-7.7, p=0.02). CONCLUSIONS: A high proportion of female and male medical students want to pursue a career in cardiology with both genders identifying major barriers of poor work-life balance, lack of flexibility, on-call requirements and the training process.
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Cardiología , Estudiantes de Medicina , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Factores Sexuales , Australia/epidemiología , Selección de Profesión , Encuestas y CuestionariosRESUMEN
We present the case of acute myocardial infarction secondary to spontaneous coronary artery dissection in a patient 2 weeks post orthotopic heart transplantation. (Level of Difficulty: Advanced.).
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BACKGROUND: Early pregnancy loss, also referred to as miscarriage, is common, affecting approximately 1 million people in the United States annually. Early pregnancy loss can be treated with expectant management, medications, or surgical procedures-strategies that differ in patient experience, effectiveness, and cost. One of the medications used for early pregnancy loss treatment, mifepristone, is uniquely regulated by the Food and Drug Administration. OBJECTIVE: This study aimed to compare the cost-effectiveness from the healthcare sector perspective of medical management of early pregnancy loss, using the standard of care medication regimen of mifepristone and misoprostol, with that of office uterine aspiration. STUDY DESIGN: We developed a decision analytical model to compare the cost-effectiveness of early pregnancy loss treatment with medical management with that of office uterine aspiration. Data on medical management came from the Pregnancy Failure Regimens randomized clinical trial, and data on uterine aspiration came from the published literature. The analysis was from the healthcare sector perspective with a 30-day time horizon. Costs were in 2018 US dollars. Effectiveness was measured in quality-adjust life-years gained and the rate of complete gestational sac expulsion with no additional interventions. Our primary outcome was the incremental cost per quality-adjust life-year gained. Sensitivity analysis was performed to identify the key uncertainties. RESULTS: Mean per-person costs were higher for uterine aspiration than for medical management ($828 [95% confidence interval, $789-$868] vs $661 [95% confidence interval, $556-$766]; P=.004). Uterine aspiration more frequently led to complete gestational sac expulsion than medical management (97.3% vs 83.8%; P=.0001); however, estimated quality-adjust life-years were higher for medical management than for uterine aspiration (0.082 [95% confidence interval, 0.8148-0.08248] vs 0.079 [95% confidence interval, 0.0789-0.0791]; P<.0001). Medical management dominated uterine aspiration, with lower costs and higher confidence interval. The probability that medical management is cost-effective relative to uterine aspiration is 97.5% for all willingness-to-pay values of ≥$5600/quality-adjust life-year. Sensitivity analysis did not identify any thresholds that would substantially change outcomes. CONCLUSION: Although office-based uterine aspiration more often results in treatment completion without further intervention, medical management with mifepristone pretreatment costs less and yields similar quality-adjust life-years, making it an attractive alternative. Our findings provided evidence that increasing access to mifepristone and eliminating unnecessary restrictions will improve early pregnancy care.
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Aborto Espontáneo , Misoprostol , Embarazo , Femenino , Humanos , Aborto Espontáneo/tratamiento farmacológico , Mifepristona/uso terapéutico , Análisis Costo-Beneficio , Misoprostol/uso terapéutico , Quimioterapia CombinadaRESUMEN
BACKGROUND: The East Timor Hearts Fund has provided cardiac services in Timor-Leste since 2010, conducting three clinics yearly. AIM: To develop collaborative telehealth services between Australia and Timor-Leste in the context of international border closures due to the COVID-19 pandemic. METHODS: Scoping discussions identified major challenges (structural, patient related and medical system related). At two pilot clinics, patient history, investigation and management were collated. Clinic metrics were compared with an index face-to-face clinic in February 2019. Post-clinic discussions identified areas of success and shortfall in the conduct of the telehealth clinics. RESULTS: Twenty-three patients were reviewed at the online telehealth clinics held onsite at Timorese medical facilities. Compared with an index 2019 clinic, there were markedly lower numbers of new referrals (2 vs 190 patients; 8.7% vs 59.4%). Patients seen at the online clinic were predominantly female (17/23; 73.9%) and Dili based (18/23; 78.3%), with a mean age of 25.9 ± 7.2 years. The majority (12/23; 52.2%) had isolated rheumatic mitral valve disease. Investigations including electrocardiography, pathology, echocardiography and 6-min walk tests were conducted in select patients. Medication advice was provided for 10 (43.5%) patients. Eleven (47.8%) patients were deemed to require urgent intervention. Post-clinic discussions indicated general satisfaction with telehealth clinics, although frustration at the current inability to provide interventional services was highlighted. CONCLUSION: Our pilot telehealth clinics indicate that capacity-building telemedicine can be rapidly implemented in an emergency setting internationally. Clinic design benefits from careful identification and resolution of challenges to optimise flow. Cardiac patients in Timor-Leste have a significant burden of disease amenable to intervention.
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COVID-19 , Telemedicina , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Masculino , COVID-19/epidemiología , Timor Oriental/epidemiología , Inundaciones , PandemiasRESUMEN
Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, health care professionals have made swift accommodations to provide consistent and safe care, including emphasizing remote access to allow physical distancing. Depot medroxyprogesterone acetate intramuscular injection (DMPA-IM) prescription is typically administered by a health care professional, whereas DMPA-subcutaneous has the potential to be safely self-injected by patients, avoiding contact with a health care professional. However, DMPA-subcutaneous is rarely prescribed despite its U.S. Food and Drug Administration approval in 2004 and widespread coverage by both state Medicaid providers and many private insurers. Depot medroxyprogesterone acetate users are disproportionately non-White, and thus the restriction in DMPA-subcutaneous prescribing may both stem from and contribute to systemic racial health disparities. We review evidence on acceptability, safety, and continuation rates of DMPA-subcutaneous, consider sources of implicit bias that may impede prescription of this contraceptive method, and provide recommendations for implementing DMPA-subcutaneous prescribing.
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COVID-19 , Anticonceptivos Femeninos/administración & dosificación , Servicios de Planificación Familiar/estadística & datos numéricos , Acetato de Medroxiprogesterona/administración & dosificación , Aceptación de la Atención de Salud/estadística & datos numéricos , Anticoncepción/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos , Servicios de Planificación Familiar/métodos , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Disparidades en Atención de Salud/estadística & datos numéricos , Humanos , Inyecciones Subcutáneas , SARS-CoV-2 , Autoadministración , Estados UnidosRESUMEN
OBJECTIVE: Significant gender disparities exist in some medical specialties, particularly cardiology. We assessed work, personal life and work-life balance in women in cardiology in Australia and New Zealand (NZ), compared with other specialties, to determine factors that may contribute to the lack of women in the specialty. METHODS: This study is a prospective survey-based cohort study comparing cardiology and non-cardiology specialties. An online survey was completed by female doctors in Australia and NZ, recruited via email lists and relevant social media groups. The survey included demographics, specialty, stage of training, work hours/setting, children and relationships, career satisfaction, income and perceptions of specialty. RESULTS: 452 participants completed the survey (median age 36 years), of which 57 (13%) worked in cardiology. Of all respondents, 84% were partnered and 75% had children, with no difference between cardiology and non-cardiology specialties. Compared with non-cardiology specialties, women in cardiology worked more hours per week (median 50 hours vs 40 hours, p<0.001), were more likely to be on call more than once per week (33% vs 12%, p<0.001) and were more likely to earn an annual income >$3 00 000 (35% vs 10%, p<0.001). Women in cardiology were less likely to agree that they led a balanced life (33% vs 51%, p=0.03) or that their specialty was female friendly (19% vs 75%, p<0.001) or family friendly (20% vs 63%, p<0.001). CONCLUSIONS: Compared with other specialties, women in cardiology reported poorer work-life balance, greater hours worked and on-call commitments and were less likely to perceive their specialty as female friendly or family friendly. Addressing work-life balance may attract and retain more women in cardiology.
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Cardiólogos/estadística & datos numéricos , Cardiología/estadística & datos numéricos , Satisfacción en el Trabajo , Encuestas y Cuestionarios , Equilibrio entre Vida Personal y Laboral/estadística & datos numéricos , Lugar de Trabajo/estadística & datos numéricos , Adulto , Selección de Profesión , Humanos , Masculino , Médicos Mujeres/estadística & datos numéricos , Estudios ProspectivosRESUMEN
OBJECTIVE: This study was aimed to evaluate opioid use after cesarean delivery (CD) and to assess implementation of an enhanced recovery after CD (ERAS-CD) pathway and its association with inpatient and postdischarge pain control and opioid use. STUDY DESIGN: We conducted a baseline survey of women who underwent CD from January to March 2017 at a single, urban academic hospital. Patients were called 5 to 8 days after discharge and asked about their pain and postdischarge opioid use. An ERAS-CD pathway was implemented as a quality improvement initiative, including use of nonopioid analgesia and standardization of opioid discharge prescriptions to ≤25 tablets of oxycodone of 5 mg. From November to January 2019, a postimplementation survey was conducted to assess the association between this initiative and patients' pain control and postoperative opioid use, both inpatient and postdischarge. RESULTS: Data were obtained from 152 women preimplementation (PRE) and 137 women post-implementation (POST); complete survey data were obtained from 102 women PRE and 98 women POST. The median inpatient morphine milligram equivalents consumed per patient decreased significantly from 141 [range: 90-195] PRE to 114 [range: 45-168] POST (p = 0.002). On a 0- to 10-point scale, median patient-reported pain scores at discharge decreased significantly (PRE: 7 [range: 5-8] vs. POST 5 [range: 3-7], p < 0.001). The median number of pills consumed after discharge also decreased significantly (PRE: 25 [range: 16-30] vs. POST 17.5 [range: 4-25], p = 0.001). The number of pills consumed was significantly associated with number prescribed (p < 0.001). The median number of leftover pills and number of refills did not significantly differ between groups. Median patient-reported pain scores at the week after discharge were lower in the POST group (PRE: 4 [range: 2-6] vs. POST 3[range: 1-5], p = 0.03). CONCLUSION: Implementing an ERAS-CD pathway was associated with a significant decrease in inpatient and postdischarge opioid consumption while improving pain control. Our data suggest that even fewer pills could be prescribed for some patients. KEY POINTS: · An ERAS-CD pathway was associated with decreased opioid use.. · Outpatient opioid consumption after cesarean warrants further study.. · Physician prescribing drives patients' opioid consumption..
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Analgésicos no Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Cesárea/efectos adversos , Oxicodona/uso terapéutico , Manejo del Dolor/normas , Dolor Postoperatorio/tratamiento farmacológico , Centros Médicos Académicos , Adulto , Vías Clínicas , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Manejo del Dolor/métodos , Dimensión del Dolor , Adulto JovenRESUMEN
BACKGROUND: Binge drinking is a common atrial fibrillation (AF) trigger, however the mechanisms are poorly understood. OBJECTIVE: To investigate the effects of alcohol intoxication and hangover with rhythm monitoring and cardiac MRI. METHODS: Patients underwent serial cardiac MRI pre- and post-binge with continuous Holter monitoring. Time periods analyzed: baseline (24 h pre-binge), consumption, hangover (0- 24 h post-consumption) and post-hangover (24-48 h post-consumption). RESULTS: 50 patients (age 49 ± 15 years, 40% paroxysmal AF) completed the study (intake 8.4 ± 3.1 standard drinks). Mean heart rate increased from 72 ± 10 to 80 ± 13 beats per minute (bpm) during consumption (p < 0.001). The hangover period was characterised by higher daily atrial ectopic count (50, IQR 10-132 vs baseline 43, IQR 10-113; p = 0.04) and reduced heart rate variability (SDNN 55 ms, IQR 40-65 versus 62 ms, IQR 51-66; p = 0.007). There was evidence of heightened parasympathetic activity post-hangover with heart rate slowing (mean HR 54 ± 6 bpm; p = 0.03) and increased activity in the High frequency band when separating the complex heart rate variability waveform into its component rhythms (291 ms2, 97-538 versus baseline 237 ms2, IQR 104-332; p = 0.04). Three patients developed AF 11, 29 and 34 h post-binge. Cardiac MRI (2.7 ± 0.7 days post-binge) demonstrated a decrease in left atrial (LA) emptying fraction (57.9 ± 8.5 to 53.5 ± 6.7%; p = 0.003) but no change in LA volume, left ventricular ejection fraction or markers of ventricular inflammation. CONCLUSION: Binge drinking is associated with sympathetic activation followed by a 'rebound' parasympathetic response and atrial mechanical dysfunction which may explain the propensity and temporal association between binge drinking and AF.
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Fibrilación Atrial , Consumo Excesivo de Bebidas Alcohólicas , Adulto , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/epidemiología , Consumo Excesivo de Bebidas Alcohólicas/diagnóstico por imagen , Consumo Excesivo de Bebidas Alcohólicas/epidemiología , Frecuencia Cardíaca , Vacaciones y Feriados , Humanos , Persona de Mediana Edad , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab. METHODS: This observational, dose-finding study was done in a clinical trials facility in Melbourne (VIC, Australia). Groups of healthy volunteers aged 18-40 years, at low risk of complicated S pyogenes disease, and without high type-specific anti-emm75 IgG antibodies against the challenge strain were challenged and closely monitored as inpatients for up to 6 days, and then as outpatients for 6 months. Antibiotics were started upon diagnosis (clinical signs and symptoms of pharyngitis and a positive rapid molecular test) or after 5 days in those without pharyngitis. Rapid test results were confirmed by standard bacterial culture. After a sentinel participant, cohorts of five and then ten participants were challenged, with protocol-directed dose-escalation or de-escalation for subsequent cohorts. The primary outcome was the proportion of participants at each dose level with pharyngitis by day 5 after challenge. The study is registered with ClinicalTrials.gov, NCT03361163. FINDINGS: Between July 10, 2018, and Sept 23, 2019, 25 healthy adults were challenged with emm75 S pyogenes and included in analyses. Pharyngitis was diagnosed in 17 (85%; 95% CI 62-97) of 20 participants at the starting dose level (1-3 × 105 colony-forming units [CFU]/mL). This high proportion prompted dose de-escalation. At the lower dose level (1-3 × 104 CFU/mL), pharyngitis was diagnosed in one of five participants. Immunological, biochemical, and microbiological results supported the clinical picture, with acute symptomatic pharyngitis characterised by pharyngeal colonisation by S pyogenes accompanied by significantly elevated C-reactive protein and inflammatory cytokines (eg, interferon-γ and interleukin-6), and modest serological responses to streptolysin O and deoxyribonuclease B. There were no severe (grade 3) or serious adverse events related to challenge. INTERPRETATION: We have established a reliable pharyngitis human infection model with reassuring early safety findings to accelerate development of vaccines and other interventions to control disease due to S pyogenes. FUNDING: Australian National Health and Medical Research Council.
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Faringitis , Escarlatina , Adulto , Australia , Humanos , Faringitis/tratamiento farmacológico , Faringe/microbiología , Streptococcus pyogenesRESUMEN
BACKGROUND: The World Health Organisation previously recommended routine screening in school-aged children in countries with a high prevalence of rheumatic heart disease (RHD); however, it is unclear if screening-detected (latent) valve disease will inevitably evolve to a pathological lesion. Understanding the natural history of latent RHD is essential prior to recommendation of screening in endemic areas. Studies documenting the progression of latent RHD have had contrasting conclusions about the pathogenicity of latent valvular lesions. This review provides estimates of rates of progression of latent RHD. METHODS AND FINDINGS: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, Global Index Medicus, Africa Wide, Cochrane Database of Systematic Reviews and Global Health Database for studies published before April 30, 2019. Study data were extracted from all studies which reported follow-up data on progression of latent valve lesions. Studies with control cohorts were used to calculate comparative prevalence ratios. This study is registered with PROSPERO, number CRD42019119427. We identified 12 studies reporting follow-up data on latent RHD for 950 people in 9 countries. The estimated pooled prevalence rate for progression per year of latent RHD was 5%/year (95% CI 2-8). Eight studies reported on the progression of borderline latent RHD with an estimated pooled prevalence of 2%/year (95% CI 0-4). Three studies included control groups. There was a significant increase in the risk of progression of valvular disease in the latent group compared with controls (RR = 3.57 (95%CI = 1.65-7.70, P = 0.001). The overall risk of bias was low. Given most studies included penicillin administration we were unable to document the natural history of latent RHD. Furthermore, we were unable to perform a sensitivity analysis to determine the effect of administering penicillin prophylaxis on progression of valve disease given prescription of penicillin was not standardised. CONCLUSION: Latent RHD has a slow rate of progression but it is significantly higher compared to controls, with definite latent RHD having a higher rate of progression compared with borderline latent disease. There are a massive number of individuals at risk for RHD in the developing world as well as logistical challenges of screening and delivering penicillin prophylaxis. The low rate of progression from untargeted screening may be an important consideration in resource-constrained environments.