Skin sympathetic nerve activity in symptomatic and asymptomatic paroxysmal atrial fibrillation.

BACKGROUND: It remains unclear what causes symptoms in patients with paroxysmal atrial fibrillation (AF). OBJECTIVE: This study aimed to correlate the magnitudes of the skin sympathetic nerve activity (SKNA) with symptoms in patients with AF. METHODS: We prospectively enrolled patients with symptomatic paroxysmal AF for ambulatory electrocardiogram and SKNA recording. Heart rhythms at time of symptoms were categorized as AF or normal sinus rhythm (NSR). Maximal and average SKNA (aSKNA) and heart rate (HR) were compared between symptomatic and asymptomatic AF and NSR episodes using mixed effects models to account for within-patient correlations. RESULTS: Among the 31 enrolled patients, 16 (52%) had at least one episode of AF, and 24 (77%) endorsed symptoms during the monitoring period. Compared with asymptomatic AF episodes, symptomatic AF episodes had higher maximal aSKNA (1.260 [IQR 1.114-1.723] µV vs. 1.108 [IQR 0.974-1.312] µV, p<0.001) and higher maximal HR (152±24 bpm vs. 132±19 bpm, p<0.001). Symptomatic NSR episodes were associated with higher maximal aSKNA (1.612 [IQR 1.287-2.027] µV vs. 1.332 [IQR 1.033-1.668] µV, p=0.001) and higher maximal HR (152±24 bpm vs. 105±16 bpm, p<0.001) than asymptomatic NSR episodes. Of the symptomatic episodes, 66 (73%) occurred during NSR and 24 (27%) during AF. All p-values were obtained from mixed effects models. CONCLUSION: Symptomatic episodes in patients with paroxysmal AF were more frequently associated with NSR than AF. Symptomatic AF and NSR episodes were associated with higher aSKNA than asymptomatic episodes. In patients with paroxysmal AF, symptoms correlate better with SKNA than heart rhythm.

Polymorphic ventricular tachycardia and cardiac arrest from abiraterone-induced hypokalemia: a case report.

BACKGROUND: Polymorphic ventricular tachycardia (PMVT) is an unstable and often fatal cardiac tachyarrhythmia. While there are many causes of this rhythm, including electrolyte imbalances, ischemia, and genetic disorders, iatrogenic etiologies are important to recognize. Abiraterone is an androgen synthesis antagonist effective in treating prostate cancer, but here we describe a case of severe hypokalemia secondary to abiraterone resulting in polymorphic ventricular tachycardia and cardiac arrest. While this is a potential adverse effect of the medication, severe hypokalemia causing polymorphic ventricular tachycardia and cardiac arrest, as seen in our patient's case, has not been described. CASE PRESENTATION: A 78-year-old African-American man with history of prostate cancer presents with polymorphic ventricular tachycardia and cardiac arrest. After resuscitation, he was found to be severely hypokalemic and refractory to large doses of repletion. Evaluation of secondary causes of hypokalemia identified the likely culprit to be adverse effects from prostate cancer treatment. CONCLUSION: A broad differential diagnosis for polymorphic ventricular tachycardia is essential in identifying and treating patients presenting in this rhythm. Here we present a case of iatrogenic polymorphic ventricular tachycardia secondary to oncologic treatment.

Risk Factors for the Development of New-Onset Persistent Atrial Fibrillation: Subanalysis of the VITAL Study.

BACKGROUND: Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF. METHODS: We prospectively examined the differential associations between lifestyle, clinical, and socioeconomic risk factors and AF pattern (persistent versus paroxysmal) at the time of diagnosis among 25 119 participants without a history of cardiovascular disease, AF, or cancer in the VITAL rhythm study (Vitamin D and Omega-3). RESULTS: During a median follow-up of 5.3 years, 900 participants developed AF and 346 (38.4%) were classified as persistent at the time of diagnosis. In multivariable competing risk models, increasing age, male sex, White race, height, weight, body mass index ≥30 kg/m2, hypertension, current or past smoking, alcohol intake ≥2 drinks/day, postcollege education, and randomized treatment with vitamin D were significantly associated with incident persistent AF. Compared with paroxysmal AF, increasing age, male sex, weight, body mass index ≥30 kg/m2, and postcollege education were more strongly associated with persistent AF in multivariable models regardless of whether interim cardiovascular disease and heart failure events were censored. CONCLUSIONS: In a prospective cohort without baseline AF or cardiovascular disease, over one-third of AF at the time of diagnosis is persistent. Older age, male sex, postcollege education, and obesity were preferentially associated with persistent AF and represent a high-risk AF subset for population-based intervention.

A highly efficient needle-free-injection delivery system for mRNA-LNP vaccination against SARS-CoV-2.

Despite the various vaccines that have been developed to combat the coronavirus disease 2019 (COVID-19) pandemic, the persistent and unpredictable mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) require innovative and unremitting solutions to cope with the resultant immune evasion and establish a sustainable immune barrier. Here we introduce a vaccine-delivery system with a combination of a needle-free injection (NFI) device and a SARS-CoV-2-Spike-specific mRNA-Lipid Nanoparticle (LNP) vaccine. The benefits are duller pain and a significant increase of immunogenicity compared to the canonical needle injection (NI). From physicochemical and bioactivity analyses, the structure of the mRNA-LNP maintains stability upon NFI, contradictory to the belief that LNPs are inclined towards destruction under the high-pressure conditions of NFI. Moreover, mRNA-LNP vaccine delivered by NFI induces significantly more binding and neutralizing antibodies against SARS-CoV-2 variants than the same vaccine delivered by NI. Heterogeneous vaccination of BA.5-LNP vaccine with NFI enhanced the generation of neutralizing antibodies against Omicron BA.5 variants in rabbits previously vaccinated with non-BA.5-specific mRNA-LNP or other COVID-19 vaccines. NFI parameters can be adjusted to deliver mRNA-LNP subcutaneously or intramuscularly. Taken together, our results suggest that NFI-based mRNA-LNP vaccination is an effective substitute for the traditional NI-based mRNA-LNP vaccination.

Cardiac MRI structural and functional predictors of left ventricular ejection fraction recovery following PVC catheter ablation.

Frequent premature ventricular contractions (PVCs) can induce cardiomyopathy (PVC CM). We sought to use cardiac magnetic resonance imaging (CMR) to quantify changes in cardiac structure and function of cardiomyopathy patients following catheter ablation for PVCs. Patients undergoing PVC ablation at the Johns Hopkins Hospital with pre-procedural CMR from 2010 to 2018 were included in this study. CMR Images were analyzed to collect information on cardiac structure and function as well as to quantify scar. Of the total 51 included patients, PVC CM (LVEF < 45%) was observed in 51% (n = 29). Of these, 19 had post-ablation ejection fractions quantified, with 78.9% (n = 15) recovering function. Global longitudinal strain was significantly correlated with LVEF (OR 1.831, p < 0.01) but did not predict recovery of function. RV origin of PVCs was more common in the preserved LVEF group but was also significantly correlated with persistently reduced EF post-ablation in the PVC CM group. Scar burden was not correlated with either cardiac function or post-ablation recovery of function. In this cohort, there were no significant CMR findings to predict subsequent recovery of EF after ablation among those with PVC CM. PVC origin in the RV was associated with persistently reduced LVEF after ablation.

Pregnancy and fertility-related adverse outcomes associated with Chlamydia trachomatis infection: a global systematic review and meta-analysis.

BACKGROUND: Genital chlamydia infection in women is often asymptomatic, but may result in adverse outcomes before and during pregnancy. The purpose of this study was to examine the strength of the relationships between chlamydia infection and different reproductive health outcomes and to assess the certainty of the evidence. METHODS: This review was registered and followed the Cochrane guidelines. We searched three databases to quantitatively examine adverse outcomes associated with chlamydia infection. We included pregnancy and fertility-related outcomes. We performed meta-analyses on different study designs for various adverse outcomes using unadjusted and adjusted analyses. RESULTS: We identified 4730 unique citations and included 107 studies reporting 12 pregnancy and fertility-related outcomes. Sixty-eight studies were conducted in high-income countries, 37 studies were conducted in low-income or middle-income countries, and 2 studies were conducted in both high-income and low-income countries. Chlamydia infection was positively associated with almost all of the 12 included pregnancy and fertility-related adverse outcomes in unadjusted analyses, including stillbirth (OR=5.05, 95% CI 2.95 to 8.65 for case-control studies and risk ratio=1.28, 95% CI 1.09 to 1.51 for cohort studies) and spontaneous abortion (OR=1.30, 95% CI 1.14 to 1.49 for case-control studies and risk ratio=1.47, 95% CI 1.16 to 1.85 for cohort studies). However, there were biases in the design and conduct of individual studies, affecting the certainty of the overall body of evidence. The risk of adverse outcomes associated with chlamydia is higher in low-income and middle-income countries compared with high-income countries. CONCLUSION: Chlamydia is associated with an increased risk of several pregnancy and fertility-related adverse outcomes in unadjusted analyses, especially in low-income and middle-income countries. Further research on how to prevent the sequelae of chlamydia in pregnant women is needed. TRIAL REGISTRATION NUMBER: CRD42017056818.

Driving force of condomless sex after online intervention among Chinese men who have sex with men.

BACKGROUND: Condom use remains consistently low among Chinese men who have sex with men (MSM). This study aims to identify factors associated with condom use after online video intervention. METHODS: This is a secondary data analysis of data collected from an online non-inferiority trial comparing the effectiveness of two condom use promotion video interventions among Chinese MSM. Participants from the two groups were combined since the effectiveness of two video interventions were shown to be non-inferior. Univariable and multivariable logistic regression were used to identify factors associated with condomless sex after the intervention during the follow-up interval. RESULTS: Overall, 1173 participants were recruited at baseline and 791 (67.4%) completed the three-month follow-up survey. 57.3% (453/791) of the participants reported condomless sex after intervention in the three-month follow-up interval. MSM who have had sex under the influence of alcohol in the last 3 months (Odds Ratio(OR) = 1.90; 95% CI: 1.22, 2.97; Adjusted OR(AOR) = 1.79; 95% CI: 1.13, 2.83) and ever have had sex tourism (OR = 2.75; 95% CI: 1.34, 5.63; AOR = 2.40; 95% CI: 1.15, 5.07) at baseline were more likely to have condomless sex after intervention in the three-month follow-up period. MSM who had a higher level of community engagement in sexual health (OR = 0.54; 95% CI: 0.35, 0.82; AOR = 0.49; 95% CI: 0.32, 0.75 with substantial engagement) and who viewed additional condom promotion videos during the follow-up period by themselves (OR = 0.67; 95% CI = 0.50, 0.89; AOR = 0.67; 95% CI: 0.50, 0.91). were less likely to have condomless sex during the follow-up period. CONCLUSION: The intervention appeared to be effective among MSM who reported viewing additional condom promotion videos by themselves and more community engagement after the intervention. In MSM who reported risky sexual behaviors at baseline, the intervention appeared less effective. Tailored intervention videos that target particular subgroups, active in-person community engagement, and optimized intervention frequency should be considered in future sexual health interventions.

Reimagining Health Communication: A Noninferiority Randomized Controlled Trial of Crowdsourced Intervention in China.

BACKGROUND: Crowdsourcing, the process of shifting individual tasks to a large group, may be useful for health communication, making it more people-centered. We aimed to evaluate whether a crowdsourced video is noninferior to a social marketing video in promoting condom use. METHODS: Men who have sex with men (≥16 years old, had condomless sex within 3 months) were recruited and randomly assigned to watch 1 of the 2 videos in 2015. The crowdsourced video was developed through an open contest, and the social marketing video was designed by using social marketing principles. Participants completed a baseline survey and follow-up surveys at 3 weeks and 3 months postintervention. The outcome was compared with a noninferiority margin of +10%. RESULTS: Among the 1173 participants, 907 (77%) and 791 (67%) completed the 3-week and 3-month follow-ups. At 3 weeks, condomless sex was reported by 146 (33.6%) of 434 participants and 153 (32.3%) 473 participants in the crowdsourced and social marketing arms, respectively. The crowdsourced intervention achieved noninferiority (estimated difference, +1.3%; 95% confidence interval, -4.8% to 7.4%). At 3 months, 196 (52.1%) of 376 individuals and 206 (49.6%) of 415 individuals reported condomless sex in the crowdsourced and social-marketing arms (estimated difference: +2.5%, 95% confidence interval, -4.5 to 9.5%). The 2 arms also had similar human immunodeficiency virus testing rates and other condom-related secondary outcomes. CONCLUSIONS: Our study demonstrates that crowdsourced message is noninferior to a social marketing intervention in promoting condom use among Chinese men who have sex with men. Crowdsourcing contests could have a wider reach than other approaches and create more people-centered intervention tools for human immunodeficiency virus control.

Sex tourism among Chinese men who have sex with men: a cross-sectional observational study.

BACKGROUND: Sex tourism among men who have sex with men (MSM) may exacerbate transmission of HIV and other sexually transmitted infections (STIs). Sex tourism is defined as purchasing sex with gifts or money outside of one's hometown. Our objective was to characterize the frequency, socio-demographic characteristics, and sexual risk behaviors among Chinese MSM sex tourists. METHODS: An online, cross-sectional survey for high-risk MSM throughout China was conducted in November 2015 covering sociodemographic characteristics, sexual risk behaviors, and sex tourism. Univariate and multivariable logistic regressions were performed to identify correlates of sex tourism. The mean MSM HIV prevalence of sex tourism journey origins and destinations were compared. RESULTS: Of 1189 MSM who completed the survey, 62 (5%) men identified as sex tourists; among these sex tourists, twenty (32%) traveled primarily to purchase sex and the remainder purchased sex while traveling for another purpose. There was minimal socio-demographic and behavioral difference between the two groups. In multivariable analyses, adjusting for age and income, sex tourism was correlated with high-risk sexual behaviors, higher income (aOR 4.44, 95%CI 1.77-11.18) and living with HIV (aOR 2.79, 95%CI 1.03-7.55). Sex tourism was more often from locations with lower to higher MSM HIV prevalence (mean = 4.47, SD = 2.01 versus mean = 6.86, SD = 5.24). CONCLUSION: MSM sex tourists were more likely to have risky sexual behaviors and travel to locations with a higher HIV prevalence. MSM sex tourists may be part of core groups that are disproportionately responsible for MSM HIV transmission. Enhanced surveillance and interventions tailored to MSM sex tourists should be considered.

HIV Linkage to Care and Retention in Care Rate Among MSM in Guangzhou, China.

Quantifying HIV service provision along the HIV care continuum is increasingly important for monitoring and evaluating HIV interventions. We examined factors associated with linkage and retention in care longitudinally among MSM (n = 1974, 4933 person-years) diagnosed and living in Guangzhou, China, in 2008-2014. We measured longitudinal change of retention in care (≥2 CD4 tests per year) from linkage and antiretroviral therapy initiation (ART). We examined factors associated with linkage using logistic regression and with retention using generalized estimating equations. The rate of linkage to care was 89% in 2014. ART retention rate dropped from 71% (year 1) to 46% (year 2), suggesting that first-year retention measures likely overestimate retention over longer periods. Lower CD4 levels and older age predicted retention in ART care. These data can inform interventions to improve retention about some subgroups.

Disclosure of sexual orientation to health professionals in China: results from an online cross-sectional study.

BACKGROUND: Many men who have sex with men (MSM) in China are "in the closet." The low rate of disclosure may impact sexual behaviours, testing for HIV and other sexually transmitted infections (STIs), and diseases transmission. This study examines factors associated with overall sexual orientation disclosure and disclosure to healthcare professionals. METHODS: A nationwide cross-sectional online survey was conducted from September 2014 to October 2014 in China. Participants completed questions covering socio-demographic information, sexual behaviours, HIV/STI testing history, and self-reported HIV status. We defined healthcare professional disclosure as disclosing to a doctor or other medical provider. RESULTS: A total of 1819 men started the survey and 1424 (78.3%) completed it. Among the 1424 participants, 62.2% (886/1424) reported overall disclosure, and 16.3% (232/1424) disclosed to healthcare professionals. In multivariate analyses, the odds of sexual orientation disclosure were 56% higher among MSM who used smartphone-based, sex-seeking applications [adjusted odds ratio (aOR) = 1.56, 95% CI: 1.25-2.95], but were lower among MSM reporting sex while drunk or recreational drug use. The odds of disclosure to a healthcare professional were greater among MSM who had ever tested for HIV or STIs (aOR = 3.36, 95% CI: 2.50-4.51 for HIV, and aOR = 4.92, 95% CI: 3.47-6.96 for STIs, respectively) or self-reported as living with HIV (aOR = 1.59, 95% CI: 0.93-2.72). CONCLUSION: Over 80% of MSM had not disclosed their sexual orientation to health professionals. This low level of disclosure likely represents a major obstacle to serving the unique needs of MSM in clinical settings. Further research and interventions to facilitate MSM sexual orientation disclosure, especially to health professionals, are urgently needed.

Community engagement in sexual health and uptake of HIV testing and syphilis testing among MSM in China: a cross-sectional online survey.

INTRODUCTION: HIV and syphilis testing rates remain low among men who have sex with men (MSM) in low- and middle-income countries (LMICs). Community engagement has been increasingly used to promote HIV testing among key populations in high-income countries, often in settings with stronger civil society. This study aimed to assess socio-demographic, behavioural, and community engagement factors associated with HIV and syphilis testing among MSM in China. METHODS: MSM ≥16 years old who had condomless sex in the past three months were recruited nationwide to complete a cross-sectional online survey in November 2015. Data were collected on socio-demographics, sexual behaviours, HIV testing, syphilis testing, and community engagement in sexual health. We defined community engagement in sexual health using six items assessing awareness and advocacy of sexual health programmes. The underlying factor structure of a 6-item community engagement scale was determined through exploratory factor analysis. Univariate and multivariable logistic regressions identified correlates of HIV and syphilis testing. RESULTS: 1189 MSM were recruited. 54% (647/1189) of men had ever tested for HIV and 30% (354/1189) had ever tested for syphilis. Factor analysis suggested three levels of community engagement (minimal, moderate, and substantial) and this model explained 79.5% of observed variance. A quarter (26%, 312/1189) reported none to minimal engagement, over one half (54%, 644/1189) reported moderate engagement, and a fifth (20%, 233/1189) reported substantial engagement. Multivariable logistic regression showed that MSM with greater community engagement in sexual health were more likely to have ever tested for HIV (substantial vs. no engagement: aOR 7.91, 95% CI 4.98-12.57) and for syphilis (substantial vs. no engagement: aOR 5.35, 95% CI 3.16-9.04). CONCLUSION: HIV and syphilis testing are suboptimal among MSM in China. Community engagement may be useful for promoting testing in China and should be considered in intervention development and delivery. Further research is needed to better understand the role of LMIC community engagement in HIV interventions.

Comparing the effectiveness of a crowdsourced video and a social marketing video in promoting condom use among Chinese men who have sex with men: a study protocol.

INTRODUCTION: Crowdsourcing has been used to spur innovation and increase community engagement in public health programmes. Crowdsourcing is the process of giving individual tasks to a large group, often involving open contests and enabled through multisectoral partnerships. Here we describe one crowdsourced video intervention in which a video promoting condom use is produced through an open contest. The aim of this study is to determine whether a crowdsourced intervention is as effective as a social marketing intervention in promoting condom use among high-risk men who have sex with men (MSM) and transgender male-to-female (TG) in China. METHOD: We evaluate videos developed by crowdsourcing and social marketing. The crowdsourcing contest involved an open call for videos. Entries were judged on capacity to promote condom use, to be shareable or 'go viral' and to give value to the individual. 1170 participants will be recruited for the randomised controlled trial. Participants need to be MSM age 16 and over who have had condomless anal sex in the last 3 months. Recruitment will be through an online banner ad on a popular MSM web page and other social media platforms. After completing an initial survey, participants will be randomly assigned to view either the social marketing video or the crowdsourcing video. Follow-up surveys will be completed at 3 weeks and 3 months after initial intervention to evaluate condomless sex and related secondary outcomes. Secondary outcomes include condom social norms, condom negotiation, condom self-efficacy, HIV/syphilis testing, frequency of sex acts and incremental cost. ETHICS AND DISSEMINATION: Approval was obtained from the ethical review boards of the Guangdong Provincial Center for Skin Diseases and STI Control, UNC and UCSF. The results of this trial will be made available through publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02516930.

Facilitators of HCV treatment adherence among people who inject drugs: a systematic qualitative review and implications for scale up of direct acting antivirals.

BACKGROUND: While the public health benefits of new HCV treatments depend on treatment adherence, particularly among people who inject drugs (PWID), several social and medical factors can jeopardize treatment adherence. The aim of this study is to examine the qualitative literature on facilitators to HCV treatment adherence among PWID. METHODS: We searched six databases to identify qualitative research studies on HCV treatment adherence facilitators among PWID. Two reviewers independently extracted and analyzed data using PRISMA guidelines and the CASP tool to evaluate study quality. RESULTS: From ten studies representing data from 525 participants, three major themes emerged across studies: logistical facilitators within health systems enhanced HCV treatment adherence, positive social interactions between PWID and staff provided positive feedback during treatment, and HCV treatment may complicate the addiction recovery process. CONCLUSIONS: Although PWID face several barriers to adherence, we identified treatment adherence facilitators that could be incorporated into clinical practice.

Catheter ablation of accessory pathways near the coronary sinus: value of defining coronary arterial anatomy.

BACKGROUND: Accessory pathways can lie near or within the coronary sinus (CS). Radiofrequency catheter ablation of accessory pathways is a well-established treatment option, but this procedure can cause damage to adjacent coronary arteries. OBJECTIVE: The purpose of this study was to evaluate the anatomic relationship between the coronary arteries and the CS. METHODS: Retrospective data of patients who underwent catheter ablation of supraventricular tachycardia between June 2011 and August 2013 was reviewed. In addition, detailed analysis of coronary computed tomographic angiography (CTA) data from 50 patients was performed. RESULTS: Between June 2011 and August 2013, 427 patients underwent catheter ablation of supraventricular tachycardia, of whom 105 (age 28 ± 17 years, 60% male) had accessory pathway-mediated tachycardia. Of these, 23 patients had accessory pathways near the CS, and 60% (N = 14) underwent concurrent coronary angiography. In 4 patients, the posterolateral (inferolateral) branch (PLA) of the right coronary artery was in close proximity to the CS, and 2 patients (18%) had stenosis of the PLA at the site of ablation. On CTA at their closest proximity, the PLA was 1.9 ± 1.3 mm and the left circumflex artery (LCx) was 2.0 ± 0.8 mm from the body of the CS, in right and left coronary artery-dominant patients, respectively. CS ostium and PLA were 3.6 ± 1.9 mm apart. In left-dominant patients, LCx and CS ostium were 3.8 ± 1.2 mm apart. CONCLUSION: The PLA and LCx are in close proximity to the anteroinferior aspect of the CS ostium and proximal CS. The relationship of the CS and coronary arteries should be evaluated before ablation at these sites.

Computational design and biochemical characterization of maize nonspecific lipid transfer protein variants for biosensor applications.

Lipid transfer proteins (LTPs) are a family of proteins that bind and transfer lipids. Utilizing the maize LTP, we have successfully engineered fluorescent reagentless biosensors for the natural ligand of LTPs; this was achieved by using computational protein design to remove a disulfide bridge and attaching a thio-reactive fluorophore. Conformational change induced by ligand titration is thought to affect the fluorescence of the fluorophore, allowing detection of ligand binding. Fluorescence measurements show that our LTP variants have affinity to palmitate that is consistent with wild-type LTP. These molecules have the potential to be utilized as scaffolds to design hydrophobic ligand biosensors or to serve as drug carriers.