Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Cluster of Nontoxigenic Corynebacterium diphtheriae Infective Endocarditis and Rising Background C. diphtheriae Cases-Seattle, Washington, 2020-2023.

BACKGROUND: Nontoxigenic Corynebacterium diphtheriae, often associated with wounds, can rarely cause infective endocarditis (IE). Five patients with C. diphtheriae IE were identified within 12 months at a Seattle-based hospital system. We reviewed prior C. diphtheriae-positive cultures to determine if detections had increased over time and evaluated epidemiologic trends. METHODS: We conducted a formal electronic health record search to identify all patients aged ≥18 years with C. diphtheriae detected in a clinical specimen (ie, wound, blood, sputum) between 1 September 2020 and 1 April 2023. We collected patient demographics, housing status, comorbidities, substance-use history, and level of medical care required at detection. We extracted laboratory data on susceptibilities of C. diphtheriae isolates and on other pathogens detected at the time of C. diphtheriae identification. RESULTS: Between 1 September 2020 and 1 April 2023, 44 patients (median age, 44 years) had a C. diphtheriae-positive clinical culture, with most detections occurring after March 2022. Patients were predominantly male (75%), White (66%), unstably housed (77%), and had a lifetime history of injecting drugs (75%). Most C. diphtheriae-positive cultures were polymicrobial, including wound cultures from 36 (82%) patients and blood cultures from 6 (14%) patients, not mutually exclusive. Thirty-four patients (77%), including all 5 patients with C. diphtheriae IE, required hospital admission for C. diphtheriae or a related condition. Of the 5 patients with IE, 3 died of IE and 1 from COVID-19. CONCLUSIONS: Findings suggest a high-morbidity outbreak disproportionately affecting patients who use substances and are unstably housed.

Making a racket in America's fastest growing sport: Evaluation of noise exposure in pickleball.

OBJECTIVE: To measure noise exposure present on pickleball courts and assess the risk of noise-induced hearing loss (NIHL) per guidelines put forward by the National Institute of Occupational Safety and Health (NIOSH). METHODS: Observational study measuring noise levels at multiple recreational pickleball courts in the Richmond, VA area, documenting LAeq, LASmax, and LCpeak at courtside and waiting areas of pickleball courts. Measurements were completed using the NIOSH SLM application on an iPhone 13 with iMM-6 Calibrated Measurement Microphone (equivalent to IEC 61672-1 Class II) that was calibrated using ND-9 Sound Level Calibrator (IEC942 Class I). RESULTS: Average sound levels recorded at waiting areas adjacent to the courts, measured in LAeq, LASmax, and LCpeak, were 69.1 dBA, 92.0 dBA, and 112.1 dBC, respectively, while courtside measurements were 69.7 dBA, 92.2 dBA, and 115.6 dBC, respectively. These measurements were within NIOSH and OSHA recommendations. CONCLUSION: The data demonstrates that randomly sampled pickleball courts have noise levels that do not increase risk for NIHL for participants or bystanders alike based on NIOSH guidelines. However, prolonged noise exposure and ambient noise pollution may have other health implications and warrant further investigations. LEVEL OF EVIDENCE: Level 2.

Should lateral wall collapse be a contraindication for hypoglossal nerve stimulation?

OBJECTIVE: The purpose of this study is to examine how lateral wall collapse affects treatment outcomes for hypoglossal nerve stimulation (HNS) patients. METHODS: Patients (n = 111) queried from a single surgeon's database of HNS cases were divided into groups based on their degree of oropharyngeal lateral wall collapse noted on drug-induced sleep endoscopy (DISE): Complete, Partial, None. For each group, apnea hypopnea index (AHI) reduction, Epworth Sleepiness Scale (ESS) score, stimulation voltage, average nightly usage, need for alternate device configuration/awake sleep endoscopy, and rate of surgical success were collected. Patients with Complete collapse were compared to those with Partial/None via Student's t-tests and Pearson's Chi-square test. RESULTS: Of the 111 eligible patients, 45 had complete, 30 partial, and 36 had no lateral oropharyngeal wall collapse. There were no statistically significant differences found between the Complete and Partial/None groups in terms of age, BMI, sex, AHI (pre and post-op), ESS (pre and post-op), voltage, alternate device configuration, or nightly adherence. Notably, a significantly greater number of the Partial/None group had surgical success (84.84 % vs 66.67 %, p = 0.024). CONCLUSIONS: Patients with Partial/None oropharyngeal collapse were significantly more likely than patients with Complete lateral wall collapse to see surgical success. There are many factors to weigh when assessing a patient's surgical candidacy, it is clear that complete lateral wall collapse at the level of the oropharynx is a negative predictor for success in HNS.

Stakeholders' solutions to antiretroviral therapy interruption during the COVID-19 pandemic in China: a short report.

Obtaining antiretroviral therapy (ART) was a challenge for people living with HIV (PLHIV) in China during the COVID-19 outbreak. On 26 January 2020, the Chinese Center for AIDS/STD Control and Prevention issued a nationwide directive to relax restrictions on where and when PLHIV could refill ART. This qualitative study explored unexpected barriers under this directive and recommendations to improve future ART delivery. Between February 11 and February 15 2020, in-depth interviews of 4 groups of stake holders related to ART refilling (i.e., PLHIV, community-based organization employees, CDC staff, infectious disease physicians and nurses), were conducted via WeChat. Data were managed by NVivo 11.0 and transcripts were coded using thematic analysis. Sixty-two interviews were conducted. The main barriers to refilling ART included: (1) inconsistent documentation requirements to refill ART, (2) lack of specific protocols on ART refilling, (3) insufficient staffing, and (4) regimen verification and drug shortages. The most common recommendations to improve future ART delivery were: (1) to establish a nationwide system to distribute ART and (2) increase the number of pills delivered with each ART refill. Strengthening protocols and systems to refill ART and improving collaboration is key to preventing interruptions in ART among PLHIV during public health emergencies.

Barriers and Facilitators to, and Experience of, Voluntary Medical Male Circumcision Among Men Who Have Sex with Men in China: A Mixed-Methods Study.

Voluntary medical male circumcision (VMMC) may be incorporated into HIV prevention services for men who have sex with men (MSM). We conducted a mixed-methods study to elucidate barriers and facilitators to, and experience of, VMMC among MSM. Participants were MSM aged 18 years and older who were enrolled in an ongoing multicenter randomized controlled trial (RCT) to evaluate VMMC to prevent HIV among MSM in China. RCT participants completed a questionnaire before and after VMMC to assess perceptions of and complications after the procedure. A subset of RCT participants were selected for in-depth interviews. Interviewees answered open-ended questions about barriers and facilitators to and experience of undergoing VMMC. Six-step thematic analysis incorporating inductive and deductive approaches was used to interpret interview responses. A total of 457 MSM completed the pre-VMMC survey, 115 circumcised MSM completed post-VMMC surveys, and 30 MSM completed an interview. Main barriers to VMMC uptake were concerns about pain, length of wound healing, cost, lack of knowledge about or misconceptions of VMMC, and stigma related to surgery. Facilitators to VMMC could be categorized as internal factors (foreskin) and external factors (motivation and follow-up care). Interestingly, the VMMC experiences of others could be transformed from a barrier into a facilitator to VMMC in some circumstances. After VMMC participants transitioned from a negative state of pain, remorse, difficulty sleeping, and discomfort to a positive state of symptom alleviation and personal hygiene improvement. Optimizing facilitators and addressing barriers may encourage VMMC among MSM. Joint efforts should be made by relevant stakeholders to improve the awareness and uptake of VMMC among MSM.

Heroin pipe distribution to reduce high-risk drug consumption behaviors among people who use heroin: a pilot quasi-experimental study.

BACKGROUND: Heroin pipe distribution may encourage people who use heroin (PWUH) to transition from injecting to smoking heroin, reducing harms associated with injection drug use. A syringe services program (SSP) in Seattle, Washington, led by people who use drugs developed a heroin pipe distribution program. METHODS: We conducted a pretest-posttest quasi-experimental study to evaluate the impact of heroin pipe distribution on drug consumption behaviors among PWUH between March and December 2019. SSP clients were surveyed during three weeklong timepoints before and four weeklong timepoints after heroin pipe distribution. Primary outcomes were change in proportion of SSP clients who exclusively injected heroin, exclusively smoked heroin, and both injected and smoked heroin in the past seven days comparing the pre- and post-intervention periods. RESULTS: Across the seven observation timepoints, 694 unique respondents completed 957 surveys. Multiple responses from a single respondent in a given period were collapsed, resulting in 360 pre-intervention and 430 post-intervention records. Heroin use was reported in over half of pre-intervention (56%, 201/360) and post-intervention records (58%, 251/430). Compared to pre-intervention behaviors, the proportion of respondents who exclusively injected heroin was lower after the start of heroin pipe distribution (32%, 80/251 vs 43%, 86/201, p = 0.02), while the proportion of respondents who both injected and smoked heroin was higher (45%, 113/251 vs 36%, 72/201, p = 0.048). Just under half (44%, 110/251) of respondents who used heroin during the post-intervention period used a heroin pipe obtained from the SSP, of which 34% (37/110) reported heroin pipe distribution had reduced their heroin injection frequency. Self-reported hospitalization for a pulmonary cause was not associated with using a heroin pipe. CONCLUSIONS: The proportion of SSP clients who exclusively injected heroin was lower after implementation of heroin pipe distribution. Randomized studies with longer follow-up are needed to investigate whether heroin pipe distribution reduces heroin injection and improves health outcomes associated with drug use. Limited intervention exposure, loss to follow-up, and pipe availability from other sources pose methodological challenges to evaluations of route transition interventions in community settings. This pilot highlights the potential for organizations led by people who use drugs to develop, implement, and evaluate novel public health programming.

A crowdsourced intervention to decrease hepatitis B stigma in men who have sex with men in China: A cohort study.

Stigma against people with hepatitis B virus (HBV) is a barrier to prevention, diagnosis and treatment of HBV in China. Our study examined an innovative intervention to reduce HBV stigma among men who have sex with men (MSM) in China. We extracted data from a randomized controlled trial conducted in May 2018, where the intervention consisted of crowdsourced images and videos to promote viral hepatitis testing and reduce HBV stigma. HBV stigma was assessed using a 20-item scale at baseline and four weeks post-enrolment. Participants were divided into three groups based on their exposure to intervention: full exposure, partial exposure and no exposure. Linear regression was used to determine associations between baseline stigma and participant characteristics. Data from 470 MSM were analysed. Mean participant age was 25 years old and 56% had less education than a college bachelor's degree. Full exposure to intervention was associated with significant stigma reduction (adjusted beta = -3.49; 95% CI = -6.11 to -0.87; P = .01), while partial exposure led to stigma reduction that was not statistically significant. The mean stigma score was 50.6 (SD ± 14.7) at baseline, and stigma was most prominent regarding physical contact with HBV carriers. Greater HBV stigma was associated with not having a recent doctor's visit (adjusted beta = 4.35, 95% CI = 0.19 to 8.52; P = .04). In conclusion, crowdsourcing can decrease HBV stigma among MSM in China and may be useful in anti-stigma campaigns for vulnerable populations in low- and middle-income countries.

Crowdsourcing to promote hepatitis C testing and linkage-to-care in China: a randomized controlled trial protocol.

BACKGROUND: Hepatitis C virus (HCV) is a growing public health problem with a large disease burden worldwide. In China many people living with HCV are unaware of their hepatitis status and not connected to care and treatment. Crowdsourcing is a technique that invites the public to create health promotion materials and has been found to increase HIV testing uptake, including in China. This trial aims to evaluate crowdsourcing as a strategy to improve HCV awareness, testing and linkage-to-care in China. METHODS: A randomized controlled, two-armed trial (RCT) is being conducted in Shenzhen with 1006 participants recruited from primary care sectors of The University of Hong Kong-Shenzhen Hospital. Eligible participants are ≥30 years old; a resident in Shenzhen for at least one month after recruitment; no screening for HCV within the past 12 months and not known to have chronic HCV; and, having a WeChat social media account. Allocation is 1:1. Both groups will be administered a baseline and a follow-up survey (4-week post-enrollment). The intervention group will receive crowdsourcing materials to promote HCV testing once a week for two weeks and feedback will be collected thereafter, while the control group will receive no promotional materials. Feedback collected will be judged by a panel and selected to be implemented to improve the intervention continuously. Those identified positive for HCV antibodies will be referred to gastroenterologists for confirmation and treatment. The primary outcome will be confirmed HCV testing uptake, and secondary outcomes include HCV confirmatory testing and initiation of HCV treatment with follow-ups with specialist providers. Data will be collected on Survey Star@ via mobile devices. DISCUSSION: This will be the first study to evaluate the impact of crowdsourcing to improve viral hepatitis testing and linkage-to-care in the health facilities. This RCT will contribute to the existing literature on interventions to improve viral hepatitis testing in primary care setting, and inform future strategies to improve HCV care training for primary care providers in China. TRIAL REGISTRATION: Chinese Clinical Trial Registry. ChiCTR1900025771. Registered September 7th, 2019, http://www.chictr.org.cn/showprojen.aspx?proj=42788.

Impact of outcomes data on the management of postoperative hypocalcemia in head and neck endocrine surgery patients.

Postoperative hypocalcemia is a well-described outcome following thyroid and parathyroid surgery with symptoms ranging from clinically insignificant laboratory findings to tetany and seizures. The aims of this study were 1. To identify the characteristics and management patterns of postoperative hypocalcemia in head and neck endocrine surgery patients and 2. To compare outcomes between patients treated with empiric calcium and patients treated using a biochemically driven calcium replacement algorithm. Clinical electronic medical record (EMR) data was collected from patients who had undergone total thyroidectomy, completion thyroidectomy, and/or parathyroidectomy at Wake Forest Baptist Medical Center (WFBMC), a tertiary referral and academic institution. Between July 1, 2016, and June 30, 2017, 298 adult patients underwent surgery by a WFBMC Head & Neck (H&N) endocrine surgeon. Objective calcium and parathyroid hormone levels, postoperative supplementation with calcium and Vitamin D, 30-day physician access line (PAL) phone call utilization, emergency department (ED) encounters, and readmission rates were queried. The overall rate of hypocalcemia was 17.4%. No statistically significant difference in PAL utilization, ED visits, or readmissions was found between the empiric supplementation group and those whose supplementation was biochemically directed (PAL 5.0% vs. 5.0% [p = 0.983], ED visit 3.3% vs. 2.5% [p = 0.744], Readmission 1.7% vs. 0% [p = 0.276]). The overall postoperative rates of hypocalcemia and hypoparathyroidism following H&N endocrine surgery were consistent with the reported literature. Neither method of calcium supplementation was superior in reducing PAL utilization, ED encounters, or readmission.

Surgical management of Eagle syndrome: A 17-year experience with open and transoral robotic styloidectomy.

Eagle Syndrome (ES) is a rare disorder that can present with symptoms ranging from globus sensation to otalgia that is attributed to an elongated styloid process and/or calcified stylohyoid ligament. No standardized treatment algorithm exists, and although various surgical approaches have been described, data on the use of transoral robotic surgery (TORS) in this population is limited. To investigate the utility of TORS in the treatment of ES, a retrospective review in 19 ES patients was carried out at a single academic, tertiary medical center between 2000 and 2017. Nineteen patients underwent twenty-one styloid resections: 6 performed via TORS and 15 via transcervical approach. Across all patients, 90% reported some degree of lasting improvement in symptoms while 55% reported significant improvement. When TORS was compared to transcervical resection, there was no difference in the subjective rate of "meaningful" (83 vs. 57%) versus rate of "non-meaningful" symptom improvement (17 vs. 43%) (p = 0.35). There was a trend towards less estimated blood loss (EBL), operative time, and post-operative length of stay (LOS) with TORS versus transcervical cases (9.2 mL vs. 30.0 mL, 98 vs. 156 min, and 0.7 vs. 1.2 days); however, these did not reach statistical significance (p = .11, 0.13, and 0.42, respectively). Three patients experienced complications associated with an open approach, as compared to none with TORS. In select patients, TORS styloidectomy is a reasonable surgical alternative to traditional transoral and transcervical techniques as it provides similar symptom improvement, and reduced length of stay, blood loss, and operative time.

Association between rectal douching and HIV and other sexually transmitted infections among men who have sex with men: a systematic review and meta-analysis.

BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by HIV and other STIs worldwide. Rectal douching, which is commonly used by MSM in preparation for anal sex, may increase the risk of HIV and other STIs by injuring the rectal mucosa. Results from individual studies reporting associations between rectal douching and HIV and other STIs among MSM are inconsistent. We performed a systematic review and meta-analysis to estimate the association between rectal douching and HIV and other STIs among MSM. METHODS: We searched PubMed, Embase, Scopus and Web of Science for studies published from January 1970 to November 2018. Studies that reported ORs and 95% CIs of associations between rectal douching and infection with HIV/STIs, or reported enough data to calculate these estimates, were included. We assessed risk of bias using the Newcastle-Ottawa Scale. ORs were pooled using a random effects model. RESULTS: Twenty-eight eligible studies were identified in our review, of which 24 (20 398 participants) were included in the meta-analysis. Rectal douching was associated with increased odds of infection with HIV (OR 2.80, 95% CI 2.32 to 3.39), and any STI other than HIV (including hepatitis B virus (HBV), hepatitis C virus (HCV), chlamydia, gonorrhoea, syphilis and human papillomavirus) (OR 2.46, 95% CI 1.95 to 3.11) among MSM. For specific STIs, douching was associated with increased odds of viral hepatitis (HBV, HCV) (OR 3.29, 95% CI 2.79 to 3.87), and chlamydia or gonorrhoea (OR 3.25, 95% CI 2.02 to 5.23). These associations remained significant in studies that adjusted for potential confounders. CONCLUSION: Rectal douching may put MSM at increased risk for infection with HIV and other STIs. Longitudinal studies are needed to clarify this association, and health education materials should inform men of the potential for increased risk of infection with rectal douching.

Forming and implementing community advisory boards in low- and middle-income countries: a scoping review.

BACKGROUND: Community advisory boards (CABs) have expanded beyond high-income countries (HICs) and play an increasing role in low- and middle-income country (LMIC) research. Much research has examined CABs in HICs, but less is known about CABs in LMICs. The purposes of this scoping review are to examine the creation and implementation of CABs in LMICs, including identifying frequently reported challenges, and to discuss implications for research ethics. METHODS: We searched five databases (PubMed, Embase, Global Health, Scopus, and Google Scholar) for publications describing or evaluating CABs in LMICs. Two researchers independently reviewed articles for inclusion. Data related to the following aspects of CABs were extracted from included publications: time, country, financial support, research focus, responsibilities, and challenges. Thematic analyses were used to summarize textual data describing challenges. RESULTS: Our search yielded 2005 citations, 83 of which were deemed eligible for inclusion. Most studies (65) were published between 2010 and 2017. Upper-middle-income countries were more likely to have studies describing CABs, with South Africa (17), China (8), and Thailand (7) having the greatest numbers. The United States National Institutes of Health was the main source of financial support for CABs. Many CABs (53/88, 60%) focused on HIV research. Thirty-four studies reported how CABs influenced the informed consent process for clinical trials or other aspects of research ethics. CAB responsibilities were related to clinical trials, including reviewing study protocols, educating local communities about research activities, and promoting the ethical conduct of research. Challenges faced by CABs included the following: incomplete ethical regulations and guidance; limited knowledge of science among members of communities and CABs; unstable and unbalanced power relationships between researchers and local communities; poor CAB management, including lack of formal participation structures and absence of CAB leadership; competing demands for time that limited participation in CAB activities; and language barriers between research staff and community members. Several challenges reflected shortcomings within the research team. CONCLUSIONS: Our findings examine the formation and implementation of CABs in LMICs and identify several ethical challenges. These findings suggest the need for further ethics training among CAB members and researchers in LMICs.

HBV and HCV test uptake and correlates among men who have sex with men in China: a nationwide cross-sectional online survey.

OBJECTIVES: Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause substantial morbidity and mortality in low-income and middle-income countries, including China. WHO guidelines recommend men who have sex with men (MSM) receive HBV and HCV screening. The purpose of this study was to determine the proportion of MSM in China who have HBV and HCV tested and identify correlates of test uptake. METHODS: We conducted an online cross-sectional survey of young MSM in China. Respondents were asked to report previous HBV and HCV testing, sociodemographic information, sexual risk factors for hepatitis infection, other STI testing and primary care physician (PCP) status. Associations were analysed by logistic regression. RESULTS: 503 eligible MSM completed the survey. 41.0% (206/503) of MSM had HCV tested, and 38.2% (60/157) of MSM with no or uncertain HBV vaccination had HBV tested. In multivariate analysis, HCV testing was correlated with HBV testing (adjusted OR (aOR) 22.98, 95% CI 12.11 to 43.60), HIV testing (aOR 3.64, 95% CI 1.92 to 6.91), HIV-positive status (aOR 1.78, 95% CI 1.07 to 2.98) and having a PCP (aOR 2.40, 95% CI 1.44 to 3.98). Among MSM with no or uncertain HBV vaccination, HBV testing was correlated with HCV testing (aOR 80.85, 95% CI 20.80 to 314.33), HIV testing (aOR 5.26, 95% CI 1.81 to 15.28), HIV-positive status (aOR 3.00, 95% CI 1.22 to 7.37) and having a PCP (aOR 2.69, 95% CI 1.00 to 7.26). CONCLUSIONS: Our data suggest many young MSM in China have not received hepatitis testing. HCV testing rates were lower than those recently reported among MSM in Australia and the USA. The strong correlation between HBV and HCV testing suggests bundled testing interventions may be useful for MSM in China. Men with a PCP were more likely to have received hepatitis testing, consistent with literature demonstrating the importance of primary care in expanding access to testing.

A crowdsourced intervention to promote hepatitis B and C testing among men who have sex with men in China: study protocol for a nationwide online randomized controlled trial.

BACKGROUND: The World Health Organization recommends all men who have sex with men (MSM) receive Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) testing. MSM in China are a high-risk group for HBV and HCV infection, but test uptake is low. Crowdsourcing invites a large group to solve a problem and then shares the solution with the public. This nationwide online randomized controlled trial will evaluate the effectiveness of a crowdsourced intervention to increase HBV and HCV testing among MSM in China. METHODS: Seven hundred MSM will be recruited through social media operated by MSM organizations in China. Eligible participants will be born biologically male, age 16 years or older, report previous anal sex with another man, and reside in China. After completing a baseline online survey, participants will be randomly assigned to intervention or control arms with a 1:1 allocation ratio. The intervention will include two components: (1) a multimedia component will deliver two videos and two images promoting HBV and HCV testing developed through a crowdsourcing contest in China; (2) a participatory component will invite men to submit suggestions for how to improve crowdsourced videos and images. The control arm will not view any images or videos and will not be invited to submit suggestions. All participants will be offered reimbursement for HBV and HCV testing costs. The primary outcome is HBV and HCV test uptake confirmed through electronic submission of test report photos within four weeks of enrolment. Secondary outcomes include self-reported HBV and HCV test uptake, HBV vaccination uptake, and change in stigma toward people living with HBV after four weeks. Primary and secondary outcomes will be calculated using intention to treat and as-exposed analyses and compared using two-sided 95% confidence intervals. DISCUSSION: Few previous studies have evaluated interventions to increase HBV and HCV testing in middle-income countries with a high burden of hepatitis. Delivering a crowdsourced intervention using social media is a novel approach to increasing hepatitis testing rates. HBV and HCV test uptake will be confirmed through test report photos, avoiding the limitations of self-reported testing outcomes. TRIAL REGISTRATION: NCT03482388 (29 March 2018).

Rate of language evolution is affected by population size.

The effect of population size on patterns and rates of language evolution is controversial. Do languages with larger speaker populations change faster due to a greater capacity for innovation, or do smaller populations change faster due to more efficient diffusion of innovations? Do smaller populations suffer greater loss of language elements through founder effects or drift, or do languages with more speakers lose features due to a process of simplification? Revealing the influence of population size on the tempo and mode of language evolution not only will clarify underlying mechanisms of language change but also has practical implications for the way that language data are used to reconstruct the history of human cultures. Here, we provide, to our knowledge, the first empirical, statistically robust test of the influence of population size on rates of language evolution, controlling for the evolutionary history of the populations and formally comparing the fit of different models of language evolution. We compare rates of gain and loss of cognate words for basic vocabulary in Polynesian languages, an ideal test case with a well-defined history. We demonstrate that larger populations have higher rates of gain of new words whereas smaller populations have higher rates of word loss. These results show that demographic factors can influence rates of language evolution and that rates of gain and loss are affected differently. These findings are strikingly consistent with general predictions of evolutionary models.

Chaperone-mediated 26S proteasome remodeling facilitates free K63 ubiquitin chain production and aggresome clearance.

Efficient elimination of misfolded proteins by the proteasome system is critical for proteostasis. Inadequate proteasome capacity can lead to aberrant aggregation of misfolded proteins and inclusion body formation, a hallmark of neurodegenerative disease. The proteasome system cannot degrade aggregated proteins; however, it stimulates autophagy-dependent aggregate clearance by producing unanchored lysine (K)63-linked ubiquitin chains via the proteasomal deubiquitinating enzyme Poh1. The canonical function of Poh1, which removes ubiquitin chains en bloc from proteasomal substrates prior to their degradation, requires intact 26S proteasomes. Here we present evidence that during aggresome clearance, 20S proteasomes dissociate from protein aggregates, while Poh1 and selective subunits of 19S proteasomes are retained. The dissociation of 20S proteasome components requires the molecular chaperone Hsp90. Hsp90 inhibition suppresses 26S proteasome remodeling, unanchored ubiquitin chain production, and aggresome clearance. Our results suggest that 26S proteasomes undergo active remodeling to generate a Poh1-dependent K63-deubiquitinating enzyme to facilitate protein aggregate clearance.

Impact of elexacaftor/tezacaftor/ivacaftor CFTR modulator therapy on rates of endoscopic sinus surgery in cystic fibrosis.

BACKGROUND: Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear. METHODS: The TriNetX Analytics Research Network, consisting of 120 million global de-identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery.1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA-approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF-related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS. RESULTS: ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5-2.75; p-value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54-5.85; p-value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non-CFTR modulator groups, except for reduced CF-related pulmonary exacerbations from 0 to 6 months post-FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators. CONCLUSIONS: In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF.

Respiratory Sensing Lead Malfunction in Upper Airway Stimulation: A Single Institution Report.

OBJECTIVES: Upper airway stimulation (UAS) is an effective treatment for patients with obstructive sleep apnea. The device consists of a stimulating electrode, an internal pulse generator, and a respiratory sensing lead. The purpose of this study is to characterize the incidence of sensing lead malfunction necessitating revision surgery in a high-volume center in conjunction with a review of the FDA Manufacturer and User Facility Device Experience (MAUDE) database reports on adverse events associated with the sensing lead component. METHODS: Patients age ≥18 implanted with the device were reviewed between July 2017 and June 2022. Those determined to have sensing lead malfunction were analyzed. The FDA MAUDE database was reviewed for reports associated with "Inspire Model 4323 Respiratory" and "Inspire Model 4340 Respiratory" between January 2014 and September 2022. RESULTS: One hundred ninety patients underwent UAS at our institution during the study period and four (2.1%) patients were found to have sensing lead malfunction. Analysis of the MAUDE database revealed 122 reports of adverse events associated with the sensing lead component, with 72% (88/122) of these requiring revision surgery. The most frequently reported adverse event was sensing lead tip separation from lead body, noted in 46% of these reports (56/122). CONCLUSION: The functionality of the sensing lead component is vital to the integrity of the UAS device and is measurable through waveform analysis. To provide optimal care after device implantation, it is essential to have a comprehensive understanding of the scenarios in which this component fails, the incidence of such events, and appropriate management. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1479-1484, 2024.

Influence of grandchildren on COVID-19 vaccination uptake among older adults in China: a parallel-group, cluster-randomized controlled trial.

The uptake of COVID-19 booster vaccination among older adults in China is suboptimal. Here, we report the results of a parallel-group cluster-randomized controlled trial evaluating the efficacy of promoting COVID-19 booster vaccination among grandparents (≥60 years) through a health education intervention delivered to their grandchildren (aged ≥16 years) in a Chinese cohort (Chinese Clinical Trial Registry: ChiCTR2200063240 ). The primary outcome was the uptake rate of COVID-19 booster dose among grandparents. Secondary outcomes include grandparents' attitude and intention to get a COVID-19 booster dose. A total of 202 college students were randomized 1:1 to either the intervention arm of web-based health education and 14 daily reminders (n = 188 grandparents) or control arm (n = 187 grandparents) and reported their grandparents' COVID-19 booster vaccination status at baseline and 21 days. Grandparents in the intervention arm were more likely to receive COVID-19 booster vaccination compared to control cohort (intervention, 30.6%; control, 16.9%; risk ratio = 2.00 (95% CI, 1.09 to 3.66)). Grandparents in the intervention arm also had greater attitude change (ß = 0.28 (95% CI, 0.04 to 0.52)) and intention change (ß = 0.32 (95% CI, 0.12 to 0.52)) to receive a COVID-19 booster dose. Our results show that an educational intervention targeting college students increased COVID-19 booster vaccination uptake among grandparents in China.