Coatings for Permanent Meshes Used to Enhance Healing in Abdominal Hernia Repair: A Scoping Review.

INTRODUCTION: Hernia meshes are used to reduce recurrence and pain rates, but the rates are still high. This could be improved with coatings of the mesh. This scoping review aimed to provide an overview of mesh coatings used to promote healing in abdominal hernia repair and to report beneficial and unbeneficial effects. METHODS: We included human and animal studies with abdominal hernias that were repaired with non-commercially coated meshes. We searched Pubmed, Embase, Cochrane Central, LILACS, and CNKI without language constraints. RESULTS: Of 2933 identified studies, 58 were included: six studies had a total of 408 humans and 52 studies had 2679 animals. The median follow-up was 12 months (range 1-156), and 95% of the hernias were incisional. There were 44 different coatings which included platelet-rich plasma, mesenchymal stem cells, growth factors, vitamin E, collagen-derived products, various polysaccharides, silk proteins, chitosan, gentamycin, doxycycline, nitrofurantoin, titanium, and diamond-like carbon. Mesenchymal stem cells and platelet-rich plasma were the most researched. Mesenchymal stem cells notably reduced inflammation and foreign body reactions but did not impact other healing metrics. In contrast, platelet-rich plasma positively influenced tissue ingrowth, collagen deposition, and neovascularization and had varying effects on inflammation and foreign body reactions. CONCLUSION: We identified 44 different mesh coatings and they showed varying results. Mesenchymal stem cells and platelet-rich plasma were the most studied, with the latter showing considerable promise in improving biomechanical properties in hernia repair. Further investigations are needed to ascertain their definitive use in humans.

Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study.

BACKGROUND: Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes. METHODS: In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery. FINDINGS: The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors. INTERPRETATION: Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment. FUNDING: US National Institutes of Health.

A Pilot Randomized Controlled Trial of an mHealth Intervention to Improve PrEP Adherence Among Young Sexual Minority Men.

This randomized controlled study assessed the feasibility, acceptability, and preliminary impact of the PrEP iT! mHealth intervention designed to improve PrEP adherence among young men who have sex with men (YMSM). A national sample of 80 YMSM in the U.S. (Mage = 25 years; 54% racial/ethnic minority), recruited through social media ads, were randomized to either the PrEP iT! or usual PrEP care conditions. Participants completed online surveys and submitted self-collected dried blood sample (DBS) data as measures of PrEP adherence. Differences in PrEP adherence across treatment arms and between participants with high versus low engagement in PrEP iT! were assessed. Retention was high at the three (94%) and six (93%) month assessment, and participants in PrEP iT! reported satisfactory acceptability of the intervention. There were no significant differences in self-reported or DBS-derived PrEP adherence between randomized groups. However, YMSM in the PrEP iT! group with high PrEP adherence (the equivalent of four or more doses/week through self-report and DBS-derived measures) demonstrated significantly higher engagement in the intervention than those with low PrEP adherence (the equivalent of 3 or fewer doses/week). Overall, the PrEP iT! intervention demonstrated strong feasibility and acceptability. The finding that high PrEP iT! intervention engagement was associated with protective levels of PrEP adherence suggests it is a viable adherence support tool that should be further evaluated in definitive trial among YMSM who need basic support, or as part of a more comprehensive adherence support package for those who need greater assistance.Trial registration Clinical Trials # NCT04509076 (registered August 10, 2020).

MAVMET trial: maraviroc and/or metformin for metabolic dysfunction-associated fatty liver disease(MAFLD) in adults with suppressed HIV.

OBJECTIVE: Metabolic dysfunction-associated fatty liver disease (MAFLD) is over-represented in people living with HIV (PLWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism. DESIGN: Open-label, 48-week randomised trial with a 2x2 factorial design. SETTING: Multicentre HIV clinics. PARTICIPANTS: Nondiabetic, virologically-suppressed PLWH, aged ≥35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features). INTERVENTION: Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone. PRIMARY OUTCOME: Change in liver fat fraction (LFF) between baseline and week-48 using Magnetic Resonance Proton Density Fat Fraction (MR PDFF). RESULTS: Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between 19-Mar-2018 and 11-November-2019. 70% had imaging/biopsy plus ≥1 MAFLD criteria. The analysis included 82/90 with week-0 and -48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40%, 38%, 8%, and 14% had grade zero, one, two, and three steatosis respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% CI 2.97, 5.48], P < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53-0.68, P = 0.45]), MET (-0.62 [-1.81-0.56, P = 0.30]), and MVC+MET (-1.04 [-2.74-0.65, P = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%. CONCLUSIONS: Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced MR PDFF compared to ART alone.

Sexual Racism on Geosocial Networking Applications and Identity Outness Among Sexual Minority Men in the US.

Although the use of geosocial networking (GSN) applications for relationship seeking is prevalent among sexual minority men (SMM), SMM of color may be vulnerable to sexual racism online. Little is known about how sexual racism relates to SMM of color's identity outness, which is integral to the minority stress model and the focus of this study. Eighty SMM, recruited through social media (53.7% racial/ethnic minority), reported their experiences of race-based discrimination on GSN apps and identity outness. Chi-squared and Fisher's tests examined differences in race-based discrimination online by participants' race/ethnicity. A factorial MANOVA was performed on outness to family, peers, and healthcare providers. Nearly one-third of participants experienced race-based discrimination online. Higher percentages of SMM of color experienced race-based discrimination than White SMM. SMM who experienced race-based discrimination online reported lower outness to family than those who had not. Post-hoc analyses revealed that Asian SMM reported consistently lower outness than other groups. Our findings resonated with the mediation framework of minority stress, suggesting that sexual racism online may be a distal stressor that contributes to the group-specific process of identity outness. This also illustrated the importance of addressing sexual racism on GSN apps to buffer existing stress with outness among SMM of color.

Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract in Cystic Fibrosis.

PURPOSE OF REVIEW: To discuss all the various motility disorders impacting people with Cystic Fibrosis (PwCF) and provide diagnostic and management approaches from a group of pediatric and adult CF and motility experts and physiologists with experience in the management of this disease. RECENT FINDINGS: Gastrointestinal (GI) symptoms coexist with pulmonary symptoms in PwCF regardless of age and sex. The GI manifestations include gastroesophageal reflux disease, esophageal dysmotility gastroparesis, small bowel dysmotility, small intestinal bacterial overgrowth syndrome, distal idiopathic obstruction syndrome, constipation, and pelvic floor disorders. They are quite debilitating, limiting the patients' quality of life and affecting their nutrition and ability to socialize. This genetic disorder affects many organ systems and is chronic, potentially impacting fertility and future family planning, requiring a multidisciplinary approach. Our review discusses the treatments of motility disorders in CF, their prevalence and pathophysiology. We have provided a framework for clinicians who care for these patients that can help to guide their clinical management.

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978.

Cardio-renal-metabolic disease in primary care setting.

In the primary care setting providers have more tools available than ever before to impact positively obesity, diabetes, and their complications, such as renal and cardiac diseases. It is important to recognise what is available for treatment taking into account diabetes heterogeneity. For those who develop type 2 diabetes (T2DM), effective treatments are available that for the first time have shown a benefit in reducing mortality and macrovascular complications, in addition to the well-established benefits of glucose control in reducing microvascular complications. Some of the newer medications for treating hyperglycaemia have also a positive impact in reducing heart failure (HF). Technological advances have also contributed to improving the quality of care in patients with diabetes. The use of technology, such as continuous glucose monitoring systems (CGM), has improved significantly glucose and glycated haemoglobin A1c (HbA1c) values, while limiting the frequency of hypoglycaemia. Other technological support derives from the use of predictive algorithms that need to be refined to help predict those subjects who are at great risk of developing the disease and/or its complications, or who may require care by other specialists. In this review we also provide recommendations for the optimal use of the new medications; sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like peptide-receptor agonists 1 (GLP1RA) in the primary care setting considering the relevance of these drugs for the management of T2DM also in its early stage.

ChatGPT-4 and Human Researchers Are Equal in Writing Scientific Introduction Sections: A Blinded, Randomized, Non-inferiority Controlled Study.

Background Natural language processing models are increasingly used in scientific research, and their ability to perform various tasks in the research process is rapidly advancing. This study aims to investigate whether Generative Pre-trained Transformer 4 (GPT-4) is equal to humans in writing introduction sections for scientific articles. Methods This randomized non-inferiority study was reported according to the Consolidated Standards of Reporting Trials for non-inferiority trials and artificial intelligence (AI) guidelines. GPT-4 was instructed to synthesize 18 introduction sections based on the aim of previously published studies, and these sections were compared to the human-written introductions already published in a medical journal. Eight blinded assessors randomly evaluated the introduction sections using 1-10 Likert scales. Results There was no significant difference between GPT-4 and human introductions regarding publishability and content quality. GPT-4 had one point significantly better scores in readability, which was considered a non-relevant difference. The majority of assessors (59%) preferred GPT-4, while 33% preferred human-written introductions. Based on Lix and Flesch-Kincaid scores, GPT-4 introductions were 10 and two points higher, respectively, indicating that the sentences were longer and had longer words. Conclusion GPT-4 was found to be equal to humans in writing introductions regarding publishability, readability, and content quality. The majority of assessors preferred GPT-4 introductions and less than half could determine which were written by GPT-4 or humans. These findings suggest that GPT-4 can be a useful tool for writing introduction sections, and further studies should evaluate its ability to write other parts of scientific articles.

Attitudes Toward and Beliefs in the Effectiveness of Biomedical HIV Prevention Strategies Among Emerging and Young Adult Sexual Minority Men.

BACKGROUND: Pre-exposure prophylaxis (PrEP) and HIV treatment as prevention, which underlies the Undetectable = Untransmittable (U = U) campaign, are two effective biomedical approaches for HIV prevention among sexual minority men (SMM). Attitudes toward PrEP and U = U may differ between SMM emerging adults (EA: 18-24 years old) and young adults (YA: 25-29 years old) to drive differences in sexual behavior. However, to date, few studies assessed the degree to which YAs and EAs differ in their beliefs in the effectiveness of PrEP and U = U. METHOD: A national sample of 80 SMM in the USA (Mage = 25.1 years; 53.7% racial/ethnic minority; 38.8% EA; 61.3% YA) participated in a 6-month mHealth intervention for PrEP adherence. Non-parametric tests assessed differences in sexual behaviors and attitudes toward the effectiveness of PrEP and U = U between EAs and YAs using baseline data. RESULTS: Compared to EAs, higher proportions of YAs trusted PrEP's effectiveness and considered condom use unnecessary after taking PrEP. More YAs than EAs were willing to engage in sexual behaviors that they felt too risky before learning about U = U and were more comfortable having condomless sex with HIV-positive partners. Conversely, a greater proportion of EAs than YAs preferred to use condoms even when their partners are on anti-HIV medications. CONCLUSION: Overall, YAs trusted the effectiveness of U = U and PrEP more than EAs, underscoring developmental differences in SMM's perspectives on biomedical HIV prevention tools. Our findings underscore the importance of tailoring messages on biomedical HIV prevention options differently for EAs and YAs to optimize uptake.

Parental Distress and Parenting Behavior in Families of Preschool Children with and Without ASD: Spillover and Buffering.

Parents of children with autism spectrum disorder (ASD) report increased distress relative to parents of children with neurotypical development. Parent well-being is generally considered a key determinant of parenting behavior, thus increased distress may spill over into less optimal parenting in families of children with ASD. However, evidence is mixed regarding the degree to which parenting is actually compromised in this population, suggesting the possibility of buffering, wherein the parenting of children with ASD may be robust against spillover from increased parental distress. The current study tested competing spillover and buffering models with regard to relations among child ASD status, parental distress, and parenting behavior. Parents of preschoolers with (n = 73) and without (n = 55) ASD completed self-report measures of parenting stress, depressive symptoms, and emotion dysregulation, as well as of positive and negative parenting behaviors. Families of preschoolers with ASD reported higher distress and negative parenting, and lower positive parenting than did their counterparts. Findings supported the spillover model for negative parenting such that increased parental distress accounted for status-group differences in negative parenting. In contrast, potential buffering was observed for positive parenting in that an inverse association between distress and parenting was observed for parents of children with neurotypical development only. Findings highlight the potential benefit of intervention to reduce parental distress in families of children with ASD, but also suggest some existing ability of these families to buffer certain parenting behaviors from deleterious effects of parent distress.

A comparison of cover letters written by ChatGPT-4 or humans.

INTRODUCTION: Artificial intelligence has started to become a part of scientific studies and may help researchers with a wide range of tasks. However, no scientific studies have been published on its ussefulness in writing cover letters for scientific articles. This study aimed to determine whether Generative Pre-Trained Transformer (GPT)-4 is as good as humans in writing cover letters for scientific papers. METHODS: In this randomised non-inferiority study, we included two parallel arms consisting of cover letters written by humans and by GPT-4. Each arm had 18 cover letters, which were assessed by three different blinded assessors. The assessors completed a questionnaire in which they had to assess the cover letters with respect to impression, readability, criteria satisfaction, and degree of detail. Subsequently, we performed readability tests with Lix score and Flesch Kincaid grade level. RESULTS: No significant or relevant difference was found on any parameter. A total of 61% of the blinded assessors guessed correctly as to whether the cover letter was written by GPT-4 or a human. GPT-4 had a higher score according to our objective readability tests. Nevertheless, it performed better than human writing on readability in the subjective assessments. CONCLUSION: We found that GPT-4 was non-inferior at writing cover letters compared to humans. This may be used to streamline cover letters for researchers, providing an equal chance to all researchers for advancement to peer-review. FUNDING: This study received no financial support from external sources. TRIAL REGISTRATION: This study was not registered before the study commenced.

Nerve identification during open inguinal hernia repair: a systematic review and meta-analyses.

PURPOSE: Inguinal hernia repair is one of the most common operations worldwide and despite this, the incidence of chronic pain remains high after inguinal hernia repair. The optimal nerve handling strategy is controversial and the rate at which nerves are identified remains uncertain. This study aimed to determine the identification rates of the ilioinguinal, iliohypogastric, and genitofemoral nerves as well as nerve handling strategies. METHODS: This review was registered on PROSPERO (CRD 42023416576). PubMed, Embase, and Cochrane Central were systematically searched. Studies with more than 10 patients were included if they reported an identification rate for at least one of the nerves during elective open inguinal hernia repair in adults. Studies requiring nerve identification in their study design were excluded. Bias was assessed with the JBI critical appraisal tool and Cochrane's RoB-2 tool. The overall estimate of the prevalence was analysed with prevalence meta-analyses. RESULTS: A total of 23 studies were included. The meta-analyses included 18 studies, which resulted in an identification rate of 82% (95% CI: 76-87%) for the ilioinguinal nerve, 62% (95% CI: 54-71%) for the iliohypogastric nerve, and 41% (95% CI: 27-55%) for the genitofemoral nerve. Nerves were spared in 82% of all repairs. CONCLUSION: The ilioinguinal, iliohypogastric, and genitofemoral nerves were identified in 82%, 62%, and 41% of surgeries, respectively. Most studies used a nerve-preserving strategy. The role of nerve identification in the development of chronic pain remains uncertain, as well as the optimal nerve handling strategy.

Myocardial extracellular volume fraction is positively associated with activated monocyte subsets among cART-treated persons living with HIV in South Africa.

BACKGROUND: Despite treatment with combination antiretroviral therapy (cART), persons living with HIV (PLWH) are at higher risk of cardiac structural abnormalities that may presage clinical heart failure, including myocardial fibrosis. This study assessed whether circulating cellular and soluble protein markers of immune activation cross-sectionally associate with myocardial fibrosis among cART-treated PLWH in South Africa. METHODS: Participants were enrolled in Khayelitsha township near Cape Town, SA. Cardiac magnetic resonance imaging was performed. Plasma protein biomarkers were measured using enzyme-linked immunoassays and monocyte phenotypes were evaluated using flow cytometry. Associations were assessed using multivariable linear and logistic regression. RESULTS: Among 69 cART-treated PLWH, mean (SD) age was 48 (10) years, 71% were female, and time since HIV diagnosis was 9 (6) years. Evidence of left ventricular fibrosis by late gadolinium enhancement was present in 74% of participants and mean (SD) extracellular volume fraction (ECV) was 30.9 (5.9)%. Degree of myocardial fibrosis/inflammation measured by ECV was positively associated with percentages of circulating non-classical and intermediate monocyte phenotypes reflecting inflammation and tissue injury. CONCLUSION: These data generate hypotheses on possible immune mechanisms of HIV-associated non-ischemic myocardial disease, specifically among cART-treated PLWH in sub-Saharan Africa, where the majority of the HIV burden exists globally.

An open label randomized controlled trial of atorvastatin versus aspirin in elite controllers and antiretroviral-treated people with HIV.

BACKGROUND: Residual inflammation in people with HIV (PWH) despite suppression of HIV replication is associated with many comorbidities including cardiovascular disease. Targeting inflammation may decrease the risk of cardiovascular disease. METHODS: An open label randomized study was conducted to evaluate the effect of nine months of 81 mg aspirin versus 40 mg atorvastatin in antiretroviral therapy (ART) treated PWH and elite controllers (EC), not on ART. Biomarkers associated with inflammation and virologic indices were measured and analyzed using nonparametric and linear mixed effect models. RESULTS: Fifty-three participants were randomized and 44 were included in the final analysis. Median age was 54 years, 72% were male, 59% were Black. Median CD4 + count was 595 cells/µl in the aspirin and 717 cells/µl in the atorvastatin arm. After 9 months of treatment, plasma soluble (s) CD14 + was reduced in the aspirin group within both treated PWH and EC ( P  = 0.0229), yet only within treated PWH in the atorvastatin group ( P  = 0.0128). A 2.3% reduction from baseline in tissue factor levels was also observed in the aspirin arm, driven by the EC group. In the atorvastatin arm, there was a 4.3% reduction in interleukin-8 levels ( P  = 0.02) and a small decrease of activated CD4 + T cells ( P  < 0.001). No statistically significant differences were observed in the plasma HIV viral load and cell-associated (CA) HIV DNA and RNA. CONCLUSIONS: Aspirin and atorvastatin could play a role in targeting HIV-associated inflammation. Elite controllers may warrant special consideration for anti-inflammatory strategies.

Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations.

BACKGROUND & AIMS: Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings. METHODS: Leaders in medical and surgical gastroenterology and physical therapy with interest in anorectal disorders were surveyed regarding practice patterns and utilization of these technologies. Subsequently, a roundtable was held to discuss survey results, explore current diagnostic and therapeutic challenges with these technologies, review the literature, and generate consensus-based recommendations. RESULTS: ARM identifies key pathophysiological abnormalities such as dyssynergic defecation, anal sphincter weakness, or rectal sensory dysfunction, and is a critical component of biofeedback therapy, an evidence-based treatment for patients with dyssynergic defecation and fecal incontinence. Additionally, ARM has the potential to enhance health-related quality of life and reduce healthcare costs. However, it has significant barriers that include a lack of education and training of healthcare providers regarding the utility and availability of ARM and biofeedback procedures, as well as challenges with condition-specific testing protocols and interpretation. Additional barriers include understanding when to perform, where to refer, and how to use these technologies, and confusion over billing practices. CONCLUSIONS: Overcoming these challenges with appropriate education, training, collaborative research, and evidence-based guidelines for ARM testing and biofeedback therapy could significantly enhance patient care of anorectal disorders.

Derivation of a Protein Risk Score for Cardiovascular Disease Among a Multiracial and Multiethnic HIV+ Cohort.

Background Cardiovascular disease risk prediction models underestimate CVD risk in people living with HIV (PLWH). Our goal is to derive a risk score based on protein biomarkers that could be used to predict CVD in PLWH. Methods and Results In a matched case-control study, we analyzed normalized protein expression data for participants enrolled in 1 of 4 trials conducted by INSIGHT (International Network for Strategic Initiatives in Global HIV Trials). We used dimension reduction, variable selection and resampling methods, and multivariable conditional logistic regression models to determine candidate protein biomarkers and to generate a protein score for predicting CVD in PLWH. We internally validated our findings using bootstrap. A protein score that was derived from 8 proteins (including HGF [hepatocyte growth factor] and interleukin-6) was found to be associated with an increased risk of CVD after adjustment for CVD and HIV factors (odds ratio: 2.17 [95% CI: 1.58-2.99]). The protein score improved CVD prediction when compared with predicting CVD risk using the individual proteins that comprised the protein score. Individuals with a protein score above the median score were 3.10 (95% CI, 1.83-5.41) times more likely to develop CVD than those with a protein score below the median score. Conclusions A panel of blood biomarkers may help identify PLWH at a high risk for developing CVD. If validated, such a score could be used in conjunction with established factors to identify CVD at-risk individuals who might benefit from aggressive risk reduction, ultimately shedding light on CVD pathogenesis in PLWH.

The Use of Daily and On-Demand Oral Pre-Exposure Prophylaxis Dosing Strategies Among Young Adult Gay, Bisexual and Other Men who have Sex with Men Enrolled in an mHealth Adherence Intervention.

Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention option for gay, bisexual and other men who have sex with men (GBMSM). However, with newer PrEP options, a greater understanding of whether and why GBMSM switch dosing strategies is needed to inform clinical practice and research. We assessed the dosing strategies (daily or on-demand) of GBMSM enrolled in an mHealth PrEP adherence pilot intervention at four timepoints over approximately 10 months. Among GBMSM with complete data (n = 66), a consistent daily dosing strategy was used by most (73%) participants across all time points, while on-demand PrEP was used at least once during the study period by 27% of participants. A higher percentage of on-demand PrEP users self-reported as Asian/Pacific Islander and had less positive attitudes toward PrEP, adjusting for key sociodemographic variables and intervention arm. Daily PrEP users reported high numbers of sexual partners, and the primary reason that they would switch to on-demand PrEP is reduced sexual activity. At the final assessment, 75% of participants were taking daily PrEP, of whom 27% reported that they would like to switch to another option, including on-demand and long-acting injectable PrEP. While findings were largely descriptive, they showed that switches in PrEP dosing strategies are relatively common and PrEP strategy choice may vary across racial and ethnic groups.

Beyond Undetectable: Modeling the Clinical Benefit of Improved Antiretroviral Adherence in Persons With Human Immunodeficiency Virus With Virologic Suppression.

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown. Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials. Comparatively, assuming 100% ART adherence in a PWH who achieves viral suppression, we estimated the number of persons in whom a decrease in adherence to <100% would need to be observed for an additional SNAE or death event to occur during 3- and 5-year follow-up. Results: Increasing ART adherence to 100% in PWH who are suppressed on ART despite imperfect adherence translated into a 6%-37% reduction in the risk of SNAEs or death. Comparatively, based on an anticipated 12% increase in IL-6, 254 and 165 PWH would need to decrease their adherence from 100% to <100% for an additional event to occur over 3- and 5-year follow-up, respectively. Conclusions: Modest gains in ART adherence could have clinical benefits beyond virologic suppression. Increasing ART adherence (eg, via an intervention or switch to long-acting ART) in PWH who remain virally suppressed despite incomplete adherence should be evaluated.