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.

Cardiovascular Disease Among Persons Living With HIV: New Insights Into Pathogenesis and Clinical Manifestations in a Global Context.

Widespread use of contemporary antiretroviral therapy globally has transformed HIV disease into a chronic illness associated with excess risk for disorders of the heart and circulatory system. Current clinical care and research has focused on improving HIV-related cardiovascular disease outcomes, survival, and quality of life. In high-income countries, emphasis on prevention of atherosclerotic coronary artery disease over the past decade, including aggressive management of traditional risk factors and earlier initiation of antiretroviral therapy, has reduced risk for myocardial infarction among persons living with human immunodeficiency virus-1 infection. Still, across the globe, persons living with human immunodeficiency virus-1 infection on effective antiretroviral therapy treatment remain at increased risk for ischemic outcomes such as myocardial infarction and stroke relative to the persons without HIV. Unique features of HIV-related cardiovascular disease, in part, include the pathogenesis of coronary disease characterized by remodeling ectasia and unusual plaque morphology, the relative high proportion of type 2 myocardial infarction events, abnormalities of the aorta such as aneurysms and diffuse aortic inflammation, and HIV cerebrovasculopathy as a contributor to stroke risk. Literature over the past decade has also reflected a shift in the profile and prevalence of HIV-associated heart failure, with a reduced but persistent risk of heart failure with reduced ejection fraction and a growing risk of heart failure with preserved ejection fraction. Cardiac magnetic resonance imaging and autopsy data have emphasized the central importance of intramyocardial fibrosis for the pathogenesis of both heart failure with preserved ejection fraction and the increase in risk of sudden cardiac death. Still, more research is needed to better characterize the underlying mechanisms and clinical phenotype of HIV-associated myocardial disease in the current era. Across the different cardiovascular disease manifestations, a common pathogenic feature is that HIV-associated inflammation working through different mechanisms may amplify underlying pathology because of traditional risk and other host factors. The prevalence and phenotype of individual cardiovascular disease manifestations is ultimately influenced by the degree of injury from HIV disease combined with the profile of underlying cardiometabolic factors, both of which may differ substantially by region globally.

A Neutralizing Monoclonal Antibody for Hospitalized Patients with Covid-19.

BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19. METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5. RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47). CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, 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.

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).

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.

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.

Investigation of Causal Effects of Protein Biomarkers on Cardiovascular Disease in Persons With HIV.

BACKGROUND: There is an incompletely understood increased risk for cardiovascular disease (CVD) among people with HIV (PWH). We investigated if a collection of biomarkers were associated with CVD among PWH. Mendelian randomization (MR) was used to identify potentially causal associations. METHODS: Data from follow-up in 4 large trials among PWH were used to identify 131 incident CVD cases and they were matched to 259 participants without incident CVD (controls). Tests of associations between 460 baseline protein levels and case status were conducted. RESULTS: Univariate analysis found CLEC6A, HGF, IL-6, IL-10RB, and IGFBP7 as being associated with case status and a multivariate model identified 3 of these: CLEC6A (odds ratio [OR] = 1.48, P = .037), HGF (OR = 1.83, P = .012), and IL-6 (OR = 1.45, P = .016). MR methods identified 5 significantly associated proteins: AXL, CHI3L1, GAS6, IL-6RA, and SCGB3A2. CONCLUSIONS: These results implicate inflammatory and fibrotic processes as contributing to CVD. While some of these biomarkers are well established in the general population and in PWH (IL-6 and its receptor), some are novel to PWH (HGF, AXL, and GAS6) and some are novel overall (CLEC6A). Further investigation into the uniqueness of these biomarkers in PWH and the role of these biomarkers as targets among PWH is warranted.

Reoperation for Recurrence is Affected by Type of Mesh in Laparoscopic Ventral Hernia Repair: A Nationwide Cohort Study.

OBJECTIVE: To compare the reoperation rate for recurrence between different mesh types in laparoscopic ventral hernia repair. SUMMARY OF BACKGROUND DATA: Ventral hernia repair has improved over the last decades. Nevertheless, recurrence rates are still high, and one type of mesh was recently found to increase it even more. METHODS: A nationwide cohort study based on prospectively collected data from the Danish Ventral Hernia Database. We included adult patients that had undergone a laparoscopic ventral hernia repair for either an incisional or a primary hernia. The primary and incisional hernias were analyzed in separate cohorts. The mesh-group with the lowest reoperation for recurrence curve was used as the reference. The outcome was reoperation for recurrence. RESULTS: Study population comprised 2874 patients with primary hernias and 2726 with incisional hernias. For primary hernias, Physiomesh [HR = 3.45 (2.16-5.51)] and Proceed Surgical Mesh [HR = 2.53 (1.35-4.75)] had a significantly higher risk of reoperation for recurrence than DynaMesh-IPOM. For incisional hernias, Physiomesh [HR = 3.90 (1.80-8.46), Ventralex Hernia Patch (HR = 2.99 (1.13-7.93), Parietex Composite (incl. Optimized) (HR = 2.55 (1.17-5.55), and Proceed Surgical Mesh (HR = 2.63 (1.11-6.20)] all had a significantly higher risk of reoperation for recurrence than Ventralight ST Mesh. CONCLUSION: For primary hernias, Physiomesh and Proceed Surgical Mesh had a significantly higher risk of reoperation for recurrence compared with DynaMesh-IPOM. For incisional hernias, the risk was significantly higher for Physiomesh, Parietex Composite, Ventralex Hernia Patch, and Proceed Surgical Mesh compared with Ventralight ST Mesh. This indicates that type of mesh may be associated with outcomes, and mesh choice could therefore depend on hernia type.

Development of a Simple, Point-of-Care Device to Test Anorectal Function in Patients with Constipation: Randomized Clinical Trial.

Functional constipation (FC) is one of the most frequently encountered gastrointestinal conditions in practice.1 Practice guidelines universally recommend that patients with typical constipation symptoms and no alarm features be treated empirically with dietary/lifestyle interventions and laxative therapy.2,3 Unfortunately, by the time a patient reaches a gastroenterologist, these treatments frequently have already been tried. Anorectal function testing (anorectal manometry [ARM] and balloon expulsion test [BET]) is the next best step in management guidelines in this all-too-common scenario, because treatment can then be targeted toward pelvic floor dysfunction or colon transit abnormalities. Unfortunately, more than 95% of patients continue to take only over-the-counter laxatives and receive empirical dietary advice, whereas fewer than 2% undergo physiologic evaluation to ascertain the cause of their symptoms.4 Indeed, more than 90% of patients desire more effective treatment options. These observations call into question the wisdom of a management strategy that fails to recognize the intrinsic diversity of the constipation universe and reinforces the misguided "one size fits all" empirical treatment strategy.

Can a Defecation Posture Modifying Device Correct an Abnormal Balloon Expulsion Test in Chronically Constipated Patients?

Evacuation disorders are common among chronically constipated (CC) patients who fail to respond to laxatives and are typically diagnosed by anorectal manometry (ARM) and/or balloon expulsion testing (BET).1,2 Recently, there has been emerging interest in the use of defecation posture-modifying devices (DPMDs) to improve constipation symptoms, presumably by replicating the physiologic benefits of squatting on stool evacuation, such as straightening of the anorectal angle and relaxing the pelvic floor. However, the ability of DPMDs to normalize anorectal function in adult patients with CC has not been studied.

Risk Factors for Abdominal Pain-Related Disorders of Gut-Brain Interaction in Adults and Children: A Systematic Review.

BACKGROUND & AIMS: Many studies have assessed risk factors of irritable bowel syndrome (IBS) and other abdominal pain-related disorders of gut-brain interaction (AP-DGBI); however, the role of these factors is unclear due to heterogeneous study designs. The aim of this systematic review was to extensively evaluate the literature and determine clinical risk and protective factors for the presence and persistence of AP-DGBI in children and adults. METHODS: A PubMed search identified studies investigating potential risk and protective factors for AP-DGBI in adults and children. Inclusion criteria included fully published studies with a control group; exclusion criteria included poor-quality studies (using a validated scale). For each factor, the proportion of studies that found the factor to be a risk factor, protective factor, or neither was summarized. The number of studies, diagnostic criteria, number of subjects, and average study quality rating provided further context. Whenever possible, a meta-analysis generated pooled odds ratios or mean difference. RESULTS: The systematic review included 348 studies. Female sex, gastroenteritis, abuse, stress, psychological disorders, somatic symptoms, and poor sleep were consistent risk factors for developing AP-DGBI in adults and children. In adults, additional risk factors included obesity, smoking, and increased use of medical resources. Protective AP-DGBI factors in adults included social support and optimism; no studies for protective factors were found for children. CONCLUSIONS: There are multiple risk factors for AP-DGBI in adults and children. These include female sex, gastroenteritis, abuse, stress, poor sleep, obesity, psychological disorders, and somatic symptoms. Additional studies are needed in children, on protective factors, and on factors associated with persistence of AP-DGBI.

An Office-Based, Point-of-Care Test Predicts Treatment Outcomes With Community-Based Pelvic Floor Physical Therapy in Patients With Chronic Constipation.

BACKGROUND & AIMS: Rectal evacuation disorders are common among constipated patients. We aimed to evaluate the accuracy of an investigational point-of-care test (rectal expulsion device [RED]) to predict outcomes with community-based pelvic floor physical therapy. METHODS: We enrolled patients meeting Rome IV criteria for functional constipation failing fiber/laxatives for more than 2 weeks. RED was inserted and self-inflated, and then time-to-expel was measured in a left lateral position. All patients underwent empiric community-based pelvic floor physical therapy in routine care with outcomes measured at 12 weeks. The primary end point was global clinical response (Patient Assessment of Constipation Symptoms score reduction, >0.75 vs baseline). Secondary end points included improvement in health-related quality-of-life (Patient Assessment of Constipation Quality of Life score reduction, >1.0) and complete spontaneous bowel movement frequency (Food and Drug Administration complete spontaneous bowel movement responder definition). RESULTS: Thirty-nine patients enrolled in a feasibility phase to develop the use-case protocol. Sixty patients enrolled in a blinded validation phase; 52 patients (mean, 46.9 y; 94.2% women) were included in the intention-to-treat analysis. In the left lateral position, RED predicted global clinical response (generalized area under the curve [gAUC], 0.67; 95% CI, 0.58-0.76]), health-related quality-of-life response (gAUC, 0.67; 95% CI, 0.58-0.77; P < .001), and complete spontaneous bowel movement response (gAUC, 0.63; 95% CI, 0.57-0.71; P < .001). As a screening test, a normal RED effectively rules out evacuation disorders (expected clinical response, 8.9%; P = .042). Abnormal RED in the left lateral position (defined as expulsion within 5 seconds or >120 seconds) predicted 48.9% clinical response to physical therapy. A seated maneuver enhanced the likelihood of clinical response (71.1% response with seated RED retained >13 seconds) but likely is unnecessary in most settings. CONCLUSIONS: RED offers an opportunity to disrupt the paradigm by offering a personalized approach to managing chronic constipation in the community (Clinicaltrials.gov: NCT04159350).

Utility of Anorectal Testing to Predict Outcomes With Pelvic Floor Physical Therapy in Chronic Constipation: Pragmatic Trial.

BACKGROUND & AIMS: We performed a clinical trial that aimed to inform the clinical utility of anorectal manometry (ARM) and balloon expulsion time (BET) as up-front tests to predict outcomes with community-based pelvic floor physical therapy as the next best step to address chronic constipation after failing an empiric trial of soluble fiber supplementation or osmotic laxatives. METHODS: We enrolled 60 treatment-naïve patients with Rome IV functional constipation failing 2 weeks of soluble fiber supplementation or osmotic laxatives. All patients underwent ARM/BET (London protocol) followed by community-based pelvic floor physical therapy. Outcomes were assessed at baseline and 12 weeks. The primary end point was clinical response (Patient Assessment of Constipation-Symptoms instrument). RESULTS: Fifty-three patients completed pelvic rehabilitation and the post-treatment questionnaire. Contemporary frameworks define dyssynergia on balloon expulsion time and dyssynergic patterns (ARM), but these parameters did not inform clinical outcomes (area under the curve [AUC], <0.6). Squeeze pressure (>192.5 mm Hg on at least 1 of 3 attempts; sensitivity, 47.6%; specificity, 83.9%) and limited squeeze duration (inability to sustain 50% of squeeze pressure for >20 seconds; sensitivity, 71.4%; specificity, 58.1%) were the strongest predictors of clinical outcomes. Combining BET with squeeze duration (BET greater than 6.5 seconds and limited squeeze duration) improved predictive accuracy (AUC, 0.75; 95% CI, 0.59-0.90). BET poorly predicted outcomes as a single test (AUC, 0.54; 95% CI, 0.38-0.69). CONCLUSIONS: Using ARM to evaluate squeeze profiles, rather than dyssynergia, appears useful to screen patients with chronic constipation for up-front pelvic floor physical therapy based on likelihood of response. BET appears noninformative as a single screening test (ClinicalTrials.gov: NCT04159350).

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.

HIV-PASS (Pain and Sadness Support): Randomized Controlled Trial of a Behavioral Health Intervention for Interference Due to Pain in People Living With HIV, Chronic Pain, and Depression.

OBJECTIVE: This study aimed to determine whether HIV-Pain and Sadness Support (HIV-PASS), a collaborative behavioral health intervention based on behavioral activation, is associated with decreased pain-related interference with daily activities, depression, and other outcomes in people living with HIV. METHODS: We conducted a three-site clinical trial ( n = 187) in which we randomly assigned participants to receive either HIV-PASS or health education control condition. In both conditions, participants received seven intervention sessions, comprising an initial in-person joint meeting with the participant, their HIV primary care provider and a behavioral health specialist, and six, primarily telephone-based, meetings with the behavioral health specialist and participant. The intervention period lasted 3 months, and follow-up assessments were conducted for an additional 9 months. RESULTS: Compared with health education, HIV-PASS was associated with significantly lower pain-related interference with daily activities at the end of month 3 (our primary outcome; b = -1.31, 95% confidence interval = -2.28 to -0.34). We did not observe other differences between groups at 3 months in secondary outcomes that included worst or average pain in the past week, depression symptoms, anxiety, and perceived overall mental and physical health. There were no differences between groups on any outcomes at 12 months after enrollment. CONCLUSIONS: A targeted intervention can have positive effects on pain interference. At the end of intervention, effects we found were in a clinically significant range. However, effects diminished once the intervention period ended. TRIAL REGISTRATION: ClinicalTrials.gov NCT02766751.

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.

Strategies Used to Manage Chronic Pain in HIV-Disease: Comparing Persons Prescribed Opioids Versus Persons not Receiving Opioids.

Chronic pain is common in people living with HIV (PLWH), causes substantial disability and is associated with limitations in daily activities. Opioids are commonly prescribed for pain treatment among PLWH, but evidence of sustained efficacy is mixed. There is little information available on how PLWH who have chronic pain use multimodal strategies in pain management. The current cross-sectional study examined background characteristics, self-reported pain, and the use of other pain treatments among 187 PLWH with chronic pain and depressive symptoms who were and were not prescribed opioids. Approximately 20.9% of participants reported using prescription opioids at the time of the study interview. These individuals were significantly more likely to report having engaged in physical therapy or stretching, strengthening or aerobic exercises in the previous 3 months, recent benzodiazepine use, and receiving disability payments. There were no significant differences in pain characteristics (pain-related interference, average pain severity, and worst pain severity) between the two groups. Those not prescribed opioids were more likely to report better concurrent physical functioning and general health, and fewer physical role limitations, but higher depression symptom severity. Our findings suggest that many PLWH with chronic pain and depressive symptoms express high levels of pain with deficits in physical function or quality of life despite their use of opioids. The high rate of co-use of opioids and benzodiazepines (30.8%) is a concern because it may increase risk of overdose. An integrated care approach that includes a variety of effective non-pharmacologic treatment strategies such as physical therapy may be beneficial in reducing the reliance on opioids for pain management.

Anger and substance use in HIV-positive patients with chronic pain.

Chronic pain increases the risk of substance use in people living with HIV (PLWH). Depression and anxiety have also been identified as risk factors for substance use among PLWH. Relatedly, other negative mood states, such as anger, may influence chronic pain among PLWH. The current cross-sectional study examined whether the distinct negative mood state of anger is associated with substance use among 187 PLWH who report chronic pain. Using negative binomial regression analyses, we found higher levels of anger were positively associated with alcohol use. Higher levels of anger were inversely associated with benzodiazepine use. No association was found between anger and marijuana use, and there were no significant interactions between anger and pain severity on substance use. Our findings suggest that anger is an independent risk factor for substance use among PLWH and chronic pain. Addressing anger may be useful when adapting behavioral therapies in the treatment of pain among PLWH.

The relationship between substance use and physical activity among people living with HIV, chronic pain, and symptoms of depression: a cross-sectional analysis.

ABSTRACTChronic pain, depression, and substance use are common among people living with HIV (PLWH). Physical activity can improve pain and mental health. Some substances such as cannabis may alleviate pain, which may allow PLWH to participate in more physical activity. However, risks of substance use include poorer mental health and HIV clinical outcomes. This cross-sectional analysis examined the relationships of self-reported substance use (alcohol, cannabis, and nicotine use), gender, and age with self-reports of walking, moderate physical activity, and vigorous physical activity, converted to Metabolic Equivalent of Task Units (METs), among 187 adults living with HIV, chronic pain, and depressive symptoms in the United States. Women reported less walking, vigorous activity, and total physical activity compared to men. Individuals who used cannabis reported more vigorous physical activity relative to those who did not use cannabis. These findings were partially accounted for by substance use*gender interactions: men using cannabis reported more vigorous activity than all other groups, and women with alcohol use reported less walking than men with and without alcohol use. Research is needed to increase physical activity among women who use substances and to evaluate reasons for the relationship between substance use and physical activity among men.