Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19.

BACKGROUND: REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS: We randomly assigned, in a 1:1 ratio, participants (≥12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARS-CoV-2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase-quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS: Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P<0.001). In weeks 2 to 4, a total of 2 of 753 participants in the REGEN-COV group (0.3%) and 27 of 752 participants in the placebo group (3.6%) had symptomatic SARS-CoV-2 infection (relative risk reduction, 92.6%). REGEN-COV also prevented symptomatic and asymptomatic infections overall (relative risk reduction, 66.4%). Among symptomatic infected participants, the median time to resolution of symptoms was 2 weeks shorter with REGEN-COV than with placebo (1.2 weeks and 3.2 weeks, respectively), and the duration of a high viral load (>104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS: Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04452318.).

Correlates of Recent HIV Testing Among People Who Inject Drugs in Rural Areas: A Multi-site Cross-Sectional Study, 2018-2020.

The Rural Opioid Initiative surveyed 2693 people who inject drugs (PWID) in eight rural U.S. areas in 2018-2020 about self-reported HIV testing in the past 6 months. Correlates of interest included receipt of any drug-related services, incarceration history, and structural barriers to care (e.g., lack of insurance, proximity to syringe service programs [SSP]). Overall, 20% of participants reported receiving an HIV test within the past 6 months. Multivariable generalized estimating equations showed that attending substance use disorder (SUD) treatment (OR 2.11, 95%CI [1.58, 2.82]), having health insurance (OR 1.42, 95%CI [1.01, 2.00]) and recent incarceration (OR 1.49, 95%CI [1.08, 2.04]) were positively associated with HIV testing, while experiencing a resource barrier to healthcare (inability to pay, lack of transportation, inconvenient hours, or lack of child care) had inverse (OR 0.73, 95%CI [0.56, 0.94]) association with HIV testing. We found that the prevalence of HIV testing among rural PWID is low, indicating an unmet need for testing. While SUD treatment or incarceration may increase chances for HIV testing for rural PWID, other avenues for expanding HIV testing, such as SSP, need to be explored.

Intersection of Syphilis and Human Immunodeficiency Virus (HIV) Networks to Identify Opportunities to Enhance HIV Prevention.

BACKGROUND: Human immunodeficiency virus (HIV) and syphilis infection continue at disproportionate rates among minority men who have sex with men (MSM) in the United States. The integration of HIV genetic clustering with partner services can provide important insight into local epidemic trends to guide interventions and control efforts. METHODS: We evaluated contact networks of index persons defined as minority men and transgender women diagnosed with early syphilis and/or HIV infection between 2018 and 2020 in 2 North Carolina regions. HIV clusters were constructed from pol sequences collected through statewide surveillance. A combined "HIV-risk" network, which included persons with any links (genetic or sexual contact) to HIV-positive persons, was evaluated by component size, demographic factors, and HIV viral suppression. RESULTS: In total, 1289 index persons were identified and 55% named 1153 contacts. Most index persons were Black (88%) and young (median age 30 years); 70% had early syphilis and 43% had prevalent HIV infection. Most people with HIV (65%) appeared in an HIV cluster. The combined HIV-risk network (1590 contact network and 1500 cluster members) included 287 distinct components; however, 1586 (51%) were in a single component. Fifty-five percent of network members with HIV had no evidence of viral suppression. Overall, fewer index persons needed to be interviewed to identify 1 HIV-positive member without viral suppression (1.3 vs 4.0 for contact tracing). CONCLUSIONS: Integration of HIV clusters and viral loads illuminate networks with high HIV prevalence, indicating recent and ongoing transmission. Interventions intensified toward these networks may efficiently reach persons for HIV prevention and care re-engagement.

Hepatitis C coinfection and extrahepatic cancer incidence among people living with HIV.

OBJECTIVES: We assessed the incidence of extrahepatic cancer among people with HIV/HCV coinfection and the potential impact of direct-acting antivirals (DAAs) on extrahepatic cancer risk among people with HIV/HCV coinfection. DESIGN: Our study cohort included adults who initiated HIV care at a CNICS site in the US during 1995-2017, excluding those with previous cancer and without HCV testing. METHODS: We used Cox regression to estimate hazard ratios for extrahepatic cancer incidence among patients with HIV/HCV coinfection compared with those with HIV monoinfection. Standardized morbidity ratio (SMR) weights were used to create a 'pseudopopulation' in which all patients were treated with antiretroviral therapy (ART), and to compare extrahepatic cancer incidence among patients with untreated HIV/HCV coinfection with the incidence that would have been observed if they had been successfully treated for HCV. RESULTS: Of 18 422 adults, 1775 (10%) had HCV RNA and 10 899 (59%) were on ART at baseline. Incidence rates of any extrahepatic cancer among patients with HIV/HCV coinfection and HIV monoinfection were 1027 and 771 per 100 000 person-years, respectively. In SMR-weighted analyses, the risk of any extrahepatic cancer among patients with untreated HCV coinfection at baseline was similar to the risk if they had been successfully treated for HCV. Patients with untreated HCV coinfection at baseline had higher incidence of kidney, lung and inflammation-related cancers than if their HCV had been successfully treated, but these associations were not statistically significant. CONCLUSIONS: We did not find evidence that treating HCV coinfection with DAAs would reduce the incidence of extrahepatic cancers among people with HIV receiving ART.

Beyond Disease Intervention: Exploring an Expanded Role for Partner Services in the MATRix-NC Demonstration Project.

BACKGROUND: Disease intervention specialists (DIS) provide partner services for sexually transmitted infections (STIs). We assessed an expansion of DIS services for clients with HIV and/or syphilis, and contacts within their social and sexual networks. METHODS: Black and Latinx cisgender men and transgender women who have sex with men diagnosed with HIV and/or syphilis in 4 urban North Carolina counties were referred to designated DIS, who were trained to recruit clients as "seeds" for chain-referral sampling of sociosexual network "peers." All received HIV/STI testing and care; referrals for preexposure prophylaxis (PrEP) and social, behavioral, and non-STI medical services were offered. Participants completed baseline, 1-month, and 3-month computerized surveys. RESULTS: Of 213 cases referred to DIS from May 2018 to February 2020, 42 seeds (25 with syphilis, 17 with HIV) and 50 peers participated. Median age was 27 years; 93% were Black and 86% were cisgender men. Most peers came from seeds' social networks: 66% were friends, 20% were relatives, and 38% were cisgender women. Incomes were low, 41% were uninsured, and 10% experienced recent homelessness. More seeds than peers had baseline PrEP awareness; attitudes were favorable, but utilization was poor. Thirty-seven participants were referred for PrEP 50 times; 17 (46%) accessed PrEP by month 3. Thirty-nine participants received 129 non-PrEP referrals, most commonly for housing assistance, primary care, Medicaid navigation, and food insecurity. CONCLUSIONS: Chain-referral sampling from partner services clients allowed DIS to access persons with significant medical and social service needs, demonstrating that DIS can support marginalized communities beyond STI intervention.

Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Increased Attentional Focus on Walking by Older Adults Limits Maximum Speed and Is Related to Dynamic Stability.

BACKGROUND AND PURPOSE: Older adults with lower balance confidence demonstrate a reduced willingness to experience instability as the task of walking becomes more challenging (i.e., walking with a faster speed). However, the specific reason why is not known. The purpose of this study was to investigate the extent to which capacity of increasing walking speeds relates to the attentional requirements (i.e., automaticity) of walking. METHODS: Sixteen young (31 ± 5.85 years) and 15 older participants (69 ± 3.04 years) began walking on a treadmill at 0.4 m/s, and speed was increased by 0.2 m/s until the participant either chose to stop or reached a speed of 2.0 m/s. Sixty steps were collected at steady-state speed for each walking trial. Kinematic data were collected, and the margin of stability in the anterior direction (MOSAP) at heelstrike was quantified for each step. The timed up and go (TUG) and TUG dual (TUGdual) task were performed, from which an automaticity index (TUG/TUGdual × 100) was calculated. Older individuals were grouped based on whether they did or did not complete all walking speeds (i.e., completers [n = 9] or noncompleters [n = 6]). The fastest walking speed attempted (FSA), automaticity index, and MOSAP were compared, and correlations were assessed between the FSA/MOSAP and the automaticity index. RESULTS: A significant difference was identified in an average MOSAP at heelstrike between older completer and noncompleter groups (p < 0.001). Further, older adults with lower automaticity index choose to stop walking at lower speeds (p = 0.001). The FSA was positively correlated with the automaticity index (ρ = 0.81, p < 0.001). Finally, the average MOSAP at FSA and the automaticity index were also negatively correlated (r = -0.85, p < 0.001). CONCLUSION: Older adults with lower automaticity of walking choose to stop walking at speeds before they completed all walking speeds, which may relate with increased attentional demands required to maintain dynamic stability at higher walking speeds. Given that these were otherwise healthy adults, the combination of FSA and an automaticity of walking may help to identify individuals who should be considered for an assessment to identify walking problems.

Effect of Increasing Obstacle Distances Task on Postural Stability Variables During Gait Initiation in Older Nonfallers and Fallers.

OBJECTIVE: To compare the scaling of the postural stability variables between older nonfallers and fallers during gait initiation (GI) while stepping over increasing obstacle distances. DESIGN: Cross-sectional study. SETTING: University research laboratory. PARTICIPANTS: A sample of participants (N=24) divided into 2 groups: older nonfallers (n=12) and older fallers (n=12). Participants had no known neurologic, musculoskeletal, or cardiovascular conditions that could have affected their walking, and all were independent walkers. All the participants had an adequate cognitive function to participate as indicated by a score of more than 24 on the Mini-Mental State Examination. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary dependent variables were peak anterior-posterior (AP) center of mass (CoM)-center of pressure (CoP) separation during anticipatory postural adjustments (APAs), AP CoM-CoP separation at the toe-off, and peak AP CoM-CoP separation during the swing. Secondary dependent variables were AP trunk angle during GI. Within- and between-repeated measures analysis of variance was used to compare means between groups across different task conditions for all the dependent variables. RESULTS: There was a main effect of group for peak AP CoM-CoP separation during APA (P=.018), an interaction effect between group and condition for AP CoM-CoP separation at toe-off (P=.009), and a main effect of condition for peak AP CoM-CoP separation during the swing (P<.001). We also found a main effect of group for peak AP trunk angle during the swing (P=.028). CONCLUSIONS: For GI while stepping over increasing obstacle distances, older fallers adopt a more conservative strategy of AP CoM-CoP separation than nonfallers prior to toe-off and demonstrate increased peak AP trunk lean during the swing. AP CoM-CoP separation prior to toe-off during the GI task may be a critical marker to identify fallers and warrants additional investigation.

Perceptions, experiences, and preferences for partner services among Black and Latino men who have sex with men and transwomen in North Carolina.

OBJECTIVES: In the United States, sexually transmitted infections (STIs) disproportionately affect men who have sex with men (MSM) and transwomen of color. Partner services can prevent STI transmission by facilitating testing and treatment for partners of individuals diagnosed with an STI. Understanding client perspectives towards partner services is critical to their acceptance and uptake. This study examined perceptions, experiences, and preferences for partner services among Black and Latino MSM and transwomen in North Carolina. DESIGN: We conducted seven audio-recorded focus groups in English (n = 5) and Spanish (n = 2). The audio was transcribed verbatim and we inductively analyzed data using field notes, systematic coding, and thematic comparison. RESULTS: Black MSM reported the most exposure and experiences with partner services, and most perceived partner services negatively. Feeling supported and having flexibility characterized positive experiences with partner services among Black MSM; feeling judged or harassed characterized negative experiences. Black transwomen had less exposure to partner services and had a mix of positive reactions to the approach, along with concerns about client confidentiality. Most Latino participants were unaware of partner services and expressed openness to their potential. All participants preferred self-notifying and wanted flexible, discreet, supportive partner services with linkages to other wellness resources. CONCLUSION: Building off positive partner services experiences and responding to client preferences can enhance trust, acceptability, and service use.

Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial.

Importance: Easy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage. Objective: To evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2-infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020-January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) testing are reported. Interventions: Individuals were randomized 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156). Main Outcomes and Measures: The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Results: Among 314 randomized participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P = .04; absolute risk difference, -13.3% [95% CI, -26.3% to -0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P = .03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P = .001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19. Conclusions and Relevance: Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04452318.

Development of Dynamic Measures to Assess Balance Confidence and State Anxiety While Walking at Increasing Speeds in Young and Older Adults.

The purpose of this study was to determine the test-retest reliability and construct validity of tools to assess how balance confidence (BC) and state anxiety (SA) change with progressively increasing walking speeds. Sixteen young adults and 15 older adults attended two sessions. Individuals began walking on a treadmill at 0.4 m/s Participants chose to continue increasing the treadmill speed (up to 2.0 m/s) or to discontinue the protocol while rating their BC and SA after completing each speed. BC at participants' fastest speed attempted demonstrated high and moderate test-retest reliability among young (intraclass correlation coefficient [ICC] = .908) and older adults (ICC = .704). SA for young adults and older adults was good (ICC = .833) and fair (ICC = .490), respectively. Our measures also correlated with measures of dynamic stability while walking for young (r = -.67, p = .008) and older adults (r = .54, p = .046). Our dynamic measures of BC and SA are valid and reliable in young and older adults.

Circulating biomarkers and outcomes from a randomised phase 2 trial of gemcitabine versus capecitabine-based chemoradiotherapy for pancreatic cancer.

BACKGROUND: The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC). METHODS: Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors. RESULTS: Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5low) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5high; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037). CONCLUSIONS: CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer. CLINICAL TRIAL REGISTRATION: The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).

Technique for inguino-femoral lymph node dissection in vulvar cancer: an international survey.

BACKGROUND: Vulvar cancer is a rare disease and despite broad adoption of sentinel lymph node mapping to assess groin metastases, inguino-femoral lymph node dissection still plays a role in the management of this disease. Inguino-femoral lymph node dissection is associated with high morbidity, and limited research exists to guide the best surgical approach. OBJECTIVE: To determine international practice patterns in key aspects of the inguino-femoral lymph node dissection technique and provide data to guide future research. METHODS: A survey addressing six key domains of practice patterns in performing inguino-femoral lymph node dissection was distributed internationally to gynecologic oncology surgeons between April and October 2020. The survey was distributed using the British Gynecological Cancer Society, the Society of Gynecologic Oncology, authors' direct links, the UK Audit and Research in Gynecology Oncology group, and Twitter. RESULTS: A total of 259 responses were received from 18 countries. The majority (236/259, 91.1%) of respondents reported performing a modified oblique incision, routinely dissecting the superficial and deep inguino-femoral lymph nodes (137/185, 74.1%) with sparing of the saphenous vein (227/258, 88%). Most respondents did not routinely use compression dressings/underwear (169/252 (67.1%), used prophylactic antibiotics at the time of surgery only (167/257, 65%), and closed the skin with sutures (192 74.4%). Also, a drain is placed at the time of surgery by 243/259 (93.8%) surgeons, with most practitioners (144/243, 59.3%) waiting for drainage to be less than 30-50 mL in 24 hours before removal; most respondents (66.3%) routinely discharge patients with drain(s) in situ. CONCLUSION: Our study showed that most surgeons perform a modified oblique incision, dissect the superficial and deep inguino-femoral lymph nodes, and spare the saphenous vein when performing groin lymphadenectomy. This survey has demonstrated significant variability in inguino-femoral lymph node dissection in cases of vulvar cancer among gynecologic oncology surgeons internationally.

Pharmacist attitudes and provision of harm reduction services in North Carolina: an exploratory study.

BACKGROUND: Pharmacists are among the most accessible healthcare providers in the United States and uniquely positioned to provide harm reduction services. The availability of pharmacy-based harm reduction services and pharmacist attitudes toward delivering these services have been understudied to date. We examine North Carolina (NC) pharmacists' experiences with and attitudes about harm reduction services and explore differences between rural and urban pharmacists. METHODS: A convenience sample of NC pharmacists participated in an anonymous, online survey regarding harm reduction services: non-prescription syringe sales; naloxone dispensing; and human immunodeficiency virus (HIV) and hepatitis C virus (HCV) screening. Urban-rural differences were analyzed using Pearson's chi-square or Fisher's exact tests. Open-ended responses were analyzed thematically. RESULTS: Three hundred pharmacists responded to the survey; 68 (23%) practiced in rural counties. Dispensing non-prescription syringes and naloxone at least occasionally was reported by 77% (n = 231) and 88% (n = 263) pharmacists, respectively. Pharmacy-delivered HIV or HCV screening was rare. Urban pharmacists dispensed naloxone more frequently than rural pharmacies (p = 0.04). Only 52% of pharmacists agreed that persons who inject drugs should always be allowed to buy non-prescription syringes. Rural pharmacists' attitudes toward harm reduction services for persons who inject drugs were statistically, though marginally, less supportive when compared to urban pharmacists' attitudes. The most common barrier to non-prescription syringe access was requiring patients to provide proof of prescription injection medication use, which 21% of pharmacists reported was required by their pharmacy's policy on non-prescription syringe sales. CONCLUSIONS: Although most pharmacies distributed naloxone and sold non-prescription syringes, pharmacy store policies and personal beliefs inhibited naloxone and non-prescription syringe dispensing. NC community pharmacies infrequently offer HIV and HCV screening. Paired with disseminating the evidence of the positive impact of harm reduction on individual and public health outcomes to NC pharmacists, institutional and systems changes to practice and policy may be important to promote harm reduction service availability, particularly for rural NC residents. TRIAL REGISTRATION: N/A.

Effects of Thrust Magnitude and Duration on Immediate Postspinal Manipulation Trunk Muscle Spindle Responses.

OBJECTIVE: The purpose of this study was to characterize trunk muscle spindle responses immediately after high-velocity, low-amplitude spinal manipulation (HVLA-SM) delivered at various thrust magnitudes and thrust durations. METHODS: Secondary analysis from multiple studies involving anesthetized adult cats (N = 70; 2.3-6.0 kg) receiving L6 HVLA-SM. Muscle spindle afferent recordings were obtained from L6 dorsal rootlets before, during, and immediately after HVLA-SM. L6 HVLA-SM was delivered posteriorly-to-anteriorly using a feedback motor with peak thrust magnitudes of 25%, 55%, and 85% of cat body weight (BW) and thrust durations of 25, 50, 75, 100, 150, 200, and 250 ms. Time to the first action potential and muscle spindle discharge frequency at 1 and 2 seconds post-HVLA-SM were determined. RESULTS: A significant association between HVLA-SM thrust magnitude and immediate (≤2 s) muscle spindle response was found (P < .001). For non-control thrust magnitude, pairwise comparisons (25%, 55%, 85% BW), 55% BW thrust magnitude had the most consistent effect on immediate post-HVLA-SM discharge outcomes (false discovery rate < 0.05). No significant association was found between thrust duration and immediate post-HVLA-SM muscle spindle response (P > .05). CONCLUSION: The present study found that HVLA-SM thrust magnitudes delivered at 55% BW were more likely to affect immediate (≤2 s) post-HVLA-SM muscle spindle response.

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Randomized, Controlled Trial of Exercise on Objective and Subjective Sleep in Parkinson's Disease.

BACKGROUND: Sleep dysfunction is common and disabling in persons with Parkinson's Disease (PD). Exercise improves motor symptoms and subjective sleep quality in PD, but there are no published studies evaluating the impact of exercise on objective sleep outcomes. The goal of this study was to to determine if high-intensity exercise rehabilitation combining resistance training and body-weight interval training, compared with a sleep hygiene control improved objective sleep outcomes in PD. METHODS: Persons with PD (Hoehn & Yahr stages 2-3; aged ≥45 years, not in a regular exercise program) were randomized to exercise (supervised 3 times a week for 16 weeks; n = 27) or a sleep hygiene, no-exercise control (in-person discussion and monthly phone calls; n = 28). Participants underwent polysomnography at baseline and post-intervention. Change in sleep efficiency was the primary outcome, measured from baseline to post-intervention. Intervention effects were evaluated with general linear models with measurement of group × time interaction. As secondary outcomes, we evaluated changes in other aspects of sleep architecture and compared the effects of acute and chronic training on objective sleep outcomes. RESULTS: The exercise group showed significant improvement in sleep efficiency compared with the sleep hygiene group (group × time interaction: F = 16.0, P < 0.001, d = 1.08). Other parameters of sleep architecture also improved in exercise compared with sleep hygiene, including total sleep time, wake after sleep onset, and slow-wave sleep. Chronic but not acute exercise improved sleep efficiency compared with baseline. CONCLUSIONS: High-intensity exercise rehabilitation improves objective sleep outcomes in PD. Exercise is an effective nonpharmacological intervention to improve this disabling nonmotor symptom in PD. © 2020 International Parkinson and Movement Disorder Society.

Older but not younger adults rely on multijoint coordination to stabilize the swinging limb when performing a novel cued walking task.

Motor flexibility, the ability to employ multiple motor strategies to meet task demands, may facilitate ambulation in complex environments that constrain movements; loss of motor flexibility may impair mobility. The purpose of this study was to determine the effects of obesity (a specific model of mobility impairment) and advanced age on motor flexibility during a task that constrained foot placement while walking. Twenty-one community-dwelling obese (OB) and 25 normal weight (NW) older adults (46 total older adults-OA) and 10 younger adults (YA) walked normally on a treadmill (baseline) then walked while stepping on lighted cues projected onto the treadmill at locations corresponding to average foot placement during normal walking (cued). The uncontrolled manifold (UCM) analysis was used to partition total variance in a set of seven lower-limb segment angles into components that did ("bad" variance) and did not ("good" variance) affect step-to-step variance in the trajectory of the swing foot. Motor flexibility was operationalized as an increase (baseline to cued) in total variance with an increase in good variance that exceeded the change in bad variance. There was no significant group × walking task interaction for total and good variance for OB vs NW, but there was a strong and significant interaction effect for OA vs YA (p < 0.01; Cohen's d > 1.0). Whereas YA reduced both good and bad variance, OA increased good variance beyond the change in bad variance. In OA, these changes were associated with several functional measures of mobility. Cued walking may place greater demands on OA requiring greater reliance on motor flexibility, although otherwise healthy older obese adults may be able to compensate for functional and cognitive declines associated with obesity by increasing motor flexibility under such tasks. The extent to which motor flexibility is employed during novel or constrained tasks may be a biomarker of healthy aging and a target for (re)habilitation.

Comparison of Resistance-Based Walking Cardiorespiratory Test to the Bruce Protocol.

Hurt, CP, Bamman, M, Naidu, A, and Brown, DA. Comparison of resistance-based walking cardiorespiratory test to the Bruce Protocol. J Strength Cond Res 34(12): 3569-3576, 2020-Cardiorespiratory fitness is assessed through graded exercise tests that determine the maximum amount of sustained mechanical work that an individual can perform while also providing health- and fitness-related information. This article describes a novel method to perform graded exercise tests that use posteriorly directed resistive forces. The purpose of this investigation was to validate a novel resistance-based test (RBT) in comparison with a traditional speed- and incline-based test (SIBT) in a cohort of nonimpaired individuals. Twenty nonimpaired individuals, 8 men and 20 women age 28.4 ± 9.6, range 20-54 years old performed 2 maximal exercise tests. The SIBT used the Bruce Protocol and increased treadmill incline and speed every 3 minutes. The RBT used a robotic device interfaced with the treadmill that provided specified horizontal resistive forces at the center of mass calculated to match each Bruce Protocol stage while individuals walked at 1.1 m·s. Subjects obtained ∼3% higher maximum V[Combining Dot Above]O2 measure using the speed- and incline-based method (dependent t-test p = 0.08). V[Combining Dot Above]O2peaks between tests were strongly correlated (r = 0.93, p < 0.001). Peak values of secondary physiologic measures (i.e., max heart rate and respiratory exchange ratio) were within 3% between tests. We found a significant linear relationship between mass-specific work rate and measured V[Combining Dot Above]O2 stage by stage for both tests, but no significant difference between each linear fit (p = 0.84). These data suggest that horizontal resistive forces, while walking on a treadmill, can be used to increase aerobic effort in a way that closely simulates work rates of the Bruce Protocol.

The Effects of Hepatitis C Infection and Treatment on All-cause Mortality Among People Living With Human Immunodeficiency Virus.

BACKGROUND: Persons living with human immunodeficiency virus (HIV; PLwH) are commonly co-infected with hepatitis C virus (HCV). Most co-infected individuals can achieve a sustained HCV virologic response after treatment with direct-acting antivirals (DAA). However, the effect of HCV co-infection and DAA treatment on mortality after initiating antiretroviral therapy (ART) is unknown for PLwH. METHODS: We analyzed data from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. Participants included those who had prevalent HIV or seroconverted during follow-up; all were antiretroviral-naive and acquired immunodeficiency syndrome (AIDS)-free prior to their first visit after 1 October 1994. The follow-up lasted 10 years or until 30 September 2015. We used parametric g-computation to estimate the effects of HCV infection and DAA treatment on mortality had participants initiated ART at study entry. RESULTS: Of the 3056 eligible participants, 58% were female and 18% had HCV. The estimated 10-year all-cause mortality risk in the scenario in which no PLwH had HCV was 10.4% (95% confidence interval [CI] 6.0-18.0%). The 10-year mortality risk difference for HCV infection was 4.3% (95% CI 0.4-8.9%) and the risk ratio was 1.4 (95% CI 1.0-1.9). The risk difference for DAA treatment was -3.8% (95% CI -9.2-0.9%) and the risk ratio was 0.8 (95% CI 0.6-1.1). CONCLUSIONS: HCV co-infection remains an important risk factor for mortality among PLwH after initiating ART according to modern guidelines, and DAAs are effective at reducing mortality in this population. HCV prevention and treatment interventions should be prioritized to reduce mortality among PLwH.