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Aims We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone. Methods Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [ n  = 8]), naltrexone plus placebo (NAL-PLAC [ n  = 7]), prazosin plus placebo (PRAZ-PLAC [ n  = 7]), or placebo plus placebo (PLAC-PLAC [ n  = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD). Results In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial. Conclusion These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. Methods The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. Results Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI},.86–1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI,.28–1.30]). Statistical power to assess effect modification in other subgroups was limited. Conclusions In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259. [ABSTRACT FROM AUTHOR]

Background Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. Methods In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA). Results We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10   Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin. Grade 3–4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P =.05), particularly for anemia (21% vs 44%; P =.01) and potassium (5% vs 17%; P =.04). Conclusions This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin. Clinical Trials Registration NCT04031833. [ABSTRACT FROM AUTHOR]

Background and Objectives Outdoor falls can negatively affect the independence and well-being of community-dwelling older adults. Although there is some overlap, there are also differences in risk factors for indoor and outdoor falls. There are no existing community-based fall prevention programs that specifically target outdoor fall prevention. To fill this gap, the Stroll Safe program was developed. Research Design and Methods A cluster-randomized controlled trial design was used with randomization at the site level. Participants (N = 86) were aged 60 and older, with a history of an outdoor fall or who had a fear of falling outdoors. Eight naturally occurring retirement community program sites were randomly assigned to the treatment or wait list control group. Outcome measures included the Outdoor Falls Questionnaire, the Falls Behavioral Scale for the Older Person, and the Falls Efficacy Scale-International to examine knowledge of risks, safe strategy use, protective behaviors, and fear of falling. An Analysis of Covariance (ANCOVA) was used to compare change scores between groups with covariates included for any initial differences between groups. A linear mixed model was also conducted to account for any clustering effects. Results Significant differences (p s <.05) were found between groups for knowledge of outdoor fall risks and safe strategy use. Effect sizes were large (Cohen's d = 1.2–1.9). Results were retained at 6-week follow-up. Discussion and Implications Stroll Safe is effective in improving knowledge of outdoor fall risks and increasing safe strategy use for community mobility. Stroll Safe fills a gap in outdoor fall prevention programs. Clinical Trials Registration Number: NCT03624777 [ABSTRACT FROM AUTHOR]

Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n  = 18), baclofen 30 mg/day (N  = 20), or baclofen 60 mg/day (N  = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P  = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P  = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment. [ABSTRACT FROM AUTHOR]

Background Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. Methods Participants ages 4–21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. Results The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. Conclusions Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. Clinical Trials No NCT03982069 [ABSTRACT FROM AUTHOR]

Objective Our main aim was to investigate the effect of a single oral dose of C21, a selective angiotensin II type 2 receptor agonist, on cold-induced vasoconstriction in SSc-related RP. Methods This was a phase IIa, randomized, double-blind, cross-over, single-dose, placebo-controlled, single-centre study. Twelve female patients with SSc (median age 58.5 years, median duration of RP 19.0 years) attended on four occasions: screening, treatment visits 1 and 2 (separated by 3–7 days) and follow-up. At the first treatment visit, patients were randomized to receive either a single oral dose of C21 (200 mg) or placebo, then the opposite treatment on the second visit. Forty min after each treatment, each patient underwent a standard hand cold challenge. The primary end point was the area under the curve (AUC) for rewarming for each finger (eight fingers) over 15 min. Secondary end points included the maximum finger temperature after rewarming (MAX). Statistical analyses were performed by multiplicative ANCOVA models. Results For all eight fingers combined, mean AUC for rewarming was higher after treatment with C21 than after placebo (geometric mean 20 046°C*s vs 19 558°C*s), but not significantly (P  = 0.380) and MAX (at 15 min) was also higher (geometric mean 23.5°C vs 22.5°C; P  = 0.036). C21 was well tolerated. Conclusion Despite the small trial size, a signal emerged suggesting that even in patients with established SSc, C21 may confer benefit for RP and deserves further investigation. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT04388176. [ABSTRACT FROM AUTHOR]

Aims Tai Chi is a promising exercise option in cardiac rehabilitation to manage coronary heart disease (CHD). Increasing attention was paid on home-based cardiac rehabilitation to improve participation rate, but no study has yet emphasized the effect of home-based Tai Chi. A single-blinded randomized controlled trial is used to examine the effects of a group- plus home-based Tai Chi program on functional health. Methods and results Ninety-eight community-dwelling patients with CHD were randomly assigned to the Tai Chi and control groups. Participants in the Tai Chi group attended 6-week group- plus 6-week home-based Tai Chi program. Outcome measures included physical functions, cardiovascular risk factors, and exercise self-efficacy. Data were collected at baseline, 6-week, 12-week, and 24-week. Intervention effects were analysed using the generalized estimating equation model. Compared with changes in the control group, the intervention group achieved significant improvements in aerobic endurance, lower-body strength, agility and dynamic balance, diastolic blood pressure, and exercise self-efficacy over the 24-week study period (all Ps < 0.05). Intervention adherence was high (79.6% of participants attending >75% of all Tai Chi sessions). Conclusions This Tai Chi program significantly improved the functional health of patients with CHD, indicating that Tai Chi could be taught in group sessions and then continued independently as a home exercise routine for health promotion. [ABSTRACT FROM AUTHOR]

Background No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. Methods Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. Results A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (−1.41 vs −1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (−3.37 vs −3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. Conclusions In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care. [ABSTRACT FROM AUTHOR]

Background Antibiotic overprescribing in long-term care settings is driven by prescriber preferences and is associated with preventable harms for residents. We aimed to determine whether peer comparison audit and feedback reporting for physicians reduces antibiotic overprescribing among residents. Methods We employed a province wide, difference-in-differences study of antibiotic prescribing audit and feedback, with an embedded pragmatic randomized controlled trial (RCT) across all long-term care facilities in Ontario, Canada, in 2019. The study year included 1238 physicians caring for 96 185 residents. In total, 895 (72%) physicians received no feedback; 343 (28%) were enrolled to receive audit and feedback and randomized 1:1 to static or dynamic reports. The primary outcomes were proportion of residents initiated on an antibiotic and proportion of antibiotics prolonged beyond 7 days per quarter. Results Among all residents, between the first quarter of 2018 and last quarter of 2019, there were temporal declines in antibiotic initiation (28.4% to 21.3%) and prolonged duration (34.4% to 29.0%). Difference-in-differences analysis confirmed that feedback was associated with a greater decline in prolonged antibiotics (adjusted difference −2.65%, 95% confidence interval [CI]: −4.93 to −.28%, P =.026), but there was no significant difference in antibiotic initiation. The reduction in antibiotic durations was associated with 335 912 fewer days of treatment. The embedded RCT detected no differences in outcomes between the dynamic and static reports. Conclusions Peer comparison audit and feedback is a pragmatic intervention that can generate small relative reductions in the use of antibiotics for prolonged durations that translate to large reductions in antibiotic days of treatment across populations. Clinical Trials Registration. NCT03807466. [ABSTRACT FROM AUTHOR]

Aims This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Invasive coronary angiography (ICA) is used to investigate HF patients. CCTA may be a non-invasive cost-effective alternative to ICA. This randomized controlled trial sought to determine the financial impact of an initial diagnostic strategy of coronary computed tomography angiography (CCTA) in patients with heart failure (HF) of unknown aetiology. Methods and results This multicentre, international trial enrolled patients with HF of unknown aetiology. The primary outcome was the cost of CCTA vs. ICA strategies at 12 months. Clinical outcomes were also collected. An 'intention-to-diagnose' analysis was performed and a secondary 'as-tested' analysis was based on the modality received. Two hundred and forty-six patients were randomized (age = 57.8 ± 11.0 years, ejection fraction = 30.1 ± 10.1%). The severity of coronary artery disease was similar in both groups. In the 121 CCTA patients, 93 avoided ICA. Rates of downstream ischaemia and viability testing were similar for both arms. There were no significant differences in the composite clinical outcomes or quality of life measures. The cost of CCTA trended lower than ICA [CDN −$871 (confidence interval, CI −$4116 to $3028)]. Using an 'as-tested' analysis, CCTA was associated with a decrease in healthcare costs (CDN −$2932, 95% CI −$6248 to $746). Conclusion In patients with HF of unknown aetiology, costs were not statistically different between the CCTA and ICA strategies. Clinical Trials.gov NCT01283659 [ABSTRACT FROM AUTHOR]

Background The obturator nerve runs along the posterolateral walls of the bladder and electrosurgical stimulation in this region can result in adductor spasm which can occur suddenly and unexpectedly with potentially catastrophic results. Methods Sixty patients were prospectively randomized to receive either a single-injection ultrasound-guided obturator nerve block (ONB) or intravenous rocuronium after induction of general anesthesia (i.e. neuromuscular block [NMB]). The primary objective was to compare the incidence of adductor spasm during posterolateral bladder tumor resection when ONB or NMB was used. Secondary objectives included assessment of fall risk and incidence of adverse events. Results Five patients in the ONB group and six in the NMB group had nonlateral wall lesions. One patient in the ONB group suffered a cardiac arrest after induction of general anesthesia. Of the remaining 48 patients, six (10.2%) experienced adductor spasm. Most of these patients were in the NMB group (5/24, 20.8%), with only one patient (1/24, 4.2%) experiencing obturator reflex in the ONB group; this difference was not statistically significant (P =0.19). Patients in the ONB group had a greater decrease in mean hip adductor strength. Our study population was found to be at high risk of falls before surgery. There were no statistically significant group differences in the Timed Up and Go test, with time to perform the test increasing in both groups. Conclusions Both techniques are safe and efficacious for preventing adductor spasm. Our data and experience suggest that the ONB is relatively easy to perform and should be considered in patients with posterolateral bladder tumors. [ABSTRACT FROM AUTHOR]

Aims: Medical procedures and hospitalizations can be experienced as traumatic and can lead to post-traumatic stress reactions. Eye movement desensitization and reprocessing (EMDR) shows promising results but very few long-term studies have been published. Therefore, our aim was to test the long-term (8 months post-treatment) effectiveness of EMDR in children and adolescents with medically related subthreshold post-traumatic stress disorder (PTSD). Methods and results: Seventy-four children (including 39 with congenital or acquired heart disease) aged 4–15 (M = 9.6 years) with subthreshold PTSD after previous hospitalization were included into a parallel group randomized controlled trial. Participants were randomized to EMDR (n = 37) or care-as-usual (CAU) (n = 37; medical care only). The primary outcome was PTSD symptoms of the child. Secondary outcomes were symptoms of depression and blood–injection–injury (BII) phobia, sleep problems, and health-related quality of life (HrQoL) of the child. Assessments of all outcomes were planned at baseline and 8 weeks and 8 months after the start of EMDR/CAU. We hypothesized that the EMDR group would show significantly more improvements on all outcomes over time. Both groups showed improvements over time on child's symptoms of PTSD (only parent report), depression, BII phobia, sleep problems, and most HrQoL subscales. GEE analyses showed no significant differences between the EMDR group (nT2 = 33, nT3 = 30) and the CAU group (nT2 = 35, nT3 = 32) on the primary outcome. One superior effect of EMDR over time was found for reducing parent-reported BII phobia of the child. Conclusion: EMDR did not perform better than CAU in reducing subthreshold PTSD up to 8 months post-treatment in previously hospitalized children. Possible explanations and clinical implications are discussed. [ABSTRACT FROM AUTHOR]

Accumulating studies have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) may improve cognitive dysfunction of the patients with schizophrenia (SCZ), but with inconsistent results. The present study aims to assess the efficacy of different frequencies of neuronavigated rTMS in ameliorating cognitive impairments and alleviating the psychotic symptoms. A total of 120 patients were randomly assigned to 3 groups: 20 Hz rTMS (n = 40), 10 Hz rTMS (n = 40), or sham stimulation (n = 40) for 8 weeks, and then followed up at week 32. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess the cognitive functions of the patients at baseline, at the end of week 8, and week 32 follow-up. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of week 2, week 4, week 6, week 8, and week 32 follow-up. Our results demonstrated that 20 Hz rTMS treatment produced an effective therapeutic benefit on immediate memory of patients with chronic SCZ at week 8, but not in the 10 Hz group. Interestingly, both 10 Hz and 20 Hz rTMS treatments produced delayed effects on cognitive functions at the 6-month follow-up. Moreover, in both 10 Hz rTMS and 20 Hz rTMS, the improvements in RBANS total score were positively correlated with the reduction of PANSS positive subscore at the 6-month follow-up. Stepwise regression analysis identified that the visuospatial/constructional index, immediate memory index, and prolactin at baseline were predictors for the improvement of cognitive impairments in the patients. Our results suggest that add-on HF rTMS could be an effective treatment for cognitive impairments in patients with chronic SCZ, with a delayed effect. Trial registration: clinicaltrials.gov identifier—NCT03774927. [ABSTRACT FROM AUTHOR]

Background Although adults with low vitamin D status are at increased risk of acute respiratory infection (ARI), randomized controlled trials of vitamin D supplementation have provided inconsistent results. Methods We performed a randomized, double-blinded, placebo-controlled trial of 5110 adults aged 50–84 years. In 2011–2012, participants were randomized to an initial oral dose of 200 000 IU vitamin D3 followed by 100 000 IU monthly (n = 2558) or placebo (n = 2552) until late 2013 (median follow-up, 1.6 years). Participants reported upper and lower ARIs on monthly questionnaires. Cox models analyzed time to first ARI (upper or lower) by treatment group. Results Participants' mean age was 66 years and 58% were male; 83% were of European/other ethnicity, with the rest Maori, Polynesian, or South Asian. Mean (SD) baseline blood 25-hydroxyvitamin D [25(OH)D] level was 63 (24) nmol/L; 25% were <50 nmol/L. In a random sample (n = 441), vitamin D supplementation increased mean 25(OH)D to 135 nmol/L at 3 years, while those on placebo remained at 63 nmol/L. During follow-up, 3737 participants reported ≥1 ARI: 74.1% in the vitamin D group versus 73.7% in the placebo group. The hazard ratio for vitamin D compared with placebo was 1.01 (95% CI, 0.94, 1.07). Similar results were seen in most subgroups, including those with baseline 25(OH)D <50 nmol/L and in analyses of the upper/lower components of the ARI outcome. Conclusions Monthly high-dose vitamin D supplementation does not prevent ARI in older adults with a low prevalence of profound vitamin D deficiency at baseline. Whether effects of daily or weekly dosing differ requires further study. Clinical Trials Registration Australian New Zealand Clinical Trials Registry, identifier ACTRN12611000402943. [ABSTRACT FROM AUTHOR]

Background To achieve the World Health Organization hepatitis C virus (HCV) elimination targets, it is essential to increase access to direct-acting antivirals (DAAs), especially among people who inject drugs (PWID). We aimed to determine the effectiveness of providing DAAs in primary care, compared with hospital-based specialist care. Methods We randomized PWID with HCV attending primary care sites in Australia or New Zealand to receive DAAs at their primary care site or local hospital (standard of care [SOC]). The primary outcome was to determine whether people treated in primary care had a noninferior rate of sustained virologic response at Week 12 (SVR12), compared to historical controls (consistent with DAA trials at the time of the study design); secondary outcomes included comparisons of treatment initiation, SVR12 rates, and the care cascade by study arm. Results We recruited 140 participants and randomized 136: 70 to the primary care arm and 66 to the SOC arm. The SVR12 rate (100%, 95% confidence interval [CI] 87.7–100) of people treated in primary care was noninferior when compared to historical controls (85% assumed). An intention-to-treat analysis revealed that the proportion of participants commencing treatment in the primary care arm (75%, 43/57) was significantly higher than in the SOC arm (34%, 18/53; P <.001; relative risk [RR] 2.48, 95% CI 1.54–3.95), and the proportion of participants with SVR12 was significantly higher in the primary care arm, compared to in the SOC arm (49% [28/57] and 30% [16/53], respectively; P =.043; RR 1.63, 95% CI 1.0–2.65). Conclusions Providing HCV treatment in primary care increases treatment uptake and cure rates. Approaches that increase treatment uptake among PWID will accelerate elimination strategies. Clinical Trials Registration NCT02555475. [ABSTRACT FROM AUTHOR]

Background: The role of postoperative radiotherapy in pathological T2–3N0M0 esophageal squamous cell carcinoma is unknown. We aimed to evaluate the efficacy and safety of postoperative radiotherapy in patients with pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma. Materials and Methods: Patients aged 18–72 years with pathological stage T2–3N0M0 esophageal squamous cell carcinoma after radical surgery and without neoadjuvant therapy were eligible. Patients were randomly assigned to surgery alone or to receive postoperative radiotherapy of 50.4 Gy in supraclavicular field and 56 Gy in mediastinal field in 28 fractions over 6 weeks. The primary endpoint was disease‐free survival. The secondary endpoints were local‐regional recurrence rate, overall survival, and radiation‐related toxicities. Results: From October 2012 to February 2018, 167 patients were enrolled in this study. We analyzed 157 patients whose follow‐up time was more than 1 year or who had died. The median follow‐up time was 45.6 months. The 3‐year disease‐free survival rates were 75.1% (95% confidence interval [CI] 65.9–85.5) in the postoperative radiotherapy group and 58.7% (95% CI 48.2–71.5) in the surgery group (hazard ratio 0.53, 95% CI 0.30–0.94, p =.030). Local‐regional recurrence rate decreased significantly in the radiotherapy group (10.0% vs. 32.5% in the surgery group, p =.001). The overall survival and distant metastasis rates were not significantly different between two groups. Grade 3 toxicity rate related to radiotherapy was 12.5%. Conclusion: Postoperative radiotherapy significantly increased disease‐free survival and decreased local regional recurrence rate in patients with pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma with acceptable toxicities in this interim analysis. Further enrollment and follow‐up are warranted to validate these findings in this ongoing trial. Implications for Practice: The value of adjuvant radiotherapy for patients with node‐negative esophageal cancer is not clear. The interim results of this phase III study indicated that postoperative radiotherapy significantly improved disease‐free survival and decreased local‐regional recurrence rate in patients with pathological T2–3N0M0 thoracic esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. The distant metastasis rates and overall survival rates were not different between the two groups. Adjuvant radiotherapy should be considered for pathologic T2–3N0M0 thoracic esophageal squamous cell carcinoma. Prospective trials to identify high‐risk subgroups are needed. This phase III randomized controlled study compared surgery alone with surgery followed by postoperative radiotherapy in patients with pathological T2‐3N0M0 esophageal squamous cell carcinoma. Interim results are reported. [ABSTRACT FROM AUTHOR]

Objectives Existing treatments for fibromyalgia have limited efficacy, and only a minority of individuals clinically respond to any single intervention. This study was a prospective, multicenter, randomized, double-blind, controlled clinical trial to evaluate the feasibility of alternating magnetic field therapy in fibromyalgia patients by comparing the Angel Touch device (AT-02) with a sham control (S-01). Methods Two sites enrolled 44 subjects with diagnosed fibromyalgia. After informed consent, subjects taking prohibited concomitant drugs underwent a washout period of two or more weeks. All subjects then began a one-week run-in period. Numerical rating scale (NRS) pain scores were collected without device intervention for one day, followed by S-01 application to four or more painful sites for 10 minutes at each site, twice daily for six days. Subjects were then randomized to AT-02 or S-01, applied to four or more painful sites for 10 minutes at each site, twice daily for eight weeks. NRS scores were obtained twice daily during the entire treatment period. Results The primary end point (change in NRS ± SD at week 8 vs baseline) was –0.94 ± 1.33 in the AT-02 group and –0.22 ± 1.38 in the S-01 group. A trend toward a between-group difference in eight-week NRS scores favored the AT-02 group (–0.73, 95% confidence interval = –1.56 to 0.11, P  = 0.086). An adjusted repeated measure analysis detected a significant difference in NRS scores (P  = 0.039). Conclusions The reduction in NRS scores for AT-02 relative to sham was comparable to reductions observed in meta-analyses of fibromyalgia drug therapy. The unadjusted results and the persistence of the pain score reductions remain encouraging. [ABSTRACT FROM AUTHOR]

Behavioral economics hold great promise in changing patterns of behavior that influence human health. Handwashing with soap is one such behavior that is important in reducing exposure to pathogens, and in school-age children, handwashing helps reduce absenteeism through the prevention of respiratory and diarrheal diseases. However, the gap between knowledge on the importance of handwashing and actual handwashing practice, especially with soap, persists. Many traditional behavior change communication approaches have failed in achieving and sustaining improved handwashing practices. Cognitive psychology research on habits as well as nudge theory, a component of behavioral economics predicated on the idea of making a behavior as easy as possible to do, suggests that introducing a disruptive cue into the environment may be able to interrupt current habitual neurological patterns to effect and then sustain behavior change. We used a participatory process to identify and introduce a locally appropriate disruptive cue to improve handwashing behavior in schools in Zambia. We then utilized a school-randomized controlled trial to test the soap-on-a-rope in 50 government schools in Namwala District of Southern Province. Two outcomes were considered among school children; washing hands with water and using soap while washing hands. Following the intervention, soap use was more likely in intervention schools than control schools [Odds ratio = 7.23, 95% confidence interval = (1.76–29.71)], though both intervention and control schools saw an increase in handwashing without soap. This low-cost intervention could be scaled throughout Zambia and may work well in other countries of similar circumstances. [ABSTRACT FROM AUTHOR]

A pilot study of the effects of metacognition-oriented social skills training (MOSST) on social functioning in patients with schizophrenia spectrum disorders (SSDs) reported promising results. The main purpose of the current trial was to compare the effectiveness and potential benefits of MOSST vs conventional social skills training (SST). Single-blind randomized controlled trial with 2 groups of patients aged 18–65 with SSDs on partial hospitalization. Participants were randomly assigned (1:1) to receive 16 group sessions with MOSST or conventional SST, both in addition to standard care, over 4 months, with a 6-month follow-up. Psychosocial functioning, metacognition, and symptom outcomes were measured by blind assessors. Statistical analyses used mixed models to estimate treatment effects in each postrandomization time point. Thirty-six patients were randomly assigned to the MOSST group and 33 patients to the conventional SST group. Between-group differences were significant in favor of MOSST on Social and Occupational Functioning Assessment Scale (SOFAS) and Personal and Social Performance Scale (PSP) total scores at post-treatment and follow-up. Concerning PSP subscales, there were significant between-group differences in favor of MOSST at follow-up on socially useful activities, personal and social relationships, and disturbing and aggressive behaviors. Metacognition only improved following MOSST group. For people with SDDs, MOSST appears to have short- and long-term beneficial effects on social functioning and symptoms. Further studies are required to replicate the current results in other samples. [ABSTRACT FROM AUTHOR]

Objective. To study for the first time in a randomized controlled trial the feasibility, safety and efficacy of an exercise training programme in children and adolescents with JDM. Methods. Patients were randomly assigned to the Intervention Group (IG; n = 14) or Waiting Control Group (WCG; n = 12). The intervention comprised an individually tailored 12-week home-based exercise programme of treadmill interval training and strength exercises. The efficacy of the IG over usual care (WCG) was examined with mixed linear regression (intention-to-treat). Effect sustainability during 12 weeks follow-up was also examined. Results. Seventy-five percent of the participants completed the intervention. Reasons for discontinuation were motivation/fatigue, recurrent infections and increasing physical complaints. No hospitalizations occurred and immune suppressive therapy remained stable or decreased in the patients who participated in the intervention. The estimated marginal means after the intervention period were significantly in favour of the IG compared with the WCG for standing long jump distance [difference between groups (95% CI): 13cm (2-23)], the 30-s number of push-ups [8 (3-13)] and sit-ups [4 (0.4-8)], and the parent Childhood Health Assessment Questionnaire 30 + 8 score [-0.13 (-0.24 to-0.01)] and effects sustained at follow-up. A trend was seen for the maximal oxygen uptake divided by body mass during maximal exercise treadmill testing; the IG scored 3.0ml/kg/min (-1.3 to 7.3) higher compared with the WCG. Other outcomes (e.g. isometric muscle strength and perception of fatigue) did not differ between IG and WCG. Conclusion. Exercise training is of value in the clinical management of JDM. [ABSTRACT FROM AUTHOR]

Purpose: The United States faces a growing population of older adults and accompanying functional disabilities, coupled with constrained public resources and diminishing informal supports. A variety of interventions that aim to improve client outcomes have been studied, but to date, there is limited translational research that examines the efficacy of moving such interventions from clinical trials to agency settings. Methods: A randomized controlled trial was conducted to evaluate a restorative occupational therapy intervention relative to “usual care” among community-dwelling older adults. The intervention included a detailed assessment from a person–environment perspective and provision of adaptive equipment and home modifications where appropriate. The intervention (n = 31) and control groups (n = 29) were evaluated at 3 months and assessed for changes in functional status, home safety, falls, health-related quality of life (HRQoL; EQ5D), depression, social support, and fear of falling; a 4 subgroup analysis also examined outcomes by waiting list status. An informal economic evaluation compared the intervention to usual care. Results: Findings indicated improvements in home safety (p < .0005, b = −15.87), HRQoL (p = .03, b = 0.08), and fear of falling (p < .05, b = 2.22). Findings did not show improvement in functional status or reduction in actual falls. The intervention resulted in a 39% reduction in recommended hours of personal care, which if implemented, could result in significant cost savings. Implications: The study adds to the growing literature of occupational therapy interventions for older adults, and the findings support the concept that restorative approaches can be successfully implemented in public agencies. [ABSTRACT FROM PUBLISHER]

Purpose: To examine independence in activities of daily living (ADL) at the 1- and 2-year follow-ups of the health-promoting study Elderly Persons in the Risk Zone. Design and Method: A randomized, three-armed, single-blind, and controlled study. A representative sample of 459 independent and community-dwelling older adults, 80 years and older, were included. A preventive home visit was compared with four weekly multiprofessional senior group meetings including a follow-up home visit. Results: Analysis showed a significant difference in favor of the senior meetings in postponing dependence in ADL at the 1-year follow-up (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.19–3.10) and also in reducing dependence in three (OR = 0.52, 95% CI = 0.31–0.86) and four or more ADL (OR = 0.40, 95% CI = 0.22–0.72) at the 2-year follow-up. A preventive home visit reduced dependence in two (OR = 0.40, 95% CI = 0.24–0.68) and three or more ADL (OR = 0.37, 95% CI = 0.17–0.80) after 1 year. Implications: A long-term evaluation of Elderly Persons in the Risk Zone showed that both senior meetings and a preventive home visit reduced the extent of dependence in ADL after 1 year. The senior meetings were superior to a preventive home visit since additional significant effects were seen after 2 years. To further enhance the long-term effects of the senior meetings and support the process of self-change in health behavior, it is suggested that booster sessions might be a good way of reinforcing the intervention. [ABSTRACT FROM PUBLISHER]

Lessons Learned: The primary endpoint of this phase II study that evaluated the efficacy and safety of the investigational compound, AGS‐16C3F, versus axitinib in previously treated patients with metastatic renal cell carcinoma (mRCC) was not met.Median progression‐free survival, the primary endpoint, was 2.9 months with AGS‐16C3F and 5.7 months with axitinib (HR, 1.676; 95% CI, 1.107–2.537; p =.015), per investigator assessmentThe safety profile for each study drug was as expected, with the most commonly reported adverse events being fatigue (53%) and nausea (47%) in the AGS‐16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm.These results provide a benchmark for axitinib use in heavily pretreated patients with mRCC. Background: AGS‐16C3F is a novel antibody‐drug conjugate that targets cell‐surface ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) and is conjugated to a microtubule disruptive agent. Here we present findings from a phase II study of AGS‐16C3F versus axitinib in metastatic renal cell carcinoma (mRCC). Methods: Patients with mRCC of any histology and disease progression during or after their last treatment regimen were randomized 1:1 to intravenous AGS‐16C3F 1.8 mg/kg every 3 weeks or oral axitinib 5 mg twice daily (starting dose). The primary objective was investigator‐assessed progression‐free survival (PFS) of AGS‐16C3F versus axitinib (RECIST version 1.1). Results: In the total population (N = 133), 63% (n = 84) of patients had completed the study at data cutoff (August 21, 2019). Median PFS was 2.9 months with AGS‐16C3F and 5.7 months with axitinib (hazard ratio [HR], 1.676; 95% confidence interval [CI], 1.107–2.537; p =.015). There were no significant differences between arms in secondary efficacy endpoints, including overall survival (13.1 months, AGS‐16C3F and 15.4 months, axitinib; HR, 1.079; 95% CI, 0.681–1.707; p =.747). In the safety population (n = 131), the most commonly reported adverse events were fatigue (53%) and nausea (47%) in the AGS‐16C3F arm and fatigue (57%) and diarrhea (48%) in the axitinib arm. The incidence of diarrhea was lower in the AGS‐16C3F arm than in the axitinib arm (17% vs. 48%), and ocular toxicities were more frequent in the AGS‐16C3F arm than in the axitinib arm (44% vs. 26%). Conclusion: The investigational compound, AGS‐16C3F, did not meet the primary endpoint of this trial. These study results provide a benchmark for axitinib use in heavily pretreated patients with mRCC. [ABSTRACT FROM AUTHOR]