Humans

Background
The frequency and impact of undiagnosed benign paroxysmal positional vertigo (BPPV) in people identified with high falls risk has not been investigated.

Objective
To determine the frequency and impact on key psychosocial measures of undiagnosed BPPV in adult community rehabilitation outpatients identified with a high falls risk.

Design
A frequency study with cross-sectional design.

Setting
A Community Rehabilitation Program in Melbourne, Australia.

Subjects
Adult community rehabilitation outpatients with a Falls Risk for Older People in the Community Screen score of four or higher.

Methods
BPPV was assessed in 34 consecutive high falls risk rehabilitation outpatients using the Dix–Hallpike test and supine roll test. Participants were assessed for anxiety, depression, fear of falls, social isolation and loneliness using the Hospital Anxiety and Depression Scale, Falls Efficacy Scale-International and De Jong Gierveld 6-Item Loneliness Scale.

Results
A total of 18 (53%; 95% confidence interval: 36, 70) participants tested positive for BPPV. There was no significant difference between those who tested positive for BPPV and those who did not for Falls Risk for Older People in the Community Screen scores (P = 0.555), Hospital Anxiety and Depression Scale (Anxiety) scores (P = 0.627), Hospital Anxiety and Depression Scale (Depression) scores (P = 0.368) or Falls Efficacy Scale-International scores (P = 0.481). Higher scores for the De Jong Gierveld 6-Item Loneliness Scale in participants with BPPV did not reach significance (P = 0.056).

Conclusions
Undiagnosed BPPV is very common and associated with a trend towards increased loneliness in adult rehabilitation outpatients identified as having a high falls risk.

Importance
The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.

Objective
To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.

Design, Setting, and Participants
Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.

Interventions
Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).

Main Outcomes and Measures
The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.

Results
Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction = .73).

Conclusions and Relevance
Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Trial Registration
ISRCTN Identifier: ISRCTN76888927

Objectives. To evaluate the evidence on benefits and harms of cannabinoids and similar plant-based compounds to treat chronic pain.

Data sources. Ovid® MEDLINE®, PsycINFO®, Embase®, the Cochrane Library, and SCOPUS® databases, reference lists of included studies, submissions received after Federal Register request were searched to July 2021.

Review methods. Using dual review, we screened search results for randomized controlled trials (RCTs) and observational studies of patients with chronic pain evaluating cannabis, kratom, and similar compounds with any comparison group and at least 1 month of treatment or followup. Dual review was used to abstract study data, assess study-level risk of bias, and rate the strength of evidence. Prioritized outcomes included pain, overall function, and adverse events. We grouped studies that assessed tetrahydrocannabinol (THC) and/or cannabidiol (CBD) based on their THC to CBD ratio and categorized them as high-THC to CBD ratio, comparable THC to CBD ratio, and low-THC to CBD ratio. We also grouped studies by whether the product was a whole-plant product (cannabis), cannabinoids extracted or purified from a whole plant, or synthetic. We conducted meta-analyses using the profile likelihood random effects model and assessed between-study heterogeneity using Cochran’s Q statistic chi square and the I2 test for inconsistency. Magnitude of benefit was categorized into no effect or small, moderate, and large effects.

Results. From 2,850 abstracts, 20 RCTs (N=1,776) and 7 observational studies (N=13,095) assessing different cannabinoids were included; none of kratom. Studies were primarily short term, and 75 percent enrolled patients with a variety of neuropathic pain. Comparators were primarily placebo or usual care. The strength of evidence (SOE) was low, unless otherwise noted. Compared with placebo, comparable THC to CBD ratio oral spray was associated with a small benefit in change in pain severity (7 RCTs, N=632, 0 to10 scale, mean difference [MD] −0.54, 95% confidence interval [CI] −0.95 to −0.19, I2=28%; SOE: moderate) and overall function (6 RCTs, N=616, 0 to 10 scale, MD −0.42, 95% CI −0.73 to −0.16, I2=24%). There was no effect on study withdrawals due to adverse events. There was a large increased risk of dizziness and sedation and a moderate increased risk of nausea (dizziness: 6 RCTs, N=866, 30% vs. 8%, relative risk [RR] 3.57, 95% CI 2.42 to 5.60, I2=0%; sedation: 6 RCTs, N=866, 22% vs. 16%, RR 5.04, 95% CI 2.10 to 11.89, I2=0%; and nausea: 6 RCTs, N=866, 13% vs. 7.5%, RR 1.79, 95% CI 1.20 to 2.78, I2=0%). Synthetic products with high-THC to CBD ratios were associated with a moderate improvement in pain severity, a moderate increase in sedation, and a large increase in nausea (pain: 6 RCTs, N=390 to 10 scale, MD −1.15, 95% CI −1.99 to −0.54, I2=39%; sedation: 3 RCTs, N=335, 19% vs. 10%, RR 1.73, 95% CI 1.03 to 4.63, I2=0%; nausea: 2 RCTs, N=302, 12% vs. 6%, RR 2.19, 95% CI 0.77 to 5.39; I²=0%). We found moderate SOE for a large increased risk of dizziness (2 RCTs, 32% vs. 11%, RR 2.74, 95% CI 1.47 to 6.86, I2=0%). Extracted whole-plant products with high-THC to CBD ratios (oral) were associated with a large increased risk of study withdrawal due to adverse events (1 RCT, 13.9% vs. 5.7%, RR 3.12, 95% CI 1.54 to 6.33) and dizziness (1 RCT, 62.2% vs. 7.5%, RR 8.34, 95% CI 4.53 to 15.34). We observed a moderate improvement in pain severity when combining all studies of high-THC to CBD ratio (8 RCTs, N=684, MD −1.25, 95% CI −2.09 to −0.71, I2=50%; SOE: moderate). Evidence on whole-plant cannabis, topical CBD, low-THC to CBD, other cannabinoids, comparisons with active products, and impact on use of opioids was insufficient to draw conclusions. Other important harms (psychosis, cannabis use disorder, and cognitive effects) were not reported.

Conclusions. Low to moderate strength evidence suggests small to moderate improvements in pain (mostly neuropathic), and moderate to large increases in common adverse events (dizziness, sedation, nausea) and study withdrawal due to adverse events with high- and comparable THC to CBD ratio extracted cannabinoids and synthetic products in short-term treatment (1 to 6 months). Evidence for whole-plant cannabis, and other comparisons, outcomes, and PBCs were unavailable or insufficient to draw conclusions. Small sample sizes, lack of evidence for moderate and long-term use and other key outcomes, such as other adverse events and impact on use of opioids during treatment, indicate that more research is needed.

Importance Local steroid injection is commonly used in treating patients with idiopathic carpal tunnel syndrome, but evidence regarding long-term efficacy is lacking.

Objective To assess the long-term treatment effects of local steroid injection for carpal tunnel syndrome.

Design, Setting, and Participants This exploratory 5-year extended follow-up of a double-blind, placebo-controlled randomized clinical trial was conducted from November 2008 to March 2012 at a university hospital orthopedic department. Participants included patients aged 22 to 69 years with primary idiopathic carpal tunnel syndrome and no prior treatment with local steroid injections. Data were analyzed from May 2018 to August 2018.

Interventions Patients were randomized to injection of 80 mg methylprednisolone, 40 mg methylprednisolone, or saline.

Main Outcomes and Measures The coprimary outcomes were the symptom severity score and rate of subsequent carpal tunnel release surgery on the study hand at 5 years. Secondary outcomes were time from injection to surgical treatment, SF-36 bodily pain score, and score on the 11-item disabilities of the arm, shoulder, and hand scale.

Results A total of 111 participants (mean [SD] age at follow-up, 52.9 [11.6] years; 81 [73.0%] women and 30 [27.0%] men) were randomized, with 37 in the 80 mg methylprednisolone group, 37 in the 40 mg methylprednisolone group, and 37 in the saline placebo group. Complete 5-year follow-up data were obtained from all 111 participants with no dropouts (100% follow-up). At baseline, mean (SD) symptom severity scores were 2.93 (0.85) in the 80 mg methylprednisolone group, 3.13 (0.70) in the 40 mg methylprednisolone group, and 3.18 (0.75) in the placebo group, and at the 5-year follow up, mean (SD) symptom severity scores were 1.51 (0.66) in the 80 mg methylprednisolone group, 1.59 (0.63) in the 40 mg methylprednisolone group, and 1.67 (0.74) in the placebo group. Compared with placebo, there was no significant difference in mean change in symptom severity score from baseline to 5 years for the 80 mg methylprednisolone group (0.14 [95%CI, −0.17 to 0.45]) or the 40 mg methylprednisolone group (0.12 [95%CI, −0.19 to 0.43]). After injection, subsequent surgical treatment on the study hand was performed in 31 participants (83.8%) in the 80 mg methylprednisolone group, 34 participants (91.9%) in the 40 mg methylprednisolone group, and 36 participants (97.3%) in the placebo group; the number of participants who underwent surgical treatment between the 1-year and 5-year follow-ups was 4 participants (10.8%) in the 80 mg methylprednisolone group, 4 participants (10.8%) in the 40 mg methylprednisolone group, and 2 participants (5.4%) in the placebo group. All surgical procedures were conducted while participants and investigators were blinded to type of injection received. The mean (SD) time from injection to surgery was 180 (121) days in the 80 mg methylprednisolone group, 185 (125) days in the 40 mg methylprednisolone group, and 121 (88) days in the placebo group. Kaplan-Meier survival curves showed statistically significant difference in time to surgical treatment (log-rank test: 80 mg methylprednisolone vs placebo, P = .002 ; 40 mg methylprednisolone vs placebo, P = .02; methylprednisolone 80 mg vs 40 mg, P = .37).

Conclusions and Relevance These findings suggest that in idiopathic carpal tunnel syndrome, local methylprednisolone injection resulted in statistically significant reduction in surgery rates and delay in need for surgery.

Trial Registration ClinicalTrials.gov Identifiers: NCT00806871 and NCT02652390