Humans

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

Objectives. To review the association between malnutrition and clinical outcomes among hospitalized patients, evaluate effectiveness of measurement tools for malnutrition on clinical outcomes, and assess effectiveness of hospital-initiated interventions for patients diagnosed with malnutrition.

Data sources. We searched electronic databases (Embase®, MEDLINE®, PubMed®, and the Cochrane Library) from January 1, 2000, to June 3, 2021. We hand-searched reference lists of relevant studies and searched for unpublished studies in ClinicalTrials.gov.

Review methods. Using predefined criteria and dual review, we selected (1) existing systematic reviews (SRs) to assess the association between malnutrition and clinical outcomes, (2) randomized and non-randomized studies to evaluate the effectiveness of malnutrition tools on clinical outcomes, and (3) randomized controlled trials (RCTs) to assess effectiveness of hospital-initiated treatments for malnutrition. Clinical outcomes of interest included mortality, length of stay, 30-day readmission, quality of life, functional status, activities of daily living, hospital acquired conditions, wound healing, and discharge disposition. When appropriate, we conducted meta-analysis to quantitatively summarize study findings; otherwise, data were narratively synthesized. When available, we used pooled estimates from existing SRs to determine the association between malnutrition and clinical outcomes, and assessed the strength of evidence.

Results. Six existing SRs (including 43 unique studies) provided evidence on the association between malnutrition and clinical outcomes. Low to moderate strength of evidence (SOE) showed an association between malnutrition and increased hospital mortality and prolonged hospital length of stay. This association was observed across patients hospitalized for an acute medical event requiring intensive care unit care, heart failure, and cirrhosis. Literature searches found no studies that met inclusion criteria and assessed effectiveness of measurement tools. The primary reason studies did not meet inclusion criteria is because they lacked an appropriate control group. Moderate SOE from 11 RCTs found that hospital-initiated malnutrition interventions likely reduce mortality compared with usual care among hospitalized patients diagnosed with malnutrition. Low SOE indicated that hospital-initiated malnutrition interventions may also improve quality of life compared to usual care.

Conclusions. Evidence shows an association between malnutrition and increased mortality and prolonged length of hospital stay among hospitalized patients identified as malnourished. However, the strength of this association varied depending on patient population and tool used to identify malnutrition. Evidence indicates malnutrition-focused hospital-initiated interventions likely reduce mortality and may improve quality of life compared to usual care among patients diagnosed with malnutrition. Research is needed to assess the clinical utility of measurement tools for malnutrition.

An otherwise healthy 71-year-old woman presented to our clinic with a history of pruritus and burning of the vulva. On examination, we observed an atrophic, white, shiny plaque involving the vulva, perineum and perianal areas. The clitoral hood and labia minora were completely scarred and the introitus was narrow (Figure 1). We diagnosed vulvar lichen sclerosus, a chronic inflammatory disease affecting the anogenital area that can present in any age group, though it is most common before puberty and after menopause. We noted no areas of concern for malignant disease, so we did not take a biopsy. We treated the patient with high-potency steroids (clobetasol ointment twice daily for 6 wk, then weekly). She responded well to treatment, and once her disease settled, we switched her to mid-potency steroids (betamethasone valerate 0.1% ointment daily).