Comparative effectiveness of salvage chemotherapy regimens and chimeric antigen T-cell receptor therapies in relapsed and refractory diffuse large B cell lymphoma: a network meta-analysis of clinical trials.

The optimal salvage chemotherapy regimen (SC) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) prior to autologous stem cell transplant remains unclear. Moreover, although chimeric antigen receptor T cell (CAR-T) therapies were recently approved for primary refractory DLBCL, head-to-head comparisons are lacking. We searched MEDLINE, EMBASE and CENTRAL to July 2022, for randomized trials that enrolled adult patients with R/R DLBCL and performed network meta-analyses (NMA) to assess the efficacy of SC and CAR-T therapies. NMA of SC (6 trials, 7 regimens, n = 1831) indicated that rituximab with gemcitabine, dexamethasone, cisplatin (R-GDP) improved OS and PFS over compared regimens. NMA of 3 CAR-T trials (n = 865) indicated that both axi-cel and liso-cel improved PFS over standard of care, with no difference in OS. Our results indicate that R-GDP may be preferred for R/R DLBCL over other SC compared. Longer follow-up is required for ongoing comparative survival analysis as data from CAR-T trials matures.

Declared Rationale for Cannabis Use Before and After Legalization for Nonmedical Use: A Longitudinal Study of Community Adults in Ontario.

Objectives: To examine the proportion of individuals using cannabis for medical purposes who reported nonmedical use of cannabis after it became legal to do so. Materials and Methods: We acquired data from the Population Assessment for Tomorrow's Health, the Cannabis Legalization Surveillance Study on a subpopulation of participants residing in Hamilton, Ontario, Canada, who reported using cannabis for medical purposes. Specifically, we acquired data 6 months before, and again 6 months after, legalization of cannabis for nonmedical purposes. We constructed a logistic regression model to explore the association between potential explanatory factors and endorsing exclusively nonmedical use after legalization and reported associations as odds ratios and 95% confidence intervals. Results: Our sample included 254 respondents (mean age 33±13; 61% female), of which 208 (82%) reported both medical and nonmedical use of cannabis (dual motives) before legalization for nonmedical purposes, and 46 (18%) reported cannabis use exclusively for medical purposes. Twenty-five percent (n=63) indicated they had medical authorization to use medical cannabis, of which 37 (59%) also endorsed nonmedical use. After legalization of nonmedical cannabis, ∼1 in 4 previously exclusive cannabis users for medical purposes declared dual use (medical and nonmedical), and ∼1 in 4 previously dual users declared exclusively nonmedical use of cannabis. No individual with medical authorization reported a change to exclusively nonmedical use after legalization. Our adjusted regression analysis found that younger age, male sex, and lacking authorization for cannabis use were associated with declaring exclusively nonmedical use of cannabis after legalization. Anxiety, depression, impaired sleep, pain, and headaches were among the most common complaints for which respondents used cannabis therapeutically. Most respondents reported using cannabis as a substitute for prescription medication at least some of the time, and approximately half reported using cannabis as a substitute for alcohol at least some of the time. Conclusions: In a community sample of Canadian adults reporting use of cannabis for medical purposes, legalization of nonmedical cannabis was associated with a substantial proportion changing to either dual use (using cannabis for both medical and nonmedical purposes) or exclusively nonmedical use. Younger men without medical authorization for cannabis use were more likely to declare exclusively nonmedical use after legalization.

Predictors of Persistent Post-Surgical Pain Following Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. METHODS: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study. RESULTS: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. CONCLUSIONS: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery.

Benefits and Concerns regarding Use of Cannabis for Therapeutic Purposes Among People Living with Chronic Pain: A Qualitative Research Study.

OBJECTIVE: Although there is growing interest in medically authorized cannabis for chronic pain, little is known about patients' perspectives. We explored perceptions of people living with chronic pain regarding benefits and concerns surrounding their use of cannabis for therapeutic purposes. SETTING: A hospital-based clinic in Hamilton and two community-based interdisciplinary pain clinics in Burlington, Ontario, Canada. METHODS: In this qualitative descriptive study, we conducted semi-structured interviews with 13 people living with chronic pain who used cannabis therapeutically, living in Ontario, Canada. We used thematic analysis, with data collection, coding, and analysis occurring concurrently. RESULTS: People living with chronic pain reported important benefits associated with use of cannabis for therapeutic purposes, including reduced pain, improved functionality, and less risk of harms compared to prescription opioids. Most patients also acknowledged harms, such as grogginess and coughing, and there was considerable variability in patient experiences. Financial costs and stigma were identified as important barriers to use of cannabis. CONCLUSION: Evidence-based guidance that incorporates patients' values and preferences may be helpful to inform the role of cannabis in the management of chronic pain.

Medical cannabis and cannabinoids for impaired sleep: a systematic review and meta-analysis of randomized clinical trials.

STUDY OBJECTIVES: We conducted a systematic review to explore the effectiveness of medical cannabis for impaired sleep. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and PsychINFO to January 2021 for randomized trials of medical cannabis or cannabinoids for impaired sleep vs. any non-cannabis control. When possible, we pooled effect estimates for all patient-important sleep-related outcomes and used the GRADE approach to appraise the certainty of evidence. RESULTS: Thirty-nine trials (5100 patients) were eligible for review, of which 38 evaluated oral cannabinoids and 1 administered inhaled cannabis. The median follow-up was 35 days, and most trials (33 of 39) enrolled patients living with chronic cancer or noncancer chronic pain. Among patients with chronic pain, moderate certainty evidence found that medical cannabis probably results in a small improvement in sleep quality versus placebo (modeled risk difference [RD] for achieving the minimally important difference [MID], 8% [95% CI, 3 to 12]). Moderate to high certainty evidence shows that medical cannabis vs. placebo results in a small improvement in sleep disturbance for chronic non-cancer pain (modeled RD for achieving the MID, 19% [95% CI, 11 to 28]) and a very small improvement in sleep disturbance for chronic cancer pain (weighted mean difference of -0.19 cm [95%CI, -0.36 to -0.03 cm]; interaction p = .03). Moderate to high certainty evidence shows medical cannabis, versus placebo, results in a substantial increase in the risk of dizziness (RD 29% [95%CI, 16 to 50], for trials with ≥3 months follow-up), and a small increase in the risk of somnolence, dry mouth, fatigue, and nausea (RDs ranged from 6% to 10%). CONCLUSION: Medical cannabis and cannabinoids may improve impaired sleep among people living with chronic pain, but the magnitude of benefit is likely small.

Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To determine the benefits and harms of medical cannabis and cannabinoids for chronic pain. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, AMED, PsycInfo, CENTRAL, CINAHL, PubMed, Web of Science, Cannabis-Med, Epistemonikos, and trial registries up to January 2021. STUDY SELECTION: Randomised clinical trials of medical cannabis or cannabinoids versus any non-cannabis control for chronic pain at ≥1 month follow-up. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently assessed risk of bias and extracted data. We performed random-effects models meta-analyses and used GRADE to assess the certainty of evidence. RESULTS: A total of 32 trials with 5174 adult patients were included, 29 of which compared medical cannabis or cannabinoids with placebo. Medical cannabis was administered orally (n=30) or topically (n=2). Clinical populations included chronic non-cancer pain (n=28) and cancer related pain (n=4). Length of follow-up ranged from 1 to 5.5 months. Compared with placebo, non-inhaled medical cannabis probably results in a small increase in the proportion of patients experiencing at least the minimally important difference (MID) of 1 cm (on a 10 cm visual analogue scale (VAS)) in pain relief (modelled risk difference (RD) of 10% (95% confidence interval 5% to 15%), based on a weighted mean difference (WMD) of -0.50 cm (95% CI -0.75 to -0.25 cm, moderate certainty)). Medical cannabis taken orally results in a very small improvement in physical functioning (4% modelled RD (0.1% to 8%) for achieving at least the MID of 10 points on the 100-point SF-36 physical functioning scale, WMD of 1.67 points (0.03 to 3.31, high certainty)), and a small improvement in sleep quality (6% modelled RD (2% to 9%) for achieving at least the MID of 1 cm on a 10 cm VAS, WMD of -0.35 cm (-0.55 to -0.14 cm, high certainty)). Medical cannabis taken orally does not improve emotional, role, or social functioning (high certainty). Moderate certainty evidence shows that medical cannabis taken orally probably results in a small increased risk of transient cognitive impairment (RD 2% (0.1% to 6%)), vomiting (RD 3% (0.4% to 6%)), drowsiness (RD 5% (2% to 8%)), impaired attention (RD 3% (1% to 8%)), and nausea (RD 5% (2% to 8%)), but not diarrhoea; while high certainty evidence shows greater increased risk of dizziness (RD 9% (5% to 14%)) for trials with <3 months follow-up versus RD 28% (18% to 43%) for trials with ≥3 months follow-up; interaction test P=0.003; moderate credibility of subgroup effect). CONCLUSIONS: Moderate to high certainty evidence shows that non-inhaled medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning, and sleep quality among patients with chronic pain, along with several transient adverse side effects, compared with placebo. The accompanying BMJ Rapid Recommendation provides contextualised guidance based on this body of evidence. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/3pwn2.

The quality of subgroup analyses in chronic pain randomized controlled trials: a methodological review.

The quality of subgroup analyses (SGAs) in chronic non-cancer pain trials is uncertain. The purpose of this study was to address this issue. We conducted a comprehensive search in MEDLINE and EMBASE from January 2012 to September 2018 to identify eligible trials. Two pairs of reviewers assessed the quality of the SGAs and the credibility of subgroup claims using the 10 criteria developed by Sun et al. in 2012. The associations between the quality of the SGAs and the studies' characteristics including risk of bias, funding sources, sample size, and the latest impact factor, were assessed using multivariable logistic regression. Our search retrieved 3,401 articles of which 66 were eligible. The total number of SGAs was 177 of which 52 (29.4%) made a subgroup claim. Of these, only 15 (8.5%) were evaluated as being of high quality. Among the 30 SGAs that claimed subgroup effects using an appropriate method of performing interaction tests, the credibility of only 5 were assessed as high. None of the subgroup claims met all the credibility criteria. No significant association was found between the quality of SGAs and the studies' characteristics. The quality of the SGAs performed in chronic pain trials was poor. To enhance the quality of SGAs, scholars should consider the developed criteria when designing and conducting trials, particularly those which need to be specified a priori .

Hormone Replacement Therapy and Opioid Tapering for Opioid-Induced Hypogonadism Among Patients with Chronic Noncancer Pain: A Systematic Review.

OBJECTIVE: To systematically review evidence addressing the efficacy of testosterone replacement therapy (TRT) and opioid tapering for opioid-induced hypogonadism among patients with chronic noncancer pain. STUDY DESIGN: Systematic review of randomized controlled trials (RCTs) and observational studies. METHODS: We searched MEDLINE, CINAHL, AMED, CENTRAL, CINAHL, DARE, EMBASE, and PsycINFO through August 2017. Eligible studies enrolled ≥10 patients with chronic noncancer pain and opioid-induced hypogonadism and reported the effect of TRT or opioid tapering on a patient-important outcome collected ≥14 days after treatment. Pairs of reviewers independently screened for eligible studies, assessed risk of bias, and extracted data. We used the GRADE approach to rate quality of evidence. RESULTS: Of 666 abstracts reviewed, five studies including one RCT (N = 84) and four observational studies (N = 157) were eligible. No studies explored the effect of opioid tapering for opioid-induced hypogonadism. Very low-quality evidence found that TRT was associated with improvements in pain (median reduction of 2 points on the 11-point numerical rating scale for pain; 95% confidence interval [CI] = -1.4 to -2.6; minimally important difference [MID] = 2 points), and emotional functioning (mean increase of 9 points on the 100-point SF-36 Mental Component Summary score; 95% CI = 4.40 to 13.60; MID = 5 points). Low-quality evidence suggested that TRT had no effect on sleep quality, sexual function, physical functioning, role functioning, or social functioning; very low-quality evidence suggested no association with depressive symptoms. CONCLUSIONS: Low-quality to very low-quality evidence suggests that TRT may improve pain and emotional functioning, but not other outcomes, in chronic noncancer pain patients with opioid-induced hypogonadism.

The effect of a 12-week combinational exercise program on CD4 count and mental health among HIV infected women: A randomized control trial.

BACKGROUND/OBJECTIVE: There are conflicting results regarding the effects of exercise on immune function of HIV positive patients. Exercise can also be beneficial to psychological functioning of the patients. The purpose of this study was to determine the impact of a 12-week aerobic and resistance exercise training program on mental health and CD4 counts among female HIV+ patients. METHODS: This clinical trial was conducted between September and December 2013. Forty participants (women age range 20-40) were carefully selected from 240 HIV-positive women referred to Voluntary Counseling and Treatment Center (VCT) and randomly assigned to either exercise (80 min of aerobic and strength training while receiving the VCT's routine services) group (n = 20) or control (received the VCT's routine services only) group (n = 20). To assess their mental health status, all participants completed GHQ28 questionnaire. Blood samples were collected to measure CD4 and T-cell counts at baseline and at the end of the 12-week intervention. RESULTS: From a sample of 40 women with HIV infection, the data of 30 participants [experimental group (14) and control group (16)] were analyzed (participation rate 75%). The results indicated that after the intervention program, a significant difference in CD4 cell counts was found between the two groups (P = 0.01). With regard to mental health, after performing intervention, significant improvement in all subscales including anxiety disorder, social function, depression and mental health's total score was observed in the exercise compared to the control groups (P < 0.001). CONCLUSION: Exercise training can be included in health care services in order to improve the mental health status of women with HIV infection. No effect on CD4 count was detected.

Corrigendum: Author's Name and Affiliation Correction. The Effect of 12 Weeks Aerobic, Resistance, and Combined Exercises on Omentin-1 Levels and Insulin Resistance among Type 2 Diabetic Middle-Aged Women.

This corrects the article on p. 205 in vol. 41, PMID: 28537059.

The Effect of 12 Weeks Aerobic, Resistance, and Combined Exercises on Omentin-1 Levels and Insulin Resistance among Type 2 Diabetic Middle-Aged Women.

BACKGROUND: Recent studies have shown that omentin-1 derived from adipokines can affect physiological regulations and some metabolic dis-eases such as type 2 diabetes mellitus (T2DM). METHODS: The purpose of this study was to examine the impact of 12 weeks of aerobic (cycle ergometer), resistance, and combined exercises on omentin-1 level, glucose and insulin resistance indices in overweight middle age women with T2DM. In this study, 60 overweight middle age diabetic women were selected using simple random sampling and they were assigned to three groups of aerobic exercise (n=12), resistant exercise (n=12) and combined exercise (n=13), and one control group (n=15). Exercises were done in a three times per week sessions for a total of 12 weeks. Blood samples were collected before each exercise session and 24 hours after of the last session. RESULTS: Present study showed that fasting blood sugar decreased significantly in all intervention groups, while homeostasis model assessment of insulin resistance (HOMA-IR) decreased only in the aerobic and combined exercises groups. Furthermore, there was a significant increase in the omentin-1 level only in the combined exercise group. CONCLUSION: Compared to aerobic and resistance exercises, 12 weeks of combined exercise was more efficient in improving HOMA-IR and increasing serum omentin-1 among women with T2DM.