Medical Cannabis and Cannabinoids for Impaired Sleep: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

SLEEP ◽  
2021 ◽  
Author(s):  
Mahmood AminiLari ◽  
Li Wang ◽  
Samuel Neumark ◽  
Taranah Adli ◽  
Rachel J Couban ◽  
...  

Abstract 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 (5,100 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 (WMD of -0.19cm [95%CI, -0.36 to -0.03cm]; interaction p=0.03). 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.

BMJ ◽  
2021 ◽  
pp. n1034 ◽  
Author(s):  
Li Wang ◽  
Patrick J Hong ◽  
Curtis May ◽  
Yasir Rehman ◽  
Yvgeniy Oparin ◽  
...  

Abstract 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


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A139-A140
Author(s):  
Janannii Selvanathan ◽  
Chi Pham ◽  
Mahesh Nagappa ◽  
Philip Peng ◽  
Marina Englesakis ◽  
...  

Abstract Introduction Patients with chronic non-cancer pain often report insomnia as a significant comorbidity. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as the first line of treatment for insomnia, and several randomized controlled trials (RCTs) have examined the efficacy of CBT-I on various health outcomes in patients with comorbid insomnia and chronic non-cancer pain. We conducted a systematic review and meta-analysis on the effectiveness of CBT-I on sleep, pain, depression, anxiety and fatigue in adults with comorbid insomnia and chronic non-cancer pain. Methods A systematic search was conducted using ten electronic databases. The duration of the search was set between database inception to April 2020. Included studies must be RCTs assessing the effects of CBT-I on at least patient-reported sleep outcomes in adults with chronic non-cancer pain. Quality of the studies was assessed using the Cochrane risk of bias assessment and Yates quality rating scale. Continuous data were extracted and summarized using standard mean difference (SMD) with 95% confidence intervals (CIs). Results The literature search resulted in 7,772 articles, of which 14 RCTs met the inclusion criteria. Twelve of these articles were included in the meta-analysis. The meta-analysis comprised 762 participants. CBT-I demonstrated a large significant effect on patient-reported sleep (SMD = 0.87, 95% CI [0.55–1.20], p &lt; 0.00001) at post-treatment and final follow-up (up to 9 months) (0.59 [0.31–0.86], p &lt; 0.0001); and moderate effects on pain (SMD = 0.20 [0.06, 0.34], p = 0.006) and depression (0.44 [0.09–0.79], p= 0.01) at post-treatment. The probability of improving sleep and pain following CBT-I at post-treatment was 81% and 58%, respectively. The probability of improving sleep and pain at final follow-up was 73% and 57%, respectively. There were no statistically significant effects on anxiety and fatigue. Conclusion This systematic review and meta-analysis showed that CBT-I is effective for improving sleep in adults with comorbid insomnia and chronic non-cancer pain. Further, CBT-I may lead to short-term moderate improvements in pain and depression. However, there is a need for further RCTs with adequate power, longer follow-up periods, CBT for both insomnia and pain, and consistent scoring systems for assessing patient outcomes. Support (if any):


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A265-A266
Author(s):  
Yishi Sun ◽  
Isabelle Laksono ◽  
Janannii Selvanathan ◽  
Aparna Saripella ◽  
Mahesh Nagappa ◽  
...  

Abstract Introduction In individuals with chronic pain, sleep disturbances have been suggested to increase suffering, perception of pain, and to negatively affect long-term prognosis. This systematic review and meta-analysis aims to determine the pooled prevalence of sleep disturbances in chronic non-cancer pain patients with no other sleep disorders, using the patient-rated questionnaires Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). Methods Multiple databases were searched for studies reporting the prevalence of sleep disturbances in chronic pain patients. Chronic pain was defined as pain &gt;3 months. Comorbid sleep disorders such as sleep disordered breathing and restless leg syndrome were excluded. Sleep disturbances were defined using the PSQI cutoff of &gt; 5 (poor sleep quality) and ISI ≥ 8 (subthreshold to clinical insomnia). The meta-analysis was conducted to examine the pooled prevalence of PSQI and ISI data using the inverse-variance random-effects model and to examine mean differences in PSQI scores. Results The systematic search resulted in 25,486 articles and 20 were included for analysis. In 12 studies using PSQI, the pooled prevalence of sleep disturbance was 75.3% among 3,597 chronic pain patients (mean age 53 ± 12 years; 74% female). In eight studies using ISI, the pooled prevalence was 72.9% among 2,578 chronic pain patients (mean age 63 ± 12 years; 57% female). The meta-analysis showed a significant mean difference of 2.75 (p &lt; 0.001) in the global PSQI score between the chronic pain group versus the non-chronic pain group. The meta-analysis also showed a significant mean difference in the scores of four of seven PSQI components: sleep latency, sleep efficiency, sleep duration, and sleep disturbances (p &lt; 0.05). Conclusion In chronic pain patients, the pooled prevalence of sleep disturbances as measured by PSQI (75.3%) and ISI (72.9%) studies was much higher than those reported for the general population. The relatively high prevalence of sleep disturbances in chronic pain patients emphasizes the importance of further characterizing the relationship between sleep and chronic pain. Support (if any):


Author(s):  
Sansano-Nadal ◽  
Giné-Garriga ◽  
Brach ◽  
Wert ◽  
Jerez-Roig ◽  
...  

Exercise is a form of physical activity (PA). PA is an important marker of health and quality of life in older adults. The purpose of this study was to conduct a systematic review of the literature to assess the effect of exercise-based interventions on an at least six-month follow up PA measure, and to describe the specific strategies implemented during the intervention to strengthen the sustainability of PA in community-dwelling 65+ year-old adults. We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42017070892) of randomized clinical trials (RCT). We searched three electronic databases during January 2018 to identify RCT assessing any type of exercise-based intervention. Studies had to report a pre-, post-, and at least 6-month post-intervention follow-up. To be included, at least one PA outcome had to be assessed. The effect of exercise-based interventions was assessed compared to active (e.g., a low-intensity type of exercise, such as stretching or toning activities) and non-active (e.g., usual care) control interventions at several time points. Secondary analyses were conducted, restricted to studies that reported specific strategies to enhance the sustainability of PA. The intervention effect was measured on self-reported and objective measures of time spent in PA, by means of standardized mean differences. Standardized mean differences of PA level were pooled. Pooled estimates of effect were computed with the DerSimonian–Laird method, applying a random effects model. The risk of bias was also assessed. We included 12 studies, comparing 18 exercise intervention groups to four active and nine non-active control groups. Nine studies reported specific strategies to enhance the long-term sustainability of PA. The strategies were mostly related to the self-efficacy, self-control, and behavior capability principles based on the social cognitive theory. Exercise interventions compared to active control showed inconclusive and heterogeneous results. When compared to non-active control, exercise interventions improved PA time at the six-months follow up (standardized mean difference (SMD) 0.30; 95%CI 0.15 to 0.44; four studies; 724 participants; I2 0%), but not at the one- or two-years follow-ups. No data were available on the mid- and long-term effect of adding strategies to enhance the sustainability of PA. Exercise interventions have small clinical benefits on PA levels in community-dwelling older adults, with a decline in the observed improvement after six months of the intervention cessation.


2021 ◽  
Vol 34 ◽  
Author(s):  
Michel Marcos Dalmedico ◽  
Caroline Machado de Toledo ◽  
Paula Karina Hembecker ◽  
Juliana Londero Silva Ávila ◽  
Chayane Karla Lucena de Carvalho ◽  
...  

Abstract Introduction: Cancer pain has a considerable impact on patients’ health and quality of life, and its treatment is essentially based on opioid use. Objective: To report the effectiveness of acupuncture in relieving cancer pain (secondary to the disease or to the corresponding therapy) or in decreasing opioid use compared to other interventions. Methods: A systematic review of randomized clinical trials was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The trials were selected from the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: The search strategy resulted in the inclusion of eight trials, of which five compared acupuncture and drug therapy and three compared acupuncture and placebo. Seven trials reported decreased pain and analgesic use. The trials showed clinical heterogeneity, making a meta-analysis unfeasible. Conclusion: The findings herein provided no robust evidence to support the routine use of acupuncture as an adjuvant therapy in the treatment of cancer pain. However, its use is promising since the results showed a trend toward decreased pain and analgesic use, thus justifying further studies in the future.


Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 447
Author(s):  
Diogo Pinto ◽  
Andréa Marques ◽  
Joana F. Pereira ◽  
Paulo J. Palma ◽  
João Miguel Santos

Background and objectives: The long-term outcome of endodontic microsurgery (EMS) performed on root-filled teeth affected by post-treatment apical periodontitis (AP) has been a matter of debate, re-launched by the introduction of novel root-end filling materials which have been proven to improve the short-term outcome of EMS. The purpose of this systematic review and meta-analysis is to evaluate the clinical and radiographic long-term outcome of endodontic microsurgery in teeth diagnosed with secondary AP through radiographic evaluation. Materials and Methods: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion and exclusion criteria were defined a priori to select the best longitudinal evidence. Only randomized clinical trials (RCT) and prospective clinical studies (PCS), with a follow-up ≥ 2-year, and exhibiting well-established clinical and radiographic outcome criteria, were selected. Results: A total of 573 articles were obtained, from which 10 fulfill inclusion criteria: 6 PCS and 4 RCT. Meta-analysis showed a pooled proportion of success rate of 91.3%, from an overall amount of 453 treated teeth included in RCT; from overall 839 included teeth in PCS, a pooled success rate of 78.4% was observed, with the follow-up time ranging from 2 to 13-years. Survival rate outcomes varied from 79 to 100% for the same follow-up period. Five prognostic factors with influence on the outcome were disclosed: smoking habits, tooth location and type, absence/presence of dentinal defects, interproximal bone level, and root-end filling material. Conclusions: High success rates and predictable results can be expected when EMS is performed by trained endodontists, allowing good prognosis and preservation of teeth affected by secondary AP.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yuzhao Huang ◽  
Qiufang Deng ◽  
Liuqing Yang ◽  
Jiahui Ma ◽  
Ziyang Wang ◽  
...  

Background. Knee osteoarthritis (KOA) is a common degenerative disease associated with joint dysfunction and pain. Ultrasound-guided radiofrequency (RF) may be a promising therapy in the treatment of chronic pain for KOA patients. Objective. To evaluate the efficacy and safety of ultrasound-guided RF treatment for chronic pain in patients with KOA. Design. A systematic review was conducted, and a meta-analysis was carried out when possible. Setting. We examined the studies evaluating the clinical efficiency of ultrasound-guided RF on chronic pain in KOA population. Method. A systematic review for the efficacy and safety of ultrasound-guided RF treatment for pain management of KOA patients was carried out in PubMed, EMBASE, Cochrane Library, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) from the date of inception to February 2020, and a meta-analysis was conducted. The primary outcomes of pain intensity (visual analogue scale or numerical rating scale) and knee function [the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)] were evaluated from baseline to various follow-up times by random-effects model. Heterogeneity was assessed by I2 statistic and the potential sources of heterogeneity by subgroup and metaregression analyses, respectively. Results. Eight publications with 256 patients were included in the meta-analysis. RF could relieve pain with −4.196 of pooled mean difference and improve knee function by decreasing 23.155 points in WOMAC. Three patients had ecchymosis, two with hypoesthesia and one with numbness after the procedure, and improved within 6 months. Furthermore, study design and treatment target were the sources of heterogeneity by subgroup and metaregression analyses, accounting for 37% and 74% of variances, respectively. Target of genicular nerve achieved better pain relief than intra-articular or sciatic nerve. Sensitivity analysis showed that removal of any single study was unlikely to overturn the findings. Limitations. There were some limitations in the study. Firstly, the small number of relevant studies limited the confidence level of the meta-analysis. Also, the significant heterogeneity may not be explained due to the limited data. Secondly, the direct comparison of two different guidance methods (ultrasound vs. fluoroscopy) for RF therapy is lacking. In addition, the outcomes were blindly assessed in the meta-analysis from all studies according to evaluation of bias, which could affect the reality of the data. Finally, most of the studies only provided short follow-up times, so we could not analyze the long-term effectiveness of ultrasound-guided RF in the treatment of patients with KOA. Conclusions. Ultrasonography is an effective, safe, nonradiative, and easily applicable guidance method for RF in pain relief and functional improvement in KOA patients.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 698
Author(s):  
Elisabet Roca-Millan ◽  
Albert Estrugo-Devesa ◽  
Alexandra Merlos ◽  
Enric Jané-Salas ◽  
Teresa Vinuesa ◽  
...  

Systemic antibiotics are routinely prescribed in implant procedures, but the lack of consensus causes large differences between clinicians regarding antibiotic prophylaxis regimens. The objectives of this systematic review are to assess the need to prescribe antibiotics to prevent early implant failure and find the most appropriate antibiotic prophylaxis regimen. The electronic search was conducted in PubMed/MEDLINE, Scielo and Cochrane Central Trials Database for randomized clinical trials of at least 3 months of follow-up. Eleven studies were included in the qualitative analysis. Antibiotics were found to statistically significantly reduce early implant failures (RR = 0.30, 95% CI: 0.19–0.47, p < 0.00001; heterogeneity I2 = 0%, p = 0.54). No differences were seen between preoperative or both pre- and postoperative antibiotic regimens (RR = 0.57, 95% CI: 0.21–1.55, p = 0.27; heterogeneity I2 = 0%, p = 0.37). A single preoperative antibiotic prophylaxis dose was found to be enough to significantly reduce early implant failures compared to no antibiotic (RR = 0.34, 95% CI: 0.21–0.53, p < 0.00001; heterogeneity I2 = 0%, p = 0.61). In conclusion, in healthy patients a single antibiotic prophylaxis dose is indicated to prevent early implant failure.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250385
Author(s):  
Dimitrios A. Koutoukidis ◽  
Elizabeth Morris ◽  
John A. Henry ◽  
Yusra Shammoon ◽  
Matthew Zimmerman ◽  
...  

Background and aim Trials of treatments for non-alcoholic steatohepatitis require endpoint assessment with liver biopsies. Previous large-scale trials have calculated their sample size expecting high retention but on average did not achieve this. We aimed to quantify the proportion of participants with a valid follow-up biopsy. Methods We conducted a systematic review of MEDLINE and Embase until May 2020 and included randomized clinical trials of any intervention in non-alcoholic steatohepatitis with at least 1-year follow-up. We were guided by Cochrane methods to run a meta-analysis with generalized linear mixed models with random effects. Results Forty-one trials (n = 6,695) were included. The proportion of participants with a valid follow-up biopsy was 82% (95%CI: 78%-86%, I2 = 92%). There was no evidence of a difference by location, trial length, or by allocated treatment group. Reasons for missing follow-up biopsies were, in ranked order, related to participants (95 per 1,000 participants (95%CI: 69–129, I2 = 92%), medical factors, protocol, trial conduct, and other/unclear. Biopsy-related serious adverse events occurred in 16 per 1,000 participants (95% CI: 8–33, I2 = 54%). No biopsy-related deaths were reported. Conclusions The proportion of participants with a valid follow-up biopsy in therapeutic trials in non-alcoholic steatohepatitis is on average 82%, with around 1 in 10 participants declining a follow-up biopsy. These findings can inform adequately-powered trials.


2015 ◽  
Vol 49 (1) ◽  
pp. 152-161 ◽  
Author(s):  
Gisely Blanc ◽  
Marineli Joaquim Meier ◽  
Janislei Giseli Dorociaki Stocco ◽  
Hellen Roehrs ◽  
Karla Crozeta ◽  
...  

OBJECTIVE To evaluate the effectiveness of enteral nutritional therapy (ENT) in the healing process of pressure ulcers (PU) in adults and the elderly. METHOD A systematic review whose studies were identified through the databases of Cochrane, MEDLINE/PubMed, SciELO, LILACS, EMBASE, CINAHL, Web of Science, and manual searches. It included randomized clinical trials (RCTs) without delimiting the period or language of publication, which addressed adults and elderly patients with pressure ulcers in a comparative treatment of enteral nutritional therapy and placebo or between enteral nutritional therapy with different compositions and dosages. RESULTS We included ten studies that considered different interventions. It resulted in more pressure ulcers healed in the groups that received the intervention. The included studies were heterogeneous with regard to patients, the type of intervention, the sample and the follow-up period, all of which made meta-analysis impossible. CONCLUSION Although the enteral nutritional therapy demonstrates a promotion of pressure ulcer healing, sufficient evidence to confirm the hypothesis was not found.


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