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.

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence. RESULTS: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%). CONCLUSIONS: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.

Clinical applications of three-dimensional printing in otolaryngology-head and neck surgery: A systematic review.

OBJECTIVES: Medical three-dimensional (3D) printing, the fabrication of handheld models from medical images, has the potential to become an integral part of otolaryngology-head and neck surgery (Oto-HNS) with broad impact across its subspecialties. We review the basic principles of this technology and provide a comprehensive summary of reported clinical applications in the field. METHODS: Standard bibliographic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, and The Cochrane Central Registry for Randomized Trials) were searched from their inception to May 2018 for the terms: "3D printing," "three-dimensional printing," "rapid prototyping," "additive manufacturing," "computer-aided design," "bioprinting," and "biofabrication" in various combinations with the terms: "ptolaryngology," "head and neck surgery," and "otology." Additional articles were identified from the references of retrieved articles. Only studies describing clinical applications of 3D printing were included. RESULTS: Of 5,532 records identified through database searching, 87 articles were included for qualitative synthesis. Widespread implementation of 3D printing in Oto-HNS is still at its infancy. Nonetheless, it is increasingly being utilized across all subspecialties from preoperative planning to design and fabrication of patient-specific implants and surgical guides. An emerging application considered highly valuable is its use as a teaching tool for medical education and surgical training. CONCLUSIONS: As technology and training standards evolve and as healthcare moves toward personalized medicine, 3D printing is emerging as a key technology in patient care in Oto-HNS. Treating physicians and surgeons who wish to stay abreast of these developments will benefit from a fundamental understanding of the principles and applications of this technology. Laryngoscope, 129:2045-2052, 2019.

Comparing Cephalic Index and Midsagittal Vector Analysis in Assessing Morphology in Sagittal Synostosis: A CT-Based Morphometric Analysis.

INTRODUCTION: Assessment of cranial dysmorphism in sagittal synostosis is often subjective but objective measures can be applied. These include cephalic index (CI) and midsagittal vector analysis (MSVA). OBJECTIVE: To assess discriminant validity, construct validity, and responsiveness of CI and MSVA measured from computed tomography (CT) in patients with sagittal synostosis. METHODS: Patients with nonsyndromic isolated sagittal synostosis with complete preoperative (n = 30) and postoperative (n = 13) CT data were included. Age-matched control group (n = 24) comprised of normocephalic patients who underwent CT for reasons related to trauma. OUTCOME MEASURES: Retrospective CT evaluation of CI and MSVA was conducted and correlated with a dysmorphism numeric rating scale (D-NRS) that measured surgeon-rated severity of sagittal synostosis. Responsiveness of CI and MSVA was evaluated using dysmorphism global rating of change (D-GRC). RESULTS: Thirty patients with sagittal synostosis were demographically similar to 24 normocephalic patients. The difference in CI and MSVA was statistically significant between normocephalic and scaphocephalic patients. Cephalic index had a good correlation with D-NRS (r = -0.665, ρ = -0.667), but not with MSVA (r = 0.250, ρ = 0.203). Change in CI (r = 0.738, ρ = 0.657) was well correlated with D-GRC, but not with MSVA (r = -0.409, ρ = -0.301). CONCLUSION: Cephalic index appears to quantify the severity of sagittal synostosis better than MSVA. Cephalic index also has better responsiveness than MSVA to measure a reduction in severity of disease; however, MSVA is a better descriptive craniometric measurement. Midsagittal vector analysis was able to quantify the shift in morphology in sagittal synostosis following surgical treatment.

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis.

Importance: Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit. Objective: To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life. Data Sources: For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016. Study Selection: Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies. Data Extraction and Synthesis: We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions. Main Outcome and Measure: The association between PFS duration and HRQoL. Results: Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were -0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, -0.27 to 0.52); for physical HRQoL (n = 20 trials) it was -0.20 (95% CI, -0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, -0.05 to 1.60). Conclusions and Relevance: We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

Weight loss surgery for obstructive sleep apnoea with obesity in adults: a systematic review and meta-analysis protocol.

INTRODUCTION: Obstructive sleep apnoea (OSA) is caused by complete or partial obstruction of the upper airway resulting in repeated episodes of interrupted or shallow breaths. OSA is associated with significant morbidity and mortality. The prevalence is estimated to range from 3% to 7% in the general population but may be much higher. Several studies show that weight loss or bariatric surgery may have a role in treating OSA. The aim of this systematic review is to assess the safety and efficacy of randomised controlled trials (RCTs) of weight loss surgery for adults with OSA and comorbid obesity. METHODS AND ANALYSIS: A search of the Cochrane Central Register of Controlled Trials, PubMed, EMBASE and two major Chinese biomedical databases will be performed to identify related trials published as of October 2018. This study will include RCTs, comparing different types of weight loss surgery for OSA with obesity or weight loss surgery for OSA with obesity with other upper airway surgeries. The primary outcomes that will be measured are apnoea-hypopnoea index, excess weight loss and in-hospital mortality. The secondary outcomes will include duration of hospital stay, neck circumference, reoperation, waist circumference, body mass index, Epworth Sleepiness Scale score, overt complications (eg, gastric fistula, bleeding, delayed gastric emptying, wound infection), quality of life, quality of sleep and/or functionality. The systematic review will be conducted according to the recommendations as outlined by the Cochrane collaboration. ETHICS AND DISSEMINATION: The systematic review and meta-analysis will include published data available online and thus ethics approval will not be required. The findings will be disseminated and published in a peer-reviewed journal. Review updates will be conducted if there is new evidence that may cause any change in review conclusions. Any changes to the study protocol will be updated in the PROSPERO trial registry accordingly. PROSPERO REGISTRATION NUMBER: CRD42017081743.

Predictors of Unemployment After Breast Cancer Surgery: A Systematic Review and Meta-Analysis of Observational Studies.

Purpose Breast cancer surgery is associated with unemployment. Identifying high-risk patients could help inform strategies to promote return to work. We systematically reviewed observational studies to explore factors associated with unemployment after breast cancer surgery. Methods We searched MEDLINE, EMBASE, CINAHL, and PsycINFO to identify studies that explored risk factors for unemployment after breast cancer surgery. When possible, we pooled estimates of association for all independent variables reported by more than one study. Results Twenty-six studies (46,927 patients) reported the association of 127 variables with unemployment after breast cancer surgery. Access to universal health care was associated with higher rates of unemployment (26.6% v 15.4%; test of interaction P = .05). High-quality evidence showed that unemployment after breast cancer surgery was associated with high psychological job demands (odds ratio [OR], 4.26; 95% CI, 2.27 to 7.97), childlessness (OR, 1.30; 95% CI, 1.11 to 1.53), lower education level (OR, 1.15; 95% CI, 1.05 to 1.25), lower income level (OR, 1.46; 95% CI, 1.24 to 1.73), cancer stage II, III or IV (OR, 1.43; 95% CI, 1.13 to 1.82), and mastectomy versus breast-conserving surgery (OR, 1.18; 95% CI, 1.07 to 1.30). Moderate-quality evidence suggested an association with high physical job demands (OR, 2.11; 95%CI, 1.52 to 2.93), African-American ethnicity (OR, 1.89; 95% CI, 1.21 to 2.96), and receipt of chemotherapy (OR, 1.95; 95% CI, 1.36 to 2.79). High-quality evidence demonstrated no significant association with part-time hours, blue-collar work, tumor size, positive lymph nodes, or receipt of radiotherapy or endocrine therapy; moderate-quality evidence suggested no association with age, marital status, or axillary lymph node dissection. Conclusion Addressing high physical and psychological job demands may be important in reducing unemployment after breast cancer surgery.