Beyond traditional therapies: a network meta-analysis on the treatment efficacy for chronic phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) frequently affects individuals with limb amputations. When PLP evolves into its chronic phase, known as chronic PLP, traditional therapies often fall short in providing sufficient relief. The optimal intervention for chronic PLP remains unclear. OBJECTIVE: The objectives of this network meta-analysis (NMA) were to examine the efficacy of different treatments on pain intensity for patients with chronic PLP. EVIDENCE REVIEW: We searched Medline, EMBASE, Cochrane CENTRAL, Scopus, and CINAHL EBSCO, focusing on randomized controlled trials (RCTs) that evaluated interventions such as neuromodulation, neural block, pharmacological methods, and alternative treatments. An NMA was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was pain score improvement, and the secondary outcomes were adverse events. FINDINGS: The NMA, incorporating 12 RCTs, indicated that neuromodulation, specifically repetitive transcranial magnetic stimulation, provided the most substantial pain improvement when compared with placebo/sham groups (mean difference=-2.9 points, 95% CI=-4.62 to -1.18; quality of evidence (QoE): moderate). Pharmacological intervention using morphine was associated with a significant increase in adverse event rate (OR=6.04, 95% CI=2.26 to 16.12; QoE: low). CONCLUSIONS: The NMA suggests that neuromodulation using repetitive transcranial magnetic stimulation may be associated with significantly larger pain improvement for chronic PLP. However, the paucity of studies, varying patient characteristics across each trial, and absence of long-term results underscore the necessity for more comprehensive, large-scale RCTs. PROSPERO REGISTRATION NUMBER: CRD42023455949.

High Dosage Omega-3 Fatty Acids Outperform Existing Pharmacological Options for Migraine Prophylaxis: A Network Meta-Analysis.

Migraine is a highly prevalent neurologic disorder with prevalence rates ranging from 9% to 18% worldwide. Current pharmacologic prophylactic strategies for migraine have limited efficacy and acceptability, with relatively low response rates of 40% to 50% and limited safety profiles. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are considered promising therapeutic agents for migraine prophylaxis. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various dosages of EPA/DHA and other current Food and Drug Administration-approved or guideline-recommended prophylactic pharmacologic interventions for migraine. Randomized controlled trials (RCTs) were eligible for inclusion if they enrolled participants with a diagnosis of either episodic or chronic migraine. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed were 1) changes in migraine frequency and 2) acceptability (i.e., dropout for any reason). Secondary outcomes included response rates, changes in migraine severity, changes in the frequency of using rescue medications, and frequency of any adverse events. Forty RCTs were included (N = 6616; mean age = 35.0 y; 78.9% women). Our analysis showed that supplementation with high dosage EPA/DHA yields the highest decrease in migraine frequency [standardized mean difference (SMD): -1.36; 95% confidence interval (CI): -2.32, -0.39 compared with placebo] and the largest decrease in migraine severity (SMD: -2.23; 95% CI: -3.17, -1.30 compared with placebo) in all studied interventions. Furthermore, supplementation with high dosage EPA/DHA showed the most favorable acceptability rates (odds ratio: 1.00; 95% CI: 0.06, 17.41 compared with placebo) of all examined prophylactic treatments. This study provides compelling evidence that high dosage EPA/DHA supplementation can be considered a first-choice treatment of migraine prophylaxis because this treatment displayed the highest efficacy and highest acceptability of all studied treatments. This study was registered in PROSPERO as CRD42022319577.

Primary antibiotic resistance of Helicobacter pylori in the Asia-Pacific region between 1990 and 2022: an updated systematic review and meta-analysis.

BACKGROUND: We previously showed rising primary antibiotic resistance of Helicobacter pylori during 1990-2015 in the Asia-Pacific region. However, whether primary antibiotic resistance continues to rise is unknown. Therefore, we aimed to assess the latest prevalence of H pylori antibiotic resistance in this region. METHODS: We did an updated systematic review and meta-analysis of observational studies and randomised controlled trials published in PubMed, Embase, and Cochrane Library between Jan 1, 1990, and July 12, 2023. Studies investigating primary H pylori resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, or tetracycline in individuals naive to eradication therapy in the Asia-Pacific region (as defined by the UN geoscheme) were eligible for inclusion. There were no language restrictions. Studies that focused on specific subpopulations (eg, children) were excluded. Using a standardised extraction form, two authors independently reviewed and extracted summary data from all eligible articles. The updated prevalence of antibiotic resistance was generated by meta-analysis under a random-effects model and subgroup analyses were done by countries and periods of study. Between-study variability was assessed by use of I2. The study is registered in PROSPERO, CRD42022339956. FINDINGS: A total of 351 studies, including 175 new studies and 176 studies from our previous analysis, were included in this meta-analysis. The overall prevalence of primary antibiotic resistance of H pylori between 1990 and 2022 was 22% (95% CI 20-23; I2=96%) for clarithromycin, 52% (49-55; I2=99%) for metronidazole, 26% (24-29; I2=96%) for levofloxacin, 4% (3-5; I2=95%) for tetracycline, and 4% (3-5; I2=95%) for amoxicillin. Prevalence varied considerably between countries and across study periods. From 1990 to 2022, the prevalence of primary resistance increased for clarithromycin, metronidazole, and levofloxacin but remained stable for amoxicillin and tetracycline. The latest primary resistance prevalences were 30% (95% CI 28-33; I2=93%) for clarithromycin, 61% (55-66; I2=99%) for metronidazole, 35% (31-39; I2=95%) for levofloxacin, 4% (2-6; I2=96%) for tetracycline, and 6% (4-8; I2=96%) for amoxicillin in the Asia-Pacific region. INTERPRETATION: Treatment guidelines should be adapted in response to the rising primary resistance of key antibiotics for H pylori eradication. A global policy to control and monitor the antibiotic resistance of H pylori is urgently needed. FUNDING: Ministry of Health and Welfare of Taiwan, National Science and Technology Council of Taiwan, and National Taiwan University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Comparisons Between Endoscopic Band Ligation, Radiofrequency Ablation and Endoscopic Thermal Therapy for Gastric Antral Vascular Ectasia: A Meta-Analysis.

BACKGROUND: Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) have emerged as alternative therapies of gastric antral vascular ectasia (GAVE) in addition to endoscopic thermal therapy (ETT), but the optimum choice remains inconclusive. AIM: We conducted a meta-analysis in order to compare these three treatments for GAVE. METHODS: We searched the electronic databases of PubMed, Embase and Cochrane Central Register of Controlled Trials without any language restrictions and also performed a manual literature search of bibliographies located in both retrieved articles and published reviews for eligible publications prior to December 8, 2021. We included comparative trials which had evaluated the efficacy and safety of interventions in adults (aged ≥ 18 years) diagnosed with symptomatic GAVE and was confirmed according to clinical backgrounds and upper gastrointestinal endoscopy. We included reports that compared three interventions, ETT, EBL, and RFA. The study was comprised of adults diagnosed with GAVE and focused on overall mortality, bleeding cessation, endoscopic improvement, complications, hospitalization, hemoglobin improvement, number of sessions and transfusion requirements. RESULTS: Twelve studies were performed involving a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation (OR 4.48, 95% CI 1.36-14.77, p = 0.01), higher hemoglobin improvement (MD 0.57, 95% CI 0.31-0.83, p < 0.01) and lower number of sessions (MD - 1.44, 95% CI - 2.54 to - 0.34, p = 0.01). Additionally, EBL was superior to ETT in endoscopic improvement (OR 6.00, 95% CI 2.26-15.97, p < 0.01), hospitalization (MD - 1.32, 95% CI - 1.91 to - 0.74, p < 0.01) and transfusion requirement (MD - 2.66, 95% CI - 4.67 to - 0.65, p = 0.01) with statistical significance, with the exception of mortality (OR 0.58, 95% CI 0.19-1.77, p = 0.34) and complication rate (OR 5.33, 95% CI 0.58-48.84, p = 0.14). CONCLUSION: For GAVE, we suggest that EBL be initially recommended, and APC and RFA be used as alternative treatment choices based upon a very low quality of evidence.

Omega-3 polyunsaturated fatty acids in sarcopenia management: A network meta-analysis of randomized controlled trials.

Sarcopenia frequently occurs with aging and leads to major adverse impacts on activities of daily living and quality of life in elderly individuals. Omega-3 polyunsaturated fatty acid (omega-3 PUFAs) supplements are considered promising therapeutic agents for sarcopenia management; however, the evidence remains inconsistent. We reviewed randomized controlled trials (RCTs) about omega-3 PUFA supplementation in patients with sarcopenia or in those at high risk for sarcopenia. Network meta-analysis (NMA) procedures were conducted using a frequentist model. The primary outcomes were (1) upper-extremity muscle strength and (2) lower-extremity physical function. The NMA of 16 RCTs showed that the high-dose (more than 2.5 g/day omega-3 PUFAs) group yielded the greatest improvement in both upper-extremity muscle strength and lower-extremity physical function [compared to placebo/standard care groups, standardized mean difference (SMD)= 1.68, 95% confidence interval (95%CI)= 0.03-3.33, and SMD= 0.73, 95%CI= 0.16-1.30, respectively], and the effects were reaffirmed in subgroup analyses of placebo-controlled RCTs or those excluding concurrent resistance training programs. None of the investigated omega-3 PUFAs supplementation was associated with significantly increased skeletal muscle mass, fat mass, or overall body weight. Our findings provide a basis for future large-scale RCTs to investigate the dose effects and clinical application of omega-3 PUFA supplementation in sarcopenia management. TRIAL REGISTRATION: The current study was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (TSGHIRB No. B-109-29) and registered in PROSPERO (CRD42022347161).

Effects of Vitamin D Supplementation on Cognitive Outcomes: A Systematic Review and Meta-Analysis.

Clinical studies examining the effects of vitamin D on cognition have reported inconsistent results. To date, no comprehensive study has examined this effect on the basis of sample characteristics or intervention model-related factors. This systematic review and meta-analysis of randomized controlled trials investigated the effects of vitamin D supplementation on global cognitive function and specific cognitive domains. This review was preregistered in the PROSPERO database (CRD42021249908) and comprised 24 trials enrolling 7557 participants (mean age: 65.21 years; 78.54% women). The meta-analysis revealed that vitamin D significantly influenced global cognition (Hedges' g = 0.128, p = .008) but not specific cognitive domains. A subgroup analysis indicated that the effect size of vitamin D was stronger for vulnerable populations (Hedges' g = 0.414) and those with baseline vitamin D deficiency (Hedges' g = 0.480). On the basis of subgroup analyses in studies without biological flaws (Hedges' g = 0.549), we suggest that an intervention model should correct baseline vitamin D deficiency. Our results indicate that vitamin D supplementation has a small but significant positive effect on cognition in adults.

Black cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysis.

OBJECTIVE: Menopausal symptoms are common in midlife women and have broad impacts on their daily functioning and quality of life. Black cohosh extracts have been widely used to relieve menopausal symptoms. However, the comparative benefits of different combined black cohosh regimens remain inconclusive. The aim of the current updated meta-analysis is to address the comparative efficacies of different black cohosh regimens in improving menopausal symptoms. METHODS: Random-effect model pairwise meta-analysis of randomized controlled trials was conducted to investigate the treatment effect on menopausal symptoms by the black cohosh extract both alone or combined with other related active ingredients. The outcomes studied were changes in menopausal symptoms after treatment with black cohosh extracts in menopausal women. RESULTS: Twenty-two articles including information on 2,310 menopausal women were included in the analyses. Black cohosh extracts were associated with significant improvements in overall menopausal symptoms (Hedges' g = 0.575, 95% CI = 0.283 to 0.867, P < 0.001), as well as in hot flashes (Hedges' g = 0.315, 95% CIs = 0.107 to 0.524, P = 0.003), and somatic symptoms (Hedges' g = 0.418, 95% CI = 0.165 to 0.670, P = 0.001), compared with placebo. However, black cohosh did not significantly improve anxiety (Hedges' g = 0.194, 95% CI = -0.296 to 0.684, P = 0.438) or depressive symptoms (Hedges' g = 0.406, 95% CI = -0.121 to 0.932, P = 0.131). The dropout rate for black cohosh products was similar to that for placebo (odds ratio = 0.911, 95% CI = 0.660 to 1.256, P = 0.568). CONCLUSIONS: This study provides updated evidence regarding the potentially beneficial effects of black cohosh extracts for relieving menopausal symptoms in menopausal women.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy.

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

The role of omega-3 polyunsaturated fatty acids (PUFAs) in primary and secondary prevention on major cardiovascular events (MCE) is inconclusive due to the potential heterogeneity in study designs of formulas, dosages, and ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from the findings of previous randomized controlled trials (RCTs). Here we conducted a comprehensive narrative review of pre-clinical studies and updated a network meta-analysis (NMA) to determine the comparative efficacy against MCE with different EPA/DHA dosages and formulas. We found that pure EPA was ranked the best option in the secondary prevention (hazard ratio: 0.72, 95% confidence interval: 0.65 to 0.81) from the NMA of 39 RCTs with 88,359 participants. There was no evidence of omega-3 PUFAs' efficacy in primary prevention. The mechanisms of omega-3 PUFAs' cardiovascular protection might link to the effects of anti-inflammation and stabilization of endothelial function from PUFA's derivatives including eicosanoids and the special pre-resolving mediators (SPMs).

Comparative efficacy of exercise regimens on sleep quality in older adults: A systematic review and network meta-analysis.

The efficacies of various exercise modalities in improving older adults' sleep quality remain unclear. Therefore, in this study, network meta-analysis was performed by comparing the efficacies of various exercise regimens in improving sleep quality in this age group. Six electronic databases were searched for relevant studies between the date of database creation and August 13, 2021. Only randomized controlled trials reporting the effects of exercise on sleep quality in this population were included. Random-effects network meta-analysis based on a frequentist framework was conducted. In total, 35 trials involving 3519 older adults were included. Cognitive behavioral therapy for insomnia, muscle endurance training combined with walking, Tai chi, Baduanjin, resistance training combined with walking, and resistance training significantly improved sleep quality to a greater degree than did usual care (P < 0.05). Muscle endurance training combined with walking led to significantly higher sleep quality than did regimens involving sleep hygiene, Pilates, only walking, health education, resistance training, Taichi, resistance training combined with walking, or yoga. Muscle endurance training combined with walking was identified as the optimal exercise program (88.9%) for enhancing sleep quality in older adults. The results of this study support the claim that exercise can improve sleep quality in this population. PROSPERO registration number: CRD42020178209.

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. OBJECTIVE: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). METHODS: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). RESULTS: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. CONCLUSION: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials.

BACKGROUND: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. METHODS: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. FINDINGS: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. INTERPRETATION: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. FUNDING: none.

Effectiveness of low level laser therapy versus cryotherapy in cancer patients with oral mucositis: Systematic review and network meta-analysis.

OBJECTIVE: The purpose of this network meta-analysis was to analyze the relative effects of low level laser therapy (LLLT) and/or cryotherapy in cancer patients with oral mucositis (OM). METHODS: This literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Physiotherapy Evidence Database (PEDro) up to 2020. Only randomized control trials which involved comparisons of groups receiving the interventions of combined cryotherapy and LLLT, LLLT, cryotherapy and usual care (the control group) in patients with cancer were eligible for inclusion. The effect sizes are presented as odds ratios for the occurrence of severe, moderate and none/mild OM. The mixed treatment comparison was conducted using generalized linear mixed models to analyze the direct and indirect comparisons of interventions. The critical appraisal was assessed using Cochrane Collaboration's tool. Heterogeneity between studies was assessed using I2 statistics, and publication bias was evaluated by constructing a funnel plot. RESULTS: Twenty-six randomized controlled trials with a total enrollment of 1830 cancer patients with OM were included. The outcome of none/mild OM is desirable, and odds ratios of more than 1 favor the intervention group. Moderate and severe OM are defined as adverse outcomes, and ORs less than 1 favor the intervention group. The treatment effects of the combined cryotherapy and LLLT were better than those of usual care for none/mild and severe OM (ORs = 106.23 [95% CI = 12.15 to 929.17] and 0.01 [95% CI = 0 to 0.57], respectively). Treatment effects with cryotherapy alone and LLLT alone were better than those with usual care for none/mild and severe OM (ORs = 3.13 [95%CI = 1.56 to 6.27]; ORs = 7.56 [95%CI = 3.84 to 14.88] and 0.25 [95%CI = 0.11 to 0.54]; ORs = 0.13 [95%CI = 0.07 to 0.24], respectively). Nevertheless, for patients with none/mild OM, treatment effects with combined use of cryotherapy and LLLT were better than those with only LLT or cryotherapy (ORs = 14.06 [95%CI = 1.79 to 110.30] and 33.95 [95%CI = 3.50 to 329.65], respectively). For patients with moderate OM, treatment effect did not reach statistical significance among comparisons. The limitations include the wide variability in treatment protocols and the non-uniform outcome measurements across the studies examined. CONCLUSION: Compared with no intervention, the treatment effects of combined cryotherapy and LLLT, laser alone, and cryotherapy alone are beneficial for the reduction of severe OM. There is no difference in treatment effects among cryotherapy and/or LLLT intervention in cancer patients with moderate OM. Results of this study provide an implicative basis for LLLT and cryotherapy as viable interventions that can significantly improve severe OM.

Effects of Protein Supplementation Combined with Exercise Training on Muscle Mass and Function in Older Adults with Lower-Extremity Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Trials.

Aging and osteoarthritis (OA) are associated with a high risk of muscle mass loss, which can lead to physical disability. This study investigated the effectiveness of protein supplementation combined with exercise training (PS + ET) in improving muscle mass and functional outcomes in older adults with lower-limb OA. A comprehensive search of online databases was performed to identify randomized controlled trials (RCTs) on the effectiveness of PS + ET in older adults with hip or knee OA. Meta-analysis and risk of bias assessment of the included RCTs were conducted. Six RCTs were included in this systemic review; they had a median (range/total) Physiotherapy Evidence Database (PEDro) score of 7 (6-9) out of 10, respectively. Five RCTs that enrolled patients who underwent total joint replacement were included in this meta-analysis. The PS + ET group exhibited significant improvements in muscle mass (standard mean difference [SMD] = 1.13, p < 0.00001), pain (SMD = 1.36, p < 0.00001), and muscle strength (SMD = 0.44, p = 0.04). Our findings suggest that PS + ET improves muscle mass, muscle strength, and functional outcomes and reduces pain in older adults with lower-limb OA, particularly in those who have undergone total joint replacement.

The association between melatonin and episodic migraine: A pilot network meta-analysis of randomized controlled trials to compare the prophylactic effects with exogenous melatonin supplementation and pharmacotherapy.

Although exogenous melatonin supplementation has been suggested to be effective for episodic migraine prophylaxis, there is no conclusive evidence comparing the efficacy of exogenous melatonin supplementation to the other FDA-approved pharmacotherapy for episodic migraine prophylaxis. The aim of the current network meta-analysis (NMA) was to compare the efficacy of exogenous melatonin supplementation in patients with episodic migraine. The randomized placebo-controlled trials or randomized controlled trials (RCTs) incorporating a placebo in the study designs were included in our analyses. All of the NMA procedures were conducted under the frequentist model. The primary outcome was changes in frequency of migraine days and response rate after migraine prophylaxis with melatonin supplementation or pharmacological interventions. We included 25 RCTs in total with 4499 patients (mean age = 36.0 years, mean female proportion = 78.9%). The NMA demonstrated that migraine prophylaxis with oral melatonin 3 mg/d (immediate-release) at bedtime was associated with the greatest improvement in migraine frequency [mean difference = -1.71 days, 95% confidence interval (CI): -3.27 to -0.14 days compared to placebo] and the second highest response rate (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo). Furthermore, oral melatonin 3 mg (immediate-release) at bedtime was the most preferred pharmacological intervention among all of the investigated interventions when improvements in migraine frequency, response rate, dropout rate, and rates of any adverse events were taken into account. This pilot NMA suggests the potential prophylactic role of exogenous melatonin supplementation in patients with episodic migraine.

Comparative Effectiveness of Different Nonsurgical Treatments for Patellar Tendinopathy: A Systematic Review and Network Meta-analysis.

PURPOSE: To investigate the functional improvement and pain reduction of different nonsurgical treatments for patellar tendinopathy (PT), a systematic review with network meta-analysis was performed. METHODS: Studies were comprehensively searched for without language restrictions in the CENTRAL, MEDLINE, EMBASE, Web of Science, Physiotherapy Evidence Database, and SPORTDiscus databases from inception to May 2018. Randomized controlled trials about nonsurgical treatments for PT were included. The outcome measurements were the Victorian Institute of Sports Assessment (VISA) scale and pain scores (such as the visual analog scale or Numerical Rating Scale). Study quality was evaluated using the Physiotherapy Evidence Database score. Direct comparisons were performed using pairwise meta-analysis, whereas network meta-analysis was performed using a frequentist method in a multivariate random-effects model. RESULTS: Eleven studies with 430 affected patellar tendons were included in the systematic review. The summary mean difference of improvement in the VISA scale versus the control group for corticosteroid injection was -23.00 (95% confidence interval [CI] -36.73 to -9.27), for leukocyte-rich platelet-rich plasma (LR-PRP) was 13.22 (95% CI 2.37-24.07), for focused extracorporeal shockwave therapy (ESWT) was -1.28 (95% CI -6.25 to 3.68), for radial ESWT was -6.68 (95% CI -20.20 to 6.84), for ultrasound was -0.70 (95% CI -11.23 to 9.83), for autologous blood injection was -0.60 (95% CI -9.30 to 8.10), for dry needling was 17.51 (95% CI -2.57 to 37.60), for topical glyceryl trinitrate was -0.90 (95% CI -13.07 to 11.27), and for skin-derived tendon-like cells was 10.40 (95% CI -1.59 to 22.39). LR-PRP (Surface Under the Cumulative Ranking curve [SUCRA] = 87.5%) or dry needling (SUCRA = 90.5%) was most likely to be ranked the best in terms of improvement on the VISA scale. Compared with the control group, the summary mean difference of the change in pain score for corticosteroid injection was 0.80 (95% CI -3.48 to 5.08), for LR-PRP was -1.87 (95% CI -3.28 to -0.46), for focused ESWT was 0.13 (95% CI -0.68 to 0.93), for radial ESWT was 0.03 (95% CI -1.92 to 1.98), for ultrasound was -0.20 (95% CI -1.49 to 1.09), for autologous blood injection was 0.60 (95% CI -0.73 to 1.93), for dry needling was -0.37 (95% CI -2.71 to 1.97), and for topical glyceryl trinitrate was -0.50 (95% CI -2.55 to 1.55). The treatment most likely to be ranked the best in terms of change in pain score was LR-PRP (SUCRA = 94.9%). CONCLUSIONS: The network meta-analysis demonstrated that LR-PRP has the greatest functional improvement and pain reduction for PT compared with other treatment options. However, the treatment effect estimates can be biased by the possible intransitivity and should not be overestimated. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I studies.

Comparative efficacy and safety of new surgical treatments for benign prostatic hyperplasia: systematic review and network meta-analysis.

OBJECTIVE: To assess the efficacy and safety of different endoscopic surgical treatments for benign prostatic hyperplasia. DESIGN: Systematic review and network meta-analysis of randomised controlled trials. DATA SOURCES: A comprehensive search of PubMed, Embase, and Cochrane databases from inception to 31 March 2019. STUDY SELECTION: Randomised controlled trials comparing vapourisation, resection, and enucleation of the prostate using monopolar, bipolar, or various laser systems (holmium, thulium, potassium titanyl phosphate, or diode) as surgical treatments for benign prostatic hyperplasia. The primary outcomes were the maximal flow rate (Qmax) and international prostate symptoms score (IPSS) at 12 months after surgical treatment. Secondary outcomes were Qmax and IPSS values at 6, 24, and 36 months after surgical treatment; perioperative parameters; and surgical complications. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted the study data and performed quality assessments using the Cochrane Risk of Bias Tool. The effect sizes were summarised using weighted mean differences for continuous outcomes and odds ratios for binary outcomes. Frequentist approach to the network meta-analysis was used to estimate comparative effects and safety. Ranking probabilities of each treatment were also calculated. RESULTS: 109 trials with a total of 13 676 participants were identified. Nine surgical treatments were evaluated. Enucleation achieved better Qmax and IPSS values than resection and vapourisation methods at six and 12 months after surgical treatment, and the difference maintained up to 24 and 36 months after surgical treatment. For Qmax at 12 months after surgical treatment, the best three methods compared with monopolar transurethral resection of the prostate (TURP) were bipolar enucleation (mean difference 2.42 mL/s (95% confidence interval 1.11 to 3.73)), diode laser enucleation (1.86 (-0.17 to 3.88)), and holmium laser enucleation (1.07 (0.07 to 2.08)). The worst performing method was diode laser vapourisation (-1.90 (-5.07 to 1.27)). The results of IPSS at 12 months after treatment were similar to Qmax at 12 months after treatment. The best three methods, versus monopolar TURP, were diode laser enucleation (mean difference -1.00 (-2.41 to 0.40)), bipolar enucleation (0.87 (-1.80 to 0.07)), and holmium laser enucleation (-0.84 (-1.51 to 0.58)). The worst performing method was diode laser vapourisation (1.30 (-1.16 to 3.76)). Eight new methods were better at controlling bleeding than monopolar TURP, resulting in a shorter catheterisation duration, reduced postoperative haemoglobin declination, fewer clot retention events, and lower blood transfusion rate. However, short term transient urinary incontinence might still be a concern for enucleation methods, compared with resection methods (odds ratio 1.92, 1.39 to 2.65). No substantial inconsistency between direct and indirect evidence was detected in primary or secondary outcomes. CONCLUSION: Eight new endoscopic surgical methods for benign prostatic hyperplasia appeared to be superior in safety compared with monopolar TURP. Among these new treatments, enucleation methods showed better Qmax and IPSS values than vapourisation and resection methods. STUDY REGISTRATION: CRD42018099583.

Comparative Effectiveness of Injection Therapies in Rotator Cuff Tendinopathy: A Systematic Review, Pairwise and Network Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the effectiveness of diverse injections in patients with rotator cuff tendinopathy using pairwise and network meta-analysis. DATA SOURCES: PubMed, EMBASE, Scopus, and Cochrane Library were searched for studies published up to September 31, 2017. STUDY SELECTION: We included all published or unpublished randomized controlled trials (RCTs) comparing diverse injections including corticosteroid, nonsteroidal anti-inflammatory drugs, hyaluronic acid, botulinum toxin, platelet-rich plasma (PRP), and prolotherapy in patients with rotator cuff tendinopathy. Among the 1495 records screened, 18 studies were included in the meta-analysis. DATA EXTRACTION: The quality of RCTs was assessed with Cochrane Risk of Bias Tool by 2 independent raters. The primary outcome was pain reduction, and the secondary outcome was functional improvement. DATA SYNTHESIS: Standardized mean difference (SMD) was used for pairwise and network meta-analysis. In pairwise meta-analysis, corticosteroid was more effective only in the short term in both pain reduction and functional improvement. Network meta-analysis indicated that prolotherapy significantly reduced pain compared with placebo in the long term (over 24wk; SMD: 2.63; 95% confidence interval [CI], 1.88-3.38); meanwhile PRP significantly improved shoulder function compared with placebo in the long term (over 24wk; SMD: 0.44; 95% CI, 0.05-0.84). CONCLUSIONS: For patients with rotator cuff tendinopathy, corticosteroid plays a role in the short term (3-6wk) but not in long-term (over 24wk) pain reduction and functional improvement. By contrast, PRP and prolotherapy may yield better outcomes in the long term (over 24wk). On account of heterogeneity, interpreting these results with caution is warranted.

Autologous Blood-Derived Products Compared With Corticosteroids for Treatment of Plantar Fasciopathy: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review article evaluated the efficacy of autologous blood-derived products, including whole blood and platelet-rich plasma, in reducing pain and improving function compared with corticosteroids for plantar fasciopathy patients. DESIGN: Literature comparing autologous blood-derived product and corticosteroids for the treatment of plantar fasciopathy was systematically reviewed. Twelve randomized controlled trials and four quasi-experimental studies were included. The visual analog scale pain score and American Orthopedic Foot and Ankle Society hindfoot score were evaluated at 1.5, 3, and 6 mos' follow-up. Subgroup analyses were performed concerning platelet-rich plasma preparation techniques, injection regiments, and study designs. RESULTS: Corticosteroids were found to reduce pain more effectively than whole blood at 1.5 and 3 mos, but the effect disappeared at 6 mos. Platelet-rich plasma reduced pain more effectively at 6 mos' postinjection than corticosteroids. However, there was no significant difference in the American Orthopedic Foot and Ankle Society score between platelet-rich plasma and corticosteroids injections at any time point. In the subgroup analyses, pain was significantly reduced at 6 mos by self-prepared platelet-rich plasma, one-step separation platelet-rich plasma, platelet-rich plasma of more than 3 ml, and platelet-rich plasma without local analgesics. CONCLUSIONS: The results of this meta-analysis suggest that platelet-rich plasma may provide a long-term effect in relieving pain in plantar fasciopathy patients. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Compare the efficacy of whole blood (WB), platelet-rich plasma (PRP), and corticosteroid (CS) in short-term pain reduction in patients with plantar fasciopathy (PF); (2) Compare the efficacy of WB, PRP, and CS in long-term pain reduction in patients with PF; (3) Identify the potential complication of corticosteroid injection for plantar fasciopathy; and (4) Identify the components of whole blood that might influence the growth factors in healing process. LEVEL: Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Music intervention for pain and anxiety management of the primiparous women during labour: A systematic review and meta-analysis.

AIMS: To determine the effect of music on the management of pain and anxiety in primiparous women during labour. BACKGROUND: Music is cost-effective intervention in clinical practice to reduce pain, stress, and anxiety. However, a systematic review with meta-analysis for investigating its effects during labour is still lacking. DESIGN: A systematic review with meta-analysis. DATA SOURCES: MEDLINE, EMBASE, and CINAHL databases. REVIEW METHODS: Randomized controlled trials or quasi-experimental trials concerning the effects of music among primiparous women who were expected to give normal spontaneous delivery were searched and screened up to 31 July 2017. The recruited trials for this review were compliant with the standards of the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 392 primiparous pregnant women (197 in the music intervention group and 195 in the routine care group) from five studies were included in this review. Music as an intervention seemed to lower the pain scores for primiparous women during labour, but the effect was not statistically significant. However, there was a significant benefit of music intervention compared with routine care for primiparous women during labour. In the sensitivity analysis, music intervention showed significant effect on the improvement of pain and anxiety for primiparous women during labour. CONCLUSION: Music intervention may be an effective intervention for the management of pain and anxiety for primiparous women during labour.