The Effectiveness and Safety of Platelet-Rich Plasma for Chronic Wounds: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the effectiveness and adverse events of autologous platelet-rich plasma (PRP) in individuals with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.Patients and MethodsWe searched multiple databases from database inception to June 11, 2020, for randomized controlled trials and observational studies that compared PRP to any other wound care without PRP in adults with lower-extremity diabetic ulcers, lower-extremity venous ulcers, and pressure ulcers.ResultsWe included 20 randomized controlled trials and five observational studies. Compared with management without PRP, PRP therapy significantly increased complete wound closure in lower-extremity diabetic ulcers (relative risk, 1.20; 95% CI, 1.09 to 1.32, moderate strength of evidence [SOE]), shortened time to complete wound closure, and reduced wound area and depth (low SOE). No significant changes were found in terms of wound infection, amputation, wound recurrence, or hospitalization. In patients with lower-extremity venous ulcers or pressure ulcers, the SOE was insufficient to estimate an effect on critical outcomes, such as complete wound closure or time to complete wound closure. There was no statistically significant difference in adverse events.ConclusionAutologous PRP may increase complete wound closure, shorten healing time, and reduce wound size in individuals with lower-extremity diabetic ulcers. The evidence is insufficient to estimate an effect on wound healing in individuals with lower-extremity venous ulcers or pressure ulcers.Trial RegistrationPROSPERO Identifier: CRD42020172817     

Comparative Effectiveness of Orthoses for Thumb Osteoarthritis: A Systematic Review and Network Meta-analysis

ObjectiveTo evaluate the best option among orthoses for carpometacarpal (CMC) osteoarthritis (OA) of the thumb, using a network meta-analysis.Data SourcesMedline, Embase, Cochrane, and ClinicalTrials.gov registry databases were used. PubMed, Embase, Cochrane Controlled Trials Register, Cochrane, and other databases were used without language restrictions.Study SelectionWe searched randomized controlled trials (RCTs) on adults with OA of the thumb by studying any orthosis from the beginning to March 10, 2020.Data ExtractionData were extracted and checked for accuracy and completeness by pairs of reviewers. Outcomes were pain and function. Comparative treatment effects were analyzed by random-effects model for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect evidence.Data SynthesisEleven RCTs involving 619 patients were included. We evaluated 5 groups, for 4 different orthoses: short thermoplastic CMC splint (rigid CMC) (n=5), long thermoplastic carpometacarpal-metacarpophalangeal splint (rigid CMC-MCP) (n=7), short neoprene CMC splint (soft CMC) (n=1), long neoprene CMC-MCP splint (soft CMC-MCP) (n=5), and one as a control group (n=5). Our results show that all splints were superior to placebo to reduce pain intensity and the top-ranked intervention was the rigid CMC-MCP (surface under the cumulative ranking curve analysis [SUCRA], score: 65.4). In function evaluation, we report a 71.6 SUCRA for rigid CMC.ConclusionsAlthough the current evidence is unclear on the use of the splint in OA of the thumb, it is not known which orthosis is more effective and whether the orthosis is more effective than other interventions. The network meta-analysis shows that a long thermoplastic splint it is the best choice for pain relief and the short thermoplastic CMC splint is the best treatment to increase function. These results may suggest initial treatment with a long rigid orthosis and then a short rigid orthosis.     

Effectiveness of Botulinum Toxin A in Treatment of Hemiplegic Shoulder Pain: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the effectiveness of botulinum toxin A (BTX-A) in the treatment of hemiplegic shoulder pain.Data SourcesPubMed, EMBASE, Elsevier, Springer, Cochrane Library, Physiotherapy Evidence Database, CNKI, and VIP were researched from the earliest records to September 1, 2020.Study SelectionRandomized controlled trials that compared shoulder BTX-A injections vs a control intervention in patients with a history of hemiplegic shoulder pain after stroke were selected. Among the 620 records screened, 9 trials with 301 eligible patients were included.Data ExtractionOutcome data were pooled according to follow-up intervals (1, 2, 4, and 12 wk). The primary evaluation indices were pain reduction (visual analog scale [VAS] score) and range of motion (ROM) improvement. The second evaluation indices were upper limb functional improvement, spasticity improvement, and incidence of adverse events. Cochrane risk-of-bias was used to assess the methodological quality of studies independently by 2 evaluators.Data SynthesisMeta-analysis revealed a statistically significant decrease in the VAS score in the BTX group vs the control group at 1, 4, and 12 weeks postinjection (wk 1: standardized mean difference [SMD], 0.91; 95% confidence interval [CI], 0.27 to 1.54; wk 4: SMD, 1.63; 95% CI, 0.76 to 2.51; wk 12: SMD, 1.96; 95% CI, 1.44 to 2.47). Furthermore, the meta-analysis demonstrated a statistically significant increase in abduction at 1, 4, and 12 weeks postinjection (wk 1: SMD, 3.71; 95% CI, 0 to 7.41; wk 4: SMD, 8.8; 95% CI, 2.22 to 15.37; wk 12: SMD, 19.59; 95% CI, 9.05 to 30.13) and external rotation at 1, 2, 4 weeks postinjection (wk 1: SMD, 5.67; 95% CI, 0.88 to 10.47; wk 2: SMD, 9.62; 95% CI, 5.57 to 13; wk 4: SMD, 6.89; 95% CI, 2.45 to 11.33) in the BTX group.ConclusionsBTX-A injection provided greater analgesic effects and increased shoulder abduction and external rotation ROM compared with steroid or placebo injection for the treatment of HSP.     

Effectiveness of Physical Therapy Interventions in Reducing Fear of Falling Among Individuals With Neurologic Diseases: A Systematic Review and Meta-analysis

ObjectiveTo summarize the effectiveness of physical therapy interventions to reduce fear of falling (FOF) among individuals living with neurologic diseases.Data SourcesPubMed, Physiotherapy Evidence Database, Scopus, Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health, and SportDiscuss were searched from inception until December 2019.Study SelectionClinical trials with either the primary or secondary aim to reduce FOF among adults with neurologic diseases were selected.Data ExtractionPotential articles were screened for eligibility, and data were extracted by 2 independent researchers. Risk of bias was assessed by the Cochrane Risk of Bias tool for randomized controlled trials and the National Institutes of Health Quality Assessment Tool for pre-post studies. A meta-analysis was performed among trials presenting with similar clinical characteristics. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to rate the overall quality of evidence.ResultsSixty-one trials with 3954 participants were included in the review and 53 trials with 3524 participants in the meta-analysis. The included studies presented, in general, with a low to high risk of bias. A combination of gait and balance training was significantly more effective compared with gait training alone in reducing FOF among individuals with Parkinson disease (PD) (mean difference [MD]=11.80; 95% CI, 8.22-15.38; P<.001). Home-based exercise and leisure exercise demonstrated significant improvement in reducing FOF over usual care in multiple sclerosis (MS) (MD=15.27; 95% CI, 6.15-24.38; P=.001). No statistically significant between-groups differences were reported among individuals with stroke and spinal cord injury. The overall quality of evidence presented in this review ranges from very low to moderate according to the assessment with the GRADE approach.ConclusionsGait with lower limb training combined with balance training is effective in reducing FOF in individuals with PD. Also, home-based or leisure exercise is effective among individuals with MS. However, because of several limitations of the included studies, further research is needed to examine the effectiveness of FOF intervention among individuals with neurologic diseases.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Edaravone for Acute Ischemic Stroke: A Systematic Review and Meta-analysis

PurposeThe management of acute stroke is challenging. The aim of this meta-analysis was to determine the efficacy and tolerability of edaravone, with or without thrombolytic therapy, in the treatment of patients with acute ischemic stroke.MethodsThe PubMed, EMBASE, and Cochrane databases were searched for randomized controlled trials (RCTs) and cohort studies. Mean differences (MD), risk ratios (RR), 95% confidence interval (CI), and heterogeneity were calculated.FindingsTotals of nine RCTs and four cohort studies were included, for a total of 2102 patients. In patients with acute ischemic stroke, edaravone monotherapy was associated with significantly improved Barthel Index of functioning in activities for daily living (MD, 23.95; 95% CI, 18.48 to 29.41; P < 0.001) and neurologic deficit, (as measured using the National Institutes of Health Stroke Scale score) (MD = –3.49; 95% CI, –5.76 to 1.22; P = 0.003), on short-term follow-up. However, edaravone was not associated with an improved rate of death or disability (RR = 0.75; 95% CI, 0.45 to 1.23; P = 0.25) on long-term follow-up.When plus to thrombolytic therapy, edaravone was associated with significant improvements in recanalization rate (RR = 1.71; 95% CI, 1.05 to 2.77; P = 0.03) and neurologic deficit (MD = 3.97; 95% CI, 5.14 to 2.79; P < 0.001), without an increase in the prevalence of bleeding events (RR = 1.11; 95% CI, 0.76 to 1.62; P = 0.59). However, edaravone did not have a significant effect on death or disability (RR = 0.85; 95% CI, 0.69 to 1.04; P = 0.12).ImplicationsBased on the findings from the present meta-analysis, edaravone was an effective and well-tolerated neuroprotective agent in these patients with ischemic stroke. With the use of edaravone, activities of daily living and neurologic deficits, along with recanalization rates, were improved on short-term follow-up, but the long-term effects still need confirmation in larger-scale clinical trials.     

Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis

ObjectiveTo assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials.Patients and MethodsWe performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk.ResultsWe included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I²=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up.ConclusionWe found insufficient evidence to support an increased risk of JAK inhibitor–associated VTE based on currently available data.     

Effectiveness of Botulinum Toxin Treatment for Upper Limb Spasticity Poststroke Over Different ICF Domains: A Systematic Review and Meta-Analysis

ObjectiveTo provide a comprehensive overview of reported effects and scientific robustness of botulinum toxin (BoNT) treatment regarding the main clinical goals related to poststroke upper limb spasticity, using the International Classification of Functioning, Disability and Health.Data SourcesEmbase, PubMed, Wiley/Cochrane Library, and Ebsco/CINAHL were searched from inception up to May 16, 2018.Study SelectionWe included randomized controlled trials comparing upper limb BoNT injections with a control intervention in patients with a history of stroke. A total of 1212 unique records were screened by 2 independent reviewers. Forty trials were identified, including 2718 patients with history of stroke.Data ExtractionOutcome data were pooled according to assessment timing (ie, 4-8wk and 12wk after injection), and categorized into 6 main clinical goals (ie, spasticity-related pain, involuntary movements, passive joint motion, care ability, arm and hand use, and standing and walking performance). Sensitivity analyses were performed for the influence of study and intervention characteristics, involvement of pharmaceutical industry, and publication bias.Data SynthesisRobust evidence is shown for the effectiveness of BoNT in reducing resistance to passive movement, as measured with the (Modified) Ashworth Score, and improving self-care ability for the affected hand and arm after intervention (P<.005) and at follow-up (P<.005). In addition, robust evidence is shown for the absence of effect on arm-hand capacity at follow-up. BoNT was found to significantly reduce involuntary movements, spasticity-related pain, and caregiver burden, and improve passive range of motion, while no evidence was found for arm and hand use after intervention.ConclusionsIn view of the robustness of current evidence, no further trials are needed to investigate BoNT for its favorable effects on resistance to passive movement of the spastic wrist and fingers, and on self-care. No trials are needed to further confirm the lack of effects of BoNT on arm-hand capacity, whereas additional trials are needed to establish the suggested favorable effects of BoNT on other body functions, which may result in clinically meaningful outcomes at activity and participation levels.     

Whole Body Vibration Exercise for Chronic Musculoskeletal Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveThis study systematically reviews previous work on the effects of whole body vibration exercise (WBVE) on pain associated with chronic musculoskeletal disorders.Data SourcesSeven electronic databases (PubMed, Embase, CINAHL, Web of Science, Cochrane, Physiotherapy Evidence Database [PEDro], and the China National Knowledge Infrastructure) were searched for articles published between January 1980 and September 2018.Study SelectionRandomized controlled trials involving adults with chronic low back pain (CLBP), osteoarthritis (OA), or fibromyalgia were included. Participants in the WBVE intervention group were compared with those in the nontreatment and non-WBVE control groups.Data ExtractionData were independently extracted using a standardized form. Methodological quality was assessed using PEDro.Data SynthesisSuitable data from 16 studies were pooled for meta-analysis. A random effects model was used to calculate between-groups mean differences at 95% confidence interval (CI). The data were analyzed depending on the duration of the follow-up, common disorders, and different control interventions.ResultsAlleviation of pain was observed at medium term (standardized mean difference [SMD], -0.67; 95% CI, -1.14 to -0.21; I², 80%) and long term (SMD, -0.31; 95% CI, -0.59 to -0.02; I², 0%). Pain was alleviated in osteoarthritis (OA) (SMD, -0.37; 95% CI, -0.64 to -0.10; P<.05; I², 22%) and CLBP (SMD, -0.44; 95% CI, -0.75 to -0.13; P<.05; I², 12%). Long-term WBVE could relieve chronic musculoskeletal pain conditions of OA (SMD, -0.46; 95% CI, -0.80 to -0.13; P<.05; I², 0%). WBVE improved chronic musculoskeletal pain compared with the treatment “X” control (SMD, -0.37; 95% CI, -0.61 to -0.12; P<.05; I², 26%), traditional treatment control (SMD, -1.02; 95% CI, -2.44 to 0.4; P>.05; I², 94%) and no treatment control (SMD, -1; 95% CI, -1.76 to -0.24; P<.05; I², 75%).ConclusionsEvidence suggests positive effects of WBVE on chronic musculoskeletal pain, and long durations of WBVE could be especially beneficial. However, WBVE does not significantly relieve chronic musculoskeletal pain compared with the traditional treatment. Further work is required to identify which parameters of WBVE are ideal for patients with chronic musculoskeletal pain.     

The Effect of Convalescent Plasma Therapy on Mortality Among Patients With COVID-19: Systematic Review and Meta-analysis

To determine the effect of COVID-19 convalescent plasma on mortality, we aggregated patient outcome data from 10 randomized clinical trials, 20 matched control studies, 2 dose-response studies, and 96 case reports or case series. Studies published between January 1, 2020, and January 16, 2021, were identified through a systematic search of online PubMed and MEDLINE databases. Random effects analyses of randomized clinical trials and matched control data demonstrated that patients with COVID-19 transfused with convalescent plasma exhibited a lower mortality rate compared with patients receiving standard treatments. Additional analyses showed that early transfusion (within 3 days of hospital admission) of higher titer plasma is associated with lower patient mortality. These data provide evidence favoring the efficacy of human convalescent plasma as a therapeutic agent in hospitalized patients with COVID-19.     

Newer P2Y12 Inhibitors vs Clopidogrel in Acute Myocardial Infarction With Cardiac Arrest or Cardiogenic Shock: A Systematic Review and Meta-analysis

ObjectiveTo evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y₁₂ inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS).Patients and MethodsMEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y₁₂ inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y₁₂ inhibitors and clopidogrel in patients with AMI-CA/CS.ResultsEight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y₁₂ cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies).ConclusionIn patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y₁₂ inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.     

Ballistic Resistance Training: Feasibility,Safety, and Effectiveness for Improving Mobility in Adults With Neurologic Conditions: A Systematic Review

ObjectivesTo determine whether ballistic resistance training is feasible, safe, and effective in improving muscle strength, power generation, and mobility in adults with neurologic conditions.Data SourcesNine electronic databases were searched from inception to March 2019 in addition to the reference lists of included articles.Study SelectionArticles were independently screened by 2 authors and were included if they were full-text; English-language articles published in a peer-reviewed journal; investigated ballistic resistance training for adults with a neurologic condition; and reported on feasibility, safety, strength, power, or mobility.Data ExtractionTwo authors independently extracted data. Study quality was assessed using the McMaster critical review form and the Physiotherapy Evidence Database scale.Data SynthesisThe search identified 1540 articles, with 13 articles describing 9 studies meeting the criteria for inclusion. Five studies were randomized controlled trials and 4 were cohort studies. Ballistic resistance training was feasible and safe with only 1 intervention-related adverse event reported. Findings indicated improvements in strength for hip abduction, leg press, knee flexion, and ankle dorsiflexion, but not for hip flexion, hip extension, knee extension, or ankle plantarflexion. Muscle power generation improved for hip flexion, hip abduction, leg press, knee extension, and knee flexion, but not for ankle plantarflexion. Treatment effect was positive for self-selected walking speed, with a standardized mean difference (SMD) of 0.69 (95% confidence interval [CI], 0.01-1.38) from 3 studies. However, fastest comfortable walking speed results were inconclusive with a SMD from 4 studies of 0.45 (95% CI, –0.01 to 0.91).ConclusionsBallistic training is safe and feasible for people with a neurologic condition. The effects on muscle strength, power generation, and mobility were found to be positive but not conclusive.     

Continuous Passive Motion After Total Knee Arthroplasty: A Systematic Review and Meta-analysis of Associated Effects on Clinical Outcomes

ObjectiveTo evaluate the efficacy of continuous passive motion (CPM) after total knee arthroplasty (TKA) and whether the use of CPM is related to improved clinical and functional outcomes.Data SourcesA systematic MEDLINE search via Web of Science, Cochrane Library, and PubMed databases was conducted.Study SelectionEnglish-language articles published between January 2000 and May 2018 reporting the related clinical outcomes of CPM after TKA were included. A total of 3334 titles and abstracts were preliminarily reviewed, of which 16 studies were included according to the eligibility criteria.Data ExtractionTwo different reviewers were selected to perform the study extraction, independent of each other. If there were any disagreements regarding the final list of studies, the third reviewer reviewed the list as an arbitrator for completeness.Data SynthesisA total of 16 trials with 1224 patients were included. The pooled results revealed that use of CPM did not show a statistically significant improvement of postoperative knee range of motion (ROM) except for middle-term passive knee extension and long-term active knee flexion ROM. Also, CPM therapy did not show a significant positive effect on the functional outcomes. No significant reduction in length of stay (LOS) and incidence of adverse events (AEs) was identified.ConclusionAmong patients undergoing TKA, neither the ROM nor the functional outcomes could be improved by CPM therapy. Moreover, the risk of AEs and LOS could not be reduced by application of CPM. The current available evidence suggested that this intervention was insufficient to be used routinely in clinical practice.     

Systematic review and meta-analysis for impacts of oral antibiotic treatment on pregnancy outcomes in chronic endometritis patients

BackgroundChronic endometritis is a persistent inflammatory condition of the endometrium that negatively affects pregnancy outcomes. The Centers for Disease Control and Prevention guidelines recommend oral antibiotic treatment for chronic endometritis. However, a recent randomized controlled trial concluded that it was unclear whether antibiotic treatment improved pregnancy outcomes. Hence, we performed a systematic review and meta-analysis to validate the impact of oral antibiotic treatments on pregnancy outcomes among patients with chronic endometritis.MethodsWe systematically searched the PubMed, Scopus, Ichushi, CINAHL, and EMBASE databases until May 2021. We compared the pregnancy outcomes in patients with chronic endometritis with and without antibiotic treatment. We then focused on the implantation rate, intrauterine pregnancy rate, and live birth rate to evaluate pregnancy outcomes.ResultsSeven studies were included in the meta-analysis. Three hundred seventy-two patients were treated with antibiotics, while 1024 patients were not treated with antibiotics. Various antibiotic regimens were administered during the study period [14–21 days]. Antibiotic treatments for chronic endometritis did not increase the implantation rate (odds ratios [OR] 1.02, 95% confidence interval [CI], 0.78–1.33), intrauterine pregnancy rate (OR 1.08, 95% CI 0.72–1.63), or live birth rate (OR 1.13, 95% CI 0.65–1.97).ConclusionsOur meta-analysis proved that oral antibiotic treatment did not improve pregnancy outcomes in patients with chronic endometritis. Accordingly, further studies are needed to elucidate the treatment to improve pregnancy outcomes.     

Pediatric tuina for the treatment of anorexia in children under 14 years: a systematic review and meta-analysis of randomized controlled trials

BackgroundPediatric tuina is used to prevent and treat disease by employing various manipulative techniques on specific parts of the body, appropriate to the child’s specific physiological and pathological characteristics.ObjectiveTo evaluate the effects and safety of pediatric tuina as a non-pharmaceutical therapy for anorexia in children under 14 years.MethodsRandomized controlled trials (RCTs) comparing pediatric tuina with medicine for anorexia were included in this review. Six electronic databases were searched from inception to June 2019. Two authors independently extracted data and assessed the risk of bias. Significant effective rate (defined as appetite improved and food intake returning to 3/4 or more of normal intake) was used as primary outcome. Secondary outcomes included food intake, compliance and adverse events. Trial sequential analysis (TSA) was used to calculate the required information size in a meta-analysis and to detect the robustness of the results. Certainty of the evidence was assessed using the online GRADEpro tool.ResultsOf the included 28 RCTs involving 2650 children, the majority had a high or unclear risk of bias in terms of allocation concealment, blinding, and selective reporting. All trials compared tuina with western medicine or Chinese herbs. For significant effective rate, meta-analysis showed that tuina was superior to western medicine (risk ratio (RR) 1.68, 95 % confidence interval (CI) [1.35, 2.08]) and Chinese herbs (RR 1.36, 95 % CI [1.19, 1.55]). For food intake, 9 trials evaluated it in the form of score (1 points, 2 points, 4 points and 6 points) calculated according to the reduction degree of food intake. Six points represented the most serious. Meta-analysis showed tuina was superior to western medicine (mean difference (MD) -0.88, 95 % CI [-1.27, -0.50]) and Chinese herbs (MD -0.69, 95 % CI [-1.00, -0.38]) on lightening the reduction degree of food intake. Two trials reported compliance and six trials reported no adverse events occurred in pediatric tuina group. TSA for significant effective rate demonstrated that the pooled data had insufficient power regarding both numbers of trials and participants.ConclusionsLow certainty of evidence suggested pediatric tuina was beneficial and safe for the treatment of anorexia in children under 14 years. Furthermore well-designed RCTs with adequate sample sizes are needed.     

The impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis: A competing risk regression analysis

While advanced age is a main prognostic factor in patients with tuberculosis, the factors that specifically affect tuberculosis-related death are unclear because elderly people are at a risk for other age-related lethal diseases. We aimed to assess the impact of performance status on tuberculosis-related death among elderly patients with lung tuberculosis. Elderly patients (≥65 years of age) admitted to our hospital for bacteriologically-diagnosed lung tuberculosis were included, and analyzed the influence of performance status on tuberculosis-related in-hospital death, with non-tuberculosis-related death as a competing risk. Forty and 19 of the 275 patients died from tuberculosis-related causes and non-tuberculosis-related causes, respectively. The tuberculosis-related death group had a greater number of patients with a poor performance status (defined as category 3 and 4 [HR 21.022; 95%CI 2.881–153.414; p = 0.003]), a lower serum albumin level (HR 0.179; 95%CI 0.090–0.359; p < 0.001) and a higher C-reactive protein level (HR1.076; 95%CI 1.026–1.127; p = 0.002). A multivariate competing risk regression analysis showed that a poor performance status (HR 7.311; 95%CI 1.005–53.181; p = 0.049) and low albumin level (HR 0.228; 95%CI 0.099–0.524); p = 0.001) significantly predicted tuberculosis-related death. Performance status can be a useful scale for predicting tuberculosis-related death among elderly patients with pulmonary tuberculosis.     

Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living,Interactive Systematic Review and Network Meta-analysis

ObjectiveTo maintain living, interactive evidence (LIvE) on the benefits and harms of different treatment options in adults with cancer-associated thrombosis (CAT).MethodsWe have used a novel LIvE synthesis framework to maintain this living, interactive systematic review since September 19, 2018. Randomized controlled trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) compared with low-molecular-weight heparin for CAT are included in this analysis. Details of LIvE synthesis framework are available at the website https://cat.network-meta-analysis.com.ResultsThe results are constantly updated as new information becomes available (https://cat.network-meta-analysis.com/CAT.html). The living, interactive systematic review currently includes 4 randomized controlled trials (N=2894). Direct comparisons show that DOACs significantly decrease recurrent venous thromboembolism (VTE) events compared with dalteparin (odds ratio [OR], 0.59; 95% CI, 0.41 to 0.86; I², 25%) without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 to 2.18; I², 28%). Mixed treatment comparisons show that apixaban (OR, 0.41; 95% credible interval [CrI], 0.16 to 0.95) and rivaroxaban (OR, 0.58; 95% CrI, 0.37 to 0.90) significantly decrease VTE recurrent events compared with dalteparin. Edoxaban significantly increases major bleeding compared with dalteparin (OR, 1.73; 95% CrI, 1.04 to 3.16), and rivaroxaban significantly increases clinically relevant nonmajor bleeding compared with dalteparin and other DOACs. There are no significant differences between DOACs in terms of VTE recurrences and major bleeding.ConclusionDOACs should be considered a standard of care for the treatment of CAT except in patients with a high risk of bleeding. Current evidence favors the use of apixaban for the treatment of CAT among other DOACs.RegistrationOpen Science Framework (https://osf.io/dth86).     

Disseminated tuberculosis with paradoxical reactions caused by a Mycobacterium tuberculosis strain belonging to the Indo-Oceanic lineage: An imported case in Japan

Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages.     

Efficacy and Safety of High-Frequency Repetitive Transcranial Magnetic Stimulation for Poststroke Depression: A Systematic Review and Meta-analysis

ObjectiveTo summarize and systematically review the efficacy and safety of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) for depression in patients with stroke.Data SourcesSix databases (Wanfang, the China National Knowledge Infrastructure, PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until November 15, 2018.Study SelectionSeventeen randomized controlled trials were included for meta-analysis.Data ExtractionTwo independent reviewers selected potentially relevant studies based on the inclusion criteria, extracted data, and evaluated the methodological quality of the eligible trials using the Physiotherapy Evidence Database.Data SynthesisWe calculated the combined effect size (standardized mean difference [SMD] and odds ratio [OR]) for the corresponding effects models. Physiotherapy Evidence Database scores ranged from 7 to 8 points (mean=7.35). The study results indicated that HF-rTMS had significantly positive effects on depression in patients with stroke. The effect sizes of the SMD ranged from small to large (SMD, -1.01; 95% confidence interval [CI], -1.36 to -0.66; P<.001; I², 85%; n=1053), and the effect sizes of the OR were large (response rates, 58.43% vs 33.59%; OR, 3.31; 95% CI, 2.25-4.88; P<.001; I², 0%; n=529; remission rates, 26.59% vs 12.60%; OR, 2.72; 95% CI, 1.69-4.38; P<.001; I², 0%; n=529). In terms of treatment side effects, the HF-rTMS group was more prone to headache than the control group (OR, 3.53; 95% CI, 1.85-8.55; P<.001; I², 0%; n=496).ConclusionsHF-rTMS is an effective intervention for poststroke depression, although treatment safety should be further verified via large sample multicenter trials.