Potential Risk Of Bias Research Articles

Quality of clinical trials for the prevention of keratinocyte cancer.

Keratinocyte cancer (KC) is the most common form of cancer in humans. To our knowledge, no previous publications assessing the methodological quality of clinical trials for the prevention of KC have been recently published. We aim to assess the methodological quality of clinical trials focused on the prevention of KC in high-risk groups not receiving immunosuppressive therapy (NRIT) and propose solutions to improve the design of future trials. We searched clinical trials in which the main outcome was the prevention of KC in high-risk NRIT groups using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. Consolidated Standards of Reporting Trials (CONSORT)criteria and the Cochrane Collaboration risk of bias tool were used to assess methodological quality. We analyzed 23 clinical trials. We found a high risk of attrition and reporting bias in 86.9% and 60.9% of the trials, respectively. Regarding the CONSORT criteria, in at least 40% of the trials, the authors omitted the following information: a description of the trial design, the number of losses and exclusions after randomization, the results of subgroup and adjusted analysis, the estimated effect size and the precision of primary and secondary outcomes. Methodological quality was improved in the recently published clinical trials compared to those published before the CONSORT criteria development. All clinical trials should report in detail the information used to assess potential risks of bias.

Barrier Protection Measures for the Management of Allergic Rhinitis: A Systematic Review and Meta-analysis

Pharmacotherapy for allergic rhinitis (AR) still remains unsatisfying regarding its effect and safety. Barrier protection measures may be a good choice for the patients with AR. To assess the efficacy and safety of barrier protection measures in the treatment of AR. We selected relevant randomized controlled trials published between January 1, 1990, and February 20, 2019, by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. The primary outcome for this analysis was rhinitis symptom scores, overall quality of life, nasal peak inspiratory flow (NPIF), and adverse events. Differences were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs) for continuous outcomes. Statistical heterogeneity across trials was assessed with the statistic (P < .1) and the I2 statistic. Fifteen RCTs (with data for 1154 participants) satisfied our inclusion criteria. The types of barrier protection measures comprised cellulose, pollen blocker cream, microemulsion, and nasal filter. To reduce the potential risk of bias and heterogeneity, we carried out subgroup analysis according to different types of barrier protection measures (cellulose: WMD = -2.18, 95% CI, -3.01 to -1.35, P < .00001; pollen blocker cream: WMD = -4.55, 95% CI, -6.10 to -3.00, P < .00001; microemulsion: WMD = -0.22, 95% CI, -0.42 to -0.03, P = .03). Findings from our meta-analysis show that, compared with placebo, barrier protection measures can yield improved symptomatic control for AR, with no increase in adverse events. Furthermore, barrier protection measures can improve the quality of life and NPIF. Although further studies are still needed, our findings clearly lend support to barrier protection measures as a safe and efficacious option for the treatment of AR patients.

Effects of non-pharmacological therapies for people with mild cognitive impairment. A Bayesian network meta-analysis.

To compare the effects of non-pharmacological therapies (NPTs) on improving the cognition of people with mild cognitive impairment (MCI) by performing a Bayesian network meta-analysis (NMA). We searched eight databases for potentially eligible studies. Physical exercise (PE), cognitive stimulation (CS), cognitive training (CT), cognitive rehabilitation (CR), musical therapy (MT) and multi-domain interventions (MI). Pairwise meta-analyses were performed by estimating the weighted mean differences with 95% confidence interval (CI) for mini-mental state examination. The NMA was undertaken to compare different interventions. CS, PE, MI, MT and CT may all be effective in improving the cognition of patients with MCI. CR was unable to show a significant efficacy. Our NMA ranking results suggest the effectiveness of the six NPTs to be ranked from best to worst as follows: CS, PE, MI, MT, CT and CR. NPT has great potential to improve the cognition of the elderly with MCI. CS has the highest probability of being the optimal NPT. However, the result should be interpreted with cautions given the limited number and small samples of included randomized controlled trials (RCTs) in this field, large diversity existing in different study designs and potential risk of bias. Future RCTs with high quality and large sample sizes are required to confirm our results. NPT, as a whole definition, has great potential to improve the cognition of the elderly with MCI. Our NMA ranking results suggest the effectiveness of the six NPTs to be ranked from best to worst as follows: CS, PE, MI, MT, CT and CR.

The Association Between Elevated Foot Skin Temperature and the Incidence of Diabetic Foot Ulcers: A Meta-Analysis

Prior to the appearance of any foot ulcer, there is an increase in the local temperature due to the presence of an underlying inflammatory process. The use of thermometry to identify inflammation could make patients increase preventive measures until the inflammation disappears. We carried out a meta-analysis to determine the effectiveness of the daily measurement of the foot temperature in 6 points to prevent the occurrence of foot ulcers in patients with diabetes. Patients with temperature differences >4°F (2.2°C) between left and right corresponding sites should reduce activity and increase preventive measures until temperature is normalized. We searched the literature in MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, and clinicaltrials.gov. We have only included randomized clinical trials where individuals were assigned to receive enhanced care (temperature measurement and standard care) versus standard care (education, self-care practices, and periodic clinical visits). We found 4 trials comprising 462 patients from the United States and Norway that met our inclusion criteria. The duration of follow-up varied from 4.5 to 15 months. Overall, 18 (7.9%) subjects in the enhanced foot care group and 53 (22.6%) in the standard foot care group developed foot ulcers (pooled risk ratio = 0.37; 95% confidence interval = 0.21-0.66; P = .0008; percentage of heterogeneity [I2], 25%; P = .26). The number needed to treat was 7 (95% confidence interval = 5-11). The results were robust after analysis by subgroups according to the potential risk of bias in the studies and the duration of follow-up.

Effect of nephrology follow-up on long-term outcomes in patients with acute kidney injury: A systematic review and meta-analysis.

Acute kidney injury (AKI) is associated with poor short-term and long-term clinical outcomes. The role of nephrology follow-up in post-AKI management remains uncertain. A systematic review and meta-analysis were performed examining all randomized controlled trials and observational studies assessing the effect of nephrology follow-up on patients' clinical outcomes. The primary outcome was all-cause mortality. The secondary outcomes were renal outcomes, which were defined as a composite of requirement of permanent dialysis and recurrent AKI. Pooled analysis was performed using a random-effect model. We identified six studies (8972 patients, mean follow-up of 49 months). Five were retrospective cohort studies and one was a prospective cohort study. Risk of bias was a concern with all studied. Only four studies reported primary and/or secondary outcomes and were included. Compared with patients without nephrology follow-up, patients with nephrology follow-up had significantly reduced mortality by 22% (three studies, 3240 patients, relative risk [RR] = 0.78, 95% confidence interval [CI] = 0.70-0.88, I2 = 0.0%). Nephrology follow-up did not improve composite renal outcomes with high heterogeneity due to significant differences in reported renal outcomes and follow-up period (two studies, 2537 patients, RR = 1.72, 95% CI = 0.49-6.05, I2 = 90.1%). Current evidence from observational studies is biased. It suggests long-term survival benefits with post-discharge nephrology follow-up in AKI patients. However, due to its low quality, such evidence is only hypothesis-generating. Nonetheless, it provides a rationale for future randomized controlled trials of nephrology follow-up in AKI patients. SUMMARY AT A GLANCE The present meta-analysis assessed the effect of nephrology follow-up on patients' clinical outcomes, and suggested long-term survival benefits in acute kidney injury (AKI) survivors. Although the study inherently comprises potential risks of bias due to paucity of available data, the results provide a rationale for future randomized controlled trials.

The effects of diagnosis-related groups payment on hospital healthcare in China: a systematic review

BackgroundThere has been a growing interest in using diagnosis-related groups (DRGs) payment to reimburse inpatient care worldwide. But its effects on healthcare and health outcomes are controversial, and the evidence from low- and middle- income countries (LMICs) is especially scarce. The objective of this study is to evaluate the effects of DRGs payment on healthcare and health outcomes in China.MethodA systematic review was conducted. We searched literature databases of PubMed, Cochrane Library, EMBASE, Web of Science, Chinese National Knowledge Infrastructure and SinoMed for empirical studies examining the effects of DRGs payment on healthcare in mainland China. We performed a narrative synthesis of outcomes regarding expenditure, efficiency, quality and equity of healthcare, and assessed the quality of evidence.ResultsTwenty-three publications representing thirteen DRGs payment studies were included, including six controlled before after studies, two interrupted time series studies and five uncontrolled before-after studies. All studies compared DRGs payment to fee-for-service, with or without an overall budget, in settings of tertiary (7), secondary (7) and primary care (1). The involved participants varied from specific groups to all inpatients. DRGs payment mildly reduced the length of stay. Impairment of equity of healthcare was consistently reported, especially for patients exempted from DRGs payment, including: patient selection, cost-shifting and inferior quality of healthcare. However, findings on total expenditure, out of pocket payment (OOP) and quality of healthcare were inconsistent. The quality of the evidence was generally low or very low due to the study design and potential risk of bias of included studies.ConclusionDRGs payment may mildly improve the efficiency but impair the equity and quality of healthcare, especially for patients exempted from this payment scheme, and may cause up-coding of medical records. However, DRGs payment may or may not contain the total expenditure or OOP, depending on the components design of the payment. Policymakers should very carefully consider each component of DRGs payment design against policy goals. Well-designed randomised trials or comparative studies are warranted to consolidate the evidence of the effects of DRGs payment on healthcare and health outcomes in LMICs to inform policymaking.

Drivers of the opioid crisis: An appraisal of financial conflicts of interest in clinical practice guideline panels at the peak of opioid prescribing.

Starting in the late 1990s, the pharmaceutical industry sought to increase prescribing of opioids for chronic non-cancer pain. Influencing the content of clinical practice guidelines may have been one strategy industry employed. In this study we assessed potential risk of bias from financial conflicts of interest with the pharmaceutical industry in guidelines for opioid prescribing for chronic non-cancer pain published between 2007 and 2013, the peak of opioid prescribing. We used the Guideline Panel Review (GPR) to appraise the guidelines included in the 2014 systematic review and critical appraisal by Nuckols et al. These were English language opioid prescribing guidelines for adults with chronic non-cancer pain published between July 2007 and July 2013, the peak of opioid prescribing. The GPR assigns red flags to items known to introduce potential bias from financial conflicts of interest. We operationalized the GPR by creating specific definitions for each red flag. Two reviewers independently evaluated each guideline. Disagreements were resolved with discussion. We also compared our score to the critical appraisal scores for overall quality from the study by Nuckols et al. We appraised 13 guidelines, which received 43 red flags in total. Guidelines had 3.3 red flags on average (out of a possible seven) with range from one to six. Four guidelines had missing information, so red flags may be higher than reported. The guidelines with the highest and second highest scores for overall quality in the 2014 critical appraisal by Nuckols et al. had five and three red flags, respectively. Our findings reveal that the guidelines for opioid prescribing chronic non-cancer pain from 2007 to 2013 were at risk of bias because of pervasive conflicts of interest with the pharmaceutical industry and a paucity of mechanisms to address bias. Even highly-rated guidelines examined in a 2014 systematic review and critical appraisal had many red flags.

Surgical management of male genital lymphedema: A systematic review.

Genital lymphedema (GL) is an uncommon and disabling disease that manifests as enlargement of the genital region resulting from the disturbance of lymphatic drainage. Although conservative treatment such as decompression is typically the first-line approach, surgical intervention has been shown to be effective in certain cases. This study aimed to systematically review studies evaluating available surgical alternatives for the treatment of male GL. A systematic search strategy using keyword and subject headings was applied to PubMed, Scopus, EMBASE, and Cochrane Library in May 2019. Studies investigating various surgical techniques to treat penile and scrotal lymphedema were included. The potential risk of bias of included trials was evaluated using the methodological index for non-randomized studies (MINORS). In total, 13 studies met the inclusion criteria, nine of which were determined to be high-quality. The average MINORS score was 12.45 for studies involving excision and 14 for studies involving lymphovenous anastomosis (LVA). The most common reason for a low score was a failure to describe the inclusion criteria. Recurrence of lymphedema during follow-up was reported in four studies involving excision and in no studies involving LVA. In general, the quality of the included literature was considered to be fair. Although surgical intervention might not always prevent the recurrence of lymphedema, all of the studies reported improved quality of life after the procedure. This study could be used as the basis for evidence-based guidelines to be applied in clinical practice for managing male GL.

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients.

The domains, methods, and tools used in human exposome studies

PDS 71: Exposome, Johan Friso Foyer, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: The “human exposome” emerges as a new concept in health sciences, comprising the totality of environmental exposures from conception and throughout lifespan. Dynamic by nature, the exposome has been divided into three domains: general external, specific external and internal. Numerous assessment methods, tools and study designs have been used to date, to explore specific exposome domain(s), in various populations at critical life stages. However, a commonly understood exposome language, methods and tools need to be set that will pave the way for the future of exposome research and its utility. Objective: A systematic review was conducted to answer the question: “Which domains of the human exposome have been included in the literature and what tools of exposure/disease metrics and data discovery/validation techniques have been used?” Methods: A comprehensive search of articles published up to February 2019 was conducted. Original, peer-reviewed articles focused on human studies that contained the word exposom* in text were included. A protocol was developed based on Cochrane guidelines and registered in PROSPERO, evaluating the potential risk of bias, rating the quality and strength of the body of evidence for each included study, using the Effective Public Health Practice Project Tool. Results: A total of 1033 references were screened and 84 human exposome studies were identified that met our inclusion criteria. Initial screening showcased the non-consistent use of the human exposome definition and its tools. Various study designs were presented, ranging from case-studies to prospective cohorts, from secondary data analysis to primary data collection using targeted and/or untargeted biomarker measurements with -omics platforms, occasionally relying upon environment-wide association study (EWAS) tools. The final results of rating the quality of the evidence, including the most/least frequently encountered exposome study characteristics will be laid out.

P1022Upstream therapy using preoperative renin-angiotensin system inhibitors in prevention of postoperative atrial fibrillation and adverse events: a collaborative pooled-analysis over 27,000 patients

Abstract Background Renin-angiotensin-system inhibitors (RASIs) have been suggested as an upstream therapy for selected AF patients; however, the evidence in surgical setting is limited. Objective We aimed to evaluate the role of preoperative RASIs in prevention of postoperative atrial fibrillation (POAF) and adverse events for patients undergoing cardiac surgery. Methods In this collaborative pooled-analysis, both randomized and nonrandomized controlled trials comparing preoperative RASIs with no preoperative RASIs treatment on the incidence of POAF were identified. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall-effect, and meta-regression to explore the potential risk of bias. The primary outcome was POAF, and the secondary outcomes includes rate of stroke, mortality and duration of hospitalization. Results Eleven trials involving 27885 patients (male 74%, median age 65yrs) were included. As compared to the control group, preoperative RASIs did not significantly reduce the risk of POAF (OR: 1.04, 95% CI: 0.91–1.19), stroke (OR: 0.86, 95% CI: 0.62–1.19), death (OR: 1.07, 95% CI: 0.85–1.35), composite adverse cardiac events (OR: 1.04, 95% CI: 0.91–1.18), and hospital stay (WMD: −0.04, 95% CI: −1.05 to 0.98). Pooled-analysis of randomized trials showed consistent results. The primary overall-effect was maintained in sensitivity and subgroup analyses. Meta-regression showed that male-gender was a significant risk-factor of POAF and use of Beta-blockers was associated with a significantly reduced risk in developing POAF. Conclusion and relevance This study demonstrates that preoperative RASIs do not offer additional benefit in reducing the risk of postoperative AF, stroke, death and hospitalization in the setting of cardiac surgery. The results provide no support for use of RASIs for the prevention of POAF and adverse events in patients undergoing cardiac surgery.

Oral non-steroidal anti-inflammatory drug therapy for lung disease in cystic fibrosis.

Progressive lung damage causes most deaths in cystic fibrosis. Non-steroidal anti-inflammatory drugs (such as ibuprofen) may prevent progressive pulmonary deterioration and morbidity in cystic fibrosis. This is an update of a previously published review. To assess the effectiveness of treatment with oral non-steroidal anti-inflammatory drugs in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, hand searches of relevant journals and abstract books of conference proceedings. We contacted manufacturers of non-steroidal anti-inflammatory drugs and searched online trials registries.Latest search of the Group's Trials Register: 21 November 2018. Randomized controlled trials comparing oral non-steroidal anti-inflammatory drugs, at any dose for at least two months, to placebo in people with cystic fibrosis. Two authors independently assessed trials for inclusion the review and their potential risk of bias. Two authors independently rated the quality of the evidence for each outcome using the GRADE guidelines. The searches identified 17 trials; four are included (287 participants aged five to 39 years; maximum follow-up of four years) and one is currently awaiting classification pending publication of the full trial report and two are ongoing. Three trials compared ibuprofen to placebo (two from the same center with some of the same participants); one trial assessed piroxicam versus placebo.The three ibuprofen trials were deemed to have good or adequate methodological quality, but used various outcomes and summary measures. Reviewers considered measures of lung function, nutritional status, radiological assessment of pulmonary involvement, intravenous antibiotic usage, hospital admissions, survival and adverse effects. Combined data from the two largest ibuprofen trials showed a lower annual rate of decline for lung function, % predicted forced expiratory volume in one second (FEV1), mean difference (MD) 1.32 (95% confidence interval (CI) 0.21 to 2.42) (moderate-quality evidence); forced vital capacity (FVC), MD 1.27 (95% CI 0.26 to 2.28) (moderate-quality evidence); forced expiratory flow (FEF25%-75%), MD 1.80 (95% CI 0.15 to 3.45). The post hoc analysis of data from two trials split by age showed a slower rate of annual decline of FEV1 % predicted and FVC in the ibuprofen group in younger children, MD 1.41% (95% CI 0.03 to 2.80) (moderate-quality evidence) and MD 1.32% (95% CI 0.04 to 2.60) (moderate-quality evidence) respectively. Data from four trials demonstrated the proportion of participants with at least one hospitalization may be slightly lower in the ibuprofen group compared to placebo, Peto odds ratio 0.61 (95% CI 0.37 to 1.01) (moderate-quality evidence). In one trial, long-term use of high-dose ibuprofen was associated with reduced intravenous antibiotic usage, improved nutritional and radiological pulmonary status. No major adverse effects were reported, but the power of the trials to identify clinically important differences in the incidence of adverse effects was low.We did not have any concerns with regards to risk of bias for the trial comparing piroxicam to placebo. However, the trial did not report many data in a form that we could analyze in this review. No data were available for the review's primary outcome of lung function; available data for hospital admissions showed no difference between the groups. No analyzable data were available for any other review outcome. High-dose ibuprofen can slow the progression of lung disease in people with cystic fibrosis, especially in children, which suggests that strategies to modulate lung inflammation can be beneficial for people with cystic fibrosis.

Yoga for Osteoarthritis: a Systematic Review and Meta-analysis.

This study aims to systematically review and summarise the efficacy and safety of yoga for osteoarthritis. Medline (through PubMed), Scopus, and the Cochrane Library were searched through April 2018 for randomised controlled trials of yoga for osteoarthritis. Primary outcomes were pain intensity, function, and quality of life; secondary outcomes were mental health and safety. Risk of bias was assessed using the Cochrane tool and quality of evidence through GRADE. Nine trials including 640 individuals with mainly lower extremity osteoarthritis aged 50-80years were identified, with 80.3% female participants (median). Meta-analyses revealed very low-quality evidence for the effects of yoga on pain (vs. exercise: standardised mean difference (SMD) = - 1.07; 95%CI - 1.92, - 0.21; p= 0.01; vs. non-exercise: SMD = - 0.75; 95%CI - 1.18, - 0.31; p< 0.001), physical function (vs. exercise: SMD = 0.80; 95%CI 0.36; 1.24; p< 0.001; vs. non-exercise: SMD = 0.60; 95%CI 0.30, 0.98; p< 0.001), and stiffness (vs. exercise: SMD = - 0.92; 95%CI - 1.69, - 0.14; p= 0.008; vs. non-exercise: SMD = - 0.76; 95%CI - 1.26, - 0.26; p= 0.003) in individuals with knee osteoarthritis. Effects were not robust against potential methodological bias. No effects were found for quality of life, and depression, or for hand osteoarthritis. Safety was rarely reported. The findings of this meta-analysis indicate that yoga may be effective for improving pain, function, and stiffness in individuals with osteoarthritis of the knee, compared to exercise and non-exercise control groups. Due to the low methodological quality and potential risk of bias, only a weak recommendation can be made at this time for the use of yoga in adults with osteoarthritis of the knee.

Efficacy of adjunctive anti-plaque chemical agents in managing gingivitis: A systematic review and network meta-analyses.

The aim of this network meta-analysis (NMA) was to compare the efficacy of different oral hygiene products for chemical biofilm control, in 6-month home-use, randomized clinical trials (RCTs), in terms of changes in gingival index (GI). Six-month RCTs assessing GI were identified and screened for inclusion. Relevant information was extracted, and quality and potential risk of bias were estimated. Mean differences between baseline and end were calculated to obtain standardized mean differences (SMDs). NMA protocols were applied to assess direct and indirect comparisons among products using Löe & Silness GI, modified GI and gingival severity index. Fifty-three papers were included, 19 studies for mouth rinses, 32 for dentifrices, comprising data from 5,775 and 2,682 subjects, respectively. When ranking treatments, similar results were observed for all tested dentifrices, with the lowest effect observed for sanguinarine and baking soda. For mouth rinses, essential oils, triclosan-copolymer, chlorhexidine (at concentrations≥0.10%) and cetylpyridinium chloride (>0.05%) demonstrated the greatest effect. Although NMA revealed significant differences when comparing placebo versus some active agents, when comparing among active agents, no differences were found for dentifrices, while mouth rinses containing essential oils showed the greatest effect on GI scores.

Effectiveness of vibratory stimulation on needle-related procedural pain in children: a systematic review.

The objective of this systematic review was to identify, evaluate and synthesize evidence of the effectiveness of vibratory stimulation to reduce needle-related procedural pain in children aged 18 years and younger. Needle-related procedures (NRPs) are common medical procedures associated with pain. Children, in particular, experience unpredictable and severe pain in response to NRPs. The gate control theory is commonly used to countermeasure this pain. Based on this theory, various types of vibratory stimulation have been used to reduce pain in several clinical studies. Participants were 0- to 18-year-old children who underwent NRPs for any condition. The intervention included any type of vibratory stimulation during the NRPs. The main outcome was pain measured on any pain scale, including both self-rated and observer-rated pain scales. The secondary outcomes were anxiety, the duration of the procedure and the success rate. All studies were randomized controlled trials (RCTs) or quasi-randomized trials published in English. The search strategy aimed to identify both published and unpublished studies. A three-step search strategy was utilized in this review. An initial search of MEDLINE and CINAHL was undertaken, followed by a search for unpublished studies. Nine databases were used for the search in October 2017. Papers selected for retrieval were assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments. Any disagreements that arose between the reviewers were resolved through discussion. Quantitative data were extracted from papers included in the review using a standardized data extraction tool. Where possible, quantitative data were pooled in the statistical meta-analysis. All results were subject to double data entry. Effect sizes were expressed as risk ratios (for categorical data) and weighted mean differences (for continuous data), and their 95% confidence intervals were calculated for analysis. Twenty-one RCTs involving 1727 children were identified. Blinding of the participants and those delivering the treatment was not achieved in all studies, introducing a potential risk of bias. Overall, the vibratory stimulation was significantly effective in reducing NRP pain in children as shown by measurement of self-rated pain outcomes (standardized mean difference [SMD]: -0.55, 95% confidence interval [CI]: -0.92 to -0.18) and observer-rated pain outcomes (SMD: -0.47, 95% CI: -0.76 to -0.18). Among secondary outcomes, the effect on the child's anxiety (SMD: -1.03, 95% CI: -1.85 to -0.20) was significant. Vibratory stimulation was effective in reducing NRP pain in children; however, blinding was not possible in the trials. Moreover, heterogeneity was high. Therefore, the confidence in the evidence is low. Personal preference should be a priority when using vibratory stimulation in the clinical setting.

Acupuncture for Primary Insomnia: An Updated Systematic Review of Randomized Controlled Trials.

Introduction: Acupuncture as one of the alternative therapies for insomnia is widely used in Asia and increasingly employed in western countries. Objectives: To provide updated evidence from randomized controlled trials (RCTs) on the effectiveness and safety of acupuncture for primary insomnia. Methods: A comprehensive literature search in 11 databases was conducted from January 2008 to October 2017. Two authors independently extracted data and assessed risk of bias independently. Statistical analysis was performed using RevMan 5.3 software. According to predefined protocol, we combined data in meta-analysis and performed trial sequential analysis when appropriate. Grading of Recommendations Assessment, Development, and Evaluation was also conducted to assess the quality of evidence. Results: A total of 73 RCTs involving 5533 participants were analyzed. The pooled results showed better effect from real acupuncture than no treatment (mean difference [MD] -5.58, 95% confidence interval [CI] -6.85 to -4.31, I2 = 0%, p < 0.00001, 2 trials, fixed effect model, 105 participants) on reducing Pittsburgh Sleep Quality Index (PSQI) scores with "very low quality" evidence. Acupuncture plus drugs showed better improvement than drugs alone on decreasing the PSQI total scores (MD -3.17, 95% CI -4.74 to -1.61, I2 = 72%, 4 trials, random-effects model (REM), p < 0.0001, 253 participants, low quality). Similar benefit favored acupuncture compared with no treatment (MD -8.46, 95% CI -9.59 to -7.33, I2 = 0%, p < 0.00001, 2 trials, 65 participants). Acupuncture showed more benefit than estazolam on PSQI (with enough statistical power). Athens Insomnia Scale (MD -1.64, 95% CI -2.40 to -0.89, I2 = 0%, p < 0.0001, 3 trials, fixed-effects model, 180 participants) or SPIEGEL (MD -2.86, 95% CI -3.54 to -2.18, p < 0.00001, I2 = 0%, 5 trials, fixed-effects model, 326 participants) with "very low-quality" evidence. Furthermore, low-quality evidence showed less adverse events from acupuncture than western medications (risk ratio 0.23, 95% CI 0.11-0.48, I2 = 56%, p < 0.0001, 11 trials, REM, 914 participants). Publication bias was likely present based on the PSQI total scores. Conclusions: The summary estimates indicate that acupuncture might result in improvement than no treatment on PSQI scores and appears safe. However, the quality of the evidence is varied from very low to low due to the potential risk of bias and inconsistency among included trials. Further large sample size and rigorously designed RCTs are still needed.

Electrical Stimulation in the Treatment of Hemiplegic Shoulder Pain

The aim of the study was to determine the effect of electrical stimulation in the treatment of hemiplegic shoulder pain. Eight databases were systematically searched for randomized controlled trials with a treatment duration of at least 2 wks comparing electrical stimulation with sham stimulation or no stimulation for patients with hemiplegic shoulder pain. Shoulder pain on the hemiplegic side after stroke at baseline was required at study selection. The overall effects of electrical stimulation were calculated using a meta-analytic method. Six studies were included. The pooled data indicated that electrical stimulation may have a positive effect for patients with hemiplegic shoulder pain on pain reduction (n = 193, standardized mean difference = -1.89, 95% confidence interval = -3.05 to -0.74) and pain-free external rotation (n = 164, weighted mean difference = 18.92, 95% confidence interval = 7.00 to 30.84). Meta-analysis also showed better recovery of activities of daily living independence in patient groups receiving electrical stimulation (n = 167, weighted mean difference = 8.96, 95% confidence interval = 5.26 to 12.66). Electrical stimulation may be an effective pain management methodology for hemiplegic shoulders and may contribute to pain-free range of external rotation as well as activities of daily living recovery. However, these results should be interpreted with caution, given the low number of selected studies and risk of potential bias.

Repetitive transcranial magnetic stimulation of lower limb motor function in patients with stroke: a systematic review and meta-analysis of randomized controlled trials

Objective: The aim of this study was to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on the post-stroke recovery of lower limb motor function. Data sources: We searched the databases of PubMed, Cochrane Library, and Embase. The randomized controlled trials were published by 25 January 2019. Review methods: We included randomized controlled trials that evaluated the effects of rTMS on lower limb motor recovery in patients with stroke. Two reviewers independently screened the searched records, extracted data, and assessed the risk of bias. The treatment effect sizes were pooled in a meta-analysis by using the RevMan 5.3 software. The internal validity was assessed using topics suggested by the Physiotherapy Evidence Database (PEDro). Results: Eight studies with 169 participants were included in the meta-analysis. Pooled estimates demonstrated that rTMS significantly improved the body function of the lower limbs (standardized mean difference (SMD) = 0.66; P < 0.01), lower limb activity (SMD = 0.66; P < 0.01), and motor-evoked potential (SMD = 1.13; P < 0.01). The subgroup analyses results also revealed that rTMS improved walking speed (SMD = 1.13) and lower limb scores on the Fugl-Meyer Assessment scale (SMD = 0.63). We found no significant differences between the groups in different mean post-stroke time or stimulation mode over lower limb motor recovery. Only one study reported mild adverse effects. Conclusion: rTMS may have short-term therapeutic effects on the lower limbs of patients with stroke. Furthermore, the application of rTMS is safe. However, this evidence is limited by a potential risk of bias.

Association between occurrence of urinary bladder cancer and treatment with statin medication.

The incidence of urinary bladder cancer (UBC) has increased in Sweden despite decreased smoking, indicating that other factors might be associated. The increased use of statin medication for elevated blood lipids might be one such influencing factor. The aim of the present study was to assess whether statins are afflicted with an increased incidence of UBC. Data from the Swedish National Register of Urinary Bladder Cancer, National Population Register, and Swedish Prescribed Drug Register were extracted. There were 22,936 patients with new diagnosed UBC between 2005 and 2014. Statin prescription was defined as any medication prescribed with the Anatomical Therapeutic Classification code C10A. For each patient, 10 control individuals were matched by age, gender, and living area, comprising 229,326 individuals. The Cochran-Mantel-Haenszel test was used to evaluate the hazards ratios. Statins were more frequently used in patients with UBC (33.8%) than in controls (29.8%, p<0.0001). The use of statins was afflicted with a 23% increased odds ratio (OR) for UBC (OR 1.23 (1.19-1.27), p<0.001). Subgroup analyses showed that an increased OR was found in non-muscle invasive UBC only. There was a tendency that OR was stronger for men and for younger patients. Limitations include its retrospective register-based design and potential risk of bias of confounding factors, such as smoking and body mass index. This nationwide register study suggests an association between the occurrence of UBC and patients using statins. The association was found in patients with non-muscle invasive disease only. Confounding factors, such as smoking, cannot be overruled.

Interventions to Teach Medical Students About Disability: A Systematic Search and Review.

Historically, medical students have received little training about working with patients with disability, but there is now a greater recognition of the need to educate medical students in this domain. The aims of this review were to define the body of literature and to determine effective strategies for teaching medical students about disability. A systematic search protocol executed across six databases identified journal articles reporting interventions implemented to teach disability to medical students. Seventy-seven articles spanning 1960-2018 met inclusion criteria. Most articles reported objectives related to increasing knowledge and skills or changing attitudes. However, only half included evaluations for all of their stated objectives in those domains. In addition, few articles used longitudinal evaluations, resulting in most articles basing conclusions on immediate posttest evaluations. Overall, the reported interventions exhibit a high risk of potential bias, with only 10% of the articles receiving a global quality rating of "good." Thus, although several articles have reported educational interventions to teach medical students about disability, the high risk of bias, incomplete reporting, and limitations of the evaluations prevent evidence-based determinations of effective strategies for teaching medical students about disability. The findings highlight ways to improve future studies in this domain.