Evaluation of a flexible piecewise linear mixed-effects model in the analysis of randomized cross-over trials.

Cross-over designs are commonly used in randomized clinical trials to estimate efficacy of a new treatment. They have received a lot of attention, particularly in connection with regulatory requirements for new drugs. The main advantage of using cross-over designs over conventional parallel designs is increased precision, thanks to within-subject comparisons. In the statistical literature, more recent developments are discussed in the analysis of cross-over trials, in particular regarding repeated measures. A piecewise linear model within the framework of mixed effects has been proposed in the analysis of cross-over trials. In this article, we report on a simulation study comparing performance of a piecewise linear mixed-effects (PLME) model against two commonly cited models-Grizzle's mixed-effects (GME) and Jones & Kenward's mixed-effects (JKME) models-used in the analysis of cross-over trials. Our simulation study tried to mirror real-life situation by deriving true underlying parameters from empirical data. The findings from real-life data confirmed the original hypothesis that high-dose iodine salt have significantly lowering effect on diastolic blood pressure (DBP). We further sought to evaluate the performance of PLME model against GME and JKME models, within univariate modeling framework through a simulation study mimicking a 2 × 2 cross-over design. The fixed-effects, random-effects and residual error parameters used in the simulation process were estimated from DBP data, using a PLME model. The initial results with full specification of random intercept and slope(s), showed that the univariate PLME model performed better than the GME and JKME models in estimation of variance-covariance matrix (G) governing the random effects, allowing satisfactory model convergence during estimation. When a hierarchical view-point is adopted, in the sense that outcomes are specified conditionally upon random effects, the variance-covariance matrix of the random effects must be positive-definite. The PLME model is preferred especially in modeling an increased number of random effects, compared to the GME and JKME models that work equally well with random intercepts only. In some cases, additional random effects could explain much variability in the data, thus improving precision in estimation of the estimands (effect size) parameters.

Anaesthesia for mechanical thrombectomy: a narrative review.

Stroke is a leading cause of death and disability, and is associated with a huge societal and economic burden. Interventions for the immediate treatment of ischaemic stroke due to large vessel occlusion are dependent on recanalisation of the occluded vessel. Trials have provided evidence supporting the efficacy of mechanical thrombectomy in ischaemic stroke due to large vessel occlusion. This has resulted in changes in management and organisation of stroke care worldwide. Major determinants of effectiveness of thrombectomy include: time between stroke onset and reperfusion; location of occlusion and local collateral perfusion; adequacy of reperfusion; patient age; and stroke severity. The role of anaesthetic technique on outcome remains controversial with published research showing conflicting results. As a result, choice of conscious sedation or general anaesthesia for mechanical thrombectomy is often dependent on individual operator choice or institutional preference. More recent randomised controlled trials have suggested that protocol-driven general anaesthesia is no worse than conscious sedation and may even be associated with better outcomes. These and other studies have highlighted the importance of optimal blood pressure management as a major determinant of patient outcome. Anaesthetic management should be tailored to the individual patient and circumstances. Acute ischaemic stroke is a neurological emergency; clinicians should focus on minimising door-to-groin puncture time and the provision of high-quality periprocedural care with a particular emphasis on the maintenance of an adequate blood pressure.

Pregnancy-related complications and perinatal outcomes following progesterone supplementation before 20 weeks of pregnancy in spontaneously achieved singleton pregnancies: a systematic review and meta-analysis.

BACKGROUND: Progesterone supplementation is widely performed in women with threatened miscarriage or a history of recurrent miscarriage; however, the effects of early progesterone supplementation on pregnancy-related complications and perinatal outcomes in later gestational weeks remain unknown. METHODS: Ovid MEDLINE, the Cochrane Library, Embase and ClinicalTrials.gov were searched until April 3rd, 2021. Randomized controlled trials regarding spontaneously achieved singleton pregnancies who were treated with progestogen before 20 weeks of pregnancy and were compared with those women in unexposed control groups were selected for inclusion. We performed pairwise meta-analyses with the random-effects model. The risk of bias was assessed according to the Cochrane Collaboration tool. The primary outcomes included preeclampsia (PE), and gestational diabetes mellitus (GDM), with the results presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We identified nine eligible studies involving 6439 participants. The pooled OR of subsequent PE following early progestogen supplementation was 0.64 (95% CI 0.42-0.98, moderate quality of evidence). A lower OR for PE was observed in the progestogen group when the subgroup analysis was performed in the vaginal subgroup (OR 0.62, 95%CI 0.40-0.96). There was insufficient evidence of a difference in the rate of GDM between pregnant women with early progestogen supplementation and unexposed pregnant women (OR 1.02, 95% CI 0.79-1.32, low quality of evidence). The pooled OR of low birth weight (LBW) following oral dydrogesterone was 0.57 (95% CI 0.34-0.95, moderate quality of evidence). The results were affected by a single study and the total sample size of enrolled women did not reach the required information size. CONCLUSION: Use of vaginal micronized progesterone (Utrogestan) in spontaneously achieved singleton pregnancies with threatened miscarriage before 20 weeks of pregnancy may reduce the risk of PE in later gestational weeks. Among spontaneously achieved singleton pregnancies with threatened miscarriage or a history of recurrent miscarriage, use of oral dydrogesterone before 20 weeks of pregnancy may result in a lower risk of LBW in later gestational weeks. However, the available data were not sufficient to reach definitive conclusions, which highlighted the need for future studies.

Effect of saffron supplementation on liver enzymes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Possible protective effects of saffron (Crocus sativus L) have been reported in several randomized clinical trials (RCTs). Current systematic review was performed to summarize the efficacy of saffron intake on liver enzymes. METHODS: An electronic database search was conducted on PubMed/Medline, Scopus, Web of Science, and Cochrane for RCTs comparing effect of saffron and placebo on liver enzymes from inception to July 2021. There was no restriction in language of included studies and we calculated the standardized mean difference (SMD) and 95% Confidence Intervals (CI) for each variable. Random-effect model was used to calculate effect size. RESULTS: Eight studies (n = 463 participants) were included in the systematic review. The saffron intake was associated with a statistically significant decrease in aspartate aminotransferase (AST) (SMD: -0.18; 95% CI: -0.34, -0.02; I2 = 0%) in comparison to placebo intake. Our results also indicated that saffron consumption did not have a significant effect on alanine aminotransferase (ALT) (SMD: -0.14; 95% CI: -0.36, 0.09; I2 = 47.0%) and alkaline phosphatase (ALP) levels (SMD: 0.14; 95% CI: -0.18, 0.46; I2 = 42.9%) compared to placebo. CONCLUSIONS: Saffron intake showed beneficial impacts on circulating AST levels. However, larger well-designed RCTs are still needed to clarify the effect of saffron intake on these and other liver enzymes.

The effectiveness and safety of Chuna manual therapy adjuvant to Western medicine in patients with chronic obstructive pulmonary disease: Study protocol for a randomized, single-blind, investigator-initiated, pilot trial.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) management, greater emphasis has been placed on symptomatic improvement and enhanced quality of life in patients. Manual therapy among respiratory rehabilitation programs has received much attention recently, with the publication of numerous studies. In South Korea, a method known as Chuna Manual Therapy (CMT) has been applied in the management of COPD patients and in clinical practice, but the clinical basis for safety and effectiveness is yet to be established. Therefore, rigorously designed randomized controlled trials are required. We aimed to evaluate the feasibility of assessing the add-on effect and safety of CMT administered with standard Western medicine therapy for the treatment of COPD. METHODS: This is a randomized, single-blind, single-center clinical pilot trial. Patients with COPD receiving standard drug therapy are randomly divided into an experimental group (n = 20) and a control group (n = 20) at a 1:1 ratio. The experimental group receives CMT adding to the standard medical therapy once a week for 8 weeks. The control group receives only the standard drug treatment. The trial is conducted with an outcome assessor and statistician blinding. The primary outcome is the 6-minute walk test. The secondary outcomes include the pulmonary function test, the Modified Medical Research Council, visual analog scale for dyspnea, COPD assessment test, quality of life using the St. George's respiratory questionnaire, EuroQOL five dimensions questionnaire, and Korean pattern identification questionnaire. Adverse events are also be evaluated. CONCLUSIONS: The results of this study will provide the feasibility of a large-scale clinical trial to establish high-quality clinical evidence of CMT for COPD. TRIAL REGISTRATION: Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0006119).

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity.

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomized clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.

Effectiveness of autogenic relaxation training in addition to usual physiotherapy on emotional state and functional independence of stroke survivors.

INTRODUCTION: The occurrence of post-stroke emotional problems is significant during the early post-stroke stage and affects the recovery of functionality among the survivors. Because stroke survivors require active engagement in rehabilitation to optimize the process of neuroplasticity in the initial stage of stroke, there is a need to integrate an intervention, preferably therapists-mediated during rehabilitation, which reduce emotional problems thus improve motivation level among the survivors. One such technique is autogenic relaxation training (ART). ART has been found to reduce anxiety and depression among patients with several medical conditions. However, its usage in stroke survivors during rehabilitation has been limited to date. Therefore, this study is intended to evaluate the effectiveness of ART in addition to usual physiotherapy in improving emotional state and functional level of stroke survivors during rehabilitation. METHODS: This is an assessor blinded randomized controlled trial comparing 2 intervention approaches namely ART-added physiotherapy (experimental group) and usual physiotherapy (control group). A total of 70 post-stroke patients will be recruited and allocated into either the ART-added physiotherapy or the usual physiotherapy group. The ART-added physiotherapy group will undergo a 20-minute ART session followed by 40 minutes of usual physiotherapy. While the usual physiotherapy group will receive usual physiotherapy alone for 60 minutes. All participants will be treated once a week and are required to carry out a set of home exercises for 2 times per week during the 12-week intervention. Assessment of emotional status and functional independence will be carried out at pre-intervention and week 13 of the intervention with the use of Hospital anxiety and depression scale, Barthel index, and EuroQol-5 dimensions-5 levels. All data will be analyzed using descriptive and inferential statistics. DISCUSSION: The expected main study outcome is an enhanced evidence-based physiotherapy program that may be used by physiotherapists in the rehabilitation of stroke patients with emotional disturbances. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619001664134 (last updated on 28/11/2019).

Single-inhaler triple vs single-inhaler dual therapy in patients with chronic obstructive pulmonary disease: a meta-analysis of randomized control trials.

BACKGROUND: In some RCTs comparing triple therapy with dual therapy in COPD, there might be a bias resulting from the use of multiple inhaler devices. This meta-analysis included only RCTs that compared ICS/LABA/LAMA vs. LABA/LAMA or ICS/LABA using a single device. METHODS: We systematically reviewed randomized controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. We searched the PubMed, MEDLINE (OvidSP), EMBASE and Cochrane Library databases to investigate the effect of single-inhaler triple therapy in COPD. The primary end points were the effect of single-inhaler triple therapy compared with single-inhaler dual therapy on all-cause mortality, the risk of acute exacerbation of COPD (AECOPD), and some safety endpoints. The Cochrane Collaboration tool was used to assess the quality of each randomized trial and the risk of bias. RESULTS: A total of 25,171 patients suffering from COPD were recruited for the 6 studies. This meta-analysis indicated that single-inhaler triple therapy resulted in a significantly lower rate of all-cause mortality than LABA/LAMA FDC (risk ratio, 0.70; 95% CI 0.56-0.88). Single-inhaler triple therapy reduced the risk of exacerbation and prolonged the time to first exacerbation compared with single-inhaler dual therapy. The FEV1 increased significantly more under single-inhaler triple therapy than under ICS/LABA FDC (mean difference, 103.4 ml; 95% CI 64.65-142.15). The risk of pneumonia was, however, significantly higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC (risk ratio, 1.55; 95% CI 1.35-1.80). CONCLUSIONS: This meta-analysis suggests that single-inhaler triple therapy is effective in reducing the risk of death of any cause and of moderate or severe exacerbation in COPD patients. However, the risk of pneumonia is higher with ICS/LAMA/LABA FDC than with LABA/LAMA FDC. Trial registration PROSPERO #CRD42020186726.

Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis.

BACKGROUND: Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial. METHODS: We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest. RESULTS: We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64-0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18-0.48) and mortality (odds ratio 0.66, 95% CI 0.50-0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16-2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA. Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference. CONCLUSION: Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations. CLINICAL TRIAL REGISTRATION: PROSPERO; CRD42020191978.

Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.

BACKGROUND/OBJECTIVE: Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1ß [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION: Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.

Lidocaine Infusions for Pain Management in Pediatrics.

Lidocaine is an amino amide with a well-established role as a local anesthetic agent. Systemic intravenous administration expands its clinical use to include acute and chronic pain circumstances, such as postoperative pain, neuropathic pain, postherpetic neuralgia, hyperalgesia, visceral pain, and centrally mediated pain. For refractory pain that has not responded to conventional therapy or if further escalation of treatment is prevented by contraindications or side effects to standard therapies, a continuous infusion of lidocaine may be considered as a single intervention or as a sequence of infusions. Here, we review and evaluate published data reflecting the use of lidocaine continuous infusions for pain management in the pediatric population.

Lithium carbonate as add-on therapy to radioiodine in the treatment on hyperthyroidism: a systematic review and meta-analysis.

BACKGROUND: The main purpose is to investigate the effect of LiCO3 as an add-on therapy with radioactive iodine in increasing the cure and decreasing the T4 level compared to radioactive iodine alone. The primary outcome is the cure rate as defined by the number of hyperthyroid patients who became euthyroid or hypothyroid. The secondary outcome is the T4 level. METHODS: Four databases were searched (PubMed, Scopus, Web of Science, and Cochrane central library). The inclusion criteria were randomized and non-randomized clinical trials of hyperthyroidism patients receiving LiCO3 with radioiodine compared with hyperthyroidism patients receiving radioactive iodine alone. Included studies were appraised with the risk of bias version 2 tool, according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. RESULTS: Nine studies were eligible for inclusion in the study, six randomized control trials and three non-randomized control trials. There were 477 patients in the intervention group and 451 patients in the control group. The cure rate was not significantly different between the two groups, while it was significantly increased with 5000 to 6500 mg optimized cumulative dose of LiCO3 compared with the control group, P = 0.0001. The T4 level showed no significant difference between the two groups, P = 0.13. CONCLUSIONS: LiCO3 adjunct to radioactive iodine did not show significant differences compared with radioactive iodine alone in terms of cure rate or decreasing T4 level. However, the dose of 5000 to 6000 mg of LiCO3 may increase the cure rate.

A meta-analysis of randomized clinical trials on the impact of oral vitamin C supplementation on first-year outcomes in orthopedic patients.

This meta-analysis aimed at investigating the impact of oral vitamin C supplementation on the post-procedural recovery of orthopedic patients, including functional outcomes and complex regional pain syndrome type I (CRPS I). Literature search using the Medline, Cochrane Library, and Embase databases from inception till March 2021 identified seven eligible randomized controlled trials with 1,361 participants. Forest plot revealed no significant difference in the functional outcomes at 6-12 months [standardized mean difference (SMD) = -0.00, 95% CI - 0.19 to 0.18, 467 patients], risk of overall complications (RR = 0.98, 95% CI 0.68 to 1.39, 426 patients), and pain severity at 3-6 months (SMD = - 0.18, 95% CI - 0.49 to 0.12, 486 patients) between patients with and without oral vitamin C supplementation. Pooled analysis showed that vitamin C treatment reduced the risk of CRPS I regardless of dosage (RR = 0.46, 95% CI 0.25 to 0.85, 1143 patients). In conclusion, the current meta-analysis demonstrated that oral vitamin C supplementation may reduce the risk of complex regional pain syndrome type I but did not improve the functional outcomes in orthopedic patients. Nevertheless, because of the small number of trials included in the present study, further large-scale clinical studies are warranted to support our findings.

Evaluating the methodology of studies conducted during the global COVID-19 pandemic: A systematic review of randomized controlled trials.

BACKGROUND: The therapeutic evidence collected from well-designed studies is needed to help manage the global pandemic of the coronavirus disease 2019 (COVID-19). Evaluating the quality of therapeutic data collected during this most recent pandemic is important for improving future clinical research under similar circumstances. OBJECTIVE: To assess the methodological quality and variability in implementation of randomized controlled trials (RCTs) for treating COVID-19, and to analyze the support that should be provided to improve data collected during an urgent pandemic situation. SEARCH STRATEGY: PubMed, Excerpta Medica Database, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP, and the preprint repositories including Social Science Research Network and MedRxiv were systematically searched, up to September 30, 2020, using the keywords "coronavirus disease 2019 (COVID-19)," "2019 novel coronavirus (2019-nCoV)," "severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2)," "novel coronavirus pneumonia (NCP)," "randomized controlled trial (RCT)" and "random." INCLUSION CRITERIA: RCTs studying the treatment of COVID-19 were eligible for inclusion. DATA EXTRACTION AND ANALYSIS: Screening of published RCTs for inclusion and data extraction were each conducted by two researchers. Analysis of general information on COVID-19 RCTs was done using descriptive statistics. Methodological quality was assessed using the risk-of-bias tools in the Cochrane Handbook for Systematic Reviews of Interventions (Version 5.1.0). Variability in implementation was assessed by comparing consistency between RCT reports and registration information. RESULTS: A total of 5886 COVID-19 RCTs were identified. Eighty-one RCTs were finally included, of which, 45 had registration information. Methodological quality of the RTCs was not optimal due to deficiencies in five main domains: allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. Comparisons of consistency between published protocols and registration information showed that the 45 RCTs with registration information had common deviations in seven items: inclusion and exclusion criteria, sample size, outcomes, research sites of recruitment, interventions, and blinding. CONCLUSION: The methodological quality of COVID-19 RCTs conducted in early to mid 2020 was consistently low and variability in implementation was common. More support for implementing high-quality methodology is needed to obtain the quality of therapeutic evidence needed to provide positive guidance for clinical care. We make an urgent appeal for accelerating the construction of a collaborative sharing platform and preparing multidisciplinary talent and professional teams to conduct excellent clinical research when faced with epidemic diseases of the future. Further, variability in RCT implementation should be clearly reported and interpreted to improve the utility of data resulting from those trials.

Diabetic Neuropathy: a Critical, Narrative Review of Published Data from 2019.

PURPOSE OF REVIEW: This manuscript is a systematic, narrative review that compiles and describes all data available from 2019 related to epidemiologic, diagnostic, and therapeutic advances in diabetic neuropathy (DN). RECENT FINDINGS: Epidemiology of DN is discussed. Diagnostic modalities include predictive models, electrodiagnostics, imaging, and biomarkers. A majority of studies on the treatment of diabetic peripheral neuropathy (DPN) involve pharmacotherapy, but complementary and alternative medicine, exercise, modalities, psychological, interventional, and surgical options are also explored. DN is a highly prevalent and debilitating consequence of diabetes that can present challenges to the clinician as the assessment is largely subjective with different phenotypic presentations among patients. Treatment of DN is largely symptomatic as the pathogenesis of DN is not fully understood and is likely multifactorial. It is evident from the broad range of treatments that too often provide unsatisfactory relief that there is no consensus about a single most effective treatment for DN, and monotherapy rarely proves to be successful.

Interventional Modalities to Treat Complex Regional Pain Syndrome.

PURPOSE OF REVIEW: Complex regional pain syndrome (CRPS) is a debilitating pain condition that often requires a multidisciplinary approach including medication, physical therapy, occupational therapy, psychological therapy, and interventional procedures to restore the patient's quality of life. This article reviews the interventional treatments for pain resulting from CRPS. RECENT FINDINGS: Sympathetic nerve blocks (stellate ganglion and lumbar sympathetic) are the first-line interventional treatment options for patients with CRPS of the upper and lower extremities, respectively. Fluoroscopic techniques for lumbar sympathetic blocks have not significantly changed throughout the years. However, both novel fluoroscopic and ultrasound approaches to stellate ganglion blockade have arisen. In addition, novel neuromodulation therapies to treat CRPS have been developed to include new waveforms with dorsal column stimulation and entirely new nerve targets such as dorsal root ganglion stimulation. This paper will review the latest interventional treatment options available for the treatment of CRPS.

Effects of non-drug interventions on depression, anxiety and sleep in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVE: Patients with Coronavirus Disease 2019 (COVID-19) suffer from anxiety, depression and sleep disorders due to isolation treatment, among other reasons. Whether non-drug interventions can be alternative therapies for COVID-19 patients with anxiety, depression and sleep disorders is controversial. Therefore, we conducted a meta-analysis and systematic review to evaluate the effects of non-drug interventions on anxiety, depression and sleep in patients with COVID-19 to provide guidance for clinical application. MATERIALS AND METHODS: We searched the following databases for randomized controlled trials (RCTs) from December 2019 to July 2020: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP Chinese Science and Technology Periodical Database (VIP), Wanfang, Cochrane Library, Web of Science, PubMed, MEDLINE and Embase. Two investigators independently screened the literature according to the inclusion and exclusion criteria, extracted data and evaluated the risk of bias in the included studies. Meta-analysis was performed using RevMan5.3 software. RESULTS: A total of 5 articles with 768 subjects were included. Meta-analysis results indicated that non-drug interventions can reduce anxiety [SMD=-1.40, 95% CI (-1.62, -1.17), p<0.00001] and depression [SMD=-1.22, 95% CI (-2.01, -0.43), p=0.002] scores in patients with COVID-19. Descriptive analysis indicated that non-drug interventions can improve the sleep status of COVID-19 patients. Sensitivity analysis indicated that the meta-analysis results were stable. Egger's test and Begg's test showed no publication bias. CONCLUSIONS: This meta-analysis found that non-drug interventions can reduce the anxiety and depression scores of patients with COVID-19. Due to the limitations of this study, more high-quality studies are needed to verify the findings, especially the effect of non-drug interventions on improving the sleep status of COVID-19 patients.

The Efficacy of Vitamin D Supplementation for Migraine: A Meta-Analysis of Randomized Controlled Studies.

INTRODUCTION: The efficacy of vitamin D for migraine remains controversial. We conduct a systematic review and meta-analysis to explore the influence of vitamin D versus placebo on treatment in migraine patients. METHODS: We search PubMed, EMbase, Web of Science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials assessing the effect of vitamin D versus placebo on treatment efficacy in migraine patients. This meta-analysis is performed using the random-effect model. RESULTS: Five randomized controlled trials are included in the meta-analysis. Overall, compared with control group in migraine patients, vitamin D treatment is associated with substantially reduced number of headache days (standard mean difference [SMD], -0.53; 95% confidence interval [CI], -0.83 to -0.23; P = 0.0006), frequency of headache attacks (SMD, -1.09; 95% CI, -1.86 to -0.32; P = 0.006), headache severity (SMD, -0.55; 95% CI, -0.91 to -0.19; P = 0.0003), and Migraine Disability Assessment score (SMD, -0.76; 95% CI, -1.11 to -0.40; P < 0.0001). CONCLUSIONS: Vitamin D treatment is effective to alleviate migraine.

Efficacy of transcutaneous perineal electrostimulation versus intracavitary anal electrostimulation in the treatment of urinary incontinence after a radical prostatectomy: randomized controlled trial study protocol.

BACKGROUND: Radical prostatectomy is the gold standard treatment for men with localized prostate cancer. This technique is associated with post-operative urinary incontinence. Pelvic floor physiotherapy is a conservative, painless and economical treatment for this specific situation. Kegel exercises and perineal electrostimulation are common techniques to train pelvic floor muscles. The perineal electrostimulation can be applied to the patient with surface electrodes or by an intra-cavitary anal probe. This study proposes that transcutaneous perineal electrostimulation is as effective as intra-cavitary electrostimulation in reducing urinary incontinence secondary to radical prostatectomy. The main objective is to compare the efficacy of the treatment with transcutaneous perineal electrostimulation versus the same intra-cavitary treatment to reduce the magnitude of urinary incontinence after radical prostatectomy, and the impact on the quality of life. METHODS: This single-blind equivalence randomized controlled trial will include 70 man who suffer urinary incontinence post radical prostatectomy. Participants will be randomized into surface electrodes group and intra-anal probe group. The groups will receive treatment for 10 consecutive weeks. Outcomes include changes in the 24-h Pad Test, and ICIQ-SF, SF-12 and I-QoL questionnaires. Clinical data will be collected at baseline, 6 and 10 weeks after the first session, and 6 months after the end of treatment. DISCUSSION: The results will allow us to prescribe the most beneficial perineal electrostimulation technique in the treatment of urinary incontinence derived from radical prostatectomy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03587402. 27/06/2018.

Pediatric Osteopathic Manipulative Medicine: A Scoping Review.

CONTEXT: A common reproach precluding the use of osteopathic manipulative medicine (OMM) in pediatrics is a lack of evidence regarding its safety, feasibility, and effectiveness. OBJECTIVE: We conducted a systematic, scoping review of pediatric osteopathic medicine to identify gaps in the literature and make recommendations for future research. DATA SOURCES: We searched 10 databases using 6 key words and medical subject heading terms for any primary articles reporting OMM use in children published from database inception until initiation of the study. STUDY SELECTION: Articles were selected if they reported primary data on OMM conducted in the United States on patient(s) 0 to 18 years old. DATA EXTRACTION: Baseline study characteristics were collected from each article and the Grading of Recommendations, Assessment, Development, and Evaluations system was used to critically appraise each study. RESULTS: Database search yielded 315 unique articles with 30 studies fulfilling inclusion and exclusion criteria. Of these, 13 reported the data required to demonstrate statistically significant results, and no significant adverse events were reported. The majority of studies were graded as providing weak clinical evidence because of significant methodologic flaws and biases. LIMITATIONS: The review was limited to US-based studies and reports. Minimal discrepancies between reviewers were resolved via an objective third reviewer. CONCLUSIONS: There is little strong, scientific, evidence-based literature demonstrating the therapeutic benefit of OMM for pediatric care. No strong clinical recommendations can be made, but it can be medically tolerated given its low risk profile. High-quality, scientifically rigorous OMM research is required to evaluate safety, feasibility, and efficacy in pediatrics.