Double-blind RCTs Research Articles

Could tocilizumab be used in familial Mediterranean Fever? A systematic review.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as interleukin-1β (IL-1β), TNF-α, and interleukin-6 (IL-6) inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented. To evaluate the efficacy and safety of tocilizumab in the treatment of FMF. Following PRISMA guidelines, we identified 237 articles on the use of TCZ in FMF. After selection, 14 articles were included: 2 double-blind RCTs, 2 retrospective studies, and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in pediatric FMF. This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Efficacy and safety of interspinous process device compared with alone decompression for lumbar spinal stenosis: A systematic review and meta-analysis.

Systematic review and meta-analysis. Interspinous process devices (IPD) were used as a treatment in selected patients with lumbar spinal stenosis (LSS). However, the use of IPD was still debated that it had significantly higher reoperation rates compared to traditional decompression. Therefore, the purpose of the meta-analysis was to evaluate the effectiveness and safety of IPD treatment in comparison to traditional treatment. The databases were searched of PubMed, Embase and the Cochrane, Chinese National Knowledge Infrastructure, Chongqing VIP Database and Wan Fang Database up to January 2024. Relevant studies were identified by using specific eligibility criteria and data was extracted and analyzed based on primary and secondary endpoints. A total of 13 studies were included (5 RCTs and 8 retrospective studies). There was no significant difference of Oswestey Disability Index (ODI) score in the last follow-up (MD = -3.81, 95% CI: -8.91-1.28, P = .14). There was significant difference of Visual Analog Scale (VAS) back pain scoring in the last follow-up (MD = -1.59, 95% CI: -3.09--0.09, P = .04), but there existed no significant difference of leg pain in the last follow-up (MD = -2.35, 95% CI: -6.15-1.45, P = .23). What's more, operation time, bleeding loss, total complications and reoperation rate had no significant difference. However, IPD had higher device problems (odds ratio [OR] = 9.00, 95% CI: 2.39-33.91, P = .001) and lesser dural tears (OR = 0.32, 95% CI: 0.15-0.67, P = .002) compared to traditional decompression. Although IPD had lower back pain score and lower dural tears compared with traditional decompression, current evidence indicated no superiority for patient-reported outcomes for IPD compared with alone decompression treatment. However, these findings needed to be verified in further by multicenter, double-blind and large sample RCTs.

What is the Evidence for Using Intranasal Medicine in the Prehospital Setting? A Systematic Review

Objectives Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone. Methods A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, “Cochrane Central Register of Controlled Trials,” Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received. Results From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating “high concerns” for bias. Conclusions Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs.

Use of problem-based learning in orthopaedics education: a systematic review and meta-analysis of randomized controlled trials

BackgroundCurrently, problem-based learning (PBL) has been widely used in many disciplines, but no systematic review has explored the advantages and disadvantages of PBL in orthopaedics education.MethodsWe searched the PubMed, Cochrane Library, Embase, Web of Science, Scopus, Chongqing VIP Database (VIP), Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases up to April 2023 to identify for relevant studies. Relevant studies were identified by using specific eligibility criteria, and data were extracted.ResultsA total of 51 randomized controlled trials with 4268 patients were included. Compared with traditional education, PBL teaching yielded significantly higher knowledge scores (SMD=1.10, 95% CI: 0.78~1.41, P<0.00001), procedural skill scores and clinical skill scores than traditional teaching (SMD=2.07, 95% CI: 1.61~2.53, P<0.00001; SMD=1.20, 95% CI: 0.88~1.52, P<0.00001). Moreover, the total scores were higher in the PBL teaching group than in the traditional teaching group (MD=5.69, 95% CI: 5.11~6.26, P<0.00001). Students also expressed higher levels of interest and satisfaction in the PBL teaching group than in the traditional teaching group (OR=4.70, 95% CI: 3.20~6.93, P<0.00001; OR=5.43, 95% CI: 3.83~7.69, P<0.00001). However, there was less learning time and higher levels of learning pressure in the PBL teaching group (OR=0.12, 95% CI: 0.06~0.24, P<0.00001; OR=5.95, 95% CI: 3.16~11.23, P<0.00001).ConclusionCurrent evidence indicates that PBL teaching can increase knowledge scores, procedural skill scores, and clinical skill scores. Students have higher levels of interest in teaching and higher levels of teaching satisfaction in the PBL group. However, students can feel higher levels of study pressure and experience less study time. The findings of the current study need to be further verified in multicentre, double-blind and large-sample RCTs.

Assessing the Impact of Stem Cell-based Therapy on Periodontal Health: A Meta-analysis of Clinical Studies.

While clinical trials exploring stem cells for regenerating periodontal tissues have demonstrated positive results, there is a limited availability of systematic literature reviews on this subject. To gain a more comprehensive understanding of stem cell interventions in periodontal regeneration, this meta-analysis is undertaken to assess the beneficial effects of stem cells in human periodontal regeneration. "PubMed," "Cochrane Library," "Web of Science," "Embase," "Wanfang," and "CNKI," were used to extract clinical studies related to the utilization of stem cells in repairing periodontal tissue defects. This search included studies published up until October 5, 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell-free therapy for regenerating periodontal tissues. Meta-analysis was conducted using Review Manager software (version 5.4). This meta-analysis synthesized findings from 15 selected studies investigating the impact of stem cell interventions on periodontal tissue regeneration. The "stem cell" group displayed a substantial reduction in clinical attachment level (CAL) compared to the "control" group within 3 to 12 months post-surgery. However, no significant differences in CAL gain were found between groups. Probing pocket depth (PPD) significantly decreased in the "stem cell" group compared to the "control" group, particularly for follow-up periods exceeding 6 months, and dental stem cell treatment exhibited notable improvements. Conversely, no significant differences were observed in PPD reduction. Gingival recession (GR) significantly decreased in the "stem cell" group compared to the "control" group at 3 to 12 months post-surgery. No significant differences were observed in GR reduction between groups. No significant differences were identified in cementoenamel junction-bone distance reduction, infrabony defect reduction, or bone mineral density increase between the two groups. Furthermore, no significant changes were observed in the gingival index, plaque index, or width of keratinized gingiva. In conclusion, while stem cell-based therapy offers promising prospects for periodontal defect treatment, there are notable limitations in the current body of research. Larger, multicenter, double-blind RCTs with robust methodologies are needed to provide more reliable evidence for stem cell-based intervention in periodontitis.

COMPARISON OF PHARMACOLOGY AGENTS EFFECT IN TREATING URETERAL STENT RELATED SYMPTOMS: SYSTEMATIC REVIEW &amp; META-ANALYSIS OF RANDOMIZED CONTROLLED TRIAL¬

Objective: We wish to update existing meta-analyses to assess the effectiveness of pharmacological agents against ureteral stent-related symptoms with better design of RCTs, as well as more valid and reliable measurement methods. Material &amp; Methods: Relevant published articles up to February 2022 were obtained from PubMed, CENTRAL, Google Scholar, Science Direct, and DOAJ. All single-blind or double-blind RCTs with various comparisons using pharmacological agents and/or placebo in patients with ureteral stent-related symptoms, with outcome assessment using USSQ at week 1 and week 4 during stent placement was included in the study. Statistical parameter Mean Difference (MD) with 95% CI was used to measure effect size. The p value less than 0.05 indicates statistical significance. Results: Alpha blockers (2 studies, 85 samples) significantly reduced fourth week UIS compared to placebo (MD: – 5.46, 95% CI: – 7.47 to -3.46, I2 = 0%, P = &lt; 0.001), and alpha blockers (2 studies, 42 samples) significantly reduced first week SIS compared to combination therapy (MD: – 0.82, 95% CI: – 1.56 to – 0.08, I2 = 0%, P = 0.03). The results of the meta-analysis of USSQ scores in other domains have no significant differences. Conclusion: Alpha blockers were better than placebo in reducing UIS due to ureteral stent in the fourth week of stent placement, and better than combination therapy in reducing SIS due to ureteral stent in the first-week post stenting. However, more RCTs are needed with larger samples and better designs to reach valid conclusions.&#x0D; Keywords: Stents, Randomized Controlled Trials as Topic, Single-Blind Method.

The 'placebo effect' in the conservative treatment of plantar fasciitis: a systematic review and meta-analyses.

The study of the placebo effect is key to elucidate the 'real effect' of conservative interventions for plantar fasciitis. The aim of this meta-analysis was to quantify the impact of placebo in the different conservative treatments of plantar fasciitis. A systematic literature review was performed on double-blind placebo-controlled trials (RCTs) according to PRISMA guidelines on PubMed, Embase, and Web of Science. The meta-analysis primary outcome was the 0-10 pain variation after placebo treatments analyzed at 1 week, 1, 3, 6, and 12 months. The risk of bias was assessed using the RoB 2.0 tool, while the overall quality of evidence was graded according to the GRADE guidelines. The placebo effect for conservative treatments was studied in 42 double-blind RCTs on 1724 patients. The meta-analysis of VAS pain showed a statistically significant improvement after placebo administration of 2.13/10 points (P < 0.001), being highest at 12 months with 2.79/10 points (P < 0.001). The improvement of the placebo groups was higher in the extracorporeal shock wave therapy studies compared to the injection studies (2.59 vs 1.78; P = 0.05). Eight studies had a low risk of bias, 23 studies had 'some concerns,' and 4 studies had a high risk of bias. The GRADE evaluation showed an overall high quality of evidence. This systematic review and meta-analysis demonstrated that the placebo effect represents an important component of all conservative approaches to treat plantar fasciitis. This effect is statistically and clinically significant, increases over time, and depends on the type of conservative treatment applied to address plantar fasciitis.

Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.

Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear. We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al. Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy. The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.

Thiazide diuretics alone or combined with potassium-sparing diuretics to treat hypertension: a systematic review and network meta-analysis of randomized controlled trials.

The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.

Efficacy and safety of anteriortransposition of the ulnar nerve for distal humerus fractures: A systematic review and meta-analysis.

This systematic review and meta-analysis was performed to summarize available evidence of anterior transposition of the ulnar nerve for patients with distal humerus fractures. The databases were searched from PubMed, Cochrane, Embase, Scopus, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP Database (VIP), and Wan Fang Database up to June 2022. The clinical outcome included operation time, fracture healing time, hospital stays, elbow joint function, and ulnar neuritis rate. Statistical analysis was performed with Review Manager 5.3 (Cochrane Collaboration). A total of 17 studies were included (8 RCTs and 9 retrospective studies), and 1280 patients were analyzed. The results of this meta-analysis showed anterior transposition group had longer operation time (MD = 20.35 min, 95%CI: 12.56-28.14, P < 0.00001). There was no significant difference in fracture healing time (SMD = -0.50, 95%CI: -1.50-0.50, P = 0.33), hospital stays (MD = -1.23 days, 95%CI: -2.72--0.27, P = 0.11), blood loss (MD = 2.66 ml, 95%CI: -2.45-7.76, P = 0.31), and ulnar neuritis rate (OR = 1.23, 95%CI: 0.63-2.42, P = 0.54) between two groups. Finally, elbow joint motion, elbow joint function, fracture nonunion, and post-operative infection (P > 0.05) between two groups were not significantly statistic difference. This meta-analysis showed that anterior transposition group is not superior to non-transposition group for patients with distal humerus fractures without ulnar nerve injury. On the contrary, non-transposition group have shorter operation time than that of anterior transposition group. Non-transposition group did not increase the post-operative ulnar neuritis rate. Therefore, both anterior transposition group and non- transposition group are the treatment options for patients with distal humerus fractures without ulnar nerve injury. Besides, these findings need to be further verified by multi-center, double-blind, and large sample RCTs.

Adjunctive tDCS for treatment-refractory auditory hallucinations in schizophrenia: A meta-analysis of randomized, double-blinded, sham-controlled studies.

Treatment-refractory auditory hallucinations (TRAH) in schizophrenia often do not improve with pharmacotherapy. We performed a meta-analysis of randomized, double-blind, sham-controlled clinical trials (RCTs) that systematically examined the therapeutic effects and tolerability of adjunctive active versus sham active transcranial direct current stimulation (tDCS) for auditory hallucinations as measured by the Auditory Hallucination Rating Scale (AHRS) in schizophrenia patients with TRAH. Relevant data were extracted, checked and analyzed using the Review Manager, Version 5.3 by three independent investigators. Eight double-blind RCTs covering 329 schizophrenia patients (168 in active tDCS group, 161 in sham tDCS group) were included. Although no advantage of active tDCS on auditory hallucinations [7 RCTs, n=224; standardized mean difference (SMD): -0.33 (95% confidence interval (CI): -0.71, 0.05), P=0.09; I2 =46%] was found compared to sham, subgroup analyses revealed that active tDCS with twice-daily stimulation [6 RCTs, n=198; SMD: -0.42 (95%CI: -0.82, -0.02), P=0.04; I2 =44%] and active tDCS with ≥10 stimulation sessions [6 RCTs, n=198; SMD: -0.42 (95%CI: -0.82, -0.02), P=0.04; I2 =44%] showed a significantly better therapeutic effect than sham in improving auditory hallucinations symptoms. Meta-analyses of total psychopathology and discontinuation due to any reason were not significantly different between the active and sham tDCS groups. This meta-analysis demonstrated that the effects of tDCS for auditory hallucinations symptoms were influenced by the tDCS parameters. Twice-daily stimulation and ≥10 stimulation sessions may be needed to improve auditory hallucinations symptoms in schizophrenia with TRAH.

The impact of FDA and EMA regulatory decision-making process on the access to CFTR modulators for the treatment of cystic fibrosis

BackgroundOver the past decade, a new class of drugs called CFTR (cystic fibrosis transmembrane conductance regulator) modulators have shown to be able to improve clinical outcomes in patient with Cystic Fibrosis. In this analysis, we have extensively reviewed the regulatory pathways and decisions adopted by FDA and EMA to speed up the development, the review and the approval of these drugs, with the aim of identifying possible clinical and public health implications associated with differences.ResultsCFTR modulators have been developed towards addressing three main genetic domains: (1) F508del homozygous (F508del/F508del), (2) F508del heterozygous, and (3) genotypes not carrying F508del mutation; and expanded from adult to paediatric population. Programs to expedite the reviewing and licensing of CFTR modulators were extensively adopted by FDA and EMA. All CFTR modulators have been licensed in the US as orphan drugs, but in the EU the orphan status for LUM/IVA was not confirmed at the time of marketing authorization as results from the pivotal trial were not considered clinically significant. While FDA and EMA approved CFTR modulators on the basis of results from phase III double-blind RCTs, main differences were found on the extension of indications: FDA accepted non-clinical evidence considering a recovery of the CFTR function ≥ 10% based on chloride transport, a reliable indicator to correlate with improvement in clinical outcomes. By contrast, EMA did not deem preclinical data sufficient to expand the label of CFTR modulators without confirmatory clinical data.ConclusionsRegulators played an important role in fostering the development and approval of CFTR modulators. However, differences were found between FDA and EMA in the way of reviewing and licensing CFTR modulators, which extended beyond semantics affecting patients’ eligibility and access: FDA’s approach was more mechanistic/biology-driven while the EMA’s one was more oriented by clinical evidence. This might refer to the connection between the EMA and the Member States, which tends to base decisions on pricing and reimbursement on clinical data rather than pre-clinical ones. Here we have proposed a two-step personalized-based model to merge the ethical commitment of ensuring larger access to all potential eligible patients (including those harboring very rare mutations) with the one of ensuring access to clinically assessed and effective medicines through Real World Data.

The therapeutic potential of psilocybin: a systematic review

ABSTRACT Introduction Psychedelic drugs were used quite extensively before their prohibition in 1968 which delayed research. However, since the 1990s, studies on the potential therapeutic benefits of psychedelics have rapidly increased. Areas covered This systematic review provides an overview of the clinical effects of psilocybin in the treatment of a variety of mental disorders. Only (randomized) clinical trials were selected. A total of 11 studies (15 publications) were selected, including seven randomized controlled trials (eight publications) and four single arm open-label studies (seven publications). In total, 488 patients were included in the selected studies: 333 patients treated with psilocybin and 155 patients treated with (active) placebo. In nine studies, psychotherapeutic support was provided as an integral part of the psilocybin treatment. The findings of these studies collectively show that psilocybin has a positive benefit–risk balance in the treatment of various mental disorders with an immediate and prolonged effect following 1–3 doses of psilocybin and a few (serious) adverse events. Expert opinion Psilocybin – mostly combined with psychotherapy or psychotherapeutic support – shows a promise as a treatment for various (treatment-resistant) mental disorders. Larger double-blind RCTs with objective (long-term) outcomes are needed to confirm these findings before standard clinical use of psilocybin can be considered.

Comparative Efficacy of Xianling Gubao Capsules in Improving Bone Mineral Density in Postmenopausal Osteoporosis: A Network Meta-Analysis.

ObjectiveThe clinical efficacy of Xianling Gubao capsule (XLGB) and its combination therapy in the treatment of postmenopausal osteoporosis (PMOP) was systematically evaluated by frequency-based network meta-analysis.MethodsWe searched the China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, PubMed, Embase and Cochrane Library databases to identify clinical trials of XLGB for the treatment of PMOP from the establishment of each database to November 22, 2021. The quality of the included studies was evaluated by using the risk of bias assessment tool version 2.0 (Rob 2.0) recommended by Cochrane. Stata 14.0 was applied for statistical analysis of the data, and the surface under the cumulative ranking curve (SUCRA) was used to rank the intervention measures of each outcome index.ResultsThis study included 22 clinical trials (including 19 RCTs and 3 non-RCTs) involving 12 drug therapies. According to the results of the network meta-analysis and SUCRA, the best three interventions for improving lumbar bone mineral density (BMD) are XLGB+BP+calcium (83.7%), XLGB+BP (68.5.7%) and XLGB+VD (67.1%). XLGB+calcium was the best combination regimen for improving femoral neck BMD and increasing bone Gla protein (BGP) and alkaline phosphatase (ALP) contents in serum. The SUCRA values of XLGB+calcium for improving the three outcome indicators were 68.0%, 59.5% and 82.1%, respectively.ConclusionsThe results of this network meta-analysis show that combined application of XLGB can effectively improve BMD and serum BGP and ALP compared to calcium alone, VD or BP. In the future, multicenter, large-sample and double-blind clinical RCTs should be carried out to supplement and verify the results of this study.

Early erythropoietin for preventing necrotizing enterocolitis in preterm neonates - an updated meta-analysis.

There is moderate to low-quality evidence that early prophylactic EPO reduces any stage and ≥ Stage II NEC in preterm neonates. Prospectively registered, adequately powered, double-blind RCTs are required to confirm these findings. • Experimental studies have shown that erythropoietin (EPO) has gastrointestinal trophic effects. • Systematic reviews have shown that early treatment with EPO may decrease the risk of gut injury in preterm or low birth weight infants. • Early EPO supplementation significantly reduced the incidence of any stage NEC and definite NEC in preterm infants < 34 weeks of gestation. • EPO had no significant effect on definite NEC in the analyses that included only double-blinded and prospectively registered RCTs. How might it impact clinical practice in the foreseeable future? • Early prophylactic EPO can be recommended for NEC prevention if its benefits are consistently demonstrated in adequately powered randomized trials with a low risk of bias.

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28weeks, cinacalcet normalizes serum calcium (≤ 10.3mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 - 68.52, I2 = 0%, pheterogeneity < 0·00001)]. Serum PTH levels decreased significantly after 2weeks and up to 28weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I2 = 92%, pheterogeneity < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI -0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option.

Safety and efficacy of Rudraksha Churna in the treatment of essential hypertension—a single-arm multicentre trial

BACKGROUND: Essential hypertension (EHTN) is one of the most prevalent lifestyle disorders globally. In Ayurveda, the powdered seed of Elaeocarpus ganitrus Roxb. ex G.Don [Rudraksha Churna (RC)] is indicated for headache, the most common symptom of EHTN. Pharmacological studies on an aqueous extract of E. ganitrus have shown that it can be used to treat anxiety and EHTN. However, no research has been done on the therapeutic efficacy of RC in the treatment of EHTN. Therefore, the present study was designed to evaluate the safety and efficacy of RC in the treatment of EHTN. MATERIALS AND METHODS: The multicentre single arm trial was conducted at the Regional Ayurveda Research Institutes at Jaipur and Itanagar. A total of 150 individuals who met the screening criteria were enrolled in the trial after obtaining written informed consent. The participants were administered two 500 mg capsules of RC twice daily (2 g daily) with water for 12 weeks. The outcome measures were reduction in blood pressure, improvement in Hamilton Anxiety Rating Scale Score (HAM-A), SF-36-Health Survey Questionnaire (HSQ), visual analog scale for headache, anxiety, dizziness, tinnitus, fatigue, and amelioration in clinical parameters at every 14-day interval during the trial period of 98 days comprising 84 days of treatment and 14 days of follow-up. RESULTS: The results showed a significant decrease in mean systolic and diastolic blood pressure (P &lt; 0.001). Significant relief (P &lt; 0.001) was also observed in outcome measures such as headache, anxiety, dizziness, fatigue, shortness of breath, palpitation, HAM-A, and HSQ score. Safety parameters such as liver function tests and renal function tests were within the reference range during the study, indicating the therapeutic safety of RC. CONCLUSION: EHTN and its symptoms can be managed with RC. However, double-blind RCTs with adequate sample size may be planned to validate the findings of this study before generalizing the study results.

A systematic review and meta-analysis of the success of blinding in antidepressant RCTs

Successful blinding in double-blind RCTs is crucial for minimizing bias, however studies rarely report information about blinding. Among RCTs for depression, the rates of testing and success of blinding is unknown. We conducted a systematic review and meta-analysis of the rates of testing, predictors, and success of blinding in RCTs of antidepressants for depression. Following systematic search, further information about blinding assessment was requested from corresponding authors of the included studies. We reported the frequency of blinding assessment across all RCTs, and conducted logistic regression analyses to assess predictors of blinding reporting. Participant and/or investigator guesses about treatment allocation were used to calculate Bang's Blinding Index (BI). The BI between RCT arms was compared using meta-analysis. Across the 295 included trials, only 4.7% of studies assessed blinding. Pharmaceutical company sponsorship predicted blinding assessment; unsponsored trials were more likely to assess blinding. Meta-analysis suggested that blinding was unsuccessful among participants and investigators. Results suggest that blinding is rarely assessed, and often fails, among RCTs of antidepressants. This is concerning considering controversy around the efficacy of antidepressant medication. Blinding should be routinely assessed and reported in RCTs of antidepressants, and trial outcomes should be considered in light of blinding success or failure.

Combination of ipratropium bromide and salbutamol in children and adolescents with asthma: A meta-analysis.

BackgroundA combination of ipratropium bromide (IB) and salbutamol is commonly used to treat asthma in children and adolescents; however, there has been a lack of consistency in its usage in clinical practice.ObjectiveTo evaluate the efficacy and safety of IB + salbutamol in the treatment of asthma in children and adolescents.MethodsThe MEDLINE, Embase, and Cochrane Library as well as other Chinese biomedical databases (including China Biological Medicine Database, Chinese National Knowledge Infrastructure, Chongqing VIP, and Wanfang Chinese language bibliographic database) were systematically searched from the earliest record date to September 2020 for randomized controlled trials in children and adolescents (≤18 years) with asthma who received IB + salbutamol or salbutamol alone. The primary outcomes included hospital admission and adverse events. A random effects model with a 95% confidence interval (CI) was used. Subgroup analysis was performed according to age, severity of asthma, and co-interventions with other asthma controllers. This study was registered with PROSPERO.ResultsOf the 1061 studies that were identified, 55 met the inclusion criteria and involved 6396 participants. IB + salbutamol significantly reduced the risk of hospital admission compared with salbutamol alone (risk ratio [RR] 0.79; 95% CI 0.66–0.95; p = 0.01; I2 = 40%). Subgroup analysis only showed significant difference in the risk of hospital admission in participants with severe asthma exacerbation (RR 0.73; 95% CI 0.60–0.88; p = 0.0009; I2 = 4%) and moderate-to-severe exacerbation (RR 0.69; 95% CI 0.50–0.96; p = 0.03; I2 = 3%). There were no significant differences in the risk of adverse events between IB + salbutamol group and salbutamol alone group (RR 1.77; 95% CI 0.63–4.98).ConclusionIB + salbutamol may be more effective than salbutamol alone for the treatment of asthma in children and adolescents, especially in those with severe and moderate to severe asthma exacerbation. The very low to high quality of evidence indicated that future well-designed double-blind RCTs with large sample are needed for research on evaluating the effectiveness of IB + salbutamol treatment for asthma in children and adolescents.

Clinician certainty with the evidence: In practice, it's complicated

Clinician certainty with the evidence: In practice, it's complicated