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Contains fulltext : 237435.pdf (Publisher’s version ) (Open Access) Objective: We evaluated reporting completeness and transparency in randomised controlled trials (RCTs) conducted using administrative data based on 2021 CONSORT Extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study Design and Setting: MEDLINE and the Cochrane Methodology Register were searched (2011 and 2018). Eligible RCTs used administrative databases for identifying eligible participants or collecting outcomes. We evaluated reporting based on CONSORT-ROUTINE, which modified eight items from CONSORT 2010 and added five new items. Results: Of 33 included trials (76% used administrative databases for outcomes, 3% for identifying participants, 21% both), most were conducted in the United States (55%), Canada (18%), or the United Kingdom (12%). Of eight items modified in the extension; six were adequately reported in a majority (>50%) of trials. For the CONSORT-ROUTINE modification portion of those items, three items were reported adequately in >50% of trials, two in

Background Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Introduction The efficacy of Nigella sativa supplementation for asthma control remains controversial. We have conducted a systematic review and meta-analysis to explore the influence of Nigella sativa supplementation on asthma control. Material and methods We have searched PubMed, EMBASE, Web of science, EBSCO, and Cochrane library databases through June 2019 for randomized controlled trials (RCTs) assessing the efficacy of Nigella sativa supplementation for asthma control. Results Four RCTs are included in the meta-analysis. Overall, compared with the control group for asthma, Nigella sativa supplementation is associated with the increased ACT scores (SMD = 0.50; 95% CI: 0.11-0.88; p = 0.01), and FEV1 (SMD = 1.84; 95% CI: 0.07-3.60; p = 0.04), but demonstrates no obvious impact on PEF (SMD = 3.11; 95% CI: -1.30 to 7.52; p = 0.17), IL-4 (SMD = -0.31; 95% CI: -1.21 to 0.59; p = 0.50), or IFN-γ (SMD = 1.11; 95% CI: -0.44 to 2.67; p = 0.16). Conclusions Nigella sativa supplementation may provide additional benefits for the treatment of asthma.

Digital therapeutics is a new approach to treat hypertension via using software programs such as smartphone apps and/or device algorithms. We develop a HERB system—new interactive smartphone app (HERB Mobile) with web‐based patient management console (HERB Console)—to lower blood pressure (BP) based on an algorithm that helps users to promote lifestyle modifications in conjunction with medically validated non‐pharmacological interventions. The app can assess the personalities, behavior characteristics, and hypertension determinants of each patient with hypertension to provide adequate guidance. To demonstrate the efficacy of the system, we designed a randomized, controlled, multicenter, open‐label trial “HERB‐DH1 (HERB digital hypertension 1)” to assess the efficacy of HERB system in patients with essential hypertension. The authors allocate patients to the intervention group (HERB system + standard lifestyle modification) or to the control group (standard lifestyle modification alone). In the intervention group, we provide the HERB Mobile for patients and the HERB Console for their primary physicians for 24 weeks. Both groups are instructed for standard lifestyle modifications based on the current recommendations in the Japanese Society of Hypertension 2019 guideline. The primary outcome is the mean change from baseline to 12 weeks in 24‐hour systolic BP measured by ambulatory BP monitoring. We started this study in December of 2019, and the trial results will be expected in early 2021. We believe that this trial enables us to verify the efficacy of the HERB system in patients with essential hypertension.

Objective: To compare the incidence and severity of diarrhea among different tumor types and treatment regimens, and also compared with CTLA-4 inhibitors in randomized controlled trials. Methods: MEDLINE, PMC database and EMBASE were retrieved until December 2018. Studies were eligible if they were randomized controlled trials and included participants undergoing PD-1/PD-L1 inhibitors for cancer, measured a treatment side effect of diarrhea, and reported quantitative data. The risks of diarrhea in PD-1/PD-L1 inhibitors were compared among different treatment regimens. Results: Totally 21 studies involving 11554 patients were included for meta-analysis. For all-grade diarrhea, the risk after the PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor combination was 1.90 times significantly higher than that of monotherapy, and the risk was 0.69 and 0.60 times significantly lower than that of monotherapy compared with chemotherapy and ipilimumab. The incidence of diarrhea was not significantly different between PD-1/PD-L1 inhibitor monotherapy versus placebo or between low-doses versus high-doses. For high-grade (grade ≥ 3) diarrhea, the risk after the PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor combination was 3.29 times significantly higher than that of monotherapy, the risk in PD-1/PD-L1 inhibitors monotherapy was 0.50 and 0.38 times significantly lower than chemotherapy and ipilimumab respectively. No significant difference was found in the incidence of diarrhea between PD-1/PD-L1 inhibitor monotherapy versus placebo or between low-doses versus high-doses whether in all-grade or high-grade group. Conclusions: PD-1/PD-L1 inhibitors have a lower risk of developing diarrhea than chemotherapy and CTLA-4 inhibitor. There is no direct relationship between the dose of PD-1/PD-L1 inhibitors and the risk of developing diarrhea.

Introduction The influence of mometasone furoate for paediatric asthma remains controversial. Aim We conducted a systematic review and meta-analysis to explore the efficacy and safety of mometasone furoate for paediatric asthma. Material and methods We have searched PubMed, Embase, Web of science, EBSCO, and Cochrane library databases through October 2019 for randomized controlled trials assessing the effect of mometasone furoate versus placebo for paediatric asthma. This meta-analysis was performed using the random-effects model. Results Four RCTs were included in the meta-analysis. Overall, as compared to placebo for paediatric asthma, mometasone furoate is associated with substantially increased predicted forced expiratory volume in 1 s (FEV1) (mean difference (MD) = 7.53; 95% CI: 7.02-8.04; p < 0.00001), FEV1 (MD = 0.11; 95% CI: 0.10-0.12; p < 0.00001), and morning peak expiratory flow (AM PEF) (MD = 17.70; 95% CI: 9.91-25.49; p < 0.00001), but demonstrates no obvious effect on pharyngitis (RR = 0.96; 95% CI: 0.59-1.58; p = 0.89), upper respiratory tract infections (RR = 0.73; 95% CI: 0.50-1.05; p = 0.09), or adverse events (RR = 1.05; 95% CI: 0.84-1.31; p = 0.69). Conclusions Mometasone furoate may be effective and safe for paediatric asthma.

Objective: With the increasing recognition of the over-diagnosis and over-treatment of prostate cancer (PCa), the choice of a better prostate biopsy strategy had confused both the patients and clinical surgeons. Hence, this network meta-analysis was conducted to clarify this question. Methods: In the current network meta-analysis, twenty eligible randomized controlled trials (RCTs) with 4,571 participants were comprehensively identified through Pubmed, Embase and Web of Science databases up to July 2017. The pooled odds ratio (OR) with 95% credible interval (CrI) was calculated by Markov chain Monte Carlo methods. A Bayesian network meta-analysis was conducted by using R-3.4.0 software with the help of package “gemtc” version 0.8.2. Results: Six different PCa biopsy strategies and four clinical outcomes were ultimately analyzed in this study. Although, the efficacy of different PCa biopsy strategies by ORs with corresponding 95% CrIs had not yet reached statistical differences, the cumulative rank probability indicated that overall PCa detection rate from best to worst was FUS-GB plus TRUS-GB, FUS-GB, CEUS, MRI-GB, TRUS-GB and TPUS-GB. In terms of clinically significant PCa detection, CEUS, FUS-GB or FUS-GB plus TRUS-GB had a higher, whereas TRUS-GB or TPUS-GB had a relatively lower significant detection rate. Meanwhile, TPUS-GB or TRUS-GB had a higher insignificant PCa detection rate. As for TRUS-guided biopsy, the general trend was that the more biopsy cores, the higher overall PCa detection rate. As for targeted biopsy, it could yield a comparable or even a better effect with fewer cores, compared with traditional random biopsy. Conclusion: Taken together, in a comprehensive consideration of four clinical outcomes, our outcomes shed light on that FUS-GB or FUS-GB plus TRUS-GB showed their superiority, compared with other puncture methods in the detection of PCa. Moreover, TPUS or TRUS-GB was more easily associated with the over-diagnosis and over-treatment of PCa. In addition, targeted biopsy was obviously more effective than traditional random biopsy. The subsequent RCTs with larger sample sizes were required to validate our findings.

// Fei Liang 1, * , Xinmei Guo 2, * , Sheng Zhang 1 , Hongxi Xue 3 , Qiang Chen 4 and Xichun Hu 1 1 Shanghai Cancer Center and Shanghai Medical College, Fudan University, Shanghai, China 2 Interventional treatment unit, Shandong Chest Hospital, Jinan, China 3 Rizhao City Hospital of Traditional Chinese Medicine, Rizhao, China 4 Department of Clinical Biochemistry, School of Public Health Taishan Medical University, Taian, China * These authors share first co-authorship of this study Correspondence to: Sheng Zhang, email: wozhangsheng@hotmail.com Keywords: primary endpoints, protocols, randomized controlled trials, cancer Received: June 21, 2017 Accepted: September 18, 2017 Published: October 03, 2017 ABSTRACT Background: Decisions by leading journals to require trial registration and to make protocols of phase III randomized clinical trials (RCTs) publicly accessible were landmark events in clinical trial reporting. Materials and Methods: We identified phase III cancer RCTs published between 2013 and 2015 in New England Journal of Medicine ( NEJM ), The Lancet, The lancet Oncology, JAMA and Journal of Clinical Oncology (JCO). Results: We identified 345 reports of phase III RCTs of which 217 (62.9%) had available protocols. The availability rates for NEJM , The Lancet, The Lancet Oncology, JAMA and JCO were 98.0%, 33.3%, 22.7%, 55.6% and 88.3%, respectively. Journal and publication year were significantly associated with protocol availability. Eight of 215 trials (3.7%) with English language protocols had a discrepancy in primary endpoints between publication and protocol. Discrepancies of primary endpoints between protocol and registration existed in 16 (7.7%) of 209 trials. Conclusions: The policy of providing protocols with articles reporting RCTs has not been enforced rigorously. Selective reporting of primary endpoints only remains in a small fraction of phase III trials. Further improvement in consistency between primary endpoints registered and that in protocol is necessary.

// Helei Jia 1 , Changqing Lu 1 and Panli Sun 2 1 Department of Emergency, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province 450002, China 2 Department of Cardiology, Henan Provincial Hospital, Zhengzhou, Henan Province 450000, China Correspondence to: Changqing Lu, email: lcq0217@163.com Keywords: percutaneous coronary intervention, acute coronary syndrome, randomized controlled trials, tirofiban Received: May 17, 2017 Accepted: June 30, 2017 Published: July 12, 2017 ABSTRACT We assessed the efficacy and safety of tirofiban intracoronary versus intravenous administration during percutaneous coronary intervention for patients with acute coronary syndrome. The databases of PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang Database were retrieved. A total of 437 articles were found, according to inclusive and exclusive criteria, 13 of which were finally included. Compared with subjects with intravenous administration, those with intracoronary administration were more likely to reach thrombolysis in myocardial infarction trial grade 3 flow (relative risk = 1.17, 95% confidence interval: 1.11–1.22), improve left ventricular ejection fraction (Standardized mean difference = 0.65, 95% confidence interval: 0.20–1.11). Intracoronary administration resulted in a reduced risk of major adverse cardiovascular events at 30-day follow-up (relative risk = 0.47, 95% confidence interval: 0.34–0.65). However, incidence of bleeding complications was not statistically significant between two groups (relative risk = 0.76, 95% confidence interval: 0.55–1.04). Intracoronary administration of tirofiban can be more effective in increasing coronary blood flow and microvascular perfusion, more effective in improving postoperative myocardial reperfusion, more significantly in reducing the incidence of adverse cardiovascular events at 30-day’s follow-up and improving the prognosis after percutaneous coronary intervention without increasing the risk of bleeding.

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD.ObjectiveWe sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD.MethodsWe conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English.ResultsIn all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application.LimitationsWe included RCT data only.ConclusionThis review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.

// Jie Liu 1 , Feixiang Yuan 1 , Jian Gao 2 , Boer Shan 3 , Yulan Ren 3 , Huaying Wang 3 and Ying Gao 1 1 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China 2 Nutrition Department, Affiliated Zhongshan Hospital of Fudan University, Shanghai, China 3 Department of Female Tumor, Fudan University Shanghai Cancer Center, Shanghai, China Correspondence to: Ying Gao, email: // Keywords : isoflavone supplementation, endometrial thickness, meta-analysis, randomized controlled trials, Gerotarget Received : January 25, 2016 Accepted : February 23, 2016 Published : March 07, 2016 Abstract Background: Isoflavone from soy and other plants modulate hormonal effects in women, and the hormone disorder might result in different caners including endometrial cancer. However, it’s effect on the risk of endometrial cancer is still inconclusive. We aimed to assess the effects of isoflavone on endometrial thickness, a risk factor of endometrial cancer in peri- and post-menopausal women. Methods: A meta-analysis of randomized controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endometrial thickness in peri- and post-menopausal women. Electronic searches were performed on the PubMed, Embase, the Cochrane Library, web of science, CINAHL, and WHO ICTRP to August 1 st , 2015. Reviews and reference lists of relevant articles were also searched to identify more studies. Summary estimates of standard mean differences (SMD’s) and 95%CIs were obtained with random-effects models. Heterogeneity was evaluated with meta-regression and stratified analyses. Results: A total of 23 trials were included in the current analysis. The overall results did not show significant change of endometrial thickness after oral isoflavone supplementation (23 studies, 2167subjects; SMD:-0.05; 95%CI:-0.23, 0.13; P =0.60). Stratified analysis suggested that a daily dose of more than 54mg could decrease the endometrial thickness for 0.26mm (10 trials, 984subjects; SMD:-0.26; 95%CI:-0.45, -0.07; P =0.007). Furthermore, isoflavone supplementation significantly decrease the endometrial thickness for 0.23mm in North American studies (7 trials, 726 subjects; SMD:-0.23; 95%CI:-0.44, -0.01; P =0.04), but it suggested an increase for 0.23mm in Asian studies (3 trials, 224 subjects; SMD: 0.23; 95%CI:-0.04, 0.50; P =0.10). Conclusion: Oral isoflavone supplementation might have different effects in different populations and at different daily doses. Multiple-centre, larger, and long-term trials are deserved to further evaluate its effect.

Background Wearable trackers are an increasingly popular tool among healthy adults and are used to facilitate self-monitoring of physical activity. Objective We aimed to systematically review the effectiveness of wearable trackers for improving physical activity and weight reduction among healthy adults. Methods This review used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology and reporting criteria. English-language randomized controlled trials with more than 20 participants from MEDLINE, CINAHL, Cochrane Library, Web of Science, PubMed, and Scopus (2000-2017) were identified. Studies were eligible for inclusion if they reported an intervention group using wearable trackers, reporting steps per day, total moderate-to-vigorous physical activity, activity, physical activity, energy expenditure, and weight reduction. Results Twelve eligible studies with a total of 1693 participants met the inclusion criteria. The weighted average age was 40.7 years (95% CI 31.1-50.3), with 64.4% women. The mean intervention duration was 21.4 weeks (95% CI 6.1-36.7). The usage of wearable trackers was associated with increased physical activity (standardized mean difference 0.449, 95% CI 0.10-0.80; P=.01). In the subgroup analyses, however, wearable trackers demonstrated no clear benefit for physical activity or weight reduction. Conclusions These data suggest that the use of wearable trackers in healthy adults may be associated with modest short-term increases in physical activity. Further data are required to determine if a sustained benefit is associated with wearable tracker usage.

Background Adolescents who self-harm are often unsure how or where to get help. We developed a Web-based personalized decision aid (DA) designed to support young people in decision making about seeking help for their self-harm. Objective The aim of this study was to evaluate the feasibility and acceptability of the DA intervention and the randomized controlled trial (RCT) in a school setting. Methods We conducted a two-group, single blind, randomized controlled feasibility trial in a school setting. Participants aged 12 to 18 years who reported self-harm in the past 12 months were randomized to either a Web-based DA or to general information about mood and feelings. Feasibility of recruitment, randomization, and follow-up rates were assessed, as was acceptability of the intervention and study procedures. Descriptive data were collected on outcome measures examining decision making and help-seeking behavior. Qualitative interviews were conducted with young people, parents or carers, and staff and subjected to thematic analysis to explore their views of the DA and study processes. Results Parental consent was a significant barrier to young people participating in the trial, with only 17.87% (208/1164) of parents or guardians who were contacted for consent responding to study invitations. Where parental consent was obtained, we were able to recruit 81.7% (170/208) of young people into the study. Of those young people screened, 13.5% (23/170) had self-harmed in the past year. Ten participants were randomized to receiving the DA, and 13 were randomized to the control group. Four-week follow-up assessments were completed with all participants. The DA had good acceptability, but qualitative interviews suggested that a DA that addressed broader mental health problems such as depression, anxiety, and self-harm may be more beneficial. Conclusions A broad-based mental health DA addressing a wide range of psychosocial problems may be useful for young people. The requirement for parental consent is a key barrier to intervention research on self-harm in the school setting. Adaptations to the research design and the intervention are needed before generalizable research about DAs can be successfully conducted in a school setting. Trial Registration International Standard Randomized Controlled Trial registry: ISRCTN11230559; http://www.isrctn.com/ISRCTN11230559 (Archived by WebCite at http://www.webcitation.org/6wqErsYWG)

// Changqing Lu 1 , Helei Jia 1 and Zhentao Wang 2 1 Department of Emergency, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province 450002, China 2 Department of Cardiovascular Disease, Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province 450002, China Correspondence to: Zhentao Wang, email: wangzhentaodoc@126.com Keywords: percutaneous coronary intervention, atorvastatin, intervention, meta-analysis, randomized controlled trials Abbreviation: PCI, percutaneous coronary intervention Received: April 18, 2017 Accepted: June 19, 2017 Published: July 31, 2017 ABSTRACT We systematically searched in PubMed, Web of Science, Embase and China National Knowledge Infrastructure from the inception to March 31, 2017, identified relevant trials about efficacy of high-does Atorvastatin for patients with percutaneous coronary intervention. Twelve studies with the number of 2801 patients were included in the meta-analysis. Compared with control group, high-does Atorvastatin significantly reduced the risk of myocardial infarction in patients with percutaneous coronary intervention (Relative risk =0.62, 95% confidence interval: 0.49-0.78), with low level of heterogeneity (I 2 =22.6%, P=0.228). Nine studies with 2248 patients reported the adverse cardiovascular events. A fixed-effect model was applied. Compared with control group, patients with high-does Atorvastatin taken, the risk of adverse cardiovascular events was degraded by 65% (Relative risk, RR=0.65, 95% confidence interval (CI): 0.50-0.84), which was confirmed by trial sequential analysis as the cumulative Z curve entered the futility area. The subgroup analyses found that decreased risks of myocardial infarction among trails (RR=0.64, 95%CI: 0.50-0.83, RR=0.55, 95%CI: 0.34-0.88). Egger and Begg’s test found no publication bias (t=-1.670, P =0.129; Z=1.560, P =0.119). The use of high-dose Atorvastatin could reduce the risk of myocardial infraction and cardiovascular adverse events in patients with percutaneous coronary intervention. High-dose Atorvastatin was recommended as an adjunct to aid percutaneous coronary intervention.

Infliximab, an inhibitor of TNF-α, is one of the most widely used biological disease-modifying antirheumatic drugs. Recent studies indicated that baseline serum TNF-α could be considered as a key indicator for optimal dosing of infliximab for RA treatment to achieve the clinical response and its sustained remission. The Remission induction by Raising the dose of Remicade in RA (RRRR) study is an open-label, parallel group, multicenter randomized controlled trial to compare the proportions of clinical remission based on the simplified disease activity index (SDAI) after 1 year of treatment and its sustained remission rate after another 1 year between the investigational treatment strategy (for which the dose of infliximab was chosen based on the baseline serum TNF) and the standard strategy of 3 mg/kg per 8 weeks of infliximab administration in infliximab-naïve patients with RA showing an inadequate response to MTX. The primary endpoint is the proportion of patients who kept discontinuation of infliximab 1 year after discontinued infliximab at the time of 54 weeks after the first administration of infliximab. The secondary endpoints are the proportion of clinical remission based on SDAI and changes in SDAI from baseline at each time point, other clinical parameters, quality of life measures and adverse events. Target sample size of randomized patients is 400 patients in total. The main results of the RRRR study are expected to be published at the end of 2017.

// Cheng Qian 1 , Hong Feng 1 , Jianlei Cao 1 , Guangyu Zhang 1 and Yanggan Wang 1 1 Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China Correspondence to: Yanggan Wang, email: wb000813@whu.edu.cn Keywords: intravascular ultrasound, drug-eluting stents, meta-analysis, trial sequential analysis, randomized controlled trials Received: July 28, 2016 Accepted: July 11, 2017 Published: July 27, 2017 ABSTRACT Objective: Previous evidence suggested that intravascular ultrasound (IVUS) guidance could improve outcomes after drug-eluting stents (DES) placement, largely driven by data from observational studies. We, therefore, performed a meta-analysis and trial sequential analysis of randomized controlled trials to overcome this limitation. Results: The retrieval process yielded 7 RCTs with 3,192 patients. Compared to the angiography guidance, IVUS-guided DES implantation was associated with a significant reduction in the major adverse cardiac events (MACE) (OR 0.60, 95% CI 0.46-0.78; P < 0.001), target vessel revascularization (OR 0.60, 95% CI 0.40-0.91; P = 0.02) and target lesion revascularization (OR 0.60, 95% CI 0.42-0.85; P = 0.004). IVUS and conventional angiography guidance showed similar incidence of stent thrombosis (ST) (OR 0.56, 95% CI 0.25-1.23; P = 0.15), cardiac death (OR 0.47, 95% CI 0.19-1.15; P = 0.10) and myocardial infarction (OR 0.85, 95% CI 0.45-1.61; P = 0.62). Trial sequential analysis revealed a definite reduction in MACE with IVUS guidance without solid evidence for ST. Materials and Methods: A systematical literature search was performed in the databases of PubMed, the Cochrane Library and ClinicalTrials. gov , complemented with reference screening from relevant articles. Primary endpoints were MACE and ST. Conclusions: IVUS-guided DES implantation is associated with a lower risk of MACE and revascularization without conclusive benefits for ST.

// Xiao-Hua Zhang 1 , Shuai Hao 1 , Bo Gao 1 , Wu-Guo Tian 1 , Yan Jiang 1 , Shu Zhang 1 , Ling-Ji Guo 1 , Dong-Lin Luo 1 1 Department of Breast, Thyroid Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, P.R. China Correspondence to: Dong-lin Luo, email: luodonglin50@163.com Keywords: metastatic/advanced breast cancer, chemotherapy, toxicity, randomized controlled trials, bayesian network model Received: June 08, 2016 Accepted: October 17, 2016 Published: November 02, 2016 ABSTRACT Objective: To compare the incidence of toxicity of 8 different chemotherapy regimens, including doxorubicin + paclitaxel, doxorubicin, capecitabine, CMF (cyclophosphamide + methotrexate + 5-fluorouracil), FAC (fluorouracil + doxorubicin + cyclophosphamide), doxorubicin + docetaxel, doxorubicin + cyclophosphamide and paclitaxel in the treatment of metastatic/advanced breast cancer. Results: This network meta-analysis included 8 randomized controlled trials (RCTs). The findings revealed that, with regard to capecitabine alone regimen exhibited higher incidence of nausea/vomiting than doxorubicin + paclitaxel regimen, doxorubicin alone regimen and paclitaxel alone regimen in the treatment of patients with metastatic/advanced breast cancer (OR = 32.48, 95% CI = 1.65~2340.57; OR = 22.75, 95% CI = 1.03~1923.52; OR = 59.63, 95% CI = 2.22~5664.88, respectively). Furthermore, doxorubicin + cyclophosphamide regimen had lower incidence of febrile neutropenia than doxorubicin + docetaxel (OR = 0.17, 95% CI = 0.03~0.96). No significant difference in the incidence of stomatitis was observed among eight chemotherapy regimens. Materials and methods: We initially searched PubMed, Cochrane Library and Embase databases from the founding of these databases to January 2016. Eligible studies investigating the 8 different chemotherapy regimens for treatment of metastatic/advanced breast cancer were included for direct and indirect comparison. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the incidence of toxicity among eight chemotherapy regimens were analyzed. Conclusions: Capecitabine alone regimen and doxorubicin + docetaxel regimen may have a more frequent toxicity in the treatment of metastatic/advanced breast cancer.

Background: Chemoprevention could significantly reduce cancer burden. Assessment of efficacy and risk/benefit balance is at best achieved through randomized clinical trials. Methods: At a periodic health examination center 1463 adults were asked to complete a questionnaire about their willingness to be involved in different kinds of preventive clinical trials. Results: Among the 851 respondents (58.2%), 228 (26.8%) agreed to participate in a hypothetical chemoprevention trial aimed at reducing the incidence of lung cancer and 116 (29.3%) of 396 women agreed to a breast cancer chemoprevention trial. Randomization would not restrain participation (acceptability rate: 87.7% for lung cancer and 93.0% for breast cancer). In these volunteers, short-term trials (1 year) reached a high level of acceptability: 71.5% and 73.7% for lung and breast cancer prevention respectively. In contrast long-term trials (5 years or more) were far less acceptable: 9.2% for lung cancer (OR=7.7 CI95% 4.4-14.0) and 10.5 % for breast cancer (OR=6.9 CI95% 3.2-15.8). For lung cancer prevention, the route of administration impacts on acceptability with higher rate 53.1% for a pill vs. 7.9% for a spray (OR=6.7 CI95% 3.6-12.9). Conclusion: Overall healthy individuals are not keen to be involved in chemo-preventive trials, the design of which could however increase the acceptability rate.

There is as yet no consensus as to the best choice among the three treatment options (maintenance, complete chemotherapy-free intervals [CFIs], and continuous) for metastatic colorectal cancer (CRC). We performed a meta-analysis of six trials (N = 2, 454 patients) to compare the safety and efficacy of those three treatment strategies. Maintenance appeared to offer an advantage over CFI with respect to progression-free survival (PFS) (hazard ratio [HR]: 0.53, 95% confidence interval [CI], 0.40-0.69). PFS and overall survival (OS) were comparable between the maintenance and continuous strategies (HR: 1.18, 95% CI, 0.96-1.46; HR: 1.05, 95% CI, 0.98-1.27, respectively), as was OS between the maintenance and CFI strategies (HR: 0.84; 95% CI, 0.70-1.00). The incidence of grade 3/4 toxicity, including neutropenia, neuropathy, hand-foot syndrome and fatigue, was lower with maintenance than with continuous therapy. A maintenance regimen utilizing bevacizumab-based doublets appeared to confer a slight advantage over bevacizumab monotherapy with respect to PFS (P = 0.011). Maintenance appeared to reduce cumulative grade 3/4 toxicity as compared to the continuous strategy, while showing comparable efficacy. Bevacizumab-based doublets appeared to be of particular value in patients with metastatic CRC.

Background: Evidence of benefit for telehealth for chronic conditions is mixed. Two linked randomized controlled trials tested the Healthlines Service for 2 chronic conditions: depression and high risk of cardiovascular disease (CVD). This new telehealth service consisted of regular telephone calls from nonclinical, trained health advisers who followed standardized scripts generated by interactive software. Advisors facilitated self-management by supporting participants to use Web-based resources and helped to optimize medication, improve treatment adherence, and encourage healthier lifestyles. Participants were recruited from primary care. The trials identified moderate (for depression) or partial (for CVD risk) effectiveness of the Healthlines Service. Objective: An embedded qualitative study was undertaken to help explain the results of the 2 trials by exploring mechanisms of action, context, and implementation of the intervention. Methods: Qualitative interview study of 21 staff providing usual health care or involved in the intervention and 24 patients receiving the intervention. Results: Interviewees described improved outcomes in some patients, which they attributed to the intervention, describing how components of the model on which the intervention was based helped to achieve benefits. Implementation of the intervention occurred largely as planned. However, contextual issues in patients’ lives and some problems with implementation may have reduced the size of effect of the intervention. For depression, patients’ lives and preferences affected engagement with the intervention: these largely working-age patients had busy and complex lives, which affected their ability to engage, and some patients preferred a therapist-based approach to the cognitive behavioral therapy on offer. For CVD risk, patients’ motivations adversely affected the intervention whereby some patients joined the trial for general health improvement or from altruism, rather than motivation to make lifestyle changes to address their specific risk factors. Implementation was not optimal in the early part of the CVD risk trial owing to technical difficulties and the need to adapt the intervention for use in practice. For both conditions, enthusiastic and motivated staff offering continuity of intervention delivery tailored to individual patients’ needs were identified as important for patient engagement with telehealth; this was not delivered consistently, particularly in the early stages of the trials. Finally, there was a lack of active engagement from primary care. Conclusions: The conceptual model was supported and could be used to develop further telehealth interventions for chronic conditions. It may be possible to increase the effectiveness of this, and similar interventions, by attending to the human as well as the technical aspects of telehealth: offering it to patients actively wanting the intervention, ensuring continuity of delivery by enthusiastic and motivated staff, and encouraging active engagement from primary care staff. [J Med Internet Res 2016;18(6):e163]

Antimicrobial peptides represent an important component of the innate immune defenses of living organisms, including humans. They are broad-spectrum surface-acting agents secreted by the epithelial cells of the body in response to infection. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides. The objectives of the study were to examine if addition of L-isoleucine to oral rehydration salts (ORS) solution would reduce stool output and/or duration of acute diarrhoea in children and induce antimicrobial peptides in intestine. This double-blind randomized controlled trial was conducted at the Dhaka Hospital of ICDDR,B. Fifty male children, aged 6-36 months, with acute diarrhoea and some dehydration, attending the hospital, were included in the study. Twenty-five children received L-isoleucine (2 g/L)-added ORS (study), and 25 received ORS without L-isoleucine (control). Stool weight, ORS intake, and duration of diarrhoea were the primary outcomes. There was a trend in reduction in mean +/- standard deviation (SD) daily stool output (g) of children in the L-isoleucine group from day 2 but it was significant on day 3 (388 +/- 261 vs. 653 +/- 446; the difference between mean [95% confidence interval (CI) (-)265 (-509, -20); p = 0.035]. Although the cumulative stool output from day 1 to day 3 reduced by 26% in the isoleucine group, it was not significant. Also, there was a trend in reduction in the mean +/- SD intake of ORS solution (mL) in the L-isoleucine group but it was significant only on day 1 (410 +/- 169 vs. 564 +/- 301), the difference between mean (95% CI) (-)154 (-288, -18); p = 0.04. The duration (hours) of diarrhoea was similar in both the groups. A gradual increase in stool concentrations of beta-defensin 2 and 3 was noted but they were not significantly different between the groups. L-isoleucine-supplemented ORS might be beneficial in reducing stool output and ORS intake in children with acute watery diarrhoea. A further study is warranted to substantiate the therapeutic effect of L-isoleucine.

Community-based data relating to factors influencing zinc deficiency among preschool children in India are inadequate. Data of a large, double-blinded, randomized, controlled zinc-supplementation trial were used for assessing the descriptive epidemiology of zinc deficiency among children aged 6-35 months (n = 940). In total, 609 children were followed up for 120 days for information on morbidity. Of these children, 116 from the control group belonging to the upper and the lower 25th quartile of plasma zinc status at baseline were selected for assessing the association of zinc deficiency with prospective morbidity. At baseline, demographic, socioeconomic and dietary information was collected, and anthropometric measurements and levels of plasma zinc were assessed. At baseline, 73.3% of the children were zinc-deficient (plasma zinc < 70 microg/dL), of which 33.8% had levels of plasma zinc below 60 microg/dL. A significantly higher risk of morbidity was prevalent among the subjects with lower plasma zinc compared to those with higher levels of plasma zinc.

In a community-based double-blind randomized trial in children aged 6-35 months, both intervention and control groups received a multi-vitamin syrup containing vitamin A, while the intervention group had zinc gluconate (equivalent to 10 mg of elemental zinc) additional in the syrup. There was a significant decrease in diarrhoea and pneumonia in the intervention group. This study was undertaken to investigate if addition of zinc to vitamin A had improved plasma retinol levels, which, in turn, was responsible for the effects observed in the intervention group. In a randomly-selected subsample of 200 children--100 each from the intervention and the control group, plasma retinol levels after 120 days of supplementation were measured. There was no difference in the mean plasma retinol levels [the difference in the mean 0.46 microg/dL (95% confidence interval -1.42-2.36)] between the two groups following supplementation. No difference in plasma retinol levels was observed in the subgroups based on base-line nutritional status and plasma zinc levels. Addition of zinc to low-dose vitamin A in this study did not improve the vitamin A status of children and cannot explain morbidity effects of the intervention.

BACKGROUND: Online computer-tailored smoking cessation programs have not yet been compared directly. OBJECTIVE: To compare the efficacy of two Internet-based, computer-tailored smoking cessation programs. METHODS: Randomized controlled trial conducted in 2003-2004. Visitors to a smoking cessation website were randomly assigned to either an original online, interactive smoking cessation program or to a modified program. Both programs consisted of tailored, personalized counseling letters based on participants' characteristics, followed by monthly email reminders. The original program was based on psychological and addiction theory, and on preliminary research conducted in the same population. The modified program was shorter and contained more information on nicotine replacement therapy and nicotine dependence, and less information on health risks and coping strategies. In both programs, 1 month and 2 months after entering the study, participants were invited by email to answer the same tailoring questionnaire again in order to receive a second counseling letter. Participants in both programs obtained, on average, 1.2 feedback counseling letters over 2.5 months, and 84% received only 1 feedback letter. The outcome was self-reported smoking abstinence (no puff of tobacco in the previous 7 days), assessed 2.5 months after entry in the program. We report results from intention-to-treat (ITT) analyses, where all non-respondents at follow-up were counted as smokers. RESULTS: The baseline questionnaire was answered by a total of 11969 current (74%) and former (26%) smokers, and the follow-up survey by 4237 people (35%). In an ITT analysis, abstinence rates in baseline current smokers were respectively 10.9% and 8.9% (odds ratio [OR]=1.24, 95% confidence interval [CI]1.08-1.43, P=.003) in the original and modified programs, and 25.2% and 15.7% (OR=1.81, CI 1.51-2.16, P

In 2019, Esther Duflo, Abhijit Banerjee and Michael Kremer were awarded the Nobel Memorial Prize in Economic Sciences “for their experimental approach to alleviating global poverty.” This ap-proach is mainly based on randomized controlled trials (RCTs). Therefore, a goal of the paper is to ana-lyze and review major findings of the Nobel Prize winners and to show directions for their application in Central Asia. The methodology of the paper is based on the analysis of RCTs conducted by the Nobel Prize winners and in Central Asia. The paper finds that there are a lot of factors restricting poverty al-leviation in developing countries, including underdevelopment of educational and healthcare systems. These problems can be addressed using experimental studies in different fields. The paper also reviews the main findings of the Central Asia-based RCTs. Their results were positive in terms of identifying problems and providing solutions that can be useful for further policymaking and can positively affect in-stitutional, educational, healthcare and social issues. The paper shows that the potential priority sectors for the regional RCTs are educational and agricultural policies, where they can be conducted in order to test the efficiency of the existing programs and develop recommendations for future policy improve-ments. However, the RCTs alone are not enough for poverty alleviation and the paper emphasizes on the essential role of economic growth. The paper can be useful for policymakers, who form anti-poverty policy and development programs.

International audience; A fixation on ‘scaling up’ has captured current innovation discourses and, with it, political and economic life at large. Perhaps most visible in the rise of platform technologies, big data and concerns about a new era of monopolies, scalability thinking has also permeated public policy in the search for solutions to ‘grand societal challenges’, ‘mission-oriented innovation’ or transformations through experimental ‘living labs’. In this paper, we explore this scalability zeitgeist as a key ordering logic of current initiatives in innovation and public policy. We are interested in how the explicit preoccupation with scalability reconfigures political and economic power by invading problem diagnoses and normative understandings of how society and social change function. The paper explores three empirical sites – platform technologies, living labs and experimental development economics – to analyze how scalability thinking is rationalized and operationalized. We suggest that social analysis of science and technology needs to come to terms with the ‘politics of scaling’ as a powerful corollary of the ‘politics of technology’, lest we accept the permanent absence from key sites where decisions about the future are made. We focus in on three constitutive elements of the politics of scaling: solutionism, experimentalism and future-oriented valuation. Our analysis seeks to expand our vocabulary for understanding and questioning current modes of innovation that increasingly value scaling as an end in itself, and to open up new spaces for alternative trajectories of social transformation.

Guidelines for designing, conducting, documenting, and reporting human nutrition randomized controlled trials (RCTs) have as yet to be developed and disseminated as reference for investigators, funders, regulators, institutions, assessors, trainees, and others involved in human nutrition research. Diet-related interventions can include diet and/or behavioral manipulation, provision of foods or entire meals, or delivery of dietary components in individual food items or supplements. This Perspective introduces a series of papers that outline core principles for the design and conduct of human nutrition RCTs, documentation and reporting of all aspects of clinical trial management, and data analysis and reporting of results. Human nutrition RCTs have unique considerations delineated in these papers. Conducting them with the highest scientific rigor is essential to the development of evidence-based dietary guidance for promoting optimal health and advancing health care.

Randomized controlled trials are considered the gold standard in assessing treatment regimens, and since abstracts may be the only part of a paper that a physician reads, accurate reporting of data in abstracts is essential. The CONSORT checklist for abstracts was designed to standardize data reporting; however, for papers submitted to anesthesiology journals, the level of adherence to the CONSORT checklist for abstracts is unknown. Therefore, we commend Janackovic and Puljak for their efforts in determining the adherence of reports of trials in the highest-impact anesthesiology journals between 2014 and 2016. The results of their study are extremely important; however, we believe that that study had some methodological limitations, which we discuss in this manuscript.

Objectives: Controlled human infection, the intentional infection of healthy volunteers, allows disease pathogenesis to be studied and vaccines and therapeutic interventions to be evaluated in a controlled setting. A systematic review of randomized controlled trials of countermeasures for influenza that used the experimental human infection platform was performed. The primary objective was to document the scope of trials performed to date and the main efficacy outcome in the trials. The secondary objective was to assess safety and identify serious adverse events. Methods: The PubMed database was searched for randomized controlled influenza human challenge studies with predetermined search terms. Review papers, papers without outcomes, community-acquired infections, duplicated data, pathogenesis studies, and observational studies were excluded. Results: Twenty-six randomized controlled trials published between 1947 and 2014 fit the study inclusion criteria. Two-thirds of these trials investigated antivirals and one-third investigated influenza vaccines. Among 2462 subjects inoculated with influenza virus, the incidence of serious adverse events was low (0.04%). These challenge studies helped to down-select three antivirals and one vaccine that were subsequently approved by the US Food and Drug Administration (FDA). Conclusions: Controlled human infection studies are an important research tool in assessing promising influenza vaccines and antivirals. These studies are performed quickly and are cost-effective and safe, with a low incidence of serious adverse events.

The debate on the use and misuse of P values has risen and fallen throughout their almost century-long existence in scientific discovery. Over the past few years, the debate has again received front-page attention, particularly through the public reminder by the American Statistical Association on how P values should be used and interpreted. At the core of the issue lies a fault in the way that scientific evidence is dichotomized and research is subsequently reported, and this fault is exacerbated by researchers giving license to statistical models to do scientific inference. This paper highlights a different approach to handling the evidence collected during a randomized controlled trial, one that does not dichotomize, but rather reports the evidence collected. Through the use of a coin flipping experiment and reanalysis of real-world data, the traditional approach of testing null hypothesis significance is contrasted with a Bayesian approach. This paper is meant to be understood by those who rely on statistical models to draw conclusions from data, but are not statisticians and may therefore not be able to grasp the debate that is primarily led by statisticians.

A number of publishers and funders, including PLOS, have recently adopted policies requiring researchers to share the data underlying their results and publications. Such policies help increase the reproducibility of the published literature, as well as make a larger body of data available for reuse and re-analysis. In this study, we evaluate the extent to which authors have complied with this policy by analyzing Data Availability Statements from 47,593 papers published in PLOS ONE between March 2014 (when the policy went into effect) and May 2016. Our analysis shows that compliance with the policy has increased, with a significant decline over time in papers that did not include a Data Availability Statement. However, only about 20% of statements indicate that data are deposited in a repository, which the PLOS policy states is the preferred method. More commonly, authors state that their data are in the paper itself or in the supplemental information, though it is unclear whether these data meet the level of sharing required in the PLOS policy. These findings suggest that additional review of Data Availability Statements or more stringent policies may be needed to increase data sharing.

SummaryTo highlight methodologic challenges pertinent to design, analysis, and reporting of results of randomized clinical trials in OA and offer practical suggestions to overcome these challenges.The topics covered in this paper include subject selection, randomization, approaches to handling missing data, subgroup analysis, sample size, and issues related to changing design mid-way through the study. Special attention is given to standardizing the reporting of results and economic analyses.Key findings include the importance of blinding and concealment, the distinction between superiority and non-inferiority trials, the need to minimize missing data, and appropriate analysis and interpretation of subgroup effects.Investigators may use the findings and recommendations advanced in this paper to guide design and conduct of randomized controlled trials of interventions for osteoarthritis.

The present paper deals with the problem of evaluating empirical evidence for therapeutic decisions in medicine. The article discusses the views of Nancy Cartwright and John Worrall on the function that randomization plays in ascertaining causal relations with reference to the therapies applied. The main purpose of the paper is to present a general idea of alternative method of evaluating empirical evidence. The method builds on data analysis that makes use of rough set theory. The first attempts to apply the method show that it is an interesting alternative to randomized controlled trials.

This paper summarizes the literature on the impact of state subsidized or social health insurance schemes that have been offered, mostly on a voluntary basis, to the informal sector in low-and middle-income countries. A substantial number of papers provide estimations of average treatment on the treated effect for insured persons. We summarize papers that correct for the problem of self-selection into insurance and papers that estimate the average intention to treat effect. Summarizing the literature was difficult because of the lack of (1) uniformity in the use of meaningful definitions of outcomes that indicate welfare improvements and (2) clarity in the consideration of selection issues. We find the uptake of insurance schemes, in many cases, to be less than expected. In general, we find no strong evidence of an impact on utilization, protection from financial risk, and health status. However, a few insurance schemes afford significant protection from high levels of out-of-pocket expenditures. In these cases, however, the impact on the poor is weaker. More information is needed to understand the reasons for low enrollment and to explain the limited impact of health insurance among the insured. JEL codes: I10, I15. © The Author 2012. Published by Oxford University Press on behalf of the International Bank for Reconstruction and Development/ THE WORLD BANK. All rights reserved.

BackgroundDisorganised attachment patterns in infants have been linked to later psychopathology. Services have variable practices for identifying and providing interventions for families of children with disorganised attachment patterns, which is the attachment pattern leading to most future psychopathology. Several recent government reports have highlighted the need for better parenting interventions in at risk groups.ObjectivesThe objective of this review and meta-analysis was to evaluate the clinical effectiveness of available parenting interventions for families of children at high risk of developing, or already showing, a disorganised pattern of attachment.MethodsPopulation: Studies were included if they involved parents or caregivers of young children with a mean age under 13 years who had a disorganised classification of attachment or were identified as at high risk of developing such problems. Included interventions were aimed at parents or caregivers (e.g. foster carers) seeking to improve attachment. Comparators included an alternative intervention, an attention control, treatment as usual or no intervention. The primary outcome was a disorganised pattern in childhood measured using a validated attachment instrument. Studies that did not use a true Randomised Controlled Trial (RCT) design were excluded from the review. Both published and unpublished papers were included, there were no restrictions on years since publication and foreign language papers were included where translation services could be accessed within necessary timescales.ResultsA comprehensive search of relevant databases yielded 15,298 papers. This paper reports a systematic review as part of an NIHR HTA study identifying studies pre-2012, updated to include all papers to October 2016. Two independent reviewers undertook two stage screening and data extraction of the included studies at all stages. A Cochrane quality assessment was carried out to assess the risk of bias. In total, fourteen studies were included in the review. In a meta-analysis of these fourteen studies the interventions saw less disorganised attachment at outcome compared to the control (OR = 0.50, (0.32, 0.77), p = 0.008). The majority of the interventions targeted maternal sensitivity. We carried out exploratory analyses to examine factors that may influence treatment outcome but these should be treated with caution given that we were limited by small numbers of studies.ConclusionsParenting interventions that target parental sensitivity show promise in reducing disorganised attachment. This is limited by few high quality studies and the fact that most studies are with mothers. More high quality randomised controlled trials are required to elucidate this further.

Objective: To assess whether there has been any improvement in the quality and quantity of randomized controlled trials (RCTs) in nationally published journals through the application of standardized and validated scores. Methods: We electronically selected all RCTs published in the two indexed Brazilian journals that focus on orthopedics, over the period 2000-2009: Acta Ortopedica Brasileira (AOB) and Revista Brasileira de Ortopedia (RBO). These RCTs were identified and scored by two independent researchers in accordance with the Jadad scale and the Cochrane Bone, Joint and Muscle Trauma Group score. The studies selected were grouped as follows: 1) publication period (2000-2004 or 2004-2009); 2) journal of publication (AOB or RBO). Results: Twenty-two papers were selected: 10 from AOB and 12 from RBO. No statistically significant differences were found between the proportions (nRCT/nTotal of published papers) of RCTs published in the two journals (p = 0.458), or in the Jadad score (p = 0.722) and Cochrane score (p = 0.630). Conclusion: The relative quality and quantity of RCTs in the journals analyzed were similar. There was a trend towards improvement of quality, but there was no increase in the number of RCTs between the two periods analyzed.

OBJETIVO: Verificar se houve melhora da qualidade e quantidade dos ensaios clínicos randomizados (ECRs) publicados na literatura nacional, por meio da aplicação de escores estruturados e validados na literatura. MÉTODOS: Selecionamos, eletronicamente, todas as edições das duas revistas indexadas e de escopo ortopédico da literatura nacional - Acta Ortopédica Brasileira (AOB) e Revista Brasileira de Ortopedia (RBO), no período de 2000-2009, todos os ECRs publicados. Dois pesquisadores independentes identificaram e pontuaram os ECRs de acordo com as escalas de JADAD e do grupo de trauma musculoesquelético da Colaboração Cochrane. Os trabalhos selecionados foram agrupados: 1) pelo período de publicação 2000-2004 e 2004-2009; 2) periódico de publicação (AOB e RBO). RESULTADOS: Vinte e dois trabalhos foram selecionados, sendo10 da AOB e 12 da RBO. Não houve diferença entre o número proporcional (nECR/nTotal de trabalhos publicados) de ensaios clínicos randomizados publicados nos dois periódicos (p = 0,458), assim como para os escores de JADAD (p = 0,722) e da Colaboração Cochrane (p = 0,630). CONCLUSÃO: A qualidade e quantidade relativa de ensaios clínicos randomizados nos periódicos analisados foi semelhante. Há uma tendência de melhora da qualidade; contudo, não há acréscimo da quantidade de ensaios clínicos randomizados nos dois períodos analisados. OBJECTIVE: To assess whether there was an improvement in the quality and quantity of randomized controlled trials (RCTs) in nationally published journals through an application of standardized and validated scores. METHODS: We selected, electronically, for the period of 2000-2009, all RCTs published at the two indexed, orthopaedics-focused Brazilian journals: Acta Ortopédica Brasileira(AOB) and Revista Brasileira de Ortopedia (RBO). These RCTs were identified and scored by two independent researchers according to the JADAD scale and Cochrane Bone, Joint and Muscle Trauma Group score. The selected studies were grouped: 1) by publication period (2000-2004 and 2004-2009); 2) journal of publication (AOB and RBO). RESULTS: Twenty-two papers were selected, 10 from AOB and 12 from RBO. No statistically significant differences were found between the proportion (nRCT/nTotal of published papers) of RCTs published in the two journals (p=0.458), as well as for the JADAD score (p=0.722) and Cochrane score (p=0.630). CONCLUSION: The quality and quantity of randomized clinical trials in the period was similar in the journals analyzed. There is a trend of improvement of quality, yet there was no increase in the number of randomized clinical trials in both periods. Universidade Federal de São Paulo (UNIFESP) Departamento de Ortopedia e Traumatologia Universidade Federal de São Paulo (UNIFESP) Departamento de Ortopedia e Traumatologia Setor de Ombro e Cotovelo da Disciplina de Mão e Membro Superior UNIFESP, Depto. de Ortopedia e Traumatologia UNIFESP, Depto. de Ortopedia e Traumatologia Setor de Ombro e Cotovelo da Disciplina de Mão e Membro Superior SciELO

In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research., Author summary In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. We conducted a systematic review to explore the nature and prevalence of spin in the biomedical literature. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research.

Background Diabetes is a chronic disease commonly managed by family physicians, with the most prevalent complication being cardiovascular disease (CVD). Clinical practice guidelines have been developed to support clinicians in the care of diabetic patients. We conducted a pragmatic cluster randomized controlled trial (RCT) of a printed educational toolkit aimed at improving CVD management in diabetes in primary care, and found no effect, and indeed, the possibility of some harm. We conducted a qualitative evaluation to study the strategy for guideline implementation employed in this trial, and to understand its effects. This paper focuses solely on the qualitative findings, as the RCT’s quantitative results have already been reported elsewhere. Methods and Findings All family practices in the province of Ontario had been randomized to receive the educational toolkit by mail, in either the summer of 2009 (intervention arm) or the spring of 2010 (control arm).A subset of 80 family physicians (representing approximately 10% of the practices randomized and approached, with records on 1,592 randomly selected patients with diabetes at high risk for CVD) then took part in a chart audit and reflective feedback exercise related to their own practice in comparison to the guideline recommendations. They were asked to complete two forms (one pre- and one post-audit) in order to understand their awareness of the guidelines pre-trial, their expectations regarding their individual performance pre-audit, and their reflections on their audit results. In addition, individual interviews with thirteen other family physicians were conducted. Textual data from interview transcripts and written commentary from the pre- and post-audit forms underwent qualitative descriptive analysis to identify common themes and patterns. Analysis revealed four main themes: impressions of the toolkit, awareness was not the issue, ‘it’s not me it’s my patients’, and chart audit as a more effective intervention than the toolkit. Participants saw neither the toolkit content nor its dissemination strategy to be effective, indicating they perceived themselves to be aware of the guidelines pre-trial. However, their accounts also indicated that they may be struggling to prioritize CVD management in the midst of competing demands for their attention. Upon receiving their chart audit results, many participants expressed surprise that they had not performed better. They reported that the audit results would be an important motivator for behaviour change. Conclusions The qualitative findings outlined in this paper offer important insights into why the intervention was not effective. They also demonstrate that physicians have unperceived needs relative to CVD management and that the chart audit served to identify shortcomings in their practice of which they had been hitherto unaware. The findings also indicate that new methods of intervention development and implementation should be explored. This is important given the high prevalence of diabetes worldwide; appropriate CVD management is critical to addressing the morbidity and mortality associated with the disease.

Background: Rheumatoid arthritis has the characteristics of slow progression, long course, and repeated attacks. At present, western medicine commonly used in clinical practice not only reduces pain and improves symptoms, but also has more adverse reactions, affecting the health, and life of patients. In ancient China, Huangqi Guizhi Wuwu decoction was used by doctors to treat rheumatoid arthritis, with remarkable effect. In recent years, many clinical studies have also shown that Huangqi Guizhi Wuwu decoction has reliable effect in treating rheumatoid arthritis, but there is no evidence of evidence-based medicine. Therefore, this study aims to systematically evaluate the clinical efficacy and safety of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. Methods: Using computer to retrieve PubMed, The Cochrance Library, Embase, Web of Science, CNKI, VIP and Wanfang database, in addition manually retrieve Google academic and Baidu academic to collect all randomized controlled trials for Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis, including relevant academic journal and conference papers, dissertations, from the establishment of the database to July 2020. After 2 evaluators independently screened the literature, extracted the data, and evaluated the risk of bias included in the study, RevMan5.3 software was used to analyze the data. Results: This research evaluate the efficacy and safety of Huangqi Guizhi Wuwu decoction in treating Rheumatoid arthritis from the aspects of clinical efficacy rate, visual analog scale (VAS), swollen joint count (SJC), morning stiffness time, Rrythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), and adverse reaction incidence. Conclusion: This study will provide reliable evidence for the clinical application of Huangqi Guizhi Wuwu decoction in the treatment of rheumatoid arthritis. Ethics and dissemination: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF Registration number: DOI 10.17605/OSF.IO/RZY3V.

PURPOSE: The CONSORT extension for patient reported outcomes (PROs) aims to improve reporting, but guidance on the optimal integration with clinical data is lacking. This study examines in detail the reporting of PROs and clinical data from randomized controlled trials (RCTs) in gastro-intestinal cancer to inform design and reporting of combined PRO and clinical data from trials to improve the 'take home' message for clinicians to use in practice.MATERIALS AND METHODS: The case study was undertaken in gastro-intestinal cancer trials. Well-conducted RCTs reporting PROs with validated instruments were identified and categorized into those combining PRO and clinical data in a single paper, or those separating data into linked primary and supplemental papers. Qualitative methods were developed to examine reporting of the critical interpretation of the trial results (trial exegesis) in the papers in relation of the PRO and clinical outcomes and applied to each publication category. Results were used to inform recommendations for practice.RESULTS: From 1917 screened abstracts, 49 high quality RCTs were identified reported in 36 combined and 15 linked primary and supplemental papers. In-depth analysis of manuscript text identified three categories for understanding trial exegesis: where authors reported a "detailed", "general", or absent PRO rationale and integrated interpretation of clinical and PRO results. A total of 11 (30%) and 6 (16%) combined papers reported "detailed" PRO rationale and integrated interpretation of results although only 2 (14%) and 1 (7%) primary papers achieved the same standard respectively. Supplemental papers provide better information with 11 (73%) and 3 (20%) achieving "detailed" rationale and integrated interpretation of results. Supplemental papers, however, were published a median of 20 months after the primary RCT data in lower impact factor journals (median 16.8 versus 5.2).CONCLUSION: It is recommended that single papers, with detailed PRO rationale and integrated PRO and clinical data are published to optimize trial exegesis. Further work to examine whether this improves the use of PRO data to inform practice is needed.

Training to ensure good documentation practices and adherence to regulatory requirements in human nutrition randomized controlled trials has not been given sufficient attention. Furthermore, it is difficult to find this information conveniently organized or in a form relevant to nutrition protocols. Current gaps in training and research surveillance exist in clinical nutrition research because training modules emphasize drugs and devices, promote reliance on monitoring boards, and lack nutrition expertise on human nutrition research teams. Additionally, because eating is essential, ongoing, and highly individualized, it is difficult to distinguish risks associated with interventions from eating under free-living conditions. Controlled-feeding trials provide an option to gain more experimental control over food consumed, but at a price of less external validity, and may pose human behavior issues that are unrelated to the intervention. This paper covers many of the expected practices for documentation and regulation that may be encountered in planning and conducting nutrition intervention trials with examples and references that should be useful to clinical nutrition researchers, funders of research, and research institutions. Included are definitions and guidance on clinical nutrition research oversight (institutional review boards, data safety and monitoring boards, US FDA); participant safety; standard operating procedures; training of investigators, staff, and students; and local culture and reporting requirements relevant to diet-related clinical research conduct and documentation.

Background Latina adolescents in the USA report some of the lowest rates of physical activity of any demographic subgroup; this is paralleled by a markedly higher lifetime risk of obesity, type 2 diabetes, and other conditions related to inactivity. Despite this, to date, no fully powered clinical trials have tested physical activity interventions specifically for this population. High use of mobile technologies (including text messages, smartphone apps, and social media) suggests this could be an appropriate intervention channel, while also having potential for broad reach. This paper describes the protocol for Chicas Fuertes, a fully powered randomized trial of a mobile technology-based physical activity intervention for Latina adolescents. Methods We plan to recruit 200 Latina teens (age 13–18) in San Diego, CA, currently engaging in ≤ 150 min/week of moderate-to-vigorous physical activity (MVPA) to be assigned 1:1 to the intervention or control groups. Those randomly assigned to the intervention group receive a one-on-one goal setting session followed by 6 months of mobile technology-based intervention, including a personalized website, Fitbit activity tracker and app, individually tailored text messages based on Fitbit data, and daily intervention content on Instagram. Those randomized to the control group receive only a Fitbit activity tracker. The main outcome is change in weekly minutes of MVPA from baseline to 6 months, measured both objectively (ActiGraph accelerometers and Fitbit Inspire HR) and subjectively (7-Day Physical Activity Recall Interview). Additional outcomes are maintenance of activity change at 12 months and changes in psychosocial constructs, including social support and self-efficacy, engagement with mobile technology channels, and costs of intervention delivery. We are also examining the potential mediators and moderators of the intervention. The efficacy of the intervention is analyzed using a mixed effects regression model, adjusting for any potential confounders not balanced by randomization. All analyses of accelerometer measured MVPA are also adjusted for wear time. Discussion The Chicas Fuertes trial uses widely available mobile technologies to target critical health behavior, physical activity, in Latina teens, a population with a high lifetime risk of lifestyle-related diseases. The results will speak to the efficacy and acceptability of the intervention, which has the potential for broad dissemination. Trial registration ClinicalTrials.govNCT04190225. Registered on November 20, 2019

Policy Points Social policies might not only improve economic well-being, but also health. Health policy experts have therefore advocated for investments in social policies both to improve population health and potentially reduce health system costs. Since the 1960s, a large number of social policies have been experimentally evaluated in the United States. Some of these experiments include health outcomes, providing a unique opportunity to inform evidence-based policymaking. Our comprehensive review and meta-analysis of these experiments find suggestive evidence of health benefits associated with investments in early life, income support, and health insurance interventions. However, most studies were underpowered to detect health outcomes. CONTEXT: Insurers and health care providers are investing heavily in nonmedical social interventions in an effort to improve health and potentially reduce health care costs. METHODS: We performed a systematic review and meta-analysis of all known randomized social experiments in the United States that included health outcomes. We reviewed 5,880 papers, reports, and data sources, ultimately including 61 publications from 38 randomized social experiments. After synthesizing the main findings narratively, we conducted risk of bias analyses, power analyses, and random-effects meta-analyses where possible. Finally, we used multivariate regressions to determine which study characteristics were associated with statistically significant improvements in health outcomes. FINDINGS: The risk of bias was low in 17 studies, moderate in 11, and high in 33. Of the 451 parameter estimates reported, 77% were underpowered to detect health outcomes. Among adequately powered parameters, 49% demonstrated a significant health improvement, 44% had no effect on health, and 7% were associated with significant worsening of health. In meta-analyses, early life and education interventions were associated with a reduction in smoking (odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.86-0.99). Income maintenance and health insurance interventions were associated with significant improvements in self-rated health (OR = 1.20, 95% CI 1.06-1.36, and OR = 1.38, 95% CI 1.10-1.73, respectively), whereas some welfare-to-work interventions had a negative impact on self-rated health (OR = 0.77, 95% CI 0.66-0.90). Housing and neighborhood trials had no effect on the outcomes included in the meta-analyses. A positive effect of the trial on its primary socioeconomic outcome was associated with higher odds of reporting health improvements. We found evidence of publication bias for studies with null findings. CONCLUSIONS: Early life, income, and health insurance interventions have the potential to improve health. However, many of the included studies were underpowered to detect health effects and were at high or moderate risk of bias. Future social policy experiments should be better designed to measure the association between interventions and health outcomes.

Introduction In June 2021, United Nations (UN) Member States committed to ambitious targets for scaling up community-led responses by 2025 toward meeting the goals of ending the AIDS epidemic by 2030. These targets build on UN Member States 2016 commitments to ensure that 30% of HIV testing and treatment programmes are community-led by 2030. At its current pace, the world is not likely to meet these nor other global HIV targets, as evidenced by current epidemiologic trends. The COVID-19 pandemic threatens to further slow momentum made to date. The purpose of this paper is to review available evidence on the comparative advantages of community-led HIV responses that can better inform policy making towards getting the world back on track. Methods We conducted a scoping review to gather available evidence on peer- and community-led HIV responses. Using UNAIDS’ definition of ‘community-led’ and following PRISMA guidelines, we searched peer-reviewed literature published from January 1982 through September 2020. We limited our search to articles reporting findings from randomized controlled trials as well as from quasi-experimental, prospective, pre/post-test evaluation, and cross-sectional study designs. The overall goals of this scoping review were to gather available evidence on community-led responses and their impact on HIV outcomes, and to identify key concepts that can be used to quickly inform policy, practice, and research. Findings Our initial search yielded 279 records. After screening for relevance and conducting cross-validation, 48 articles were selected. Most studies took place in the global south (n = 27) and a third (n = 17) involved youth. Sixty-five percent of articles (n = 31) described the comparative advantage of peer- and community-led direct services, e.g., prevention and education (n = 23) testing, care, and treatment programs (n = 8). We identified more than 40 beneficial outcomes linked to a range of peer- and community-led HIV activities. They include improved HIV-related knowledge, attitudes, intentions, self-efficacy, risk behaviours, risk appraisals, health literacy, adherence, and viral suppression. Ten studies reported improvements in HIV service access, quality, linkage, utilization, and retention resulting from peer- or community-led programs or initiatives. Three studies reported structural level changes, including positive influences on clinic wait times, treatment stockouts, service coverage, and exclusionary practices. Conclusions and recommendations Findings from our scoping review underscore the comparative advantage of peer- and community-led HIV responses. Specifically, the evidence from the published literature leads us to recommend, where possible, that prevention programs, especially those intended for people living with and disproportionately affected by HIV, be peer- and community-led. In addition, treatment services should strive to integrate specific peer- and community-led components informed by differentiated care models. Future research is needed and should focus on generating additional quantitative evidence on cost effectiveness and on the synergistic effects of bundling two or more peer- and community-led interventions.

Background Extended reality, which encompasses virtual reality (VR), augmented reality (AR), and mixed reality (MR), is increasingly used in medical education. Studies assessing the effectiveness of these new educational modalities should measure relevant outcomes using outcome measurement tools with validity evidence. Objective Our aim is to determine the choice of outcomes, measurement instruments, and the use of measurement instruments with validity evidence in randomized controlled trials (RCTs) on the effectiveness of VR, AR, and MR in medical student education. Methods We conducted a systematic mapping review. We searched 7 major bibliographic databases from January 1990 to April 2020, and 2 reviewers screened the citations and extracted data independently from the included studies. We report our findings in line with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Results Of the 126 retrieved RCTs, 115 (91.3%) were on VR and 11 (8.7%) were on AR. No RCT on MR in medical student education was found. Of the 115 studies on VR, 64 (55.6%) were on VR simulators, 30 (26.1%) on screen-based VR, 9 (7.8%) on VR patient simulations, and 12 (10.4%) on VR serious games. Most studies reported only a single outcome and immediate postintervention assessment data. Skills outcome was the most common outcome reported in studies on VR simulators (97%), VR patient simulations (100%), and AR (73%). Knowledge was the most common outcome reported in studies on screen-based VR (80%) and VR serious games (58%). Less common outcomes included participants’ attitudes, satisfaction, cognitive or mental load, learning efficacy, engagement or self-efficacy beliefs, emotional state, competency developed, and patient outcomes. At least one form of validity evidence was found in approximately half of the studies on VR simulators (55%), VR patient simulations (56%), VR serious games (58%), and AR (55%) and in a quarter of the studies on screen-based VR (27%). Most studies used assessment methods that were implemented in a nondigital format, such as paper-based written exercises or in-person assessments where examiners observed performance (72%). Conclusions RCTs on VR and AR in medical education report a restricted range of outcomes, mostly skills and knowledge. The studies largely report immediate postintervention outcome data and use assessment methods that are in a nondigital format. Future RCTs should include a broader set of outcomes, report on the validity evidence of the measurement instruments used, and explore the use of assessments that are implemented digitally.

OBJECTIVE: The purpose of this study was to characterize recent alcohol brief intervention (ABI) efficacy and effectiveness trials, summarize outcomes, and show how variability in outcomes and reporting compromises the evidence base.METHOD: A systematic review and narrative synthesis of articles from 10 databases were undertaken (January 2000-November 2017); study selection represented recent, readily available publications. The National Institute of Care Excellence (NICE) Public Health Guideline 24 (Alcohol use disorders: prevention) informed ABI definitions. The review was conducted using Centre for Reviews and Dissemination (CRD) guidance and pre-registered on PROSPERO (CRD42016047185). Seven a priori specified domains were used to classify outcomes: biomarkers, alcohol-related outcomes, economic factors/resource use, health measures, life impact, intervention factors, and psychological/behavioral factors.RESULTS: The search identified 405 trials from 401 eligible papers. In 405 trials, 2,641 separate outcomes were measured in approximately 1,560 different ways. The most common outcomes used were the number of drinks consumed in a week and frequency of heavy episodic drinking. Biomarkers were least frequently used. The most common primary outcome was weekly drinks. By trial type, the most frequent outcome in efficacy and effectiveness trials was frequency of heavy drinking.CONCLUSIONS: Consumption outcomes predominated; however, no single outcome was found in all trials. This comprehensive outcome map and methodological detail on ABI effectiveness and efficacy trials can aid decision making in future trials. There was a diversity of instruments, time points, and outcome descriptions in methods and results sections. Compliance with reporting guidance would support data synthesis and improve trial quality. This review establishes the need for a core outcome set (COS)/minimum data standard and supports the Outcome Reporting in Brief Interventions: Alcohol initiative (ORBITAL) to improve standards in the ABI field through a COS for effectiveness and efficacy randomized trials.

Background: Correction of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) disorders is the standard of treatment in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), but the side effects and adverse reactions brought by western medicine (WM) are still the main problems. More importantly, the lack of protection of kidney function in the treatment greatly affects the health of patients. Although traditional Chinese medicine (TCM), specifically tonifying kidney and strengthen bone (TKSB) therapy is wildly applied for patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we pretent to conduct this protocol to evaluate the efficacy and safety of TKSB therapy combined with WM for non-dialysis patients with CKD-MBD. Methods: A system research of randomized controlled trials (RCTs) of TKSB therapy for CKD-MBD will be conducted by 2 investigators from 7 electronic databases. Methodological quality evaluations will be performed by using the Cochrane collaboration tool and data analysis will be conducted by RevMan V5.3 software and STATA v15.0. Results: The results of this paper will be submitted to a peer-reviewed journal for publication. Conclusion: This research will determine the safety and efficacy of TKSB therapy in treating non-dialysis patients with CKD-MBD. INPLASY registration number: INPLASY2020120086

Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes.Methods/design: The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18–65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients’ clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes..Discussion: Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes. © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

This article belongs to the Special Issue A Commemorative Issue in Honor of Centennial of the Discovery of Vitamin D-The Central Role of Vitamin D in Physiology., This is a narrative review of the evidence supporting vitamin D’s anticancer actions. The first section reviews the findings from ecological studies of cancer with respect to indices of solar radiation, which found a reduced risk of incidence and mortality for approximately 23 types of cancer. Meta-analyses of observational studies reported the inverse correlations of serum 25-hydroxyvitamin D [25(OH)D] with the incidence of 12 types of cancer. Case-control studies with a 25(OH)D concentration measured near the time of cancer diagnosis are stronger than nested case-control and cohort studies as long follow-up times reduce the correlations due to changes in 25(OH)D with time. There is no evidence that undiagnosed cancer reduces 25(OH)D concentrations unless the cancer is at a very advanced stage. Meta-analyses of cancer incidence with respect to dietary intake have had limited success due to the low amount of vitamin D in most diets. An analysis of 25(OH)D-cancer incidence rates suggests that achieving 80 ng/mL vs. 10 ng/mL would reduce cancer incidence rates by 70 ± 10%. Clinical trials have provided limited support for the UVB-vitamin D-cancer hypothesis due to poor design and execution. In recent decades, many experimental studies in cultured cells and animal models have described a wide range of anticancer effects of vitamin D compounds. This paper will review studies showing the inhibition of tumor cell proliferation, dedifferentiation, and invasion together with the sensitization to proapoptotic agents. Moreover, 1,25-(OH)2D3 and other vitamin D receptor agonists modulate the biology of several types of stromal cells such as fibroblasts, endothelial and immune cells in a way that interferes the apparition of metastases. In sum, the available mechanistic data support the global protective action of vitamin D against several important types of cancer., The work in A.M. laboratory is funded by the Agencia Estatal de Investigación (PID2019-104867RB-I00/AEI/10.13039/501100011033) and the Instituto de Salud Carlos III—Fondo Europeo de Desarrollo Regional (CIBERONC/CB16/12/00273).