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ObjectivesOur objectives were to examine the magnitude of the proportion attributable to contextual effects (PCE), which shows what proportion of the treatment arm response can be achieved by the placebo arm across various interventions, and to examine PCE variability by outcome type and condition.DesignWe conducted a meta-epidemiological study.SettingWe searched the Cochrane Database of Systematic Reviews with the keyword ‘placebo’ in titles, abstracts and keywords on 1 January 2020.ParticipantsWe included reviews that showed statistically significant beneficial effects of the intervention over placebo for the first primary outcome.Main outcome measuresWe performed a random-effects meta-analysis to calculate PCEs based on the pooled result of each included review, grouped by outcome type and condition. The PCE quantifies how much of the observed treatment response can be achieved by the contextual effects.Public and patient involvement statementNo patient or member of the public was involved in conducting this research.ResultsWe included 328 out of 3175 Cochrane systematic reviews. The results of meta-analyses showed that PCEs varied greatly depending on outcome type (I2=98%) or condition (I2=98%), but mostly lie between 0.40 and 0.95. Overall, the PCEs were 0.65 (95% CI 0.59 to 0.72) on average. Subjective outcomes were 0.50 (95% CI 0.41 to 0.59), which was significantly smaller than those of semiobjective (PCE 0.78; 95% CI 0.72 to 0.85) or objective outcomes (PCE 0.94; 95% CI 0.91 to 0.97).ConclusionsThe results suggest that much of the observed benefit is not just due to the specific effect of the interventions. The specific effects of interventions may be larger for subjective outcomes than for objective or semiobjective outcomes. However, PCEs were exceptionally variable. When we evaluate the magnitude of PCEs, we should consider each PCE individually, for each condition, intervention and outcome in its context, to assess the importance of an intervention for each specific clinical setting.

[Objectives] This study aims to describe the distribution of anchor-based minimal important change (MIC) estimates in standard deviation (SD) units and examine if the robustness of such estimates depends on the specific SD used or on the methodological credibility of the anchor-based estimates. [Design and Setting] We included all anchor-based MIC estimates from studies published in MEDLINE and relevant literature databases upto October 2018. Each MIC was converted to SD units using baseline, endpoint, and change from baseline SDs. We performed a descriptive analysis of MICs in SD units and checked how the distribution would change if MICs with low methodological credibility were excluded from the analysis. [Results] We included 1, 009 MIC estimates from 182 studies. The medians and interquartile ranges of MICs in SD units were 0.43 (0.25 to 0.69), 0.42 (0.22 to 0.70), and 0.51 (0.28 to 0.78) for baseline, endpoint, and change SD units, respectively. Some MICs were extremely large or small. The distribution did not change significantly after excluding MICs estimated by less credible methods. [Conclusions] The size of the universally applicable MIC in SD units could not be determined. Anchor-based MICs in SD units were widely distributed, with more than half in the range of 0.2 to 0.8.

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.

BackgroundThe number of new noncommercial clinical studies conducted in Japan declined within the first year of the implementation of the Clinical Trials Act (CTA) on April 1, 2018. This study aimed to examine the impact of the CTA’s enforcement on the number of new noncommercial clinical studies registered in the Japanese Clinical Trial Registry.MethodsAn interrupted time-series design was used in the analysis, which was conducted for the period of April 2015 to March 2019. We collected data for trials registered in the Clinical Trial Registry, managed by the University Hospital Medical Information Network.ResultsIn total, 35,811 studies were registered in the registry; of these, 16,455 fulfilled the eligibility criteria. The difference in the trend of monthly number of new trials after CTA enforcement decreased significantly by 15.0 trials (95% CI, −18.7 to −11.3), and the level decreased by 40.8 (95% CI, −68.2 to −13.3) from the pre-enforcement to the post-enforcement period. Multigroup analyses indicated that the act exerted a significant effect on the trend of new clinical trials, particularly those with smaller sample sizes, interventional study designs, and nonprofit funding sponsors.ConclusionsThe number of Japanese noncommercial clinical studies declined significantly following implementation of the CTA. It is necessary to establish a system to promote clinical studies in Japan while ensuring transparency and safety.

Objectives To assess the proportion of the recent Cochrane reviews that included outcomes in their literature search strategy, how often they acknowledged these limitations, and how qualitatively different the results of outcomes included and not included in the search strategy were. Design and Setting We identified all the Cochrane reviews of the interventions published in 2020 that used a search strategy connecting outcome terms with “AND.” Reviews were defined as acknowledging the limitations of searching for outcomes if they mentioned them in the discussion. We compared the characteristics of outcomes included and not included in the search strategy. Results Of the 523 Cochrane reviews published in 2020, 51 (9.8%) included outcomes in their search strategy. Only one review acknowledged it as a limitation. Forty-seven (92%) assessed outcomes not included in the search strategy. Outcomes included in the search strategies tended to include a larger number of studies and show their effects in favor of the intervention. Conclusions Around ten percent of the recent Cochrane reviews included outcomes in their search, which may have resulted in more outcomes significantly in favor of the intervention. Reviewers should be more explicit in acknowledging the potential implications of searching for outcomes.

The purpose of this systematic review with meta-analysis was to examine the effectiveness of exercise with behavior change techniques (BCTs) on core outcome sets in people with knee osteoarthritis.We searched randomized controlled trials (RCTs) in eight databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO, PEDro, ICTRP, and ClinicalTrials.gov) up to November 4, 2021.Eligible participants were people with knee osteoarthritis. The intervention was exercise with BCTs. Primary outcomes included physical function, quality of life (QOL) 6 to 12 months after intervention, and adverse events. Secondary outcomes were knee pain, exercise adherence, mobility, and self-efficacy 3 months or more after intervention. The bias risk was assessed using the Risk of Bias 2 tool. The random-effects model was used for the meta-analysis.We found 16 individual BCTs, and 37.7% of trials used a single BCT. For meta-analysis, we included 21 RCTs (n = 1623). Most outcomes had a very low certainty of evidence, and the risk of bias was the consistent reason for downgrading evidence levels. The standardized mean difference (SMD) with 95% confidence interval (95% CI) was 0.00 (-0.24, 0.24) in physical function, 0.33 (-0.51, 1.17) in exercise adherence, and 0.04 (-0.39, 0.47) in self-efficacy. The risk ratio (95% CI) of adverse events was 3.6 (0.79, 16.45). QOL was not pooled due to insufficient data (very low certainty of evidence). In contrast, the SMD (95% CI) for knee pain reduction and mobility improvement was -0.33 (-0.53, -0.13) and 0.21 (-0.05, 0.47) with moderate and low certainty of evidence, respectively.The evidence is inconclusive regarding the effectiveness of BCTs with exercises on core outcome sets. Further research should explore the effectiveness of BCTs with valid design.PROSPERO (CRD42020212904).

A customized micro-arc oxidation (MAO) treatment technique was developed to obtain antibacterial properties with no toxicity on Ti surfaces. A two-step MAO treatment was used to fabricate a specimen containing both Ag and Zn in its surface oxide layer, and the optimal incorporation conditions were determined. Surface characterization by EDS was performed followed by the antibacterial properties against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) and osteogenic cell compatibility evaluations. In addition, metal ion release tests were performed to evaluate the contents of Ag and Zn and the ion release behavior in order to simulate practical usage. MAO-treated specimens prepared using proper concentrations of Ag and Zn (0.5Ag-5Zn: 0.5 mM AgNO3 and 5.0 mM ZnCl, respectively) exhibited excellent antibacterial properties against E. coli and S. aureus and no toxicity to MC3T3-E1 in antibacterial and cytotoxic evaluations, respectively. The antibacterial property of 0.5Ag-5Zn against S. aureus was sustained even after two months of immersion in physiological saline, simulating the in vivo environment.

We aimed to compare the methodological quality of physical therapy-related trials published in open access with that of trials published in subscription-based journals, adjusting for subdiscipline, intervention type, endorsement of the consolidated standards of reporting trials (CONSORT), impact factor, and publication language.In this meta-epidemiological study, we searched the Physiotherapy Evidence Database (PEDro) on May 8, 2021, to include any physical therapy-related trials published from January 1, 2020. We extracted variables such as CONSORT endorsement, the PEDro score, and publication type. We compared the PEDro score between the publication types using a multivariable generalized estimating equation (GEE) by adjusting for covariates.A total of 2,743 trials were included, with a mean total PEDro score (SD) of 5.8 (±1.5). Trials from open access journals had a lower total PEDro score than those from subscription-based journals (5.5 ± 1.5 vs. 5.9 ± 1.5, mean difference [MD]: -0.4; 95% confidence interval: 0.3-0.5). GEE revealed that open access publication was significantly associated with the total PEDro score (MD: -0.42; P0.001).In the recent physical therapy-related trials, open access publications demonstrated lower methodological quality than subscription-based publications, although with a small difference.

The cytocompatibility and osteoconductivity of the Zr-14Nb-5Ta-1Mo alloy were investigated using a mouse osteoblastic cell line (MC3T3-E1) to promote the application of this newly developed alloy in dental/medical treatment. The initial cell-attached morphology was visualized by fluorescent staining, and cells cultured on the Zr alloy showed similar cell adhesion behavior to cells cultured on titanium (Ti). In our 5-day proliferation investigation, similar cell numbers were obtained with both Zr alloy and Ti. These results indicate that the cytocompatibility of Zr alloy is similar to that of Ti. In addition, the similar results in the evaluation of alkaline phosphatase (ALP) activity and staining of deposited calcium using alizarin red S with both Zr alloy and Ti indicated that the osteoconductivity of the Zr alloy is similar to that of Ti. Our results prove the good cytocompatibility and osteoconductivity of the Zr-14Nb-5Ta-1Mo alloy, enabling its promotion for use in dental/medical applications.

ObjectiveThe Japan Coma Scale (JCS) is widely used in clinical practice to evaluate levels of consciousness in Japan. There have been several studies on the usefulness of JCS in adults. However, its usefulness in evaluating children has not been reported. Therefore, this study aimed to assess the usefulness of the JCS for the prediction of mortality in children.MethodsThis is a multicenter cohort study which used data from a national trauma registry (Japan Trauma Data Bank). This study included patients under 16 years of age who were treated between 2004 and 2015.The primary outcome measure was in-hospital mortality. Two models were used to examine each item of the Glasgow Coma Scale (GCS) and the JCS. Model A included the discrete levels of each index. In model B, data regarding age, sex, vital signs on arrival to hospital, the Injury Severity Score, and blunt trauma were added to each index. The effectivity of the JCS score was then evaluated using the area under the curve (AUC) for discrimination, a calibration plot, and the Hosmer-Lemeshow test for calibration.ResultsA total of 9045 patients were identified. The AUCs of the GCS and JCS were 0.929 (95% confidence interval (CI) 0.904 to 0.954) and 0.930 (95% CI 0.906 to 0.954) in model A and 0.975 (95% CI 0.963 to 0.987) and 0.974 (95% CI 0.963 to 0.985) in model B, respectively. The results of the Hosmer-Lemeshow test were 0.00 (p=1.00) and 0.00 (p=1.00) in model A and 4.14 (p=0.84) and 8.55 (p=0.38) in model B for the GCS and JCS, respectively.ConclusionsWe demonstrated that the JCS is as valid as the GCS for predicting mortality. The findings of this study indicate that the JCS is a useful and relevant tool for pediatric trauma care and future research.

Ti-Zr alloys have been investigated as an alternative to commercially pure Ti (c.p.Ti). According to our previous studies on the mechanical properties of Ti-Zr alloys, a Zr proportion in the range of 30-50 mol% has competitive advantages over Ti-10Zr and c.p.Ti. The aim of this study is to evaluate the biological response to Ti-Zr alloys with different compositions and their surface characteristics. Alloy surfaces are modified by sandblasting and sulfuric acid etching. As a result, similar surface structures are observed for c.p.Ti, Ti-10Zr, and Ti-30Zr, whereas Ti-50Zr does not form a micro-rough structure by the same treatment process. No significant difference is found in the viability of cells on c.p.Ti, Ti-10Zr, and Ti-30Zr, whereas lower cell attachment levels are detected on Ti-50Zr. In summary, Ti-30Zr reliably forms a micro-rough structure, which provides one evidence for its application in a new dental implant material.

An electrochemical surface treatment was developed to visualize the corrosion-inducing inclusions of Zr in chloride environments. Pure Zr and Zr alloy (Zr–0.5O–0.5C) were evaluated in this study. The electrochemical surface treatment consisted of repeated galvanostatic anodic polarization and potentiostatic cathodic polarization. After the electrochemical surface treatment, only one brittle and non-conductive shell of Zr oxide was observed at the corrosion initiation site on the tested surface. The corrosion-inducing inclusions were found inside the corrosion pit under the optimum polarization conditions. At the corrosion initiation site on pure Zr, the area inside the corrosion pit contained larger amounts of O, C, and Si than the surrounding matrix. In the case of the Zr-0.5O–0.5C alloy, relatively larger inclusions were observed after the treatment. Extremely large amounts of Si, together with O and C, were present in the inclusions. The inclusions that induced localized corrosion on the pure Zr and Zr-0.5O–0.5C specimens were found to be precipitated, involving the specific aggregation of Si. The surface treatment developed in this study is expected to be utilized as a powerful tool to elucidate the localized corrosion mechanism of Zr in chloride environments.