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Meta-analyses examining dichotomous outcomes often include single-zero studies, where no events occur in intervention or control groups. These pose challenges, and several methods have been proposed to address them. A fixed continuity correction method has been shown to bias estimates, but it is frequently used because sometimes software (e.g., RevMan software in Cochrane reviews) uses it as a default. We aimed to empirically compare results using the continuity correction with those using alternative models that do not require correction. To this aim, we reanalyzed the original data from 885 meta-analyses in Cochrane reviews using the following methods: (i) Mantel-Haenszel model with a fixed continuity correction, (ii) random effects inverse variance model with a fixed continuity correction, (iii) Peto method (the three models available in RevMan), (iv) random effects inverse variance model with the treatment arm continuity correction, (v) Mantel-Haenszel model without correction, (vi) logistic regression, and (vii) a Bayesian random effects model with binominal likelihood. For each meta-analysis we calculated ratios of odds ratios between all methods, to assess how the choice of method may impact results. Ratios of odds ratios <0.8 or <1.25 were seen in [approximately]30% of the existing meta-analyses when comparing results between Mantel-Haenszel model with a fixed continuity correction and either Mantel-Haenszel model without correction or logistic regression. We concluded that injudicious use of the fixed continuity correction in existing Cochrane reviews may have substantially influenced effect estimates in some cases. Future updates of RevMan should incorporate less biased statistical methods.

Abstract Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the “Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit” to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions. Graphical Abstract

Objectives Researchers have identified cases in which newspaper stories have exaggerated the results of medical studies reported in original articles. Moreover, the exaggeration sometimes begins with journal articles. We examined what proportion of the studies quoted in newspaper stories were confirmed.Methods We identified newspaper stories from 2000 that mentioned the effectiveness of certain treatments or preventions based on original studies from 40 main medical journals. We searched for subsequent studies until June 2022 with the same topic and stronger research design than each original study. The results of the original studies were verified by comparison with those of subsequent studies.Results We identified 164 original articles from 1298 newspaper stories and randomly selected 100 of them. Four studies were not found to be effective in terms of the primary outcome, and 18 had no subsequent studies. Of the remaining studies, the proportion of confirmed studies was 68.6% (95% CI 58.1% to 77.5%). Among the 59 confirmed studies, 13 of 16 studies were considered to have been replicated in terms of effect size. However, the results of the remaining 43 studies were not comparable.Discussion In the dichotomous judgement of effectiveness, about two-thirds of the results were nominally confirmed by subsequent studies. However, for most confirmed results, it was impossible to determine whether the effect sizes were stable.Conclusions Newspaper readers should be aware that some claims made by high-quality newspapers based on high-profile journal articles may be overturned by subsequent studies within the next 20 years.

Psychological dysfunction is one of the considerable health-related outcomes among critically-ill patients and their informal caregivers. Follow-up of intensive care unit (ICU) survivors has been conducted in a variety of different ways, with different timing after discharge, targets of interest (physical, psychological, social) and measures used. Of diverse ICU follow-up, the effects of follow-ups which focused on psychological interventions are unknown. Our research question was whether follow-up with patients and their informal caregivers after ICU discharge improved mental health compared to usual care. We published a protocol for this systematic review and meta-analysis in https://www.protocols.io/ (https://dx.doi.org/10.17504/protocols.io.bvjwn4pe). We searched PubMed, Cochrane Library, EMBASE, CINAHL and PsycInfo from their inception to May 2022. We included randomized controlled trials for follow-ups after ICU discharge and focused on psychological intervention for critically ill adult patients and their informal caregivers. We synthesized primary outcomes, including depression, post-traumatic stress disorder (PTSD), and adverse events using the random-effects method. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate the certainty of evidence. From the 10,471 records, we identified 13 studies (n = 3, 366) focusing on patients and four (n = 538) focusing on informal caregivers. ICU follow-up for patients resulted in little to no difference in the prevalence of depression (RR 0.89, 95% CI [0.59–1.34]; low-certainty evidence) and PTSD (RR 0.84, 95% CI [0.55–1.30]; low-certainty evidence) among patients; however, it increased the prevalence of depression (RR 1.58 95% CI [1.01–2.46]; very low-certainty evidence), PTSD (RR 1.36, 95% CI [0.91–2.03]; very low-certainty evidence) among informal caregivers. The evidence for the effect of ICU follow-up on adverse events among patients was insufficient. Eligible studies for informal caregivers did not define any adverse event. The effect of follow-ups after ICU discharge that focused on psychological intervention should be uncertain.

Background: The 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. Methods: An interrupted time-series design was used in the analysis, which was conducted from April 2015 to March 2019. We collected data for studies registered in the Clinical Trial Registry, managed by the University Hospital Medical Information Network. Results: In total, 35,811 studies were registered; of these, 16,455 fulfilled the eligibility criteria. The difference in the trend of monthly number of new studies after CTA enforcement decreased significantly by 15.0 (95% confidence interval [CI], −18.7 to −11.3), and the level decreased by 40.8 (95% CI, −68.2 to −13.3) studies 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 studies, particularly those with smaller sample sizes, interventional study designs, and nonprofit funding sponsors. Conclusions: The 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.

Abstract The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.

Abstract Background The low data publication rate for Food and Drug Administration (FDA)-approved drugs, and discrepancies between FDA-submitted versus published data, remain a concern. We investigated the publication statuses of sponsor-submitted clinical trials supporting recent anticancer drugs approved by the FDA, with a focus on immune checkpoint inhibitors (ICPis). Methods We identified all ICPis approved between 2011 and 2014, thereby obtaining 3 years of follow-up data. We assessed the clinical trials performed for each drug indication and matched each trial with publications in the literature. The primary benchmark was the publication status 2 years post-approval. We examined the association between time to publication and drug type using a multilevel Cox regression model that was adjusted for clustering within drug indications and individual covariates. Results Between 2011 and 2014, 36 anticancer drugs including 3 ICPis were newly approved by the FDA. Of 19 trials investigating the 3 ICPis, 11 (58%) were published within 2 years post-approval. We randomly selected 10 of the 33 remaining anticancer drugs; 68 of 101 trials investigating these drugs (67%) were published. Overall, the publication rate was 66% at 2 years post-approval with a median time to publication of 2.3 years. There was no significant difference in the time to trial publication between ICPis and other anticancer drugs (adjusted hazard ratio [HR], 1.1; 95% confidence interval [CI], 0.8–1.7; P = 0.55). However, findings related to non-ICPis investigated specifically in randomized phase 2 or phase 3 trials were significantly more likely to be published earlier than those related to ICPis (adjusted HR, 7.4; 95% CI, 1.8–29.5; P = 0.005). Conclusion One in 3 sponsor-submitted trials of the most recently approved anticancer drugs remained unpublished 2 years post-FDA approval. We found no evidence that the drug type was associated with the time to overall trial publication.

In order to depress the “susceptibility artifacts” in magnetic resonance imaging (MRI), improve the mechanical reliability for biomedical structural applications and realize tailor-made medical devices with complex shape, low magnetic Zr-1Mo(wt%) alloy builds with high relative density (c.a. 99.9%) fabricated by laser powder bed fusion process(L-PBF) were subjected to various heat treatment conditions followed by water quenching. After quenching process acicular α′ microsturcture in as-build Zr-1Mo(wt%) alloy builds changed to basket weave α + β structure, unique retained α + ultra fine (α′ + α″) martensite structure or retained α + acicular α′ microsturcture depending on quenching conditions. X-ray diffraction (XRD) and high resolution-transmission electron microscope(HR-TEM) revealed a unique retained α + ultra fine (α′ + α″) martensite microstructure in 1123 K specimens. The stress-induced competition between β to α′ transformation and β to α″ transformation contributed to this unique microstructure. This unique microstructure contributed to a good balance between strength (UTS:822 MPa) and ductility (Elongation:11.7%). The volume magnetic susceptibility of quenched Zr-1Mo(wt%) alloy builds maintained low(about 1.01 × 10−4) indicating good MRI compatibility. The magnetic susceptibility of each phase was modified to be χα″ > χβ > χα > χα′ > χω. Zr-1Mo(wt%) alloy quenched from 1123 K will be an promising candidates for tailor made devices under MRI environments. Keywords: Powder bed fusion process, Zr-based alloy, Quenching process, Microstructure, Magnetic resonance imaging compatibility

BACKGROUND:Helicopter emergency medical services' (HEMS) effectiveness for pediatric trauma patients remains unclear. We aimed to examine the relation between HEMS and reduced mortality in pediatric trauma patients. METHODS:This retrospective cohort study utilized data from the Japan Trauma Data Bank, a national multicenter clinical trauma database. Participants were aged

Diamond-like carbon (DLC) material is used in blood contacting devices as the surface coating material because of the antithrombogenicity behavior which helps to inhibit platelet adhesion and activation. In this study, DLC films were doped with boron during pulsed plasma chemical vapor deposition (CVD) to improve the blood compatibility. The ratio of boron to carbon (B/C) was varied from 0 to 0.4 in the film by adjusting the flow rate of trimethylboron and acetylene. Tribological tests indicated that boron doping with a low B/C ratio of 0.03 is beneficial for reducing friction (μ = 0.1), lowering hardness and slightly increasing wear rate compared to undoped DLC films. The B/C ratio in the film of 0.03 and 0.4 exhibited highly hydrophilic surface owing to their high wettability and high surface energy. An in vitro platelet adhesion experiment was conducted to compare the blood compatibility of TiNb substrates before and after coating with undoped and boron doped DLC. Films with highly hydrophilic surface enhanced the blood compatibility of TiNb, and the best results were obtained for DLC with the B/C ratio of 0.03. Boron doped DLC films are promising surface coatings for blood contacting devices.

Abstract Background Although many hemodynamically unstable trauma patients undergo computed tomography (CT) to identify a source of bleeding, this practice is currently only recommended by a few guidelines. To clarify whether CT has harmful effects among these patients, we examined the association between CT during initial management and mortality among unstable blunt trauma patients. Methods This was a retrospective cohort study based on Japan Trauma Data Bank 2004–2014 registry data. Study population was adult blunt trauma patients with hypotension on arrival. The primary outcome was the in-hospital mortality. Two types of analyses were performed to adjust for confounding factors including propensity score inverse probability of treatment weighted (IPTW) and instrumental variable (IV) analysis. Results Among 5,809 patients who met inclusion criteria, 5,352 (92.1%) underwent CT. The No CT group was more likely to have severe physiological conditions and lower probability of survival than those of the CT group. In IPTW analysis adjusting for measured confounders, we found a significant protective effect of undergoing CT on in-hospital mortality (excess deaths: −20.6 per 100 patients, 95% CI −26.2 to −14.9). In IV analysis adjusting both for measured and unmeasured confounders, the association between CT and mortality was not statistically significant (excess deaths: −4.1 per 100 patients, 95% CI −23.1 to 14.8). Discussion We did not find clinically meaningful harmful effect of CT on survival for unstable blunt trauma patients even after adjusting both for measured and unmeasured confounders. Conclusions Our results did not support the recommendation of current guideline. We suggest physicians should consider CT as one of the diagnostic options even when patients are unstable.

Vehicles can be classified by configuration as either bonnet-type or cab-over type according to engine location. Compared to bonnet-type, the front compartment of cab-over type vehicles is considerably shorter; thus, it may be less likely to absorb the energy generated in a collision, and in turn be unable to prevent deformation of the occupant space and protect occupants from injury. This study was a cohort study involving 943 occupants of mini-vehicles who were injured in frontal collision accidents between 2001 and 2015 and transferred to Ohta Nishinouchi Hospital. The vehicle configuration was divided into bonnet-type and cab-over type (i.e., truck-type and wagon-type). The tested outcomes were anatomical-specific severe injury of the pelvis and extremities, the head and neck, the abdomen, and the chest. To estimate adjusted odds ratios (AOR) for associations between vehicle configuration and anatomical-specific severe injury, we fitted generalized estimating equations for each outcome. Compared with bonnet-type vehicles, a greater risk of serious pelvis and extremities injury was found for both truck (AOR: 2.21; 95% Confidence Interval [95% CI]: 1.22-4.00) and wagon-type vehicles (AOR: 3.43; 95%CI 1.60-7.39). For serious head and neck injury, truck-type vehicles were associated with greater risk (AOR: 2.04; 95% CI: 1.10-3.79) than bonnet-type vehicles, whereas wagon-type vehicles were not. Compared with the occupants of bonnet-type vehicles, cab-over type vehicle occupants were more likely to have serious pelvis and extremities injury during frontal collisions. Additionally, truck-type vehicle occupants were more likely to have serious head and neck injury than bonnet-type vehicle occupants. These findings are expected to promote safer behaviors for vehicle occupants and the automobile industry.

Recent studies indicate that biodegradable magnesium alloys and composites are attracting a great deal of attention in orthopedic applications. In this study, magnesium–hydroxyapatite (Mg–HAP) composites with different compositions and grain size were fabricated by a spark plasma sintering (SPS) method. Their mechanical properties and corrosion behavior in a pseudo-physiological environment were investigated by pH measurements and inductivity coupled plasma (ICP) elemental analysis after an immersion test using Hanks’ solution. The results clearly showed that the addition of HAP improved both the mechanical properties and corrosion resistance. The results also indicated that the finer grain size improved most of the properties that are needed in a material for an orthopedic implant. Furthermore, the authors reveal that there is a strong correlation between the compressive strength and the porosity. In order to achieve the same compressive strength as human bone using these fabrication conditions, it is revealed that the porosity should be lower than 1.9%.

Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO2) layer. Ag- and Cu-incorporated TiO2 layers were formed by micro-arc oxidation (MAO) treatment using the electrolyte with Ag and Cu ions. Ag- and Cu-incorporated specimens were incubated in saline during a period of 0–28 days. The changes in both the concentrations and chemical states of the Ag and Cu were characterized using X-ray photoelectron spectroscopy (XPS). The durability of the antibacterial effects against Escherichia coli (E. coli) were evaluated by the international organization for standardization (ISO) method. As a result, the Ag- and Cu-incorporated porous TiO2 layers were formed on a Ti surface by MAO. The chemical state of Ag changed from Ag2O to metallic Ag, whilst that of Cu did not change by incubation in saline for up to 28 days. Cu existed as a stable Cu2O compound in the TiO2 layer during the 28 days of incubation in saline. The concentrations of Ag and Cu were dramatically decreased by incubation for up to 7 days, and remained a slight amount until 28 days. The antibacterial effect of Ag-incorporated specimens diminished, and that of Cu was maintained even after incubation in saline. Our study suggests the importance of the time-transient effects of Ag and Cu on develop their antibacterial effects.

The effects of Ti, Nb, Ta, Zr, and Ag on cellular and bacterial adhesion were investigated in this study. Moreover, the relationships between surface compositions, metal ion release behaviors, and biological responses were examined. As a result, MC3T3-E1 cells and S. aureus were able to better attach to Ti and Zr rather than the Nb and Ta specimens. For the Ag specimen, the amount of Ag ions released into Hanks’ solution was the largest among all the specimens. Cellular and bacterial adhesion onto the Ag specimen was inhibited compared with the other specimens, because of Ag ion release. Alternatively, Nb and Ta specimens exhibited specific biological responses. Cellular adhesion on Nb and Ta specimens was similar to that on Ti, while bacterial adhesion on Nb and Ta specimens was inhibited compared with that on Ti. This study proved that Nb and Ta inhibited bacterial adhesion and exhibited no harmful effects on cellular adhesion. In addition, these results indicate that the passive layer on Nb and Ta plays a key role in the inhibition of bacterial adhesion.

Zr alloy is expected to decrease the artifact volume of magnetic resonance imaging (MRI) due to its relatively small magnetic susceptibility. To improve the mechanical properties of a Zr–1mass%Mo alloy that yielded a reduced artifact volume during MRI, the alloy was melted, hot-forged, and cold-swaged with area reduction ratios of 30%, 50%, 60%, 70%, and 84%. The effects of cold swaging on the microstructure, mechanical properties, and magnetic susceptibility of the alloy were investigated. Before cold swaging, the microstructure consisted of laminated and layered α- and β-phases; however, after cold swaging, the α- and β-phases were bent and distorted, and the α-phase became oriented along the {10 1¯ 0} plane. The ultimate tensile strength and elongation to fracture of the Zr–1Mo alloy after cold swaging with an 84% area reduction were 1001 MPa and 10.7%, respectively. The alloy only experienced work-hardening when subjected to large deformations. On the other hand, the change in magnetic susceptibility with cold-swaging was small, from 13.85 × 10−9 to 14.87 × 10−9 m3·kg−1. Thus, a good balance of mechanical properties and low magnetic susceptibility in the Zr–1Mo alloy was obtained by cold swaging. Therefore, this alloy is suitable for utilization in medical devices and is expected to decrease the artifact volume.