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Abstract The fluorinated thymidine analog trifluridine (FTD) is a chemotherapeutic drug commonly used to treat cancer; however, the mechanism by which FTD induces cytotoxicity is not fully understood. In addition, the effect of gain-of-function (GOF) missense mutations of the TP53 gene (encoding p53), which promote cancer progression and chemotherapeutic drug resistance, on the chemotherapeutic efficacy of FTD is unclear. Here, we revealed the mechanisms by which FTD-induced aberrant mitosis and contributed to cytotoxicity in both p53-null and p53-GOF missense mutant cells. In p53-null mutant cells, FTD-induced DNA double-stranded breaks, single-stranded DNA accumulation, and the associated DNA damage responses during the G2 phase. Nevertheless, FTD-induced DNA damage and the related responses were not sufficient to trigger strict G2/M checkpoint arrest. Thus, these features were carried over into mitosis, resulting in chromosome breaks and bridges, and subsequent cytokinesis failure. Improper mitotic exit eventually led to cell apoptosis, caused by the accumulation of extensive DNA damage and the presence of micronuclei encapsulated in the disrupted nuclear envelope. Upon FTD treatment, the behavior of the p53-GOF-missense mutant, isogenic cell lines, generated by CRISPR/Cas9 genome editing, was similar to that of p53-null mutant cells. Thus, our data suggest that FTD treatment overrode the effect on gene expression induced by p53-GOF mutants and exerted its anti-tumor activity in a manner that was independent of the p53 function.

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02–1.05; p

Abstract Background Systemic edema is an adverse effect of docetaxel chemotherapy and causes distress to patients, including those receiving this agent for breast cancer. However, its characteristics and factors related to its effect on quality of life (QoL) have not been adequately investigated. In this study, we assessed systemic edema quantitatively, explored related factors, and evaluated QoL in patients receiving docetaxel for breast cancer. Methods The study had a prospective cohort design and included 37 patients with no known history of swelling who were treated with docetaxel between September 2019 and April 2022. Patients were examined at the start, middle, and end of their course of treatment and 1 and 2 months later. Body water content, body mass, fat mass, and muscle mass were quantified using bioelectrical impedance analysis. Systemic edema was evaluated with reference to the Common Terminology Criteria for Adverse Events. The timing of development of systemic edema at any anatomical site that was grade 2 or worse was recorded. QoL was assessed using the Quality of Life-Anti Cancer Drug scale. Nutrition was evaluated using the Brief-type self-administered diet history questionnaire. Multivariable logistic regression analysis was performed to identify related factors. QoL was also compared between patients with edema and those without edema. Results Systemic edema developed in 67% of the study participants and was most prevalent at the end of treatment. Body fat mass (adjusted odds ratio [aOR] 0.802, 95% confidence interval [CI] 0.651–0.988, p = 0.038), disease stage (aOR 3.279, 95% CI 0.493–21.793, p = 0.219), and history of alcohol consumption (aOR 0.141, 95% CI 0.013–1.521, p = 0.106) were identified as risk factors for docetaxel-induced edema. Participants who developed systemic edema experienced more physical, vital, and emotional distress 1 month after treatment than those who did not. There was no association between systemic edema and nutrition. Conclusions Systemic edema may develop after treatment with docetaxel and increase distress in patients with a high body fat mass. Patients at risk of systemic edema should be informed in advance about the potential frequency, location, and timing of its onset and encouraged to self-manage this condition.

Background: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). Methods: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). Results: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39–0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32–0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13–0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098–0.75, p = 0.012) than the Ab-negatives (n = 11). Conclusion: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

Objectives To assess whether acoustic stimulations relieve venipuncture pain and determine which stimulation is the most effective type.Design Systematic review and network meta-analysis.Data sources PubMed, Cochrane Central Register of Controlled Trials, Excerpta Medica dataBASE, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov and the International Clinical Trials Registry Platform databases were systematically searched in September 2023.Study selection Randomised controlled trials evaluating the efficacy of acoustic stimulations on patients undergoing venipuncture were eligible. Acoustic stimulations were classified into seven categories: five types of acoustic stimulations (music medicine (researcher selected), music medicine (patient selected), music therapy, sounds with linguistic meaning and sounds without linguistic meaning) and two controls (only wearing headphones and no treatment).Primary and secondary outcome measures Primary outcomes included self-reported pain intensity assessed during venipuncture and treatment cost, and secondary outcomes were self-reported mental distress and adverse events.Results Of 6406 citations, this network meta-analysis included 27 studies including 3416 participants; the mean age was 31.5 years, and 57% were men. Among the five types of acoustic stimulations, only musical interventions, such as music medicine (patient selected) (standardised mean difference (SMD) −0.44 (95% CI: −0.84 to –0.03); low confidence), music medicine (researcher selected) (SMD −0.76 (95% CI: −1.10 to –0.42); low confidence) and music therapy (SMD −0.79 (95% CI: −1.44 to –0.14); low confidence), were associated with improved pain relief during venipuncture compared with no treatment. No significant differences existed between the types of acoustic stimulations. Free-of-charge acoustic stimulations were provided to patients, and no specific adverse events were reported. In many studies, the risk of bias was rated high because of the difficulty of blinding the intervention to the participants and the self-reported pain outcome.Conclusions Music interventions were associated with reduced venipuncture pain. Comparisons between types of acoustic stimulations revealed no significant differences. Therefore, music intervention could be a safe and inexpensive pain relief method for venipuncture.PROSPERO registration number CRD42022303852.

AbstractBackground Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively.Methods This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I.Results Seventy-six studies were included in the systematic review (sample size, 23–121,853; enrollment year, 1968–2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66–0.92]), and lower death-censored graft failure (0.81 [0.67–0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58–1.40); biopsy-proven acute rejection, 0.75 (0.55–1.03); cytomegalovirus infection, 1.04 (0.85–1.29); and urinary tract infection, 0.89 (0.61–1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification.Conclusions The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.

Abstract Background Mechanically aligned total knee arthroplasty (MATKA) is a well-established procedure. Kinematically aligned TKA (KATKA) has been proposed to restore and preserve pre-arthritic knee anatomy. However, normal knee anatomy varies widely, and there have been concerns regarding restoring unusual anatomy. Accordingly, restricted KATKA (rKATKA) was introduced to reproduce constitutional knee anatomy within a safe range. This network meta-analysis (NMA) aimed to evaluate the clinical and radiological outcomes of the surgeries. Methods We performed a database search on August 20, 2022, which included randomized controlled trials (RCTs) comparing any two of the three surgical TKA techniques for knee osteoarthritis. We conducted a random-effects NMA within the frequentist framework and evaluated confidence in each outcome using the Confidence in Network Meta-Analysis tool. Results Ten RCTs with 1,008 knees and a median follow-up period of 1.5 years were included. The three methods might result in little to no difference in range of motion (ROM) between methods. In patient-reported outcome measures (PROMs), the KATKA might result in a slight improvement compared with the MATKA (standardized mean difference, 0.47; 95% confidence interval [CI], 0.16–0.78; very low confidence). There was little to no difference in revision risk between MATKA and KATKA. KATKA and rKATKA showed a slight valgus femoral component (mean difference [MD], -1.35; 95% CI, -1.95–[-0.75]; very low confidence; and MD, -1.72; 95% CI, -2.63–[-0.81]; very low confidence, respectively) and a slight varus tibial component (MD, 2.23; 95% CI, 1.22–3.24; very low confidence; and MD, 1.25; 95% CI, 0.01–2.49; very low confidence, respectively) compared with MATKA. Tibial component inclination and hip–knee–ankle angle might result in little to no difference between the three procedures. Conclusions KATKA and rKATKA showed similar ROM and PROMs and a slight variation in the coronal component alignment compared with MATKA. KATKA and rKATKA are acceptable methods in short- to mid-term follow-up periods. However, long-term clinical results in patients with severe varus deformity are still lacking. Surgeons should choose surgical procedures carefully. Further trials are warranted to evaluate the efficacy, safety, and subsequent revision risk.

Evidence on the optimal antibiotic strategy for empyema is lacking. Our database study aimed to evaluate the effectiveness of empirical anti-pseudomonal antibiotics in patients with empyema. We utilised a Japanese real-world data database, focusing on patients aged ≥40 diagnosed with empyema, who underwent thoracostomy and received intravenous antibiotics either upon admission or the following day. Patients administered intravenous vasopressors were excluded. We compared thoracic surgery and death within 90 days after admission between patients treated with empirical anti-pseudomonal and non-anti-pseudomonal antibiotics. Cause-specific hazard ratios for thoracic surgery and death were estimated using Cox proportional hazards models, with adjustment for clinically important confounders. Subgroup analyses entailed the same procedures for patients exhibiting at least one risk factor for multidrug-resistant organisms. Between March 2014 and March 2023, 855 patients with empyema meeting the inclusion criteria were enrolled. Among them, 271 (31.7%) patients received anti-pseudomonal antibiotics. The Cox proportional hazards models indicated that compared to empirical non-anti-pseudomonal antibiotics, empirical anti-pseudomonal antibiotics were associated with higher HRs for thoracic surgery and death within 90 days, respectively. Thus, regardless of the risks of multidrug-resistant organisms, empirical anti-pseudomonal antibiotics did not extend the time to thoracic surgery or death within 90 days.

Abstract An 84‐year‐old woman who was admitted for protein‐losing gastroenteropathy associated with radiation enteritis 10 years after pelvic radiotherapy developed pyelonephritis. She became anuric despite having an indwelling bladder catheter. Imaging studies revealed bladder wall thickening, bilateral hydroureter formation, and hydronephrosis. Autopsy findings led to a diagnosis of gangrenous cystitis (GC). Our case indicates that radiation‐induced late effects may be an indirect cause of GC, not a direct cause as previously suggested, and that GC may induce bilateral vesicoureteral junction obstruction.

Abstract Background No studies have demonstrated medium- or long-term skill retention of cardiac point-of-care ultrasound (POCUS) curriculum for medical student. Based on the American Society of Echocardiography (ASE) curriculum framework, we developed a blended-learning cardiac POCUS curriculum with competency evaluation. The objective of this study was to investigate the curriculum impact on image acquisition skill retention 8 weeks after initial training. Methods This study was a prospective, pre-post education intervention study for first- and second-year medical students, with blinded outcome assessment. The curriculum included a pre-training ASE online module and healthy volunteer hands-on training to obtain 5 views: parasternal long-axis (PLAX), parasternal short-axis (PSAX), apical 4-chamber (A4C), subcostal 4-chamber (S4C), and subcostal inferior vena cava (SIVC) views. Students took 5-view image acquisition skill tests at pre-, immediate post-, and 8-week post-training, using a healthy volunteer. Three blinded assessors rated the image quality using a validated 10-point maximum scoring system. Students used a hand-held ultrasound probe (Butterfly iQ). Results Fifty-four students completed hands-on training, and pre- and immediate post-training skill tests. Twenty-seven students completed 8-week post-training skill tests. Skill test score improvement between pre- and 8-week post-training was 2.11 points (95% CI, 1.22–3.00; effect size, 1.13). Conclusion The cardiac POCUS curriculum demonstrated medium-term skill retention. The curriculum was sufficient for S4C and SIVC skill retention, but inadequate for PLAX, PSAX, and A4C. Therefore, instructional design modifications or re-training for PLAX, PSAX, and A4C are needed to make the curriculum more effective for clinically relevant skill retention.

Abstract Background Although corticosteroid therapy with dose tapering is the most commonly used treatment for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), there is no consensus on the tapering regimen. This study aimed to investigate the association between early corticosteroid dose tapering and in-hospital mortality in patients with AE-IPF. Methods In this retrospective cohort study, we analyzed the data of a cohort from eight Japanese tertiary care hospitals and routinely collected administrative data from a cohort from 185 Japanese hospitals. Patients with AE-IPF were classified into the early and non-early tapering groups depending on whether the maintenance dose of corticosteroids was reduced within two weeks of admission. Propensity score analysis with inverse probability weighting (IPW) was performed to estimate the effect of early corticosteroid dose tapering. Results The multi-center cohort included 153 eligible patients, of whom 47 (31%) died, whereas the administrative cohort included 229 patients, of whom 51 (22%) died. Patients with early tapering tended to have a better prognosis than those without it (unadjusted hazard ratio [95% confidence interval] 0.41 [0.22–0.76] and 0.65 [0.36–1.18] in the multi-center and administrative cohorts, respectively). After IPW, the early tapering group had a better prognosis than the non-early tapering group (IPW-adjusted hazard ratio [95% confidence interval] 0.37 [0.14–0.99] and 0.27 [0.094–0.83] in the multi-center and administrative cohorts, respectively). Conclusion Early corticosteroid dose tapering was associated with a favorable prognosis in patients with AE-IPF. Further studies are warranted to confirm the effects of early corticosteroid dose tapering in patients with AE-IPF.

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.

Abstract We performed a systematic review and meta‐analysis to re‐evaluate the effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) in the reduction of pneumonia risk. We searched relevant publications in five databases. All studies included patients older than 18 years, who had used ACE‐I as an intervention, and had assessed pneumonia. Seven RCTs (n = 8704) and 38 observational studies (n = 1,705,030) were included. The overall risk of bias was high. ACE‐I‐treated patients were associated with a slightly lower risk of pneumonia, both from pooled estimates of RCTs [pooled odds ratio (OR), 0.75; 95% confidence interval (CI), 0.62–0.90; low certainty of evidence] and observational studies (pooled OR, 0.85; 95% CI, 0.78–0.92; very low certainty of evidence). Considering the small effect size of ACE‐I in preventing pneumonia and the low quality of the evidence, routine use of ACE‐I for pneumonia prevention is not recommended.

Abstract Background We compared the prognostic value of serum high mobility group box 1 protein (HMGB1) and histone H3 levels with the International Society on Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC) scores for 28-day in-hospital mortality in patients with DIC caused by various underlying diseases. Methods We conducted a multicenter prospective cohort study including two hematology departments, four emergency departments, and one general medicine department in Japan, between August 2017 and July 2021. We included patients diagnosed with DIC by the ISTH DIC scoring system. Results Overall, 104 patients were included: 50 with hematopoietic disorders, 41 with infections, and 13 with the other diseases. The 28-day in-hospital mortality rate was 21%. The receiver operator characteristic (ROC) curve showed that a DIC score of 6 points, serum HMGB1 level of 8 ng/mL, and serum histone H3 level of 2 ng/mL were the optimal cutoff points. The odds ratios of more than these optimal cutoff points of the DIC score, serum HMGB1, and histone H3 levels were 1.58 (95% confidence interval [CI]: 0.60 to 4.17, p = 0.36), 5.47 (95% CI: 1.70 to 17.6, p = 0.004), and 9.07 (95% CI: 2.00 to 41.3, p = 0.004), respectively. The area under the ROC curve of HMGB1 (0.74, 95% CI: 0.63 to 0.85) was better than that of the ISTH DIC scores (0.55, 95% CI: 0.43 to 0.67, p = 0.03), whereas that of histone H3 was not (0.71, 95% CI: 0.60 to 0.82, p = 0.07). Calibration and net reclassification plots of HMGB1 identified some high-risk patients, whereas the ISTH DIC scores and histone H3 did not. The category-free net reclassification improvement of HMGB1 was 0.45 (95% CI: 0.01 to 0.90, p = 0.04) and that of histone H3 was 0.37 (95% CI: − 0.05 to 0.78, p = 0.08). Conclusions Serum HMGB1 levels have a prognostic value for mortality in patients with DIC. This finding may help physicians develop treatment strategies.

Objectives To find the optimal treatment duration with antibiotics for community-acquired pneumonia (CAP) in adults.Design Systematic review and duration-effect meta-analysis.Data sources MEDLINE, Embase and CENTRAL through 25 August 2021.Eligibility criteria All randomised controlled trials comparing the same antibiotics used at the same daily dosage but for different durations for CAP in adults. Both outpatients and inpatients were included but not those admitted to intensive care units. We imposed no date, language or publication status restriction.Data extraction and synthesis Data extraction by two independent reviewers. We conducted a random-effects, one-stage duration-effect meta-analysis with restricted cubic splines. We tested the non-inferiority with the prespecified non-inferiority margin of 10% examined against 10 days . The primary outcome was clinical improvement on day 15 (range 7–45 days). Secondary outcomes: all-cause mortality, serious adverse events and clinical improvement on day 30 (15–60 days).Results We included nine trials (2399 patients with a mean (SD) age of 61.2 (22.1); 39% women). The duration-effect curve was monotonic with longer duration leading to a lower probability of improvement, and shorter treatment duration (3–9 days) was likely to be non-inferior to 10-day treatment. Harmful outcome curves indicated no association. The weighted average percentage of the primary outcome in the 10-day treatment arms was 68%. Using that average, the absolute clinical improvement rates of the following durations were: 3-day treatment 75% (95% CI: 68% to 81%), 5-day treatment 72% (95% CI: 66% to 78%) and 7-day treatment 69% (95% CI: 61% to 76%).Conclusions Shorter treatment duration (3–5 days) probably offers the optimal balance between efficacy and treatment burden for treating CAP in adults if they achieved clinical stability. However, the small number of included studies and the overall moderate-to-high risk of bias may compromise the certainty of the results. Further research on the shorter duration range is required.PROSPERO registration number CRD 42021273357.

Abstract Aims/Introduction This systematic review and meta‐analysis aimed to investigate the efficacy and safety of acceptance and commitment therapy (ACT) for people with type 2 diabetes mellitus. Materials and Methods Several electronic databases were examined on 16 January 2021, including PubMed, CENTRAL, PsycINFO, International Clinical Trials Registry Platform and ClinicalTrials.gov. Randomized controlled trials were included to compare ACT with usual treatment for people with type 2 diabetes reported in any language. Primary outcome measures were glycated hemoglobin, self‐care ability assessed by the summary of diabetes self‐care activities and all adverse events. The secondary outcome measure was acceptance assessed by the acceptance and action diabetes questionnaire. Results Of 678 publications initially identified, three trials were included in the meta‐analysis. ACT resulted in a reduction in glycated hemoglobin (mean difference −0.62 points lower in the intervention group; 95% confidence interval −1.07 to −0.16; I2 = 0%; low‐quality evidence). In addition, ACT increased the score of the summary of diabetes self‐care activities (mean difference 8.48 points higher in the intervention group; 95% confidence interval 2.16–14.80; high‐quality evidence). Adverse events were not measured in all trials. ACT increased scores of the acceptance and action diabetes questionnaire (mean difference 5.98 points higher in the intervention group; 95% confidence interval, 1.42–10.54; I2 = 43%; low‐quality evidence). Conclusions ACT might reduce glycated hemoglobin, and increase self‐care ability and acceptance among people with type 2 diabetes.

This systematic review and meta-analysis examined the efficacy of neuromuscular electrical stimulation (NMES) on lower limb muscle strength and health-related quality of life (HR-QOL) after thoracic and abdominal surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Excerpta Medica Database via Elsevier, Physiotherapy Evidence Database, Cumulative Index to Nursing and Allied Health Literature, World Health Organization International Clinical Trials Registry Platform via their dedicated search portal, and ClinicalTrials.gov on November 2021 and updated in April 2023 to identify randomized controlled trials that examined the effects of NMES after thoracic and abdominal surgery. The primary outcomes were lower limb muscle strength, HR-QOL, and adverse events. We used the Cochrane Risk of Bias Tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence. A total of 18 randomized control trials involving 915 participants, including 10 on cardiovascular surgery, two on pulmonary surgery, five on digestive system surgery, and one on other surgery, were included. NMES slightly increased lower limb muscle strength and adverse events in cardiovascular surgery. Adverse events (hypotension, pain, and muscle discomfort) occurred in seven patients. HR-QOL was measured in two studies on cardiovascular surgery, but these were not pooled due to concept heterogeneity. Overall, NMES slightly increases lower limb muscle strength after cardiovascular surgery without serious adverse events. However, higher-quality randomized control trials in thoracic and abdominal surgeries are needed.

Introduction An easy-to-access and effective psychotherapy for bereaved informal caregivers has not been established. People with higher self-compassion status tend to have lower bereavement related grief, psychotherapy focused on self-compassion can be promising for this population. This study aimed to examine the feasibility of online self-compassion focused psychotherapy for bereaved informal caregivers.Method and analysis A total of 60 study participants will undergo an intervention programme comprising online sessions of 2 hours per week for five consecutive weeks and undertake postsession work. The intervention personnel will comprise psychologists who have received more than 10 hours of structured training. The primary endpoint will be assessed on the intervention completion rate, with secondary endpoints consisting of the Complicated Grief Questionnaire, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7, Brief Resilience Scale and Self-Compassion Scale. Evaluations will be conducted preintervention, immediately after intervention, and 4 and 12 weeks after intervention.Ethics and dissemination This study has been reviewed and approved by the Ethics Committee of the Kyoto University Graduate School and Faculty of Medicine, Kyoto University Hospital, Japan (Approved ID: C1565). The results of this study will be disseminated through publication in a peer-reviewed journal and conference presentations.Trial registration number UMIN000048554.

Abstract Although frequent chronic obstructive pulmonary disease (COPD) exacerbation has been associated with the isolation of Pseudomonas aeruginosa (PA) in sputum cultures, it remains unknown whether the empirical use of anti-pseudomonal antibiotics can improve outcomes in patients with frequent COPD exacerbations. This multicenter retrospective cohort study evaluated whether the empirical use of anti-pseudomonal antibiotics improves the length of the hospital stay in patients with recurrent COPD exacerbation (≥ 2 admissions from April 1, 2008 to July 31, 2020). For statistical analysis, a log-linked Gamma model was used. Parameters were estimated using a generalized estimating equation model with an exchangeable correlation structure accounting for repeated observations from a single patient. Covariates included age, body mass index, home oxygen therapy use, respiratory rate, heart rate, oxygen use on admission, mental status, systemic steroid use, activities of daily living, and the number of recurrences. Hospital-specific effects were specified as fixed effects. In total, 344 patients and 965 observations of recurrent COPD exacerbations were selected. Anti-pseudomonal antibiotics were used in 173 patients (18%). The estimated change in the length of the hospital stay between anti-pseudomonal and non-anti-pseudomonal antibiotics groups was 0.039 days [95% confidence interval; − 0.083, 0.162]. Anti-pseudomonal antibiotics could not shorten the length of the hospital stay.

Abstract Background Patient–ventilator asynchrony (PVA) is a common problem in patients undergoing invasive mechanical ventilation (MV) in the intensive care unit (ICU), and may accelerate lung injury and diaphragm mis-contraction. The impact of PVA on clinical outcomes has not been systematically evaluated. Effective interventions (except for closed-loop ventilation) for reducing PVA are not well established. Methods We performed a systematic review and meta-analysis to investigate the impact of PVA on clinical outcomes in patients undergoing MV (Part A) and the effectiveness of interventions for patients undergoing MV except for closed-loop ventilation (Part B). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, ClinicalTrials.gov, and WHO-ICTRP until August 2020. In Part A, we defined asynchrony index (AI) ≥ 10 or ineffective triggering index (ITI) ≥ 10 as high PVA. We compared patients having high PVA with those having low PVA. Results Eight studies in Part A and eight trials in Part B fulfilled the eligibility criteria. In Part A, five studies were related to the AI and three studies were related to the ITI. High PVA may be associated with longer duration of mechanical ventilation (mean difference, 5.16 days; 95% confidence interval [CI], 2.38 to 7.94; n = 8; certainty of evidence [CoE], low), higher ICU mortality (odds ratio [OR], 2.73; 95% CI 1.76 to 4.24; n = 6; CoE, low), and higher hospital mortality (OR, 1.94; 95% CI 1.14 to 3.30; n = 5; CoE, low). In Part B, interventions involving MV mode, tidal volume, and pressure-support level were associated with reduced PVA. Sedation protocol, sedation depth, and sedation with dexmedetomidine rather than propofol were also associated with reduced PVA. Conclusions PVA may be associated with longer MV duration, higher ICU mortality, and higher hospital mortality. Physicians may consider monitoring PVA and adjusting ventilator settings and sedatives to reduce PVA. Further studies with adjustment for confounding factors are warranted to determine the impact of PVA on clinical outcomes. Trial registration protocols.io (URL: https://www.protocols.io/view/the-impact-of-patient-ventilator-asynchrony-in-adu-bsqtndwn , 08/27/2020).

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P

Abstract Background Research engagement contributes to the improvement of patient care. A systematic review is a suitable first scholarly activity because it entails summarization of publicly available data and usually requires neither rigorous ethical review nor research funding. Methods This study aimed to develop a model workshop for healthcare staff to acquire skills in creating systematic review protocols based on their own clinical questions at teaching hospitals. We used an action research method to create a model workshop at four hospitals in Japan from April 2015 to March 2017. To improve the program, we solicited reflections using participant questionnaires for each lecture and examined the quality of homework submitted by participants after each lecture. We administered a revised final version of the workshop at five hospitals from April 2016 to March 2017. We evaluated the participants’ scholarly productivity related to these workshops. The observation period was a minimum of 2 years following the workshops. Results Most participants had never developed a formal clinical research protocol and voluntarily participated in the workshop. The action research was developed and implemented at nine teaching hospitals in Japan, including one university hospital. The study developed a model nine-step workshop curriculum: 1) Research question development, 2) Search strategy development, 3) Search strategy brush-up, 4) Exclusion and inclusion criteria development, 5) Risk of bias assessment planning, 6) Meta-analysis planning, 7) Subgroup and sensitivity analysis planning, 8) Planning the presentation of results, and 9) Presentation protocols. A total of 233 participants, including medical doctors and other health professionals, produced 414 research questions. Seventy-nine participants (34%) completed the workshop, and 47 review teams accomplished systematic review protocols. The participants published 13 peer-reviewed articles as a result of the workshop. Conclusions We developed a structured scholarly productive model workshop for healthcare staff working at hospitals. We found healthcare staff with clinical subspecialties were able to develop an unexpectedly high number of research questions through this workshop. Medical teachers at hospitals with prior systematic review experience could teach how to develop systematic review protocols using this model. Further research is needed to increase the academic productivity of such workshops. Trial registration UMIN (https://www.umin.ac.jp/ctr/), UMIN000017107 (4/15/2015), UMIN000025580 (1/10/2017).

Abstract Background While conducting systemic reviews, searching for ongoing or unpublished trials is critical to address publication bias. As of April 2019, records of ongoing or unpublished randomized and/or quasi-randomized controlled trials registered in the International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov are available in the Cochrane Central Register of Controlled Trials (CENTRAL). These records registered in CENTRAL include studies published since the inception of ICTRP and ClinicalTrials.gov . Whether systematic reviewers can search CENTRAL to identify ongoing or unpublished trials instead of ICTRP and ClinicalTrials.gov is unknown. Methods This was a cross-sectional study. A consecutive sample of ongoing or unpublished studies published from June 1, 2019 to December 27, 2019 was selected from the Cochrane Reviews. The sensitivity and the number needed to read (NNR) were assessed from among the studies selected from CENTRAL instead of ICTRP and ClinicalTrials.gov and also assessed the characteristics of studies not identified by searching CENTRAL. Results In total, 247 records from 50 Cochrane reviews were included; of these, 200 were identified by searching CENTRAL, whereas the remaining 47 records were not. The sensitivity of searching CENTRAL was 0.81 (95% confidence interval [CI]: 0.76, 0.85). The NNR was 115 (95% CI: 101, 133). The 47 unidentified studies were registered through ClinicalTrials.gov or ICTRP. Sixteen unidentified studies were not indexed in CENTRAL. Conclusions For systematic reviewers, searching CENTRAL could not substitute for searching ClinicalTrials.gov and/or ICTRP. Systematic reviewers should not only search CENTRAL but also ICTRP and ClinicalTrials.gov to identify unpublished trials. Trial registration A pre-specified protocol was applied to conduct this study. The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). Trial registration number: UMIN000038981 .

The aim of this review is to investigate the diagnostic accuracy or performance of contrast‐enhanced computed tomography (CT) and magnetic resonance imaging (MRI) for acute pelvic inflammatory disease (PID) in an emergency care setting. We searched for studies on the diagnostic test accuracy of contrast‐enhanced CT or MRI for women of reproductive age with acute abdominal pain using MEDLINE, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and ClinicalTrials.gov. The reference standard was gynecological examinations by gynecologists using standard diagnostic criteria with or without laparoscopy or transcervical endometrial biopsy. Two reviewers undertook screening of records, data extraction, and assessment of the risk of bias in each included study using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. A bivariate model was used for the meta‐analysis. Of 2,619 screened studies, three studies investigating contrast‐enhanced CT and one study investigating MRI were eligible, including a total 635 patients and with a median prevalence of acute PID of 29%. All of the included studies had a high risk of bias for a reference standard and had some applicability concerns. Contrast‐enhanced CT had a pooled sensitivity of 0.79 (95% confidence interval [CI], 0.52–0.93) and specificity of 0.99 (95% CI, 0.94–1.00). Magnetic resonance imaging had a sensitivity of 0.95 (95% CI, 0.76–1.00) and specificity of 0.89 (95% CI, 0.52–1.00). Contrast‐enhanced CT might serve as a practical alternative to gynecological examination in the diagnosis of acute PID in an emergency care setting, however, the evidence was uncertain. The evidence on MRI was also very uncertain.

Introduction There is no established clinical prediction model for in-hospital death among patients with pneumonic COPD exacerbation. We aimed to externally validate BAP-65 and CURB-65 and to develop a new model based on the eXtreme Gradient Boosting (XGBoost) algorithm. Methods This multicentre cohort study included patients aged ≥40 years with pneumonic COPD exacerbation. The input data were age, sex, activities of daily living, mental status, systolic and diastolic blood pressure, respiratory rate, heart rate, peripheral blood eosinophil count and blood urea nitrogen. The primary outcome was in-hospital death. BAP-65 and CURB-65 underwent external validation using the area under the receiver operating characteristic curve (AUROC) in the whole dataset. We used XGBoost to develop a new prediction model. We compared the AUROCs of XGBoost with that of BAP-65 and CURB-65 in the test dataset using bootstrap sampling. Results We included 1190 patients with pneumonic COPD exacerbation. The in-hospital mortality was 7% (88 out of 1190). In the external validation of BAP-65 and CURB-65, the AUROCs (95% confidence interval) of BAP-65 and CURB-65 were 0.69 (0.66–0.72) and 0.69 (0.66–0.72), respectively. XGBoost showed an AUROC of 0.71 (0.62–0.81) in the test dataset. There was no significant difference in the AUROCs of XGBoost versus BAP-65 (absolute difference 0.054; 95% CI −0.057–0.16) or versus CURB-65 (absolute difference 0.0021; 95% CI −0.091–0.088). Conclusion BAP-65, CURB-65 and XGBoost showed low predictive performance for in-hospital death in pneumonic COPD exacerbation. Further large-scale studies including more variables are warranted.

This study assesses the gender differences in health and anxiety, especially pertaining to mental health problems and time-course effects. We surveyed 121 patients admitted to a hospital with a COVID-19 diagnosis between March 1 and August 31, 2020. Their mental status was evaluated on admission using the Japanese General Health Questionnaire-28 (GHQ-28) and State–Trait Anxiety Inventory—Form JYZ (STAI). The patients were divided into two groups depending on the period of prevalence, that is, the first and second waves of the pandemic in Japan (from the beginning of March to the end of May 2020, Time 1 = T1; and from the beginning of June to the end of August 2020, Time 2 = T2). A multivariate analysis of covariance revealed significant differences in gender by time interactions in the GHQ-28 subscale “Insomnia and anxiety” and STAI subscale “State–Anxiety.” Post-hoc t-tests revealed that the scores of “Insomnia and Anxiety” and “State–Anxiety” were higher in women than in men at T1. However, no difference was observed at T2. Further, “Insomnia and Anxiety” and “State–Anxiety” were significantly higher at T1 than at T2 in female patients. There was no significant difference in males. Thus, female patients were more anxious and depressed in the early phase of the pandemic, whereas male patients had difficulties in coping with anxiety. We suggest more gender-specific mental care, particularly for women at the early stages of infection.

This paper investigates the burnishing characteristics of a developed sliding burnishing method with active rotary tool targeting a martensitic stainless steel. Two types of martensitic stainless steel, annealing (AN) stainless steel and quenching and tempering (QT) stainless steel, were targeted. The burnishing characteristics evaluated included surface roughness, profile, microstructure, subsurface hardness, bending property, and corrosion resistance. A sufficiently smooth surface, approximately Ra = 0.1 μm and Ra = 0.016 μm in both materials, respectively, was obtained using the developed burnishing method; irregular profile smoothing occurred due to the material flow of the subsurface. The subsurface hardness increased at a depth of 40 μm or more when using the developed burnishing method on the AN material, but no effect was observed for the QT material. Moreover, the bending yield point and strength of the sheet shape workpiece increased by applying the burnishing process to the AN material. The influence of the burnishing process on the bending properties was also observed for the QT material. Corrosion resistance, which evaluated by the salt-spray test, can be improved through the burnishing process in AN material.

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.

Abstract Objective The risk of atherosclerotic cardiovascular disease (ASCVD) is estimated using the American College of Cardiology (ACC)/American Heart Association (AHA) Pooled Cohort Equations (PCEs). However, the accuracy of this tool remains controversial, particularly among patients who are recommended statin therapy according to the ACC/AHA guidelines. We performed external validation of PCEs among patients eligible for statin therapy using data from the systolic blood pressure intervention trial (SPRINT). Results Our study included 4057 patients from among the 9361 patients in SPRINT. The mean patient age was 64.5 years, and the median predicted 10-year risks of ASCVD were 17.2% and 12.3% for men and women, respectively. Over a median follow-up of 3.3 years, 133 primary events (including 23 cardiovascular deaths) were noted, whereas 304 events were predicted by the PCEs. The PCEs demonstrated poor calibration (Hosmer–Lemeshow test, p

Abstract Background Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients. Methods Using free word and control terms related to “non-small cell lung cancer” and “rebiopsy,” we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions. Results Of the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p

Ali-M3, an artificial intelligence program, analyzes chest computed tomography (CT) and detects the likelihood of coronavirus disease (COVID-19) based on scores ranging from 0 to 1. However, Ali-M3 has not been externally validated. Our aim was to evaluate the accuracy of Ali-M3 for detecting COVID-19 and discuss its clinical value. We evaluated the external validity of Ali-M3 using sequential Japanese sampling data. In this retrospective cohort study, COVID-19 infection probabilities for 617 symptomatic patients were determined using Ali-M3. In 11 Japanese tertiary care facilities, these patients underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. They also underwent chest CT to confirm a diagnosis of COVID-19. Of the 617 patients, 289 (46.8%) were RT-PCR-positive. The area under the curve (AUC) of Ali-M3 for predicting a COVID-19 diagnosis was 0.797 (95% confidence interval: 0.762‒0.833) and the goodness-of-fit was P = 0.156. With a cut-off probability of a diagnosis of COVID-19 by Ali-M3 set at 0.5, the sensitivity and specificity were 80.6% and 68.3%, respectively. A cut-off of 0.2 yielded a sensitivity and specificity of 89.2% and 43.2%, respectively. Among the 223 patients who required oxygen, the AUC was 0.825. Sensitivity at a cut-off of 0.5% and 0.2% was 88.7% and 97.9%, respectively. Although the sensitivity was lower when the days from symptom onset were fewer, the sensitivity increased for both cut-off values after 5 days. We evaluated Ali-M3 using external validation with symptomatic patient data from Japanese tertiary care facilities. As Ali-M3 showed sufficient sensitivity performance, despite a lower specificity performance, Ali-M3 could be useful in excluding a diagnosis of COVID-19.

BackgroundThe clinical effect of enteral administration of sleep-promoting medication (SPM) in mechanically ventilated patients remains unclear. This study aimed to investigate the relationship between enteral SPM administration and the intravenous sedative dose and examine the safety and cost of enteral SPM administration.MethodsThis single-center retrospective cohort study was conducted in a Japanese tertiary hospital intensive care unit (ICU). The exposure was enteral SPM administration during mechanical ventilation. The outcome was the average daily propofol dose per body weight administered as a continuous sedative during mechanical ventilation. Patients were divided into three groups based on the timing of SPM administration at ICU admission: "administration within 48 hours (early administration [EA])," "administration after 48 hours (late administration [LA])," and "no administration (NA)." We used multiple linear regression models.ResultsOf 123 included patients, 37, 50, and 36 patients were assigned to the EA, LA, and NA groups, respectively. The average daily propofol dose per body weight was significantly lower in the EA group than in the LA and NA groups (β -5.13 [95% confidence interval (CI) -8.93 to -1.33] and β -4.51 [95% CI -8.59 to -0.43], respectively). Regarding safety, enteral SPM administration did not increase adverse events, including self-extubation. The total cost of neuroactive drugs tended to be lower in the EA group than in the LA and NA groups.ConclusionsEarly enteral SPM administration reduced the average daily propofol dose per body weight without increasing adverse events.

This systematic review aimed to evaluate the diagnostic accuracy of thoracic ultrasound in malignant pleural effusion. Articles published until December 2019 in MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the International Clinical Trials Registry Platform were screened by two authors independently to extract data and evaluate the risks of bias and applicability using the modified Quality Assessment of Diagnostic Accuracy Studies-2 tool. We described the forest plots of each thoracic ultrasound finding. We estimated the pooled sensitivity and specificity of pleural nodularity using the bivariate random-effects model. We included seven articles and found that each thoracic ultrasound finding had low sensitivity. The pooled specificity of pleural nodularity was 96.9% (95% CI 93.2%–98.6%). In conclusion, thoracic ultrasound is not useful in ruling out malignant pleural effusion. Physicians can proceed rigorously to repeat thoracentesis or other invasive procedures when pleural nodularity is detected.

Background and study aims We aimed to assess the efficacy and safety of the starting position during colonoscopy. Patients and methods We searched CENTRAL, MEDLINE, EMBASE, and the WHO International Clinical Trials Registry Platform through February 2019 to identify studies reporting the comparison between the right/supine/prone/tilt-down and left lateral starting position during colonoscopy. The primary outcomes were mean cecal insertion time and adverse events requiring medication. Two reviewers performed study selection and risk of bias assessment. We determined the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation method. This study was registered in PROSPERO (CRD42019124360). Results We identified 10 randomized controlled trials (RCTs) (2083 participants), including three trials on right/tilt-down versus left, two trials on supine/prone versus left, respectively. Mean difference in mean cecal insertion time in supine versus left was –41.0 s (95 % confidence interval [CI] –57.3 to –24.7) in one study and in tilt-down versus left was – 37.3 s (95 % CI –72.1 to –2.4; I2 = 58 %) in three studies; however, there were no statistically significant differences in prone/right versus left position (very low certainty of evidence). Four of eight studies noted adverse effects requiring medication (moderate certainty of evidence). One RCT applying the tilt-down position was terminated because of increased occurrence of oxygen desaturation. Conclusion We could not conclusively determine the efficacy and safety of the starting position during colonoscopy because of low certainty of evidence. Further studies are needed to confirm the efficacy and safety of the starting potion during colonoscopy.

Few studies have delineated the real-world, long-term trends of prescription patterns of antidepressants for patients with major depressive disorder (MDD). This study aims to describe their vicissitudes in the nationally representative sample of the US from 1996 to 2015 and explore their characteristics. We used the Medical Expenditure Panel Survey, a nationally representative database of the US population, between 1996 and 2015. We estimated the prevalence of MDD among adults, calculated the proportions of those on antidepressant treatment as well as those on specific drugs through the two decades, and determined their dosages in 2015. We conducted multivariable regression to find possible factors related to their suboptimal prescriptions. The prevalence of adults diagnosed with MDD increased from 6.1% (95% CI, 5.7–6.6%) in 1996 to 10.4% (9.7–11.1%) in 2015. The proportion of patients without any antidepressant therapy decreased but still accounted for 30.6% (28.3–33.1%) in 2015. Sertraline and fluoxetine were among the most frequently prescribed antidepressants throughout the 20 years, while the trend for some new drugs changed dramatically. 16.1% (12.5–20.2%) of patients of MDD on antidepressant monotherapy were prescribed with suboptimal doses in 2015; the risk was lower for those who had higher Body Mass Index (OR 0.94 [0.90–0.99]), longer-term prescriptions (OR 0.92 [0.87–0.97]), and the risk was higher for those who were prescribed with tricyclic antidepressants (OR 11.21 [2.12–59.34], compared with serotonin reuptake inhibitors (SSRIs)), and antidepressants other than SSRIs and serotonin and norepinephrine reuptake inhibitors (OR 4.12 [1.95, 8.73], compared with SSRIs). This study confirmed the growing numbers of patients with MDD and the increase in the antidepressant prescriptions among them. However, the existence of patients without any antidepressant prescriptions or with suboptimal prescriptions and the variable prescription patterns through the decades might suggest some unresolved gaps between evidence and practice.

Background: Writing letters to the editor based on critical appraisal can serve as the first step in scholarly activity. The workshop in this study focused on educating physicians about the best ways to write letters to the editor. Methods: We conducted a 90-minute workshop as a part of scientific conference. Participants were physicians and medical students who chose to join this workshop. We developed the following learning outcomes for participants: 1) to be able to explain falsificationism; 2) to be able to explain how to check author instructions; 3) to be able to explain how to write a letter to the editor. Results: Twenty-eight participants, including three medical students, attended the workshop. Participants' satisfaction with the workshop had a mean of 4.5 points out of 5 (standard deviation: 0.5). Nearly 80% of participants achieved the learning outcomes. Four participants' groups submitted letters within a month after the workshop, and all four were published. These four groups encompassed a total of 13 authors. In addition, none of the first author of each letter had previously written a clinical research paper. Findings and Discussion: This workshop improved not only the participants' knowledge but it also led to the concrete result of four published letters. Japanese physicians would be able to use this framework to write letters to the editor.

Phlebosclerotic colitis presents with ischemic bowels and calcification of the mesenteric veins. Owing to its rarity, we have little information on the complications of this disease. Herein, we report on a 77-year-old woman with phlebosclerotic colitis and interstitial lung disease. She was diagnosed as having phlebosclerotic colitis by CT and colonoscopy. At the same time, chest CT also showed interstitial lung disease. After 4 years, she experienced exacerbation of interstitial lung disease. She recovered without treatment. The occurrence of interstitial lung disease may have been associated with her phlebosclerotic colitis.

Abstract Objective PROSPERO, an international prospective register of systematic reviews, was launched in February 2011 to reduce publication bias of systematic reviews (SRs). A questionnaire survey of SR researchers conducted in 2005 indicated the existence of unpublished SRs and the potential influence of lack of funding as a reason for non-publication. Here, we investigated the publication status of registered SRs in the 1st year that PROSPERO launched and assessed the association between publication and the existence of funding or conflicts of interest (COIs). Results We identified 326 SRs registered in PROSPERO from February 2011 through February 2012. Among them, 85 SRs (26%) remained unpublished at least 65 months after registration. We found 241 published reports, including four conference abstracts and one poster presentation. Median time to publication from protocol registration was 16.3 months. Funding for SRs was associated with publication [odds ratio (OR) = 2.10; 95% confidence interval (CI) = 1.26 to 3.50]. We found no significant association of author-reported COIs with publication (OR = 2.35; 95% CI = 0.67 to 8.20). Twenty SRs were not published despite the authors reporting completion of the reviews in PROSPERO.

Background: Malignant pleural effusion reduces cancer patients’ quality of life. Some experts have suggested that chest tubes should be directed posteriorly during pleurodesis. We conducted this study to clarify whether a posteriorly positioned chest tube has a better success rate than does an interlobular or anterior one. Methods: We performed a retrospective chart review of patients undergoing pleurodesis between April 2011 and September 2016, and 86 patients were enrolled and divided into two groups based on the chest tube position: posterior (group 1) and others [interlobular and anterior (group 2)]. The primary endpoint was the success rate of pleurodesis, and the secondary endpoint was the complication rate (pain and fever). P

[This corrects the article DOI: 10.1371/journal.pone.0201292.].

The purpose of this study was to investigate the effect of the air permeability of ski jumping suit fabric on aerodynamic characteristics. In the study, four types of fabric with different air permeabilities were installed onto a fabric-clothed elliptic cylinder, and the flow behavior around its surface was investigated through wind tunnel experiments. The stall was delayed by using the fabric with higher air permeability. The air flow permeated the surface of the elliptic cylinder through the fabric for the fabric with high air permeability. This air flowed out into the separation region through the fabric again, which suppress stall. The stall characteristics for the fabric-clothed elliptic cylinder were influenced by the air permeability of the fabric. The boundary layer thickness on the outer surface and the turbulence levels of the boundary layer affected the air permeability of the fabric. The higher air permeability fabrics improved the stall characteristics.