Prehospital shock index predicts 24-h mortality in trauma patients with a normal shock index upon emergency department arrival.

BACKGROUND: The shock index (heart rate divided by systolic blood pressure) of trauma patients upon emergency department arrival predicts blood loss and death. However, some patients with normal shock indices (0.4 < shock index <0.9) upon emergency department arrival also have poor prognoses. This study aimed to determine whether abnormal prehospital shock indices in trauma patients with normal shock indices upon emergency department arrival were predictors of a high risk of mortality. METHODS: We conducted a retrospective cohort study of emergency department-admitted trauma patients from 2004 to 2017. The study included 89,495 consecutive trauma patients aged ≥16 years, with Abbreviated Injury Scale score of ≥3, who were transported to the emergency department directly from the field and had a normal shock index upon emergency department arrival. According to the prehospital shock index scores, the patients were categorized into low shock index (≤ 0.4), normal shock index, and high shock index (≥0.9) groups. Odds ratios and 95% confidence intervals were calculated using logistic regression analysis. RESULTS: The 89,495 patients had a median age of 64 (interquartile range: 43-79) years, and 55,484 (62.0%) of the patients were male. There were 1350 (1.5%) 24-h deaths in total; 176/4263 (4.1%), 1017/78,901 (1.3%), and 157/6331 (2.5%) patients were in the low, normal, and high prehospital shock index groups, respectively. The adjusted odds ratios for 24-h mortality compared with the normal shock index group were 1.63 (95% confidence interval: 1.34-1.99) in the low shock index group and 1.62 (95% confidence interval: 1.31-1.99) in the high shock index group. CONCLUSION: Trauma patients with abnormal prehospital shock indices but normal shock indices upon emergency department arrival are at a higher risk of 24-h mortality. Identifying these indices could improve triage and targeted care for patients.

Impact of the Clinical Trials Act on Noncommercial Clinical Research in Japan: An Interrupted Time-series Analysis.

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.

Characteristics of Children Cared for by a Physician-Staffed Helicopter Emergency Medical Service.

OBJECTIVES: The effectiveness of Japanese helicopter emergency medical services (HEMS) and interventions at the scene is not clear as regard children. For effective use of HEMS at the clinical scene, we need to clarify the characteristics of pediatric patients cared for by HEMS. Therefore, the objective of this study was to describe the characteristics of pediatric scene flights and to describe the procedures performed on the patients. METHODS: This was a retrospective cohort study based on the database for children aged younger than 18 years who were cared for by physician-staffed HEMS of Ibaraki prefecture, in Japan. We reviewed the database for air medical transports conducted at our institution from July 2010 to December 2016. RESULTS: During the 6.5-year period, the Ibaraki HEMS attended to 288 children. The median age of the children was 11 (interquartile range, 5-14) years. Of the total, 196 (68.1%) of the children had trauma-related injuries. The head was the most common site of significant injuries (12.4%). The most common cause of nontrauma incidents was seizure (9.0%). In 65.9% of the patients, the injury or illness was of mild or moderate severity at the scene. An intervention was applied at the scene in 76.0% of the cases: 75.1%, intravenous route; 6.9%, intubation; and 13.4%, drug administration. Of those patients, 29.1% were discharged from the emergency department. In-hospital mortality accounted for 1.5% (n = 2) of the cases. CONCLUSIONS: Although the condition at the scene of most of the pediatric patients transported by the physician-staffed HEMS was not severe, an intervention was frequently applied from the scene. Improving the dispatch criteria and monitoring compliance are needed for appropriate use of HEMS.

Publication statuses of clinical trials supporting FDA-approved immune checkpoint inhibitors: a meta-epidemiological investigation.

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.

Synthesis of Single-Walled Carbon Nanotubes Coated with Thiol-Reactive Gel via Emulsion Polymerization.

Single-walled carbon nanotubes (SWNTs) have unique near-infrared absorption and photoemission properties that are attractive for in vivo biological applications such as photothermal cancer treatment and bioimaging. Therefore, a smart functionalization strategy for SWNTs to create biocompatible surfaces and introduce various ligands to target active cancer cells without losing the unique optical properties of the SWNTs is strongly desired. This paper reports the design and synthesis of a SWNT/gel hybrid containing maleimide groups, which react with various thiol compounds through Michael addition reactions. In this hybrid, the method called carbon nanotube micelle polymerization was used to noncovalently modify the surface of SWNTs with a cross-linked polymer gel layer. This method can form an extremely stable gel layer on SWNTs; such stability is essential for in vivo biological applications. The monomer used to form the gel layer contained a maleimide group, which was protected with furan in endo-form. The resulting hybrid was treated in water to induce deprotection via a retro-Diels-Alder reaction and then functionalized with thiol compounds through Michael addition. The functionalization of the hybrid was explored using a thiol-containing fluorescent dye as a model thiol, and the formation of the SWNT-dye conjugate was confirmed by energy transfer from the dye to SWNTs. Our strategy offers a promising SWNT-based platform for biological functionalization for cancer targeting, imaging, and treatment.

Mortality and Morbidity After Hartmann's Procedure Versus Primary Anastomosis Without a Diverting Stoma for Colorectal Perforation: A Nationwide Observational Study.

BACKGROUND: The benefit of primary anastomosis (PA) without a diverting stoma over Hartmann's procedure (HP) for colorectal perforation remains controversial. We compared postoperative mortality and morbidity between HP and PA without a diverting stoma for colorectal perforation of various etiologies. METHODS: Using the Japanese Diagnosis Procedure Combination database, we extracted data on patients who underwent emergency open laparotomy for colorectal perforation of various etiologies from July 1, 2010 to March 31, 2014. We compared 30-day mortality, postoperative complication rates, and postoperative critical care interventions between HP and PA groups using propensity score matching, inverse probability of treatment weighting, and instrumental variable analyses to adjust for measured and unmeasured confounding factors. RESULTS: We identified 8500 eligible patients (5455 HP and 3045 PA). In the propensity score-matched model, a significant difference between the HP and PA groups was detected in 30-day mortality (7.7% vs. 9.6%; risk difference, 1.9%; 95% confidence interval [CI], 0.5-3.4). The inverse probability of treatment weighting showed similar results (8.8% vs. 10.7%; risk difference, 1.9%; 95% CI, 1.0-2.8). In the instrumental variable analysis, the point estimate suggested similar direction to that of the propensity score analyses (risk difference, 4.4%; 95% CI, -3.3 to 12.1). The PA group had significantly higher rates of secondary surgery for complications (4.6% vs. 8.4%; risk difference, 3.8%; 95% CI, 2.5-4.1) and slightly longer duration of postoperative critical care interventions. CONCLUSIONS: This study revealed a significant difference in 30-day mortality between HP and PA without a diverting stoma.

Whole-Body Computed Tomography During Initial Management and Mortality Among Adult Severe Blunt Trauma Patients: A Nationwide Cohort Study.

BACKGROUND: Whole-body computed tomography (WBCT) is increasingly being incorporated into the initial management of blunt trauma patients. Several observational studies have suggested that, compared to selective CT, WBCT is associated with lower mortality. In contrast, a randomized controlled trial found no significant difference in survival between patients undergoing WBCT compared to selective CT. Our objective was to confirm the association between WBCT and in-hospital mortality among adult severe blunt trauma patients. METHODS: This was a retrospective cohort study based on Japan Trauma Data Bank 2004-2015 registry data. The study population comprised adult severe blunt trauma patients with at least one abnormal vital sign: systolic blood pressure ≤100 mmHg, heart rate ≥120, respiratory rate ≥30 or ≤10, or Glasgow Coma Score ≤13. The primary outcome was in-hospital mortality. To adjust for both measured and unmeasured confounders, we performed instrumental variable (IV) analysis to compare the in-hospital mortality of patients undergoing WBCT with those undergoing selective CT. RESULTS: Of 40,435 patients who were eligible for this study, 19,766 (48.9%) patients underwent WBCT. The proportion of patients undergoing WBCT significantly increased during the study period, from 10.7% in 2004 to 59.6% in 2015. Primary IV analysis showed a significant association between WBCT and lower in-hospital mortality (odds ratio 0.84, 95% confidence interval 0.72-0.98). CONCLUSIONS: WBCT can be beneficial in patients with blunt trauma which has compromised vital signs. These findings from a nationwide study suggest that physicians should consider WBCT for blunt trauma patients when warranted by vital signs.

Deposition of boron doped DLC films on TiNb and characterization of their mechanical properties and blood compatibility.

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.

Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a metabolite of phosphatidylcholine generated by gut microbiota and liver enzymes, and has recently been recognized as contributing to atherosclerosis. Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease (sudden death, myocardial infarction, or stroke) in patients undergoing elective coronary angiography. We aimed to clarify whether TMAO levels are associated with the number of infarcted coronary arteries as a measure of the severity of atherosclerosis, with adjustment using a priori-defined covariates such as kidney function. METHODS: By conducting a cross-sectional study of 227 patients who underwent cardiovascular surgery for coronary artery disease, valvular heart disease, or aortic disease, the association between serum TMAO levels as measured by HPLC-APCI-MS/MS and the number of infarcted coronary arteries was evaluated using ordered logistic regression models with adjustment of 10 covariates, including chronic kidney disease (CKD) stage. Unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined. RESULTS: Significantly higher TMAO levels were observed in advanced-stage CKD (p ≤ 0.001). In fully adjusted models with the 10 covariates, a significantly increased number of infarcted coronary arteries was identified in the highest quartile and quintile of TMAO compared to the lowest quartile (OR 11.9; 95 % CI 3.88-36.7, p ≤ 0.001) and quintile (OR 14.1; 95 % CI 3.88-51.2; p ≤ 0.001), respectively, independent of dyslipidemia. CONCLUSIONS: Higher serum TMAO levels may be associated with advanced CKD stages and with an increased number of infarcted coronary arteries in patients who undergo cardiovascular surgery.

[Pulmonary Artery Catheter Injured by Ablation Device during Maze Procedure].

We report a case of pulmonary artery catheter (PAC) injury by radio frequency device for maze procedure. A 64-year-old female with severe mitral insufficiency, tricuspid insufficiency and paroxysmal atrial fibrillation was scheduled for mitral valve repair, tricuspid annulo- plasty and maze procedure including right-sided maze. Under general anesthesia, a PAC was inserted to pul- monary artery (PA) uneventfully. After radio frequency maze procedure and mitral valve repair, PAC was removed from right atrium by the surgeon for tricus- pid annuloplasty. Thereafter, the surgeon reinserted the PAC under transesophageal echocardiographic guidance since PAC balloon could not be inflated. PA pressure and cardiac output were not shown despite other parameters were correct We removed the PAC and reinserted a new one after the surgery. The PAC was compressed at about 25 cm from the tip and it appears to have been injured during right-sided maze procedure with radio frequency device. Complications of PAC are well known, including PA rupture and suture entrapment to the right atrium. To best of our knowledge, this is the first reported case of PAC injury by radio frequency device. Fortunately the PAC was not torn in our case ; however, there might have been a risk of infection through the thermodilu- tion cable.

Modulation of friction dynamics in water by changing the combination of the loop- and graft-type poly(ethylene glycol) surfaces.

A Velcro-like poly(ethylene glycol) (PEG) interface was prepared in order to control the friction dynamics of material surfaces. Graft- and loop-type PEGs were formed on mirror-polished Ti surfaces using an electrodeposition method with mono- and di-amine functionalized PEGs. The friction dynamics of various combinations of PEG surfaces (i.e., graft-on-graft, loop-on-loop, graft-on-loop, and loop-on-graft) were investigated by friction testing. Here, only the Velcro-like combinations (graft-on-loop and loop-on-graft) exhibited a reversible friction behavior (i.e., resetting the kinetic friction coefficient and the reappearance of the maximum static friction coefficient) during the friction tests. The same tendency was observed when the molecular weights of loop- and graft-type PEGs were tested at 1 k and 10 k, respectively. This indicates that a Velcro-like friction behavior could be induced by simply changing the conformation of PEGs, which suggests a novel concept of altering polymer surfaces for the effective control of friction dynamics.

The impact of continuity correction methods in Cochrane reviews with single-zero trials with rare events: A meta-epidemiological study.

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 ~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.

Association between a history of major osteoporotic fractures and subsequent hip fracture: a systematic review and meta-analysis.

PURPOSE: A history of fractures involving the distal radius, proximal humerus, spine, and hip may be associated with the incidence of subsequent hip fractures in older people. However, a comprehensive summary of this association using a rigorous methodology is lacking. Our objective was to systematically review the literature and examine the association between four major osteoporotic fractures and subsequent hip fractures in individuals aged ≥ 50 years. METHODS: We searched MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov on February 15, 2023. The search included cohort or case-control studies investigating the association between these four types of osteoporotic fractures and subsequent hip fractures. We pooled the hazard ratios (HRs) with 95% confidence intervals (CI) using the random-effects model. We used the Quality In Prognosis Studies tool to assess the risk of bias in the included studies, and the grading of recommendations assessment, development, and evaluation approach to determine the certainty of evidence. RESULTS: The selection process identified 48 studies for qualitative synthesis and 23 studies (2,239,217 participants) for meta-analysis. The overall methodological quality had a low risk of bias in 65% of the included studies. The association between a history of major osteoporotic fractures and subsequent hip fracture varied, with a high certainty of evidence for a history of proximal humerus and hip fractures (HR 2.02, 95% CI 1.75-2.33 and 2.86, 95% CI 1.92-4.25, respectively), moderate certainty for distal radius fractures (HR 1.66, 95% CI 1.53-1.81), and low certainty for spine fractures (HR 1.53, 95% CI 1.38-1.69). CONCLUSIONS: In conclusion, a history of major osteoporotic fractures, particularly distal radius, proximal humerus, and hip fractures, is associated with subsequent hip fractures in older adults. Further research is needed to verify the association between a history of spine fracture and subsequent hip fractures. PROTOCOL REGISTRATION: Open Science Framework ( https://osf.io/7fjuc ).

Methodological Quality of Physical Therapy-Related Trials Published in Open Access and Subscription Journal: A Cross-sectional Meta-Epidemiological Study.

OBJECTIVE: 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, impact factor, and publication language. DESIGN: In this meta-epidemiological study, we searched the Physiotherapy Evidence Database on May 8, 2021, to include any physical therapy-related trials published from January 1, 2020. We extracted variables such as Consolidated Standards of Reporting Trials endorsement, the Physiotherapy Evidence Database score, and publication type. We compared the Physiotherapy Evidence Database score between the publication types using a multivariable generalized estimating equation by adjusting for covariates. RESULTS: A total of 2743 trials were included, with a mean total Physiotherapy Evidence Database score (standard deviation) of 5.8 (±1.5). Trials from open access journals had a lower total Physiotherapy Evidence Database score than those from subscription-based journals (5.5 ± 1.5 vs. 5.9 ± 1.5, mean difference = -0.4; 95% confidence interval = 0.3-0.5). Generalized estimating equation revealed that open access publication was significantly associated with the total Physiotherapy Evidence Database score (mean difference = -0.42; P < 0.001). CONCLUSIONS: In the recent physical therapy-related trials, open access publications demonstrated lower methodological quality than subscription-based publications, although with a small difference.

Follow-up focused on psychological intervention initiated after intensive care unit in adult patients and informal caregivers: a systematic review and meta-analysis.

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.

The effectiveness of exercise with behavior change techniques in people with knee osteoarthritis: A systematic review with meta-analysis.

OBJECTIVE: 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. LITERATURE SURVEY: We searched randomized controlled trials (RCTs) in eight databases (MEDLINE, Embase, CENTRAL, CINAHL, PsycINFO, PEDro, ICTRP, and ClinicalTrials.gov) up to November 4, 2021. METHODOLOGY: 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. SYNTHESIS: 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. CONCLUSION: 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. PROTOCOL REGISTRATION: PROSPERO (CRD42020212904).

Twenty-year follow-up of promising clinical studies reported in highly circulated newspapers: a meta-epidemiological study.

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.

Proportion attributable to contextual effects in general medicine: a meta-epidemiological study based on Cochrane reviews.

OBJECTIVES: Our 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. DESIGN: We conducted a meta-epidemiological study. SETTING: We searched the Cochrane Database of Systematic Reviews with the keyword 'placebo' in titles, abstracts and keywords on 1 January 2020. PARTICIPANTS: We included reviews that showed statistically significant beneficial effects of the intervention over placebo for the first primary outcome. MAIN OUTCOME MEASURES: We 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 STATEMENT: No patient or member of the public was involved in conducting this research. RESULTS: We 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). CONCLUSIONS: The 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.

An open competition involving thousands of competitors failed to construct useful abstract classifiers for new diagnostic test accuracy systematic reviews.

There are currently no abstract classifiers, which can be used for new diagnostic test accuracy (DTA) systematic reviews to select primary DTA study abstracts from database searches. Our goal was to develop machine-learning-based abstract classifiers for new DTA systematic reviews through an open competition. We prepared a dataset of abstracts obtained through database searches from 11 reviews in different clinical areas. As the reference standard, we used the abstract lists that required manual full-text review. We randomly splitted the datasets into a train set, a public test set, and a private test set. Competition participants used the training set to develop classifiers and validated their classifiers using the public test set. The classifiers were refined based on the performance of the public test set. They could submit as many times as they wanted during the competition. Finally, we used the private test set to rank the submitted classifiers. To reduce false exclusions, we used the Fbeta measure with a beta set to seven for evaluating classifiers. After the competition, we conducted the external validation using a dataset from a cardiology DTA review. We received 13,774 submissions from 1429 teams or persons over 4 months. The top-honored classifier achieved a Fbeta score of 0.4036 and a recall of 0.2352 in the external validation. In conclusion, we were unable to develop an abstract classifier with sufficient recall for immediate application to new DTA systematic reviews. Further studies are needed to update and validate classifiers with datasets from other clinical areas.