External validation and update of the International Medical Prevention Registry on Venous Thromboembolism bleeding risk score for predicting bleeding in acutely ill hospitalized medical patients: a retrospective single-center cohort study in Japan.

BACKGROUND: The International Medical Prevention Registry for Venous Thromboembolism (IMPROVE) Bleeding Risk Score is the recommended risk assessment model (RAM) for predicting bleeding risk in acutely ill medical inpatients in Western countries. However, few studies have assessed its predictive performance in local Asian settings. METHODS: We retrospectively identified acutely ill adolescents and adults (aged ≥ 15 years) who were admitted to our general internal medicine department between July 5, 2016 and July 5, 2021, and extracted data from their electronic medical records. The outcome of interest was the cumulative incidence of major and nonmajor but clinically relevant bleeding 14 days after admission. For the two-risk-group model, we estimated sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively). For the 11-risk-group model, we estimated C statistic, expected and observed event ratio (E/O), calibration-in-the-large (CITL), and calibration slope. In addition, we recalibrated the intercept using local data to update the RAM. RESULTS: Among the 3,876 included patients, 998 (26%) were aged ≥ 85 years, while 656 (17%) were hospitalized in the intensive care unit. The median length of hospital stay was 14 days. Clinically relevant bleeding occurred in 58 patients (1.5%), 49 (1.3%) of whom experienced major bleeding. Sensitivity, specificity, NPV, and PPV were 26.1% (95% confidence interval [CI]: 15.8-40.0%), 84.8% (83.6-85.9%), 98.7% (98.2-99.0%), and 2.5% (1.5-4.3%) for any bleeding and 30.9% (95% CI: 18.8-46.3%), 84.9% (83.7-86.0%), 99.0% (98.5-99.3%), and 2.5% (1.5-4.3%) for major bleeding, respectively. The C statistic, E/O, CITL, and calibration slope were 0.64 (95% CI: 0.58-0.71), 1.69 (1.45-2.05), - 0.55 (- 0.81 to - 0.29), and 0.58 (0.29-0.87) for any bleeding and 0.67 (95% CI: 0.60-0.74), 0.76 (0.61-0.87), 0.29 (0.00-0.58), and 0.42 (0.19-0.64) for major bleeding, respectively. Updating the model substantially corrected the poor calibration observed. CONCLUSIONS: In our Japanese cohort, the IMPROVE bleeding RAM retained the reported moderate discriminative performance. Model recalibration substantially improved the poor calibration obtained using the original RAM. Before its introduction into clinical practice, the updated RAM needs further validation studies and an optimized threshold.

Association between intrarenal venous flow from Doppler ultrasonography and acute kidney injury in patients with sepsis in critical care: a prospective, exploratory observational study.

BACKGROUND: Intrarenal venous flow (IRVF) patterns assessed using Doppler renal ultrasonography are real-time bedside visualizations of renal vein hemodynamics. Although this technique has the potential to detect renal congestion during sepsis resuscitation, there have been few studies on this method. We aimed to examine the relationship between IRVF patterns, clinical parameters, and outcomes in critically ill adult patients with sepsis. We hypothesized that discontinuous IRVF was associated with elevated central venous pressure (CVP) and subsequent acute kidney injury (AKI) or death. METHODS: We conducted a prospective observational study in two tertiary-care hospitals, enrolling adult patients with sepsis who stayed in the intensive care unit for at least 24 h, had central venous catheters placed, and received invasive mechanical ventilation. Renal ultrasonography was performed at a single time point at the bedside after sepsis resuscitation, and IRVF patterns (discontinuous vs. continuous) were confirmed by a blinded assessor. The primary outcome was CVP obtained at the time of renal ultrasonography. We also repeatedly assessed a composite of Kidney Disease Improving Global Outcomes of Stage 3 AKI or death over the course of a week as a secondary outcome. The association of IRVF patterns with CVP was examined using Student's t-test (primary analysis) and that with composite outcomes was assessed using a generalized estimating equation analysis, to account for intra-individual correlations. A sample size of 32 was set in order to detect a 5-mmHg difference in CVP between IRVF patterns. RESULTS: Of the 38 patients who met the eligibility criteria, 22 (57.9%) showed discontinuous IRVF patterns that suggested blunted renal venous flow. IRVF patterns were not associated with CVP (discontinuous flow group: mean 9.24 cm H2O [standard deviation: 3.19], continuous flow group: 10.65 cm H2O [standard deviation: 2.53], p = 0.154). By contrast, the composite outcome incidence was significantly higher in the discontinuous IRVF pattern group (odds ratio: 9.67; 95% confidence interval: 2.13-44.03, p = 0.003). CONCLUSIONS: IRVF patterns were not associated with CVP but were associated with subsequent AKI in critically ill adult patients with sepsis. IRVF may be useful for capturing renal congestion at the bedside that is related to clinical patient outcomes.

Iodinated Contrast Media Substitution to Prevent Recurrent Hypersensitivity Reactions: A Systematic Review and Meta-Analysis.

Background Changing iodinated contrast media (ICM) may reduce the risk of recurrent ICM-induced hypersensitivity reactions in patients with a prior reaction. Purpose To perform a systematic review on the effectiveness of ICM change in comparison with no change to prevent recurrent ICM immediate hypersensitivity reactions. Materials and methods Multiple data bases were searched without language restriction between January 1990 and August 2021 to identify comparative studies of any design that included patients with a prior ICM hypersensitivity reaction to low-osmolality ICM and re-exposure to intravascular ICM. The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, and random-effects meta-analysis. The primary outcome was the incidence of all-grade immediate recurrent hypersensitivity reactions. Secondary outcomes were the incidence of severe immediate recurrent hypersensitivity reactions and other adverse events associated with ICM change. Results Six retrospective observational studies at moderate to severe risk of bias assessed 7155 adult patients (4329 in the ICM change group and 2826 in the no-change group). Studies adopted nonstandardized switching methods, and the proportions of the ICM change group ranged between 19% (five of 27 examinations) and 80% (3104 of 3880 examinations). A Bayesian meta-analysis revealed that changing ICM was associated with a reduced risk of recurrent hypersensitivity reaction by 61% (risk ratio = 0.39; 95% credible interval [CrI]: 0.24, 0.58). The wide-ranging estimates of risk reduction were not explained by the risk of bias ratings, the event rates in the no-change group, the index-reaction severity, or the co-administered nonstandard premedication. Rare severe recurrent reactions (five studies with five events) precluded a conclusion (risk ratio = 0.34, favoring ICM change; CrI: 0.01, 3.74). Adverse events associated with ICM change were not reported. Conclusion In observational evidence of limited quality, iodinated contrast media (ICM)-change was associated with a reduced risk of recurrent immediate hypersensitivity reaction in patients with a prior ICM-induced hypersensitivity reaction. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by McDonald in this issue.

Predictors of Diagnostic Contributions and Spontaneous Remission of Symptoms Associated with Positron Emission Tomography with Fluorine-18-Fluorodeoxy Glucose Combined with Computed Tomography in Classic Fever or Inflammation of Unknown Origin: a Retrospective Study.

BACKGROUND: In patients with fever or inflammation of unknown origin (fever of unknown origin [FUO] or inflammation of unknown origin [IUO], respectively), expert consensus recommends the use of positron emission tomography with fluorine-18-fluorodeoxy glucose combined with computed tomography (FDG-PET/CT) when standard work-up fails to identify diagnostic clues. However, the clinical variables associated with successful localization of the cause by FDG-PET/CT remain uncertain. Moreover, the long-term outcomes of patients with unexplained FUO or IUO after negative FDG-PET/CT results are unknown. Therefore, we assessed predictors of successful diagnosis of FUO or IUO caused by FDG-PET/CT and associations of spontaneous remission of symptoms with FDG-PET/CT results. METHODS: All patients with FUO or IUO, who underwent FDG-PET/CT from 2013 to 2019 because diagnostic work-up failed to identify a cause, were retrospectively included. We calculated the diagnostic yield and performed multivariable logistic regression to assess characteristics previously proposed to be associated with successful localization of FUO or IUO causes. We also assessed whether the FDG-PET/CT results were associated with spontaneous remissions. RESULTS: In total, 50 patients with diagnostically challenging FUO or IUO (35 with FUO and 15 with IUO) were assessed. Other than one case of infection, all the identified causes were either malignancy or non-infectious inflammatory diseases (each with 18 patients), and FDG-PET/CT correctly localized the cause in 29 patients (diagnostic yield = 58%). None of the proposed variables was associated with successful localization. All 13 patients with sustained unexplained cause remained alive (median follow-up, 190 days). Spontaneous remission was observed in 4 of 5 patients with a negative FDG-PET/CT, and 1 of 8 with a positive result (P = 0.018). CONCLUSION: In the current cohort, the proposed variables were not predictive for successful localization by FDG-PET/CT. A negative FDG-PET/CT scan may be prognostic for spontaneous remission in patients with sustained FUO or IUO.

Sputum Gram Stain for Bacterial Pathogen Diagnosis in Community-acquired Pneumonia: A Systematic Review and Bayesian Meta-analysis of Diagnostic Accuracy and Yield.

BACKGROUND: The clinical role of sputum Gram stain (SGS) in community-acquired pneumonia (CAP) diagnosis remains controversial. A 1996 meta-analysis of the diagnostic accuracy of SGS reported heterogeneous results. To update the available evidence, we performed a systematic review and a Bayesian standard and latent-class model meta-analysis. METHODS: We searched Medline, Embase, and Cochrane Central by 23 August 2018 to identify studies reporting on the diagnostic accuracy, yield (percentage of patients with any pathogen[s] correctly identified by SGS), and clinical outcomes of SGS in adult patients with CAP. Two reviewers extracted the data. We quantitatively synthesized the diagnostic accuracy and yield, and descriptively analyzed other outcomes. RESULTS: Twenty-four studies with 4533 patients were included. The methodological and reporting quality of the included studies was limited. When good-quality sputum specimens were selected, SGS had a summary sensitivity of 0.69 (95% credible interval [CrI], .56-.80) and specificity of 0.91 (CrI, .83-.96) for detecting Streptococcus pneumoniae, and a sensitivity of 0.76 (CrI, .60-.87) and specificity of 0.97 (CrI, .91-.99) for Haemophilus influenzae. Adjusted analyses accounting for imperfect reference standards provided higher-specificity estimates than the unadjusted analyses. Bacterial pathogens were identified in 73% (CrI, 26%-96%) of good-quality specimens, and 36% (CrI, 22%-53%) of all specimens regardless of quality. Evidence on other bacteria was sparse. CONCLUSIONS: SGS was highly specific to diagnose S. pneumoniae and H. influenzae infections in patients with CAP. With good-quality specimens, SGS can provide clinically actionable information for pathogen-directed antibiotic therapies.

Diagnostic accuracy of DAT-SPECT and MIBG scintigraphy for dementia with Lewy bodies: an updated systematic review and Bayesian latent class model meta-analysis.

PURPOSE: Imperfect clinical reference standards can preclude accurately estimating the diagnostic accuracy of DAT-SPECT and MIBG myocardial scintigraphy for diagnosing DLB. To investigate the validity of unadjusted accuracy, we updated our previous meta-analysis. METHODS: Literature search was updated to March 18, 2018. We also examined published systematic review reports. Two investigators extracted data and rated study validity using the QUADAS-2 tool. We performed a Bayesian latent class model meta-analysis accounting for imperfect reference standards. RESULTS: We evaluated 27 studies including 2236 patients. With the exception of two DAT-SPECT studies that involved postmortem neuropathological verification, studies were susceptible to bias from imperfect reference standards. Compared with the unadjusted accuracy estimates, the adjusted sensitivity values were similar, whereas the adjusted specificity values were generally lower for detecting α-synuclein pathology in the brain. The adjusted summary sensitivity and specificity were 0.86 (95% credible interval [CrI], 0.76-0.95) and 0.81 (CrI, 0.70-0.92), and 0.93 (CrI, 0.74-1.00) and 0.75 (CI, 0.47-0.94) for visual and semi-quantitative assessments of DAT-SPECT, respectively; 0.92 (CrI, 0.81-0.99) and 0.80 (CrI, 0.67-0.93), and 0.87 (CrI, 0.74-0.98) and 0.80 (CrI, 0.69-0.93), for delayed- and early-phase scans of MIBG scintigraphy, respectively. When diagnosing the typical clinical syndrome, the adjusted accuracy values were similar to the unadjusted estimates. The adjusted sensitivity and specificity were 0.89 (CrI, 0.75-0.98) and 0.87 (CrI, 0.72-0.97), and 0.97 (CrI, 0.78-1.0) and 0.70 (CrI, 0.43-0.92) for visual and semi-quantitative assessments of DAT-SPECT, respectively; and 0.93 (CrI, 0.81-0.98) and 0.90 (CrI, 0.73-0.97), and 0.85 (CrI, 0.66-0.96) and 0.96 (95% CI, 0.83-1.0) for delayed- and early-phase scans of MIBG scintigraphy, respectively. CONCLUSIONS: In our adjusted analyses, both imaging biomarkers had high diagnostic accuracy for detecting the hallmark pathology in the brain and for diagnosing the typical clinical syndrome.

Frequency of unsatisfactory cervical cytology smears in cancer screening of Japanese women: A systematic review and meta-analysis.

The Bethesda system (TBS) has been used for cervical cytological diagnosis in Japan since 2008. Evaluation of specimen adequacy is the most important aspect of quality assurance and for precise diagnosis in TBS. A systematic review and meta-analysis were carried out to assess the unsatisfactory specimen rate in the primary cervical cancer screening setting in Japan. Ovid Medline and Ichushi-Web databases were searched from inception through to May 2017. Prospective and retrospective studies that reported the proportion of unsatisfactory specimens in healthy asymptomatic Japanese women in a cervical cancer screening program were eligible for inclusion; 17 studies were included in the meta-analysis. The random-effects model meta-analysis calculated summary estimates of the unsatisfactory rate of 0.60% (95% confidence interval [CI], 0.18-1.96%; I2 = 99%) for conventional cytology and 0.04% (95% CI, 0.00-0.35%; I2 = 99%) for liquid-based cytology (LBC). However, comparative results between conventional and liquid-based cytology, based on four direct and nine comparative studies, showed no significant difference (summary odds ratio = 3.5 × 10-2 favoring LBC [95% CI, 6.9 × 10-4 -1.7]; I2 = 98%). In the subgroup analyses and meta-regressions, use of non-cotton devices for conventional cytology and use of a particular platform for LBC were associated with lower unsatisfactory rates. Meta-regression also suggested chronological improvement in unsatisfactory rates for both tests. In Japanese cervical cancer screening programs, conventional cytology remains prevalent. Future research needs to focus on evaluating the impact of screening programs using LBC by comparing the accuracy, performance, and cost-effectiveness with conventional cytology in the Japanese population.

Clinical features of patients with infective endocarditis presenting to the emergency department: a retrospective case series.

Infective endocarditis (IE) is an uncommon clinical problem with diverse, nonspecific presentations. Therefore, information on the clinical features of IE patients presenting to emergency departments (EDs) is scarce. To descriptively analyze the pertinent data, we performed a retrospective chart review. We reviewed 15 consecutive IE patients admitted directly from ED in a university hospital in Japan between 2013 and 2015. We compared their clinical features with those of 14 IE patients admitted during the same period without ED presentations. Patients admitted directly from ED were older than those without ED presentations (median, 78 vs. 52 years; adjusted p = 0.036) and were more likely to have come without referrals (referral rate, 21% vs. 86%; adjusted p = 0.012). These patients were less likely to have been treated with antibiotics before admission (antibiotic-exposure rate, 7% vs. 64%; adjusted p = 0.013) and had earlier blood-culture positivity (median, 2 vs. 5 days; adjusted p = 0.012), resulting in earlier diagnosis (median duration of symptoms before diagnosis, 5 vs. 30 days; adjusted p = 0.012). Other clinical features, including causative pathogens and IE-related comorbidities, were similar between the groups, consistent with previous a nationwide Japanese study. In conclusion, most IE patients admitted to the hospital from ED were elderly, were antibiotic-naïve, and had presented without a referral. Relatively few patients had classical presentations of IE. Given the limited data, more research is needed to confirm that IE patients presenting to EDs constitute a unique group of elderly patients with specific clinical features.

Blood levels of glial fibrillary acidic protein for predicting clinical progression to Alzheimer's disease in adults without dementia: a systematic review and meta-analysis protocol.

BACKGROUND: There is urgent clinical need to identify reliable prognostic biomarkers that predict the progression of dementia symptoms in individuals with early-phase Alzheimer's disease (AD) especially given the research on and predicted applications of amyloid-beta (Aß)-directed immunotherapies to remove Aß from the brain. Cross-sectional studies have reported higher levels of cerebrospinal fluid and blood glial fibrillary acidic protein (GFAP) in individuals with AD-associated dementia than in cognitively unimpaired individuals. Further, recent longitudinal studies have assessed the prognostic potential of baseline blood GFAP levels as a predictor of future cognitive decline in cognitively unimpaired individuals and in those with mild cognitive impairment (MCI) due to AD. In this systematic review and meta-analysis, we propose analyzing longitudinal studies on blood GFAP levels to predict future cognitive decline. METHODS: This study will include prospective and retrospective cohort studies that assessed blood GFAP levels as a prognostic factor and any prediction models that incorporated blood GFAP levels in cognitively unimpaired individuals or those with MCI. The primary outcome will be conversion to MCI or AD in cognitively unimpaired individuals or conversion to AD in individuals with MCI. Articles from PubMed and Embase will be extracted up to December 31, 2023, without language restrictions. An independent dual screening of abstracts and potentially eligible full-text reports will be conducted. Data will be dual-extracted using the CHeck list for critical appraisal, data extraction for systematic Reviews of prediction Modeling Studies (CHARMS)-prognostic factor, and CHARMS checklists, and we will dual-rate the risk of bias and applicability using the Quality In Prognosis Studies and Prediction Study Risk-of-Bias Assessment tools. We will qualitatively synthesize the study data, participants, index biomarkers, predictive model characteristics, and clinical outcomes. If appropriate, random-effects meta-analyses will be performed to obtain summary estimates. Finally, we will assess the body of evidence using the Grading of Recommendation, Assessment, Development, and Evaluation Approach. DISCUSSION: This systematic review and meta-analysis will comprehensively evaluate and synthesize existing evidence on blood GFAP levels for prognosticating presymptomatic individuals and those with MCI to help advance risk-stratified treatment strategies for early-phase AD. TRIAL REGISTRATION: PROSPERO CRD42023481200.

Comparison of diagnostic spectrum between inflammation of unknown origin and fever of unknown origin: A systematic review and meta-analysis.

BACKGROUND: Patients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. METHODS: PubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. RESULTS: A total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25-39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36-0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05-0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23-3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16-10.69]; I2 0 %). CONCLUSION: Based on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.

PET in the clinical management of glioma: evidence map.

OBJECTIVE: Several studies have assessed PET to complement the anatomic information obtained from other imaging modalities in various clinical contexts for the management of glioma. We constructed an evidence map of clinical evidence on the use of PET in glioma and identified research gaps. MATERIALS AND METHODS: We searched PubMed and Scopus (from inception through June 30, 2011) to identify studies assessing the use of PET for glioma regardless of setting of care or indication. We extracted test objectives, study characteristics, and phases of diagnostic evidence and then assessed research diversity and temporal trends in the literature. We excluded studies assessing only technical feasibility and optimization of PET. RESULTS: A total of 129 studies were considered eligible; the number of articles published annually has greatly increased over time (p for trend < 0.001). Most studies (n = 118, 91%) assessed diagnostic or prognostic performance; fewer studies reported on the impact of PET on diagnostic thinking (n = 4, 3%), therapeutic decisions (n = 4, 3%), or patient-relevant clinical outcomes (n = 3; 2%). Fluorine-18 FDG (n = 73, 57%) or (11)C-methionine (n = 44, 34%) were the two most commonly evaluated PET tracers. Pretherapy assessment (n = 72, 56%) and monitoring of treatment response (n = 48, 37%) were the most common settings of test use assessed in the research studies. CONCLUSION: More primary studies, particularly studies of newer tracers focusing on biopsy or treatment planning, are needed to better characterize the role of PET in specific contexts.

External validation of the Michigan PICC catheter-associated bloodstream infections score (MPC score) for predicting the risk of peripherally inserted central catheter-associated bloodstream infections: A single-center study in Japan.

The Michigan peripherally inserted central catheter-associated bloodstream infection score (MPC score) had been developed for hospitalized medical patients but had not been externally validated. A retrospective analysis of a clinically heterogeneous case-mix in a university hospital cohort in Japan failed to validate its originally reported good performance.

External Validation of the Padua and IMPROVE-VTE Risk Assessment Models for Predicting Venous Thromboembolism in Hospitalized Adult Medical Patients: A Retrospective Single-Center Study in Japan.

Objectives: To assess the external validity of the Padua and International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE) risk assessment models (RAMs) for predicting venous thromboembolism (VTE) within 90 days of admission among hospitalized medical patients in Japan. Materials and Methods: A university hospital cohort comprising 3876 consecutive patients ages ≥15 years admitted to a general internal medicine department between July 2016 and July 2021 was retrospectively analyzed using data extracted from their medical records. Results: A total of 74 VTE events (1.9%), including six cases with pulmonary embolism (0.2%), were observed. Both RAMs had poor discriminative performance (C-index=0.64 for both) and generally underestimated VTE risks. However, recalibrating the IMPROVE-VTE RAM to update the baseline hazard improved the calibration (calibration slope=1.01). Decision curve analysis showed that a management strategy with no prediction model outperformed a clinical management strategy guided by the originally proposed RAMs. Conclusions: Both RAMs require an update to function in this particular setting. Further studies with a larger-sized cohort, including re-estimation of the individual regression coefficients with additional, more context-specific predictors, are needed to create a useful model that would help advance risk-oriented VTE prevention programs.

Radiographic and endoscopic screening to reduce gastric cancer mortality: a systematic review and meta-analysis.

Background: Previous systematic reviews naïvely combined biased effects of screening radiography or endoscopy observed in studies with various designs. We aimed to synthesize currently available comparative data on gastric cancer mortality in healthy, asymptomatic adults by explicitly classifying the screening effects through study designs and types of intervention effects. Methods: We searched multiple databases through October 31, 2022 for this systematic review and meta-analysis. Studies of any design that compared gastric cancer mortality among radiographic or endoscopic screening and no screening in a community-dwelling adult population were included. The method included a duplicate assessment of eligibility, double extraction of summary data, and validity assessment using the Risk Of Bias In Non-randomized Studies of Interventions tool. Bayesian three-level hierarchical random-effects meta-analysis synthesized data corrected for self-selection bias on the relative risk (RR) for per-protocol (PP) and intention-to-screen (ITS) effects. The study registration number at PROSPERO is CRD42021277126. Findings: We included seven studies in which a screening program was newly introduced (median attendance rate, 31%; at moderate-to-critical risk of bias), and seven cohort and eight case-control studies with ongoing screening programs (median attendance rate, 21%; all at critical risk of bias); thus, data of 1,667,117 subjects were included. For the PP effect, the average risk reduction was significant for endoscopy (RR 0.52; 95% credible interval: 0.39-0.79) but nonsignificant for radiography (0.80; 0.60-1.06). The ITS effect was not significant for both radiography (0.98; 0.86-1.09) and endoscopy (0.94; 0.71-1.28). The magnitude of the effects depended on the assumptions for the self-selection bias correction. Restricting the scope to East Asian studies only did not change the results. Interpretation: In limited-quality observational evidence from high-prevalence regions, screening reduced gastric cancer mortality; however, the effects diminished at a program level. Funding: National Cancer Center Japan; and Japan Agency for Medical Research and Development.

The effect of introducing a nurse-practitioner-led peripherally inserted central venous catheter placement program on the utilization of central venous access device: A retrospective study in Japan.

BACKGROUND: Nurse-led peripherally inserted central venous catheter (PICC) placement teams are common in western hospitals, but they are still in their infancy in Japan. Although implementing a dedicated program may improve ongoing vascular-access management, the direct hospital-level effects of launching a nurse-led PICC team on specific outcomes have not been formally investigated. OBJECTIVES: To evaluate the effect of introducing a nurse practitioner (NP)-led PICC-placement program on subsequent utilization of centrally inserted central catheters (CICCs) and to contrast the quality of PICC placements conducted by physicians and NPs. MATERIALS AND METHODS: Patients who underwent central venous access devices (CVADs) between 2014 and 2020 at a university hospital in Japan were evaluated retrospectively using an interrupted time-series analysis on the trend for monthly CVAD utilization and logistic regression and propensity score-based analyses for PICC-related complications. RESULTS: Among 6007 CVAD placements, 2230 PICCs were inserted into 1658 patients (725 by physicians and 1505 by NPs). The monthly number of CICC utilization fell from 58 in April 2014 to 38 in March 2020, while PICC placements by the NP PICC team increased from 0 to 104. The implementation of the NP PICC program reduced the immediate rate (by 35.5; 95% confidence interval [CI]: 24.1-46.9; p < 0.001) and post-intervention trend (by 2.3; 95% CI: 1.1-3.5; p < 0.001) of monthly CICC utilization. Overall immediate complication rates were lower in the NP group than the physician group (1.5% vs 5.1%; adjusted odds ratio = 0.31; 95% CI: 0.17-0.59; p < 0.001). The cumulative incidences of central line-associated bloodstream infections were comparable between the NP and physician groups (5.9% vs 7.2%; adjusted hazard ratio = 0.96; 95% CI: 0.53-1.75; p = .90). CONCLUSIONS: This NP-led PICC program reduced CICC utilization without affecting the quality of PICC placement or complication rate.

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.

Systematic review: Anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer.

BACKGROUND: KRAS mutations have been extensively investigated as predictive biomarkers for treatment of advanced colorectal cancer with the anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab. PURPOSE: To summarize whether KRAS mutation status modifies effects of anti-EGFR-based treatments for patients with advanced colorectal cancer and whether KRAS status predicts clinical outcomes among such patients. DATA SOURCES: MEDLINE and 2 curated genetics databases (through 24 March 2010) were searched for observational studies. MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects (through 1 September 2010) were searched for randomized, controlled trials. No search was restricted by language. STUDY SELECTION: Three reviewers screened titles and abstracts to identify published studies assessing KRAS mutations as predictors of overall and progression-free survival or treatment failure for patients who received anti-EGFR-based therapy for metastatic colorectal cancer. DATA EXTRACTION: Three investigators extracted data on population and study-design characteristics, including quality items, and on outcomes of interest. Random-effects meta-analyses were done on nonoverlapping studies. DATA SYNTHESIS: In 4 reanalyses of randomized trials of anti-EGFR-based therapy versus best supportive care or cytotoxic chemotherapy, no significant benefit was found for overall or progression-free survival from anti-EGFR-based treatment among KRAS-positive patients (hazard ratio [HR], 1.0). However, evidence favors anti-EGFR therapy among KRAS wild-type patients; the relative HR across KRAS-positive and wild-type patients was 1.30 (95% CI, 0.95 to 1.78) for overall survival and 2.22 (CI, 1.74 to 2.84) for progression-free survival by random-effects meta-analysis. In 13 cohorts of patients who received anti-EGFR antibodies, the summary HR for overall survival was 1.79 (CI, 1.48 to 2.17), with better survival in wild-type patients. The corresponding HR for progression-free survival was 2.11 (CI, 1.74 to 2.55 [16 cohorts]). In random-effects bivariate meta-analysis of 22 studies, the summary sensitivity of KRAS mutations for predicting lack of response was 0.49 (CI, 0.43 to 0.55), and summary specificity was 0.93 (CI, 0.87 to 0.97). LIMITATIONS: Limited evidence from randomized studies exists. Patient-level data are needed to assess modifiers of the mutation-by-treatment interaction. Publication bias could be a concern. CONCLUSION: KRAS mutations are consistently associated with reduced overall and progression-free survival and increased treatment failure rates among patients with advanced colorectal cancer treated with anti-EGFR antibodies. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Studies suggest that vitamin D supplementation may reduce cancer and fracture risks. PURPOSE: To examine the benefits and harms of vitamin D with or without calcium supplementation on clinical outcomes of cancer and fractures in adults. DATA SOURCES: English-language studies identified from MEDLINE and the Cochrane Central Register of Controlled Trials through July 2011. STUDY SELECTION: Randomized, controlled trials (RCTs), prospective cohort studies, and nested case-control studies reporting incidence of or death from cancer and fracture outcomes. DATA EXTRACTION: Multiple reviewers extracted details about participant characteristics, including baseline vitamin D status and use of supplements; details of statistical analyses, including adjustments for confounding; and methodological quality. Differences were resolved by consensus. DATA SYNTHESIS: 19 RCTs (3 for cancer and 16 for fracture outcomes) and 28 observational studies (for cancer outcomes) were analyzed. Limited data from RCTs suggested that high-dose (1000 IU/d) vitamin D supplementation can reduce the risk for total cancer, and data from observational studies suggested that higher blood 25-hydroxyvitamin D (25-[OH]D) concentrations might be associated with increased risk for cancer. Mixed-effects dose-response meta-analyses showed that each 10-nmol/L increase in blood 25-(OH)D concentration was associated with a 6% (95% CI, 3% to 9%) reduced risk for colorectal cancer but no statistically significant dose-response relationships for prostate and breast cancer. Random-effects model meta-analysis showed that combined vitamin D and calcium supplementation reduced fracture risk (pooled relative risk, 0.88 [CI, 0.78 to 0.99]) in older adults, but the effects differed according to study setting: institution (relative risk, 0.71 [CI, 0.57 to 0.89]) versus community-dwelling (relative risk, 0.89 [CI, 0.76 to 1.04]). One RCT showed adverse outcomes associated with supplementation, including increased risk for renal and urinary tract stones. LIMITATIONS: Most trial participants were older (aged≥65 years) postmenopausal women. Observational studies were heterogeneous and were limited by potential confounders. CONCLUSION: Combined vitamin D and calcium supplementation can reduce fracture risk, but the effects may be smaller among community-dwelling older adults than among institutionalized elderly persons. Appropriate dose and dosing regimens, however, require further study. Evidence is not sufficiently robust to draw conclusions regarding the benefits or harms of vitamin D supplementation for the prevention of cancer. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.