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.

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.

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.

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.

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.

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.

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.

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.

Association of Repeated Blood Cultures With Mortality in Adult Patients With Gram-Negative Bacilli Bacteremia: A Systematic Review and Meta-analysis.

Background: Performing repeat blood cultures after an initial positive culture (ie, follow-up blood cultures [FUBCs]) in patients with gram-negative bacilli (GNB) bacteremia is controversial. We aimed to comprehensively review the association of FUBCs with improvement in patient-relevant clinical outcomes in GNB bacteremia. Methods: We performed a systematic review and random-effects meta-analysis to calculate summary effect estimates. We used hazard ratios as the effect measure. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were length of treatment and length of hospital stay. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (Central) without language restrictions from inception to April 29, 2022. Original clinical studies evaluating the association between FUBCs and mortality in adult patients with GNB bacteremia were included. FUBC details were reviewed. Two independent reviewers used the Risk of Bias in Non-randomised Studies of Interventions tool. Results: We identified 9 eligible retrospective studies. In total, 7778 hospitalized patients with GNB bacteremia were included. The studies were clinically heterogeneous and had a critical risk of bias. The utilization of FUBCs varied across studies (18%-89%). Random-effects meta-analysis of covariate-adjusted estimates found that FUBC use was associated with reduced mortality. Although not a result of the meta-analysis, lengths of treatment and hospital stay were longer for patients with FUBCs than for those without. Adverse events were not reported. Conclusions: FUBC acquisition was associated with lower mortality and longer hospital stay and treatment duration in GNB bacteremia. The risk of bias was critical, and no firm data were available to support mechanisms.

Serial high-sensitivity cardiac troponin testing for the diagnosis of myocardial infarction: a scoping review.

OBJECTIVES: We aimed to assess the diversity and practices of existing studies on several assays and algorithms for serial measurements of high-sensitivity cardiac troponin (hs-cTn) for risk stratification and the diagnosis of myocardial infarction (MI) and 30-day outcomes in patients suspected of having non-ST-segment elevation MI (NSTEMI). METHODS: We searched multiple databases including MEDLINE, EMBASE, Science Citation Index, the Cochrane Database of Systematic Reviews and the CENTRAL databases for studies published between January 2006 and November 2021. Studies that assessed the diagnostic accuracy of serial hs-cTn testing in patients suspected of having NSTEMI in the emergency department (ED) were eligible. Data were analysed using the scoping review method. RESULTS: We included 86 publications, mainly from research centres in Europe, North America and Australasia. Two hs-cTn assays, manufactured by Abbott (43/86) and Roche (53/86), dominated the evaluations. The studies most commonly measured the concentrations of hs-cTn at two time points, at presentation and a few hours thereafter, to assess the two-strata or three-strata algorithm for diagnosing or ruling out MI. Although data from 83 studies (97%) were prospectively collected, 0%-90% of the eligible patients were excluded from the analysis due to missing blood samples or the lack of a final diagnosis in 53 studies (62%) that reported relevant data. Only 19 studies (22%) reported on head-to-head comparisons of alternative assays. CONCLUSION: Evidence on the accuracy of serial hs-cTn testing was largely derived from selected research institutions and relied on two specific assays. The proportions of the eligible patients excluded from the study raise concerns about directly applying the study findings to clinical practice in frontline EDs. PROSPERO REGISTRATION NUMBER: CRD42018106379.

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.

Treatment of acute hypernatremia caused by sodium overload in adults: A systematic review.

BACKGROUND: Rapid-onset, acute hypernatremia caused by sodium overload is a rare, life-threatening condition. Although experts recommend rapid correction of sodium concentration [Na] based on pathophysiological theories, only a few reports have documented the specific details of sodium correction methods. The objective of this study was to systematically review the reported treatment regimens, achieved [Na] correction rates, and treatment outcomes. METHODS: PubMed, Ichushi-database, and references without language restrictions, from inception to January 2021, were searched for studies that described ≥1 adult (aged ≥18 years) patients with rapid-onset hypernatremia caused by sodium overload, whose treatment was initiated ≤12 hours from the onset. The primary outcome of interest was the [Na] correction rate associated with mortality. RESULTS: Eighteen case reports (18 patients; median [Na], 180.5 mEq/L) were included. The cause of sodium overload was self-ingestion in 8 patients and iatrogenic sodium gain in 10 patients; baseline [Na] and symptoms at presentation were comparable for both groups. Individualized rapid infusion of dextrose-based solutions was the most commonly adopted fluid therapy, whereas hemodialysis was also used for patients already treated with hemodialysis. The correction rates were more rapid in 13 successfully treated patients than in 5 fatal patients. The successfully treated patients typically achieved [Na] ≤160 within 8 hours, [Na] ≤150 within 24 hours, and [Na] ≤145 within 48 hours. Hyperglycemia was a commonly observed treatment-related adverse event. CONCLUSION: The limited empirical evidence derived from case reports appears to endorse the recommended, rapid, and aggressive sodium correction using dextrose-based hypotonic solutions.

Comparative accuracy of cervical cancer screening strategies in healthy asymptomatic women: a systematic review and network meta-analysis.

To compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.

Effectiveness of decision aids on cancer-screening decision-making: an umbrella review protocol.

INTRODUCTION: Although systematic reviews have shown how decision aids about cancer-related clinical decisions improve selection of key options and shared decision-making, whether or not particular decision aids, defined by their specific presentation formats, delivery methods and other attributes, can perform better than others in the context of cancer-screening decisions is uncertain. Therefore, we planned an overview to address this issue by using standard umbrella review methods to repurpose existing systematic reviews and their component comparative studies. METHODS AND ANALYSIS: We will search PubMed, Embase, the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effects from inception through 31 December 2021 with no language restriction and perform full-text evaluation of potentially relevant articles. We will include systematic reviews of randomised controlled trials or non-randomised studies of interventions that assessed a decision aid about cancer-screening decisions and compared it with an alternative tool or conventional management in healthy average-risk adults. Two reviewers will extract data and rate the study validity according to standard quality assessment measures. Our primary outcome will be intended and actual choice and adherence to selected options. The secondary outcomes will include attributes of the option-selection process, achieving shared decision-making and preference-linked psychosocial outcomes. We will qualitatively assess study, patient and intervention characteristics and outcomes. We will also take special care to investigate the presentation format, delivery methods and quality of the included decision aids and assess the degree to which the decision aid was delivered and used as intended. If appropriate, we will perform random-effects model meta-analyses to quantitatively synthesise the results. ETHICS AND DISSEMINATION: Ethics approval is not applicable as this is a secondary analysis of publicly available data. The review results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021235957.

Gallium citrate-67 single-photon emission computed tomography/computed tomography for localizing the foci of classic fever and inflammation of unknown origin: A retrospective study of diagnostic yield.

OBJECTIVES: Only few studies have assessed the use of gallium citrate-67 single-photon emission computed tomography/computed tomography (67Ga-SPECT/CT) for localizing the foci of classic fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Hence, the current study aimed to assess the diagnostic contribution of 67Ga-SPECT/CT in a tertiary referral setting where nuclear imaging tests are performed after an unsuccessful comprehensive primary diagnostic workup. METHODS: We retrospectively assessed the medical records of 27 adult patients with FUO/IUO who had an unsuccessful diagnostic workup and who underwent 67Ga-SPECT/CT for the localization of FUO/IUO foci in our university hospital between 2013 and 2019. The primary outcome was diagnostic yield. The secondary outcomes were overall clinical efficacy and spontaneous remission of FUO/IUO symptoms in patients with a negative 67Ga-SPECT/CT finding. RESULTS: Almost all patients completed the recommended diagnostic workup, except for urine culture and abdominal ultrasonography. Moreover, prior to 67Ga-SPECT/CT, all patients underwent thoraco-abdominopelvic CT scan, which was a non-diagnostic procedure. After a median follow-up of 843 days, the cause was identified in 16 (59%) patients. 67Ga-SPECT/CT successfully localized the FUO/IUO foci in eight patients (diagnostic yield = 30%; 95% confidence interval [CI]: 14%-50%). However, the causes remained unknown during follow-up in 11 (41%) patients. Among them, five experienced spontaneous regression of symptoms. 67Ga-SPECT/CT was negative in four of the five patients with spontaneous regression in symptoms without a definite cause. Considering this an important event, the overall clinical efficacy of 67Ga-SPECT/CT increased to 44% (95% CI: 25%-65%). CONCLUSION: 67Ga-SPECT/CT had an acceptable diagnostic yield for the localization of FUO/IUO foci, which are challenging to diagnose, in a contemporary tertiary referral care setting. In patients who experienced spontaneous regression in symptoms with an unexplained cause, the absence of abnormal uptake might indicate prospective spontaneous remission. Thus, 67Ga-SPECT/CT could be an active first-line nuclear imaging modality in settings where fluorine-18-fluorodeoxy glucose positron emission tomography and computed tomography is not available for the assessment of FUO/IUO causes.

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.

National Data Analysis and Systematic Review for Human Resources for Cervical Cancer Screening in Japan.

BACKGROUND: Although cervical cancer screening has been performed as a national program since 1983 in Japan, the participation rate has remained below 20%. Equity of access is a basic requirement for cancer screening. However, taking smears from the cervix has been limited to gynecologists or obstetricians in Japan and it might be a barrier for accessibility. We examined the current access and its available human resources for cervical cancer screening in Japan. METHODS: We analyzed the number of gynecologists and obstetricians among 47 prefectures based on a national survey. A systematic review was performed to clarify disparity and use of human resources in cervical cancer screening, diagnosis, and treatment for cervical cancers in Japan. Candidate literature was searched using Ovid-MEDLINE and Ichushi-Web until the end of January 2020. Then, a systematic review regarding accessibility to cervical cancer screening was performed. The results of the selected articles were summarized in the tables. RESULTS: Although the total number of all physicians in Japan increased from 1996 to 2016, the proportion of gynecologists and obstetricians has remained at approximately 5% over the last 2 decades. 43.6% of municipalities have no gynecologists and obstetricians in 2016. Through a systematic review, 4 English articles and 1 Japanese article were selected. From these 5 articles, the association between human resources and participation rates in cervical cancer screening was examined in 2 articles. CONCLUSIONS: The human resources for taking smears for cervical cancer screening has remained insufficient with a huge disparity among municipalities in Japan. To improve accessibility for cervical cancer screening another option which may be considered could be involving general physicians as potential smear takers.