Rapid diagnostic tests for typhoid and paratyphoid (enteric) fever

BACKGROUND: Differentiating both typhoid (Salmonella Typhi) and paratyphoid (Salmonella Paratyphi A) infection from other causes of fever in endemic areas is a diagnostic challenge. Although commercial point-of-care rapid diagnostic tests (RDTs) for enteric fever are available as alternatives to the current reference standard test of blood or bone marrow culture, or to the widely used Widal Test, their diagnostic accuracy is unclear. If accurate, they could potentially replace blood culture as the World Health Organization (WHO)-recommended main diagnostic test for enteric fever.OBJECTIVES: To assess the diagnostic accuracy of commercially available rapid diagnostic tests (RDTs) and prototypes for detecting Salmonella Typhi or Paratyphi A infection in symptomatic persons living in endemic areas.SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, IndMED, African Index Medicus, LILACS, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 4 March 2016. We manually searched WHO reports, and papers from international conferences on Salmonella infections. We also contacted test manufacturers to identify studies.SELECTION CRITERIA: We included diagnostic accuracy studies of enteric fever RDTs in patients with fever or with symptoms suggestive of enteric fever living in endemic areas. We classified the reference standard used as either Grade 1 (result from a blood culture and a bone marrow culture) or Grade 2 (result from blood culture and blood polymerase chain reaction, or from blood culture alone).DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the test result data. We used a modified QUADAS-2 extraction form to assess methodological quality. We performed a meta-analysis when there were sufficient studies for the test and heterogeneity was reasonable.MAIN RESULTS: Thirty-seven studies met the inclusion criteria and included a total of 5080 participants (range 50 to 1732). Enteric fever prevalence rates in the study populations ranged from 1% to 75% (median prevalence 24%, interquartile range (IQR) 11% to 46%). The included studies evaluated 16 different RDTs, and 16 studies compared two or more different RDTs. Only three studies used the Grade 1 reference standard, and only 11 studies recruited unselected febrile patients. Most included studies were from Asia, with five studies from sub-Saharan Africa. All of the RDTs were designed to detect S.Typhi infection only.Most studies evaluated three RDTs and their variants: TUBEX in 14 studies; Typhidot (Typhidot, Typhidot-M, and TyphiRapid-Tr02) in 22 studies; and the Test-It Typhoid immunochromatographic lateral flow assay, and its earlier prototypes (dipstick, latex agglutination) developed by the Royal Tropical Institute, Amsterdam (KIT) in nine studies. Meta-analyses showed an average sensitivity of 78% (95% confidence interval (CI) 71% to 85%) and specificity of 87% (95% CI 82% to 91%) for TUBEX; and an average sensitivity of 69% (95% CI 59% to 78%) and specificity of 90% (95% CI 78% to 93%) for all Test-It Typhoid and prototype tests (KIT). Across all forms of the Typhidot test, the average sensitivity was 84% (95% CI 73% to 91%) and specificity was 79% (95% CI 70% to 87%). When we based the analysis on the 13 studies of the Typhidot test that either reported indeterminate test results or where the test format means there are no indeterminate results, the average sensitivity was 78% (95% CI 65% to 87%) and specificity was 77% (95% CI 66% to 86%). We did not identify any difference in either sensitivity or specificity between TUBEX, Typhidot, and Test-it Typhoid tests when based on comparison to the 13 Typhidot studies where indeterminate results are either reported or not applicable. If TUBEX and Test-it Typhoid are compared to all Typhidot studies, the sensitivity of Typhidot was higher than Test-it Typhoid (15% (95% CI 2% to 28%), but other comparisons did not show a difference at the 95% level of CIs.In a hypothetical cohort of 1000 patients presenting with fever where 30% (300 patients) have enteric fever, on average Typhidot tests reporting indeterminate results or where tests do not produce indeterminate results will miss the diagnosis in 66 patients with enteric fever, TUBEX will miss 66, and Test-It Typhoid and prototype (KIT) tests will miss 93. In the 700 people without enteric fever, the number of people incorrectly diagnosed with enteric fever would be 161 with Typhidot tests, 91 with TUBEX, and 70 with Test-It Typhoid and prototype (KIT) tests. The CIs around these estimates were wide, with no difference in false positive results shown between tests.The quality of the data for each study was evaluated using a standardized checklist called QUADAS-2. Overall, the certainty of the evidence in the studies that evaluated enteric fever RDTs was low.AUTHORS' CONCLUSIONS: In 37 studies that evaluated the diagnostic accuracy of RDTs for enteric fever, few studies were at a low risk of bias. The three main RDT tests and variants had moderate diagnostic accuracy. There was no evidence of a difference between the average sensitivity and specificity of the three main RDT tests. More robust evaluations of alternative RDTs for enteric fever are needed.</p

Assessing violence risk in first-episode psychosis: external validation, updating and net benefit of a prediction tool (OxMIV)

BACKGROUND: Violence perpetration is a key outcome to prevent for an important subgroup of individuals presenting to mental health services, including early intervention in psychosis (EIP) services. Needs and risks are typically assessed without structured methods, which could facilitate consistency and accuracy. Prediction tools, such as OxMIV (Oxford Mental Illness and Violence tool), could provide a structured risk stratification approach, but require external validation in clinical settings. OBJECTIVES: We aimed to validate and update OxMIV in first-episode psychosis and consider its benefit as a complement to clinical assessment. METHODS: A retrospective cohort of individuals assessed in two UK EIP services was included. Electronic health records were used to extract predictors and risk judgements made by assessing clinicians. Outcome data involved police and healthcare records for violence perpetration in the 12 months post-assessment. FINDINGS: Of 1145 individuals presenting to EIP services, 131 (11%) perpetrated violence during the 12 month follow-up. OxMIV showed good discrimination (area under the curve 0.75, 95% CI 0.71 to 0.80). Calibration-in-the-large was also good after updating the model constant. Using a 10% cut-off, sensitivity was 71% (95% CI 63% to 80%), specificity 66% (63% to 69%), positive predictive value 22% (19% to 24%) and negative predictive value 95% (93% to 96%). In contrast, clinical judgement sensitivity was 40% and specificity 89%. Decision curve analysis showed net benefit of OxMIV over comparison approaches. CONCLUSIONS: OxMIV performed well in this real-world validation, with improved sensitivity compared with unstructured assessments. CLINICAL IMPLICATIONS: Structured tools to assess violence risk, such as OxMIV, have potential in first-episode psychosis to support a stratified approach to allocating non-harmful interventions to individuals who may benefit from the largest absolute risk reduction

Meta-research: How many diagnostic or prognostic models published in radiological journals are evaluated externally?

OBJECTIVES: Prognostic and diagnostic models must work in their intended clinical setting, proven via "external evaluation", preferably by authors uninvolved with model development. By systematic review, we determined the proportion of models published in high-impact radiological journals that are evaluated subsequently. METHODS: We hand-searched three radiological journals for multivariable diagnostic/prognostic models 2013-2015 inclusive, developed using regression. We assessed completeness of data presentation to allow subsequent external evaluation. We then searched literature to August 2022 to identify external evaluations of these index models. RESULTS: We identified 98 index studies (73 prognostic; 25 diagnostic) describing 145 models. Only 15 (15%) index studies presented an evaluation (two external). No model was updated. Only 20 (20%) studies presented a model equation. Just 7 (15%) studies developing Cox models presented a risk table, and just 4 (9%) presented the baseline hazard. Two (4%) studies developing non-Cox models presented the intercept. Just 20 (20%) articles presented a Kaplan-Meier curve of the final model. The 98 index studies attracted 4224 citations (including 559 self-citations), median 28 per study. We identified just six (6%) subsequent external evaluations of an index model, five of which were external evaluations by researchers uninvolved with model development, and from a different institution. CONCLUSIONS: Very few prognostic or diagnostic models published in radiological literature are evaluated externally, suggesting wasted research effort and resources. Authors' published models should present data sufficient to allow external evaluation by others. To achieve clinical utility, researchers should concentrate on model evaluation and updating rather than continual redevelopment. CLINICAL RELEVANCE STATEMENT: The large majority of prognostic and diagnostic models published in high-impact radiological journals are never evaluated. It would be more efficient for researchers to evaluate existing models rather than practice continual redevelopment. KEY POINTS: • Systematic review of highly cited radiological literature identified few diagnostic or prognostic models that were evaluated subsequently by researchers uninvolved with the original model. • Published radiological models frequently omit important information necessary for others to perform an external evaluation: Only 20% of studies presented a model equation or nomogram. • A large proportion of research citing published models focuses on redevelopment and ignores evaluation and updating, which would be a more efficient use of research resources

Prognostic factors to identify resolution of small bowel obstruction without need for operative management: systematic review

OBJECTIVES: To identify imaging, clinical, and laboratory variables potentially prognostic for surgical management of small bowel obstruction. METHODS: Two researchers systematically reviewed indexed literature 2001-2021 inclusive for imaging, clinical, and laboratory variables potentially predictive of surgical management of small bowl obstruction and/or ischaemia at surgery, where performed. Risk of bias was assessed. Contingency tables for variables reported in at least 5 studies were extracted and meta-analysed to identify strong evidence of association with clinical outcomes, across studies. RESULTS: Thirty-one studies were ultimately included, reporting 4638 patients (44 to 313 per study). 11 (35%) studies raised no risk of bias concerns. CT was the modality reported most (29 studies, 94%). Meta-analysis of 21 predictors identified 5 strongly associated with surgical intervention, 3 derived from CT (peritoneal free fluid, odds ratio [OR] 3.24, 95%CI 2.45 to 4.29; high grade obstruction, OR 3.58, 95%CI 2.46 to 5.20; mesenteric inflammation, OR 2.61, 95%CI 1.94 to 3.50; abdominal distension, OR 2.43, 95%CI 1.34 to 4.42; peritonism, OR 3.97, 95%CI 2.67 to 5.90) and one with conservative management (previous abdominopelvic surgery, OR 0.58, 95%CI 0.40 to 0.85). Meta-analysis of 10 predictors identified 3 strongly associated with ischaemia at surgery, 2 derived from CT (peritoneal free fluid, OR 3.49, 95%CI 2.28 to 5.35; bowel thickening, OR 3.26 95%CI 1.91 to 5.55; white cell count, OR 4.76, 95%CI 2.71 to 8.36). CONCLUSIONS: Systematic review of patients with small bowel obstruction identified four imaging, three clinical, and one laboratory predictors associated strongly with surgical intervention and/or ischaemia at surgery. CLINICAL RELEVANCE STATEMENT: Via systematic review and meta-analysis, we identified imaging, clinical, and laboratory predictors strongly associated with surgical management of small bowel obstruction and/or ischaemia. Multivariable model development to guide management should incorporate these since they display strong evidence of potential utility. KEY POINTS: • While multivariable models incorporating clinical, laboratory, and imaging factors could predict surgical management of small bowel obstruction, none are used widely. • Via systematic review and meta-analysis we identified imaging, clinical, and laboratory variables strongly associated with surgical management and/or ischaemia at surgery. • Development of multivariable models to guide management should incorporate these predictors, notably CT scanning, since they display strong evidence of potential utility

A clinical feasibility study of the Forensic Psychiatry and Violence Oxford (FoVOx) tool

Background: Risk assessment informs decisions around admission to and discharge from secure psychiatric hospital and contributes to treatment and supervision. There are advantages to using brief, scalable, free online tools with similar accuracy to instruments currently used. We undertook a study of one such risk assessment, the Forensic Psychiatry and Violence Oxford (FoVOx) tool, examining its acceptability, feasibility, and practicality. Methods: We completed the FoVOx tool on all discharges from six secure psychiatric hospitals in one region in England over two years. We interviewed 11 senior forensic psychiatrists regarding each discharge using a standardized questionnaire. Their patient’s FoVOx score was compared to clinical risk assessment, and the senior clinicians were asked if they considered FoVOx scores accurate and useful. A modified thematic analysis was conducted, and clinicians were surveyed about current risk assessment practice on discharge. Results: Of 90 consecutive discharges, 84 were included in the final analysis. The median FoVOx probability score was 11% risk of violent recidivism in two years after discharge. We estimated that 12 (14%) individuals reoffended since discharge; all were in the medium or high risk FoVOx categories. Clinical assessment of risk agreed with the FoVOx categories in around half the cases. Clinicians were more likely to provide lower risk categories compared with FoVOx ones. FoVOx was considered to be an accurate representation of risk in 67% of cases; clinicians revised their view on some patient’s risk assessment after being informed of their FoVOx scores. Completing FoVOx was reported to be helpful in the majority of cases. Reasons included improved communication with other agencies, reassurance to clinical teams, and identifying additional factors not fully considered. 10 of the 11 respondents reported that FoVOx was practical, and seven of 11 reported that they would use it in the future, highlighting its brevity and speed of use compared to existing risk assessment tools. Conclusions: Senior clinicians in this regional forensic psychiatric service found the FoVOx risk assessment tool feasible, practical, and easy to use. Its use addressed a lack of consistency around risk assessment at the point of discharge and, if used routinely, could assist in clinical decision-making.</br

Are preoperative CT variables associated with the success or failure of subsequent ventral hernia repair: nested case-control study

OBJECTIVES: Systematic review of CT measurements to predict the success or failure of subsequent ventral hernia repair has found limited data available in the indexed literature. To rectify this, we investigated multiple preoperative CT metrics to identify if any were associated with postoperative reherniation. METHODS: Following ethical permission, we identified patients who had undergone ventral hernia repair and had preoperative CT scanning available. Two radiologists made multiple measurements of the hernia and abdominal musculature from these scans, including loss of domain. Patients were divided subsequently into two groups, defined by hernia recurrence at 1-year subsequent to surgery. Hypothesis testing investigated any differences between CT measurements from each group. RESULTS: One hundred eighty-eight patients (95 male) were identified, 34 (18%) whose hernia had recurred by 1-year. Only three of 34 CT measurements were significantly different when patients whose hernia had recurred were compared to those who had not; these significant findings were assumed contingent on multiple testing. In particular, preoperative hernia volume (recurrence 155.3 cc [IQR 355.65] vs. no recurrence 78.2 [IQR 303.52], p = 0.26) nor loss of domain, whether calculated using the Tanaka (recurrence 0.02 [0.04] vs. no recurrence 0.009 [0.04], p = 0.33) or Sabbagh (recurrence 0.019 [0.05] vs. no recurrence 0.009 [0.04], p = 0.25) methods, differed between significantly between groups. CONCLUSIONS: Preoperative CT measurements of ventral hernia morphology, including loss of domain, appear unrelated to postoperative recurrence. It is likely that the importance of such measurements to predict recurrence is outweighed by other patient factors and surgical reconstruction technique. KEY POINTS: • Preoperative CT scanning is often performed for ventral hernia but systematic review revealed little data regarding whether CT variables predict postoperative reherniation. • We found that the large majority of CT measurements, including loss of domain, did not differ significantly between patients whose hernia did and did not recur. • It is likely that the importance of CT measurements to predict recurrence is outweighed by other patient factors and surgical reconstruction technique

Assessing violence risk in first-episode psychosis: external validation, updating and net benefit of a prediction tool (OxMIV)

Violence perpetration is a key outcome to prevent for an important subgroup of individuals presenting to mental health services, including early intervention in psychosis (EIP) services. Needs and risks are typically assessed without structured methods, which could facilitate consistency and accuracy. Prediction tools, such as OxMIV (Oxford Mental Illness and Violence tool), could provide a structured risk stratification approach, but require external validation in clinical settings. We aimed to validate and update OxMIV in first-episode psychosis and consider its benefit as a complement to clinical assessment. A retrospective cohort of individuals assessed in two UK EIP services was included. Electronic health records were used to extract predictors and risk judgements made by assessing clinicians. Outcome data involved police and healthcare records for violence perpetration in the 12 months post-assessment. Of 1145 individuals presenting to EIP services, 131 (11%) perpetrated violence during the 12 month follow-up. OxMIV showed good discrimination (area under the curve 0.75, 95% CI 0.71 to 0.80). Calibration-in-the-large was also good after updating the model constant. Using a 10% cut-off, sensitivity was 71% (95% CI 63% to 80%), specificity 66% (63% to 69%), positive predictive value 22% (19% to 24%) and negative predictive value 95% (93% to 96%). In contrast, clinical judgement sensitivity was 40% and specificity 89%. Decision curve analysis showed net benefit of OxMIV over comparison approaches. OxMIV performed well in this real-world validation, with improved sensitivity compared with unstructured assessments. Structured tools to assess violence risk, such as OxMIV, have potential in first-episode psychosis to support a stratified approach to allocating non-harmful interventions to individuals who may benefit from the largest absolute risk reduction

Interobserver variability studies in diagnostic imaging: a methodological systematic review

OBJECTIVES: To review the methodology of interobserver variability studies; including current practice and quality of conducting and reporting studies. METHODS: Interobserver variability studies between January 2019 and January 2020 were included; extracted data comprised of study characteristics, populations, variability measures, key results, and conclusions. Risk of bias was assessed using the COSMIN tool for assessing reliability and measurement error. RESULTS: Seventy-nine full-text studies were included covering various imaging tests and clinical areas. The median number of patients was 47 (IQR:23-88), and observers were 4 (IQR:2-7), with sample size justified in 12 (15%) studies. Most studies used static images (n = 75, 95%), where all observers interpreted images for all patients (n = 67, 85%). Intraclass correlation coefficients (ICC) (n = 41, 52%), Kappa (κ) statistics (n = 31, 39%) and percentage agreement (n = 15, 19%) were most commonly used. Interpretation of variability estimates often did not correspond with study conclusions. The COSMIN risk of bias tool gave a very good/adequate rating for 52 studies (66%) including any studies that used variability measures listed in the tool. For studies using static images, some study design standards were not applicable and did not contribute to the overall rating. CONCLUSIONS: Interobserver variability studies have diverse study designs and methods, the impact of which requires further evaluation. Sample size for patients and observers was often small without justification. Most studies report ICC and κ values, which did not always coincide with the study conclusion. High ratings were assigned to many studies using the COSMIN risk of bias tool, with certain standards scored 'not applicable' when static images were used. ADVANCES IN KNOWLEDGE: The sample size for both patients and observers was often small without justification. For most studies, observers interpreted static images and did not evaluate the process of acquiring the imaging test, meaning it was not possible to assess many COSMIN risk of bias standards for studies with this design. Most studies reported intraclass correlation coefficient and κ statistics; study conclusions often did not correspond with results

Interobserver variability studies in diagnostic imaging:a methodological systematic review

Objectives: To review the methodology of interobserver variability studies; including current practice and quality of conducting and reporting studies. Methods: Interobserver variability studies between January 2019 and January 2020 were included; extracted data comprised of study characteristics, populations, variability measures, key results, and conclusions. Risk of bias was assessed using the COSMIN tool for assessing reliability and measurement error. Results: Seventy-nine full-text studies were included covering various imaging tests and clinical areas. The median number of patients was 47 (IQR:23–88), and observers were 4 (IQR:2–7), with sample size justified in 12 (15%) studies. Most studies used static images (n = 75, 95%), where all observers interpreted images for all patients (n = 67, 85%). Intraclass correlation coefficients (ICC) (n = 41, 52%), Kappa (κ) statistics (n = 31, 39%) and percentage agreement (n = 15, 19%) were most commonly used. Interpretation of variability estimates often did not correspond with study conclusions. The COSMIN risk of bias tool gave a very good/adequate rating for 52 studies (66%) including any studies that used variability measures listed in the tool. For studies using static images, some study design standards were not applicable and did not contribute to the overall rating. Conclusions: Interobserver variability studies have diverse study designs and methods, the impact of which requires further evaluation. Sample size for patients and observers was often small without justification. Most studies report ICC and κ values, which did not always coincide with the study conclusion. High ratings were assigned to many studies using the COSMIN risk of bias tool, with certain standards scored ‘not applicable’ when static images were used. Advances in knowledge: The sample size for both patients and observers was often small without justification. For most studies, observers interpreted static images and did not evaluate the process of acquiring the imaging test, meaning it was not possible to assess many COSMIN risk of bias standards for studies with this design. Most studies reported intraclass correlation coefficient and κ statistics; study conclusions often did not correspond with results