External validation of a lung cancer-based prediction model for two-year mortality in esophageal cancer patient cohorts.

PURPOSE/OBJECTIVE: Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients. METHODS: Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly. RESULTS: For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67). CONCLUSION: The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model.

Regularized parametric survival modeling to improve risk prediction models.

We propose to combine the benefits of flexible parametric survival modeling and regularization to improve risk prediction modeling in the context of time-to-event data. Thereto, we introduce ridge, lasso, elastic net, and group lasso penalties for both log hazard and log cumulative hazard models. The log (cumulative) hazard in these models is represented by a flexible function of time that may depend on the covariates (i.e., covariate effects may be time-varying). We show that the optimization problem for the proposed models can be formulated as a convex optimization problem and provide a user-friendly R implementation for model fitting and penalty parameter selection based on cross-validation. Simulation study results show the advantage of regularization in terms of increased out-of-sample prediction accuracy and improved calibration and discrimination of predicted survival probabilities, especially when sample size was relatively small with respect to model complexity. An applied example illustrates the proposed methods. In summary, our work provides both a foundation for and an easily accessible implementation of regularized parametric survival modeling and suggests that it improves out-of-sample prediction performance.

Can an mhealth clinical decision-making support system improve adherence to neonatal healthcare protocols in a low-resource setting?

BACKGROUND: This study assessed health workers' adherence to neonatal health protocols before and during the implementation of a mobile health (mHealth) clinical decision-making support system (mCDMSS) that sought to bridge access to neonatal health protocol gap in a low-resource setting. METHODS: We performed a cross-sectional document review within two purposively selected clusters (one poorly-resourced and one well-resourced), from each arm of a cluster-randomized trial at two different time points: before and during the trial. The total trial consisted of 16 clusters randomized into 8 intervention and 8 control clusters to assess the impact of an mCDMSS on neonatal mortality in Ghana. We evaluated health workers' adherence (expressed as percentages) to birth asphyxia, neonatal jaundice and cord sepsis protocols by reviewing medical records of neonatal in-patients using a checklist. Differences in adherence to neonatal health protocols within and between the study arms were assessed using Wilcoxon rank-sum and permutation tests for each morbidity type. In addition, we tracked concurrent neonatal health improvement activities in the clusters during the 18-month intervention period. RESULTS: In the intervention arm, mean adherence was 35.2% (SD = 5.8%) and 43.6% (SD = 27.5%) for asphyxia; 25.0% (SD = 14.8%) and 39.3% (SD = 27.7%) for jaundice; 52.0% (SD = 11.0%) and 75.0% (SD = 21.2%) for cord sepsis protocols in the pre-intervention and intervention periods respectively. In the control arm, mean adherence was 52.9% (SD = 16.4%) and 74.5% (SD = 14.7%) for asphyxia; 45.1% (SD = 12.8%) and 64.6% (SD = 8.2%) for jaundice; 53.8% (SD = 16.0%) and 60.8% (SD = 11.7%) for cord sepsis protocols in the pre-intervention and intervention periods respectively. We observed nonsignificant improvement in protocol adherence in the intervention clusters but significant improvement in protocol adherence in the control clusters. There were 2 concurrent neonatal health improvement activities in the intervention clusters and over 12 in the control clusters during the intervention period. CONCLUSION: Whether mHealth interventions can improve adherence to neonatal health protocols in low-resource settings cannot be ascertained by this study. Neonatal health improvement activities are however likely to improve protocol adherence. Future mHealth evaluations of protocol adherence must account for other concurrent interventions in study contexts.

Prevalence of left ventricular systolic dysfunction and heart failure with reduced ejection fraction in men and women with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2D) is associated with the development of left ventricular systolic dysfunction (LVSD) and heart failure with reduced ejection fraction (HFrEF). T2D patients with LVSD are at higher risk of mortality and morbidity than patients without LVSD, while progression of LVSD can be delayed or halted by the use of proven therapies. As estimates of the prevalence are scarce and vary considerably, the aim of this study was to retrieve summary estimates of the prevalence of LVSD/HFrEF in T2D and to see if there were any sex differences. METHODS: A systematic search of Medline and Embase was performed to extract the prevalence of LVSD/HFrEF in T2D (17 studies, mean age 50.1 ± 6.3 to 71.5 ± 7.5), which were pooled using random-effects meta-analysis. RESULTS: The pooled prevalence of LVSD was higher in hospital populations (13 studies, n = 5835, 18% [95% CI 17-19%]), than in the general population (4 studies, n = 1707, 2% [95% CI 2-3%]). Seven studies in total reported sex-stratified prevalence estimates (men: 7% [95% CI 5-8%] vs. women: 1.3% [95% CI 0.0.2.2%]). The prevalence of HFrEF was available in one general population study (5.8% [95% CI 3.7.6%], men: 6.8% vs. women: 3.0%). CONCLUSIONS: The summary prevalence of LVSD is higher among T2D patients from a hospital setting compared with from the general population, with a higher prevalence in men than in women in both settings. The prevalence of HFrEF among T2D in the population was only assessed in a single study and again was higher among men than women.

Selective digestive and oropharyngeal decontamination in medical and surgical ICU patients: individual patient data meta-analysis.

OBJECTIVES: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. METHODS: In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. RESULTS: Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. CONCLUSIONS: In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD.

Cardiac imaging to detect coronary artery disease in athletes aged 35 years and older. A scoping review.

Sudden cardiac death (SCD) is a devastating event in athletes. Screening efforts that were first directed at athletes younger than 35 years are now focusing on the rapidly growing group of older sportspersons. Athletes aged ≥35 years have a 10-fold increased risk of exercise-related cardiac arrest, mostly due to coronary artery disease (CAD). Although cardiac imaging is pivotal in identifying CAD, the role of imaging modalities in screening asymptomatic older sportspersons remains unclear. We performed a scoping review to identify the role of cardiac imaging to detect CAD in older sportspersons and to identify gaps in the existing literature. We searched MEDLINE, EMBASE and the Cochrane library for studies reporting data on cardiac imaging of CAD in sportspersons ≥35 years. The systematic search yielded 1737 articles, and 14 were included in this scoping review. Imaging modalities included two echocardiography, one unenhanced computed tomography (CT) for coronary artery calcium scoring (CACS), three CACS and contrast-enhanced CT angiography (CCTA), two CACS and cardiac magnetic resonance (CMR), one CCTA with CMR and echocardiography, two CCTA, two CMR, and one myocardial perfusion imaging article. The low number of relevant articles and the selection bias introduced by studying specific groups, like veteran marathon runners, indicate the need for future research. Cardiac CT (CACS and CCTA) probably has the highest potential for pre-participation screening, with high diagnostic value to detect CAD and low radiation dose. However, currently there is insufficient evidence for incorporating routine cardiac imaging in the pre-participation screening of asymptomatic sportspersons over 35 years.

Safety of a 1-hour Rule-out High-sensitive Troponin T Protocol in Patients With Chest Pain at the Emergency Department.

BACKGROUND: The 1-hour rule-out high-sensitive cardiac troponin T protocol (hs-cTnT), in which a serial troponin measurement is performed 1 hour after the first to assess the possibility of acute coronary syndrome (ACS), has been implemented in the European guidelines in 2015. Our aim was to assess the safety of this protocol in low-risk patients in the Emergency Department (ED) when implemented in daily practice. METHODS: Patients with acute chest pain presenting to the ED of our hospital and younger than 75 years were included (May 2013 to October 2014, The Netherlands). Hs-cTnT was measured at presentation (T0) and 1-1.5 hours after T0 (T1). Patients with a first troponin (T0) ≥ 0.012 ug/l were excluded. Primary endpoint was the 6-week occurrence of major adverse cardiac events (MACEs), defined as unstable angina, acute myocardial infarction (AMI), percutaneous coronary intervention, significant stenosis managed conservatively, coronary artery bypass grafting, and death. RESULTS: Of the 374 analyzed patients, 16 patients (4.3%) developed 35 MACE. Of these 16 patients with endpoints, 3 were primarily discharged with noncardiac chest pain but returned within 6 weeks with unstable angina. Importantly, no patients experienced an AMI or died during follow-up. CONCLUSION: No AMIs or deaths occurred after introducing the 1-hour hs-cTnT protocol to rule-out ACS in chest pain patients, but other MACE such as unstable angina occurred. Our results suggest the protocol is safe to implement in the ED in The Netherlands.

Risk and associated risk factors of hospitalization for specific health problems over time in childhood cancer survivors: a medical record linkage study.

Childhood cancer survivors (CCS) experience higher hospitalization rates compared to the general population for neoplasms, circulatory diseases, endocrine/nutritional/metabolic diseases and eye disorders. We studied trends in hospitalization rates and associated patient and treatment-specific risk factors for diagnosis subgroups among these four diseases. We performed medical record linkage of a ≥5-year CCS cohort with national registers, and obtained a random reference sample matched on age, gender and calendar year per CCS. For each diagnosis subgroup we compared hospitalization rates and trends over time in CCS and the reference population. Further, we analyzed risk factors for hospitalizations within the four CCS diagnosis groups. We used multivariate Poisson regression for all models. We retrieved hospitalization data from 1382 CCS and 26,583 reference persons. CCS had increased hospitalization rates for almost all diagnosis subgroups examined. Hospitalization rates for endocrine/nutritional/metabolic diseases appeared to increase with longer time since primary cancer diagnosis up to 30 years after primary cancer diagnosis. Survivors initially treated with radiotherapy had increased hospitalization rates for neoplasms (P < 0.001), those initially treated with anthracyclines (2.5 [1.1-5.5]) and radiotherapy to thorax and/or abdomen (9.3 [2.4-36.6]) had increased hospitalization rates for diseases of the circulatory system, and those initially treated with radiotherapy to head and/or neck had increased hospitalization rates for endocrine/nutritional/metabolic diseases (6.7 [3.5-12.7]) and diseases of the eye (3.6 [1.5-8.9]). Our study highlights that long-term health problems resulting in hospitalizations are still clinically relevant later in life of CCS. The identified treatment-related risk factors associated with hospitalizations support targeted follow-up care for these risk groups of CCS.

Narrow Band Imaging, Magnifying Chromoendoscopy, and Gross Morphological Features for the Optical Diagnosis of T1 Colorectal Cancer and Deep Submucosal Invasion: A Systematic Review and Meta-Analysis.

OBJECTIVES: Optical diagnosis of T1 colorectal cancer (CRC) and T1 CRC with deep submucosal invasion is important in guiding the treatment strategy. The use of advanced imaging is not standard clinical practice in Western countries. A systematic review and meta-analysis were conducted comparing the accuracy of narrow band imaging (NBI), magnifying chromoendoscopy (MCE), and gross morphological features (GMF) seen with conventional view for the optical diagnosis of T1 CRC and deep submucosal invasion. METHODS: A literature search identified studies on the optical diagnosis of T1 CRC and deep invasion using NBI, MCE, or GMF. Pooled estimates (PE) of sensitivity and specificity across studies reporting on NBI or MCE were compared using a random effects bivariate meta-regression approach, and a paired analysis focusing on studies that performed both techniques within the same patient was performed. RESULTS: Thirty-three studies with 31,568 polyps were included. For the optical diagnosis of T1 CRC, both NBI (4 studies; PE 0.85, 95% confidence interval (CI) 0.75-0.91) and MCE (5 studies; PE 0.90, 95% CI 0.83-0.94) yielded higher sensitivity as compared with GMF (3 studies; range 0.21-0.46). No significant preference for NBI or MCE was found (sensitivity relative risk (RR) 0.93, 95% CI 0.79-1.09, P=0.37; specificity RR 0.98, 95% CI 0.86-1.11, P=0.74). Similarly, for the optical diagnosis of deep invasion, both NBI (13 studies; PE 0.77, 95% CI 0.68-0.84) and MCE (17 studies; PE 0.81, 95% 0.75-0.87) yielded higher sensitivity as compared with GMF (6 studies; range 0.18-0.88), and no significant preference for either NBI or MCE was found (sensitivity RR 0.92, 95% CI 0.76-1.11, P=0.36; specificity RR 1.00, 95% CI 0.96-1.04, P=0.92). CONCLUSIONS: This review supports the use of advanced imaging techniques in preference to GMF to reduce the risk of performing piecemeal resection for T1 CRCs or unnecessary surgical referral for lesions amendable to endoscopic resection. A preference for either NBI or MCE could not be observed.

Radiological findings and radiation exposure during trauma workup in a cohort of 1124 level 1 trauma patients.

BACKGROUND: During the initial assessment of patients with potential severe injuries, radiological examinations are performed in order to rapidly diagnose clinically relevant injuries. Previous studies have shown that performing these examinations routinely is not always necessary and that trauma patients are exposed to substantial radiation doses. The aim of this study was to assess the amount and findings of radiological examinations during the initial assessment of trauma patients and to determine the radiation doses to which these patients are exposed to. METHODS: We analyzed the 1124 patients included in a randomized trial. All radiological examinations during the initial assessment (i.e., primary and secondary survey) were assessed. The examination results were categorized as positive findings (i.e., (suspicion for) traumatic injury) and normal findings. The effective radiation doses for the examinations were calculated separately for each patient. RESULTS: Eight hundred and three patients were male (71 %), median age was 38 years, and 1079 patients sustained blunt trauma (96 %). During initial assessment, almost 3900 X-rays were performed, of which 25.4 % showed positive findings. FAST of the abdomen was performed in 989 patients (88 %), with positive findings in 10.6 %. Additional CT scanning of specific body regions was performed 1890 times in 813 patients (72.1 %), of which approximately 43.4 % revealed positive findings. Hemodynamically stable patients showed more normal findings on the radiographic studies than unstable patients. The mean radiation doses for the total population was 8.46 mSv (±7.7) and for polytraumatized patients (ISS ≥ 16) 14.3 mSv (±9.5). CONCLUSION: Radiological diagnostics during initial assessment of trauma patients show a high rate of normal findings in our trauma system. The radiation doses to which trauma patients are exposed are considerable. Considering that the majority of the injured patients are hemodynamically stable, we suggest more selective use of X-ray and CT scanning.

Comparison of the GRACE, HEART and TIMI score to predict major adverse cardiac events in chest pain patients at the emergency department.

BACKGROUND: The performance of the GRACE, HEART and TIMI scores were compared in predicting the probability of major adverse cardiac events (MACE) in chest pain patients presenting at the emergency department (ED), in particular their ability to identify patients at low risk. METHODS: Chest pain patients presenting at the ED in nine Dutch hospitals were included. The primary outcome was MACE within 6weeks. The HEART score was determined by the treating physician at the ED. The GRACE and TIMI score were calculated based on prospectively collected data. Performance of the scores was compared by calculating AUC curves. Additionally, the number of low-risk patients identified by each score were compared at a fixed level of safety of at least 95% or 98% sensitivity. RESULTS: In total, 1748 patients were included. The AUC of GRACE, HEART, and TIMI were 0.73 (95% CI: 0.70-0.76%), 0.86 (95% CI: 0.84-0.88%) and 0.80 (95% CI: 0.78-0.83%), respectively (all differences in AUC highly statistically significant). At an absolute level of safety of at least 98% sensitivity, the GRACE score identified 231 patients as "low risk" in which 2.2% a MACE was missed; the HEART score identified 381 patients as "low risk" with 0.8% missed MACE. The TIMI score identified no "low risk" patients at this safety level. CONCLUSIONS: The HEART score outperformed the GRACE and TIMI scores in discriminating between those with and without MACE in chest pain patients, and identified the largest group of low-risk patients at the same level of safety.

Medical consumption compared for TIMI and HEART score in chest pain patients at the emergency department: a retrospective cost analysis.

OBJECTIVE: To investigate which risk score (TIMI score or HEART score) identifies the largest population of low-risk patients at the emergency department (ED). Furthermore, we retrospectively calculated the corresponding expected decrease in medical consumption if these patients would have been discharged from the ED. METHODS: We performed analyses in two hospitals of the multicentre prospective validation study of the HEART score, executed in 2008 and 2009. Patients with chest pain presenting to the ED were included and information was collected on major adverse cardiac events (MACEs) and on hospital admissions and diagnostic procedures within 6 weeks. The TIMI and HEART score were calculated for each patient. RESULTS: We analysed 640 patients (59% male, mean age of 60, cumulative incidence of MACE 17%). An estimated total of €763 468 was spent during follow-up on hospital admission and diagnostic procedures. In total, 256 (40%) patients had a HEART score of 0-3 and were considered low risk (miss rate 1.6%), a total of €64 107 was spent on diagnostic procedures and hospital admission after initial presentation in this group. In comparison, 105 (16%) patients with TIMI score of 0 were considered low risk (miss rate 0%), with a total of €14 670 spent on diagnostic procedures and initial hospital admission costs. With different cut-offs for low risk, HEART 0-2 (miss rate 0.7%), would have resulted in a total of €25 365 in savings, compared with €71 905 when an alternative low risk cut-off for TIMI of TIMI≤1 would be used (miss rate 3.0%). CONCLUSIONS: The HEART score identifies more patients as low risk compared with the TIMI score, which may lead to a larger reduction in diagnostic procedures and costs in this low-risk group. Future studies should prospectively investigate whether adhering to the HEART score in clinical practice and early discharge of low-risk patients is safe and leads to a reduction in medical consumption.

Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement.

Prediction models are developed to aid health-care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health-care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org).

Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD): the TRIPOD Statement.

BACKGROUND: Prediction models are developed to aid healthcare providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision-making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. METHODS: An extensive list of items based on a review of the literature was created, which was reduced after a web-based survey and revised during a 3-day meeting in June 2011 with methodologists, healthcare professionals and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. RESULTS: The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. CONCLUSION: The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. A complete checklist is available at http://www.tripod-statement.org.

Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement.

Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org).

Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): the TRIPOD statement.

Prediction models are developed to aid healthcare providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision-making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) initiative developed a set of recommendations for the reporting of studies developing, validating or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a web-based survey and revised during a 3-day meeting in June 2011 with methodologists, healthcare professionals and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study, regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org).

Paternal or maternal history of cardiovascular disease and the risk of cardiovascular disease in offspring. A systematic review and meta-analysis.

BACKGROUND: Parental history of cardiovascular disease (CVD) is an established risk factor for the development of CVD in offspring. Several studies have suggested that a maternal transmission of CVD is more important for the development of CVD than paternal transmission. METHODS: A systematic search and meta-analysis were conducted, using the Medline and Embase databases. Included were cohort, case-control and cross-sectional studies (n=26) focusing on the relation between paternal and maternal histories of cardiovascular disease and offspring CVD (myocardial infarction, stroke or cardiovascular mortality). The pooled estimates were calculated using a random-effects model. RESULTS: The pooled OR of CVD in offspring having a positive paternal history of CVD compared to not having a positive parental history was 1.91 (95% CI 1.56-2.34; I(2)53%), the RR1.54 (95% CI 1.33-1.77; I(2)96%). The OR of a maternal history was 2.16 (95% CI 1.71-2.74; I(2)50%), RR1.59 (95% CI 1.38-1.84; I(2)90%). Regarding different age limits, a maternal history <50 years (3.15, 95% CI 2.18-4.55) and paternal history <55 years (2.82, 95% CI 2.25-3.54) were associated with the highest cardiovascular risk. Additional analyses for sons demonstrated an estimate for a positive paternal history of 1.55 (95% CI 1.39-1.71; I(2)74%) and 1.56 (95% CI 1.46-1.67; I(2)16%) for maternal history. For daughters, the estimate for paternal history was 1.48 (95% CI 1.26-1.74; I(2)73%) and 1.79 (95% CI 1.50-2.13; I(2)68%) for maternal history . CONCLUSIONS: The conferred risk of CVD in offspring was not substantially different between positive paternal and maternal histories of CVD, the highest risk was observed for maternal history <50years. Since a positive parental history of CVD involves an increased cardiovascular risk, parental history inquiry is useful in clinical practice. No distinction has to be made whether the affected parent is the mother or the father.

Diagnostic accuracy of CT perfusion imaging for detecting acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: The aim of the current study was to determine the sensitivity and specificity of CT perfusion (CTP) for the detection of ischemic stroke by performing a systematic review and meta-analysis of published reports. METHODS: We searched PubMed, Embase and the Cochrane library using the terms 'perfusion computed tomography', 'ischemic stroke' and synonyms. We included studies that: (1) reported original data, (2) studied the diagnostic value of CTP for detecting ischemic stroke, (3) used MRI-DWI, follow-up MRI or follow-up CT as the reference standard, (4) included at least 10 patients who were suspected of ischemic stroke, and (5) reported the number of true positives, true negatives, false positives and false negatives for the diagnosis of ischemic stroke. RESULTS: Fifteen studies were finally included in the current review with a total of 1,107 patients. A pooled analysis resulted in a sensitivity of 80% (95% confidence interval, CI: 72-86%) and a specificity of 95% (95% CI: 86-98%). Almost two thirds of the false negatives were due to small lacunar infarcts; the remaining false negatives were mostly due to limited coverage. CONCLUSIONS: The current systematic review shows that CTP has a high sensitivity and a very high specificity for detecting infarcts.