Non-mortality Outcomes Research Articles

Quality of Life as a Non-mortality Patient-centred Outcome in the Critically Ill: A Retrospective Analysis.

Mortality is a common gauged endpoint in critically ill patients. Reduced quality of life is an aligned repercussion of protracted critical illness. Baseline status, severity of illness and its trajectory influence the outcomes. Patient-oriented outcomes are those that matter the most to a patient. However, quite often, family approves of trade-offs with survivorship in the Indian context. We looked at non-mortality outcomes in patients on high-intensity life-sustaining interventions admitted to the intensive care unit (ICU) despite poor prognosis and died on full support or survived to be completely dependent. In this retrospective chart review study, we studied patients (1) who spent more than 1 month in the hospital enduring a myriad of distressing physical and psychological vicissitudes, (2) whose primary illness was fairly advanced (3) and either succumbed or survived to be impeded in their response to cognitive assessment and with severe functional impairment. Patient demographics, comorbidities, pre-morbid functional status, burden of critical illness, use of life-sustaining therapies, functional dependence in the last week of ICU stay, best neurological status in the last week pre-death or discharge, dying trajectories and economic analysis were noted. Trends of clinical progress of 23 patients were deliberated. The mean age of males was 65 years and 61 years for females. Five patients had a Barthel index score of 10-20, indicating total dependency and two patients had a score of 21-60, indicating severe dependency. Two patients were cognitively impaired at baseline. The worst neurological status in the week before death or discharge was eye1, motor1, and verbaltracheostomised. Thirteen patients succumbed during ongoing treatment. Daily discussions on the dynamics of illness progression need to take place with family on a regular basis for patients managed in ICU. Realistic perceptions and grounded expectations from the families and caregivers are necessary for patient-centred outcomes.

Abstract 4144521: Racial disparities in heart transplantation: long term graft survival and non-mortality outcomes

Background: There is conflicting evidence on whether racial disparities still exist in heart transplant (HT) outcomes, with prior studies focusing primarily on differences in short-term mortality. We examined disparities in HT survival over a longer follow-up duration alongside a broader range of post-HT outcomes. Methods: Using the United Network for Organ Sharing (UNOS) database, we evaluated adult HT recipients between 2017 and 2022 and classified each according to race as either Black, non-Hispanic White and Other. The primary outcome was graft survival and secondary outcomes included rejection, renal dysfunction, and post-transplant diabetes. Chi-squared tests were used to compare baseline clinical factors and selected outcomes by racial group. Kaplan-Meier and Cox proportional hazards analyses were performed to compare risks of the primary outcome by race. Results: Among 15,873 recipients (63% non-Hispanic White, 23% Black, 14% Other), Black recipients were more often female, less often college educated, and more often had public (vs. private) insurance. Blacks had higher use of durable ventricular assist devices (VAD) and intra-aortic balloon pump (IABP) at the time of HT. Graft survival at one year did not differ by race (91.8% for Blacks vs. 91.1% for non-Blacks), but at three years was significantly lower for Blacks (83.4%) than non-Blacks (85.7%). Blacks had higher risk of graft failure after adjustment for baseline socioeconomic status (SES) and clinical variables (HR 1.28, CI 1.17 - 1.41). Blacks also had significantly higher prevalences of acute rejection (12.4% vs. 10.2%), diabetes (10.8% vs. 7.1%), and progression of renal dysfunction at 3-years post HT (40.9% vs. 37.1%; p < 0.05 for all). Conclusions: Racial disparities in graft survival after HT remain in the contemporary era but are only evident after longer-term follow-up. These survival disparities could be mediated by concurrent disparities in shorter term outcomes such as development of acute rejection, chronic kidney disease, and new onset diabetes.

Systematic review of multivariable prognostic models for outcomes at least 30 days after hip fracture finds 18 mortality models but no nonmortality models warranting validation

ObjectivesPrognostic models have the potential to aid clinical decision-making after hip fracture. This systematic review aimed to identify, critically appraise, and summarize multivariable prediction models for mortality or other long-term recovery outcomes occurring at least 30 days after hip fracture. Study Design and SettingMEDLINE, Embase, Scopus, Web of Science, and CINAHL databases were searched up to May 2023. Studies were included that aimed to develop multivariable models to make predictions for individuals at least 30 days after hip fracture. Risk of bias (ROB) was dual-assessed using the Prediction model Risk Of Bias ASsessment Tool. Study and model details were extracted and summarized. ResultsFrom 5571 records, 80 eligible studies were identified. They predicted mortality in n = 55 studies/81 models and nonmortality outcomes (mobility, function, residence, medical, and surgical complications) in n = 30 studies/45 models. Most (n = 46; 58%) studies were published since 2020. A quarter of studies (n = 19; 24%) reported using ‘machine-learning methods’, while the remainder used logistic regression (n = 54; 68%) and other statistical methods (n = 11; 14%) to build models. Overall, 15 studies (19%) presented 18 low ROB models, all predicting mortality. Common concerns were sample size, missing data handling, inadequate internal validation, and calibration assessment. Many studies with nonmortality outcomes (n = 11; 37%) had clear data complexities that were not correctly modeled. ConclusionThis review has comprehensively summarized and appraised multivariable prediction models for long-term outcomes after hip fracture. Only 15 studies of 55 predicting mortality were rated as low ROB, warranting further development of their models. All studies predicting nonmortality outcomes were high or unclear ROB. Careful consideration is required for both the methods used and justification for developing further nonmortality prediction models for this clinical population.

A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre

ObjectiveTo assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DesignRetrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. Setting/participantsHigh-volume non-surgical regional Australian tertiary referral centre. Main outcome measurementsIndex & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. ResultsFrom 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/− 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. ConclusionsAdvances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).

Nangibotide for precision immunomodulation in septic shock and COVID-19

Nangibotide for precision immunomodulation in septic shock and COVID-19

Defining Expectations for Infants With Hypoplastic Left Heart Syndrome Who Survive Initial Surgical Palliation.

Overall one-year non-mortality outcomes for surgically palliated hypoplastic left heart syndrome (HLHS) patients remain understudied. Using the metric Days Alive and Outside of Hospital (DAOH), the present study sought to characterize expectations for surgically palliated patients' first year of life. The Pediatric Health Information System database was used to identify by ICD-10 code all HLHS patients who underwent surgical palliation (Norwood/hybrid and/or heart transplantation [HTx]) during their index neonatal admission and were successfully discharged alive (n = 2227) and for whom one-year DAOH could be calculated. DAOH quartiles were used to group patients for analysis. Median one-year DAOH was 304 (interquartile range [IQR] 250-327), including a median index admission length of stay of 43 days (IQR 28-77). Patients required a median 2 (IQR 1-3) readmissions, each spanning 9 days (IQR 4-20). One-year readmission mortality or hospice discharge occurred in 6% of patients. Patients with lower-quartile DAOH had a median DAOH of 187 (IQR 124-226), whereas upper-quartile DAOH patients had a median DAOH of 335 (IQR 331-340) (P < .001). Readmission mortality/hospice-discharge rates were 14% and 1%, respectively (P < .01). On multivariable analysis, factors independently associated with lower-quartile DAOH included interstage hospitalization (odds ratio [OR] 44.78 [95% confidence interval [CI] 25.1-80.2]), index-admission HTx (8.73 [4.66-16.3]), preterm birth (1.97 [1.34-2.90]), chromosomal abnormality (1.85 [1.26-2.73]), age >7 days at surgery (1.50 [1.14-1.99]), and non-white race/ethnicity (1.33 [1.01-1.75]). In the current era, surgically palliated HLHS infants spend approximately 10 months alive and outside of the hospital, although outcomes are highly variable. Knowledge of the factors associated with lower DAOH can inform expectations and guide management decisions.

Correlation between prehospital and in-hospital hypotension and outcomes after traumatic brain injury

Background and objectiveHypotension has a powerful effect on patient outcome after traumatic brain injury (TBI). The relative impact of hypotension occurring in the field versus during early hospital resuscitation is unknown. We evaluated the association between hypotension and mortality and non-mortality outcomes in four cohorts defined by where the hypotension occurred [neither prehospital nor hospital, prehospital only, hospital only, both prehospital and hospital]. MethodsSubjects ≥10 years with major TBI were included. Standard statistics were used for unadjusted analyses. We used logistic regression, controlling for significant confounders, to determine the adjusted odds (aOR) for outcomes in each of the three cohorts. ResultsIncluded were 12,582 subjects (69.8% male; median age 44 (IQR 26–61). Mortality by hypotension status: No hypotension: 9.2% (95%CI: 8.7–9.8%); EMS hypotension only: 27.8% (24.6–31.2%); hospital hypotension only: 45.6% (39.1–52.1%); combined EMS/hospital hypotension 57.6% (50.0–65.0%); (p < 0.0001). The aOR for death reflected the same progression: 1.0 (reference-no hypotension), 1.8 (1.39–2.33), 2.61 (1.73–3.94), and 4.36 (2.78–6.84), respectively. The proportion of subjects having hospital hypotension was 19.0% (16.5–21.7%) in those with EMS hypotension compared to 2.0% (1.8–2.3%) for those without (p < 0.0001). Additionally, the proportion of patients with TC hypotension was increased even with EMS “near hypotension” up to an SBP of 120 mmHg [(aOR 3.78 (2.97, 4.82)]. ConclusionWhile patients with hypotension in the field or on arrival at the trauma center had markedly increased risk of death compared to those with no hypotension, those with prehospital hypotension that was not resolved before hospital arrival had, by far, the highest odds of death. Furthermore, TBI patients who had prehospital hypotension were five times more likely to arrive hypotensive at the trauma center than those who did not. Finally, even “near-hypotension” in the field was strongly and independently associated the risk of a hypotensive hospital arrival (<90 mmHg). These findings are supportive of the prehospital guidelines that recommend aggressive prevention and treatment of hypotension in major TBI.

Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension

Little is known about the out-of-hospital blood pressure ranges associated with optimal outcomes in traumatic brain injuries (TBI). Our objective was to evaluate the associations between out-of-hospital systolic blood pressure (SBP) and multiple hospital outcomes without assuming any predefined thresholds for hypotension, normotension, or hypertension. This was a preplanned secondary analysis from the Excellence in Prehospital Injury Care (EPIC) TBI study. Among patients (age ≥10 years) with major TBIs (Barell Matrix type 1 and/or Abbreviated Injury Scale-head severity ≥3) and lowest out-of-hospital SBPs of 40 to 299 mmHg, we utilized generalized additive models to summarize the distributions of various outcomes as smoothed functions of SBP, adjusting for important and significant confounders. The subjects who were enrolled in the study phase after the out-of-hospital TBI guideline implementation were used to validate the models developed from the preimplementation cohort. Among 12,169 included cases, the mortality model revealed 3 distinct ranges: (1) a monotonically decreasing relationship between SBP and the adjusted probability of death from 40 to 130 mmHg, (2) lowest adjusted mortality from 130 to 180 mmHg, and (3) rapidly increasing mortality above 180 mmHg. A subanalysis of the cohorts with isolated TBIs and multisystem injuries with TBIs revealed SBP mortality patterns that were similar to each other and to that of the main analysis. While the specific SBP ranges varied somewhat for the nonmortality outcomes (hospital length of stay, ICU length of stay, discharge to skilled nursing/inpatient rehabilitation, and hospital charges), the patterns were very similar to that of mortality. In each model, validation was confirmed utilizing the postimplementation cohort. Optimal adjusted mortality was associated with a surprisingly high SBP range (130 to 180 mmHg). Below this level, there was no point or range of inflection that would indicate a physiologically meaningful threshold for defining hypotension. Nonmortality outcomes showed very similar patterns. These findings highlight how sensitive the injured brain is to compromised perfusion at SBP levels that, heretofore, have been considered adequate or even normal. While the study design does did not allow us to conclude that the currently recommended treatment threshold (<90 mmHg) should be increased, the findings imply that the definition of hypotension in the setting of TBI is too low. Randomized trials evaluating treatment levels significantly higher than 90 mmHg are needed.

Primary Care Visit Cadence Based on Risk: A Comparison of Machine Learning and Provider Judgment

Summary More frequent primary care visits are associated with improvements in health outcomes and overall well-being and a reduction in health care disparities. Visit cadence is a core part of Oak Street Health’s value-based care model. Although its providers are generally good at predicting a patient’s risk of mortality, they are less accurate at predicting nonmortality outcomes, and they may not update each patient’s risk level in a timely manner. Oak Street launched a pilot initiative to assess whether machine-learning models could outperform provider visit cadence assignment in predicting three key outcomes: acute inpatient admissions, medical cost, and mortality. Pilot results demonstrated that the models were more accurate than provider judgment alone at identifying patients’ risk of admission and future medical cost. On the basis of these positive findings, Oak Street deployed the machine-learning tiering across the organization, with more than 90% of all eligible patients assigned a tier that is routinely refreshed using the predictive models.

Disparities in surgical outcomes of neonates with congenital heart disease across regions, centers, and populations

ObjectiveTo summarize existing literature on neonatal disparities in congenital heart disease surgical outcomes and identify potential policies to address these disparities. FindingDisparities in outcomes for neonatal congenital heart surgery were largely published under four domains: race/ethnicity, insurance type, neighborhood/socioeconomic status, and cardiac center characteristics. While existing research identifies associations between these domains and mortality, more nuanced analyses are emerging to understand the mediators between these domains and other non-mortality outcomes, as well as potential interventions and policies to reduce disparities. A broader look into social determinants of health (SDOH), prenatal diagnosis, proximity of birth to a cardiac surgical center, and post-surgical outpatient and neurodevelopmental follow-up may accelerate interventions to mitigate disparities in outcomes. ConclusionUnderstanding the mechanisms of how SDOH relate to neonatal surgical outcomes is paramount, as disparities research in neonatal congenital heart surgery continues to shift from identification and description, to intervention and policy.

Mortality risk and physical activity across the lifespan in endometrial cancer survivors.

Physical activity (pre- and post-diagnosis) has been studied in prevention and survivorship contexts for endometrial cancer. However, the association of physical activity (PA) across the lifespan on mortality risk among endometrial cancer survivors is understudied. The study's objective was to identify the association of lifetime PA on mortality risk in endometrial cancer survivors. Seven hundred forty-five endometrial cancer survivors drawn from a population-based cancer registry (diagnosed between 1991 and 1994) reported the frequency (sessions/week) of moderate- and vigorous intensity physical activity (MVPA) at age 12, age 20, and 5years pre-interview (post-diagnosis). Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals for the association between PA, all-cause, and cardiovascular disease mortality as assessed in 2016. MVPA was modeled using natural cubic splines. Diagnosis age, body mass index, and smoking (pack-years) were each positively associated with increased all-cause mortality risk. Those who did one session of MVPA 5years pre-interview had a lower mortality risk (HR 0.61; 95% CI 0.41-0.92) compared to those with no MVPA. Those reporting one session of MVPA was similarly observed at age 12 (HR 0.95; 95% CI 0.86-1.06) and at age 20 (HR 0.87; 95% CI 0.65-1.16). Those who participated in PA, compared to those who did not, in the 5years before diagnosis had a lower mortality risk. While PA was not independently protective against mortality risk at ages 12 or 20, PA is still important for endometrial cancer survivors for other non-mortality outcomes.

210 A SYSTEMATIC REVIEW OF LONG-TERM OUTCOME COLLECTION FOLLOWING HIP FRACTURE IN IRELAND FROM 2005 TO 2021

Abstract Background The Irish Hip Fracture Database (IHFD) drives clinical improvements across 16 acute hospitals for over 3,500 patients annually. The IHFD aims to begin recording long-term outcomes. Past practice in Ireland could inform this activity. This review aims to identify and summarise studies that have collected long-term outcomes following hip fracture in Ireland. Methods A search of electronic databases (MEDLINE, Embase, Scopus, Web of Science, CINAHL) and grey literature was conducted in July 2021 for articles, abstracts, theses and reports. Search terms related to hip fracture and Ireland. Studies published from 2005–2021 were included if post-hospital discharge data were collected in the Republic of Ireland for patients with hip fracture. Study and patient characteristics, data collection methods and long-term outcomes were extracted. Results From all sources, 21 articles, 3 theses and 84 abstracts from 18 clinical sites were identified. Numbers of patients with hip fracture ranged from 9 to 2,483 (median 168) across publications. The most common outcome recorded was mortality (59% of publications), most frequently at 30 days and/or one year. Ascertainment methods for mortality included electronic patient records, online death notices, phone calls to family or general practitioners and the national death register. Non-mortality long-term outcomes were assessed in 64% of publications, most commonly through outpatient or virtual clinics or phone calls. They included place of residence, function, mobility and bone-health status at time-points of 30 days, 6 weeks, 3, 4, 6 or 12 months. Only 11 publications followed patients past the 1 year time-point. One third of publications did not report data collection methods. Conclusion Meta-analyses of results will provide estimates of mortality rates and other key hip fracture outcomes. Some long-term outcomes have been collected at most hospitals treating acute hip fracture in Ireland in the last 15 years. Qualitative research in needed to identify facilitators of follow-up to inform practice nationally.

Abstract 421: Characteristics of melanoma diagnosed in patients with underlying HIV infection

Abstract Background: Melanoma is diagnosed more frequently in patients living with HIV (PLWH) compared to the general US population and HIV-infected melanoma patients also experience higher cancer-specific mortality. The mechanisms underlying these outcome disparities are poorly understood, and data describing tumor pathology and non-mortality outcomes for melanoma patients with HIV are lacking. Objective: To describe differences in tumor presentation and disease course among melanoma patients presenting with or without underlying HIV infection in the era of effective HIV therapy. Methods: We conducted an initial retrospective chart review of 29 HIV+ and 29 HIV- patients, matched as possible to HIV+ patients on age and disease stage, who presented to Moffitt Cancer Center between 2004 and 2019. Data abstracted included patient demographics, tumor pathology, treatment details, and clinical outcomes. Results: Certain melanoma pathology features differed by HIV status, with a higher prevalence of elevated mitotic rate (78.9% vs 41.2%, p=0.02) and vertical growth phase (90% vs 55%, p=0.02) in melanoma patients with HIV. Nearly all patients underwent lesion excision, but post-treatment complications were greater in PLWH (44.8% vs 24%, p=0.09). Among 16 patients who received systemic therapy after excision (HIV+ 6; HIV- 10), progressive disease was more frequent in PLWH (100% vs 30%, p=0.01), with further suggestion of higher severe side effect rates, defined as events interrupting systemic therapy (66.7% vs 30%; p=0.18). Despite these differences in progression, overall survival rate were similar in PLWH (79.3%) and uninfected patients (82.8%). Conclusions: These preliminary results suggest that PLWH and melanoma experience a unique disease course. Higher prevalence of post-excision complications and disease progression following systemic therapy in particular warrant further attention as age-related cancers, such as melanoma, are expected to grow in the US HIV population in coming years. Citation Format: Grace Wei, Sweta Sinha, Jane Messina, Anna E. Coghill. Characteristics of melanoma diagnosed in patients with underlying HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 421.

Treatment effects in randomised trials using routinely collected data for outcome assessment versus traditional trials: meta-research study

ObjectiveTo compare effect estimates of randomised clinical trials that use routinely collected data (RCD-RCT) for outcome ascertainment with traditional trials not using routinely collected data.DesignMeta-research study.Data sourceStudies included in the...

Australian Injury Comorbidity Indices (AICIs) to predict burden and readmission among hospital-admitted injury patients

BackgroundExisting comorbidity measures predict mortality among general patient populations. Due to the lack of outcome specific and patient-group specific measures, the existing indices are also applied to non-mortality outcomes in injury epidemiology. This study derived indices to capture the association between comorbidity, and burden and readmission outcomes for injury populations.MethodsInjury-related hospital admissions data from July 2012 to June 2014 (161,334 patients) for the state of Victoria, Australia were analyzed. Various multivariable regression models were run and results used to derive both binary and weighted indices that quantify the association between comorbidities and length of stay (LOS), hospital costs and readmissions. The new and existing indices were validated internally among patient subgroups, and externally using data from the states of New South Wales and Western Australia.ResultsTwenty-four comorbidities were significantly associated with overnight stay, twenty-seven with LOS, twenty-eight with costs, ten with all-cause and eleven with non-planned 30-day readmissions. The number of and types of comorbidities, and their relative impact were different to the associations established with the existing Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Measure (ECM). The new indices performed equally well to the long-listed ECM and in certain instances outperformed the CCI.ConclusionsThe more parsimonious, up to date, outcome and patient-specific indices presented in this study are better suited for use in present injury epidemiology. Their use can be trialed by hospital administrations in resource allocation models and patient classification models in clinical settings.

Inpatient and Postdischarge Outcomes Following Inhalation Injury Among Critically Injured Burn Patients.

Inhalation injury is associated with high inpatient mortality, but the impact of inhalation injury after discharge and on non-mortality outcomes is poorly characterized. To address this gap, we evaluated the effect of inhalation injury on postdischarge morbidity, mortality, and hospital readmissions among patients who sustained burn injury, as well as on in-hospital outcomes for context. This was a retrospective cohort study of patients with cutaneous fire/flame burns admitted to a burn center intensive care unit from January 1, 2009 to December 31, 2015, with or without inhalation injury. Records were linked to statewide hospital admission and vital statistics databases to assess postdischarge outcomes. Mixed-effects Poisson regression was used to assess mortality, complications, and readmissions. The overall cohort included 830 patients with cutaneous burns; of these, 201 patients had inhalation injury. In-hospital mortality was 31% among inhalation injury patients vs 6% in patients without inhalation injury (adjusted OR 2.35; 95% CI 1.66-3.31). Inhalation injury was also associated with an increased risk of in-hospital pneumonia and tracheostomy (P < .05 for all). Inhalation injury was not associated with greater postdischarge mortality, all-cause readmission, readmission for pulmonary diagnosis, or readmission requiring intubation. Among the subset of patients with bronchoscopy-confirmed inhalation injury (n = 124; 62% of inhalation injuries), a higher injury grade was not associated with greater inpatient or postdischarge mortality. Inhalation injury was associated with increased early morbidity and mortality, but did not contribute to postdischarge mortality or readmission. These findings have implications for shared decision making with patients and families and for estimating healthcare utilization after initial hospitalization.

Diagnostic accuracy, yield, and comparative effectiveness of whole-body computed tomography in blunt trauma: A protocol for systematic review and meta-analysis.

Controversies emerge over routine performances of whole-body computed tomography (WBCT) in patients with blunt polytrauma. The existing randomized and non-randomized evidence is inconclusive, and during observations of non-trauma, incidental findings, detected by WBCT, have left uncertainty regarding their consequences and optimal management. Additionally, previous meta-analyses have failed to address the limitations of primary studies and issues associated with incidental findings. Therefore, we planned a new systematic review to address these points. We will search the PubMed, EMBASE, and Cochrane Central databases from inception to December 31, 2020, with no language restriction and perform full-text evaluation of potentially relevant articles. We will include prospective and retrospective studies with a single-gate design that assessed diagnostic accuracy and/or yield of WBCT to detect traumatic injuries, and studies that assessed incidental findings detected by WBCT. Additionally, we will include randomized controlled trials and non-randomized comparative studies that assessed the effectiveness of WBCT against conventional care, including selective computed tomography (CT). Studies of patients of all ages with blunt traumatic injuries, assessed at an emergency department, will be included. Two reviewers will extract data and rate the study validity via standard quality assessment tools. The primary outcome of interest will be reduction in mortality. Our secondary outcomes will include diagnostic accuracy and yield, detection of incidental findings and clinical outcomes associated with these detections, and improvement in other non-mortality clinical outcomes. We will qualitatively assess study, patient, and intervention characteristics and clinical outcomes. If appropriate, we will perform random-effects model meta-analyses to obtain summary estimates. Finally, we will assess the certainty of evidence by the grading the quality of evidence and strength of recommendations. Ethics approval is not applicable, as this is a secondary analysis of publicly available data. The review results will be submitted for publication in peer-reviewed journals. CRD42020187852.

Impact of regionalisation and case-volume on neonatal and perinatal mortality: an umbrella review.

ObjectiveThis umbrella review summarises and critically appraises the evidence on the effects of regulated or high-volume perinatal care on outcome among very low birth weight/very preterm infants born in countries with neonatal mortality <5/1000 births.Intervention/expositionPerinatal regionalisation, centralisation, case-volume.Primary outcomesDeath.Secondary outcomesDisability, discomfort, disease, dissatisfaction.MethodsOn 29 November 2019 a systematic search in MEDLINE and Embase was performed and supplemented by hand search. Relevant systematic reviews (SRs) were critically appraised with A MeaSurement Tool to Assess systematic Reviews 2.ResultsThe literature search revealed 508 hits and three SRs were included. Effects of perinatal regionalisation were assessed in three (34 studies) and case-volume in one SR (6 studies). Centralisation has not been evaluated. The included SRs reported effects on ‘death’ (eg, neonatal), ‘disability’ (eg, mental status), ‘discomfort’ (eg, maternal sensitivity) and ‘disease’ (eg, intraventricular haemorrhages). ‘Dissatisfactions’ were not reported. The critical appraisal showed a heterogeneous quality ranging from moderate to critically low. A pooled effect estimate was reported once and showed a significant favour of perinatal regionalisation in terms of neonatal mortality (OR 1.60, 95% CI 1.33–1.92). The qualitative evidence synthesis of the two SRs without pooled estimate suggests superiority of perinatal regionalisation in terms of different mortality and non-mortality outcomes. In one SR, contradictory results of lower neonatal mortality rates were reported in hospitals with higher birth volumes.ConclusionsRegionalised perinatal care seems to be a crucial care strategy to improve the survival of very low birth weight and preterm births. To overcome the low and critically low methodological quality and to consider additional clinical and patient-reported results that were not addressed by the SRs included, we recommend an updated SR. In the long term, an international, uniformly conceived and defined perinatal database could help to provide evidence-based recommendations on optimal strategies to regionalise perinatal care.PROSPERO registration numberCRD42018094835.

Systematic review on the definition and predictors of severe Clostridiodes difficile infection.

Clostridiodes difficile infection (CDI) is one of the most common hospital-acquired infections with high mortality rates. Optimal management of CDI depends on early recognition of severity. However, currently, there is no acceptable standard of prediction. We reviewed severe CDI predictors in published literature and its definition according to clinical guidelines. We systematically reviewed studies describing clinical predictors for severe CDI in medical databases (Cochrane, EMBASE, Global Health Library, and MEDLINE/PubMed). They were independently evaluated by two reviewers. Six hundred thirty-three titles and abstracts were screened, and 31 studies were included. We excluded studies that were restricted to a specific patient population. There were 16 articles that examined mortality in CDI, as compared with 15 articles investigating non-mortality outcomes of CDI. The commonest risk factors identified were comorbidities, white blood cell count, serum albumin level, age, serum creatinine level and intensive care unit admission. Generally, the studies had small patient populations, were retrospective in nature, and mostly from Western centers. The commonest severe CDI criteria in clinical guidelines were raised white blood cell count, followed by low serum albumin and raised serum creatinine levels. There was no commonly agreed upon definition of severe CDI severity in the literature. Current clinical guidelines' definitions for severe CDI are heterogeneous. Hence, there is a need for prospective multi-center studies using standardized protocol for biospecimen investigation collection and shared data on outcomes of patients in order to devise a universally accepted definition for severe CDI.

Prevalence of Multiplicity and Appropriate Adjustments Among Cardiovascular Randomized Clinical Trials Published in Major Medical Journals

Multiple analyses in a clinical trial can increase the probability of inaccurately concluding that there is a statistically significant treatment effect. However, to date, it is unknown how many randomized clinical trials (RCTs) perform adjustments for multiple comparisons, the lack of which could lead to erroneous findings. To assess the prevalence of multiplicity and whether appropriate multiplicity adjustments were performed among cardiovascular RCTs published in 6 medical journals with a high impact factor. In this cross-sectional study, cardiovascular RCTs were selected from all over the world, characterized as North America, Western Europe, multiregional, and rest of the world. Data were collected from past issues of 3 cardiovascular journals (Circulation, European Heart Journal, and Journal of the American College of Cardiology) and 3 general medicine journals (JAMA, The Lancet, and The New England Journal of Medicine) with high impact factors published between August 1, 2015, and July 31, 2018. Supplements and trial protocols of each of the included RCTs were also searched for multiplicity. Data were analyzed December 20 to 27, 2018. Data from the selected RCTs were extracted and verified independently by 2 researchers using a structured data instrument. In case of disagreement, a third reviewer helped to achieve consensus. An RCT was considered to have multiple treatment groups if it had more than 2 arms; multiple outcomes were defined as having more than 1 primary outcome, and multiple analyses were defined as analysis of the same outcome variable in multiple ways. Multiplicity was examined only for the analysis of the primary end point. Outcomes of interest were percentages of primary analyses that performed multiplicity adjustment of primary end points. Of 511 cardiovascular RCTs included in this analysis, 300 (58.7%) had some form of multiplicity; of these 300, only 85 (28.3%) adjusted for multiplicity. Intervention type and funding source had no statistically significant association with the reporting of multiplicity risk adjustment. Trials that assessed mortality vs nonmortality outcomes were more likely to contain a multiplicity risk in their primary analysis (66.3% [177 of 267] vs 50.4% [123 of 244]; P < .001), and larger trials vs smaller trials were less likely to make any adjustments for multiplicity (35.6% [52 of 146] vs 21.4% [33 of 154]; P = .001). Findings from this study suggest that cardiovascular RCTs published in medical journals with high impact factors demonstrate infrequent adjustments to correct for multiple comparisons in the primary end point. These parameters may be improved by more standardized reporting.