Appraising clinical applicability of studies: mapping and synthesis of current frameworks, and proposal of the FrACAS framework and VICORT checklist.

BACKGROUND: Not all research findings are translated to clinical practice. Reasons for lack of applicability are varied, and multiple frameworks and criteria exist to appraise the general applicability of epidemiological and clinical research. In this two-part study, we identify, map, and synthesize frameworks and criteria; we develop a framework to assist clinicians to appraise applicability specifically from a clinical perspective. METHODS: We conducted a literature search in PubMed and Embase to identify frameworks appraising applicability of study results. Conceptual thematic analysis was used to synthesize frameworks and criteria. We carried out a framework development process integrating contemporary debates in epidemiology, findings from the literature search and synthesis, iterative pilot-testing, and brainstorming and consensus discussions to propose a concise framework to appraise clinical applicability. RESULTS: Of the 4622 references retrieved, we identified 26 unique frameworks featuring 21 criteria. Frameworks and criteria varied by scope and level of aggregation of the evidence appraised, target user, and specific area of applicability (internal validity, clinical applicability, external validity, and system applicability). Our proposed Framework Appraising the Clinical Applicability of Studies (FrACAS) classifies studies in three domains (research, practice informing, and practice changing) by examining six criteria sequentially: Validity, Indication-informativeness, Clinical relevance, Originality, Risk-benefit comprehensiveness, and Transposability (VICORT checklist). CONCLUSIONS: Existing frameworks to applicability vary by scope, target user, and area of applicability. We introduce FrACAS to specifically assess applicability from a clinical perspective. Our framework can be used as a tool for the design, appraisal, and interpretation of epidemiological and clinical studies.

Association of Intravenous Radiocontrast With Kidney Function: A Regression Discontinuity Analysis.

Importance: Radiocontrast has long been thought of as nephrotoxic; however, a number of recent observational studies found no evidence of an association between intravenous contrast and kidney injury. Because these studies are at high risk of confounding and selection bias, alternative study designs are required to enable more robust evaluation of this association. Objective: To determine whether intravenous radiocontrast exposure is associated with clinically significant long-term kidney impairment, using a study design that permits stronger causal interpretation than existing observational research. Design, Setting, and Participants: This cohort study included all emergency department patients aged 18 years or older undergoing D-dimer testing between 2013 and 2018 in the Canadian province of Alberta. A fuzzy regression discontinuity design was used, exploiting the fact that individuals just either side of the eligibility cutoff for computed tomographic pulmonary angiogram (CTPA)-typically 500 ng/mL-have markedly different probabilities of contrast exposure, but should otherwise be similar with respect to potential confounders. Exposures: Intravenous contrast in the form of a CTPA. Main Outcomes and Measures: Estimated glomerular filtration rate (eGFR) up to 6 months following the index emergency department visit. Results: During the study period 156 028 individuals received a D-dimer test. The mean age was 53 years, 68 206 (44%) were men and 87 822 (56%) were women, and the mean baseline eGFR level was 86 mL/min/1.73 m2. Patients just above and below the CTPA eligibility cutoff were similar in terms of measured confounders. There was no evidence for an association of contrast with eGFR up to 6 months later, with a mean change in eGFR of -0.4 mL/min/1.73 m2 (95% CI, -4.9 to 4.0) associated with CTPA exposure. There was similarly no evidence for an association with need for kidney replacement therapy (risk difference [RD], 0.07%; 95% CI, -0.47% to 0.61%), mortality (RD, 0.3%; 95% CI, -2.9% to 3.2%), and acute kidney injury (RD, 4.3%; 95% CI, -2.7% to 12.9%), though the latter analysis was limited by missing data. Subgroup analyses were potentially consistent with harm among patients with diabetes (mean eGFR change -6.4 mL/min/1.73 m2; 95% CI, -15.4 to 0.2), but not among those with other reported risk factors for contrast-induced nephropathy; these analyses, however, were relatively underpowered. Conclusions and Relevance: Using a cohort study design and analysis that permits stronger causal interpretation than existing observational research, we found no evidence for a harmful effect on kidney function of intravenous contrast administered for CTPA in an emergency setting.

Loss of microbial diversity and pathogen domination of the gut microbiota in critically ill patients.

Among long-stay critically ill patients in the adult intensive care unit (ICU), there are often marked changes in the complexity of the gut microbiota. However, it remains unclear whether such patients might benefit from enhanced surveillance or from interventions targeting the gut microbiota or the pathogens therein. We therefore undertook a prospective observational study of 24 ICU patients, in which serial faecal samples were subjected to shotgun metagenomic sequencing, phylogenetic profiling and microbial genome analyses. Two-thirds of the patients experienced a marked drop in gut microbial diversity (to an inverse Simpson's index of <4) at some stage during their stay in the ICU, often accompanied by the absence or loss of potentially beneficial bacteria. Intravenous administration of the broad-spectrum antimicrobial agent meropenem was significantly associated with loss of gut microbial diversity, but the administration of other antibiotics, including piperacillin/tazobactam, failed to trigger statistically detectable changes in microbial diversity. In three-quarters of ICU patients, we documented episodes of gut domination by pathogenic strains, with evidence of cryptic nosocomial transmission of Enterococcus faecium. In some patients, we also saw an increase in the relative abundance of apparent commensal organisms in the gut microbiome, including the archaeal species Methanobrevibacter smithii. In conclusion, we have documented a dramatic absence of microbial diversity and pathogen domination of the gut microbiota in a high proportion of critically ill patients using shotgun metagenomics.

Association Between Hospital Volume and Mortality in Status Epilepticus: A National Cohort Study.

OBJECTIVES: In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers. DESIGN: Cohort study, using 2010-2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre. SETTING: Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland. PATIENTS: Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure. INTERVENTIONS: Annual hospital status epilepticus admission volume. MEASUREMENTS AND MAIN RESULTS: We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers. CONCLUSIONS: We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus.

qSOFA, SIRS and NEWS for predicting inhospital mortality and ICU admission in emergency admissions treated as sepsis.

BACKGROUND: The third international consensus definition for sepsis recommended use of a new prognostic tool, the quick Sequential Organ Failure Assessment (qSOFA), based on its ability to predict inhospital mortality and prolonged intensive care unit (ICU) stay in patients with suspected infection. While several studies have compared the prognostic accuracy of qSOFA to the Systemic Inflammatory Response Syndrome (SIRS) criteria in suspected sepsis, few have compared qSOFA and SIRS to the widely used National Early Warning Score (NEWS). METHODS: This was a retrospective cohort study carried out in a UK tertiary centre. The study population comprised emergency admissions in whom sepsis was suspected and treated. The accuracy for predicting inhospital mortality and ICU admission was calculated and compared for qSOFA, SIRS and NEWS. RESULTS: Among 1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). For predicting inhospital mortality, the area under the receiver operating characteristics curve for NEWS (0.65, 95% CI 0.61 to 0.68) was similar to qSOFA (0.62, 95% CI 0.59 to 0.66) (test for difference, P=0.18) and superior to SIRS (P<0.001), which was not predictive. The sensitivity of NEWS≥5 (74%, 95% CI 68% to 79%) was similar to SIRS≥2 (80%, 95% CI 74% to 84%) and higher than qSOFA≥2 (37%, 95% CI 31% to 43%). The specificity of NEWS≥5 (43%, 95% CI 41% to 46%) was higher than SIRS≥2 (21%, 95% CI 19% to 23%) and lower than qSOFA≥2 (79%, 95% CI 77% to 81%). The negative predictive value was 88% (86%-90%) for qSOFA, 86% (82%-89%) for SIRS and 91% (88%-93%) for NEWS. Results were similar for the secondary outcome of ICU admission. CONCLUSION: NEWS has equivalent or superior value for most test characteristics relative to SIRS and qSOFA, calling into question the rationale of adopting qSOFA in institutions where NEWS is already in use.

Change in newspaper coverage of schizophrenia in Japan over 20-year period.

In Japan, schizophrenia was renamed in 2002 to reduce the stigma that people with schizophrenia are dangerous. However there has been little research on the potential anti-stigma effect of renaming. The present study aimed to examine whether portrayals of schizophrenia in newspapers as dangerous have been varied across renaming of the disease. To achieve this goal, newspaper articles containing the previous and new Japanese names for schizophrenia, published in the decades before and after the renaming, were identified through the database of the three largest Japanese national broadsheets. Identified articles were divided into two categories: a negative category, including a subcategory "danger"; and a positive category. Articles containing bipolar disorder were adopted as a control. The ratio of the number of articles on schizophrenia and danger to that of bipolar disorder was analysed as a variable of interest. The trend of this ratio was investigated to examine whether portrayals of schizophrenia changed after renaming. The search identified 4677 articles on schizophrenia, 53.0% of which were categorised as negative and 38.9% as danger. The search identified 525 articles on bipolar disorder, 24.6% of which were categorised as negative and 11.2% as danger. There was an increase of the ratio before schizophrenia was renamed (r=0.54, p=0.104), and a significant decrease after renaming (r=-0.69, p=0.028). Fisher's r-to-z transformation demonstrated a significant change in the trend of the ratio across renaming (Z=2.72, p=0.007). Renaming schizophrenia might be associated with mitigation in potentially stigmatised depiction of schizophrenia associated with violence in newspaper reports.

Moderate Alcohol Consumption Is Not Associated with Reduced All-cause Mortality.

BACKGROUND: A large body of research suggests that light or moderate alcohol consumption is associated with reduced all-cause mortality. However, concerns remain that the observed relationship is due to selection bias, misclassification of ex-drinkers, or residual confounding. METHODS: The association between alcohol consumption and all-cause mortality was analyzed using Cox regression. The analysis was performed using data from the Health and Retirement Study, a longitudinal cohort of 24,029 individuals from a nationally representative sample of US adults aged more than 50 years. Drinking level was based on alcohol consumption measured at 3 points over the 4 years before the start of follow-up. Occasional drinkers-those who reported drinking on at least 1 occasion, but always less than once per week-served as the reference category. There was extensive adjustment for sociodemographic variables, health status, and functional status. RESULTS: During 206,966 person-years of follow up, 7902 individuals died. No level of regular alcohol consumption was associated with reduced all-cause mortality. The hazard ratio and 95% confidence interval in fully adjusted analyses was 1.02 (0.94-1.11) for <7 drinks/week, 1.14 (1.02-1.28) for 7 to <14 drinks/week, 1.13 (0.96-1.35) for 14 to <21 drinks/week, and 1.45 (1.16-1.81) for ≥ 21 drinks/week. CONCLUSIONS: Moderate alcohol consumption is not associated with reduced all-cause mortality in older adults. The previously observed association may have been due to residual confounding.

Newspaper coverage of mental illness in England 2008-2011.

BACKGROUND: Better newspaper coverage of mental health-related issues is a target for the Time to Change (TTC) anti-stigma programme in England, whose population impact may be influenced by how far concurrent media coverage perpetuates stigma and discrimination. AIMS: To compare English newspaper coverage of mental health-related topics each year of the TTC social marketing campaign (2009-2011) with baseline coverage in 2008. METHOD: Content analysis was performed on articles in 27 local and national newspapers on two randomly chosen days each month. RESULTS: There was a significant increase in the proportion of anti-stigmatising articles between 2008 and 2011. There was no concomitant proportional decrease in stigmatising articles, and the contribution of mixed or neutral elements decreased. CONCLUSIONS: These findings provide promising results on improvements in press reporting of mental illness during the TTC programme in 2009-2011, and a basis for guidance to newspaper journalists and editors on reporting mental illness.

Newspaper coverage of mental illness in the UK, 1992-2008.

BACKGROUND: Recent years have seen a number of attempts to reduce the stigma related to mental illness; the media can play a significant role in perpetuating this stigma. This paper analyses trends in newspaper coverage of mental illness in the UK between 1992-2008 across a range of psychiatric diagnoses. METHODS: A content analysis was performed on a sample of articles (n = 1361) about mental illness in a range of UK newspapers in 1992, 2000, and 2008. RESULTS: There was a significant proportional reduction in negative articles about mental illness between 1992 and 2008, and a significant increase in articles explaining psychiatric disorders. Coverage improved for depression but remained largely negative for schizophrenia. CONCLUSIONS: Newspaper coverage of mental illness became less stigmatising overall in the 1990s and 2000s, but this was not true for all diagnoses.