Miracle-dz/UniFAR-FTUs huggingface dataset:
Cost‐effectiveness Analysis Appraisal and Application: An Emergency Medicine Perspective

Cost-effectiveness is an important goal for emergency care delivery. The many diagnostic, treatment, and disposition decisions made in the emergency department (ED) have a significant impact upon healthcare resource utilization. Cost-effectiveness analysis (CEA) is an analytic tool to optimize these resource allocation decisions through the systematic comparison of costs and effects of alternative healthcare decisions. Yet few emergency medicine leaders and policymakers have any formal training in CEA methodology. This paper provides an introduction to the interpretation and use of CEA with a focus on application to emergency medicine problems and settings. It applies a previously published CEA to the hypothetical case of a patient presenting to the ED with chest pain who requires risk stratification. This paper uses a widely cited checklist to appraise the CEA. This checklist serves as a vehicle for presenting basic CEA terminology and concepts. General topics of focus include measurement of costs and outcomes, incremental analysis, and sensitivity analysis. Integrated throughout the paper are recommendations for good CEA practice with emphasis on the guidelines published by the U.S. Panel on Cost-Effectiveness in Health and Medicine. Unique challenges for emergency medicine CEAs discussed include the projection of long-term outcomes from emergent interventions, costing ED services, and applying study results to diverse patient populations across various ED settings. The discussion also includes an overview of the limitations inherent in applying CEA results to clinical practice to include the lack of incorporation of noncost considerations in CEA (e.g., ethics). After reading this article, emergency medicine leaders and researchers will have an enhanced understanding of the basics of CEA critical appraisal and application. The paper concludes with an overview of economic evaluation resources for readers interested in conducting ED-based economic evaluation studies.
Beyond endoscopic mucosal healing in UC: histological remission better predicts corticosteroid use and hospitalisation over 6 years of follow-up

Background Endoscopic mucosal healing is an established treatment target for UC, yet the value of achieving histological remission remains unclear. Aims To evaluate histological remission compared to endoscopic mucosal healing for predicting patient outcomes in UC. Methods Blinded assessment of endoscopic and histological measures of disease activity was performed on patients with established UC at baseline. Concordance and prognostic values of endoscopic mucosal healing (defined by Baron score ≤1) and histological remission (defined by Truelove and Richards’ index) for predicting outcomes of corticosteroid use, hospitalisation and colectomy were determined over a median 6 years follow-up, including κ statistics and Cox regression multivariate analysis. Results 91 patients with UC were followed up for a median 72 months (IQR 54–75 months). Overall, concordance between endoscopic and histological remission was moderate (κ=0.56, 95% CI 0.36 to 0.77); 24% patients had persistent inflammation despite endoscopic remission. Histological remission predicted corticosteroid use and acute severe colitis requiring hospitalisation over the follow-up period (HR 0.42 (0.2 to 0.9), p=0.02; HR 0.21 (0.1 to 0.7), p=0.02; respectively), whereas endoscopic mucosal healing did not (HR 0.86, 95% CI 0.5 to 1.7, p0.65; HR 0.83 95% CI 0.3 to 2.4, p0.74; respectively). Conclusions Histological remission is a target distinct from endoscopic mucosal healing in UC and better predicts lower rates of corticosteroid use and acute severe colitis requiring hospitalisation, over a median of 6 years of follow-up. Our findings support the inclusion of histological indices in both UC clinical trials and practice, towards a target of ‘complete remission’.
Serous cystic neoplasm of the pancreas: a multinational study of 2622 patients under the auspices of the International Association of Pancreatology and European Pancreatic Club (European Study Group on Cystic Tumors of the Pancreas)

Objectives Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. Design Retrospective multinational study including SCN diagnosed between 1990 and 2014. Results 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58 years (16–99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40 mm (2–200)), 9% had resection beyond 1 year of follow-up (3 years (1–20), size at diagnosis: 25 mm (4–140)) and 39% had no surgery (3.6 years (1–23), 25.5 mm (1–200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1 year (n=1271), size increased in 37% (growth rate: 4 mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). Conclusions After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. Trial registration number IRB 00006477.
Impact of sleep disordered breathing on short-term post-operative outcome after elective coronary artery bypass graft surgery: a prospective observational study

Sleep disordered breathing (SDB) is common in patients with coronary disease, but its impact on post-operative recovery after coronary artery bypass graft surgery (CABG) is unclear. We therefore determined the effects of SDB on post-operative outcome after elective CABG. In this prospective two-centre study, 219 patients due to receive elective CABG underwent cardiorespiratory polygraphy for SDB prior to surgery and were monitored for post-operative complications. The primary end-point was a composite of 30-day mortality or major post-operative complications (cardiac, respiratory, surgical, infectious, acute renal failure or stroke). Key secondary end-points were single components of the primary end-point. SDB was present in 69% and moderate/severe SDB in 43% of the CABG patients. There was no difference in the composite of 30-day mortality or major postoperative complications between patients with and without SDB (OR 0.97, 95% CI 0.49–1.96) and between patients with moderate/severe SDB and no/mild SDB (OR 1.07, 95% CI 0.55–2.06). However, moderate/severe SDB was associated with higher rates of mortality (crude OR 10.1, 95% CI 1.22–83.5), sepsis (OR 2.96, 95% CI 1.17–7.50) and respiratory complications (OR 2.85, 95% CI 1.46–5.55). Although SDB was not associated with higher overall morbidity/mortality, moderate/severe SDB may increase the risk of death, and septic and respiratory complications, after elective CABG. Sleep disordered breathing increases the rate of life-threatening post-operative complications after coronary surgery http://ow.ly/Ue25307U90Q
Health-Related Quality of Life in Bipolar Disorder Patients and Their Caregivers

Introduction: The health-care implications of quality of life (QOF) in longstanding disorders such as bipolar disorder (BD) for the patients and their caregivers is significant. Objectives: This study compares QOL among BD patients, their caregivers, and healthy controls and assesses whether the level of depression correlates with the scores of QOF in BD patients. Method: We compare BD patients (n = 40), their caregivers (n = 40), and healthy controls (n = 150) on health-related QOF (HRQOL) which was assessed using the 26-item World Health Organization QOL instrument (WHOQOL-BREF, Hindi version). All BD patients were diagnosed using the Structured Clinical Interview for DSM-IV. Within the BD group, we examine the relation between HRQOL using WHOQOL BREF Hindi version and depression assessed on 17-item Hamilton Depression Rating Scale (HDRS). Results: BD patients had lower QOL on all the four domains compared to healthy controls and their caregivers. The four domains of the WHOQOL scale correlated negatively with the HDRS. Conclusions: Our findings suggest that BD depression and residual symptoms of depression are negatively correlated with QOL in BD patients. The comprehensive treatment should target in improving the QOL of both BD patients and their caregivers.
Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response

Objective To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat-enriched diet. Design We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. Results Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis-aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. Conclusions We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis.
A randomised trial of endoscopic submucosal dissection versus endoscopic mucosal resection for early Barrett’s neoplasia

Background For endoscopic resection of early GI neoplasia, endoscopic submucosal dissection (ESD) achieves higher rates of complete resection (R0) than endoscopic mucosal resection (EMR). However, ESD is technically more difficult and evidence from randomised trial is missing. Objective We compared the efficacy and safety of ESD and EMR in patients with neoplastic Barrett's oesophagus (BO). Design BO patients with a focal lesion of high-grade intraepithelial neoplasia (HGIN) or early adenocarcinoma (EAC) ≤3 cm were randomised to either ESD or EMR. Primary outcome was R0 resection; secondary outcomes were complete remission from neoplasia, recurrences and adverse events (AEs). Results There were no significant differences in patient and lesion characteristics between the groups randomised to ESD (n=20) or EMR (n=20). Histology of the resected specimen showed HGIN or EAC in all but six cases. Although R0 resection defined as margins free of HGIN/EAC was achieved more frequently with ESD (10/17 vs 2/17, p=0.01), there was no difference in complete remission from neoplasia at 3 months (ESD 15/16 vs EMR 16/17, p=1.0). During a mean follow-up period of 23.1±6.4 months, recurrent EAC was observed in one case in the ESD group. Elective surgery was performed in four and three cases after ESD and EMR, respectively (p=1.0). Two severe AEs were recorded for ESD and none for EMR (p=0.49). Conclusions In terms of need for surgery, neoplasia remission and recurrence, ESD and EMR are both highly effective for endoscopic resection of early BO neoplasia. ESD achieves a higher R0 resection rate, but for most BO patients this bears little clinical relevance. ESD is, however, more time consuming and may cause severe AE. Trial registration number NCT1871636
Cardiometabolic correlates of sleep disordered breathing in Andean highlanders

Associations between sleep disordered breathing (SDB) and cardiometabolic outcomes have not been examined in highlanders. We performed nocturnal polygraphy in Peruvian highlanders (3825 m). Multivariable linear regression models examined associations between SDB metrics and haemoglobin, glucose tolerance (haemoglobin A1c (HbA1c)), fasting glucose, homeostatic model-based assessments of insulin resistance and β-cell function (HOMA-IR and HOMA-β, respectively), blood pressure, and lipids, while adjusting for age, sex, body mass index (BMI) and wake oxygenation. Participants (n=187; 91 men) were (median (interquartile range)) 52 (45–62) years old, and had a BMI of 27.0 (24.3–29.5) kg·m−2 and 87% (85–88%) oxyhaemoglobin (arterial oxygen) saturation during wakefulness. In fully adjusted models, worsening nocturnal hypoxaemia was associated with haemoglobin elevations in men (p=0.03), independent of wake oxygenation and apnoea–hypopnoea index (AHI), whereas worsening wake oxygenation was associated with haemoglobin elevations in older women (p=0.02). In contrast, AHI was independently associated with HbA1c elevations (p<0.05). In single-variable models, nocturnal hypoxaemia was associated with higher HbA1c, HOMA-IR and HOMA-β (p<0.001, p=0.02 and p=0.04, respectively), whereas AHI was associated with HOMA-IR, systolic blood pressure and triglyceride elevations (p=0.02, p=0.01 and p<0.01, respectively). These associations were not significant in fully adjusted models. In highlanders, nocturnal hypoxaemia and sleep apnoea were associated with distinct cardiometabolic outcomes, conferring differential risk for excessive erythrocytosis and glucose intolerance, respectively. In highlanders, nocturnal hypoxaemia and sleep apnoea were associated with differential outcomes http://ow.ly/1k6z309MyDR
Genetic and environmental influences on the relationship between mastery and alcohol dependence.

BACKGROUND Sense of mastery, a personal resource, is likely to have an inverse association with alcohol dependence. Previous evidence, however, is sparse. In addition, the extent to which an association is due to genetic or environmental factors is unknown. METHODS Data were from 3,983 male twins and 2,630 female twins who had ever used alcohol, interviewed in the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Mastery was measured by a 6-item scale. Lifetime diagnosis of alcohol dependence was based on DSM-IV criteria assessed in a structured diagnostic interview. Univariate analyses modeled the relative contributions of genetic and environmental factors to mastery and alcohol dependence using Mx software. Bivariate Cholesky models were fit to the mastery and alcohol dependence raw data. RESULTS In the best-fitting model of mastery, genetic factors accounted for about 33% of the observed variance. Nonshared environmental factors, including random measurement error, accounted for the remaining 67%. Fifty-six percent of the variance in liability to alcohol dependence was genetic, and the other 44% was explained by the nonshared environment. The phenotypic polychoric correlation between mastery and alcohol dependence of -0.18 was primarily (67% in the best-fitting model) explained by genes common to both low mastery and alcohol dependence; the rest was explained by nonshared environmental factors. CONCLUSIONS The findings indicate that genetic risk for alcohol dependence overlaps with genetic factors that influence sense of mastery. Key challenges for future research are to identify the genes that influence mastery and alcohol dependence, as well as the environmental pathways by which they come to be linked.
Docosahexaenoic acid causes rapid pulmonary arterial relaxation via KCa channel-mediated hyperpolarisation in pulmonary hypertension

Cardioprotective benefits of ω-3 fatty acids such as docosahexaenoic acid (DHA) are well established, but the regulatory effect of DHA on vascular tone and pressure in pulmonary hypertension is largely unknown. As DHA is a potent regulator of K+ channels, we hypothesised that DHA modulates the membrane potential of pulmonary artery smooth muscle cells (PASMCs) through K+ channels and thus exerts its effects on pulmonary vascular tone and pressure. We show that DHA caused dose-dependent activation of the calcium-activated K+ (KCa) current in primary human PASMCs and endothelium-dependent relaxation of pulmonary arteries. This vasodilation was significantly diminished in KCa–/– (Kcnma1–/–) mice. In vivo, acute DHA returned the right ventricular systolic pressure in the chronic hypoxia-induced pulmonary hypertension animal model to the level of normoxic animals. Interestingly, in idiopathic pulmonary arterial hypertension the KCa channels and their subunits were upregulated. DHA activated KCa channels in these human PASMCs and hyperpolarised the membrane potential of the idiopathic pulmonary arterial hypertension PASMCs to that of the PASMCs from healthy donors. Our findings indicate that DHA activates PASMC KCa channels leading to vasorelaxation in pulmonary hypertension. This effect might provide a molecular explanation for the previously undescribed role of DHA as an acute vasodilator in pulmonary hypertension. Increased KCa channels in remodelled pulmonary artery of IPAH might be a therapeutic opportunity for DHA http://ow.ly/rTUl300pn7R
Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome

Objective Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO2) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. Design Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO2 nanoparticles. The proinflammatory effects of TiO2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. Results Oral administration of TiO2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO2-administered mice. In vitro, TiO2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1β and IL-18. TiO2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. Conclusion These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2 nanoparticles.
Physiological and endocrine reactions to psychosocial stress in alcohol use disorders: duration of abstinence matters.

BACKGROUND Recent research findings suggest that heavy alcohol use is associated with alterations of the hypothalamic-pituitary-adrenal axis and autonomic nervous system function and that early abstinence is associated with blunted stress responsiveness. METHODS This study investigated abstinent alcohol-dependent participants (AADs; n = 31), who had a drinking history of levels about 97 drinks per week (abstinence range: 2 weeks to 24 months), actively drinking problem drinkers (PRDs; n = 23), who reported drinking levels about 47 drinks per week and who were abstinent for at least 24 hours, and healthy control (HC) participants (n = 20). It was investigated how participants responded to a psychosocial stress task. All of them were exposed to a modified Trier Social Stress Test. Salivary cortisol, heart rate, skin conductance levels, and negative affect were assessed as stress indicators. RESULTS AADs showed stress reactions comparable to HC participants, whereas active PRDs showed increased heart rate and cortisol stress responses. In the AAD group, duration of abstinence was positively related to cortisol stress responses. CONCLUSIONS Active PRDs showed increased responses to psychosocial stress. Results indicate that duration of abstinence is a key factor when analyzing and interpreting stress responses in alcohol abuse and dependence.
Fear of Personal Death among Physicians

Many studies have tried to explain why professionals experience difficulty when dealing with, and in treating efficiently, situations connected with death. We studied levels of fear of personal death among physicians and addressed two questions: Does exposure to death on professional and personal levels affect the level of fear of personal death which physicians experience? Is there a relationship between personality variables, represented by the repression-sensitization dimension, and level of fear of personal death? A sample of 233 physicians who specialized in oncology, internal medicine, surgery, psychiatry, and pediatrics was studied. Results revealed no differences in level of fear of personal death of physicians according to specialization, but those who had been exposed to death on the personal level feared less in relation to their own death. With respect to the personality variable, tendency to sensitization, it was found that those who were sensitized exhibited a higher level of fear of their own death compared to those who were repressive. Of the various demographic variables examined, it was found that those with many years of professional experience, who were relatively older, who were nonobservant religiously, and who were in good health had lower levels of personal fear of death.