Economic factors influencing zoonotic disease dynamics: demand for poultry meat and seasonal transmission of avian influenza in Vietnam

While climate is often presented as a key factor influencing the seasonality of diseases, the importance of anthropogenic factors is less commonly evaluated. Using a combination of methods-wavelet analysis, economic analysis, statistical and disease transmission modelling-we aimed to explore the influence of climatic and economic factors on the seasonality of H5N1 Highly Pathogenic Avian Influenza in the domestic poultry population of Vietnam. We found that while climatic variables are associated with seasonal variation in the incidence of avian influenza outbreaks in the North of the country, this is not the case in the Centre and the South. In contrast, temporal patterns of H5N1 incidence are similar across these 3 regions: periods of high H5N1 incidence coincide with Lunar New Year festival, occurring in January-February, in the 3 climatic regions for 5 out of the 8 study years. Yet, daily poultry meat consumption drastically increases during Lunar New Year festival throughout the country. To meet this rise in demand, poultry production and trade are expected to peak around the festival period, promoting viral spread, which we demonstrated using a stochastic disease transmission model. This study illustrates the way in which economic factors may influence the dynamics of livestock pathogens

Risk factors associated with clinical malaria episodes in Bangladesh: A longitudinal study

Malaria is endemic to Bangladesh. In this longitudinal study, we used hydrologic, topographic, and socioeconomic risk factors to explain single and multiple malaria infections at individual and household levels. Malaria incidence was determined for 1,634 households in 54 villages in 2009 and 2010. During the entire study period 21.8% of households accounted for all (n = 497) malaria cases detected; 15.4% of households had 1 case and 6.4% had ≥2 cases. The greatest risk factors for malaria infection were low bed net ratio per household, house construction materials (wall), and high density of houses. Hydrologic and topographic factors were not significantly associated with malaria risk. This study identifies stable malaria hotspots and risk factors that should be considered for cost-effective targeting of malaria interventions that may contribute to potential elimination of malaria in Bangladesh. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene

Efficacy of tranexamic acid administration in traumatic brain injury patients: A review

BackgroundAnti-fibrinolytic medications decrease traumatic intracranial haemorrhage (ICH). Tranexamic acid (TXA) is an anti-fibrinolytic, which recently has shown effectiveness in management of traumatic haemorrhage‎.AimsTo summarize the randomized control trials (RCTs) that evaluate the efficacy of tranexamic acid administration in traumatic brain ‎injury (TBI) patients‎.‎Methods An electronic literature review, including PubMed, Google Scholar, and EBSCO that examining RCTs, observational, and experimental studies which study the efficacy of TXA administration in (TBI) patients.ResultsThe current review included 7 randomized studies reported the efficacy of TXA in management of TBI. TXA limit secondary brain injury by preventing the expansion of ICH. Administration of TXA exhibited a tendency to decrease head trauma-related mortality.ConclusionTXA significantly lower the risk of ICU expansion m and prevent brain injury related deaths

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Improving outcomes for patients with chronic kidney disease

There is clear evidence in the literature that the global burden of chronic kidney disease (CKD) is increasing. CKD patients are at high risk of cardiovascular morbidity and mortality which appeared to proportionally increase as kidney function deteriorates toward end-stage kidney disease (ESKD) requiring dialysis. Given the increasing prevalence, worsened outcomes associated with CKD as well as the financial cost associated with its management, there is a clear need for evidence-based interventions to lower the risk and improve outcomes in this high-risk population. This thesis aimed at improving outcomes in CKD patients. We have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) have renoprotective effects in type 2 diabetic patients and these effects appear more pronounced in patients with CKD. These results suggested GLP-1 RA may be attractive treatment options in patients with type 2 diabetes to slow CKD progression. In addition, our work provided important evidence demonstrating the important benefits of blood pressure lowering drugs in ESKD patients, as well as the comparative efficacy of different classes of blood pressure lowering agents in lowering cardiovascular events and mortality with clearer support for the use of aldosterone antagonists, β blockers and angiotensin receptor blockers to other classes in this patient population. This thesis also provided important insight regarding the safety of extended hours dialysis. Extended hours dialysis increased the risk of hypokalaemia and hypophosphatemia compared with standard dialysis. Awareness of such risk by patients and clinicians as well as close monitoring of potassium and phosphate may help lower this risk. The work presented in this thesis provided important evidence that may guide the management of patients with CKD, inform clinical practice guidelines globally and may potentially improve outcomes for this high-risk population

Depression screening via a smartphone app : cross-country user characteristics and feasibility

BACKGROUND AND OBJECTIVE: Smartphone applications (apps) have the potential to be valuable self-help interventions for depression screening. However, information about their feasibility and effectiveness and the characteristics of app users is limited. The aim of this study is to explore the uptake, utilization, and characteristics of voluntary users of an app for depression screening. METHODS: This was a cross-sectional study of a free depression screening smartphone app that contains the demographics, patient health questionnaire (PHQ-9), brief anxiety test, personalized recommendation based on the participant's results, and links to depression-relevant websites. The free app was released globally via Apple's App Store. Participants aged 18 and older downloaded the study app and were recruited passively between September 2012 and January 2013. FINDINGS: 8241 participants from 66 countries had downloaded the app, with a response rate of 73.9%. While one quarter of the participants had a previous diagnosis of depression, the prevalence of participants with a higher risk of depression was 82.5% and 66.8% at PHQ-9 cut-off 11 and cut-off 15, respectively. Many of the participants had one or more physical comorbid conditions and suicidal ideation. The cut-off 11 (OR: 1.4; 95% CI 1.2 to 1.6), previous depression diagnosis (OR: 1.3; 95% CI1.2 to 1.5), and postgraduate educational level (OR: 1.2; 95% CI 1.0 to 1.5) were associated with completing the PHQ-9 questionnaire more than once. CONCLUSIONS: Smartphone apps can be used to deliver a screening tool for depression across a large number of countries. Apps have the potential to play a significant role in disease screening, self-management, monitoring, and health education, particularly among younger adults.6 page(s