Use of Multinational Registries to Assess and Compare Outcomes of Patients with an Acute Coronary Syndrome: A Dissertation

Background Acute coronary syndromes (ACS) are a major cause of mortality and morbidity in the developed world. By 2020, ACS will be the leading cause of morbidity and mortality worldwide, largely due to substantial increases in ACS burden in developing countries. The developing world has been under-represented in international ACS registries. The Arabian Gulf area is a part of the developing world where little is known about the epidemiology of ACS. The first aim of the dissertation is to compare ACS patient characteristics, current practice patterns, and in-hospital outcomes in the Arabian Gulf area to a large multinational sample. Patients with an ACS suffer numerous clinical complications that worsen their prognosis. Cardiogenic shock (CS) is the most serious complication of ACS and the leading cause of in-hospital death. Despite advances in therapies; CS hospital mortality rates continue to exceed 50%. The second aim of the dissertation is to describe the characteristics of patients presenting with ACS complicated by cardiogenic shock, their management, and outcomes in a large multinational sample. In recent years, ACS has been increasingly affecting younger patients. While marked age-related differences have been observed in the risk of developing as well as the prognosis of ACS, few studies however examined time trends in the epidemiology of ACS in young adult patients. The third aim of the dissertation is to examine trends in frequency rates, patient characteristics, treatment practices, and outcomes in young adults hospitalized with an ACS. Methods Data from two large multinational registries of patients hospitalized with an ACS were used for this investigation. Nearly 65,000 patients were enrolled in the Global Registry of Acute Coronary Events (GRACE) between 2000 and 2007, while 6,700 patients participated in the Gulf Registry of Acute Coronary Events (Gulf RACE) in 2007. Results Aim1: Patients in Gulf RACE were significantly younger and were more likely to be male, diabetic, and smoke Compared to GRACE. Patients in Gulf RACE were less likely to receive evidence based therapies. Short-term mortality rates were comparable between the two patient cohorts. Aim2: Compared to patients with no CS, patients with CS were more likely to be older, female, have a history of diabetes, and heart failure. Patients with CS were less likely to receive effective cardiac catheterization and adjunctive cardiac medications. In-hospital case-fatality rate of patients with CS were 59.4%. While in-hospital mortality declines over the study period, incidence rates only showed minor declines. Aim2: Baseline characteristics of patients \u3c 55 years of age did not significantly change, while the use of evidence based therapies increased significantly during the years under study. Rates of short-term adverse outcomes and mortality significantly declined over time. Conclusions We observed marked regional differences in the risk profile, clinical management, and outcomes of patients with an ACS internationally compared to the Arab Middle East. Despite the encouraging trends in the use of evidence based therapies which have likely contributed to the improving trends in the prognosis of ACS, rates of development of ACS, as well as mortality due to ACS complications, remain high

Dynamics and within-host interaction of Theileria lestoquardi and T. ovis among naive sheep in Oman

Mixed species infections of Theileria spp. are common in nature. Experimental and epidemiological data suggest that mixed species infections elicit cross-immunity that can modulate pathogenicity and disease burden at the population level. The present study examined within-host interactions, over a period of 13 months during natural infections with two Theileria spp., pathogenic (T. lestoquardi) and non-pathogenic (T. ovis), amongst a cohort of naive sheep in Oman. In the first two months after exposure to infection, a high rate of mortality was seen among sheep infected with T. lestoquardi alone. However, subsequently mixed-infections of T. lestoquardi and T. ovis prevailed, and no further death occurred. The overall densities of both parasite species were significantly higher as single infection vs mixed infection and the higher relative density of pathogenic T. lestoquardi indicated a competitive advantage over T. ovis in mixed infection. The density of both species fluctuated significantly over time, with no difference in density between the very hot (May to August) and warm season (September to April). A high degree of genotype multiplicity was seen among T. lestoquardi infections, which increased with rising parasite density. Our results illustrate a potential competitive interaction between the two ovine Theileria spp., and a substantial reduction in the risk of mortality in mixed parasite infections, indicating that T. ovis confers heterologous protection against lethal T. lestoquardi infection

In-hospital Depression Predicts Early Hospital Readmission after an Acute Coronary Syndrome: Preliminary Data from TRACE-CORE

Background: Hospital systems, patients and providers seek to avert rehospitalizations within 30 days for patients admitted with an acute coronary syndrome (ACS). Rehospitalizations within 30 days of discharge are often considered preventable and to reflect poor in-hospital management or discharge practices. However, independent associations of psychosocial factors with early rehospitalization in patients admitted with an ACS have not been examined. Methods: A multi-racial cohort of 1,540 patients admitted with an ACS reported psychosocial factors via standardized questionnaires in an in-hospital interview. One month following discharge, patients were interviewed via phone and reported hospital readmissions. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between in-hospital psychosocial characteristics (depression, anxiety, and perceived stress), health literacy and numeracy, and cognitive status, with self-reported readmission within 30 days. Results: Participants were 34% female and 17% non-white, with a mean age of 62 years and a mean length of stay of 4.1 days. Rehospitalization was reported for 14% (n=208) of participants, 77% of which were due to CVD. In univariate analyses, in-hospital severe depression, anxiety, and high stress were associated with higher odds of early readmission, whereas low health numeracy was associated with lower odds of early readmission. Severe depression remained associated with higher odds and low health numeracy remained associated with lower odds of early readmission in a multivariable model including covariates associated on univariate testing with rehospitalization. Conclusions: Early readmission after hospitalization for an ACS was common and associated with in-hospital depression and health numeracy. Notably, depression and health numeracy were the only predictors independently associated with readmission in multivariable analyses. We speculate that the lower likelihood of readmission for those with low numeracy may be related to less engagement with the healthcare system. In-hospital screening for depression and characterization of health numeracy may help stratify risk for early rehospitalization after an ACS

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Associations between Season and Gametocyte Dynamics in Chronic Plasmodium falciparum Infections

Introduction: In a markedly seasonal malaria setting, the transition from the transmission-free dry season to the transmission season depends on the resurgence of the mosquito population following the start of annual rains. The sudden onset of malaria outbreaks at the start of the transmission season suggests that parasites persist during the dry season and respond to either the reappearance of vectors, or correlated events, by increasing the production of transmission stages. Here, we investigate whether Plasmodium falciparum gametocyte density and the correlation between gametocyte density and parasite density show seasonal variation in chronic (largely asymptomatic) carriers in eastern Sudan. Materials and Methods: We recruited and treated 123 malaria patients in the transmission season 2001. We then followed them monthly during four distinct consecutive epidemiological seasons: transmission season 1, transmission-free season, pre-clinical period, and transmission season 2. In samples collected from 25 participants who fulfilled the selection criteria of the current analysis, we used quantitative PCR (qPCR) and RT-qPCR to quantify parasite and gametocyte densities, respectively. Results and Discussion: We observed a significant increase in gametocyte density and a significantly steeper positive correlation between gametocyte density and total parasite density during the pre-clinical period compared to the preceding transmission-free season. However, there was no corresponding increase in the density or prevalence of total parasites or gametocyte prevalence. The increase in gametocyte production during the pre-clinical period supports the hypothesis that P. falciparum may respond to environmental cues, such as mosquito biting, to modulate its transmission strategy. Thus, seasonal changes may be important to ignite transmission in unstable-malaria settings

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries