The dynamics and outcomes of AKI progression during the COVID-19 pandemic.

PURPOSE: Acute kidney injury (AKI) associated with COVID-19 is associated with poor prognosis. This study assessed the hitherto uninvestigated impact of COVID-19 on the progression and clinical outcomes of patients with AKI. METHODS: Data from 576 patients with AKI admitted between 13/3/20 and 13/5/20 were studied. Increasingly complex analyses, from logistic regressions to competing-risk and multi-state models, have revealed insights into AKI progression dynamics associated with PCR-confirmed COVID-19 acquisition and death. Meta-analyses of case fatality ratios among patients with AKI were also conducted. RESULTS: The overall case-fatality ratio was 0.33 [95% CI (0.20-0.36)]; higher in COVID-19 positive (COVID+) patients 0.52 [95% CI (0.46-0.58)] than in their negative (COVID-) counterparts 0.16 [95% CI (0.12-0.20)]. In AKI Stage-3 patients, that was 0.71 [95% CI (0.64-0.79)] among COVID+ patients with 45% dead within 14 days and 0.35 [95% CI (0.25-0.44)] in the COVID- group and 28% died within 14 days. Among patients diagnosed with AKI Stage-1 within 24 h, the probability of progression to AKI Stage-3 on day 7 post admission was 0.22 [95% CI (0.17-0.27)] among COVID+ patients, and 0.06 [95% CI (0.03, 0.09)] among those who tested negative. The probability of discharge by day 7 was 0.71 [95% CI (0.66, 0.75)] in COVID- patients, and 0.27 [95% CI (0.21, 0.32)] in COVID+ patients. By day 14, in AKI Stage-3 COVID+ patients, that was 0.35 [95% CI (0.25, 0.44)] with little change by day 10, that is, 0.38 [95% CI (0.29, 0.47)]. CONCLUSION: These results are consistent with either a rapid progression in severity, prolonged hospital care, or high case fatality ratio among AKI Stage-3 patients, significantly exacerbated by COVID-19 infection.

Ethnoracial disparities in childhood growth trajectories in Brazil: a longitudinal nationwide study of four million children.

BACKGROUND: The literature contains scarce data on inequalities in growth trajectories among children born to mothers of diverse ethnoracial background in the first 5 years of life. OBJECTIVE: We aimed to investigate child growth according to maternal ethnoracial group using a nationwide Brazilian database. METHODS: A population-based retrospective cohort study employed linked data from the CIDACS Birth Cohort and the Brazilian Food and Nutrition Surveillance System (SISVAN). Children born at term, aged 5 years or younger who presented two or more measurements of length/height (cm) and weight (kg) were followed up between 2008 and 2017. Prevalence of stunting, underweight, wasting, and thinness were estimated. Nonlinear mixed effect models were used to estimate childhood growth trajectories, among different maternal ethnoracial groups (White, Asian descent, Black, Pardo, and Indigenous), using the raw measures of weight (kg) and height (cm) and the length/height-for-age (L/HAZ) and weight-for-age z-scores (WAZ). The analyses were also adjusted for mother's age, educational level, and marital status. RESULTS: A total of 4,090,271 children were included in the study. Children of Indigenous mothers exhibited higher rates of stunting (26.74%) and underweight (5.90%). Wasting and thinness were more prevalent among children of Pardo, Asian, Black, and Indigenous mothers than those of White mothers. Regarding children's weight (kg) and length/height (cm), those of Indigenous, Pardo, Black, and Asian descent mothers were on average shorter and weighted less than White ones. Regarding WAZ and L/HAZ growth trajectories, a sharp decline in average z-scores was evidenced in the first weeks of life, followed by a period of recovery. Over time, z-scores for most of the subgroups analyzed trended below zero. Children of mother in greater social vulnerability showed less favorable growth. CONCLUSION: We observed racial disparities in nutritional status and childhood growth trajectories, with children of Indigenous mothers presenting less favorable outcomes compared to their White counterparts. The strengthening of policies aimed at protecting Indigenous children should be urgently undertaken to address systematic ethnoracial health inequalities.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Epidemiology of giardiasis and assemblages A and B and effects on diarrhea and growth trajectories during the first 8 years of life: Analysis of a birth cohort in a rural district in tropical Ecuador.

BACKGROUND: There are limited longitudinal data on the acquisition of Giardia lamblia infections in childhood using molecular assays to detect and type assemblages, and measure effects of infections on diarrhea risk and childhood growth. METHODS: We analysed stool samples from a surveillance sample within a birth cohort in a rural district in tropical Ecuador. The cohort was followed to 8 years of age for the presence of G. lamblia in stools by quantitative PCR and A and B assemblages by Taqman assay or Sanger sequencing. We explored risk factors associated with infection using generalized estimating equations applied to longitudinal binary outcomes, and longitudinal panel data analysis to estimate effects of infection on diarrhea and growth trajectories. RESULTS: 2,812 stool samples collected between 1 month and 8 years of age from 498 children were analyzed and showed high rates of infection: 79.7% were infected at least once with peak prevalence (53.9%) at 5 years. Assemblage B was accounted for 56.8% of genotyped infections. Risk factors for infection included male sex (P = 0.001), daycare attendance (P<0.001), having a household latrine (P = 0.04), childhood (P<0.001) and maternal soil-transmitted helminth (P = 0.029) infections, and exposures to donkeys (age interaction P = 0.034). G. lamblia was associated with increased risk of diarrhea (per episode, RR 1.03, 95% CI 1.01-1.06, P = 0.011) during the first 3 years of life and a transient impairment of weight (age interaction P = 0.017) and height-for-age (age interaction P = 0.025) trajectories between 1 and 4 years of age. There was no increased risk of either assemblage being associated with outcomes. CONCLUSION: Our data show a relatively high edemicity of G. lamblia transmission during childhood in coastal Ecuador, and evidence that infection is associated with a transiently increased risk of diarrhea during the first 3 years of life and impairment of weight and height between 1 and 4 years.

Comparison of high-intensity interval training versus moderate-intensity continuous training in pulmonary rehabilitation for interstitial lung disease: a randomised controlled pilot feasibility trial.

OBJECTIVES: This study aimed to investigate the feasibility and efficacy of high-intensity interval training (HIIT) compared with moderate-intensity continuous training (MICT) in pulmonary rehabilitation (PR) for people with interstitial lung disease (ILD). DESIGN: Single-centre, randomised controlled feasibility, pilot trial. SETTING: Patients were recruited from the chest clinic of a tertiary ILD centre and attended circuit-based PR in the hospital's gym, followed by a personalised 6-month community programme. PARTICIPANTS: 58 patients, stratified per ILD type, were randomised into two groups: 33 to HIIT (18 males:15 females) (mean age (SD): 70.2 (11.4) years) and 25 to the MICT exercise mode (14 males:11 females) (mean age (SD): 69.8 (10.8) years). INTERVENTIONS: 8-week, twice weekly, circuit-based PR programme of exercise and education, followed by a personalised 6-month community exercise programme. OUTCOME MEASURES: Feasibility outcomes included staff-to-patient ratio and dropout rates per group. Primary outcome was the 6 min walk distance (6MWD). Secondary outcomes included the sniff nasal pressure, mouth inspiratory and expiratory pressures, handgrip and quadriceps strength and health status. Random-effects models were used to evaluate average variation in outcomes through time across the two groups. RESULTS: The 6MWD peaked earlier with HIIT compared with MICT (at 4 months vs 5 months) but values were lower at peak (mean (95% CI): 26.3 m (3.5 to 49.1) vs 51.6 m (29.2 to 73.9)) and declined faster at 6 months post-PR. Secondary outcomes showed similar faster but smaller improvements with HIIT over MICT and more consistent maintenance 6 months post-PR with MICT than HIIT. CONCLUSIONS: HIIT is feasible in circuit-based ILD PR programmes and provides quick improvements but requires closer supervision of training and resources than MICT and benefits may be less well sustained. This would make it a less attractive option for clinical PR programmes. A definitive, multicentre randomised controlled trial is required to address the role of HIIT in ILD. TRIAL REGISTRATION NUMBER: ISRCTN55846300.

Prospective study of factors associated with asthma attack recurrence (ATTACK) in children from three Ecuadorian cities during COVID-19: a study protocol.

INTRODUCTION: Asthma is a growing health problem in children in marginalised urban settings in low-income and middle-income countries. Asthma attacks are an important cause of emergency care attendance and long-term morbidity. We designed a prospective study, the Asthma Attacks study, to identify factors associated with recurrence of asthma attacks (or exacerbations) among children and adolescents attending emergency care in three Ecuadorian cities. METHODS AND ANALYSIS: Prospective cohort study designed to identify risk factors associated with recurrence of asthma attacks in 450 children and adolescents aged 5-17 years attending emergency care in public hospitals in three Ecuadorian cities (Quito, Cuenca and Portoviejo). The primary outcome will be rate of asthma attack recurrence during up to 12 months of follow-up. Data are being collected at baseline and during follow-up by questionnaire: sociodemographic data, asthma history and management (baseline only); recurrence of asthma symptoms and attacks (monthly); economic costs of asthma to family; Asthma Control Test; Pediatric Asthma Quality of life Questionnaire; and Newcastle Asthma Knowledge Questionnaire (baseline only). In addition, the following are being measured at baseline and during follow-up: lung function and reversibility by spirometry before and after salbutamol; fractional exhaled nitric oxide (FeNO); and presence of IgG antibodies to SARS-CoV-2 in blood. Recruitment started in 2019 but because of severe disruption to emergency services caused by the COVID-19 pandemic, eligibility criteria were modified to include asthmatic children with uncontrolled symptoms and registered with collaborating hospitals. Data will be analysed using logistic regression and survival analyses. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Hospital General Docente de Calderon (CEISH-HGDC 2019-001) and Ecuadorian Ministry of Public Health (MSP-CGDES-2021-0041-O N° 096-2021). The study results will be disseminated through presentations at conferences and to key stakeholder groups including policy-makers, postgraduate theses, peer-review publications and a study website. Participants gave informed consent to participate in the study before taking part.

Evaluating the role of transthoracic echocardiography in hospitalised patients with COVID-19 infection.

OBJECTIVE: To identify the most common transthoracic echocardiogram (TTE) parameters in patients hospitalised with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19) and their association with myocardial injury and outcomes. METHODS: A retrospective, single-centre, observational, exploratory cohort study was performed at the height of the COVID-19 pandemic. All SARS-CoV-2 polymerase chain reaction (PCR) positive patients who underwent a TTE during their inpatient admission between 1 March 2020 and 31 October 2020 were analysed. The most frequent cardiovascular risk factor profile and echocardiographic features were investigated. RESULTS: A total of 87 patients met the eligibility criteria. A salient 41.4% (n=36) of our cohort succumbed to this devastating virus. More than half of our hospital population (58.6%) were admitted to the intensive care unit (ITU) and this was significantly associated with inpatient mortality (OR: 7.14, CI 2.53 to 20.19, p<0.001). Hypertension was the most common cardiovascular risk factor (51.7%) with no additional prominence in non-survivors (OR: 2.33, CI 0.97 to 5.61, p=0.059). Remarkably, 90.8% of our cohort demonstrated a preserved left ventricular ejection fraction, although 69.1% had elevated troponin levels. Only 1 patient (1.1%) was given a diagnostic label of myocarditis. A raised pulmonary artery systolic pressure (36.8%) andright ventricle (RV) dysfunction (26.4%) were the most common echocardiographic features. In particular, the presence of RV dysfunction was significantly related to adverse outcomes (OR: 2.97, CI 1.11 to 7.94, p<0.03). CONCLUSIONS: In this cohort of extremely unwell patients hospitalised with COVID-19 pneumonitis, the presence of RV dysfunction or admission to ITU was significantly associated with inpatient case fatality ratio. Moreover, COVID-19-induced myocarditis remains extremely rare.

Rare Variation in Drug Metabolism and Long QT Genes and the Genetic Susceptibility to Acquired Long QT Syndrome.

BACKGROUND: Acquired long QT syndrome (aLQTS) is a serious unpredictable adverse drug reaction. Pharmacogenomic markers may predict risk. METHODS: Among 153 aLQTS patients (mean age 58 years [range, 14-88], 98.7% White, 85.6% symptomatic), computational methods identified proteins interacting most significantly with 216 QT-prolonging drugs. All cases underwent sequencing of 31 candidate genes arising from this analysis or associating with congenital LQTS. Variants were filtered using a minor allele frequency <1% and classified for susceptibility for aLQTS. Gene-burden analyses were then performed comparing the primary cohort to control exomes (n=452) and an independent replication aLQTS exome sequencing cohort. RESULTS: In 25.5% of cases, at least one rare variant was identified: 22.2% of cases carried a rare variant in a gene associated with congenital LQTS, and in 4% of cases that variant was known to be pathogenic or likely pathogenic for congenital LQTS; 7.8% cases carried a cytochrome-P450 (CYP) gene variant. Of 12 identified CYP variants, 11 (92%) were in an enzyme known to metabolize at least one culprit drug to which the subject had been exposed. Drug-drug interactions that affected culprit drug metabolism were found in 19% of cases. More than one congenital LQTS variant, CYP gene variant, or drug interaction was present in 7.8% of cases. Gene-burden analyses of the primary cohort compared to control exomes (n=452), and an independent replication aLQTS exome sequencing cohort (n=67) and drug-tolerant controls (n=148) demonstrated an increased burden of rare (minor allele frequency<0.01) variants in CYP genes but not LQTS genes. CONCLUSIONS: Rare susceptibility variants in CYP genes are emerging as potentially important pharmacogenomic risk markers for aLQTS and could form part of personalized medicine approaches in the future.

The dynamics and determinants of specific systemic and mucosal antibody responses to SARS-CoV-2 in three adult cohorts in the Ecuadorian Andes: a study protocol.

Introduction: There are limited longitudinal data on the systemic and mucosal antibody responses to SARS-CoV-2 from Latin America, a region severely affected by COVID-19, and where vaccine strategies have been implemented during the evolving pandemic. Objective: To evaluate determinants of seroprevalence and changes in levels of anti-SARS-CoV-2 antibodies longitudinally in adults with different levels of exposure to SARS-CoV-2 (defined a priori as low, medium, and high based on presumed occupational risk), in two Andean cities in Ecuador. Methods: Longitudinal cohort study of 1,000 adults aged 18 years and older with questionnaire data and sample collection done at 0, 3, 6, and 12 months during the period 2020-2023. Observations collected included WHO-ISARIC questionnaire and peripheral blood and saliva samples for measurement of IgG and IgA antibodies, respectively. Planned analyses are tailored to the longitudinal nature of the outcomes defined by participants' antibody levels and aim at estimating their average trends with time since infection in each of the occupational groups, adjusted for demographics and calendar-time levels of SARS-CoV-2 infection in the general population. The latter reflect the impact of the national control measures such as vaccinations and movement restrictions. Importance: Understanding the duration and the dynamics of waning immunity to SARS-CoV-2, in the context of exposures to emerging virus variants and immunization, will inform the implementation of targeted public health strategies in the Latin American region. Ethics and Dissemination: This study will observe the bioethical principles of the Declaration of Helsinki. Informed written consent will be obtained. Samples from participants will be stored for up to three years after which they will be destroyed. The study protocol was approved by the Ecuadorian Ministry of Public Health Ethics Committee for COVID-19 Research. Antibody results will be provided to participants and participating institutions and to the national health authorities.

The epidemiology of soil-transmitted helminth infections in children up to 8 years of age: Findings from an Ecuadorian birth cohort.

BACKGROUND: There are few prospective longitudinal studies of soil-transmitted helminth (STH) infections during early childhood. We studied the epidemiology of and risk factors for soil-transmitted helminth infections from birth to 8 years of age in tropical Ecuador. METHODS: 2,404 newborns were followed to 8 years of age with periodic stool sample collections. Stool samples were collected also from household members at the time of the child's birth and examined by microscopy. Data on social, environmental, and demographic characteristics were collected by maternal questionnaire. Associations between potential risk factors and STH infections were estimated using generalized estimated equations applied to longitudinal binary outcomes for presence or absence of infections at collection times. RESULTS: Of 2,404 children, 1,120 (46.6%) were infected with at least one STH infection during the first 8 years of life. The risk of A. lumbricoides (16.2%) was greatest at 3 years, while risks of any STH (25.1%) and T. trichiura (16.5%) peaked at 5 years. Factors significantly associated with any STH infection in multivariable analyses included age, day-care (OR 1.34, 95% CI 1.03-1.73), maternal Afro-Ecuadorian ethnicity (non-Afro vs. Afro, OR 0.55, 95% CI 0.43-0.70) and lower educational level (secondary vs. illiterate, OR 0.31, 95% CI 0.22-0.45)), household overcrowding (OR 1.53, 95% CI 1.21-1.94)), having a latrine rather than a water closet (WC vs. latrine, OR 0.77, 95% CI 0.62-0.95)), and STH infections among household members (OR 2.03, 95% CI 1.59-2.58)). T. trichiura was more associated with poverty (high vs. low socioeconomic status, OR, 0.63, 95% CI 0.40-0.99)] and presence of infected siblings in the household (OR 3.42, 95% CI 2.24-5.22). CONCLUSION: STH infections, principally with A. lumbricoides and T. trichiura, peaked between 3 and 5 years in this cohort of children in tropical Ecuador. STH infections among household members were an important determinant of infection risk and could be targeted for control and elimination strategies.

Impact of COVID-19 pandemic on asthma symptoms and management: A prospective analysis of asthmatic children in Ecuador.

BACKGROUND: Asthma affects up to 33% of children in Latin American settings. The ongoing COVID-19 pandemic has had a significant impact on access to and use of health services. We aimed to evaluate the impact of the COVID-19 lockdown on asthma exacerbations, medical facility visits, and use of asthma medications in children. METHODS: We used data from a prospective cohort of 213 children aged 5-17 years in 3 Ecuadorian cities and analysed the impact of the COVID-19 lockdown on asthma. Outcomes (asthma exacerbations, emergency room [ER] visits, planned and unplanned outpatient visits, and use of inhaled corticosteroids and Beta-2 agonists) were analysed using repeated Poisson counts (ie, number of events per participant before and during the COVID-19 lockdown). RESULTS: During compared to before lockdown: a) the number of asthma exacerbations remained constant (IRR, 0.87; 95% CI: 0.72-1.05; p = 0.152); b) outpatient visits (IRR 0.26, 95% CI 0.14-0.47, p < 0.001) declined 74% while ER visits declined 89% (IRR 0.11, 95% CI 0.04-0.32, p < 0.001); and c) there was no change in inhaled corticosteroids use (IRR 1.03, 95% CI 0.90-1.16, P = 0.699) while Beta-2 agonist use increased (IRR 1.32, 95% CI 1.10-1.58, P = 0.003). CONCLUSIONS: In a cohort of Ecuadorian children with asthma, health services attendance decreased dramatically after COVID-19 lockdown, but asthma exacerbations and use of inhaled corticosteroids were unchanged. Future analyses will address the question of the effect of SARS-CoV-2 infection on asthma exacerbations and control in this paediatric population.

Impact of early life geohelminths on wheeze, asthma and atopy in Ecuadorian children at 8 years.

BACKGROUND: Early-life exposures to geohelminths may protect against development of wheeze/asthma and atopy. OBJECTIVE: To study the effect of maternal geohelminths and infections in children during the first 5 years on atopy, wheeze/asthma and airways reactivity/inflammation at 8 years. METHODS: Birth cohort of 2404 neonates followed to 8 years in rural Ecuador. Data on wheeze/asthma were collected by questionnaire and atopy by skin prick test (SPT) reactivity to 9 allergens. We measured airways reactivity to bronchodilator, fractional exhaled nitric oxide (FeNO) and nasal eosinophilia. Stool samples were examined for geohelminths by microscopy. RESULTS: 1933 (80.4%) children were evaluated at 8 years. Geohelminths were detected in 45.8% of mothers and 45.5% of children to 5 years. Frequencies of outcomes at 8 years were as follows: wheeze (6.6%), asthma between 5 and 8 years (7.9%), SPT (14.7%), airways reactivity (10%) and elevated FeNO (10.3%) and nasal eosinophilia (9.2%). Any maternal geohelminth was associated with reduced SPT prevalence (OR 0.72). Childhood Trichuris trichiura infections during the first 5 years were associated with reduced wheeze (OR 0.57) but greater parasite burdens with Ascaris lumbricoides at 5 years were associated with increased wheeze (OR 2.83) and asthma (OR 2.60). Associations between maternal geohelminths and wheeze/asthma were modified by atopy. Parasite-specific effects on wheeze/asthma and airways reactivity and inflammation were observed in non-atopic children. CONCLUSIONS: Our data provide novel evidence for persistent effects of in utero geohelminth exposures on childhood atopy but highlight the complex nature of the relationship between geohelminths and the airways. Registered as an observational study (ISRCTN41239086).

A prospective seroepidemiological study of toxocariasis during early childhood in coastal Ecuador: potential for congenital transmission and risk factors for infection.

BACKGROUND: Although Toxocara spp. infection has a worldwide distribution, to our knowledge, no data from birth cohorts have been reported in published studies on the potential for congenital transmission and determinants of infection in early childhood. METHODS: We followed 290 mother-infant pairs from birth to 5 years of age through periodic collection of data and samples at birth, 7 and 13 months and 2, 3 and 5 years of age. Data on potential risk factors and confounders were collected by maternal questionnaire. Blood for plasma was collected from the mother at time of birth and periodically from the child for detection of anti-Toxocara spp. immunoglobulin G (IgG) antibodies using a Toxocara canis larval excretory-secretory antigen-based enzyme-linked immunosorbent assay. Stool samples were collected from the mother around the time of birth and periodically from the child for microscopic detection of soil-transmitted helminths (STH). Associations between potential risk factors and Toxocara spp. seroprevalence and seroconversion were estimated using multivariable logistic regression and generalized estimating equations. RESULTS: Toxocara spp. seroprevalence was 80.7% in mothers and in children was 0%, 9.3%, 48.4%, 64.9%, and 80.9% at 7 months, 13 months, 2, 3 and 5 years, respectively. Risk factors significantly associated with increases in seroprevalence over the first 5 years of life in multivariable analyses were age [Odds ratio (OR) 2.06, 95% confidence interval (CI) 1.39-2.27, P < 0001], male sex (female vs. male: OR 0.66, 95% CI 0.48-0.89, P = 0.006), maternal ethnicity (non-Afro vs. Afro-Ecuadorian: OR 0.65, 95% CI 0.47-0.91, P = 0.011), lower maternal educational and socioeconomic level, and childhood STH (OR 2.29, 95% CI 1.51-3.47, P < 0.001). Seroconversion rates for infection were greatest at 2 years of age (3.8%/month). Factors associated significantly with seroconversion at 2, 3 or 5 years were childhood STH infection, male sex, and more frequent domestic cat exposure. CONCLUSIONS: Our data, from an area of high Toxocara spp. endemicity, indicate no congenital transmission but high rates of seroconversion after 13 months of age reaching maternal levels of seroprevalence by 5 years of age. Factors associated with seroprevalence and seroconversion included STH infections, domestic cats, maternal ethnicity, male sex, STH infections, and markers of greater poverty.

Age-dependent seroprevalence of dengue and chikungunya: inference from a cross-sectional analysis in Esmeraldas Province in coastal Ecuador.

OBJECTIVES: There are few population-based estimates for prevalence of past exposure to dengue and chikungunya viruses despite common epidemiological features. Here, we have developed a novel statistical method to study patterns of age-dependent prevalence of immunity in a population following exposures to two viruses which share similar epidemiological features including mode of transmission and induction of long-lasting immunity. This statistical technique accounted for sociodemographic characteristics associated with individuals and households. SETTINGS: The data consist of a representative sample from an ongoing longitudinal birth cohort set-up in a tropical district in coastal Ecuador (Esmeraldas). PARTICIPANTS: We collected data and blood samples from 319 individuals belonging to 152 households following epidemics of the infections in 2015 in Latin America. PRIMARY OUTCOME: Plasma was tested for the presence of specific IgG antibodies to dengue and chikungunya viruses by commercial ELISA and defined a bivariate binary outcome indicating individuals' past exposure status to dengue and chikungunya (ie, presence/absence of IgG antibodies to dengue or chikungunya or both). RESULTS: Dengue seroprevalence increased rapidly with age reaching 97% (95% credible interval (CrI): 93%-99%) by 60 years. Chikungunya seroprevalence peaked at 42% (95% CrI: 18%-66%) around 9 years of age and averaged 27% (95% CrI: 8.7%-51.6%) for all ages. Rural areas were more likely to be associated with dengue-only exposure while urban areas and shorter distance to the nearest household were associated with exposures to both. Women living in urban settings were more likely to be chikungunya seropositive while rural men were more likely to be dengue seropositive. CONCLUSION: Dengue seroprevalence was strongly age dependent consistent with endemic exposure while that of chikungunya peaked in childhood consistent with the recent emergence of the virus in the study area. Our findings will inform control strategies for the two arboviruses in Ecuador including recommendations by the WHO on dengue vaccination.

Cardiovascular Remodeling Experienced by Real-World, Unsupervised, Young Novice Marathon Runners.

AIMS: Marathon running is a popular ambition in modern societies inclusive of non-athletes. Previous studies have highlighted concerning transient myocardial dysfunction and biomarker release immediately after the race. Whether this method of increasing physical activity is beneficial or harmful remains a matter of debate. We examine in detail the real-world cardiovascular remodeling response following competition in a first marathon. METHODS: Sixty-eight novice marathon runners (36 men and 32 women) aged 30 ± 3 years were investigated 6 months before and 2 weeks after the 2016 London Marathon race in a prospective observational study. Evaluation included electrocardiography, cardiopulmonary exercise testing, echocardiography, and cardiovascular magnetic resonance imaging. RESULTS: After 17 weeks unsupervised marathon training, runners revealed a symmetrical, eccentric remodeling response with 3-5% increases in left and right ventricular cavity sizes, respectively. Blood pressure (BP) fell by 4/2 mmHg (P < 0.01) with reduction in arterial stiffness, despite only 11% demonstrating a clinically meaningful improvement in peak oxygen consumption with an overall non-significant 0.4 ml/min/kg increase in peak oxygen consumption (P = 0.14). CONCLUSION: In the absence of supervised training, exercise-induced cardiovascular remodeling in real-world novice marathon runners is more modest than previously described and occurs even without improvement in cardiorespiratory fitness. The responses are similar in men and women, who experience a beneficial BP reduction and no evidence of myocardial fibrosis or persistent edema, when achieving average finishing times.

The Characteristics, Dynamics, and the Risk of Death in COVID-19 Positive Dialysis Patients in London, UK.

Background: Patients on dialysis with frequent comorbidities, advanced age, and frailty, who visit treatment facilities frequently, are perhaps more prone to SARS-CoV-2 infection and related death-the risk factors and dynamics of which are unknown. The aim of this study was to investigate the hospital outcomes in patients on dialysis infected with SARS-CoV-2. Methods: Data on 224 patients on hemodialysis between February 29, 2020 and May 15, 2020 with confirmed SARS-CoV-2 were analyzed for outcomes and potential risk factors for death, using a competing risk-regression model assessed by subdistribution hazards ratio (SHR). Results: Crude data analyses suggest an overall case-fatality ratio of 23% (95% CI, 17% to 28%) overall, but that varies across age groups from 11% (95% CI, 0.9% to 9.2%) in patients ≤50 years old and 32% (95% CI, 17% to 48%) in patients >80 years; with 60% of deaths occurring in the first 15 days and 80% within 21 days, indicating a rapid deterioration toward death after admission. Almost 90% of surviving patients were discharged within 28 days. Death was more likely than hospital discharge in patients who were more frail (WHO performance status, 3-4; SHR, 2.16 [95% CI, 1.25 to 3.74]; P=0.006), had ischemic heart disease (SHR, 2.28 [95% CI, 1.32 to 3.94]; P=0.003), cerebrovascular disease (SHR, 2.11 [95% CI, 1.20 to 3.72]; P=0.01), smoking history (SHR, 2.69 [95% CI, 1.33 to 5.45]; P=0.006), patients who were hospitalized (SHR, 10.26 [95% CI, 3.10 to 33.94]; P<0.001), and patients with high CRP (SHR, 1.35 [95% CI, 1.10 to 1.67]) and a high neutrophil:lymphocyte ratio (SHR, 1.03 [95% CI, 1.01 to 1.04], P<0.001). Our data did not support differences in the risk of death associated with sex, ethnicity, dialysis vintage, or other comorbidities. However, comparison with the entire dialysis population attending these hospitals, in which 13% were affected, revealed that patients who were non-White (62% versus 52% in all patients, P=0.001) and those with diabetes (54% versus 22%, P<0.001) were disproportionately affected. Conclusions: This report discusses the outcomes of a large cohort of patients on dialysis. We found SARS-CoV-2 infection affected more patients with diabetes and those who were non-White, with a high case-fatality ratio, which increased significantly with age, frailty, smoking, increasing CRP, and neutrophil:lymphocyte ratio at presentation.

Synergy Pattern of Short Cationic Antimicrobial Peptides Against Multidrug-Resistant Pseudomonas aeruginosa.

With the rise of various multidrug-resistant (MDR) pathogenic bacteria, worldwide health care is under pressure to respond. Conventional antibiotics are failing and the development of novel classes and alternative strategies is a major priority. Antimicrobial peptides (AMPs) cannot only kill MDR bacteria, but also can be used synergistically with conventional antibiotics. We selected 30 short AMPs from different origins and measured their synergy in combination with polymyxin B, piperacillin, ceftazidime, cefepime, meropenem, imipenem, tetracycline, erythromycin, kanamycin, tobramycin, amikacin, gentamycin, and ciprofloxacin. In total, 403 unique combinations were tested against an MDR Pseudomonas aeruginosa isolate (PA910). As a measure of the synergistic effects, fractional inhibitory concentrations (FICs) were determined using microdilution assays with FICs ranges between 0.25 and 2. A high number of combinations between peptides and polymyxin B, erythromycin, and tetracycline were found to be synergistic. Novel variants of indolicidin also showed a high frequency in synergist interaction. Single amino acid substitutions within the peptides can have a very strong effect on the ability to synergize, making it possible to optimize future drugs toward synergistic interaction.

The Epidemiology of Community Clostridium difficile Infection: A Five-Year Population-Based Study on the Bailiwick of Jersey, Channel Islands.

We studied healthcare-associated and community-associated Clostridium difficile infection (CDI) in Jersey, Channel Islands (2008-2012). The Island's stable population has reliable denominator data, a clearly defined at-risk population, and healthcare contact that is easily followed. The vast majority of CDI cases had had recent healthcare contact, and true community-associated disease is extremely rare.Infect Control Hosp Epidemiol 2018;39:603-607.

Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis.

Background: Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance. Methods: This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information. Results: Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent. Conclusions: Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation.

Continuous Infusion of Low-Dose Iohexol Measures Changing Glomerular Filtration Rate in Critically Ill Patients.

OBJECTIVE: Measurement of changing glomerular filtration rate in acute kidney injury remains problematic. We have previously used a continuous infusion of low-dose Iohexol to measure glomerular filtration rate in stable subjects and postulate that changes greater than 10.3% in critically ill patients indicate acute kidney injury. Our objective is to explore the extent to which continuous infusion of low-dose Iohexol can be a measure of changing glomerular filtration rate during acute kidney injury. DESIGN: Clinical observational exploratory study. SETTING: Adult ICU. PATIENTS: Three patient groups were recruited: nephrectomy group: predictable onset of acute kidney injury and outcome (n = 10); surgery group: predictable onset of acute kidney injury, unpredictable outcome (n = 11); and acute kidney injury group: unpredictable onset of acute kidney injury and outcome (n = 13). INTERVENTIONS: Continuous infusion of low-dose Iohexol was administered for 24-80 hours. Plasma (ClP) and renal (ClR) Iohexol clearances were measured at timed intervals. MEASUREMENTS AND MAIN RESULTS: Kidney Disease: Improved Global Outcomes acute kidney injury criteria were fulfilled in 22 patients (nephrectomy = 5, surgery = 4, and acute kidney injury = 13); continuous infusion of low-dose Iohexol demonstrated acute kidney injury in 29 patients (nephrectomy = 10, surgery = 8, acute kidney injury = 11). Dynamic changes in glomerular filtration rate were tracked in all patients. In the nephrectomy group, ClR decreased by an expected 50% (50.8% ± 11.0%). Agreement between ClP and ClR improved with increasing duration of infusion: bias of ClP versus ClR at 48 hours was -0.1 ± 3.6 mL/min/1.73 m (limits of agreement: -7.2 to 7.1 mL/min/1.73 m). Coefficient of variation of laboratory sample analysis was 2.4%. CONCLUSIONS: Continuous infusion of low-dose Iohexol is accurate and precise when measuring glomerular filtration rate and tracks changes in patients with differing risks of acute kidney injury. Continuous infusion of low-dose Iohexol may provide a useful standard against which to test novel biomarkers for the diagnosis of acute kidney injury.