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RATIONALE: Pneumonia is the leading cause of death in children worldwide. Identifying and appropriately managing severe pneumonia in a timely manner improves outcomes. Little is known about the readiness of healthcare facilities to manage severe pediatric pneumonia in low-resource settings. OBJECTIVES: As part of the Household Air Pollution Intervention Network (HAPIN) trial, we sought to identify healthcare facilities that were adequately resourced to manage severe pediatric pneumonia in Jalapa, Guatemala (J-GUA); Puno, Peru (P-PER); Kayonza, Rwanda (K-RWA); and Tamil Nadu, India (T-IND). We conducted a facility-based survey of available infrastructure, staff, equipment, and medical consumables. Facilities were georeferenced and a road network analysis was performed. MEASUREMENTS AND MAIN RESULTS: Of the 350 healthcare facilities surveyed, 13% had adequate resources to manage severe pneumonia, 37% had pulse oximeters, and 44% had supplemental oxygen. Mean (±SD) travel time to an adequately-resourced facility was 41±19 minutes in J-GUA, 99±64 minutes in P-PER, 40±19 minutes in K-RWA, and 31±19 minutes in T-IND. Expanding pulse oximetry coverage to all facilities reduced travel time by 44% in J-GUA, 29% in P-PER, 29% in K-RWA, and 11% in T-IND (all p

Ultrasound Core Laboratories (UCL) are used in multicenter trials to assess imaging biomarkers to define robust phenotypes, to reduce imaging variability and to allow blinded independent review with the purpose of optimizing endpoint measurement precision. The Household Air Pollution Intervention Network, a multicountry randomized controlled trial (Guatemala, Peru, India and Rwanda), evaluates the effects of reducing household air pollution on health outcomes. Field studies using portable ultrasound evaluate fetal, lung and vascular imaging endpoints. The objective of this report is to describe administrative methods and training of a centralized clinical research UCL. A comprehensive administrative protocol and training curriculum included standard operating procedures, didactics, practical scanning and written/practical assessments of general ultrasound principles and specific imaging protocols. After initial online training, 18 sonographers (three or four per country and five from the UCL) participated in a 2 wk on-site training program. Written and practical testing evaluated ultrasound topic knowledge and scanning skills, and surveys evaluated the overall course. The UCL developed comprehensive standard operating procedures for image acquisition with a portable ultrasound system, digital image upload to cloud-based storage, off-line analysis and quality control. Pre- and post-training tests showed significant improvements (fetal ultrasound: 71% ± 13% vs. 93% ± 7%, p < 0.0001; vascular lung ultrasound: 60% ± 8% vs. 84% ± 10%, p < 0.0001). Qualitative and quantitative feedback showed high satisfaction with training (mean, 4.9 ± 0.1; scale: 1 = worst, 5 = best). The UCL oversees all stages: training, standardization, performance monitoring, image quality control and consistency of measurements. Sonographers who failed to meet minimum allowable performance were identified for retraining. In conclusion, a UCL was established to ensure accurate and reproducible ultrasound measurements in clinical research. Standardized operating procedures and training are aimed at reducing variability and enhancing measurement precision from study sites, representing a model for use of portable digital ultrasound for multicenter field studies.

ObjectiveThe clinical utility of point-of-care lung ultrasound (LUS) for disease severity triage of hospitalized patients with COVID-19 is unclear.DesignProspective cohort studySettingA large tertiary care center in Maryland, USA between April 2020 to September 2021.PatientsHospitalized adults (≥18 years of age) with positive SARS-CoV-2 RT-PCR results.InterventionsNone.Measurements and Main ResultsAll patients were scanned using a standardized protocol including 12 lung zones and followed to determine clinical outcomes until hospital discharge and vital status at 28-days. Ultrasounds were independently reviewed for lung and pleural line artifacts and abnormalities, and the mean Lung Ultrasound Score (ranging from 0 to 3) across lung zones (mLUSS) was determined. The primary outcome was time to ICU-level care, defined as high flow oxygen, noninvasive, or mechanical ventilation, within 28-days of the initial ultrasound. Cox proportional hazards regression models adjusted for age and sex were fit for mLUSS and each ultrasound covariate. A total of 264 participants were enrolled in the study; the median age was 59 years and 114 (43.2) % of participants were female. The median mLUSS was 1 (interquartile range: 0.5 to 1.3). Following enrollment, 29 (11.0%) participants went on to require ICU-level care and 14 (5.3%) subsequently died by 28 days. Each increase in mLUSS at enrollment was associated with disease progression to ICU-level care (aHR = 3.63; 95% CI: 1.23 to 10.65) and 28-day mortality (aHR = 4.50; 95% CI: 1.52 to 13.31). Pleural line abnormalities were independently associated with disease progression to ICU-level care (aHR = 18.86; CI: 1.57 to 226.09).ConclusionsParticipants with a mLUSS ≥1 or pleural line changes on LUS had an increased likelihood of subsequent requirement of high flow oxygen or greater. LUS is a promising tool for assessing risk of COVID-19 progression at the bedside.

Background Household air pollution adversely affects human health and the environment, yet more than 40% of the world still depends on solid cooking fuels. The House Air Pollution Intervention Network (HAPIN) randomized controlled trial is assessing the health effects of a liquefied petroleum gas (LPG) stove and 18-month supply of free fuel in 3,200 households in rural Guatemala, India, Peru, and Rwanda. Aims We conducted formative research in Guatemala to create visual messages that support the sustained, exclusive use of LPG in HAPIN intervention households. Method We conducted ethnographic research, including direct observation ( n = 36), in-depth ( n = 18), and semistructured ( n = 6) interviews, and 24 focus group discussions ( n = 96) to understand participants’ experience with LPG. Sixty participants were selected from a pilot study of LPG stove and 2-months of free fuel to assess the acceptability and use of LPG. Emergent themes were used to create visual messages based on observations and interviews in 40 households; messages were tested and revised in focus group discussions with 20 households. Results We identified 50 codes related to household air pollution and stoves; these were reduced into 24 themes relevant to LPG stoves, prioritizing 12 for calendars. Messages addressed fear and reluctance to use LPG; preference of wood stoves for cooking traditional foods; sustainability and accessibility of fuel; association between health outcomes and household air pollution; and the need for inspirational and aspirational messages. Discussion We created a flip chart and calendar illustrating themes to promote exclusive LPG use in HAPIN intervention households.

Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.

The Household Air Pollution Intervention Network trial is a multi-country study on the effects of a liquefied petroleum gas (LPG) stove and fuel distribution intervention on women's and children's health. There is limited data on exposure reductions achieved by switching from solid to clean cooking fuels in rural settings across multiple countries. As formative research in 2017, we recruited pregnant women and characterized the impact of the intervention on personal exposures and kitchen levels of fine particulate matter (PM2.5) in Guatemala, India, and Rwanda. Forty pregnant women were enrolled in each site. We measured cooking area concentrations of and personal exposures to PM2.5 for 24 or 48 h using gravimetric-based PM2.5 samplers at baseline and two follow-ups over two months after delivery of an LPG cookstove and free fuel supply. Mixed models were used to estimate PM2.5 reductions. Median kitchen PM2.5 concentrations were 296 μg/m3 at baseline (interquartile range, IQR: 158–507), 24 μg/m3 at first follow-up (IQR: 18–37), and 23 μg/m3 at second follow-up (IQR: 14–37). Median personal exposures to PM2.5 were 134 μg/m3 at baseline (IQR: 71–224), 35 μg/m3 at first follow-up (IQR: 23–51), and 32 μg/m3 at second follow-up (IQR: 23–47). Overall, the LPG intervention was associated with a 92% (95% confidence interval (CI): 90–94%) reduction in kitchen PM2.5 concentrations and a 74% (95% CI: 70–79%) reduction in personal PM2.5 exposures. Results were similar for each site. Conclusions The intervention was associated with substantial reductions in kitchen and personal PM2.5 overall and in all sites. Results suggest LPG interventions in these rural settings may lower exposures to the WHO annual interim target-1 of 35 μg/m3. The range of exposure contrasts falls on steep sections of estimated exposure-response curves for birthweight, blood pressure, and acute lower respiratory infections, implying potentially important health benefits when transitioning from solid fuels to LPG., Highlights • There was high uptake of an LPG stove and fuel intervention in 3 rural settings. • The LPG intervention was associated with a 92% reduction in kitchen PM2.5 levels. • The intervention was associated with a 74% reduction in personal exposure to PM2.5 • Maternal PM2.5 exposure was reduced to the WHO annual interim target-1 of 35 μg/m3. • Results from 3 countries indicate switching to clean fuel could improve health., Capsule summary: LPG stove and fuel intervention can reduce kitchen area and personal PM2.5 exposure levels in a pilot study of clean cookstove intervention trial. This strongly suggests switching to clean cook can improve health.

OBJECTIVES: To determine the association between mean airway pressure and 90-day mortality in patients with acute respiratory failure requiring mechanical ventilation and to compare the predictive ability of mean airway pressure compared with inspiratory plateau pressure and driving pressure. DESIGN: Prospective observational cohort. SETTING: Five ICUs in Lima, Peru. SUBJECTS: Adults requiring invasive mechanical ventilation via endotracheal tube for acute respiratory failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of potentially eligible participants (n = 1,500), 65 (4%) were missing baseline mean airway pressure, while 352 (23.5%) were missing baseline plateau pressure and driving pressure. Ultimately, 1,429 participants were included in the analysis with an average age of 59 ± 19 years, 45% female, and a mean Pao(2)/Fio(2) ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H(2)O (interquartile range, 10–16 cm H(2)O) in participants who died compared to a median mean airway pressure of 12 cm H(2)O (interquartile range, 10–14 cm H(2)O) in participants who survived greater than 90 days (p < 0.001). Mean airway pressure was independently associated with 90-day mortality (odds ratio, 1.38 for difference comparing the 75th to the 25th percentile for mean airway pressure; 95% CI, 1.10–1.74) after adjusting for age, sex, baseline Acute Physiology and Chronic Health Evaluation III, baseline Pao(2)/Fio(2) (modeled with restricted cubic spline), baseline positive end-expiratory pressure, baseline tidal volume, and hospital site. In predicting 90-day mortality, baseline mean airway pressure demonstrated similar discriminative ability (adjusted area under the curve = 0.69) and calibration characteristics as baseline plateau pressure and driving pressure. CONCLUSIONS: In a multicenter prospective cohort, baseline mean airway pressure was independently associated with 90-day mortality in mechanically ventilated participants and predicts mortality similarly to plateau pressure and driving pressure. Because mean airway pressure is readily available on all mechanically ventilated patients and all ventilator modes, it is a potentially more useful predictor of mortality in acute respiratory failure.

Summary Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

OBJECTIVES Weaning protocols establish readiness-to-wean criteria to determine the opportune moment to conduct a spontaneous breathing trial. Weaning protocols have not been widely adopted or evaluated in ICUs in low- and middle-income countries. We sought to compare clinical outcomes between participants whose weaning trials were retrospectively determined to have been premature, opportune, or delayed based on when they met readiness-to-wean criteria. DESIGN Prospective, multicenter observational study. SETTING Five medical ICUs in four public hospitals in Lima, Peru. SUBJECTS Adults with acute respiratory failure and at least 24 hours of invasive mechanical ventilation (n = 1,657). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We established six readiness-to-wean criteria and retrospectively categorized our sample into three weaning groups: 1) premature: if the weaning trial took place before fulfilling all criteria, 2) opportune: if the weaning trial took place within 24 hours after fulfilling the criteria, and 3) delayed: if the weaning trial took place over 24 hours after fulfilling criteria. We compared 90-day mortality, ventilator-free days, ICU-free days, and hospital-free days between premature, opportune, and delayed weaning groups. In our sample, 761 participants (60.8%) were classified as having a premature weaning trial, 196 underwent opportune weaning (15.7%), and 295 experienced delayed weaning (23.6%). There was no significant difference in 90-day mortality between the groups. Both the premature and delayed weaning groups had poorer clinical outcomes with fewer ventilator-free days (-2.18, p = 0.008) and (-3.49, p < 0.001), ICU-free days (-2.25, p = 0.001) and (-3.72, p < 0.001), and hospital-free days (-2.76, p = 0.044) and (-4.53, p = 0.004), respectively, compared with the opportune weaning group. CONCLUSIONS Better clinical outcomes occur with opportune weaning compared with premature and delayed weaning. If readiness-to-wean criteria can be applied in resource-limited settings, it may improve ICU outcomes associated with opportune weaning.

Objectives We sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting. Design A longitudinal study of critically ill participants on mechanical ventilation. Setting Five intensive care units (ICUs) in four public hospitals in Lima, Peru. Patients One thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90. Results After excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23–6.95; p

Table S1. Dose Equivalency of Benzodiazepines Relative to Midazolam and Opioids relative to Fentanyl. Table S2. Ramsay Sedation and Glasgow Coma Scales conversion to the Richmond Agitation-Sedation Scale. Table S3. Sedation Status corresponding to Richmond Agitation-Sedation score. Table S4. Sedation Status and Use of Sedatives, Antipsychotics and Neuromuscular Blockers. Table S5. Sedation Status and Secondary Outcomes. Figure S1. Cumulative Incidence Plots Evaluating Sedation Status and Vital Status during ICU Stay stratified by ARDS Status at Enrollment. We plot the cumulative incidence of death (broken red line), unassisted breathing (broken blue line), and sedation status (shaded areas) among those who are receiving assisting breathing, stratified by whether participants have ARDS on admission (panel A) or no ARDS (panel B). The shaded areas were proportional to the percentage of participants who were deeply (dark blue), moderately (blue) or adequately sedated (light blue), and agitated (pink). Based on the Richmond Agitation Sedation Scale score or its conversion Figure S2. Cumulative Incidence Plots Evaluating Sedation Status and Vital Status during ICU Stay Stratified by APACHE III Score at Enrollment. We plot the cumulative incidence of death (broken red line), unassisted breathing (broken blue line), and sedation status (shaded areas) among those who are receiving assisting breathing, stratified by APACHE III score (panel A: 0–69, panel B: 70–96, panel C: 97–179). Shaded areas and categorization of sedation same as in Figure S1. Figure S3. Cumulative Incidence Plots Evaluating Sedation Status and Vital Status during ICU Stay Stratified by Admission Type. We plot the cumulative incidence of death (broken red line), unassisted breathing (blue line), and sedation status (shaded areas) among those who are receiving assisting breathing, stratified by whether admission was medical (panel A) or surgical (panel B). Shaded areas and categorization of sedation same as in Figure S1. (PDF 1953 kb)

Objective: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Design: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. Patients: A total of 6,179 critically ill patients. Setting: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Interventions: None. Measurements and Main Results: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15–21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Conclusions: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

OBJECTIVES: To estimate the effect of sex-related alcohol expectancies (SRAE) on hazardous drinking prevalence and examine gender differences in reporting SRAE. METHODS: Trained research assistants administered part of a questionnaire to 393 men and 400 women between 18 and 30 years old from a peri-urban shantytown in Lima, Peru. The remaining questions were self-administered. Two measuring instruments-one testing for hazardous drinking and one for SRAE-were used. Multivariate data analysis was performed using logistic regression. RESULTS: Based on odds ratios adjusted for socio-demographic variables (age, marital status, education, and employment status) (n = 793), men with one or two SRAE and men with three or more SRAE were 2.3 (95 percent confidence interval (CI) = 1.4-3.8; p = 0.001) and 3.9 (95 percent CI = 2.1-7.3; p 0.001) times more likely than men with no SRAE, respectively, to be hazardous drinkers. Reporting of SRAE was significantly higher in men versus women. CONCLUSION: In a shantytown in Lima, SRAE is associated with hazardous drinking among men, but not among women, and reporting of SRAE differs by gender.(AU)

The efficiency of transmission of a pathogen within families compared with that between unrelated persons can affect both the strategies needed to control or eradicate infection and how the pathogen evolves. In industrialized countries, most cases of transmission of the gastric pathogen Helicobacter pylori seems to be from mother to child. An alternative model, potentially applicable among the very poor in developing countries, where infection is more common and the sanitary infrastructure is often deficient, invokes frequent transmission among unrelated persons, often via environmental sources. In the present study, we compared the genotypes of H. pylori from members of shantytown households in Peru to better understand the transmission of H. pylori in developing-country settings. H. pylori cultures and/or DNAs were obtained with informed consent by the string test (a minimally invasive alternative to endoscopy) from at least one child and one parent from each of 62 families. The random amplified polymorphic DNA fingerprints of 57 of 81 (70%) child-mother strain pairs did not match, nor did the diagnostic gene sequences (>1% DNA sequence difference), independent of the child's age (range, 1 to 39 years). Most strains from siblings or other paired family members were also unrelated. These results suggest that H. pylori infections are often community acquired in the society studied. Transmission between unrelated persons should facilitate the formation of novel recombinant genotypes by interstrain DNA transfer and selection for genotypes that are well suited for individual hosts. It also implies that the effective prevention of H. pylori infection and associated gastroduodenal disease will require anti- H. pylori measures to be applied communitywide.

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Peru over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Peru from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Peru, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.

Alcohol use is frequently identified as a contributor to risky sexual behaviors; however research results are mixed. Given the conflicting evidence researchers have focused on other factors such as expectations about alcohols effects that might help explain the relationship of alcohol use and risky sexual behaviors. Cross-sectional data from 312 sexually experienced males aged 18-30 in a shantytown in Lima Peru were used in logistic regression models to identify associations of heavy episodic drinking and sex-related expectations about alcohol with sexual risk behaviors. Heavy episodic drinking was associated with having had two or more sexual partners and having had sex with a casual partner in the past year (odds ratio 2.8 and 2.5 respectively). After controlling for alcohol consumption sex-related expectations about alcohol were associated with these high-risk sexual behaviors as well as with not using a condom at last sex (1.2) and not using a condom at last sex with a casual partner(1.3). Beliefs about the effect of alcohol on sexual performance could help explain links between alcohol consumption and risky sexual behavior not completely accounted for by the pharmacological effects of alcohol. (authors)

Background. Gastric adenocarcinoma is associated with chronic infection by Helicobacter pylori and with the host inflammatory response triggered by it, with substantial inter-person variation in the immune response profile due to host genetic factors. Aim. To investigate the diversity of the proinflammatory genes IL8, its receptors and PTGS2 in Amerindians; to test whether candidate SNPs in these genes are associated with gastric cancer in an admixed population with high Amerindian ancestry from Lima, Peru; and to assess whether an IL8RB promoter-derived haplotype affects gene expression. Methods. We performed a Sanger-resequencing population survey, a candidate-gene association study (220 cases, 288 controls) and meta-analyses. We also performed an in vitro validation by a reporter gene assay of IL8RB promoter. Results. The diversity of the promoter of studied genes in Native Americans is similar to Europeans. Although an association between candidate SNPs and gastric cancer was not found in Peruvians, trend in our data is consistent with meta-analyses results that suggest PTGS2-rs689466-A is associated with H. pylori-associated gastric cancer in East Asia. IL8RB promoter-derived haplotype (rs3890158-A/rs4674258-T), common in Peruvians, was up-regulated by TNF-α unlike the ancestral haplotype (rs3890158-G/rs4674258-C). Bioinformatics analysis suggests that this effect stemmed from creation of a binding site for the FOXO3 transcription factor by rs3890158G>A. Conclusions. Our updated meta-analysis reinforces the role of PTGS2-rs689466-A in gastric cancer in Asians, although more studies that control for ancestry are necessary to clarify its role in Latin Americans. Finally, we suggest that IL8RB-rs3890158G>A is a cis-regulatory SNP.

Indoor smoke exposure may affect cardiovascular disease (CVD) risk via lung-mediated inflammation, oxidative stress, and endothelial inflammation. We sought to explore the association between indoor smoke exposure from burning biomass fuels and a selected group of markers for endothelial inflammation. We compared serum concentrations of amyloid A protein, E-selectin, soluble intercellular adhesion molecule 1 (ICAM-1) and VCAM-1, von Willebrand factor (vWF), and high-sensitivity C-reactive protein (hs-CRP) in 228 biomass-exposed vs. 228 non-exposed participants living in Puno, Peru. Average age was 56 years (s.d. = 13), average BMI was 26.5 kg/m(2) (s.d. = 4.4), 48% were male, 59.4% completed high school, and 2% reported a physician diagnosis of CVD. In unadjusted analysis, serum levels of soluble ICAM-1 (330 vs. 302 ng/ml; P < 0.001), soluble VCAM-1 (403 vs. 362 ng/ml; P < 0.001), and E-selectin (54.2 vs. 52.7 ng/ml; P = 0.05) were increased in biomass-exposed vs. non-exposed participants, respectively, whereas serum levels of vWF (1148 vs. 1311 mU/ml; P < 0.001) and hs-CRP (2.56 vs. 3.12 mg/l; P < 0.001) were decreased, respectively. In adjusted analyses, chronic exposure to biomass fuels remained positively associated with serum levels of soluble ICAM-1 (P = 0.03) and VCAM-1 (P = 0.05) and E-selectin (P = 0.05), and remained negatively associated with serum levels of vWF (P = 0.02) and hs-CRP (P < 0.001). Daily exposure to biomass fuel smoke was associated with important differences in specific biomarkers of endothelial inflammation and may help explain accelerated atherosclerosis among those who are chronically exposed.

The method of recovering Helicobacter pylori DNA or viable cells absorbed on a string that a person has swallowed and that is retrieved an hour later (string test) should be a useful alternative to traditional analysis of cells or DNA obtained by endoscopy, which is invasive, uncomfortable, relatively costly, and ill-suited for community-based and pediatric studies. Here we assayed the sensitivity and validity of the string test versus conventional endoscopic biopsy for detecting and analyzing H. pylori infection. Forty-four people with gastric complaints were studied using both H. pylori culture and urease gene ( ureB ) PCR. H. pylori organisms cultured from strings and biopsy specimens from the same patients were fingerprinted by the randomly amplified polymorphic DNA (RAPD) method. Biopsy sections were also hematoxylin and eosin and silver stained for H. pylori detection. H. pylori was cultured from 80% of strings and detected by PCR from 91% of strings from participants whose biopsies had been H. pylori positive by culture, PCR, and/or histology. Strains recovered from strings and biopsy specimens yielded identical or closely related RAPD profiles in each of the 24 cases tested. We conclude that the string test is a useful method for H. pylori recovery and analysis when relatively noninvasive procedures are needed.

Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (

Admixture occurs when individuals from parental populations that have been isolated for hundreds of generations form a new hybrid population. Currently, interest in measuring biogeographic ancestry has spread from anthropology to forensic sciences, direct-to-consumers personal genomics, and civil rights issues of minorities, and it is critical for genetic epidemiology studies of admixed populations. Markers with highly differentiated frequencies among human populations are informative of ancestry and are called ancestry informative markers (AIMs). For tri-hybrid Latin American populations, ancestry information is required for Africans, Europeans and Native Americans. We developed two multiplex panels of AIMs (for 14 SNPs) to be genotyped by two mini-sequencing reactions, suitable for investigators of medium-small laboratories to estimate admixture of Latin American populations. We tested the performance of these AIMs by comparing results obtained with our 14 AIMs with those obtained using 108 AIMs genotyped in the same individuals, for which DNA samples is available for other investigators. We emphasize that this type of comparison should be made when new admixture/population structure panels are developed. At the population level, our 14 AIMs were useful to estimate European admixture, though they overestimated African admixture and underestimated Native American admixture. Combined with more AIMs, our panel could be used to infer individual admixture. We used our panel to infer the pattern of admixture in two urban populations (Montes Claros and Manhuacu) of the State of Minas Gerais (southeastern Brazil), obtaining a snapshot of their genetic structure in the context of their demographic history.

Information on one Ecuadorian and three Peruvian Amerindian populations for 11 autosomal short tandem repeat (STR) loci is presented and incorporated in analyses that includes 26 other Native groups spread all over South America. Although in comparison with other studies we used a reduced number of markers, the number of populations included in our analyses is currently unmatched by any genome-wide dataset. The genetic polymorphisms indicate a clear division of the populations into three broad geographical areas: Andes, Amazonia, and the Southeast, which includes the Chaco and southern Brazil. The data also show good agreement with proposed hypotheses of splitting and dispersion of major language groups over the last 3,000 years. Therefore, relevant aspects ofNative American history can be traced using as few as 11 STR autosomal markers coupled with a broad geographic distribution of sampled populations. Am J Phys Anthropol, 2011. © 2011 Wiley-Liss, Inc.

BACKGROUND: The gastric pathogen Helicobacter pylori is extraordinary in its genetic diversity, the differences between strains from well-separated human populations, and the range of diseases that infection promotes. PRINCIPAL FINDINGS: Housekeeping gene sequences from H. pylori from residents of an Amerindian village in the Peruvian Amazon, Shimaa, were related to, but not intermingled with, those from Asia. This suggests descent of Shimaa strains from H. pylori that had infected the people who migrated from Asia into The Americas some 15,000+ years ago. In contrast, European type sequences predominated in strains from Amerindian Lima shantytown residents, but with some 12% Amerindian or East Asian-like admixture, which indicates displacement of ancestral purely Amerindian strains by those of hybrid or European ancestry. The genome of one Shimaa village strain, Shi470, was sequenced completely. Its SNP pattern was more Asian- than European-like genome-wide, indicating a purely Amerind ancestry. Among its unusual features were two cagA virulence genes, each distinct from those known from elsewhere; and a novel allele of gene hp0519, whose encoded protein is postulated to interact with host tissue. More generally, however, the Shi470 genome is similar in gene content and organization to those of strains from industrialized countries. CONCLUSIONS: Our data indicate that Shimaa village H. pylori descend from Asian strains brought to The Americas many millennia ago; and that Amerind strains are less fit than, and were substantially displaced by, hybrid or European strains in less isolated communities. Genome comparisons of H. pylori from Amerindian and other communities should help elucidate evolutionary forces that have shaped pathogen populations in The Americas and worldwide.

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.

Background Risky sexual behaviors of young adults have received increasing attention during the last decades. However, few studies have focused on the sexual behavior of young adults in shantytowns of Latin America. Specifically, studies on the association between sexual behaviors and other risk factors for sexually transmitted infections (STI) and HIV/AIDS transmission, such as the consumption of illicit drugs or alcohol are scarce in this specific context. Methods The study participants were 393 men and 400 women between 18 and 30 years of age, from a shantytown in Lima, Peru. Data were obtained via survey: one section applied by a trained research assistant, and a self-reporting section. Logistic regression was used to estimate associations between use of any illicit drug, high-risk sexual behaviors and reported STI symptoms, adjusting for alcohol consumption level and various socio-demographic characteristics. Results Among men, age of sexual debut was lower, number of lifetime sexual partners was higher, and there were higher risk types of sexual partners, compared to women. Though consistent condom use with casual partners was low in both groups, reported condom use at last intercourse was higher among men than women. Also, a lifetime history of illicit drug consumption decreased the probability of condom use at last sexual intercourse by half. Among men, the use of illicit drugs doubled the probability of intercourse with a casual partner during the last year and tripled the probability of reported STI symptoms. Conclusion Drug consumption is associated with high-risk sexual behaviors and reported STI symptoms in a Lima shantytown after controlling for alcohol consumption level. Development of prevention programs for risky sexual behaviors, considering gender differences, is discussed.

Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p0.001), from 12 to 0.5% (p0.001), and from 6.5 to 0.1% (p0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p0.001), from 28.4 to 5% (p0.001), and from 19.4 to 2.2% (p0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.

Alcohol use is frequently identified as a contributor to risky sexual behaviors; however, research results are mixed. Given the conflicting evidence, researchers have focused on other factors, such as expectations about alcohol's effects that might help explain the relationship of alcohol use and risky sexual behaviors.Cross-sectional data from 312 sexually experienced males aged 18-30 in a shantytown in Lima, Peru, were used in logistic regression models to identify associations of heavy episodic drinking and sex-related expectations about alcohol with sexual risk behaviors.Heavy episodic drinking was associated with having had two or more sexual partners and having had sex with a casual partner in the past year (odds ratios, 2.8 and 2.5, respectively). After controlling for alcohol consumption, sex-related expectations about alcohol were associated with these high-risk sexual behaviors, as well as with not using a condom at last sex (1.2) and not using a condom at last sex with a casual partner (1.3).Beliefs about the effect of alcohol on sexual performance could help explain links between alcohol consumption and risky sexual behavior not completely accounted for by the pharmacological effects of alcohol.

Introduction Mechanical ventilation is a cornerstone in the management of critically ill patients worldwide; however, less is known about the clinical management of mechanically ventilated patients in low and middle income countries where limitation of resources including equipment, staff and access to medical information may play an important role in defining patient-centred outcomes. We present the design of a prospective, longitudinal study of mechanically ventilated patients in Peru that aims to describe a large cohort of mechanically ventilated patients and identify practices that, if modified, could result in improved patient-centred outcomes and lower costs. Methods and analysis Five Peruvian intensive care units (ICUs) and the Medical ICU at the Johns Hopkins Hospital were selected for this study. Eligible patients were those who underwent at least 24 h of invasive mechanical ventilation within the first 48 h of admission into the ICU. Information on ventilator settings, clinical management and treatment were collected daily for up to 28 days or until the patient was discharged from the unit. Vital status was assessed at 90 days post enrolment. A subset of participants who survived until hospital discharge were asked to participate in an ancillary study to assess vital status, and physical and mental health at 6, 12, 24 and 60 months after hospitalisation, Primary outcomes include 90-day mortality, time on mechanical ventilation, hospital and ICU lengths of stay, and prevalence of acute respiratory distress syndrome. In subsequent analyses, we aim to identify interventions and standardised care strategies that can be tailored to resource-limited settings and that result in improved patient-centred outcomes and lower costs. Ethics and dissemination We obtained ethics approval from each of the four participating hospitals in Lima, Peru, and at the Johns Hopkins School of Medicine, Baltimore, USA. Results will be disseminated as several separate publications in different international journals.

We compared the robustness and discriminatory power of the enterobacterial repetitive intergenic consensus (ERIC) and random amplified polymorphic DNA (RAPD) fingerprinting methods for detecting cases of mixed Helicobacter pylori infection in Peruvian shantytown residents. H. pylori isolates from 63 participants were cultured, and five single colonies and a pool of additional colonies from each participant were analyzed by ERIC-PCR and by RAPD tests with four 10-nucleotide primers (one primer per reaction). There was 94% agreement between the ERIC and RAPD profiles in classifying sets of isolates as uniform versus closely related but not identical versus probably unrelated, indicating a high kappa statistic of 0.8942. Subtle differences in related ERIC or RAPD patterns likely reflect gene transfer between strains, recombination, and/or mutation, whereas markedly different patterns reflect infection by unrelated strains. At least half of infected shantytown residents seemed to carry more than one H. pylori strain, although in 19 of 31 persons, the strains were closely related. Three RAPD tests, each with a different primer, were needed to achieve the sensitivity of one ERIC test. ERIC-PCR constitutes a resource- and time-efficient method for H. pylori strain differentiation.

Additional file 1: Table S1. Baseline Characteristics, ventilatory parameters and outcomes in participants with early ARDS (

Additional file 1: Table S1. Baseline Characteristics, ventilatory parameters and outcomes in participants with early ARDS (