Mean Airway Pressure As a Predictor of 90-Day Mortality in Mechanically Ventilated Patients.

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 PaO2/FIO2 ratio of 248 ± 147 mm Hg at baseline. Overall, 90-day mortality was 50.4%. Median baseline mean airway pressure was 13 cm H2O (interquartile range, 10-16 cm H2O) in participants who died compared to a median mean airway pressure of 12 cm H2O (interquartile range, 10-14 cm H2O) 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 PaO2/FIO2 (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.

Lack of association between chronic exposure to biomass fuel smoke and markers of right ventricular pressure overload at high altitude.

BACKGROUND: Chronic exposure to biomass fuel smoke has been implicated in the development of pulmonary hypertension and right ventricular pressure/volume overload through activation of inflammation, increase in vascular resistance, and endothelial dysfunction. We sought to compare N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and echocardiography-derived pulmonary artery systolic pressure (PASP) levels in a high-altitude population-based study in Peru with and without chronic exposure to biomass fuel smoke. METHODS: NT-pro-BNP levels were measured in 519 adults (275 with and 244 without chronic exposure to biomass fuel smoke). Participants answered sociodemographics and clinical history questionnaires, underwent a clinical examination and blood testing for cardiopulmonary biomarkers. PASP was measured in a subgroup of 153 (31%) subjects. RESULTS: The study group consisted of 280 men (54%) and 239 women (46%). Average age was 56 years and average body mass index was 27 kg/m(2). In multivariable analysis, there was no association between chronic exposure to biomass fuel smoke and NT-pro-BNP (P = .31) or PASP (P = .31). In the subgroup in which both NT-pro-BNP levels and PASP were measured, there was strong evidence of an association between these two variables (ρ = 0.24, 95% CI 0.09-0.39; P = .003). We found that age, high sensitivity C-reactive protein, being male, and systolic blood pressure were positively associated with NT-pro-BNP levels whereas body mass index, low-density/high-density lipoprotein ratio, and Homeostasis Model of Assessment-Insulin Resistance were negatively associated (all P ≤ .02). CONCLUSIONS: In this population-based study in a high-altitude setting, neither NT-pro-BNP levels nor echocardiography-derived PASP were associated with chronic exposure to biomass fuel smoke.

An Update on the Pathogenesis of Fascioliasis: What Do We Know?

Fasciola hepatica is a trematode parasite distributed worldwide. It is known to cause disease in mammals, producing significant economic loses to livestock industry and burden to human health. After ingestion, the parasites migrate through the liver and mature in the bile ducts. A better understanding of the parasite's immunopathogenesis would help to develop efficacious therapeutics and vaccines. Currently, much of our knowledge comes from in vitro and in vivo studies in animal models. Relatively little is known about the host-parasite interactions in humans. Here, we provide a narrative review of what is currently know about the pathogenesis and host immune responses to F. hepatica summarizing the evidence available from the multiple hosts that this parasite infects.

Demographic Characteristics and Low Iron Status Markers Are Associated with Hemoglobin Levels and Anemia among Children Living at High Elevation in Cusco, Peru.

Anemia is a complex condition associated with diet, chronic infections, and blood loss. Children living at high altitudes have higher absolute hemoglobin levels due to hypoxemia. However, they are exposed to repeated infections and dietary limitations. We conducted a cross-sectional study to identify factors affecting the hemoglobin concentration in children living in high-altitude rural communities in the Anta province of Peru. All children 3-16 years of age attending public schools were invited to participate. We enrolled children 3-16 years old in schools and visited their homes to collect demographic, socioeconomic, medical history, and anthropometric data. Children provided blood and stool samples for complete blood counts, iron status markers, and helminth infection testing. Among the 2,000 children enrolled, the mean age was 9.9 (±3.4) years, 1,004 (50.2%) were female, and the median residence altitude was 3,398 (interquartile range 3,35-3,497) meters. The mean hemoglobin level was 15 (±1.15) mg/dL; 320 (16%) had anemia as defined by WHO. Children with anemia were more likely to have lower serum iron levels (odds ratio [OR] 2.8 [95% CI 2.2-3.6], P <0.001) and serum transferrin saturation (OR 2.8 [95% CI 2-3.9], P <0.001). Younger age (OR 0.85 [95% CI 0.82-0.89], P <0.001), stunting (OR 0.68 [95% CI 0.59-0.79], P <0.001), education of the mother (OR 0.94 [95% CI 0.91-0.98], P <0.005), and low eosinophils (OR 0.49 [95% CI 0.26-0.9], P = 0.022) were associated with anemia. Helminth infections were not associated with anemia. Anemia among children at high altitude is multifactorial, but iron deficiency is a contributing factor. Further studies are needed to evaluate iron status and anemia in children living at high altitudes.

Treatment of cryptosporidiosis: nitazoxanide yes, but we can do better.

INTRODUCTION: Cryptosporidiosis was initially recognized as an important cause of diarrhea in AIDS patients. It has been underdiagnosed in other populations. Recent studies have highlighted the importance of Cryptosporidium as a cause of diarrhea and malnutrition in young children in resource-poor countries and an emerging pathogen in organ-transplant recipients. AREAS COVERED: Nitazoxanide is FDA approved for treatment of cryptosporidiosis in immunocompetent people. However, it is less effective in HIV and transplant patients and malnourished children. In transplant recipients, there is emerging data on antiparasitic combinations for cryptosporidiosis, including combinations of nitazoxanide, azithromycin, and in one case rifaximin. High-throughput phenotypic screens have identified some potential treatments. Among them, clofazimine was no better than placebo in a trial in AIDS patients. There have also been efforts to develop drug versus specific parasite targets. However, in part due to safety issues, none of these compounds have advanced into clinical trials. EXPERT OPINION: Development of new and more efficacious therapies for cryptosporidium is imperative. Current approve therapy is far from optimal and lacks efficacy in high-risk populations, such as, patients living with HIV. Additionally, there is limited data on patients with other types of immunosuppression (Transplanted, autoimmune conditions, etc).

Risk factors for acute mountain sickness in travellers to Cusco, Peru: coca leaves, obesity and sex.

BACKGROUND: Acute mountain sickness (AMS) may occur after rapid ascents to altitudes >2500 m. Cusco (3350 m) in Peru is a popular destination for altitude inexperienced travellers. This study aimed at evaluating the incidence and risk factors for AMS among a cohort of foreign Spanish language students in Cusco. METHODS: We performed a cohort study among young healthy foreign Spanish language students arriving to Cusco between 2012 and 2016. Consenting students answered an enrollment questionnaire on demographics, travel history and intended AMS preventive behaviour within 48 h of arrival. At 4-5 days after enrollment participants answered a second questionnaire about actual preventive behaviour before symptoms and the development of symptoms compatible with AMS during their first 48 h in Cusco. We used the 2018 Lake Louise Scoring System for AMS diagnosis. Participants with headache and a score ≥ 3 were considered to have AMS. RESULTS: We enrolled 142 language students, the median age was 21 years (interquartile range 20-25) and 57% were female. Participants decreased physical activity (38%), increased fluid intake (34%), drank coca leaf tea (34%), took acetazolamide (16%) and acclimatized at a lower altitude (6%) to prevent AMS. Thirty-nine percent had AMS. In the multivariate analysis, obesity [odds ratio (OR) 14.45 (2.33-89.6)] and female sex [OR 4.32 (1.81-10.28)] were associated with increased risk of AMS. Taking acetazolamide [OR 0.13 (0.03-0.56)] was associated with decreased AMS risk. Consumption of coca leaf tea was not associated with decreased risk of AMS. CONCLUSIONS: In our cohort, AMS affected two out of five travellers. Obesity and female sex were associated with increased risk. Drinking coca leaf tea for prevention did not decrease the risk of AMS. Acetazolamide prophylaxis was associated with decreased risk of AMS.

Extensively drug-resistant Salmonella Typhi in a patient returning from Pakistan, complicated by relapse with meropenem monotherapy.

In developing countries, typhoid fever is a common cause of febrile illness accompanied by abdominal pain and weakness. It is caused by Salmonella enterica serovar Typhi. Humans are the only known reservoir of infection, and typhoid fever is common in regions where access to clean water and sanitation is limited. The antimicrobials of choice for a case of typhoid fever acquired outside Pakistan are third generation cephalosporins. Lately, cases of extensively drug-resistant (XDR) Salmonella Typhi have been reported in people with a travel history to Pakistan. We present a case of XDR typhoid fever which relapsed after treatment with meropenem.

A Comparison of the Risk for Chronic Fascioliasis between Children 3 to 5 Years and Children 6 to 12 Years of Age in the Cusco Region of Peru.

School-age children bear the highest burden of fascioliasis in endemic countries. Few studies have addressed Fasciola in preschool children. We performed a secondary data analysis using two Fasciola databases from Cusco, Peru, comparing preschoolers with elementary school children. We included 2,630 children, 50% were female, the median age was 8.4 years (interquartile range [IQR] 6.1-10.5), and 15% (396/2,630) were < 5 years of age. Children < 5 years were less likely to be infected with Fasciola hepatica (P = 0.008) and Hymenolepis nana (P < 0.001) and more likely to have anemia (P < 0.001) and a lower median height for age Z (HAZ) score (P = 0.002). Fascioliasis was less common in younger children, but this group may be at higher risk for chronic complications caused by fascioliasis.

Fasciola hepatica Infection Risk for Adult Household Members Living with Children with Fascioliasis in Cusco, Peru.

Fasciola hepatica is highly prevalent in the highlands of Peru. School-age children have the greatest risk of infection. Mass treatment of at-risk populations has been proposed to control the infection and prevent complications. However, the decreasing effectiveness of triclabendazole raises concerns regarding this strategy. Previous studies reported aggregation of Fasciola infection among family members. This study aimed to determine the risk of fascioliasis among household members living with Fasciola-infected children identified through school-based testing. We conducted a cross-sectional study including adult members of households where children with and without fascioliasis were identified. Demographic, epidemiological, and socioeconomic information was collected. One blood sample was drawn to test for Fasciola antibodies, and three stool samples were collected for microscopy for Fasciola ova. We tested 326 adults from 213 households. Of these adult subjects, chronic fascioliasis (24 of 326, 7.4%) was the most common helminth infection. Thirty-nine subjects (12.7%) tested positive for Fasciola antibodies. Combining microscopy and serum antibody tests, 13.2% (43 of 326) had evidence of Fasciola infection. One third (104 of 326, 31.9%) of the participants lived with at least one child infected with Fasciola hepatica. Adults with fascioliasis were four times more likely to live with an infected child. Poverty and diet were associated with increased risk of Fasciola infection. Adults with fascioliasis were significantly more likely to live with Fasciola-infected children.