Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

[Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social].

Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide. Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS). Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10th Revision. Comparisons were made by chapter, age, gender and evolution time. Results: Complications and comorbidities were more common in subjects aged ≥ 62 years. Out of 297 100 patients, 34.9 % had any complication; microvascular complications (32 %) prevailed in the industrial North, whereas macrovascular complications (12.3 %) did in the rural East, and comorbidities (5 %) in southern Mexico City. Complications predominated in men (any complication, 30.2 %). Heart failure and comorbidities were more common in women (5.6 % and 4.9 %, respectively). Conclusions: T2D complications and comorbidities showed geographic and gender differences, and were greater with older age and longer evolution time. It is urgent for strategies for the prevention of complications and comorbidities to be reinforced in patients with T2D.

Introducción: La prevalencia de complicaciones crónicas y comorbilidades en pacientes con diabetes tipo 2 (DT2) se han incrementado en el mundo. Objetivo: Comparar la prevalencia de complicaciones y comorbilidades crónicas en pacientes con DT2 en 36 unidades de medicina familiar de cinco delegaciones del Instituto Mexicano del Seguro Social (IMSS). Métodos: Conforme los códigos de la Décima Revisión de la Clasificación Internacional de Enfermedades se identificaron las complicaciones (hipoglucemia, pie diabético, enfermedad renal, retinopatía, enfermedad cardiaca isquémica, enfermedad cerebrovascular y falla cardiaca) y comorbilidades (enfermedad hepática, cáncer, anemia) de DT2. Se compararon por delegación, edad, sexo y tiempo de evolución. Resultados: Las complicaciones y comorbilidades fueron más comunes en personas ≥ 62 años. De 297 100 pacientes, 34.9 % presentó cualquier complicación; microvasculares en el norte industrial (32 %), macrovasculares en el este rural (12.3 %) y comorbilidades (5 %) en el sur de la Ciudad de México; estas complicaciones predominaron en los hombres (cualquier complicación 30.2 %). La falla cardiaca y las comorbilidades fueron más comunes en mujeres (5.6 y 4.9 %). Conclusiones: Las complicaciones y comorbilidades de DT2 mostraron diferencias geográficas y de sexo y fueron mayores con la edad y el tiempo de evolución. Urge reforzar estrategias para la prevención de las complicaciones y comorbilidades en los pacientes con DT2.

Evaluation of the impact on non-communicable chronic diseases of a major integrated primary health care program in Mexico.

BACKGROUND: Primary health care is the best framework for implementing actions for the prevention and control of non-communicable diseases at an appropriate scale. In 2002, the Mexican Institute for Social Security (IMSS), which provides health care to half of the Mexican population, implemented a primary care-based integrated program that included the improvement of the family health care practice and a preventive strategy called PREVENIMSS, to reduce the burden of disease. OBJECTIVE: To asess the impact of this program on selected non-communicable chronic diseases. METHODS: Morbidity and mortality were compared before and after implementation of the program and time trends in IMSS affiliates and non-affiliates using the difference-in-differences (DD) method. RESULTS: Incidence rates of diabetes and hypertension increased whereas those of cervical cancer, breast cancer and other cerebrovascular diseases decreased from 2000 to 2013. The DD in mortality rates, expressed per 100000 persons, showed a decrease of 49.4 for diabetes mellitus, 9.1 for hypertensive disease, 42.9 for ischemic heart disease, 17.4 for cerebrovascular disease, 7.5 for cervical cancer and 5.8 for breast cancer. CONCLUSIONS: The reductions in mortality rates could be explained by both changes in incidence rates and changes in case fatality rates associated with early detection and treatment. These initial findings can be interpreted as the potential impact of integrated programs based on primary health care in a developing country.

Evolution of differences in clinical presentation across epidemic waves among patients with COVID-like-symptoms who received care at the Mexican Social Security Institute.

Background: Timely monitoring of SARS-CoV-2 variants is crucial to effectively managing both prevention and treatment efforts. In this paper, we aim to describe demographic and clinical patterns of individuals with COVID-19-like symptoms during the first three epidemic waves in Mexico to identify changes in those patterns that may reflect differences determined by virus variants. Methods: We conducted a descriptive analysis of a large database containing records for all individuals who sought care at the Mexican Social Security Institute (IMSS) due to COVID-19-like symptoms from March 2020 to October 2021 (4.48 million records). We described the clinical and demographic profile of individuals tested (3.38 million, 32% with PCR and 68% with rapid test) by test result (positives and negatives) and untested, and among those tested, and the changes in those profiles across the first three epidemic waves. Results: Individuals with COVID-19-like symptoms were older in the first wave and younger in the third one (the mean age for those positive was 46.6 in the first wave and 36.1 in the third wave; for negatives and not-tested, the mean age was 41 and 38.5 in the first wave and 34.3 and 33.5 in the third wave). As the pandemic progressed, an increasing number of individuals sought care for suspected COVID-19. The positivity rate decreased over time but remained well over the recommended 5%. The pattern of presenting symptoms changed over time, with some of those symptoms decreasing over time (dyspnea 40.6 to 14.0%, cough 80.4 to 76.2%, fever 77.5 to 65.2%, headache 80.3 to 78.5%), and some increasing (odynophagia 48.7 to 58.5%, rhinorrhea 28.6 to 47.5%, anosmia 11.8 to 23.2%, dysgeusia 11.2 to 23.2%). Conclusion: During epidemic surges, the general consensus was that any individual presenting with respiratory symptoms was a suspected COVID-19 case. However, symptoms and signs are dynamic, with clinical patterns changing not only with the evolution of the virus but also with demographic changes in the affected population. A better understanding of these changing patterns is needed to improve preparedness for future surges and pandemics.

How predictive of SARS-CoV-2 infection are clinical characteristics at presentation among individuals with COVID-like symptoms treated at the Mexican Institute of Social Security.

BACKGROUND: The COVID-19 pandemic has progressed rapidly, with the emergence of new virus variants that pose challenges in treating infected individuals. In Mexico, four epidemic waves have been recorded with varying disease severity. To understand the heterogeneity in clinical presentation over time and the sensitivity and specificity of signs and symptoms in identifying COVID-19 cases, an analysis of the changes in the clinical presentation of the disease was conducted. AIM: To analyze the changes in the clinical presentation of COVID-19 among 3.38 million individuals tested for SARS-CoV-2 at the Mexican Social Security Institute (IMSS) from March 2020 to October 2021 and evaluate the predictivity of signs and symptoms in identifying COVID-19 cases. METHODS: A retrospective analysis of clinical presentation patterns of COVID-19 among individuals treated at IMSS was performed, contrasting the signs and symptoms among SARS-CoV-2-positive individuals with those who tested negative for the virus but had respiratory infection symptoms. The sensitivity and specificity of each sign and symptom in identifying SARS-CoV-2 infection were estimated. RESULTS: The set of signs and symptoms reported for COVID-19-suspected patients treated at IMSS were not highly specific for SARS-CoV-2 positivity. The signs and symptoms exhibited variability based on age and epidemic wave. The area under the receiver operating characteristic (ROC) curve was 0.62 when grouping the five main symptoms (headache, dyspnea, fever, arthralgia, and cough). Most of the individual symptoms had ROC values close to 0.5 (16 out of 22 between 0.48 and 0.52), indicating non-specificity. CONCLUSIONS: The results highlight the difficulty in making a clinical diagnosis of COVID-19 due to the lack of specificity of signs and symptoms. The variability of clinical presentation over time and among age groups highlights the need for further research to differentiate whether the changes are due to changes in the virus, who is becoming infected, or the population, particularly with respect to prior infection and vaccination status.

Effect on risk of anencephaly of gene-nutrient interactions between methylenetetrahydrofolate reductase C677T polymorphism and maternal folate, vitamin B12 and homocysteine profile.

OBJECTIVE: To evaluate the effects on anencephaly risk of the interaction between the maternal profile of folate, vitamin B12 and homocysteine and the 677C→T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). DESIGN: Case-control study paired (1:1) on maternity clinic, date of birth and state of residence. Cases of anencephaly were identified using the Registry of the Mexican Neural Tube Defect Epidemiological Surveillance System. Case and control mothers were selected from the same maternity departments. All mothers completed a structured questionnaire and blood samples were obtained to determine the MTHFR 677C→T polymorphism and biochemical profile. SETTING: Mexico, Puebla and Guerrero states, Mexico. SUBJECTS: A total of 151 mothers of cases and controls were enrolled from March 2000 to February 2001. We had complete information on biochemical profile and MTHFR C677T polymorphism for ninety-eight mothers of cases and ninety-one mothers of controls. RESULTS: The adjusted models show that the risk of anencephaly in mothers with 677TT genotype was reduced by 18 % (OR = 0·82; 95 % CI 0·72, 0·94) for each 1 ng/ml increment in serum folate. In terms of tertiles, mothers with 677TT genotype with serum folate levels in the upper tertile (>14·1 ng/ml) had a 95 % lower risk to have a child with anencephaly than mothers with serum folate levels in the first and second tertiles (P trend = 0·012). CONCLUSIONS: Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677C→T polymorphism and folate status. We observed a protective effect on anencephaly risk only in mothers with 677TT genotype as serum folate levels increased.

Mortality burden of the A/H1N1 pandemic in Mexico: a comparison of deaths and years of life lost to seasonal influenza.

BACKGROUND: The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. METHODS: Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory-confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. RESULTS: The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100,000 population and 445,000 YLL during the 3 waves of virus activity in Mexico, April-December 2009. The pandemic mortality burden was 0.6-2.6 times that of a typical influenza season and lower than that of the severe 2003-2004 influenza epidemic. Individuals aged 5-19 and 20-59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. CONCLUSIONS: Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic.

Characterizing the epidemiology of the 2009 influenza A/H1N1 pandemic in Mexico.

BACKGROUND: Mexico's local and national authorities initiated an intense public health response during the early stages of the 2009 A/H1N1 pandemic. In this study we analyzed the epidemiological patterns of the pandemic during April-December 2009 in Mexico and evaluated the impact of nonmedical interventions, school cycles, and demographic factors on influenza transmission. METHODS AND FINDINGS: We used influenza surveillance data compiled by the Mexican Institute for Social Security, representing 40% of the population, to study patterns in influenza-like illness (ILIs) hospitalizations, deaths, and case-fatality rate by pandemic wave and geographical region. We also estimated the reproduction number (R) on the basis of the growth rate of daily cases, and used a transmission model to evaluate the effectiveness of mitigation strategies initiated during the spring pandemic wave. A total of 117,626 ILI cases were identified during April-December 2009, of which 30.6% were tested for influenza, and 23.3% were positive for the influenza A/H1N1 pandemic virus. A three-wave pandemic profile was identified, with an initial wave in April-May (Mexico City area), a second wave in June-July (southeastern states), and a geographically widespread third wave in August-December. The median age of laboratory confirmed ILI cases was ∼ 18 years overall and increased to ∼ 31 years during autumn (p<0.0001). The case-fatality ratio among ILI cases was 1.2% overall, and highest (5.5%) among people over 60 years. The regional R estimates were 1.8-2.1, 1.6-1.9, and 1.2-1.3 for the spring, summer, and fall waves, respectively. We estimate that the 18-day period of mandatory school closures and other social distancing measures implemented in the greater Mexico City area was associated with a 29%-37% reduction in influenza transmission in spring 2009. In addition, an increase in R was observed in late May and early June in the southeast states, after mandatory school suspension resumed and before summer vacation started. State-specific fall pandemic waves began 2-5 weeks after school reopened for the fall term, coinciding with an age shift in influenza cases. CONCLUSIONS: We documented three spatially heterogeneous waves of the 2009 A/H1N1 pandemic virus in Mexico, which were characterized by a relatively young age distribution of cases. Our study highlights the importance of school cycles on the transmission dynamics of this pandemic influenza strain and suggests that school closure and other mitigation measures could be useful to mitigate future influenza pandemics. Please see later in the article for the Editors' Summary.

Type 1 diabetes incidence in children and adolescents in Mexico: Data from a nation-wide institutional register during 2000-2018.

AIMS: To describe the annual incidence of type 1 diabetes in children and adolescents insured by the Mexican Institute of Social Security, the main health provider in Mexico, during 2000-2018. METHODS: We conducted a secondary data analyses using the incidence registers from the Epidemiological Surveillance Coordination of the Mexican Institute of Social Security collected during 2000-2018. Incident type 1 diabetes cases (age 19 years old and below) were identified using ICD-10-CM E10 diagnostic codes. Age, sex, and geographical region and seasonal-specific incidence were calculated with their corresponding annual percentage change (APC) as well. RESULTS: In the period 2000-2018, the number of incident cases with type 1 diabetes decreased from 3.4 to 2.8 per 100,000 in insured for subjects below 20 years old. We observed an increase in the 2000-2006, followed by a decrease for the 2006-2018 period (APC +16.1 and -8.7 respectively). Females and children <5 years old had a significant decrease in the incidence rate, while inhabitants in Central Mexico showed a significant increase. No difference was found in incidence between seasons. CONCLUSIONS: Our study describes significant fluctuations of the incidence of type 1 diabetes during the period 2000-2018, which appeared to correspond to influenza outbreaks, among Mexican children and adolescents.

Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesions.

Exposure to naturally occurring inorganic arsenic (iAs), primarily from contaminated drinking water, is considered one of the top environmental health threats worldwide. Arsenic (+3 oxidation state) methyltransferase (AS3MT) is the key enzyme in the biotransformation pathway of iAs. AS3MT catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to trivalent arsenicals, resulting in the production of methylated (MAs) and dimethylated arsenicals (DMAs). MAs is a susceptibility factor for iAs-induced toxicity. In this study, we evaluated the association of the polymorphism in AS3MT gene with iAs metabolism and with the presence of arsenic (As) premalignant skin lesions. This is a case-control study of 71 cases with skin lesions and 51 controls without skin lesions recruited from a iAs endemic area in Mexico. We measured urinary As metabolites, differentiating the trivalent and pentavalent arsenical species, using the hydride generation atomic absorption spectrometry. In addition, the study subjects were genotyped to analyze three single nucleotide polymorphisms (SNPs), A-477G, T14458C (nonsynonymus SNP; Met287Thr), and T35587C, in the AS3MT gene. We compared the frequencies of the AS3MT alleles, genotypes, and haplotypes in individuals with and without skin lesions. Marginal differences in the frequencies of the Met287Thr genotype were identified between individuals with and without premalignant skin lesions (p=0.055): individuals carrying the C (TC+CC) allele (Thr) were at risk [odds ratio=4.28; 95% confidence interval (1.0-18.5)]. Also, individuals with C allele of Met287Thr displayed greater percentage of MAs in urine and decrease in the percentage of DMAs. These findings indicate that Met287Thr influences the susceptibility to premalignant As skin lesions and might be at increased risk for other adverse health effects of iAs exposure.

Night Shift Work and Risk of Breast Cancer in Women.

BACKGROUND: Night shift work involving circadian disruption has been associated with increased breast cancer rates in some epidemiological studies, but the evidence is still on debate. AIM OF THE STUDY: The objective of this study is to assess the association between night shift work and breast cancer in Mexican women. METHODS: A Case-control study was conducted with incident cases of breast cancer at the Instituto de Seguridad Social del Estado de México y Municipios. Cases were interviewed about past exposures prior to the final diagnosis. Controls were women without breast cancer matched on multiple sociodemographic characteristics. RESULTS: 101 cases and 101 matched controls were interviewed; this small sample size provided consistent, but wide estimates of the assessed associations. The multivariate conditional logistic regression showed that breast-feeding was associated with reduced risk for breast cancer (OR 0.12; 95% CI: 0.02-0.60); women who experienced early menarche (12 years) were more likely to develop breast cancer (OR 18.58; 95% CI 18: 2.19-148). Women who worked at night were more likely to develop breast cancer compared to women who never did (OR = 8.58; 95% CI: 2.19-33.8). CONCLUSIONS: Our results are consistent with studies from other countries, which positively associated night shift work with breast cancer.

Air pollution and mortality in Latin America: the role of education.

BACKGROUND: People with less education in Europe, Asia, and the United States are at higher risk of mortality associated with daily and longer-term air pollution exposure. We examined whether educational level modified associations between mortality and ambient particulate pollution (PM10) in Latin America, using several timescales. METHODS: The study population included people who died during 1998-2002 in Mexico City, Mexico; Santiago, Chile; and São Paulo, Brazil. We fit city-specific robust Poisson regressions to daily deaths for nonexternal-cause mortality, and then stratified by age, sex, and educational attainment among adults older than age 21 years (none, some primary, some secondary, and high school degree or more). Predictor variables included a natural spline for temporal trend, linear PM10 and apparent temperature at matching lags, and day-of-week indicators. We evaluated PM10 for lags 0 and 1 day, and fit an unconstrained distributed lag model for cumulative 6-day effects. RESULTS: The effects of a 10-microg/m increment in lag 1 PM10 on all nonexternal-cause adult mortality were for Mexico City 0.39% (95% confidence interval = 0.13%-0.65%); São Paulo 1.04% (0.71%-1.38%); and for Santiago 0.61% (0.40%-0.83%). We found cumulative 6-day effects for adult mortality in Santiago (0.86% [0.48%-1.23%]) and São Paulo (1.38% [0.85%-1.91%]), but no consistent gradients by educational status. CONCLUSIONS: PM10 had important short- and intermediate-term effects on mortality in these Latin American cities, but associations did not differ consistently by educational level.

Stepwise strategies to successfully recruit diabetes patients in a large research study in Mexican population.

AIMS: Describe stepwise strategies (electronic chart review, patient preselection, call-center, personnel dedicated to recruitment) for the successful recruitment of >5000 type 2 diabetes patients in four months. METHODS: Twenty-five family medicine clinics from Mexico City and the State of Mexico participated: 13 usual care, 6 specialized diabetes care and 6 chronic disease care. Appointments were scheduled from 11/3/2015 to 3/31/2016. Phone calls were generated automatically from an electronic database. A telephone questionnaire verified inclusion criteria, and scheduled an appointment, with a daily report of appointments, patient attendance, acceptance rate, and questionnaire completeness. Another recruitment log reviewed samples collected. Absolute number (percentage) of patients are reported. Means and standard deviations were estimated for continuous variables, χ2 test and independent "t" tests were used. OR and 95% CI were estimated. RESULTS: 14,358 appointments were scheduled, 9146 (63.7%) attended their appointment: 5710 (62.4%) fulfilled inclusion criteria and 5244 agreed to participate (91.8% acceptance). Those accepting participation were more likely women, younger and with longer disease duration (p<0.05). The cost of the call-center service was $3,010,000.00 Mexican pesos (∼$31.70 USD per recruited patient). CONCLUSIONS: Stepwise strategies recruit a high number of patients in a short time. Call centers offer a low cost per patient.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic.

Chronic exposure to inorganic arsenic (iAs) has been associated with increased risk of various forms of cancer and of noncancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and cancer-promoting effects of iAs exposure. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico. Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an indicator to identify individuals with increased susceptibility to toxic and cancer-promoting effects of arseniasis.

Intense seasonal A/H1N1 influenza in Mexico, winter 2013-2014.

BACKGROUND AND AIMS: A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013-2014 following a mild 2012-2013 A/H3N2 influenza season. METHODS: We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013-2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system. RESULTS: A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October 1, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 years and lower among younger age groups for the 2013-2014 A/H1N1 season compared to the previous A/H1N1 season in 2011-2012 (χ(2) test, p <0.001). The reproduction number for the winter 2013-2014 influenza season in central Mexico was estimated at 1.3-1.4, in line with that reported for the 2011-2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009. CONCLUSIONS: We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013-March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011-2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.

Reproductive effects of occupational DDT exposure among male malaria control workers.

To assess potential effects of human DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] exposure, we evaluated the reproductive history of 2,033 workers in the antimalaria campaign of Mexico. Data on occupational exposure to DDT and reproductive outcomes were gathered through a questionnaire, and workers provided information about 9,187 pregnancies. We estimated paternal exposure to DDT before each pregnancy using three approaches: a) a dichotomous indicator for pregnancies before and after exposure began, b) a qualitative index of four exposure categories, and c) an estimation of the DDT metabolite DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] accumulated in fat. To assess associations, we used logistic regression models that accounted for correlated observations and adjusted for parents' age at each child's birth, exposure to other pesticides, exposure to chemical substances in other employment, smoking, and alcohol consumption. The odds ratio for birth defects comparing pregnancies after and before the first exposure was 3.77 [95% confidence interval (95% CI), 1.19-9.52]. Compared with the lowest quartile of estimated DDE in fat, the ORs were 2.48 (95% CI, 0.75-8.11), 4.15 (95% CI, 1.38-12.46), and 3.76 (95% CI, 1.23-11.44) for quartiles 2, 3, and 4, equivalent to p,p -DDE in fat of 50, 82, and 298 microg/g fat, respectively. No significant association was found for spontaneous abortion or sex ratio. We found an increased risk of birth defects associated with high occupational exposure to DDT in this group of workers. The significance of this association at lower exposure levels found in the general population remains uncertain.

Do associations between airborne particles and daily mortality in Mexico City differ by measurement method, region, or modeling strategy?

We evaluated whether associations between PM10 and daily mortality in Mexico City differ by the PM10 measurement device or by regional differences in particle composition. Additionally, we reanalyzed previously collected data in light of recent insights about flaws in commonly used time series analysis techniques. We examined daily associations between mortality and four indicators of ambient PM10 using Poisson regression, controlling for temperature and time trends with cubic natural splines. Associations were calculated for five subregions corresponding to five monitoring sites and pooled for the entire metropolitan area. PM10 was measured with three methods: Tapered Element Oscillating Microbalance (TEOM), Sierra-Anderson High Volume (Hi-Vol) and Harvard Impactor (HI), the latter only at one site. In addition, predicted values of daily PM10 were developed using the Hi-Vol measurements, which were taken every sixth day, and weather, visibility and other pollutant data. We assigned deaths to the exposure from the monitor nearest to their residence. We also re-evaluated the HI PM2.5 and mortality association in southwest Mexico City, which was estimated previously using nonparametric statistical models. Slight decreases in effect estimates were observed (a 1.45% increase (95% CI: 0.09%, 2.83%) in total mortality per 10 microg/m(3) increment of PM2.5 at lag 0) compared to a 1.68% change (95% CI: 0.45%, 2.93%) using the previously employed nonparametric approach. Using data pooled over all the regions, PM10 measured by the TEOM and the predicted PM10 values showed little association with mortality at any of the lags examined. The pooled estimates for Hi-Vol PM10 (using one sixth of the data) were positive across all lags examined and significant for lags 3 and 5. No consistent patterns of differing associations were seen across regions that would correspond with particle toxicity or composition. Particulate air pollution, measured with gravimetric methods, is associated with daily mortality and presents a risk to health in Mexico City. The reanalysis suggests that previous research is robust to statistical method and likely to yield the same overall conclusions about the short-term effects of airborne particles on mortality.