Juan O Talavera

Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico.

Abstract Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18–64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5μg, 15μg, or 45μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15μg VLP vaccine (N =2537) or placebo (N =1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15μg and 45μg) compared to the placebo and 5μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82–92% of all subjects and in 64–85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.

Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

BackgroundIn the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults.MethodsThe study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models.ResultsThe prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95) and women (OR 0.78; 95%CI 0.64–0.94) who reported an amount of ≥30 minutes/day of leisure-time activity, and among women who reported an amount of ≥3 hours/day of workplace activity (OR 0.75; 95%CI 0.59–0.96).ConclusionOur results indicate that both leisure-time and workplace activity at different intensity levels, including low-intensity significantly reduce the risk of MS. This finding highlights the need for more recommendations regarding the specific amount and intensity of leisure-time and workplace activity needed to prevent MS.

Hemoglobin and Platelet Count Effect on Platelet Yields in Plateletpheresis

BACKGROUND Platelet transfusion in thrombocytopenic patients, especially those with marrow failure, remains one of the most important support measures available. Treatment success depends on rational use of platelet transfusion. Platelet yield, reflected in transfused platelet dose, influences platelet recovery in the patient and allows prolonging intervals between transfusions. In this study, our main objective was to identify donor laboratory and clinical factors that showed some influence on platelet yield obtained by apheresis. METHODS Healthy donor laboratory and clinical data were analyzed prior to performing plateletpheresis. Platelet yield was quantified after plateletpheresis procedure was concluded in two different ways: a) prefixed volume of 5,000 mL processed, and b) volume determined according to manufacturer recommendations. Age, gender, hemoglobin concentration, platelet and leukocyte count, height, and weight were included as yield-predicting donor variables. RESULTS In group A, two variables were significant: donor platelet count and hemoglobin (Hb) concentrations with r = 0.554, and in group B, donor platelet count, Hb concentrations, and volume with r = 0.758. CONCLUSIONS Donor platelet count and hemoglobin concentrations influence platelet yield: higher platelet count corresponds to higher yield, while hemoglobin shows an inverse relationship, i.e., the lower the hemoglobin concentrations, the higher the platelet yield.

High Doses of Dexamethasone in Adult Patients with Idiopathic Thrombocytopenic Purpura

BACKGROUND High-dose dexamethasone (DXM) has been used in treatment of patients with idiopathic thrombocytopenic purpura (ITP) who are refractory to other treatments such as prednisone and splenectomy; nevertheless, different studies show variable success rates, this postulated as possibly being due to racial differences. The objective of this study was to determine DXM effectiveness at high doses in Mexican mestizo adult patients diagnosed with ITP with and without splenectomy. METHODS Nonhospitalized adult patients with ITP were included, eight patients previously splenectomized (group 1) and 11 who had not undergone splenectomy (group 2). Patients received DXM 40 mg/day intravenously (i.v.) during 4 consecutive days every 4 weeks until six cycles were completed. RESULTS There were no differences between the two groups regarding age (mean 39 vs. 33 years of age) and initial platelet count (M 17 vs. 24 x 10(9)/L). Median evolution time was 84 months for group 1 and 7 months for group 2 (p = 0.002). Of 19 patients, nine achieved a favorable response (FR), six belonged to group 1, and three to group 2 (Fisher p = 0.07). Nevertheless, after 6 months only two group 1 patients and two group 2 patients maintained FR (Fisher exact test p = 1). Patients achieving FR to initiation of second cycle maintained FR at the end of six cycles. CONCLUSIONS Thus, the previously mentioned high-dose DXM therapy appears to be useful for both patients with ITP with and without splenectomy and high-dose DXM appears to be a good alternative therapy for postsplenectomy and relapse patients. However, duration of FR to treatment was brief; therefore, other treatment plans might be required to achieve longer remission duration. Response was similar to that observed in other studies carried out in different populations; thus, apparently no genetic or racial variations exist. In addition, whether patients not responding after second cycle should continue until completing the 6-month plan or should try a different therapeutic approach must be considered in the treatment plan.

Critical Analysis of Deaths Due to Atypical Pneumonia during the Onset of the Influenza A (H1N1) Virus Epidemic

BACKGROUND The ongoing influenza A (H1N1) pandemic stroked Mexico and posed a huge challenge to the medical care and public health systems. This report analyzes the clinical course and process of care of patients who died due to atypical pneumonia and fulfilled the clinical criteria of suspected case of novel influenza A (H1N1) virus infection. METHODS We conducted a retrospective analysis of a series of 38 patients who died between April 7 and April 28, 2009 at Instituto Mexicano del Seguro Social (IMSS) hospitals due to severe pneumonia and respiratory distress. These cases coincided with the beginning of the outbreak, so patients did not undergo laboratory testing to diagnose influenza. According to IMSS and CDC criteria, post-hoc analysis allowed considering the presumptive diagnosis of S-OIV infection. A multidisciplinary group analyzed the information from the clinical charts, laboratory tests, radiographic studies and death certificates, using descriptive statistics. RESULTS Most cases were middle-aged (mean 33 years, range: 4-62 years) and previously healthy; 18.4% had an underlying chronic disease, 23.7% were obese and 7.9% were current smokers. None had received the seasonal influenza vaccine; they had cough (92%), fever (86.8%), and malaise (73.7%). The median time from disease onset to hospital admission was 6 days (range 0-8 days). All were admitted to the intensive care unit with pneumonia and/or respiratory distress. Average time from disease onset to death was 8 days (range 4-18 days). CONCLUSIONS An increased number of severe cases of atypical pneumonia in previously healthy adults highlight the importance of the availability of a timely surveillance system able to identify sudden increases in the number of cases or presentation of apparently known diseases.

Health workers cohort study: methods and study design

Objective: To examine different health outcomes that are associated with specific lifestyle and genetic factors. Materials and methods: From March 2004 to April 2006, a sample of employees from three different health and academic institutions, as well as their family members, were enrolled in the study after providing informed consent. At baseline and follow-up (2010-2013), participants completed a self-administered questionnaire, a physical examination, and provided blood samples. Results: A total of 10 729 participants aged 6 to 94 years were recruited at baseline. Of these, 70% were females, and 50% were from the Mexican Social Security Institute. Nearly 42% of the adults in the sample were overweight, while 20% were obese. Conclusion: Our study can offer new insights into disease mechanisms and prevention through the analysis of risk factor information in a large sample of Mexicans.

Bone Speed of Sound Throughout Lifetime Assessed With Quantitative Ultrasound in a Mexican Population

The purpose of this study was to assess the bone speed of sound (SoS) through lifetime of a large Mexican population sample by determining the SoS from the radius and tibia using quantitative ultrasound (QUS). This is a cross-sectional evaluation of participants in the Mexican Health Workers Cohort Study. QUS measurements were performed using Sunlight Omnisense 8000P; Z- and T-scores were calculated for both sexes at the distal third of the radius and midshaft tibia, both on the nondominant side. A locally weighted regression smoothing scatterplot model was used to identify different phases of bone accretion and loss. A total of 9128 participants aged 1-75 yr were measured with QUS. Bone SoS accretion began 5 yr earlier in girls than boys (p<0.05). Maximal SoS or peak bone SoS was noted at 28 yr in the radius and at 22 yr in the tibia. Postmenopausal women (45-50 yr) showed significant SOS decrease at both sites (p<0.05) compared with men. Using the locally weighted regression smoothing scatterplot model, we found 5 different phases that constitute the biological development of bone over the life course, from ages 1-6, 7-12, 12-25, 25-50, and 50-75 yr (p<0.05). Our study shows the age- and sex-dependent changes and different phases of bone development expressed by SoS measurements of the radius and tibia. The values reported in this study can be used as a reference for urban Mexican population.

Physical Activity and Dark Skin Tone: Protective Factors Against Low Bone Mass in Mexican Men

A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass.

A Rating System for Prompt Clinical Diagnosis of Ischemic Stroke

BACKGROUND When a CT scan is not available, an early accurate clinical diagnosis of ischemic stroke is essential to initiate prompt therapy. Our objective was to construct a clinical index that is easy to use when stroke patients are first evaluated at the hospital, to identify those who probably are experiencing an acute ischemic episode. The study was conducted at a university-affiliated medical referral center and two community general hospitals in Mexico. METHODS Clinical records were reviewed for 801 patients with sudden onset of a focal or global neurologic dysfunction, presumably of vascular origin lasting more than 24 h. Eligibility criteria for this study were admission to the hospital within the first 24 h after symptomatic onset, CT scan diagnosis between 24 and 72 h, and age >45 years. Ischemic stroke included cases of arterial brain infarction, while nonischemic stroke included subarachnoid or intraparenchymatous hemorrhage, mass lesion, venous infarction, and in cases without a CT scan evidence that could explain the clinical manifestations. Data excerpted for analysis were age, sex, history of diabetes mellitus or previous stroke/transient ischemic attack (TIA), time of onset of symptoms, presence of headache, vomiting, neck stiffness, hemiplegia, leukocytosis or atrial fibrillation, diastolic blood pressure, and Glasgow coma scale (GCS) rating. Two multivariable analyses were used: 1) step-wise multiple logistic regression (SMLR), and 2) conjunctive consolidation (CC). RESULTS After appropriate exclusions, the study proceeded with 83 ischemic and 42 nonischemic stroke patients. With SMLR, six variables were selected as predictive for ischemic stroke, including neck stiffness, diastolic blood pressure, previous history of stroke/TIA, hemiplegia, GCS, and atrial fibrillation. An appropriate sum of weighted ratings had a positive predictive value (PPV) of 100% for ischemic stroke. With consolidated categories, the PPV was 97% when patients had the following: no neck stiffness; no atrial fibrillation but history of stroke/TIA and GCS > or =12, or no neck stiffness but atrial fibrillation. CONCLUSIONS Among patients with acute stroke, clinical data can be used to identify a group with a high probability of ischemic stroke. There are slightly different results between both methods; while SMLR includes the four variables selected by CC, the latter included neither diastolic blood pressure nor hemiplegia/hemiparesia. However, CC results seem easier to understand and interpret than with SMLR.

Pathogens and acute respiratory distress syndrome

1 is the most common reason for seeking medical attention and the fourth cause of mortality in Mexico. 2 The principal agents associated with this syndrome are viral; 3 however, bacterial agents are associated with increased mortality, and the most common microorganisms are Streptococ-cus pneumoniae, Haemophillus influenzae, Moraxella catarrhalis and Streptococcus pyo-genes. 4 In our community there is an increase in failures of common treatments, presumably provoked by an increase in resistant microorganisms or by the presence of uncommon ones. In order to determine the pathogens most frequently associated with ARDS, their prevalence, and resistance patterns to common antimicrobials, we conducted a clinical survey of 194 students with acute respiratory infection who had not previously received treatment. The students were selected from five high schools belonging to the Uni-versidad Autónoma del Estado de Mé-xico (UAEM). A clinical diagnosis and appropriate bacteriological culture from the affected sites was conducted for each case. The clinical distribution of ARDS was: pharyngitis (60.8%), pharyngoton-sillitis (34.5%), nasopharyngitis (4.1%) and rynitis (0.5%). The agents associated with these were; S. pyogenes (23%), M. catarrhalis (55.1%) and S. aureus (49.4%). In addition, no bacterial pathogen could be isolated in 27 of the cultures. A high bacterial resistance to common antimicro-bials was found: S. pyogenes showed a resistance pattern to pefloxacine (86.7%) and trimethoprim-sulfamethoxazole (51.1%), whereas the resistance of M. catarrhalis to ampicilin, trimethoprim-sulfamethoxazole, and carbenicillin was higher than 60% and lower than 21% to gentamicyn, metilmicin, and nitrofu-rantoin. The microbial resistance of S. aureus to cefotaxime, ampicillin, penicillin , dicloxacin, and cefatazidime was higher than 80% and lower than 21% for trimethoprim-sulfamethoxazole, gentamicyn, cefalotine, and erytromicin. Strains S. pyogenes producing β-lactamase were not found. ARDS is well recognized as a serious public health problem among specific age groups. 4, 5 Free access to antibiotics and self-medication in most cases, regardless of etiology, 6 have favored an increase in the rate of bacterial resistance in the three most common pathogens: S. pneu-moniae, H. influenzae and M. catarrhalis. 7 It has been suggested that the use of mi-crobiologic tests, such as cultures of the affected sites, can improve diagnostic and therapeutic accuracy and avoid the emergence of resistant strains. 8 S. pyogenes was the most common pathogen isolated in a single form; however , the indentification of M. catarrhalis in all clinical diagnoses, with the exception of nasopharyngitis, was not expected in this population. Currently, it is accepted that M. …