Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial.

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). METHODS: Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. RESULTS: Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference -15.5%; 95% confidence interval (CI) -28.3 to -1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5-21.1]). No additional differences in the other secondary outcomes were observed. CONCLUSIONS: Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation.

Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol as causing reproductive toxicity (developmental endpoint); Part I. Somatic development.

OBJECTIVES: On December 11, 2019, California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) met to consider the addition of cannabis smoke and Δ9 -THC to the Proposition 65 list as causing reproductive toxicity (developmental endpoint). As the lead state agency for implementing Proposition 65, the Office of Environmental Health Hazard Assessment (OEHHA) reviewed and summarized the relevant scientific literature in the form of a hazard identification document (HID). Here we provide reviews based on the HID: shortened, revised, and reformatted for a larger audience. METHODS: While the HID included both human and animal data, this set of three reviews will highlight the animal-derived data pertaining to somatic development (Part I), neurodevelopmental effects (Part II), and proposed neurodevelopmental mechanisms of action (Part III). RESULTS: Endogenous cannabinoids (eCBs) and their receptors serve many critical functions in normal development. Δ9 -THC can interfere with these functions. Mechanistic studies employed techniques including: blocking Δ9 -THC binding to endocannabinoid (EC) receptors, inhibiting Δ9 -THC metabolism, and/or using animals expressing knockout mutations of EC receptors. Apical somatic effects of cannabis smoke or Δ9 -THC reported in whole animal studies included decreases in offspring viability and growth. Mechanistic studies discussed in Part I focused on Δ9 -THC effects on early embryos and implantation, immune development, and bone growth. CONCLUSIONS: In reaching its decision to list cannabis and Δ9 -THC as a developmental toxicant under California's Proposition 65, the DARTIC considered biological plausibility and the consistency of mechanistic information with effects reported in human and whole animal studies.

Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol (Δ9 -THC) as causing reproductive toxicity (developmental endpoint); Part II. Neurodevelopmental effects.

This review focuses on neurodevelopmental effects observed in animal studies of cannabis smoke and Δ9 -THC. Effects in offspring after preconceptional, prenatal, or perinatal exposure to cannabis smoke or Δ9 -THC were considered. Locomotor and exploratory behavior effects were noted in rats. Cognitive effects observed included impairment of memory and learning, attention deficits, time taken to complete tasks (rats) and alterations in response to visual stimuli (rats/monkeys). Emotionality was observed in rodents as an increase in separation-induced ultrasonic vocalizations, reduced social interaction and play behavior, and increased generalized anxiety. Increased rate of acquisition of morphine self-administration and/or enhanced sensitivity towards the rewarding effects of morphine or heroin were observed in adult rats prenatally exposed to Δ9 -THC. Expression of cannabinoid receptors was examined in rodent studies along with behavioral parameters. Altered mRNA levels of genes relevant to synaptic plasticity in the nucleus accumbens (the brain region associated with compulsivity, addiction vulnerability, and reward sensitivity) were noted. Findings in zebrafish supported effects in mammalian models. Neurochemical effects on specific brain regions and neurotransmitter systems seen in these animal studies appear to impact cognitive function, motor activity, and drug sensitivity. Mechanistic studies provided evidence for the biological plausibility of effects observed. Observations from animal studies of changes in motor behavior, cognitive performance, emotionality and susceptibility to drug sensitivity later in life were among the findings from animal and human studies considered by California's Developmental and Reproductive Toxicant Identification Committee, in concluding that cannabis smoke and Δ9 -THC are developmental toxicants.

Animal evidence considered in determination of cannabis smoke and Δ9 -tetrahydrocannabinol as causing reproductive toxicity (developmental endpoint): Part III. Proposed neurodevelopmental mechanisms of action.

This review summarizes the most common potential pathways of neurodevelopmental toxicity due to perinatal exposure to Δ9 -tetrahydrocannabinol (Δ9 -THC) that lead to behavioral and other adverse outcomes (AOs). This is Part III in a set of reviews highlighting the animal-derived data considered by California's Developmental and Reproductive Toxicant Identification Committee (DARTIC) in 2019. The Hazard Identification Document (HID) provided to the DARTIC included a summary of human, whole animal, and mechanistic data on the neurodevelopmental toxicity of cannabis smoke and Δ9 -THC. The literature search for mechanistic data has been updated through 2020. We focus on mechanistic pathways relating to behavioral and other neurodevelopmental outcomes of perinatal exposure to Δ9 -THC. The endocannabinoid system (EC system) plays a crucial role in many processes involved in neurodevelopment and exposure to Δ9 -THC can alter these processes. Whole animal studies report changes in cognitive ability, behavior, and motor function after prenatal exposure to Δ9 -THC. Findings from mechanistic studies add to this evidence and further provide information regarding the pathways leading to these outcomes. Neuromechanistic studies can bridge the gaps between molecular initiating events and apical neurodevelopmental endpoints caused by a chemical. They offer insight into potential alterations in the same pathways by other chemicals that can also result in AOs. Studies of cannabinoid receptor agonist-induced molecular alterations and provide deep biological plausibility at the mechanistic level for the cognitive, behavioral, and motor impairments observed in animal studies after perinatal exposure to Δ9 -THC.

Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment.

BACKGROUND: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. OBJECTIVE: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. METHODS: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell­cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. DISCUSSION: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971.

A case-control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016.

In the Valencian Community (Spain), the programme of maternal pertussis vaccination during pregnancy started in January 2015. The objective of this study was to estimate in this region the vaccine effectiveness (VE) in protecting newborns against laboratory-confirmed pertussis infection. A matched case-control study was undertaken in the period between 1 March 2015 and 29 February 2016. Twenty-two cases and 66 controls (+/- 15 days of age difference) were included in the study. Cases were non-vaccinated infants < 3 months of age at disease onset testing positive for pertussis by real-time PCR. For every case three unvaccinated controls were selected. Odds ratios (OR) were calculated by multiple conditional logistic regression for association between maternal vaccination and infant pertussis. Other children in the household, as well as mother- and environmental covariates were taken into account. The VE was calculated as 1 - OR. Mothers of five cases (23%) and of 41 controls (62%) were vaccinated during pregnancy. The adjusted VE was 90.9% (95% confidence interval (CI): 56.6 to 98.1). The only covariate in the final model was breastfeeding (protective effect). Our study provides evidence in favour of pertussis vaccination programmes for pregnant women in order to prevent whooping cough in infants aged less than 3 months.

[Chronic diseases as a priority for the public health surveillance system in Spain]. / Las enfermedades crónicas como prioridad de la vigilancia de la salud pública en España.

At present, epidemiological surveillance in Spain remains focused on the communicable diseases included in the list of notifiable diseases. However, there has been a change in epidemiological pattern that predominated until the last few decades of the twentieth century. Infectious diseases, which used to be the leading causes of morbidity and mortality, have given way to a predominance of chronic diseases. In this regard, progress has been made in the drafting and adoption of specific legal regulations on public health monitoring. However, Spain has yet to develop this legislation which, among other elements, includes the mandate to organize the surveillance of non-communicable diseases in Spain. This article aims to describe some points that should be considered in the development of a national surveillance system linked to existing strategies for the prevention and control of chronic diseases.

Optimal Piecewise Linear Function Approximation for GPU-Based Applications.

Many computer vision and human-computer interaction applications developed in recent years need evaluating complex and continuous mathematical functions as an essential step toward proper operation. However, rigorous evaluation of these kind of functions often implies a very high computational cost, unacceptable in real-time applications. To alleviate this problem, functions are commonly approximated by simpler piecewise-polynomial representations. Following this idea, we propose a novel, efficient, and practical technique to evaluate complex and continuous functions using a nearly optimal design of two types of piecewise linear approximations in the case of a large budget of evaluation subintervals. To this end, we develop a thorough error analysis that yields asymptotically tight bounds to accurately quantify the approximation performance of both representations. It provides an improvement upon previous error estimates and allows the user to control the tradeoff between the approximation error and the number of evaluation subintervals. To guarantee real-time operation, the method is suitable for, but not limited to, an efficient implementation in modern graphics processing units, where it outperforms previous alternative approaches by exploiting the fixed-function interpolation routines present in their texture units. The proposed technique is a perfect match for any application requiring the evaluation of continuous functions; we have measured in detail its quality and efficiency on several functions, and, in particular, the Gaussian function because it is extensively used in many areas of computer vision and cybernetics, and it is expensive to evaluate.

[Invasive pneumococcal disease in the Community of Valencia. Six years of surveillance (2007-2012)]. / Enfermedad neumocócica invasiva en la Comunitat Valenciana. Seis años de vigilancia (2007-2012).

INTRODUCTION: The introduction of conjugated anti-pneumonia vaccines has led to a change in the epidemiology of Invasive Pneumococcal Disease (IPD). The aim of this study is to describe the trends in IPD in the Community of Valencia during the period 2007-2012. MATERIAL AND METHODS: A retrospective, descriptive and longitudinal study was conducted on IPD in the Community of Valencia during the period 2007-2012, The information sources used were the Epidemiological Surveillance Analysis (Análisis de la Vigilancia Epidemiológica (AVE)) and the Valencian Microbiology Network (Red Microbiológica Valenciana (RedMIVA)) of the Valencia Health Department. RESULTS: The incidence of IPD decreased between 2007 and 2012 in all age groups, mainly in the under 5 year-olds, dropping from 30.5 cases to 12.3 cases per 10(5) inhabitants (p< .001). Pneumonia was the principal presentation of the disease, with a decrease in its rates from 6.9 to 4.1 cases per 10(5) inhabitants (p< .001). A gradual, non-significant, reduction from 26% to 12% (p=.23) was observed in the proportion of cases due to the serotypes contained in the heptavalent vaccine (PCV7), mainly in the under 5 year-olds. The cases due to additional serotypes in 13-valent conjugated vaccine (1, 3, 5, 6A, 7F and 19A) also showed a decreasing trend, mainly in vaccinated under 5 year-olds (52.6% vs 14.3%; p=.03), while the cases due to non-vaccine serotypes significantly increased from 42.3% to 56.7% in the general population (p=.002), and from 47.4% to 78.6% in vaccinated under 5 year-olds (p=.08). CONCLUSIONS: The results of this study show a reduction in the incidence of IPD, with a decrease in the proportion of cases produced by vaccine serotypes, and an increase in the proportion of those not vaccinated. Epidemiological Surveillance is necessary to monitor the trends in the disease.

Genomic Investigation of a Legionellosis Outbreak in a Persistently Colonized Hotel.

OBJECTIVES: A long-lasting legionellosis outbreak was reported between November 2011 and July 2012 in a hotel in Calpe (Spain) affecting 44 patients including six deaths. Intensive epidemiological and microbiological investigations were performed in order to detect the reservoirs. METHODS: Clinical and environmental samples were tested for the presence and genetic characterization of Legionella pneumophila. Six of the isolates were subjected to whole-genome sequencing. RESULTS: Sequencing of 14 clinical and 260 environmental samples revealed sequence type (ST) 23 as the main responsible strain for the infections. This ST was found in the spa pool, from where it spread to other hotel public spaces, explaining the ST23 clinical cases, including guests who had not visited the spa. Uncultured clinical specimens showed profiles compatible with ST23, ST578, and mixed patterns. Profiles compatible with ST578 were obtained by direct sequencing from biofilm samples collected from the domestic water system, which provided evidence for the source of infection for non ST23 patients. Whole genome data from five ST23 strains and the identification of different STs and Legionella species showed that different hotel premises were likely colonized since the hotel opening thus explaining how different patients had been infected by distinct STs. CONCLUSIONS: Both epidemiological and molecular data are essential in the investigation of legionellosis outbreaks. Whole-genome sequencing data revealed significant intra-ST variability and allowed to make further inference on the short-term evolution of a local colonization of L. pneumophila.

[Reemergence of measles. Epidemic situation in the Valencian Community during the years 2011 and 2012]. / Reemergencia del sarampión. Situación epidémica en la Comunidad Valenciana durante los años 2011 y 2012.

Measles incidence declined until becomes a sporadic reporting and infrequent notification in the last decade. The reemergence of the disease reached 744 cases in 2012, a rate of 14.50×10(5) inhabitants. A classic design in Public Health Surveillance was performed: retrospective analysis of cumulative incidence and characteristics of the affected subjects. Those dates were in record linkage with Valencia Microbiology Network (RedMIVA). Finally, 976 cases of measles were confirmed in 2011-2012 epidemic period. Time-line distribution shows three waves with amplitude length on 12-15 weeks. Proportion of unvaccinated or unknown subjects came up to 85% of cases. 25 outbreaks were reported, 499 cases associated. In 7 of the 10 community outbreaks early cases were from Roma population unvaccinated. In the city of Valencia was applied post-exposure prophylaxis in 32 schools and was observed low coverage: between 63% and 77% in 8 schools and less than 50% in 4. Serum negative rate was 12.4% and we highlight the rate under 16 months: 44.8%. Cohorts of 20-59 years had negative rates between 13.5 to 5.9%. The origin of the epidemic was the importation of cases to a territory with inadequate immune protection against measles. Its impact and development was conditioned by previous immunization coverage, the social and ethnic pattern of different areas or quarters and the extensive application of post-exposure prophylaxis at school and family contacts of cases.

Estimation of glomerular filtration rate by MDRD-4 IDMS and CKD-EPI in individuals of 60 years of age or older in primary care.

OBJECTIVE: To compare the prevalence and classification of chronic kidney disease (CKD) in accordance with the estimated glomerular filtration rate (eGFR) by MDRD-4 IDMS and CKD-EPI in individuals ≥ 60 years of age in primary care. MATERIAL AND METHODS: Cross-sectional descriptive observational study. Subjects ≥ 60 years treated at 40 primary care centres with serum creatinine determination conducted between 1 January and 31 December 2010 at a single centralised laboratory. EXCLUSION CRITERIA: renal transplantation, home care. VARIABLES: socio-demographic, anthropometric, risk factors and cardiovascular disease as recorded in electronic medical records and serum creatinine concentration by a standardised compensated kinetic Jaffe method with IDMS and eGFR by MDRD-4 IDMS and CKD-EPI. Agreement was analysed using the kappa coefficient and the Bland-Altman graphical method. RESULTS: 97,554 individuals (57.3% women, mean age 70.0 [Q1: 65.0, Q3: 77.0]). Median eGFR with MDRD 78.7 [66.7, 91.0] ml/min/1.73m² (77.9 for women, 79.7 for men, P<.001) and 81.8 [68.5, 90.5] ml/min/1.73 m² (P=.311) with CKD-EPI, eFG(MDRD) prevalence <60 15.0% (16.5% women, 13.1% men and 6.5% in ≤ 70 years, 24%> 70 years) with CKD-EPI 14.2% (15.0% female, 13.0% male, 4.7% in ≤ 70 years, 24.1% in> 70 years) . There was an overall agreement of 85.6% (kappa coefficient = 0.75) in women> 70 years of 86.6% (kappa = 0.77), of 83.2% (kappa = 0.69) in men> 70 years, of 82.7% (kappa = 0.68) in women ≤ 70 years and 90% (kappa = 0.81) in men ≤ 70 years. CONCLUSIONS: CKD-EPI decreased the prevalence of CKD especially in women ≤ 70 years; the prevalence increased in men> 70 years. One in eight individuals with stage 3a was reclassified to no disease; reclassified individuals had lower comorbidity.

Dehydroepiandrosterone sulfate levels reflect endogenous luteinizing hormone production and response to human chorionic gonadotropin challenge in older female macaque (Macaca fascicularis).

OBJECTIVE: We propose that the adrenal gland of an older higher primate female animal model will respond to human chorionic gonadotropin (hCG) hormone challenge by secreting additional dehydroepiandrosterone sulfate (DHEAS). Such a response in surgically and chemically castrated animals will provide proof of concept and a validated animal model for future studies to explore the rise in DHEAS during the menopausal transition of women. METHODS: Twenty-four 18- to 26-year-old female cynomolgus monkeys were screened for ovarian function and then either ovariectomized (n = 4) or treated with a gonadotropin-releasing hormone agonist (GnRHa; n = 20) to block ovarian steroid production. After a recovery period from surgical procedure or down-regulation, a single-dose challenge (1,000 IU/animal, IM) of hCG was then administered to determine if luteinizing hormone (LH)/chorionic gonadotropin could accelerate circulating DHEAS production. Serum DHEAS, bioactive LH, and urinary metabolites of ovarian sex steroids were monitored before, during, and after these treatments. RESULTS: Circulating LH bioactivity and immunoreactive DHEAS concentrations were suppressed in all animals 14 days postadministration of GnRHa. Urinary metabolites of estradiol and progesterone remained low after the surgical procedure or a flare reaction to GnRHa. Circulating DHEAS levels were increased after hCG administration, and the increase in individual animals was proportional to the pretreatment DHEAS at baseline. Circulating DHEAS concentrations were positively correlated to endogenous LH bioactive concentrations prior to hCG challenge and were subsequently further elevated by the hCG challenge while no concomitant change in ovarian steroid hormone excretion was observed. CONCLUSIONS: These data demonstrate a positive adrenal androgen response to LH/chorionic gonadotropin in older female higher primates and suggest a mechanism for the rise in adrenal androgen production during the menopausal transition in women. These results also illustrate that the nonhuman primate animal model can be effectively used to investigate this phenomenon.

[Cardiovascular morbidity and mortality and electrocardiographic criteria of left ventricular hypertrophy in hypertensive patients treated in primary care]. / Morbilidad y mortalidad cardiovascular y criterios electrocardiográficos de hipertrofia ventricular izquierda en pacientes hipertensos en atención primaria.

UNLABELLED: FUNDAMENTALS AND OBJECTIVE: Electrocardiographic voltage criteria are the preferred method for diagnosis of left ventricular hypertrophy (LVH) in Primary Health Care (PHC). Several of these have been described as major adverse cardiovascular events (MACE) predictors. The aim of this study was to analyse the relationship between MACE occurrence in a cohort of hypertensive subjects in PHC and different electrocardiographic criteria recorded. PATIENTS AND METHODS: 265 hypertensive subjects attending PHC were randomly selected and followed up for 12 years. Standard 12-lead electrocardiograms were recorded at the beginning of the study. The occurrence of ischemic heart disease, heart failure, stroke, peripheral vascular disease, arrhythmia or cardiovascular death was considered as MACE. Electrocardiographic voltage criteria recorded were: Sokolow-Lyon, Minnesota code 3.1, Gubner and Ungerleider, Cornell voltage and Schillaci and Dalfó modifications. Data were analyzed using the life-table method and Cox regression models. RESULTS: 14,3% of patients lost to follow-up showed no differences in baseline characteristics from the rest of the cohort. The median follow-up was 10.1 years (IQR: 5.8-12.0). The cumulative survival rate was 53.5% (95% CI, 45.7-61.3%). The incidence of MACE was 5.85 (95% CI, 4.73-6.97) per 100 hypertensive patients-year. In the multivariate analysis none of the ECG criteria showed statistical association with the occurrence of MACE. CONCLUSIONS: No association has been found between different electrocardiographic LVH criteria and the incidence of MACE in a cohort of hypertensive patients followed-up in a PHC setting for 12 years.

[Pandemic influenza surveillance in the valencian community and seasonal influenza vaccines]. / Vigilancia de la gripe pandémica en la Comunidad Valenciana y vacuna antigripal estacional.

BACKGROUND: Surveillance of Pandemic influenza was carried out in the Valencian Community. Some effectiveness studies of the seasonal vaccine for AnH1N1 virus have presented no consistent results. The objective of the work consists on describing the results of the epidemic surveillance and effectiveness of the seasonal vaccine for pandemic influenza in the weeks 28 to 51, 2009. METHODS: We studied the cases in primary care, hospitalized confirmed, Polimerase Chain Reaction (PCR) and viral isolates and vaccine coverage. Vaccine effectiveness was calculated by the Farrington method of screening method, in three age groups, and two periods: vaccinated 2008-9 and 2009-10 seasons. RESULTS: In the first period (weeks 28-40) the incidence rates were highest in the group of 15-64 years (7207 cases), followed by those under 15 years (1596 cases). In the second period (weeks 45-47) children under 15 years (28218 cases) were the most affected. In both periods incidence in patients older than 65 years was low (rates of 56,3 and 125,1 respectively). In the studied period (weeks 28 at 51) 5481 cases were confirmed, of those that 1746 (31,8%) were hospitalized. The curve of hospitalization rate showed a profile similar to those in primary care and also in microbiological surveillance of the virus. The vaccine effectiveness in the second period was 25% in adults between 15 and 64 years and 51% in those older than 64 years. CONCLUSIONS: There is an age-dependent protection with positive vaccine efficacy in the elderly, although it may be confounded by natural exposure to the virus, previous immunizations or immune response.

Cardiovascular morbidity and mortality and left ventricular geometric patterns in hypertensive patients treated in primary care.

INTRODUCTION AND OBJECTIVES: Numerous hospital studies have shown that different left ventricular (LV) geometric patterns have different effects on cardiovascular risk. The aims of this study were to estimate the risk of major adverse cardiovascular events (MACEs) in hypertensive patients seen in primary care and to identify any association with LV geometric pattern. METHODS: In total, 265 hypertensive subjects attending primary care were randomly selected and followed up for 12 years. Those with cardiovascular disease, secondary hypertension, complete bundle branch block or electrocardiographic signs of ischemic heart disease were excluded. The LV geometric pattern was characterized as either concentric hypertrophy, eccentric hypertrophy, concentric remodeling or normal. A MACE was the occurrence of ischemic heart disease, heart failure, stroke, peripheral vascular disease, arrhythmia or cardiovascular death. Data were analyzed using the life-table method and Cox regression modeling. RESULTS: Although 14% of patients were lost to follow-up, their baseline characteristics were similar to those of patients who completed the study. The cumulative survival rate was 56.3% (95% confidence interval [CI], 49.8%-62.8%). The incidence of MACEs was 4.67 (95% CI, 3.79-5.55) per 100 subject-years. Moreover, the incidence was similar in the four LV geometric pattern groups (P=.889). Only age (hazard ratio [HR]=1.03; 95% CI, 1-1.05) and the presence of diabetes at study entry (HR=1.67; 95% CI, 1.03-2.69) were associated with an increased risk of a MACE. CONCLUSIONS: In the study population, only age and diabetes at study entry were associated with the occurrence of a MACE. There was no evidence for an association between MACEs and the LV geometric pattern.

[Real time information. A necessary tool in epidemiological surveillance]. / La información en tiempo real. Una herramienta necesaria en vigilancia epidemiológica.

Since 2004 an electronic epidemiological surveillance system (AVE) has been developed and implemented for infectious diseases in the autonomous region of Valencia that allows data collection from notifiable diseases in real time concerning outbreaks and alerts, as well as analysis and dissemination of the information. Within the autonomous region of Valencia, the system is used by 17 epidemiology units, which act as the first level of specialized surveillance. The electronic surveillance system is used by all these units, as well as by physicians working in primary and specialized care, who can introduce information from the ambulatory information system while the patient is in the practice room. The system is able to capture the demographic data from the patient and the physician can add any other information that is considered important for the case detected. The system receives new laboratory test results overnight from the Microbiological Surveillance Network (RedMIVA). AVE can record outbreaks of notifiable diseases as well as any unusual clusters or changing patterns of any disease. The department of epidemiology has access to the whole system for analysis of the information and for quality control of the epidemiological surveillance. The system provides timely and comprehensive information to facilitate public health action in individual cases of infectious disease.

Circulating bioactive androgens in midlife women.

CONTEXT: It is important to characterize the biological activity of circulating androgenic steroid hormones during the menopausal transition because these appear to impact the metabolic and cardiovascular health risk factors of women. OBJECTIVE: The objective of the study was to develop and characterize a cell-based bioassay that measures the androgen receptor-mediated signal transduction in serum. DESIGN: This was a clinically relevant experimental study nested in a sample population of a longitudinal cohort study. SETTING: The study was conducted at a university laboratory. METHODS: A receptor-mediated luciferase expression bioassay based on HEK 293 cells that were stably cotransfected with plasmids containing the human androgen receptor and luciferase gene was developed. In 49 samples from menstruating women aged 42-52 yr, total testosterone (T) and SHBG concentrations were measured by immunoassay; free T concentrations were calculated from the total T and SHBG concentrations. RESULTS: Mean total T concentration of the sample was 1.15 nm (sd 0.46, range 0.57-3.86 nm). The mean bioactive androgen detected was 1.00 nm (sd 0.24, range 0.53-1.60 nm). Calculated free T (mean 0.0156 nm) was significantly lower than the levels of bioactive androgens measured by receptor-mediated bioassay. There was significant positive correlation between bioactive androgen levels and total T values in young women and polycystic ovarian disorder patients, whereas no correlation was found between the two values in middle-aged women. CONCLUSIONS: An androgen receptor-mediated bioassay can provide additional information in the evaluation of total bioactive androgens in midlife women. Our data suggest that levels of circulating SHBG may have a significant impact on the levels of total circulating bioavailable androgens.

[Impact of immigration on drug resistance to Mycobacterium tuberculosis in Castellon (Spain): 1995-2003]. / Impacto de la inmigración en las resistencias de Mycobacterium tuberculosis en la provincia de Castellón: 1995-2003.

BACKGROUND AND OBJECTIVE: The aim of this study was to know the frequency of resistant Mycobacterium tuberculosis in the province of Castellon (Spain) and to determine whether immigration is associated with resistance. MATERIAL AND METHOD: All culture-positive cases diagnosed in Castellon from January 1995 to December 2003 were included in this retrospective study. Susceptibility tests were performed using the Canetti's proportion method and the MB/BacT system. Risk factors associated with tuberculosis were investigated in every case. RESULTS: Six hundred and forty-four cases of tuberculosis were studied: 560 were Spaniards and 84 foreigners. The overall frequency of resistant strains was 5%. The total rate of resistance in Spaniards was 3.7% and in foreigners 13.1%. In Spanish new cases, drug resistance was 3.2% and in foreigners new cases it was 13.9%. In previously treated cases, drug resistance was 6.7% in Spaniards and 0% in immigrants. No acquired drug resistance was detected in immigrants. Of those strains with resistance, 71.9% had resistance to only one drug, 18.7% to two drugs and 9.4% to more than two drugs. Multidrug-resistance was found in 9.4% of the resistant cases, and in 0.5% of all the studied population. The presence of resistant Mycobacterium tuberculosis was associated with the fact of having a foreign nationality (OR = 3.87; p < 0.001). CONCLUSIONS: Tuberculosis has been diminishing in Spanish patients in Castellon. Nevertheless, there is an important increase in the number of cases in foreigners, which is associated with a major percentage of resistances. Epidemiological vigilance efforts should especially concentrate on this group in order to support the progressive declivity of the disease.