Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.

BACKGROUND: Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period. METHODS: The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses. RESULTS: Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo. CONCLUSIONS: Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence.

Knowledge of stroke warning symptoms and intended action in response to stroke in Spain: a nationwide population-based study.

BACKGROUND: Worldwide thrombolysis rates remain suboptimal. Ambulance transfer is associated with greater use of this time-dependent treatment. Information on public awareness of stroke symptoms is important for planning effective education programs to promote calling of emergency services for suspected stroke. However, there is a paucity of data on this subject in European countries. Our objectives were to explore the recognition of stroke symptoms, awareness of the need to activate the emergency medical services for acute stroke events, and the association between knowledge of warning symptoms and intent to call for an ambulance among a sample representative of the adult population of Spain. This is the largest study on this subject to date in Europe. METHODS: The data were taken from the Study on Nutrition and Cardiovascular Risk in Spain, a cross-sectional study conducted in a sample representative of the Spanish noninstitutionalized population aged ≥18 years in 2008-2010. Study participants were selected by multistage clustered random sampling. The households within each section were selected by random telephone dialing using the landline telephone directory as the sampling frame. Subjects in the households were selected proportionally to the distribution of the population of Spain by sex and age. The study included a computer-assisted telephone interview on stroke symptom knowledge and the first action to perform in a stroke event, based on the American Heart Association and American Stroke Association recommendations, and two home visits to perform a physical examination and to obtain blood samples. RESULTS: Among 11,827 adults, 7,711 (65.2%; 95% CI = 64.1-66.3) identified 4-6 stroke warning symptoms, considered as adequate knowledge. A total of 1,348 (11.4%) were unable to classify any of the symptoms correctly. In the multivariate analysis, higher education was significantly associated with better knowledge of symptoms, and age ≥65 years, fair/poor self-rated health, history of obesity and known diabetes were significantly associated with less knowledge of stroke symptoms. One in 5 individuals indicated they would do something other than calling for an ambulance if they thought someone was having a stroke. The number of specific stroke warning symptoms known was directly associated with the intent to call an ambulance in a stroke event (OR adjusted for sociodemographic and clinical variables = 1.06 per symptom, 95% CI = 1.03-1.09; p < 0.001). CONCLUSIONS: In this population-based study, stroke symptom knowledge was suboptimal and only modestly associated with the intent to call for an ambulance. Educational interventions are needed to link stroke recognition more strongly to an immediate need to call for an ambulance in order to increase stroke patients' access to thrombolysis.

Differences in complexity of glycemic profile in survivors and nonsurvivors in an intensive care unit: a pilot study.

OBJECTIVE: To investigate glycemic dynamics and its relation with mortality in critically ill patients. We searched for differences in complexity of the glycemic profile between survivors and nonsurvivors in patients admitted to a multidisciplinary intensive care unit. DESIGN: Prospective, observational study, convenience sample. SETTINGS: Multidisciplinary intensive care unit of a teaching hospital in Madrid, Spain. PATIENTS: A convenience sample of 42 patients, aged 29 to 86 yrs, admitted to an intensive care unit with an Acute Physiology and Chronic Health Evaluation II score of >or=14 and with an anticipated intensive care unit stay of >72 hrs. INTERVENTIONS: A continuous glucose monitoring system was used to measure subcutaneous interstitial fluid glucose levels every 5 mins for 48 hrs during the first days of intensive care unit stay. A 24-hr period (n = 288 measurements) was used as time series for complexity analysis of the glycemic profile. MEASUREMENTS: Complexity of the glycemic profile was evaluated by means of detrended fluctuation analysis. Other conventional measurements of variability (range, sd, and Mean Amplitude of Glycemic Excursions) were also calculated. MAIN RESULTS: Ten patients died during their intensive care unit stay. Glycemic profile was significantly more complex (lower detrended fluctuation analysis) in survivors (mean detrended fluctuation analysis, 1.49; 95% confidence interval, 1.44-1.53) than in nonsurvivors (1.60; 95% confidence interval, 1.52-1.68). This difference persisted after accounting for the presence of diabetes. In a logistic regression model, the odds ratio for death was 2.18 for every 0.1 change in detrended fluctuation analysis.Age, gender, Simplified Acute Physiologic Score 3 or Acute Physiologic and Chronic Health Evaluation II scores failed to explain differences in survivorship. Conventional variability measurements did not differ between survivors and nonsurvivors. CONCLUSIONS: Complexity of the glycemic profile of critically ill patients varies significantly between survivors and nonsurvivors. Loss of complexity in glycemia time series, evaluated by detrended fluctuation analysis, is associated with higher mortality.

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 1000 consecutive cases.

AIM: To analyse the clinical features, laboratory data and foetal-maternal outcomes, and follow them up on a cohort of 1000 women with obstetric antiphospholipid syndrome (OAPS). METHODS: The European Registry of OAPS became a registry within the framework of the European Forum on Antiphospholipid Antibody projects and was placed on a website in June 2010. Thirty hospitals throughout Europe have collaborated to carry out this registry. Cases with obstetric complaints related to antiphospholipid antibodies (aPL) who tested positive for aPL at least twice were included prospectively and retrospectively. The seven-year survey results are reported. RESULTS: 1000 women with 3553 episodes were included of which 2553 were historical and 1000 were latest episodes. All cases fulfilled the Sydney classification criteria. According to the laboratory categories, 292 (29.2%) were in category I, 357 (35.7%) in IIa, 224 (22.4%) in IIb and 127 (12.7%) in IIc. Miscarriages were the most prevalent clinical manifestation in 386 cases (38.6%). Moreover, the presence of early preeclampsia (PE) and early foetal growth restriction (FGR) appeared in 181 (18.1%) and 161 (16.1%), respectively. In this series, 448 (44.8%) women received the recommended OAPS treatment. Patients with recommended treatment had a good live-birth rate (85%), but worse results (72.4%) were obtained in patients with any treatment (low-dose aspirin (LDA) or low-molecular-weight heparin (LMWH) not on recommended schedule, while patients with no treatment showed a poor birth rate (49.6%). CONCLUSION: In this series, recurrent miscarriage is the most frequent poor outcome. To avoid false-negative diagnoses, all laboratory category subsets were needed. OAPS cases have very good foetal-maternal outcomes when treated. Results suggest that we were able to improve our clinical practice to offer better treatment and outcomes to OAPS patients.

Comparative study between obstetric antiphospholipid syndrome and obstetric morbidity related with antiphospholipid antibodies.

BACKGROUND AND OBJECTIVES: To compare clinical, laboratory, treatment and live birth rate data between women with aPL-related obstetric complications (OMAPS) not fulfilling the Sydney criteria and women fulfilling them (OAPS). MATERIALS AND METHODS: Retrospective and prospective multicentre study. Data comparison between groups from The European Registry on Antiphospholipid Syndrome included within the framework of the European Forum on Antiphospholipid Antibody projects. RESULTS: 338 women were analysed: 247 fulfilled the Sydney criteria (OAPS group) and 91 did not (OMAPS group). In the OMAPS group, 24/91 (26.37%) fulfilled laboratory Sydney criteria (subgroup A) and 67/91 (74.63%) had a low titre and/or non-persistent aPL-positivity (subgroup B). Overall, aPL laboratory categories in OAPS vs. OMAPS showed significant differences: 34% vs. 11% (p<0.0001) for category I, 66% vs. 89% (p<0.0001) for category II. No differences were observed when current obstetric complications were compared (p=0.481). 86.20% of OAPS women were treated vs. 75.82% of OMAPS (p=0.0224), particularly regarding the LDA+LMWH schedule (p=0.006). No differences between groups were observed in live births, gestational, puerperal arterial and/or venous thrombosis. CONCLUSIONS: Significant differences were found among aPL categories between groups. Treatment rates were higher in OAPS. Both OAPS and OMAPS groups had similarly good foetal-maternal outcomes when treated. The proposal to modify OAPS classification criteria, mostly laboratory requirements, is reinforced by these results.

The European Registry on Obstetric Antiphospholipid Syndrome (EUROAPS): A survey of 247 consecutive cases.

AIM: To analyse the clinical features, laboratory data, foetal-maternal outcomes, and follow-up in a cohort of 247 women with obstetric antiphospholipid syndrome (OAPS). METHODS: The European Registry on APS became a Registry within the framework of the European Forum on Antiphospholipid Antibody projects and placed on a website in June 2010. Cases with obstetric complaints related to aPL who tested positive for aPL prospectively and retrospectively were included. The three-year survey results are reported. RESULTS: 338 women with 1253 pregnancy episodes were included; 915 were historical and 338 were latest episodes. All these women tested positive for aPL. 247 of the 338 fulfilled the Sydney criteria. According to the laboratory categories, 84/247 were in category I, 42 in IIa, 66 in IIb and 55 in IIc. Obstetric complications other than foetal losses, appeared in 129 cases (52.2%). 192 (77.7%) had a live birth and 55 (22.3%) did not. The latter group of only 38 cases (69%) received adequate treatment and 17 (31%) did not. 177/247 (72%) women were put on heparin plus LDA. Thrombosis appeared in two during pregnancy and in 14 during the puerperium. 7 (3%) women evolved to complete SLE. CONCLUSIONS: OAPS shows differential characteristics than classical APS. All laboratory test categories are needed to avoid false-negative diagnoses. In some cases, complement levels could act as a serological marker. OAPS has very good foetal-maternal outcomes when treated. Thrombosis and progression to SLE in mothers with OAPS are scarce compared with "classical APS", suggesting that they have different aPL-mediated pathogenic mechanisms.

Gut microbiota as an epigenetic regulator: pilot study based on whole-genome methylation analysis.

UNLABELLED: The core human gut microbiota contributes to the developmental origin of diseases by modifying metabolic pathways. To evaluate the predominant microbiota as an epigenetic modifier, we classified 8 pregnant women into two groups based on their dominant microbiota, i.e., Bacteroidetes, Firmicutes, and Proteobacteria. Deep sequencing of DNA methylomes revealed a clear association between bacterial predominance and epigenetic profiles. The genes with differentially methylated promoters in the group in which Firmicutes was dominant were linked to risk of disease, predominantly to cardiovascular disease and specifically to lipid metabolism, obesity, and the inflammatory response. This is one of the first studies that highlights the association of the predominant bacterial phyla in the gut with methylation patterns. Further longitudinal and in-depth studies targeting individual microbial species or metabolites are recommended to give us a deeper insight into the molecular mechanism of such epigenetic modifications. IMPORTANCE: Epigenetics encompasses genomic modifications that are due to environmental factors and do not affect the nucleotide sequence. The gut microbiota has an important role in human metabolism and could be a significant environmental factor affecting our epigenome. To investigate the association of gut microbiota with epigenetic changes, we assessed pregnant women and selected the participants based on their predominant gut microbiota for a study on their postpartum methylation profile. Intriguingly, we found that blood DNA methylation patterns were associated with gut microbiota profiles. The gut microbiota profiles, with either Firmicutes or Bacteroidetes as a dominant group, correlated with differential methylation status of gene promoters functionally associated with cardiovascular diseases. Furthermore, differential methylation of gene promoters linked to lipid metabolism and obesity was observed. For the first time, we report here a position of the predominant gut microbiota in epigenetic profiling, suggesting one potential mechanism in obesity with comorbidities, if proven in further in-depth studies.

The burden of blood-pressure-related cardiovascular mortality in Mexico.

This study shows that in Mexico, a country at an advanced stage in the epidemiologic transition, with the national burden of disease dominated by noncommunicable diseases, elevated blood pressure is a major clinical and public health problem. 31.7% of the Mexican individuals aged 50 and over had systolic hypertension, and 47.3% were at systolic prehypertensive levels. Also, approximately half of all cardiovascular deaths that occurred annually in the population of Mexico aged ≥50 years are attributable to above optimal levels of systolic blood pressure. We think these estimates may help order health priorities in Mexico (and other middle-income countries) at a time when the costs of medical care take a considerable share of the gross national product in most countries.

Physician perception of blood pressure control and treatment behavior in high-risk hypertensive patients: a cross-sectional study.

OBJECTIVE: We examined physician perception of blood pressure control and treatment behavior in patients with previous cardiovascular disease and uncontrolled hypertension as defined by European Guidelines. METHODS: A cross-sectional study was conducted in which 321 primary care physicians throughout Spain consecutively studied 1,614 patients aged ≥18 years who had been diagnosed and treated for hypertension (blood pressure ≥140/90 mmHg), and had suffered a documented cardiovascular event. The mean value of three blood pressure measurements taken using standardized procedures was used for statistical analysis. RESULTS: Mean blood pressure was 143.4/84.9 mmHg, and only 11.6% of these cardiovascular patients were controlled according to 2007 European Guidelines for Hypertension Management target of <130/80 mmHg. In 702 (49.2%) of the 1426 uncontrolled patients, antihypertensive medication was not changed, and in 480 (68.4%) of these cases this was due to the physicians judgment that blood pressure was adequately controlled. In 320 (66.7%) of the latter patients, blood pressure was 130-139/80-89 mmHg. Blood pressure level was the main factor associated (inversely) with no change in treatment due to physician perception of adequate control, irrespective of sociodemographic and clinical factors. CONCLUSIONS: Physicians do not change antihypertensive treatment in many uncontrolled cardiovascular patients because they considered it unnecessary, especially when the BP values are only slightly above the guideline target. It is possible that the guidelines may be correct, but there is also the possibility that the care by the physicians is appropriate since BP <130/80 mmHg is hard to achieve, and recent reviews suggest there is insufficient evidence to support such a low BP target.

Comparative study between obstetric antiphospholipid syndrome and obstetric morbidity related with antiphospholipid antibodies / Estudio comparativo entre síndrome antifisfolipídico obstétrico y morbilidad obstétrica relacionada con anticuerpos antifosfolípido

Background and objectives: To compare clinical, laboratory, treatment and live birth rate data between women with aPL-related obstetric complications (OMAPS) not fulfilling the Sydney criteria and women fulfilling them (OAPS). Materials and methods: Retrospective and prospective multicentre study. Data comparison between groups from The European Registry on Antiphospholipid Syndrome included within the framework of the European Forum on Antiphospholipid Antibody projects. Results: 338 women were analysed: 247 fulfilled the Sydney criteria (OAPS group) and 91 did not (OMAPS group). In the OMAPS group, 24/91 (26.37%) fulfilled laboratory Sydney criteria (subgroup A) and 67/91 (74.63%) had a low titre and/or non-persistent aPL-positivity (subgroup B). Overall, aPL laboratory categories in OAPS vs. OMAPS showed significant differences: 34% vs. 11% (p<0.0001) for category I, 66% vs. 89% (p<0.0001) for category II. No differences were observed when current obstetric complications were compared (p=0.481). 86.20% of OAPS women were treated vs. 75.82% of OMAPS (p=0.0224), particularly regarding the LDA+LMWH schedule (p=0.006). No differences between groups were observed in live births, gestational, puerperal arterial and/or venous thrombosis. Conclusions: Significant differences were found among aPL categories between groups. Treatment rates were higher in OAPS. Both OAPS and OMAPS groups had similarly good foetal-maternal outcomes when treated. The proposal to modify OAPS classification criteria, mostly laboratory requirements, is reinforced by these results

Fundamento Y objetivos: Comparar características clínicas, analíticas, tratamiento y tasa de hijos vivos entre gestantes con Síndrome Antifosfolípido Obstétrico (SAFO) y gestantes con morbilidad obstétrica relacionada con el síndrome que no cumplen los criterios de clasificación actuales. Material Y métodos: Estudio observacional retrospectivo y prospectivo multicéntrico: datos de once hospitales terciarios europeos recogidos en el European Registry on Antiphospholipid Syndrome. Resultados: Se analizaron 338 mujeres: 247 cumplían criterios de Sydney para SAFO (grupo OAPS), y 91 no (grupo OMAPS). En el grupo OMAPS, 24/91(26.37%) cumplían criterios analíticos, pero no clínicos para SAFO (subgrupo A) y 67/91(74.63%) presentaban títulos medio-bajos o títulos positivos no persistentes de anticuerpos antifosfolípido, con o sin cumplir criterios clínicos (subgrupo B). Se observaron diferencias significativas entre los 2 grupos en cuanto a las categorías analíticas: 34% vs. 11% (p<0.0001) para la categoría I y 66% vs. 89% (p<0.0001) para la categoría II, OAPS vs OMAPS, respectivamente. No se observaron diferencias significativas en cuanto a las complicaciones obstétricas (p=0.481). El 86.20% del grupo OAPS recibió tratamiento vs.el 75.82% del grupo OMAPS (p=0.0224). No se observaron diferencias en la tasa de hijos vivos, ni en la tasa de trombosis arterial y/o venosa gestacional y/o puerperal. Conclusiones: Ambos grupos fueron muy homogéneos, excepto en cuanto a la distribución de las categorías analíticas y en la tasa de tratamiento. Ambos grupos mostraron buenos resultados al ser tratados. Los resultados respaldan la opinión de muchos expertos de tener que revisar los criterios de clasificación actuales del Síndrome Antifosfolípido Obstétrico

Gota deformante / Deforming Gout

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