Hospital de Clínicas

The interest in the systematic study of the circadian typology (CT) is relatively recent and has developed rapidly in the two last decades. All the existing data suggest that this individual difference affects our biological and psychological functioning, not only in health, but also in disease. In the present study, we review the current literature concerning the psychometric properties and validity of CT measures as well as individual, environmental and genetic factors that influence the CT. We present a brief overview of the biological markers that are used to define differences between CT groups (sleep-wake cycle, body temperature, cortisol and melatonin), and we assess the implications for CT and adjustment to shiftwork and jet lag. We also review the differences between CT in terms of cognitive abilities, personality traits and the incidence of psychiatric disorders. When necessary, we have emphasized the methodological limitations that exist today and suggested some future avenues of work in order to overcome these. This is a new field of interest to professionals in many different areas (research, labor, academic and clinical), and this review provides a state of the art discussion to allow professionals to integrate chronobiological aspects of human behavior into their daily practice.

BACKGROUND: Kangaroo mother care (KMC), originally defined as skin-to-skin contact between a mother and her newborn, frequent and exclusive or nearly exclusive breastfeeding, and early discharge from hospital, has been proposed as an alternative to conventional neonatal care for low birthweight (LBW) infants. OBJECTIVES: To determine whether evidence is available to support the use of KMC in LBW infants as an alternative to conventional neonatal care before or after the initial period of stabilization with conventional care, and to assess beneficial and adverse effects. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches in CENTRAL (Cochrane Central Register of Controlled Trials; 2016, Issue 6), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Latin American and Caribbean Health Science Information database), and POPLINE (Population Information Online) databases (all from inception to June 30, 2016), as well as the WHO (World Health Organization) Trial Registration Data Set (up to June 30, 2016). In addition, we searched the web page of the Kangaroo Foundation, conference and symposia proceedings on KMC, and Google Scholar. SELECTION CRITERIA: Randomized controlled trials comparing KMC versus conventional neonatal care, or early-onset KMC versus late-onset KMC, in LBW infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis were performed according to the methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Twenty-one studies, including 3042 infants, fulfilled inclusion criteria. Nineteen studies evaluated KMC in LBW infants after stabilization, one evaluated KMC in LBW infants before stabilization, and one compared early-onset KMC with late-onset KMC in relatively stable LBW infants. Sixteen studies evaluated intermittent KMC, and five evaluated continuous KMC. KMC versus conventional neonatal care: At discharge or 40 to 41 weeks' postmenstrual age, KMC was associated with a statistically significant reduction in the risk of mortality (risk ratio [RR] 0.60, 95% confidence interval [CI] 0.39 to 0.92; eight trials, 1736 infants), nosocomial infection/sepsis (RR 0.35, 95% CI 0.22 to 0.54; five trials, 1239 infants), and hypothermia (RR 0.28, 95% CI 0.16 to 0.49; nine trials, 989 infants; moderate-quality evidence). At latest follow-up, KMC was associated with a significantly decreased risk of mortality (RR 0.67, 95% CI 0.48 to 0.95; 12 trials, 2293 infants; moderate-quality evidence) and severe infection/sepsis (RR 0.50, 95% CI 0.36 to 0.69; eight trials, 1463 infants; moderate-quality evidence). Moreover, KMC was found to increase weight gain (mean difference [MD] 4.1 g/d, 95% CI 2.3 to 5.9; 11 trials, 1198 infants; moderate-quality evidence), length gain (MD 0.21 cm/week, 95% CI 0.03 to 0.38; three trials, 377 infants) and head circumference gain (MD 0.14 cm/week, 95% CI 0.06 to 0.22; four trials, 495 infants) at latest follow-up, exclusive breastfeeding at discharge or 40 to 41 weeks' postmenstrual age (RR 1.16, 95% CI 1.07 to 1.25; six studies, 1453 mothers) and at one to three months' follow-up (RR 1.20, 95% CI 1.01 to 1.43; five studies, 600 mothers), any (exclusive or partial) breastfeeding at discharge or at 40 to 41 weeks' postmenstrual age (RR 1.20, 95% CI 1.07 to 1.34; 10 studies, 1696 mothers; moderate-quality evidence) and at one to three months' follow-up (RR 1.17, 95% CI 1.05 to 1.31; nine studies, 1394 mothers; low-quality evidence), and some measures of mother-infant attachment and home environment. No statistically significant differences were found between KMC infants and controls in Griffith quotients for psychomotor development at 12 months' corrected age (low-quality evidence). Sensitivity analysis suggested that inclusion of studies with high risk of bias did not affect the general direction of findings nor the size of the treatment effect for main outcomes. Early-onset KMC versus late-onset KMC in relatively stable infants: One trial compared early-onset continuous KMC (within 24 hours post birth) versus late-onset continuous KMC (after 24 hours post birth) in 73 relatively stable LBW infants. Investigators reported no significant differences between the two study groups in mortality, morbidity, severe infection, hypothermia, breastfeeding, and nutritional indicators. Early-onset KMC was associated with a statistically significant reduction in length of hospital stay (MD 0.9 days, 95% CI 0.6 to 1.2). AUTHORS' CONCLUSIONS: Evidence from this updated review supports the use of KMC in LBW infants as an alternative to conventional neonatal care, mainly in resource-limited settings. Further information is required concerning the effectiveness and safety of early-onset continuous KMC in unstabilized or relatively stabilized LBW infants, as well as long-term neurodevelopmental outcomes and costs of care.

Urinary tract infections (UTIs) are the most common outpatient infections, with a lifetime incidence of 50-60% in adult women. This is a narrative review aimed at acting as an introduction to the epidemiology and burden of UTIs. This review is based on relevant literature according to the experience and expertise of the authors. The prevalence of UTI increases with age, and in women aged over 65 is approximately double the rate seen in the female population overall. Etiology in this age group varies by health status with factors such as catheterization affecting the likelihood of infection and the pathogens most likely to be responsible. In younger women, increased sexual activity is a major risk factor for UTIs and recurrence within 6 months is common. In the female population overall, more serious infections such as pyelonephritis are less frequent but are associated with a significant burden of care due to the risk of hospitalization. Healthcare-associated UTIs (HAUTIs) are the most common form of healthcare-acquired infection. Large global surveys indicate that the nature of pathogens varies between the community and hospital setting. In addition, the pathogens responsible for HAUTIs vary according to region making adequate local data key to infection control. UTIs create a significant societal and personal burden, with a substantial number of medical visits in the United States every year being related to UTIs. European data indicate that recurrent infections are related to increased absenteeism and physician visits. In addition, quality of life measures are significantly impacted in women suffering from recurrent UTIs. Data suggest that nonantimicrobial prophylactic strategies offer an opportunity to reduce both the rate of UTIs and the personal burden experience by patients.

BACKGROUND: Immediate-function Brånemark System implants (Nobel Biocare AB, Gothenburg, Sweden) have become an accepted alternative for fixed restorations in edentulous mandibles, based on documented high success rates. Continuous development is ongoing to find simple protocols for their use. PURPOSE: The purpose of this study was to develop and document a simple, safe, and effective surgical and prosthetic protocol for immediate function (within 2 hours) of four Brånemark System implants supporting fixed prostheses in completely edentulous mandibles: the "All-on-Four" concept. MATERIALS AND METHODS: This retrospective clinical study included 44 patients with 176 immediately loaded implants, placed in the anterior region, supporting fixed complete-arch mandibular prostheses in acrylic. In addition to the immediately loaded implants, 24 of the 44 patients had 62 rescue implants not incorporated in the provisional prostheses but incorporated in final prostheses later on. RESULTS: Five immediately loaded implants were lost in five patients before the 6-month follow-up, giving cumulative survival rates of 96.7 and 98.2% for development and routine groups, respectively. The prostheses' survival was 100%, and the average bone resorption was low. CONCLUSIONS: The high cumulative implant and prostheses survival rates indicate that the "All-on-Four" immediate-function concept with Brånemark System implants used in completely edentulous mandibles is a viable concept.

RATIONALE: Recent literature in mechanical ventilation includes strong evidence from randomized trials. Little information is available regarding the influence of these trials on usual clinical practice. OBJECTIVES: To describe current mechanical ventilation practices and to assess the influence of interval randomized trials when compared with findings from a 1998 cohort. METHODS: A prospective international observational cohort study, with a nested comparative study performed in 349 intensive care units in 23 countries. We enrolled 4,968 consecutive patients receiving mechanical ventilation over a 1-month period. We recorded demographics and daily data related to mechanical ventilation for the duration of ventilation. We systematically reviewed the literature and developed 11 practice-change hypotheses for the comparative cohort study before seeing these results. In assessing practice changes, we only compared data from the 107 intensive care units (1,675 patients) that also participated in the 1998 cohort (1,383 patients). MEASUREMENTS AND MAIN RESULTS: In 2004 compared with 1998, the use of noninvasive ventilation increased (11.1 vs. 4.4%, P < 0.001). Among patients with acute respiratory distress syndrome, tidal volumes decreased (7.4 vs. 9.1 ml/kg, P < 0.001) and positive end-expiratory pressure levels increased slightly (8.7 vs. 7.7 cm H(2)O, P = 0.02). More patients were successfully extubated after their first attempt of spontaneous breathing (77 vs. 62%, P < 0.001). Use of synchronized intermittent mandatory ventilation fell dramatically (1.6 vs. 11%, P < 0.001). Observations confirmed 10 of our 11 practice-change hypotheses. CONCLUSIONS: The strong concordance of predicted and observed practice changes suggests that randomized trial results have advanced mechanical ventilation practices internationally.

RATIONALE: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES: To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

BACKGROUND: Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012. OBJECTIVES: To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty). AUTHORS' CONCLUSIONS: Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.

RATIONALE: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection. OBJECTIVES: The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure. METHODS: Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry. MEASUREMENTS AND MAIN RESULTS: Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diffuse alveolar damage was present in 20 individuals. In six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cells and granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure. CONCLUSIONS: Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes. Objective: To evaluate the association of BP indexes with death and a composite CV event. Design, Setting, and Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016). Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings). Main Outcomes and Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC). Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP. Conclusions and Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.

BACKGROUND: Immediate implant function has become an accepted treatment modality for fixed restorations in totally edentulous mandibles, whereas experience from immediate function in the edentulous maxilla is limited. PURPOSE: The purpose of this study was to evaluate a protocol for immediate function (within 3 hours) of four implants (All-on-4, Nobel Biocare AB, Göteborg, Sweden) supporting a fixed prosthesis in the completely edentulous maxilla. MATERIALS AND METHODS: This retrospective clinical study included 32 patients with 128 immediately loaded implants (Brånemark System TiUnite, Nobel Biocare AB) supporting fixed complete-arch maxillary all-acrylic prostheses. A specially designed surgical guide was used to facilitate implant positioning and tilting of the posterior implants to achieve good bone anchorage and large interimplant distance for good prosthetic support. Follow-up examinations were performed at 6 and 12 months. Radiographic assessment of the marginal bone level was performed after 1 year in function. RESULTS: Three immediately loaded implants were lost in three patients, giving a 1-year cumulative survival rate of 97.6%. The marginal bone level was, on average, 0.9 mm (SD 1.0 mm) from the implant/abutment junction after 1 year. CONCLUSION: The high cumulative implant survival rate indicates that the immediate function concept for completely edentulous maxillae may be a viable concept.

<h3>Abstract</h3> <b>Objectives:</b> To estimate the incidences of caesarean sections in Latin American countries and correlate these with socioeconomic, demographic, and healthcare variables. <b>Design:</b> Descriptive and ecological study. <b>Setting:</b> 19 Latin American countries. <b>Main outcome measures:</b> National estimates of caesarean section rates in each country. <b>Results:</b> Seven countries had caesarean section rates below 15%. The remaining 12 countries had rates above 15% (range 16.8% to 40.0%). These 12 countries account for 81% of the deliveries in the region. A positive and significant correlation was observed between the gross national product per capita and rate of caesarean section (<i>r</i>s=0.746), and higher rates were observed in private hospitals than in public ones. Taking 15% as a medically justified accepted rate, over 850 000 unnecessary caesarean sections are performed each year in the region. <b>Conclusions:</b> The reported figures represent an unnecessary increased risk for young women and their babies. From the economic perspective, this is a burden to health systems that work with limited budgets. <h3>Key messages</h3> 12 of the 19 Latin American countries studied had caesarean section rates above 15%, ranging from 16.8% to 40% These12 countries account for 81% of the deliveries in the region Better socioeconomic conditions were associated with higher caesarean section rates Over 850 000 unnecessary caesarean sections are performed each year in Latin America Reduction of caesarean section rates will need concerted action from public health authorities, medical associations, medical schools, health professionals, the general population, and the media

BACKGROUND: We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints. METHODS AND RESULTS: We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034). CONCLUSION: INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.

BACKGROUND: Cesarean section rates show a wide variation among countries in the world, ranging from 0.4 to 40 percent, and a continuous rise in the trend has been observed in the past 30 years. Our aim was to explore the association of cesarean section rates of different countries with their maternal and neonatal mortality and to test the hypothesis that in low-income countries, increasing cesarean section rates were associated with reductions in both outcomes, whereas in high-income countries, such association did not exist. METHODS: We performed a cross-sectional multigroup ecological study using data from 119 countries from 1991 to 2003. These countries were classified into 3 categories: low-income (59 countries), medium-income (31 countries), and high-income (29 countries) countries according to an international classification. We assessed the ecological association between national cesarean section rates and maternal and neonatal mortality by fitting multiple linear regression models. RESULTS: Median cesarean section rates were lower in low-income than in medium- and high-income countries. Seventy-six percent of the low-income countries, 16 percent of the medium-income countries, and 3 percent of high-income countries showed cesarean section rates between 0 and 10 percent. Three percent of low-income countries, 36 percent of medium-income countries, and 31 percent of high-income countries showed cesarean section rates above 20 percent. In low-income countries, a negative and statistically significant linear correlation was observed between cesarean section rates and neonatal mortality and between cesarean section rates and maternal mortality. No association was observed in medium- and high-income countries for either neonatal mortality or maternal mortality. CONCLUSIONS: No association between cesarean section rates and maternal or neonatal mortality was shown in medium- and high-income countries. Thus, it becomes relevant for future good-quality research to assess the effect of the high figures of cesarean section rates on maternal and neonatal morbidity. For low-income countries, and on confirmation by further research, making cesarean section available for high-risk pregnancies could contribute to improve maternal and neonatal outcomes, whereas a system of care with cesarean section rates below 10 percent would be unlikely to cover their needs.

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH) for providing haemostasis-related guidance documents for clinical laboratories. This inaugural coagulation ICSH document was developed by an ad hoc committee, comprised of international clinical and laboratory direct acting oral anticoagulant (DOAC) experts. The committee developed consensus recommendations for laboratory measurement of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban), which would be germane for laboratories assessing DOAC anticoagulation. This guidance document addresses all phases of laboratory DOAC measurements, including pre-analytical (e.g. preferred time sample collection, preferred sample type, sample stability), analytical (gold standard method, screening and quantifying methods) and post analytical (e.g. reporting units, quality assurance). The committee addressed the use and limitations of screening tests such as prothrombin time, activated partial thromboplastin time as well as viscoelastic measurements of clotting blood and point of care methods. Additionally, the committee provided recommendations for the proper validation or verification of performance of laboratory assays prior to implementation for clinical use, and external quality assurance to provide continuous assessment of testing and reporting method.

and allied fusarioid genera (www.fusarium.org).

on human and animal health.

This retrospective multicenter study compared microorganisms documented by quantitative cultures from bronchoscopic samples in episodes of ventilator-associated pneumonia (VAP) from three different institutions in Barcelona (B), Montevideo (M), and Seville (S). The observations were compared with the findings reported by Trouillet and coworkers (AJRCCM 1998;157:531-539) in Paris (P). The objective was to evaluate whether a classification of etiologies of VAP in four groups, based on the number of ventilation days and previous antimicrobial use, might contribute to establishing generalized guidelines for empirical therapy. Significant variations in etiologies (p < 0.05) were found in all of the microorganisms isolated from VAP episodes across three treatment sites when compared with the reference site (P). In Group 1 (< 7 d and absence of antibiotics), Pseudomonas aeruginosa remained extremely infrequent (3 of 89, 3.3%) in the joint category, whereas the incidence of Acinetobacter baumannii was significantly higher, owing to M findings. On the other hand, one site (B) had a significantly lower incidence of multiresistant pathogens (Methicillin-resistant Staphylococcus aureus [MRSA] and nonfermenters other than P. aeruginosa), even in Group 2 (< 7 d and antibiotics), Group 3 (>/= 7 d and absence of antibiotics), and Group 4 (antibiotics and >/= 7 days). Similar findings were documented when episodes were grouped according to Groups 1 and 3 of the ATS guidelines. We conclude that causes of VAP varied markedly across four treatment sites, resulting in the need for large-scale variations in antimicrobial prescribing practices. Instead of following general recommendations, antimicrobial prescribing practices for VAP should be based on up-to-date information of the pattern of multiresistant isolates from each institution.

Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high.The 2013 update of the World Society of Emergency Surgery (WSES) guidelines for the management of intra-abdominal infections contains evidence-based recommendations for management of patients with intra-abdominal infections.

Associations between affective disorders, anxiety disorders, and substance use disorders were examined in epidemiological studies conducted in Germany, Switzerland, Puerto Rico, and the mainland US. There was a remarkable degree of similarity across studies in the magnitude and type of specific disorders associated with the affective disorders. Comorbidity with affective disorders was greater for the anxiety disorders than for substance misuse. Panic disorder was the subtype of anxiety that was most highly comorbid with depression. Social phobia was the specific phobic type with the strongest association with the affective disorders. The magnitude of associations between substance misuse and affective disorders generally was quite low and less consistent across sites. No major differences were found in the patterns of comorbidity by gender or age group, affective subtype or prevalence period. The onset of anxiety disorders generally preceded that of depression, whereas alcohol misuse was equally likely to pre-or post-date the onset of affective disorders. Finally, comorbidity was associated with an elevation in treatment rates across all sites, confirming Berkson's paradox on an international level.

BACKGROUND: Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness. METHODS: Computerized databases from 1980 to 2016 were searched. Randomized controlled trials (RCT) evaluating clinical outcomes associated with probiotic therapy as a single strategy or in combination with prebiotic fiber (synbiotics). Overall number of new infections was the primary outcome; secondary outcomes included mortality, ICU and hospital length of stay (LOS), and diarrhea. Subgroup analyses were performed to elucidate the role of other key factors such as probiotic type and patient mortality risk on the effect of probiotics on outcomes. RESULTS: Thirty trials that enrolled 2972 patients were identified for analysis. Probiotics were associated with a significant reduction in infections (risk ratio 0.80, 95 % confidence interval (CI) 0.68, 0.95, P = 0.009; heterogeneity I (2) = 36 %, P = 0.09). Further, a significant reduction in the incidence of ventilator-associated pneumonia (VAP) was found (risk ratio 0.74, 95 % CI 0.61, 0. 90, P = 0.002; I (2) = 19 %). No effect on mortality, LOS or diarrhea was observed. Subgroup analysis indicated that the greatest improvement in the outcome of infections was in critically ill patients receiving probiotics alone versus synbiotic mixtures, although limited synbiotic trial data currently exists. CONCLUSION: Probiotics show promise in reducing infections, including VAP in critical illness. Currently, clinical heterogeneity and potential publication bias reduce strong clinical recommendations and indicate further high quality clinical trials are needed to conclusively prove these benefits.