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Objective To describe the prevalence of and factors associated with different thyroid dysfunction phenotypes in women who are asymptomatic preconception. Design Observational cohort study. Setting A total of 49 hospitals across the United Kingdom between 2011 and 2016. Participants Women aged 16 to 41years with history of miscarriage or subfertility trying for a pregnancy. Methods Prevalences and 95% confidence intervals (CIs) were estimated using the binomial exact method. Multivariate logistic regression analyses were conducted to identify risk factors for thyroid disease. Intervention None. Main Outcome Measure Rates of thyroid dysfunction. Results Thyroid function and thyroid peroxidase antibody (TPOAb) data were available for 19213 and 19237 women, respectively. The prevalence of abnormal thyroid function was 4.8% (95% CI, 4.5-5.1); euthyroidism was defined as levels of thyroid-stimulating hormone (TSH) of 0.44 to 4.50 mIU/L and free thyroxine (fT4) of 10 to 21 pmol/L. Overt hypothyroidism (TSH > 4.50 mIU/L, fT4 < 10 pmol/L) was present in 0.2% of women (95% CI, 0.1-0.3) and overt hyperthyroidism (TSH < 0.44 mIU/L, fT4 > 21 pmol/L) was present in 0.3% (95% CI, 0.2-0.3). The prevalence of subclinical hypothyroidism (SCH) using an upper TSH concentration of 4.50 mIU/L was 2.4% (95% CI, 2.1-2.6). Lowering the upper TSH to 2.50 mIU/L resulted in higher rates of SCH, 19.9% (95% CI, 19.3-20.5). Multiple regression analyses showed increased odds of SCH (TSH > 4.50 mIU/L) with body mass index (BMI) ≥ 35.0 kg/m2 (adjusted odds ratio [aOR] 1.71; 95% CI, 1.13-2.57; P = 0.01) and Asian ethnicity (aOR 1.76; 95% CI, 1.31-2.37; P < 0.001), and increased odds of SCH (TSH ≥ 2.50 mIU/L) with subfertility (aOR 1.16; 95% CI, 1.04-1.29; P = 0.008). TPOAb positivity was prevalent in 9.5% of women (95% CI, 9.1-9.9). Conclusions The prevalence of undiagnosed overt thyroid disease is low. SCH and TPOAb are common, particularly in women with higher BMI or of Asian ethnicity. A TSH cutoff of 2.50 mIU/L to define SCH results in a significant proportion of women potentially requiring levothyroxine treatment.

Introduction and objectives Episodes of extreme heat are associated with increased morbidity and mortality in chronically-ill patients but there is a need to clearly establish the relationship between extreme heat and myocardial infarction. The aim of this study was to analyze the relationship between the incidence of ST-segment elevation myocardial infarction (STEMI) and maximum temperature, in particular during heat wave alert periods (HWAP). Methods The population studied consisted of confirmed STEMI cases registered in the Infarction Code of the Community of Madrid between June 2013 and June 2017. Incidence rate ratios (IRR) adjusted for trend and seasonality and 95%CI were estimated using time series regression models. Results A total of 6465 cases of STEMI were included; 212 cases occurred during the 66-day period of HWAP and 1816 cases during the nonalert summer period (IRR, 1.14; 95%CI, 0.96-1.35). The minimum incidence rate was observed at the maximum temperature of 18 °C. Warmer temperatures were not associated with a higher incidence (IRR,1.03; 95%CI, 0.76-1.41), whereas colder temperatures were significantly associated with an increased risk (IRR, 1.25; 95%CI, 1.02-1.54). No effect modification was observed by age or sex. Conclusions We did not find an increased risk of STEMI during the 66 days of HWAP in the Community of Madrid between June 2013 and June 2017. However, an increased risk was found during colder temperatures. No extra health resources for STEMI management are required during periods of extreme heat, but should be considered during periods of cold weather. Resumen Introducción y objetivos Los episodios de calor extremo se asocian con una mayor morbimortalidad de los enfermos crónicos, pero su relación con el infarto de miocardio no está claramente establecida. El objetivo es analizar una posible relación entre la incidencia de infarto agudo de miocardio con elevación del segmento ST (IAMCEST) y la temperatura máxima, especialmente durante los periodos de alerta por ola de calor (PAOC). Métodos La población estudiada son los casos de IAMCEST confirmado registrados en Código Infarto Madrid entre junio de 2013 y junio de 2017. Se estimaron las razones de tasa de incidencia (RTI) ajustadas por tendencia y estacionalidad y sus IC95% asociadas con los PAOC y con la temperatura máxima, utilizando modelos de regresión de series temporales. Resultados Se incluyó a 6.465 casos de IAMCEST. En 66 días de PAOC hubo 212 casos y 1.816 casos durante los días de verano sin alerta (RTI = 1,14; IC95%, 0,96-1,35). La tasa de incidencia mínima se observó con temperatura máxima de 18 °C. Las temperaturas más cálidas no se asociaron con mayor incidencia (RTI = 1,03; IC95%, 0,76-1,41); por el contrario, hubo un incremento significativo con las temperaturas más frías (RTI = 1,25; IC95%, 1,02-1,54). No hubo modificación por sexo o edad. Conclusiones Durante los PAOC entre junio de 2013 y junio de 2017 en la Comunidad de Madrid, no se observó un aumento de la incidencia de IAMCEST, pero sí durante periodos de bajas temperaturas. No cabe esperar un mayor uso de los recursos sanitarios para el IAMCEST en periodos de calor extremo, pero sí durante los periodos fríos., A. Tobías received support from the Japanese Society for the Promotion of the Science (JSPS) in its grant invitation program for research in Japan (S18149).

Resumen: La visualización de datos es una herramienta relevante para explorar y comunicar resultados en la investigación médica, en especial cuando se trata de vigilancia epidemiológica. La aplicación web COVID19-Tracker analiza y produce de forma sistemática visualizaciones diarias de los datos de la epidemia de COVID-19 de casos diagnosticados y fallecimientos desde el 24 de febrero de 2020 en adelante. Se han desarrollado tres aplicaciones para: 1) análisis de la tendencia y proyecciones a corto plazo; 2) estimación de la tasa de letalidad; y 3) efecto del estado de alarma sobre la tendencia de datos incidentes. La aplicación online puede ser de utilidad para un mejor conocimiento de la epidemia de SARS-CoV-2 en España. Abstract: Data visualization is an important tool for exploring and communicating findings in medical research, and specially in epidemiological surveillance. The COVID19-Tracker web application systematically produces daily updated data visualization and analysis of SARS-CoV-2 epidemic in Spain. It collects automatically daily data on COVID-19 diagnosed cases and mortality, from February 24th, 2020 onwards. Three applications have already been developed: 1) to analyze data trends and estimating short-term projections; 2) to estimate the case fatality rate; and 3) to assess the effect of the lockdowns on the data trends. The application may help for a better understanding of the SARS-CoV-2 epidemic data in Spain.

BACKGROUND AND AIM: Although seasonal variations in mortality have been recognised for a long time, the role of temperature remains unclear. We aimed to assess seasonal variation in mortality and t...

Background Ambient temperature may contribute to seasonality of mortality; in particular, a warming climate is likely to influence the seasonality of mortality. However, few studies have investigated seasonality of mortality under a warming climate. Methods Daily mean temperature, daily counts for all-cause, circulatory, and respiratory mortality, and annual data on prefecture-specific characteristics were collected for 47 prefectures in Japan between 1972 and 2015. A quasi-Poisson regression model was used to assess the seasonal variation of mortality with a focus on its amplitude, which was quantified as the ratio of mortality estimates between the peak and trough days (peak-to-trough ratio (PTR)). We quantified the contribution of temperature to seasonality by comparing PTR before and after temperature adjustment. Associations between annual mean temperature and annual estimates of the temperature-unadjusted PTR were examined using multilevel multivariate meta-regression models controlling for prefecture-specific characteristics. Results The temperature-unadjusted PTRs for all-cause, circulatory, and respiratory mortality were 1.28 (95% confidence interval (CI): 1.27–1.30), 1.53 (95% CI: 1.50–1.55), and 1.46 (95% CI: 1.44–1.48), respectively; adjusting for temperature reduced these PTRs to 1.08 (95% CI: 1.08–1.10), 1.10 (95% CI: 1.08–1.11), and 1.35 (95% CI: 1.32–1.39), respectively. During the period of rising temperature (1.3 °C on average), decreases in the temperature-unadjusted PTRs were observed for all mortality causes except circulatory mortality. For each 1 °C increase in annual mean temperature, the temperature-unadjusted PTR for all-cause, circulatory, and respiratory mortality decreased by 0.98% (95% CI: 0.54–1.42), 1.39% (95% CI: 0.82–1.97), and 0.13% (95% CI: − 1.24 to 1.48), respectively. Conclusion Seasonality of mortality is driven partly by temperature, and its amplitude may be decreasing under a warming climate., YC was supported by a Senior Research grant (2019R1A2C1086194) from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies). YK was supported by JSPS KAKENHI Grant Number JP19K17104. AT was supported by the JSPS Invitational Fellowships for Research in Japan (Grant S18149). YG was supported by the Career Development Fellowship of the Australian National Health and Medical Research Council (Grants APP1107107 and APP1163693). AG was supported by the Medical Research Council UK (Grants MR/M022625/1 and MR/R013349/1), by the Natural Environment Research Council UK (Grant NE/R009384/1), and by the European Union’s Horizon 2020 Project Exhaustion (Grant ID: 820655). YH was supported by the Environment Research and Technology Development Fund (S-14) of the Environmental Restoration and Conservation Agency, Japan.

ObjectiveTo evaluate whether the implementation of the FAST‐M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low‐resource setting.DesignA before‐and‐after design.SettingFifteen government healthcare facilities in Malawi.PopulationWomen suspected of having maternal sepsis.MethodsThe FAST‐M complex intervention consisted of the following components: the FAST‐M maternal sepsis treatment bundle and the FAST‐M implementation programme. Performance of selected process outcomes was compared between a 2‐month baseline phase and 6‐month intervention phase with compliance used as a proxy measure of feasibility.Main outcome resultCompliance with vital sign recording and use of the FAST‐M maternal sepsis bundle.ResultsFollowing implementation of the FAST‐M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 [0%] versus 169/252 [67.1%], P P P = 0.091). In particular, women were more likely to receive antibiotics (3/12 [25.0%] versus 72/107 [67.3%], P = 0.004) within 1 hour of recognition of suspected sepsis.ConclusionImplementation of the FAST‐M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low‐resource setting such as Malawi.Tweetable AbstractImplementation of a sepsis care bundle for low‐resources improved recognition & management of maternal sepsis.

Background Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option. Objectives To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis. Search methods We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies. Selection criteria We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials. Data collection and analysis At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods. Main results Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.

BackgroundPrevious studies investigating the relationship of influenza with acute myocardial infarction (AMI) have not distinguished between AMI types 1 and 2. Influenza and cold temperature can explain the increased incidence of AMI during winter but, because they are closely related in temperate regions, their relative contribution is unknown. Methods and ResultsThe temporal relationship between incidence rates of AMI with demonstrated culprit plaque (type 1 AMI) from the regional primary angioplasty network and influenza, adjusted for ambient temperature, was studied in Madrid region (Spain) during 5 influenza seasons (from June 2013 to June 2018). A time‐series analysis with quasi‐Poisson regression models and distributed lag‐nonlinear models was used. The incidence rate of type 1 AMI according to influenza vaccination status was also explored. A total of 8240 cases of confirmed type 1 AMI were recorded. The overall risk ratio (RR) of type 1 AMI during epidemic periods, adjusted for year, month, and temperature, was 1.23 (95% CI, 1.03–1.47). An increase of weekly influenza rate of 50 cases per 100 000 inhabitants resulted in an RR for type 1 AMI of 1.16 (95% CI, 1.09–1.23) during the same week, disappearing 1 week after. When adjusted for influenza, a decrease of 1ºC in the minimum temperature resulted in an increase of 2.5% type 1 AMI. Influenza vaccination was associated with a decreased risk of type 1 AMI in subjects aged 60 to 64 years (RR, 0.58; 95% CI, 0.47–0.71) and ≥65 years (RR, 0.53; 95% CI, 0.49–0.57). ConclusionsInfluenza and cold temperature were both independently associated with an increased risk of type 1 AMI, whereas vaccination was associated with a reduced risk among older patients., This work has been partially funded by unrestricted research grants from the Fundación para la Investigación Biomédica, University Hospital “Príncipe de Asturias” (Servicio Madrileño de Salud, Madrid, Spain) (to Drs García‐Lledó and de Abajo) and funding from Sanofi‐Pasteur S.A., a manufacturer of influenza vaccines (to Dr de Abajo). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing the report. Dr Tobías received support from the Japanese Society for the Promotion of Science in its invitation‐to‐research fellowship program in Japan (S18149).

More than a year since its emergence, there is conflicting evidence on the potential influence of weather conditions on SARS-CoV-2 transmission dynamics. We used a two-stage ecological modelling approach to estimate weather-dependent signatures in SARS-CoV-2 transmission in the early phase of the pandemic, using a dataset of 3 million COVID-19 cases reported until 31 May 2020, spanning 409 locations in 26 countries. We calculated the effective reproduction number (Re) over a location-specific early-phase time-window of 10-20 days, for which local transmission had been established but before non-pharmaceutical interventions had become established as measured by the OxCGRT Government Response Index. We calculated mean levels of meteorological factors, including temperature and humidity observed in the same time window used to calculate Re. Using a multilevel meta-regression approach, we modelled nonlinear effects of meteorological factors, while accounting for government interventions and socio-demographic factors. A weak non-monotonic association between temperature, absolute humidity and Re was identified, with a decrease in Re of 0.087 (95% CI: 0.025; 0.148) between mean temperature of 10.2°C (maximum) and 20°C (minimum) and a decrease in Re of 0.061 (95% CI: 0.011; 0.111) between absolute humidity of 6.6 g/m3 (maximum) and 11 g/m3 (minimum). However, government interventions explained twice as much of the variation in Re compared meteorological factors. We find little evidence of meteorological conditions having influenced the early stages of local epidemics, and conclude that population behaviour and governmental intervention are more important drivers of transmission.

Background: Studies have quantified the associations between ambient temperature and all-cause enteric infections. Temperature sensitivity in enteric infections, however, may be pathogen dependent. Here, we sought to identify aetiology-specific associations between ambient temperature and enteric infections. Methods: We conducted a systematic review and meta-analysis study by searching PubMed, Web of Science, and Scopus for research articles published from 2000 to 2019. We only included studies that quantified the effects of ambient temperature increases on enteric infections. Two authors screened the studies, one extracted the data from the eligible studies, and four performed data verification. The overall risks were obtained by pooling the relative risk of enteric infection by aetiology for each 1°C temperature rise using random-effects modelling and robust variance estimation for the correlated effect estimates. Findings: The 2170 screened studies generated 80 eligible for systematic review and 56 eligible for meta-analysis. The overall increased risks per 1°C temperature rise were 1·05 (95%CI 1·04–1·07; I2 :97%) for salmonellosis, 1·07 (1·04–1·10; I2 :99%) for shigellosis, 1·02 (1·01–1·04; I2 :98%) for campylobacteriosis, 1·05 (1·04–1·07; I2 :36%) for cholera, 1·04 (1·01–1·07; I2 :98%) for Escherichia coli enteritis, and 1·15 (1·07–1·24; I2 :0%) for typhoid. Reduced risks per 1°C temperature rise were found for rotaviral enteritis at 0·96 (0·90–1·02; I2 :97%), and noroviral enteritis at 0·89 (0·81–0·99; I2 :96%). Interpretation: Enteric infections have varying associations with ambient temperature depending on their aetiology. Future projections for temperature-related enteric infections should account for differing temperature sensitivity in enteric pathogens. Funding: Japan Society for the Promotion of Science (Kakenhi) Grant-in-Aid for Scientific Research. Declaration of Interest: We declare no competing interests

BackgroundPostpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH.ObjectivesTo identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile.Search methodsWe searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies.Selection criteriaAll randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion.Data collection and analysisTwo review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence.Main resultsSeven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty).Authors' conclusionsThe available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.

Acknowledgement: “This Protocol of a Cochrane Review was published in the Cochrane Database of Systematic Reviews 2020, Issue 9. Cochrane Protocols and Reviews are regularly updated as new evidence emerges and in response to feedback, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Protocol.'

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated COVID-19 have caused a global emergency that requires an engaged, integrated, interdisciplinary, and rapid response from the scientific community. Climate change, ecological change, and biodiversity loss might have played an important role in the occurrence of this zoonotic pandemic. Climatic and environmental factors, such as temperature, humidity, and air pollution, are potentially influencing the transmission, spread, and severity of SARS-CoV-2 infection. Strong scientific evidence about the contributions of these environmental determinants in the COVID-19 pandemic is needed, in combination with an understanding of the role of other important societal factors and public health interventions. This evidence will support the public health community in responding to the current crisis, and inform strategies to prevent the recurring effects of the COVID-19 pandemic and future emergencies.

IntroductionInternal temporomandibular joint (TMJ) disorders are present in approximately 80% of patients with symptomatic temporomandibular disorders. Among the minimally invasive therapies, we find the intra-articular infiltration of substances, such as corticosteroids, hyaluronic acid or platelet-rich plasma accompanied or not by an arthrocentesis. There are several studies on minimally invasive therapy for internal TMJ disorders; however, none compares the effectiveness of the different intra-articular corticosteroids to each other.The purpose of this study is to evaluate the effectiveness of the different intra-articular corticosteroids for the treatment of internal disorders of the TMJ and compare them to each other or to other minimally invasive therapies.Methods and analysisA systematic search will be carried out up to December 2019 in the electronic databases: Medline, Cochrane Library, EMBASE, SCOPUS and LILACS.Randomised clinical trials evaluating patients with internal disorders of the TMJ, with intra-articular corticosteroid therapy and comparing these to each other and/or to other minimally invasive therapy will be included. The main outcomes will be pain and range of motion measured through validated scales.Two review authors will independently screen search results, extract data from included studies and assess the risk of bias in those studies using the Revised Cochrane Risk of Bias Tool (RoB 2.0). In the case of any discrepancy and failure to reach consensus, this will be resolved by a third reviewer.A network meta-analysis will be conducted based on direct comparisons to generate indirect comparisons of the different treatments. Data will be combined in a meta-analysis using a random effects model.The principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system will be used to assess the overall quality of the body of evidence associated with the main results.Ethics and disseminationThis protocol will not require ethical approval. The results of this review will be disseminated through peer-reviewed publications.Trial registration numberCRD42019129014.

ObjectivesTo assess if there is any association between hyperemesis gravidarum (HG), psychological morbidity and infant bonding and to quantify any psychosocial consequences of HG.DesignTwo-point prospective case–control, multicentre survey study with antenatal and postnatal data collection.SettingThree London hospitals.ParticipantsPregnant women at ≤12 completed weeks gestation recruited consecutively over 2 years. Women with HG were recruited at the time of admission; controls recruited from a low risk antenatal clinic. 106 women were recruited to the case group and 108 to the control. Response rates at antenatal data collection were 87% and 85% in the case and control groups, respectively. Postnatally, the response rate was 90% in both groups.Primary and secondary outcome measuresPrimary outcomes were psychological morbidity in the antenatal and postnatal periods, infant bonding in the postnatal period and psychosocial implications of HG. Secondary outcomes were the effects of severity and longevity of HG and assessment of correlation between Edinburgh Postnatal Depression Scale scores and maternal-to-infant bonding scores.ResultsAntenatally, 49% of cases had probable depression compared with 6% of controls (OR 14.4 (5.29 to 39.44)). Postnatally, 29% of cases had probable depression versus 7% of controls (OR 5.2 (1.65 to 17.21)). There was no direct association between HG and infant bonding. 53% of women in the HG group reported needing four or more weeks of sick leave compared with 2% in the control group (OR 60.5 (95% CI 8.4 to 2535.6)).ConclusionsLong-lasting psychological morbidity associated with HG was evident. Significantly more women in the case group sought help for mental health symptoms in the antenatal period, however very few were diagnosed with or treated for depression in pregnancy or referred to specialist perinatal mental health services. HG did not directly affect infant bonding. Women in the case group required long periods off work, highlighting the socioeconomic impact of HG.

Aims We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. Methods Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. Results We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). Conclusions Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns., JY, DY and YC were supported by a Senior Research grant (2019R1A2C1086194) from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies) and Government-wide R&D Fund project for Infectious Disease (HG18C0025). YK was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP19K17104 in Japan. AG and FS were supported by the Medical Research Council UK (Grant ID: MR/R013349/1) and Natural Environment Research Council (Grant ID: NE/R009384/1). NS was supported by the NIEHS-funded HERCULES Center (P30ES019776).

Air in urban areas is usually contaminated with particle matter. High concentrations lead to a rise in the risk of cardiovascular and respiratory diseases. Some studies have reported that ultrafine particles (UFP) play a greater role in cardiovascular diseases than other particle matter, particularly regarding hypertensive crises and DBP, although in the latter such effects were described concerning clinical blood pressure (BP). In this study, we evaluate the relationship between 24-h ambulatory BP monitoring (ABPM) and atmospheric UFP concentrations in Barcelona. Methods: An observational study of individual patients’ temporal and geographical characteristics attended in Primary Care Centres and Hypertensive Units during 2009–2014 was performed. Results: The participants were 521 hypertensive patients, mean age 56.8 years (SD 14.5), 52.4% were women. Mean BMI was 28.0 kg/m2 and the most prominent cardiovascular risk factors were diabetes (N = 66, 12.7%) and smoking (N = 79, 15.2%). We describe UFP effects at short-term and up to 1 week (from lag 0 to 7). For every 10 000 particle/cm3 UFP increase measured at an urban background site, a corresponding statistically significant increase of 2.7 mmHg [95% confidence interval = (0.5–4.8)] in 24-h DBP with ABPM for the following day was observed (lag 1). Conclusion: We have observed that a rise in UFP concentrations during the day prior to ABPM is significantly associated with an increase in 24 h and diurnal DBP. It has been increasingly demonstrated that UFP play a key role in cardiovascular risk factors and, as we have demonstrated, in good BP control. Sin financiación 4.844 JCR (2020) Q2, 17/65 Peripheral Vascular Disease 1.249 SJR (2020) Q1, 70/349 Cardiology and Cardiovascular Medicine UEM

[Background] Concerns have been raised about the possibility that inhibitors of the renin–angiotensin–aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19., [Methods] In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437., [Findings] We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62–2·41) and risk factors (1·46, 1·23–1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77–1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64–1·00) or angiotensin-receptor blockers (1·10, 0·88–1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34–0·80). The adjusted ORs were similar across severity degrees of COVID-19., [Interpretation] RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19., This study was funded by a research grant from the Institute of Health Carlos III (COV20/00027).

Research question What is the association of endometrial thickness with pregnancy losses and live births in IVF treatment and the optimal threshold that optimizes the IVF outcome? Design Data were analysed from 25,767 IVF cycles from centres of the CARE Fertility Group in the UK between 2007 and 2016. Transvaginal ultrasound was conducted to measure the maximum endometrial thickness during gonadotrophin stimulation. Live birth rates were per embryo transfer. Pregnancy loss rates included the combination of biochemical and clinical pregnancy losses. Results The live birth rate was 15.6% with 5 mm or less endometrial thickness and gradually increased to 33.1% with an endometrial thickness of 10 mm. On the other hand, the pregnancy loss rate was 41.7% with 5 mm or less endometrial thickness and gradually decreased to 26.5% with an endometrial thickness of 10 mm. Statistical modelling for optimal endometrial thickness threshold found 10 mm or more maximized live births and minimized pregnancy losses. This association was independent after adjusting for confounders such as age, oocyte number, number of transferred embryos, ovarian stimulation protocol and embryo quality for live births (crude RR 1.27; 95% CI 1.21 to 1.33; Adjusted RR 1.18; 95% CI 1.12 to 1.23) and pregnancy losses (crude RR 0.83; 95% CI 0.77 to 0.89; adjusted RR 0.86; 95% CI 0.8 to 0.92). Conclusions Endometrial thickness is strongly associated with pregnancy losses and live births in IVF, and the optimal endometrial thickness threshold of 10 mm or more maximized live births and minimized pregnancy losses.

We would like to express our concern about the limited capacity of actions taken by the Spanish Government to successfully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak and end the exponential growth phase of new cases. The measures taken so far, consisting primarily of partial restriction mobility, are in the right direction, although some researchers have warned about the pressure placed on the building blocks of the health system.1 Given that the actual extent of an epidemic can only be assessed retrospectively, governments and policy makers are forced to make decisions on the basis of mathematical models of other diseases and previous experiences by other countries taking different actions.2 In Spain, various models simulating the spread of infection and using different assumptions converge in a landscape of a high number of new cases within the next few weeks. Simulations have been done using the URV and UNIZAR models to predict the progression of the number of patients who will require admission into hospital intensive care units because of coronavirus disease 2019 (COVID-19) in three scenarios (appendix): scenario 1, no mobility restrictions; scenario 2, partial restriction of mobility (ie, movement to the workplace allowed for 30% of people); and scenario 3, complete restriction of mobility (ie, no workplace mobility allowed except for essential services).

BACKGROUND First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis. OBJECTIVES AND RATIONALE We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC). SEARCH METHODS We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (, The authors acknowledge the initial contribution of Arri Coomarasamy, Ioannis Gallos and Mary Eyo.

This study aims to estimate the prevalence of autism spectrum disorders (ASD) in 2017 and the ASD diagnosis incidence between 2009 and 2017 in children living in Catalonia region in Spain, and their temporal and geographical variability. We used administrative data for all children aged 2–17 years who were insured in the public Catalan Health System between 2009 and 2017. We identified all ASD cases diagnosed between 2009 and 2017 (ICD-9 codes 299.0, 299.1, 299.8, and 299.9). We estimated the ASD prevalence in 2017 and the overall annual incidence between 2009 and 2017, then stratified by sex, age group, and healthcare area. We used Poisson regression models to assess temporal trends in the incidence and mixed-effects Poisson regression models to assess geographical variability. We observed an ASD prevalence of 1.23% (95% confidence interval [CI] 1.21–1.25) in 2017, with 1.95% (95% CI 1.92–1.99) for boys and 0.46% (95% CI 0.44–0.48) for girls, the highest prevalence being in 11- to 17-year-olds (1.80%, 95% CI 1.76–1.83). The ASD diagnosis incidence increased from 0.07% (95% CI 0.06–0.09) in 2009 to 0.23% (95% CI 0.21–0.24) in 2017, with a higher increase in girls, and in children aged 2–5 years at the time of diagnosis. We only observed geographical differences in prevalence in the 2017 data. We also detected a threefold increase in the diagnosis incidence overall, which was even more pronounced in girls and at early ages. In conclusion, the ASD prevalence observed in this study was 1.23% in 2017, with a sex ratio of 4.5 in favor of boys, which is consistent with previous studies. Autism Res2019. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: Autism spectrum disorders (ASD) are currently well known in our society as one of the most common neurodevelopmental disorders during childhood. The results of our study showed that, in 2017 in Catalonia, slightly more than one in a 100 children had an ASD diagnosis, it was more common in boys than in girls, and also in older children. In addition, between 2009 and 2017, we observed an increase in the number of new cases diagnosed each year. The data presented in this study will assist in planning and evaluating the needs of health services in this geographical region. © 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc., The research described in this article was conducted under contract with the Health Effects Institute (HEI), an organization funded jointly by the United States Environmental Protection Agency (EPA; Assistance Award No. R-82811201) and certain motor vehicle and engine manufacturers. The contents of this article do not necessarily reflect the views of HEI or its sponsors, nor do they necessarily reflect the views and policies of the EPA or motor vehicle and engine manufacturers. M.G. is funded by a Miguel Servet fellowship (MS13/00054, CP18/00018) from the Spanish Institute of Health Carlos III. A.P. is supported by the Medical Research Council (grant numbers MR/K501256/1, MR/N013468/1). The authors would like to express their gratitude to Joan Albert d'Escofet, from the Agency for Health Quality and Assessment of the Catalan Health Department, for providing essential data and support for this study. The research materials supporting this publication can be accessed by contacting the corresponding author on reasonable request.

Background The use of obstetric early warning systems (OEWS) are recommended as an adjunct to reduce maternal morbidity and mortality. The aim of this review was to document the variation in OEWS trigger thresholds and the quality of information included within accompanying escalation protocols. Methods A review of OEWS charts and escalation policies across consultant-led maternity units in the UK (n = 147) was conducted. OEWS charts were analysed for variation in the values of physiological parameters triggering different levels of clinical escalation. Relevant data within the escalation protocols were also searched for: urgency of clinical response; seniority of responder; frequency of on-going clinical monitoring; and clinical setting recommended for on-going care. Results The values of physiological parameters triggering specific clinical responses varied significantly between OEWS. Only 99 OEWS charts (67.3%) had an escalation protocol as part of the chart. For 29 charts (19.7%), the only escalation information included was generic, for example to “contact a doctor if triggers”. Only 76 (51.7%) charts detailed the required seniority of responder, 37 (25.2%) the frequency for on-going clinical monitoring, eight (5.4%) the urgency of clinical response and two (1.4%) the recommended clinical setting for on-going care. Conclusion The observed variations in the trigger thresholds used in OEWS charts and the quality of information included within the accompanying escalation protocols is likely to lead to suboptimal detection and response to clinical deterioration during pregnancy and the post-partum period. The development of a national OEWS and escalation protocol would help to standardise care across obstetric units.

Objective This systematic review aimed to evaluate the scientific evidence on the efficacy of desensitizing mouthwashes for the treatment of dentin hypersensitivity (DH) and root sensitivity (RS). Material and methods A thorough search in MEDLINE, PubMed and Cochrane Plus Library was conducted up to February 2015. Randomized clinical trials, parallel, double-blinded and placebo-controlled, with a follow-up of at least 6 weeks, reporting changes on response to tactile stimuli, thermal/evaporative stimuli or patients’ subjective assessment of the pain experienced during their daily life after the home use of desensitizing mouthwashes were considered for inclusion. Results The screening of titles and abstracts resulted in seven publications meeting the eligibility criteria. The desensitizing agents evaluated were potassium nitrate (n = 5), aluminium lactate (n = 1) and sodium fluoride (n = 1). A meta-analysis for each of the hypersensitivity stimuli was performed. Results demonstrated statistically significant reduction in sensitivity scores favouring test group when DH was assessed by means of patients’ self-reported pain experience (SMD at 8 weeks = 0.77; 95% CI [0.23; 1.31]; P = 0.005). No significant effects were detected in response to tactile or thermal/evaporative stimuli. Meta-regression analysis demonstrated a tendency towards an increased effect favouring test group for the patients’ subjective perception, whereas tactile and thermal/evaporative stimuli showed a slight tendency towards a reduction in the efficacy of the test mouthwash. Conclusions There exists a tendency towards a decrease in DH or RS scores with time in both treatment groups, with significant differences in favour of test group when sensitivity is evaluated in terms of patients’ self-reported sensitivity symptoms.

AIM The aim of this systematic review and network meta-analysis (NMA) was to compare the efficacy of different anti-plaque chemical agents, in 6-month, home-use, randomized clinical trials (RCTs), in terms of plaque index (PlI) changes. MATERIAL AND METHODS RCTs assessing PlI were identified, screened, and evaluated for inclusion. Relevant information was extracted, and quality and risk of bias were assessed. Mean differences between baseline-end were calculated to obtain weighted mean differences and 95% confidence intervals. NMA protocols were applied to assess direct and indirect comparisons among products using Turesky PlI. RESULTS Eighty-three papers were included: 49 examined dentifrices, 32 mouthrinses and 2 both. The NMA analysed 51 studies including data from 4242 and 4180 subjects for dentifrices and mouthrinses respectively. For dentifrices, triclosan-copolymer and chlorhexidine showed the greatest effect, with significant differences when compared with stannous fluoride. For mouthrinses, essential oils and chlorhexidine showed the greatest effect, with significant differences when compared with delmopinol, alexidine and cetylpyridinium chloride. CONCLUSION Within the limitations of this study (including the severe imbalance in the amount of evidence), dentifrices containing triclosan-copolymer or chlorhexidine and mouthrinses containing essential oils or chlorhexidine showed the greatest effect on PlI scores as assessed with NMA.

Objective: To determine the effectiveness of the Phosphodiesterase 5 (PDE5) Inhibitors for the treatment of erectile dysfunction in patients with spinal trauma. Methods: A systematic review and meta-analysis comparing PDE5 inhibitors versus placebo were carried out for clinical trials conducted between 1980 and 2014 that evaluated male patients older than 18 years, diagnosed with spinal cord trauma and erectile dysfunction. We designed a search strategy for Medline, CENTRAL, EMBASE and other electronic sources. Two investigators independently and blindly screened the studies for inclusion. A random effect meta-analysis was performed. Results: Six studies involving 963 patients were included. Male patients over 18 years with ED attributable or subsequent to traumatic spinal cord injury (SCI) were included from these studies. In 4 of these studies, patients were randomized to the treatment group receiving sildenafil and the comparison group was placebo. Out of the remaining 2 trials, one compared tadalafil against the placebo and the other vardenafil versus placebo. The improvement on SCIs with PDE5 inhibitors was found to be large (standardized mean difference 0.71; 95% CI 0.39-1.03), with a high heterogeneity (I2 = 74.4%). Conclusions: PDE5 inhibitors are effective for the treatment of erectile dysfunction secondary to SCI. © 2016 S. Karger AG, Basel.

Objective To estimate the incidence of caesarean scar pregnancy (CSP) and to describe the management outcomes associated with this condition. Design A national cohort study using the UK Early Pregnancy Surveillance Service (UKEPSS). Setting 86 participating Early Pregnancy Units. Population All women diagnosed in the participating units with CSP between November 2013 and January 2015. Methods Cohort study of women identified through the UKEPSS monthly mailing system. Main outcome measures Incidence, clinical outcomes and complications. Results 102 cases of CSP were reported, with an estimated incidence of 1.5 per 10 000 (95% CI 1.1-1.9) maternities. Full outcome data were available for 92 women. Management was expectant in 21/92 (23%), medical in 15/92 (16%) and surgical in 56/92 (61%). The success rates of expectant, medical and surgical management were 43% (9/21), 46% (7/15) and 96% (54/56), respectively. The complication rates were 15/21 (71%) with expectant, 9/15 (60%) with medical and 20/56 (36%) with surgical management. Discharge from care (median number of days) was 82 (range 37-174) with expectant, 21 (range 10-31) with medical and 11 (range 4-49) with surgical management. Conclusions Surgical management appears to be associated with a high success rate, low complication rate and short post-treatment follow up. Tweetable abstract Surgery for CSP appears to be successful, with low complication rates and short post-treatment follow up.

STUDY QUESTION Is serum vitamin D associated with live birth rates in women undergoing ART? SUMMARY ANSWER Women undergoing ART who are replete in vitamin D have a higher live birth rate than women who are vitamin D deficient or insufficient. WHAT IS KNOWN ALREADY Vitamin D deficiency has been associated with an increased risk of abnormal pregnancy implantation as well as obstetric complications such as pre-eclampsia and fetal growth restriction. However, the effect of vitamin D on conception and early pregnancy outcomes in couples undergoing ART is poorly understood. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis of 11 published cohort studies (including 2700 women) investigating the association between vitamin D and ART outcomes. PARTICIPANTS/MATERIALS, SETTINGS, METHODS Literature searches were conducted to retrieve studies which reported on the association between vitamin D and ART outcomes. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Eleven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE Live birth was reported in seven of the included studies (including 2026 patients). Live birth was found to be more likely in women replete in vitamin D when compared to women with deficient or insufficient vitamin D status (OR 1.33 [1.08-1.65]). Five studies (including 1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient or insufficient in vitamin D (OR 1.34 ([1.04-1.73]). All 11 of the included studies (including 2700 patients) reported clinical pregnancy as an outcome. Clinical pregnancy was found to be more likely in women replete in vitamin D (OR 1.46 [1.05-2.02]). Six studies (including 1635 patients) reported miscarriage by vitamin D concentrations. There was no association found between miscarriage and vitamin D concentrations (OR 1.12 [0.81-1.54]. The included studies scored well on the Newcastle-Ottawa quality assessment scale. LIMITATIONS REASONS FOR CAUTION Although strict inclusion criteria were used in the conduct of the systematic review, the included studies are heterogeneous in population characteristics and fertility treatment protocols. WIDER IMPLICATIONS OF THE FINDINGS The findings of this systematic review show that there is an association between vitamin D status and reproductive treatment outcomes achieved in women undergoing ART. Our results show that vitamin D deficiency and insufficiency could be important conditions to treat in women considering ARTs. A randomized controlled trial to investigate the benefits of vitamin D deficiency treatment should be considered to test this hypothesis. STUDY FUNDING/COMPETING INTERESTS No external funding was either sought or obtained for this study. The authors have no competing interests to declare. REGISTRATION NUMBER N/A.

Background and aims Most studies show that probiotics are effective in preventing morbidity and mortality in preterm infants. Using network meta-analysis (NMA) we aim to rank treatments’ efficacy and identify the most effective strain, formulation and dose. Methods Databases searched: CENTRAL, Ovid MEDLINE EMBASE, LILACS and the Cochrane Database of Systematic Reviews. Clinicaltrials.gov; controlled-trials.com; and WHO’s ICTRP were searched for any ongoing studies. Searches completed up to November 2016 without language restriction. Reference checking, citation searching and contact with study authors were done to identify additional studies. Randomised controlled trials evaluating probiotics interventions and combinations of probiotics/strains of the same probiotic of all durations were included. 2 independent, unblinded review authors assessed the trials for inclusion and extracted data. We used standard methodology as per The Cochrane Collaboration. The protocol was registered – Cochrane Database CD012303, PROSPERO CRD42016047640. Main results 53 included trials reported outcomes on 13 630 infants. The period of studies was Jan 1986-Oct 2016. All studies enrolled infants Our preliminary results from 35 studies (10 063 patients) show evidence of significant reduction in global mortality in probiotics group (10 063 patients, RR 0.77, 95% CI 0.66 to 0.91, I2=0%). Data from 38 studies provide information on severe necrotising enterocolitis (NEC), stage 2 or 3, with a significant reduction in the incidence of NEC with prophylactic administration of probiotics (9455 patients, RR 0.52, 95% CI 0.40 to 0.68, I2=22%). And, data from 35 studies with 10 565 patients informed about any culture proven sepsis, showed a significant reduction in rates of confirmed sepsis (RR 0.82, 95% CI 0.74 to 0.92, I2=33%). Conclusion Based on our preliminary results, It seems (moderate quality of evidence) that administration of probiotics in preterm infants could reduce NEC, culture proven sepsis and even global mortality. We are currently analysing the most effective strain of probiotic. Further clinical trials of probiotics head to head will be needed to confirm our data.

Purpose Atomoxetine is a non-stimulant drug that could be an alternative to methylphenidate, whose benefit:risk balance for the treatment of adults with attention deficit hyperactivity disorder (ADHD) has recently been shown to be unclear. This study aimed to compare all-cause discontinuation rate between atomoxetine and placebo in adults with ADHD. Secondarily, efficacy and safety were investigated. Methods Systematic review and meta-analysis of randomized controlled trials comparing atomoxetine with placebo in adults with ADHD were performed. All-cause treatment discontinuation was the primary endpoint. Efficacy in reducing ADHD symptoms and safety were the secondary endpoints. Odds ratio (OR) and the standardized mean difference (SMD) were calculated for dichotomous and continuous outcomes, respectively. Data were pooled using the fixed and random effects model. The influence of study design-related, intervention-related and patient-related co-variables over the primary endpoint was investigated by means of meta-regression. This study is registered with the international prospective register of systematic reviews (PROSPERO): CRD 42012002042. Results Twelve studies (3375 patients) were included. Treatment discontinuation was larger with atomoxetine than with placebo (OR= 1.39). No co-variable was found to modify the effect of atomoxetine over treatment discontinuation. Atomoxetine showed modest efficacy in reducing ADHD symptoms irrespective of the assessor: patient (SMD=0.33); clinician (SMD=0.40). The rate of adverse events-induced discontinuation was higher with atomoxetine than with placebo (OR=2.57). Conclusion This study suggests that atomoxetine has a poor benefit–risk balance for the treatment of adults with ADHD. The recommendation of atomoxetine use in this population is weak. Copyright © 2013 John Wiley & Sons, Ltd. key words—attention deficit hyperactivity disorder; atomoxetine; discontinuation; efficacy; safety; meta-analysis; meta-regression; pharmacoepidemiology

BACKGROUND: The risk-benefit balance of pharmacological treatment for children and adolescents with ADHD and the factors that moderate this relationship are unclear. METHODS: A systematic review and meta-analysis of randomised, placebo-controlled clinical trials (RPCCTs) investigating the efficacy of pharmacological treatment in children or adolescents with ADHD was carried out. Meta-analysis of treatment discontinuation, clinician-, parent- and teacher-rated efficacy and adverse events was performed. The effect of covariates was studied. RESULTS: Sixty-three studies were included. Ten drugs were investigated, with atomoxetine and methylphenidate the most frequently studied. RPCCTs had mostly a short duration (7.9 weeks). All-cause treatment discontinuation was lower with pharmacological treatment than placebo (OR = 0.68). Pharmacological treatment was more efficacious than placebo independently of the rater (clinician, standardised mean difference (SMD) 0.74; parent, SMD = 0.63; or teacher, SMD = 0.75). Evidence of publication bias was found for clinician-rated efficacy, especially in industry-sponsored RPCCT. Psychostimulants showed a higher efficacy and were associated with a better outcome on treatment discontinuation than non-stimulant drugs. Efficacy was smaller in RPCCTs for which a psychiatric comorbid disorder was an inclusion criterion, was larger in studies with a commercial sponsorship and showed a negative association with treatment length. CONCLUSIONS: In the short term, pharmacological treatment provides moderate-high symptom relief, is safe and shows lower treatment discontinuation than placebo, suggesting a suitable risk-benefit balance, particularly with psychostimulants. The efficacy is lower in patients with a comorbid psychiatric disorder and should be assessed periodically, as it appears to reduce over time. Publication bias of clinician-rated efficacy in studies with a commercial sponsor is suggested.

Background and aim: Vehicle exhaust is the main emission source in urban areas, mainly releasing ultrafine particles ( Methods: We collected daily mortality counts due to respiratory causes (ICD10: J00-J99), COPD (J40-J44,J47), LRTI (J09-J18,J20-J22), bronchitis (J20-J22) and pneumonia (J12-J18) and daily concentrations of UFP between 2009-2012. We segregated the UFP using a method based on the high correlation between black carbon and N (Rodriguez et al, Aerosol Sci 2007;38:1207-19). The first component accounts for aerosol constituents emitted by vehicle exhaust (N1) and the second for photochemical new particle formation enhancements (N2). We evaluated short-term effects up to one week, using a time-stratified case-crossover design. Results: Daily mean UFP concentration (N) was 13,114/cm3, 45% being N1. We observed statistically significant associations for all respiratory causes and COPD, increasing risk of mortality by 6% and 10%, respectively, for 3,950/cm3 rise of N1 at lag 0. We observed positive, but not significant, associations between N1 and the other respiratory outcomes. We did not find any effect of N2. Conclusion: UFP from vehicle exhaust are more harmful for respiratory health than those from photochemical nucleation. This should have an implication for EU regulation of the UFP concentrations in urban air.

Background Psychological illness occurring in association with hyperemesis gravidarum (HG) has been widely reported. Objective To determine if there is a higher incidence of psychological morbidity in women with HG compared with women without significant nausea and vomiting in pregnancy. Search strategy PubMed, MEDLINE, Embase and PsychINFO were searched up to September 2015. Selection criteria Articles referring to psychological morbidity in relation to HG. For meta-analysis case–control studies using numerical scales to compare psychological symptoms. Data collection and analysis Articles were independently assessed for inclusion by two reviewers and methodology was appraised using the Newcastle Ottawa Scale. Comparison was made using the standard mean difference (SMD) in symptom scale scores. Main results In all, 59 articles were included in the systematic review, 12 of these were used in the meta-analysis. Meta-analysis of depression scale scores demonstrated a very large effect with statistically significantly higher depression scale scores in women with HG (SMD 1.22; 95% CI 0.80–1.64; P ≤ 0.01) compared with controls. Meta-analysis of anxiety scores demonstrated a large effect with statistically significantly higher anxiety disorder scale scores in women with HG (SMD 0.86; 95% CI 0.53–1.19; P ≤ 0.01). In both analyses significant heterogeneity was identified (depression and HG I2 = 94%, P ≤ 0.01; anxiety and HG I2 = 84%, P = 0.02). Conclusions Our systematic review and meta-analysis have shown a significantly increased frequency of depression and anxiety in women with HG. The findings should prompt service development for women with HG that includes provision of psychological care and support. Tweetable abstract Meta-analysis demonstrates an increase in #PsychologicalMorbidity in women with #HyperemesisGravidarum

Background: Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during 1995-1998. Methods: The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO 2 and NO 2), total suspended particles (TSP), ozone (O 3), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. Results: Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10μg/m 3 SO 2increments. The risk of an ER visit for the same NO 2 increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages. Conclusions: Air levels of SO 2 and NO 2 were associated with a substantial increased risk in ER visits due to asthma and COPD. The inclusion of Poaceae and Urticaceae pollen did not alter that association. © 2011 SEICAP., BACKGROUND Associations found in time-series studies on hospital emergency room (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with single air pollutants show some lack of consistency. The respiratory effects of aeroallergens in the air pollution mix are not well established. Non-linear relationships of different airborne pollen types with certain respiratory diseases have also been described. We aim to study the short-term effects of major air pollutants and aeroallergen pollen on asthma and COPD hospital ER visits in the industrial and Mediterranean Spanish city of Cartagena during 1995-1998. METHODS The association of asthma and COPD to ER visits with mean levels of sulphur and nitrogen dioxides (SO(2) and NO(2)), total suspended particles (TSP), ozone (O(3)), and the main allergenic airborne pollen types were analysed using Poisson regression with Generalised Additive Models, taking into account delayed effects and adjusting for long-term trends, seasonality, weather conditions, holidays and flu notifications. RESULTS Multipollutant models showed a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER visits per 10μg/m(3) SO(2)increments. The risk of an ER visit for the same NO(2) increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to asthma showed a positive increase with both Urticaceae and Poaceae levels, but did not substantially modify the previous percentages. CONCLUSIONS Air levels of SO(2) and NO(2) were associated with a substantial increased risk in ER visits due to asthma and COPD. The inclusion of Poaceae and Urticaceae pollen did not alter that association.

Background: Many studies have demonstrated a positive association between air pollutants and emergency visits for asthma. However, few studies have included pollen when analysing this relationship in mild–moderate asthmatic patients. Objective: To determine the importance of the pollutants such as ozone (O3), particles (PM10), nitrogen dioxide (NO2) and sulphur dioxide (SO2) in the clinical course of mild–moderate pollen-allergic asthmatic patients from two Spanish towns in La Mancha: Puertollano (high pollution levels) and Ciudad Real (low pollution levels). Methods: We used a Poisson regression model to study a cohort of 137 patients from Puertollano and Ciudad Real during two pollen seasons (2000–2001) and analysed the relationship between air pollutant and pollen levels and daily symptoms, the medication used and peak-flow measurements. Results: The number of asthma symptoms and the mean values of the PM10, SO2 and NO2 levels were higher in Puertollano than in Ciudad Real. In Puertollano, the risk of asthma increased by 6% with a 3-day lag for PM10, by 8% with a 3-day lag for O3, by 4% with a 1-day lag for SO2 and by 15% with a 3-day lag for O3 when its values exceeded the health threshold (P

Background In recent years there has been a notable increase in respiratory diseases in industrialised countries, which is attributed to a combination of chemical atmospheric pollution and the allergens existing in the atmosphere of big cities. Few studies, however, have analysed the effect of different pollen species on the different causes of hospital admissions other than those exclusively owing to asthma. Objective The aim of this investigation was to analyse the influence of the most abundant pollen species with the highest allergenic potential in Madrid’s atmosphere on daily emergency hospital admissions – from all causes and specific causes – according to different age groups. Methods An ecological time-series design was adopted in which the effects were quantified using Poisson regression models, taking into account different confusion factors, such as chemical and acoustic atmospheric pollution. Results Statistically significant associations were found between pollen species and hospital admissions due to respiratory causes, and between pollen species and all causes of hospital admissions and, to a lesser degree, circulatory causes. The impact was greater in the younger age groups. Concentrations of Poaceae and Platanus pollen species were the factors showing the highest correlation to the different causes of admission. Conclusion The relative risks analysis revealed a significant effect between the pollen species analysed and health for admitted patients of all age groups; this effect was greater than that detected for the environmental variables traditionally analysed in urban atmospheres.

Summary Background Allergic diseases have increased in industrialized countries and this increase is associated not only with genetic factors but also with lifestyle and environmental factors such as air pollution. Our hypothesis was that asthma in pollen-allergic patients from two towns with very different pollution levels in La Mancha (Spain) could be affected to a very different degree. Objective Our objectives were to assess the risk factors associated with decompensation of pollen-induced asthma in the two towns and to perform a comparison between the patients from Puertollano (high pollution level) and Ciudad Real (low pollution level) with respect to daily symptoms, medication used and peak-flow measurements. Methods We designed a cohort study with 137 patients (66 from Puertollano and 71 from Ciudad Real), conducted over 3 years (1999–2001) and including two pollen seasons. The two populations presented similar demographic and clinical characteristics. The variables studied included: area of residence, sex, age, smoking status, asthma symptoms and positive prick tests. Clinical decompensation was monitored by symptoms recorded on diary cards, twice daily peak-flow measurements and the use of protocolized medication. Results There was a clinically relevant relationship between the place of residence and clinical decompensation. The risk of clinical decompensation in patients from Puertollano was up to three times higher than that of patients in Ciudad Real (P=0.034). Furthermore, patients from Puertollano and patients with moderate asthma presented more rapid decompensation compared with patients from Ciudad Real (P=0.020) and patients with mild asthma (P=0.049). Conclusion In conclusion, pollen-allergic asthmatics in Puertollano present a poorer clinical course and become decompensated earlier than those from Ciudad Real and it could be due to air pollution.

Purpose To date, no ideal strategy has been established for treating or preventing medication-related osteonecrosis of the jaw (MRONJ). The aim of the present work was to perform a systematic literature review to determine the efficacy of autologous platelet concentrate (APC) application, for prevention or treatment of MRONJ, together with surgical debridement. Material and methods An electronic search was performed using MEDLINE (PubMed), EMBASE, and Cochrane databases until January 2015 using the following search terms: osteonecrosis, bisphosphonates, antiresorptive, antiangiogenic therapy, BRONJ, platelet concentrate, PRP, PRF, and PRGF. Two reviewers assessed the eligibility of articles independently and extracted key data. The methodology used met PRISMA criteria. The Newcastle–Ottawa scale was used to assess the quality of the articles. Results Preventive applications of platelet-rich plasma (PLP) were reported in 697 dental extractions in patients taking bisphosphonates intravenously, of whom seven patients developed osteonecrosis (five mandibular and two maxillary). In cases of established osteonecrosis, eight studies reported treatment by surgery combined with APC (seven with PRP and one with leukocyte-rich and platelet-rich fibrin) in 123 patients (34 men and 89 women) with ONJ, who received 157 treatments, of which 135 achieved complete resolution (85.98%). Conclusion There are no published scientific data to sufficiently support any specific treatment protocol, including the use of APC together with surgical debridement, for the management of MRONJ. Randomized controlled clinical trials of the use of APC are needed.

The factors underlying the variability in the results of randomized, placebo-controlled clinical trials (RPCCT) assessing pharmacological interventions for adults with attention deficit hyperactivity disorder (ADHD) are not fully understood. A systematic review and meta-analysis of RPCCT comparing pharmacological treatment and placebo in adults with ADHD was carried out. The study outcomes were all-cause treatment discontinuation, efficacy on ADHD symptoms, and safety. Patient-, intervention-, and study design-related covariates were collected. Meta-regression methods were applied. Forty-four studies involving 9952 patients were included. All-cause treatment discontinuation was slightly higher with pharmacological treatment than with placebo (odds ratio (OR) = 1.18; 95 % confidence interval (CI) 1.02, 1.36; p = 0.003). A better outcome on all-cause treatment discontinuation was observed in studies that provided concomitant psychotherapy when compared to those that did not (rate of OR (ROR) = 0.68, p = 0.048). Pharmacological treatment was efficacious for reducing ADHD symptoms (standardized mean difference (SMD) = 0.45; 95 % CI 0.37, 0.52; p

[Background] Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of children and adolescents, with a significant impact on health services and the community in terms of economic and social burdens. The objective of this systematic review will be to evaluate the comparative efficacy and safety of pharmacological and non-pharmacological treatments in children and adolescents with ADHD., [Methods] Searches involving PubMed/MEDLINE and the Cochrane Database of Systematic Reviews will be used to identify related systematic reviews and relevant randomized trials. Search results will be supplemented by reports from the regulatory and health technology agencies, clinical trials registers and by data requested from trialists and/or pharmaceutical companies. We will consider studies evaluating pharmacological interventions (e.g. stimulants, non-stimulants, antidepressants), psychological interventions (e.g. behavioural interventions, cognitive training and neurofeedback) and complementary and alternative medicine interventions (e.g. dietary interventions, supplement with fatty acids, vitamins, minerals, aminoacids, herbal treatment, homeopathy, and mind-body interventions including massage, chiropractic, acupuncture, yoga, meditation, Tai chi). Eligible control conditions will be placebo, waitlist, no treatment and usual care. Randomized controlled trials of a minimum of 3 weeks duration will be included. The primary outcomes of interest will be the proportion of patients who responded to treatment and who dropped out of the allocated treatment, respectively. Secondary outcomes will include treatment discontinuation due to adverse events, as well as the occurrences of serious adverse events and specific adverse events (decreased weight, anorexia, insomnia and sleep disturbances, anxiety, syncope and cardiovascular events). Two reviewers will independently screen references identified by the literature search, as well as potentially relevant full-text articles in duplicate. Data will be abstracted and risk of bias will be appraised by two team members independently. Conflicts at all levels of screening and abstraction will be resolved through discussion. Random-effects pairwise meta-analyses and Bayesian network meta-analyses will be conducted where appropriate. ., [Discussion] This systematic review and network meta-analysis will compare the efficacy and safety of treatments used for ADHD in children and adolescents. The findings will assist patients, clinicians and healthcare providers to make evidence-based decisions regarding treatment selection., Specific funding is provided by the Alicia Koplowitz Foundation (2014 to 2016). RT-S is supported by the Spanish Psychiatric Research Network, Spanish Ministry of Science and Innovation (CIBERSAM). ADM is partially funded by grant number R24 AT001293 from the National Center for Complementary and Alternative Medicine (NCCAM) of the US National Institutes of Health. DM is funded by a University of Ottawa Research Chair.

In this study we have explored the nature and range of sleep dysfunction that occurs in untreated Parkinson's disease (PD) comparing data obtained from the use of the Parkinson's disease sleep scale (PDSS) in an untreated PD patient group compared to advanced PD and healthy controls. 25 untreated (drug-naive, DNPD) PD patients (mean age 66.9 years, range 53-80, 18 males) completed the validated Parkinson's disease sleep scale (PDSS), mean duration of PD was 2.1 years (1-10, up to 4 years in all except one patient with tremulous PD reporting tremor duration of 10 years) and mean Hoehn and Yahr score 1.9 (1-3). Data were compared to 34 advanced PD (mean age 70.2 years, range 51-88, 23 male), mean duration of PD 11 years (range 4-22), mean Hoehn and Yahr score 3.4 (3-5) and PDSS data obtained from 131 healthy controls (mean age 66.6 years, range 50-93, 56 males). Total PDSS scores and PDSS sub-items, except PDSS item 2, were highly significantly different (p

Objective.To establish the occurrence, distribution, and secular time trend of nosocomial infections (NIs) in a surgical intensive care unit (ICU).Design and Setting.Follow-up study in a teaching hospital in Spain.Methods.In May 1995 we established an nosocomial infection surveillance system in our surgical ICU. We collected information daily for all patients who were in the ICU for at least 48 hours (546 patients from 1996 through 2000). We used the Centers for Disease Control and Prevention definitions and criteria for infections. Monthly, we determined the site-specific incidence densities of NIs, the rates of medical device use, and the Poisson probability distribution, which determined whether the case count equalled the number of expected cases (the mean number of cases during the previous year, with extreme values excluded). We compared yearly and monthly infection rates by Poisson regression, using site-specific NIs as a dependent variable and year and month as dummy variables. We tested annual trends with an alternative Poisson regression model fitting a single linear trend.Results.The average rate of catheter-associated urinary tract infections was 8.4 per 1000 catheter-days; that of ventilator-associated pneumonia, 21 per 1000 ventilator-days; and that of central line–associated bloodstream infections, 30 per 1000 central line–days. The rate of urinary tract infections did not change over the study period, but there was a trend toward decreases in the rates of central line–associated bloodstream infections and ventilator-associated pneumonia.Conclusion.An NI surveillance and control program contributed to a progressive decrease in NI rates.

Objective: The aim of this paper was to analyse the effects of the urban air pollutants and noise levels on daily emergency hospital admissions of children less than 10 years of age in Madrid. Material and methods: Poisson Regression Models were used to quantify the associations. Meteorological variables, influenza epidemics, pollen concentrations and trends and periodicities were used as controlling variables. Results: The main results obtained were the detected relationship (p

The Parkinson's Disease Sleep Scale (PDSS) is the first published bedside clinical tool to specifically measure sleep disturbances in Parkinson's disease (PD). The objective of the present study was to carry out a metric analysis of a Spanish version (PDSS-SV) using a cross-sectional study of 100 PD patients who participated in the study. Usual measures for PD and mental status were applied by neurologists. Patients completed the Epworth Sleepiness Scale, Parkinson's Disease Questionnaire-39 Items (PDQ-39), and PDSS-SV. PDSS internal consistency (Cronbach's alpha, 0.77; significant item-total correlation for 11 items) was satisfactory. PDSS showed high test-retest reliability (intraclass correlation coefficient for items, 0.79-0.99; for total score, 0.94). Standard error of measurement was 9.80 (crossover) and 5.01 (longitudinal). Scores were distributed uniformly, with low floor and ceiling effect (1%). PDSS scores were correlated significantly with depression (Hamilton Depression Rating Scale, r(S) = -0.55; P < 0.0001) and quality of life (PDQ-39 Summary Index, r(S) = -0.26; P = 0.007), but not with clinical variables. Self-perception of mood disorder, pain, or hallucinations correlated individually with PDSS scores, and a factor explaining 65% of the variance was found. The assessment of PD sleep disorders with the PDSS met some basic standards required for health status measures.

The relationship of dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk has received increasing attention since the beginning of the 1990s. Contradicting published results regarding the relationship between body burden levels of p,p'-dichlorodiphenyldichloroethane (p,p'-DDE)--the main DDT metabolite--and breast cancer, we argue that such differences stem from methodologic differences among those studies. We performed a meta-analysis of 22 articles using DerSimonian and Laird's method for random effects models. The Q-statistic was used to identify heterogeneity in the outcome variable across studies. The gradient of p,p'-DDE exposure in epidemiologic studies was homogenized to serum lipid bases (nanograms per gram). The potential for publication bias was examined by means of the Begg's test. We discuss methodologic features of the studies in an attempt to reconcile the findings. The summary odds ratio (OR) for selected studies was 0.97 (95% confidence interval, 0.87-1.09) and the gradient of exposure ranged from 84.37 to 12,948 ng/g. No overall heterogeneity in the OR was observed (chi-squared = 27.93; df = 23; p = 0.218). Neither the study design nor the lack of breast-feeding control or the type of biologic specimen used to measure p,p'-DDE levels were the causes of heterogeneity throughout the studies. Evidence for publication bias was not found (p = 0.253). Overall, these results should be regarded as a strong evidence to discard the putative relationship between p,p'-DDE and breast cancer risk. Nevertheless, the exposure to DDT during critical periods of human development--from conception to adolescence--and individual variations in metabolizing enzymes of DDT or its derivatives are still important areas to be researched in regard to breast cancer development in adulthood.

Many time-series studies have shown positive associations between air pollutants and asthma morbidity. However, few studies have included pollen as a potential confounder when examining this relationship. This study analysed the short-term association between air pollutants (sulphur dioxide (SO2), particles measured with a median aerodynamic diameter of

Background: Drug dependence is frequent in patients with attention deficit hyperactivity disorder (ADHD). Nevertheless, the efficacy and safety of pharmacological treatments in this population are unclear. Methods: A systematic review with meta-analysis was performed. Randomised placebo-controlled clinical trials investigating the efficacy of pharmacological treatment in patients with co-occurring ADHD and substance use disorder (SUD) were included. ADHD symptom severity, drug abstinence and all-cause treatment discontinuation were the primary study endpoints. The effects of patient-, intervention- and study-related covariates over the primary outcomes were investigated by means of meta-regression. Results: Thirteen studies were included, enrolling a total of 1,271 patients. A small to moderate reduction of ADHD symptoms was found. Meta-regression analysis identified the presence of a lead-in period as a covariate associated with reduced efficacy. Conversely, no beneficial effect was observed either on drug abstinence or treatment discontinuation. The efficacy on ADHD symptoms was smaller in studies with a lead-in period. A positive correlation between the efficacy for ADHD and that for SUD was found. Conclusions: The efficacy of pharmacological interventions for co-occurring ADHD and SUD has been little investigated. Mixed results were obtained: while pharmacological interventions improved ADHD symptoms, no beneficial effect on drug abstinence or on treatment discontinuation was noted. The strength of the recommendation of pharmacological treatment for co-occurring ADHD and SUD is therefore modest. The study was registered with the international prospective register of systematic reviews (PROSPERO): CRD 4212003414.

Objective The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. Methods This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. Results In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0–4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09–0.6). Conclusions We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.

To the Editor: Over the last decade, several studies have investigated the association between noise levels, primarily due to road traffic in large cities, and pathologies not related to either traditional hearing impairments or sleep disorders. These pathologies are mainly hypertension and cardiovascular, connective system and respiratory diseases [1]. Their impact on public health has been assessed in time series studies, indicating a traffic noise effect on both cardiovascular and respiratory hospital admissions rates similar to that attributed to air pollutants [2]. In addition, a recent study has shown an association of noise levels with cardiovascular mortality [3]. The description of the physiopathological mechanisms involved in this association reveal an actual impact of current road traffic noise levels on health [1]. Others question this because of the high correlation between traffic noise and air pollution [4], although a previous study in our setting showed an independent association between noise and cardiovascular mortality from the effect of the primary chemical air pollutants [5]. However, the effect of noise on respiratory mortality has not …