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Objective Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. Method The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. Results Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. Discussion The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. Conclusion PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids.We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance.Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.

During 2010-2012, we surveyed 40,010 3- to 6-year-old children in seven Chinese cities (Beijing, Taiyuan, Urumqi, Shanghai, Nanjing, Changsha, and Chongqing). Their parents reported information on household renovation, including the timing of renovation and the choice of materials for walls and floors in the child's room, and the incidence of their child's rhinitis. Multivariate and two-level (city-child) logistic regression analyses yielding adjusted odds ratios (AOR) with 95% confidence intervals were performed. Sensitivity analyses stratifying data for location and economic level were also performed. About 48.0% of the children had ever had allergic rhinitis, 41.2% had current allergic rhinitis, and 9.0% had had doctor-diagnosed rhinitis. Exposure to household renovation during early lifetime (birth to 1-year-old) had an AOR of 1.43 (1.04-1.9) for allergic rhinitis. The incidence of allergic rhinitis was significantly different in children exposed to different floor and wall covering materials. Floor or wall covering material composed of organic materials significantly increased the risk of childhood allergic rhinitis compared with tile flooring or lime wall covering. Oil paint had an AOR of 1.66 (1.28-2.14) for diagnosed rhinitis compared with lime wall covering. Adding new furniture the year before pregnancy was associated with an AOR of 1.18 (1.10-1.27) and 1.18 (1.11-1.25) for lifetime and current rhinitis. Solid wood or tiles/ceramic as floor materials, and using wallpaper, oil paint, or emulsion panels as wall materials were risk factors for doctor-diagnosed rhinitis. Sensitivity analyses showed that children living in southern or higher economic level China cities were more likely to have allergic rhinitis with household renovation.

Dose–response association between level of impairment of semen quality and risk of morbidity or premature death has been reported. Therefore, it can be presumed that men utilizing donated spermatozoa, i.e. patients with non-obstructive azoospermia, are at highest risk for adverse health outcomes. To evaluate the risks of prescription of medications for common metabolic disturbances and testosterone replacement therapy (TRT) among men who father children with donated spermatozoa—who presumably do it due to severe impairment of fertility. We used Swedish nationwide register data on all fathers who had a live-born child between 2007 and 2014 in order to compare men who fathered children with donated spermatozoa to the ones who became fathers by using own gametes. Cox regression analysis was used in order to estimate the post-conception incidence of prescription of medicines for hypertension (HT), diabetes (type 1 and 2), dyslipidaemia (DLE) or TRT. Starting the follow up at time of conception, models were adjusted for age, educational level, and previous cancer treatment. In total 410,119 childbirths were included in the analysis. Among them, for 390 fathers donated spermatozoa were utilized. Fathers to children conceived with donated spermatozoa had higher risk for having TRT prescribed (HR: 18.14; 95%CI: 11.71–28.10; p ≪ 0.001). Same was true for DLE (HR: 2.08; 95%CI: 1.27–3.39; p = 0.003) but not diabetes. Fathers to children conceived by use of donated spermatozoa are at significantly increased risk for testosterone treatment and dyslipidaemia, necessitating stringent follow up and inclusion in prevention programs.

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

BACKGROUND Patterns of dual antiplatelet therapy (DAPT) use beyond 1 year post-myocardial infarction (MI) have not been well studied. METHODS TIGRIS (NCT01866904) was a prospective, multi-center (369 centers in 24 countries), observational study of patients 1 to 3 years post-MI. We sought to identify the prevalence and determinants of DAPT use ≥1 year post-MI in patients enrolled in TIGRIS. We used multivariable logistic regression to identify determinants of DAPT use at 396 days post-MI (365 days plus a 31day overrun period to account for intended DAPT discontinuation at 1 year). Patients treated with an oral anticoagulant were excluded. RESULTS Of 7708 patients (median age 67 years, women 25%, ST-elevation MI 50%), 39% and 16% were on DAPT at 396 days and 5 years post-MI, respectively. DAPT use at 396 days post-MI was more prevalent in patients

International audience; Background: Risk prediction tools are lacking for patients with stable disease some years after myocardial infarction (MI).Hypothesis: A practical long‐term cardiovascular risk index can be developed.Methods: The long‐Term rIsk, Clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post‐myocardial infarction patients prospective global registry enrolled patients 1 to 3 years post‐MI (369 centers; 25 countries), all with ≥1 risk factor (age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, or chronic non‐end‐stage kidney disease [CKD]). Self‐reported health was assessed with EuroQoL‐5 dimensions. Multivariable Poisson regression models were used to determine key predictors of the primary composite outcome (MI, unstable angina with urgent revascularization [UA], stroke, or all‐cause death) over 2 years.Results: The primary outcome occurred in 621 (6.9%) of 9027 eligible patients: death 295 (3.3%), MI 195 (2.2%), UA 103 (1.1%), and stroke 58 (0.6%). All events accrued linearly. In a multivariable model, 11 significant predictors of primary outcome (age ≥65 years, diabetes, second prior MI, CKD, history of major bleed, peripheral arterial disease, heart failure, cardiovascular hospitalization (prior 6 months), medical management (index MI), on diuretic, and poor self‐reported health) were identified and combined into a user‐friendly risk index. Compared with lowest‐risk patients, those in the top 16% had a rate ratio of 6.9 for the primary composite, and 18.7 for all‐cause death (overall c‐statistic; 0.686, and 0.768, respectively). External validation was performed using the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events registry (c‐statistic; 0.748, and 0.849, respectively).Conclusions: In patients >1‐year post‐MI, recurrent cardiovascular events and deaths accrue linearly. A simple risk index can stratify patients, potentially helping to guide management.

We surveyed 40 010 three- to six-year-old children in seven Chinese cities (Beijing, Taiyuan, Urumqi, Shanghai, Nanjing, Changsha, and Chongqing) during 2010-2012 so as to investigate possible links between home renovation and childhood eczema. Their parents responded to questions on home renovation and childhood eczema. Multivariate and two-level (city-child) logistic regression analyses yielding odds ratios with 95% confidence intervals were performed. Sensitivity analyses stratifying data for region, climate, and income level were also performed. The prevalences of childhood eczema in children with different floor and wall covering materials were significantly different and were significantly higher with home renovation during early lifetime. Exposure to synthetic materials significantly increased the risk of childhood eczema by 20%-25%. The risks (AOR, 95% CI) of current eczema among children in families with solid wood flooring and oil paint wall covering were 1.25 (1.04-1.49) and 1.35 (1.14-1.60), respectively. Home renovation during pregnancy was related to children's lifetime and current eczema.

Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Results Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p Conclusions This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614

Pyrazinamide is a first-line drug used in the treatment of tuberculosis. High exposure to pyrazinamide and its metabolites may result in hepatotoxicity, whereas low exposure to pyrazinamide has been correlated with treatment failure of first-line antitubercular therapy. The aim of this study was to describe the pharmacokinetics and metabolism of pyrazinamide in patients coinfected with tuberculosis and HIV. We further aimed to identify demographic and clinical factors which affect the pharmacokinetics of pyrazinamide and its metabolites in order to suggest individualized dosing regimens. Plasma concentrations of pyrazinamide, pyrazinoic acid, and 5-hydroxypyrazinamide from 63 Rwandan patients coinfected with tuberculosis and HIV were determined by liquid chromatography-tandem mass spectrometry followed by nonlinear mixed-effects modeling. Females had a close to 50% higher relative pyrazinamide bioavailability compared to males. The distribution volumes of pyrazinamide and both metabolites were lower in patients on concomitant efavirenz-based HIV therapy. Furthermore, there was a linear relationship between serum creatinine and oral clearance of pyrazinoic acid. Simulations indicated that increasing doses from 25 mg/kg of body weight to 35 mg/kg and 50 mg/kg in females and males, respectively, would result in adequate exposure with regard to suggested thresholds and increase probability of target attainment to >0.9 for a MIC of 25 mg/liter. Further, lowering the dose by 40% in patients with high serum creatinine would prevent accumulation of toxic metabolites. Individualized dosing is proposed to decrease variability in exposure to pyrazinamide and its metabolites. Reducing the variability in exposure may lower the risk of treatment failure and resistance development.

Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like malformations of the microvasculature of the central nervous system. Current medical treatment of CCM lesions is limited to surgical removal of the vascular malformations. It is, therefore, important to identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in the treatment of infantile hemangioma. In addition, patients with CCM who receive propranolol have demonstrated a reduction of their lesions. Our investigation set out to provide preclinical data to support propranolol as a therapeutic treatment. Methods: An inducible endothelial-specific Ccm3 knockout murine model (CCM3 iECKO ) was used, with assessment of lesion quantity and size following oral treatment with propranolol. Scanning and transmission electron microscopy were used to characterize the CCM3 iECKO lesions and the effects of propranolol on the disease. Immunofluorescent imaging was used to investigate pericyte coverage in the propranolol-treated CCM3 iECKO mice. Results: With propranolol treatment, the lesion quantity, size, and volume decreased in both the brain and retina in the CCM3 iECKO model. Novel characteristics of the CCM3 iECKO lesions were discovered using electron microscopy, including plasmalemmal pits and thickening of the endothelial-pericyte basal membrane. These characteristics were absent with propranolol treatment. Pericyte coverage of the CCM3 iECKO lesions increased after propranolol treatment, and vascular leakage was reduced. Conclusions: This study supports the concept that propranolol can be used to reduce and stabilize vascular lesions and can, therefore, be suggested as a pharmaceutical treatment for CCM.

We investigated associations between prenatal and postnatal environmental factors and onset and remission of preschool childhood eczema across China. The study population was preschoolers in randomized day care centers in seven cities (N = 39,782). Data on eczema and prenatal and postnatal indoor and outdoor environment were obtained from a cross-sectional questionnaire sent to parents or other guardians. Reports on eczema in the first 2 years and in the past year was used to retrospectively calculate onset and remission (changes of reported eczema). Prenatal and postnatal outdoor temperature, NO2 and PM10 were modelled from official air pollution data. Associations were estimated by two-level logistic regression. Calculated onset rate was 3.2%/y and remission rate 29.2%/y. Exposure to NO2 during pregnancy was associated with onset of eczema, similarly for all trimesters. Postnatal PM10 and NO2 were related to decreased remission. Postnatal outdoor temperature was associated with onset of eczema. Pre-natal and current redecoration or buying new furniture, and perinatal as well as current dampness and indoor mould, were associated with increased onset and decreased remission. Cockroaches in current home was another indoor risk factors. Prenatal exposure to farm environment and large family size were all negatively associated with eczema. In conclusion, a warmer climate and prenatal NO2 can be associated with increased onset of eczema in Chinese preschoolers. Postnatal PM10 and NO2 can be associated with reduced remission. Perinatal and current dampness, indoor mould and cockroaches may increase onset and decrease remission. Exposure to chemical emissions from indoor materials after first year of life may increase onset. Prenatal exposure to farm environment and large family size could be protective.

ObjectiveTo assess associations of health-related quality of life (HRQoL) with patient profile, resource use, cardiovascular (CV) events and mortality in stable patients post-myocardial infarction (MI).MethodsThe global, prospective, observational TIGRIS Study enrolled 9126 patients 1–3 years post-MI. HRQoL was assessed at enrolment and 6-month intervals using the patient-reported EuroQol-5 dimension (EQ-5D) questionnaire, with scores anchored at 0 (worst possible) and 1 (perfect health). Resource use, CV events and mortality were recorded during 2-years’ follow-up. Regression models estimated the associations of index score at enrolment with patient characteristics, resource use, CV events and mortality over 2-years’ follow-up.ResultsAmong 8978 patients who completed the EQ-5D questionnaire, 52% reported ‘some’ or ‘severe’ problems on one or more health dimensions. Factors associated with a lower index score were: female sex, older age, obesity, smoking, higher heart rate, less formal education, presence of comorbidity (eg, angina, stroke), emergency room visit in the previous 6 months and non-ST-elevation MI as the index event. Compared with an index score of 1 at enrolment, a lower index score was associated with higher risk of all-cause death, with an adjusted rate ratio of 3.09 (95% CI 2.20 to 4.31), and of a CV event, with a rate ratio of 2.31 (95% CI 1.76 to 3.03). Patients with lower index score at enrolment had almost two times as many hospitalisations over 2-years’ follow-up.ConclusionsClinicians managing patients post-acute coronary syndrome should recognise that a poorer HRQoL is clearly linked to risk of hospitalisations, major CV events and death.Trial registration numberClinicalTrials.gov Registry (NCT01866904) (https://clinicaltrials.gov).

This paper studied associations between reported common cold and home dampness and mould, cleaning habits and ventilation, climate and outdoor air pollution in China among young adults without asthma or allergic rhinitis. Parents of children attending day care in eight Chinese cities answered a questionnaire on their health and home environment (75% response rate). We restricted the population to subject without asthma or allergic rhinitis (N = 37,275). Temperature and air pollution data was obtained from monitoring stations. Associations were estimated by multilevel logistic regression. Totally 12.5% reported common cold (≥3 colds) and 1.6% frequent common cold (≥5 colds) in the past 12 months. Female gender (OR = 1.53; 95% CI 1.37-1.71), residents in southern China (OR = 1.89; 95% CI 1.16-3.07) and living in homes with water leakage (OR = 1.32; 95% CI 1.16-1.50), mould odour (OR = 1.48; 95% CI 1.28-1.72), indoor mould (OR = 1.47; 95% CI 1.28-1.70), condensation on window panes (OR = 1.42; 95% CI 1.32-1.52) and damp bed clothing (OR = 1.19; 95% CI 1.11-1.28) were associated with common cold. Having many signs of dampness increased ORs. Daily cleaning (OR = 0.91; 95% CI 0.85-0.97) and mechanical ventilation in kitchen or bathroom (OR = 0.75; 95% CI 0.64-0.89) were protective. Higher mean ambient temperature (OR = 1.11 per °C; 95% CI 1.02-1.21), PM

Children spend most of their indoors time at home, which may have substantial influence on their health. We conducted a cross-sectional study in the Tianjin area, China to quantify the incidence of respiratory infections among children, and its association with home environments and lifestyles. The lifetime-ever incidences of croup, pneumonia and ear infection among children aged 0&ndash, 8 in Tianjin area was 9.2%, 28.7% and 11.6%, respectively. The incidence of common cold infections more than twice per year was 31.3%. Home environments and lifestyles included strong risk factors for childhood respiratory infections. Perceived dry air had the greatest association with childhood common colds (population attributable fraction (PAF = 15.0%). Modern floor covering had the greatest association with croup (PAF = 14.7%) and ear infection (PAF = 34.5%), while infrequent bedding sun-curing had the greatest association with pneumonia (PAF = 18.7%). Condensation (a proxy of poor ventilation) accounted for 12.2% of the incidence of croup (PAF = 12.2%) and frequent common colds (PAF = 8.4%). Our findings indicate that factors related to &ldquo, modern&rdquo, home environments and lifestyles are risks for childhood respiratory infections. Modifying such factors might reduce the incidence of respiratory infections among children.

Aims/hypothesisDyslipidemia is an important modifiable risk factor and lipid-lowering treatment (LLT) is essential to reduce the risk of cardiovascular disease (CVD). Studies in type 2 diabetes indicate that low adherence to statin therapy is a barrier to reach full protective potential, and less is known in type 1 diabetes (T1D). The aim was to assess risk of CVD by adherence and nonpersistence to LLT in T1D. MethodA population-based study with a retrospective longitudinal design was conducted between 2006 and 2010, with follow-up until December 2013. In total, 6192 adult individuals with T1D, initiating LLT between 2006 and 2010, were included. Information on LLT, socioeconomic characteristics, comorbidities and cardiovascular events were collected. After 18 months, refill adherence was estimated by calculating medication possession ratio (MPR). Nonpersistence was defined as being without medicines on hand for at least 180 days. Individuals were thereafter followed until CVD, death or end of follow-up in December 2013. Cox regression analyses were performed to assess adherence level and nonpersistence of LLT as predictor of CVD. Analyses were adjusted for cardiovascular risk factors and socioeconomic status. ResultsMean MPR was 72%, 52% of the participants had an MPR above 80% and 27% discontinued LLT. There were 637 nonfatal and 58 fatal CVD events, mean follow-up 3.6 and 3.9 years, respectively. MPR above 80% was associated with reduced risk for nonfatal CVD compared with lower MPR, HR 0.78 (95% CI 0.65 to 0.93)). For fatal CVD, results indicated a negative effect of high adherence but the association did not reach statistical significance, HR 1.96 (0.96 to 4.01). Individuals discontinuing LLT had higher risk of nonfatal CVD, HR 1.43 (95% CI 1.18 to 1.73). Conclusions/InterpretationIn T1D, the risk for nonfatal CVD was lower among individuals with high adherence and higher among those discontinuing LLT within 18 months. It is important to evaluate and emphasize adherence to prescribed LLT at clinical visits to achieve treatment goals and reduce the risk of CVD.

Bio-logging devices can provide unique insights on the life of freely moving animals. However, implanting these devices often requires invasive surgery that causes stress and physiological side-effects. While certain medications in connection to surgeries have therapeutic capacity, others may have aversive effects. Here, we hypothesized that the commonly prescribed prophylactic treatment with enrofloxacin would increase the physiological recovery rate and reduce the presence of systemic inflammation following the intraperitoneal implantation of a heart rate bio-logger in rainbow trout (Oncorhynchus mykiss). To assess post-surgical recovery, heart rate was recorded for 21 days in trout with or without enrofloxacin treatment. Contrary to our hypothesis, treated trout exhibited a prolonged recovery time and elevated resting heart rates during the first week of post-surgical recovery compared to untreated trout. In addition, an upregulated mRNA expression of TNFα in treated trout indicate a possible inflammatory response 21 days post-surgery. Interestingly, the experience level of the surgeon was observed to have a long-lasting impact on heart rate. In conclusion, our study showed no favorable effects of enrofloxacin treatment. Our findings highlight the importance of adequate post-surgical recovery times and surgical training with regards to improving the welfare of experimental animals and reliability of research outcomes.

Few Chinese population studies exist on early life risk factors for furry pet allergy.We studied childhood respiratory symptoms when in contact with furry pets in relation to early life exposure. Moreover, we studied similar environmental associations for rhinitis not related to furry pets.Children aged 3-6 y from day care centres in seven Chinese cities participated (N = 39,782). Parents answered a questionnaire on home environment and children's health, including rhinoconjunctivitis and wheeze when in contact with furry pets, and diagnosed rhinitis. Prenatal and postnatal outdoor temperature, PMTotally 2% had cats, 4% dogs, and 3.2% had rhinoconjunctivitis or wheeze when in contact with furry pets (FP symptoms). Moreover, 1.1% had furry pet related diagnosed rhinitis and 7.5% had diagnosed rhinitis not related to furry pets (other diagnosed rhinitis). Prenatal PMPrenatal outdoor PM

The extensive literature has reported adverse effects on environmental tobacco smoke (ETS) on children’s health. We aim to analyze associations of ETS with dry night cough, croup, pneumonia, and frequent common cold and to disentangle the effects of prenatal, infancy and childhood exposure by multilevel logistic regression. A cross-sectional study was conducted among 41,176 children aged 3–8 years in 8 major cities of China during 2010–2011, and obtained demographic information, smoke exposure information, and respiratory outcomes. Parents’ smoking habit and indoor tobacco smoke odor were considered as two indicators of ETS. The prevalences of respiratory outcomes were 6.0% for croup, 9.5% for frequency common cold, 17.1% for dry night cough and 32.3% for pneumonia respectively in the study. The associations between respiratory outcomes and parental smoking were not obvious, while indoor tobacco smoke odor was clearly and strongly associated with most respiratory outcomes, with adjusted odds ratios ranging from 1.06 to 1.95. Both infancy and childhood exposure to tobacco smoke odor were independent risk factors, but infancy exposure had a higher risk. The results explore that ETS increased the risk of respiratory outcomes in children, highlighting the need for raising awareness about the detrimental effects of tobacco smoke exposure.

Background Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription. Methods Observations in 2007 − 2014 for T2DM patients age ≥ 18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C ≥ 2.5 mmol/l and LDL-C ≥ 1.8 mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio. Results A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4 mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7 mmol/l. During 2007–2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age ≥ 80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention. Conclusions Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk. Electronic supplementary material The online version of this article (10.1186/s12913-018-3707-4) contains supplementary material, which is available to authorized users.

Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials.To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs.The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio.Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery.It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group.Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group.There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group.Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.

Objectives To analyse attitudes towards sales and use of over-the-counter (OTC) drugs in the Swedish adult population. Methods Data were collected through the web-based Citizen Panel comprising 21 000 Swedes. A stratified sample of 4058 participants was emailed a survey invitation. Questions concerned use of OTC drugs, and attitudes towards sales and use of OTC drugs. Correlations between the attitudinal statements were assessed using Spearman’s rank correlation. Associations between attitudes and participant characteristics were analysed using multinomial logistic regression. Key findings Participation rate was 64%. Altogether 87% reported use of OTC drugs in the last 6 months. Approximately 10% of participants stated that they used OTC drugs at the first sign of illness, and 9% stated that they used more OTC drugs compared with previously, due to increased availability. The statement on use of OTC drugs at first sign of illness correlated with the statement about using more OTC drugs with increased availability. Socio-demographic factors (age, sex and education) and frequent use of OTC drugs were associated with attitudes to sales and use of OTC drugs. Conclusions Increased use due to greater availability, in combination with OTC drug use at first sign of illness illustrates the need for continuous education of the population about self-care with OTC drugs. Increased awareness of the incautious views on OTC drugs in part of the population is important. Swedish policy-makers may use such knowledge in their continuous evaluation of the 2009 pharmacy reform to review the impact of sales of OTC drugs in retail outlets on patient safety and public health. Pharmacy and healthcare staff could be more proactive in asking customers and patients about their use of OTC drugs and offering them advice.

Objective: Knowledge about the stress response in children with cleft lip and/or palate (CL/P) is sparse and the association between the stress response and health-related quality of life (HRQoL) is unknown. Consequently, investigations on the influence of CL/P on the stress response alone and its association with HRQoL are of importance. The purpose was to determine whether salivary cortisol concentration in children with CL/P differs from that in children without clefts (controls) and whether there are any differences in salivary cortisol concentrations between ages, gender, and type of cleft. Furthermore, the final aim was to determine the correlation between salivary cortisol concentration and HRQoL. Design: The study used a cross-sectional case-control design. Participants: Ninety-one 5- and 10-year-old children with CL/P and 180 age-matched controls. Main Outcome Measures: Salivary samples were collected on 2 mornings and 1 evening for each child. Samples were analyzed using a commercial competitive radioimmunoassay and HRQoL was assessed using the KIDSCREEN-52. Results: Salivary cortisol concentrations were similar in children with CL/P and controls. There was no difference in salivary cortisol concentrations between children with different types of cleft. There was no correlation between cortisol concentration and HRQoL. Conclusion: Five- and 10-year-old children with corrected CL/P seemed not to be more stressed than controls, and there were no correlation to HRQoL. The HRQoL levels - were comparable to that of a European norm population.

Hyperuricemia and gout are common in patients with heart failure (HF) and are associated with poor outcomes. Data describing hyperuricemia and gout in patients with HF with preserved ejection fraction (HFpEF) are limited. We used data from the Duke University Health System to describe characteristics of patients with HFpEF and hyperuricemia (serum uric acid >6 mg/dl) or gout (gout diagnosis or gout medication within the previous year) and to explore associations with 5-year outcomes (death and hospitalization). We identified 7,004 patients in the Duke University Health System with a known diagnosis of HFpEF who underwent transthoracic echocardiography between January 1, 2005 and December 31, 2017. A total of 1,136 (16.2%) patients with HFpEF also had hyperuricemia or gout. Patients with HFpEF and hyperuricemia or gout had a greater co-morbidity burden, more echocardiographic findings of cardiac remodeling, and higher unadjusted rates of all-cause death, all-cause hospitalization, and HF hospitalization compared with those with HFpEF without hyperuricemia or gout. After multivariable adjustment, patients with HFpEF and hyperuricemia or gout had a significantly higher rates of first all-cause hospitalization (adjusted hazard ratio 1.10 [95% confidence interval 1.02 to 1.19]; p = 0.020) and recurrent all-cause hospitalization (associated rate ratio 1.13 [95% confidence interval 1.01 to 1.25]; p = 0.026). After adjustment, no significant differences in death or HF hospitalization were observed. In conclusion, patients with HFpEF and hyperuricemia or gout were found to have a higher burden of co-morbidities and a higher rate of all-cause hospitalization, even after multivariable adjustment, compared to patients with HFpEF without hyperuricemia or gout.

BACKGROUND: Risk prediction tools are lacking for patients with stable disease some years after myocardial infarction (MI). HYPOTHESIS: A practical long-term cardiovascular risk index can be developed. METHODS: The long-Term rIsk, Clinical manaGement and healthcare Resource utilization of stable coronary artery dISease in post-myocardial infarction patients prospective global registry enrolled patients 1 to 3 years post-MI (369 centers; 25 countries), all with ≥1 risk factor (age ≥65 years, diabetes mellitus requiring medication, second prior MI, multivessel coronary artery disease, or chronic non-end-stage kidney disease [CKD]). Self-reported health was assessed with EuroQoL-5 dimensions. Multivariable Poisson regression models were used to determine key predictors of the primary composite outcome (MI, unstable angina with urgent revascularization [UA], stroke, or all-cause death) over 2 years. RESULTS: The primary outcome occurred in 621 (6.9%) of 9027 eligible patients: death 295 (3.3%), MI 195 (2.2%), UA 103 (1.1%), and stroke 58 (0.6%). All events accrued linearly. In a multivariable model, 11 significant predictors of primary outcome (age ≥65 years, diabetes, second prior MI, CKD, history of major bleed, peripheral arterial disease, heart failure, cardiovascular hospitalization (prior 6 months), medical management (index MI), on diuretic, and poor self-reported health) were identified and combined into a user-friendly risk index. Compared with lowest-risk patients, those in the top 16% had a rate ratio of 6.9 for the primary composite, and 18.7 for all-cause death (overall c-statistic; 0.686, and 0.768, respectively). External validation was performed using the Australian Cooperative National Registry of Acute Coronary Care, Guideline Adherence and Clinical Events registry (c-statistic; 0.748, and 0.849, respectively). CONCLUSIONS: In patients >1-year post-MI, recurrent cardiovascular events and deaths accrue linearly. A simple risk index can stratify patients, potentially helping to guide management.

Semagacestat, a γ-secretase inhibitor, demonstrated an unfavorable risk–benefit profile in a Phase 3 study of patients with Alzheimer’s disease (IDENTITY trials), and clinical development was halted. To assist in future development of γ-secretase inhibitors, we report detailed safety findings from the IDENTITY study, with emphasis on those that might be mechanistically linked to γ-secretase inhibition. The IDENTITY trial was a double-blind, placebo-controlled trial of semagacestat (100 mg and 140 mg), in which 1537 patients age 55 years and older with probable Alzheimer’s disease were randomized. Treatment-emergent adverse events (TEAEs) are reported by body system along with pertinent laboratory, vital sign, and ECG findings. Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. With few exceptions, differences between semagacestat and placebo treatment groups were no longer significant after cessation of treatment with active drug. Many of these safety findings can be attributed to γ-secretase inhibition, and may be valuable to researchers developing γ-secretase inhibitors.

In an outbreak of measles in Gothenburg, Sweden, breakthrough infections (i.e. infections in individuals with a history of vaccination) were common. The objective of this study was to compare measles RNA levels between naïve (i.e. primary) and breakthrough infections. We also propose a fast provisional classification of breakthrough infections. Medical records were reviewed and real-time PCR-positive samples genotyped. Cases were classified as naïve, breakthrough or vaccine infections. We compared clinical symptoms and measles RNA cycle threshold (Ct) values between breakthrough and naïve infections. Sixteen of 28 confirmed cases of measles in this outbreak were breakthrough infections. A fast provisional classification, based on previous history of measles vaccination and detectable levels of measles IgG in acute serum, correctly identified 14 of the 16 breakthrough infections, confirmed by IgG avidity testing. Measles viral load was significantly lower in nasopharyngeal samples from individuals with breakthrough compared with naïve infections (median Ct-values: 32 and 19, respectively, p

ObjectiveTo analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients’ (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers’ (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier.ResultsCompared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%–51 % for CV events, doubled for all-cause mortality and 79%–90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%–19% for CV events, 88%–97% for all-cause and 66%–79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence ConclusionsOur results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.

The main aim was to study associations between asthma, allergic rhinitis and eczema among adults across China and dampness and mold at home. Young adults (N = 40,279) in eight cities in China answered a questionnaire in 2010–2012 (response rate 75.0%). Data on asthma, allergic rhinitis, eczema and the home environment was assessed by the questionnaire. Climate data was obtained from China Meteorological Administration and the website of Weather Underground. Health associations were analyzed by two-level logistic regression models, adjusting for covariates. Totally 1.6% had asthma, 6.6% allergic rhinitis and 2.2% eczema. Mold odor was associated with asthma (OR = 1.90) and allergic rhinitis (OR = 1.25–1.44). Window pane condensation in winter was associated with asthma (OR = 1.39), allergic rhinitis (OR = 1.26–1.58) and eczema (OR = 1.36–1.77). Presence of mold spots or damp stains was related to asthma (OR = 1.58–2.49), allergic rhinitis (OR = 1.35–1.76) and eczema (OR = 1.47–1.70). Water damage was related to asthma (OR = 1.69–1.82), allergic rhinitis (OR = 1.40–1.45) and eczema (OR = 1.44–1.96). Damp bed clothing was related to asthma (OR = 1.23), allergic rhinitis (OR = 1.23) and eczema (OR = 1.35). A higher dampness score was associated with increased odds ratios for diseases. Those living in older buildings had more asthma (OR = 1.39–1.76) and allergic rhinitis (OR = 1.16–1.21). Those living in suburban or rural areas had less asthma, allergic rhinitis and eczema as compared to those living in urban areas (OR values from 0.24 to 0.66). Stronger health associations with dampness and mold were found in southern China and in newer buildings (constructed after 2005). In conclusion, dampness and mold at home can be risk factors for asthma, allergic rhinitis and eczema among adults in China. Living in older buildings can be risk factors for asthma or allergic rhinitis while living in less urbanized areas can be protective. Keywords: Asthma, Allergic rhinitis, Eczema, Dampness, Mold, Climate

Objective The objective of the study is to assess how well the emergency department (ED) personnel succeed in instructing the patient at discharge. Methods In November and December 2016 at Peijas Hospital ED, Finland, a structured questionnaire was conducted during a phone interview on patients the day after discharge. Results A total of 132 patients interviewed. Ninety percent had received discharge instructions from the ED staff, most of them (75%) about medication. Almost half of the patients (45%) were satisfied with the communication at discharge, those not satisfied (47%) felt that the staff did not know enough of their background to give discharge instructions. Of the patients, 20% thought that they did not have the opportunity to ask questions during the guidance session, and 41% thought that the session was too short and restricted. Some patients (20%) felt that the instructions were ambiguous, but 63% (83/132) felt they were able to follow them well or very well. Conclusion The pace of care in the ED is fast and duration of the stay is short. The patients must be able to take responsibility of their self-care. Failure to follow medical discharge instructions could lead to non-compliance. Attention should be paid to enhancing the quality of discharge instructing and the instructions provided by the ED personnel, as recurring visits and inquiry calls add to the ED workload.

Asthma, rhinitis, and eczema are becoming increasingly prevalent among children in China. Studies have shown that the perinatal period is critical and impacts children’s health. However, research on the associations between perinatal factors and childhood allergic diseases in China are few. We investigated 7366 children of ages 0–8 years old. The childhood asthma and allergies were surveyed by distributing questionnaires, modelled after Dampness in Buildings and Health (DBH) study in Sweden and had been validated. To determine the prevalence of the allergic conditions, explore for potential confounders, and analyze the associations between the allergies and the home environmental factors, chi-square test and binary logistic regression models (enter method) were employed. The prevalence of children’s doctor-diagnosed asthma, rhinitis, and eczema were 4.4%, 9.5%, and 39.1%, respectively. After adjusting for sociodemographic factors, the negative effect of dampness/humidity on children’s health became more obvious, with odd ratios (aORs) of up to 1.70 (95% confidence interval (CI): 1.12–2.57) for doctor-diagnosed asthma (DDA), 2.12 (95% CI: 1.38–3.25) for doctor-diagnosed rhinitis (DDR) and 1.79 (95% CI: 1.46–2.21) for doctor-diagnosed eczema (DDE). With parental smoking, aORs of up to 4.66 (95% CI: 1.99–10.92) for DDA and 1.74 (95%: 1.00–3.02) for DDE. Renovation exhibited aORs of up to 1.67 (95% CI: 1.13–2.47) for DDR. Although they showed no significant associations with some of the health outcomes, contact with animals, in general, were risk factors for the allergic conditions. Generally, the indoor environmental factors around the perinatal period were significant risk factors for the doctor-diagnosed allergic conditions discussed in this study.

Background Evidence linking long-term exposure to outdoor air pollution with allergic rhinitis (AR) in children is scare, and the role of components of air pollution and timing of exposure remains unclear. Objective To assess the association of pre- and post-natal exposure to air pollution with life-time prevalence of AR in preschool children. Methods We conducted a cohort study of 2598 children aged 3–6 years in Changsha, China. The lifetime prevalence of AR was assessed by a questionnaire administered by parents. Children's exposures to dioxide nitrogen (NO 2 ), sulfur dioxide (SO 2 ) and particulate matter with an aerodynamic diameter ≤ 10 μm (PM 10 ) during different pre- and post-natal timing windows were estimated using the measured concentrations at monitoring stations. The odds ratio (OR) and 95% confidence interval (CI) of childhood AR for exposure to different air pollutants during different timing windows were assessed by logistic regression model in terms of an interquartile range (IQR) increase in exposure level. Results Life-time prevalence of AR in preschool children (7.3%) was associated with both pre- and post-natal exposure to traffic-related air pollution (TRAP), but only significant during the third trimester of pregnancy with adjusted OR = 1.40 (95% CI: 1.08–1.82) for a 15 μg/m 3 increase in NO 2 and during the first-year of life with adjusted OR = 1.36 (95% CI: 1.03–1.78) and 1.54 (95% CI: 1.07–2.21) respectively for 11 and 12 μg/m 3 increase in NO 2 and PM 10 . The association of early life exposure to TRAP with childhood AR was robust by adjusting for other air pollutants and timing windows. Sensitivity analysis indicated that the association was higher in the children who are male, young, with genetic predisposition by parental atopy, and living in damp houses. Conclusion Early life exposure to traffic-related air pollutant during pregnancy and first-year of life may contribute to childhood AR.

Whether ambient air pollution is associated with childhood atopic eczema is controversial. In this paper, we selected 3358 preschool children who had not altered residences since pregnancy from a cross-sectional study during 2011-2012 in Shanghai, China, and obtained parent-reported data regarding childhood atopic eczema using an improved ISAAC questionnaire. We recorded daily concentrations of SO2, NO2, and PM10 throughout the child's lifetime (2006-2012), and calculated period-averaged concentrations for each district where the child lived to represent the child's exposure levels of these pollutants during different periods. In the multiple logistic regression analyses adjusted for potential confounders as well as for the other pollutants in the same periods, childhood atopic eczema was significantly associated with increments of NO2 in the approximate interquartile range (20μg/m3) during gestational period (adjusted OR, 95% CI for eczema lifetime-ever: 1.80, 1.29-2.49; for eczema in the year prior to the survey: 2.32, 1.57-3.43) and during the first year of life (2.00, 1.40-2.84; 2.16, 1.43-3.28). Exposure to elevated NO2 in the first two years, three years and total lifetime, as well as exposure to mixtures containing NO2 in each of these periods, were consistently associated with increased likelihood of childhood eczema. The highest odds ratios were found between exposure to a mixture of SO2 and NO2 during total lifetime (increment: 35μg/m3) and childhood eczema (adjusted OR, 95% CI: 2.80, 1.75-4.48; 3.50, 1.98-6.19). No significant associations were found between childhood eczema and ambient SO2 and PM10 individually or in mixtures. This study indicates that gestational and lifetime exposures to ambient NO2 are risk factors for atopic eczema in childhood. Exposure to ambient SO2 and PM10 may enhance the effect of NO2 exposure on childhood eczema.

The purpose of this study are to analyse adherence to antidepressant treatment over 2 years in Sweden among women and men who initiated treatment with citalopram and to identify groups at risk of non-adherence using trajectory models.The study population, including individuals 18-85 years who initiated citalopram use between 1 July 2006 and 30 June 2007, was identified in the Swedish Prescribed Drug Register and followed for 2 years. Adherence was estimated with continuous measure of medication acquisition (CMA) and group-based trajectory modelling, a method which describes adherence patterns over time by estimating trajectories of adherence and the individual's probability of belonging to a specific trajectory.The study population included 54,248 individuals, 64 % women. Mean CMA was 52 % among women and 50 % among men (p 0.001). Five different adherence patterns (Trajectories) were identified. Similar proportion of women and men belonged to each Trajectory. Around 29 % of the women and 27 % of the men belonged to the Trajectory which showed full adherence throughout the 2-year study period. The other four Trajectories showed adherence that declined to different degrees and at different stages in time. Having low socioeconomic status was more common among individuals in Trajectories showing declining adherence than in the adherent Trajectory.Using trajectory modelling, five Trajectories describing different patterns of adherence to citalopram treatment over time were identified. A large proportion discontinued treatment early and having low socioeconomic status increased the risk of being non-adherent.

Background: Associations of ambient air pollutants with respiratory health are inconsistent. Objectives: We analyzed the associations of gestational and early life exposures to air pollutants with doctor-diagnosed asthma, allergic rhinitis, and pneumonia in children. Methods: We selected 3358 preschool children who did not alter residences after birth from a cross-sectional study in 2011–2012 in Shanghai, China. Parents reported children's respiratory health history, home environment, and family lifestyle behaviors. We collected daily concentrations of sulphur dioxide (SO2), nitrogen dioxide (NO2), and particulate matter with an aerodynamic diameter ≤10 μm (PM10) during the child's total lifetime (2006–2012) for each district where the children lived. We analyzed the associations using logistic regression models. Results: After adjusting for covariates and the other studied pollutants, we found that exposure to NO2 (increment of 20 μg/m3) during the first year of life was significantly associated with asthma [odds ratio (OR) = 1.77; 95% confidence interval (CI): 1.29–2.43] and allergic rhinitis (OR = 1.67; 95% CI: 1.07–2.61). Exposure to NO2 during gestation, the first two and three years, and over total lifetimewas all consistently associated with increased odds of allergic rhinitis. Quartiles of NO2 concentration during different exposure periods showed a slight dose–response relationship with the studied diseases. These diseases had significant associations with pollutant mixtures that included NO2, but had no significant association with exposures to SO2 and PM10 individually or in mixtures. Conclusions: Gestational and early life exposures to ambient NO2 are risk factors for childhood respiratory diseases. Keywords: Ambient air pollution, Asthma, Allergic rhinitis, Pneumonia, Childhood, Shanghai

In Finland, the care of older persons is shifting from institutional care to family care. Research shows that family caregivers experience their situation much in the same way as professional nurses. The nurses' experiences have been studied in terms of vulnerability, and the same perspective could deepen our understanding of family caregivers' experiences. The aim of this study was to gain knowledge of the vulnerability of older caregivers taking care of an ageing family member. The research questions were as follows: How do family caregivers experience vulnerability? How do their experiences relate to vulnerability as understood by nurses? The study was done as a secondary analysis of focus group interviews on the experiences and daily life of older family caregivers. Four caregivers had taken part in monthly interviews during a period of 10 months. The interviews were analysed by deductive and inductive content analysis. The results showed that the caregivers saw caregiving as part of being human. They experienced a variety of feelings and moral agony and were harmed physically, mentally and socially. They showed courage, protected themselves and recognised that being a caregiver also was a source of maturing and developing. These results corresponded with the nurses' understanding of vulnerability. Shame, the experience of duty as a burden, worry and loneliness were themes that were found only among the family caregivers. The use of a matrix may have restricted the analysis, but using it in an unconstrained way allowed for new themes to be created. The results indicate a common humanness and vulnerability in professional and family caregiving. They also show that family caregivers need more support both from society and professionals.

Introduction Mild-Alzheimer's disease (AD) subjects without significant Aβ pathology represent a confounding finding for clinical trials because they may not progress clinically on the expected trajectory, adding variance into analyses where slowing of progression is being measured. Methods A prediction model based on structural magnetic resonance imaging (MRI) in combination with baseline demographics and clinical measurements was used to impute Aβ status of a placebo-treated mild-AD sub-cohort (N = 385) of patients participating in global phase 3 trials. The clinical trajectories of this cohort were evaluated over 18 months duration of the trial, stratified by imputed Aβ status within a mixed-model repeated measures statistical framework. Results In the imputed Aβ-positive cohort, both cognitive (ADAS-Cog 14 and MMSE) and functional (ADCS-iADL) measures declined more rapidly than in the undifferentiated population. Discussion Our results demonstrate imputing Aβ status from MRI scans in mild-AD subjects may be a useful screening tool in global clinical trials if amyloid measurement is not available.

During 2010–2012, we conducted an observational study on household environment and health outcomes among 40,010 preschool children from seven cities of China. Here we examined associations of six dampness-related indicators (visible mold spots, visible damp stains, damp clothing and/or bedding, water damage, condensation on windowpane, moldy odor) in the current residence and three dampness-related indicators (visible mold spots, condensation on windowpane, moldy odor) in the early residence with childhood asthma and rhinitis. In the multi-level logistic regression analyses, visible mold spots and visible damp stains in the current residence were significantly associated with the increased odds of doctor-diagnosed asthma and allergic rhinitis during lifetime-ever (adjusted odd ratios (AORs) range: 1.18–1.35). All dampness-related indicators were significantly associated with increased odds of wheeze and rhinitis during lifetime-ever and in the past 12 months (AORs range: 1.16–2.64). The cumulative numbers of damp indicators had positively dose-response relationships with the increased odds of the studied diseases. These associations for wheeze and rhinitis were similar between northern children and southern children. Similar results were found in the sensitive analyses among children without a family history of allergies and among children without asthma and allergic rhinitis. For 3–6 years-old children in mainland of China in 2011, we speculated that about 90,000 (2.02%) children with asthma and about 59,000 (1.09%) children with allergic rhinitis could be attributable to exposing to visible mold spots in the current residence. Our results suggested that early and lifetime exposures to household dampness indicators are risk factors for childhood asthma and rhinitis. Keywords: Home, Dampness, Asthma, Rhinitis, Children, China

The frequency of viral respiratory pathogens in asymptomatic subjects is poorly defined. The aim of this study was to explore the prevalence of respiratory pathogens in the upper airways of asymptomatic adults, compared with a reference population of symptomatic patients sampled in the same centers during the same period. Nasopharyngeal (NP) swab samples were prospectively collected from adults with and without ongoing symptoms of respiratory tract infection (RTI) during 12 consecutive months, in primary care centers and hospital emergency departments, and analyzed for respiratory pathogens by a PCR panel detecting 16 viruses and four bacteria. Altogether, 444 asymptomatic and 75 symptomatic subjects completed sampling and follow-up (FU) at day 7. In the asymptomatic subjects, the detection rate of viruses was low (4.3%), and the most common virus detected was rhinovirus (3.2%). Streptococcus pneumoniae was found in 5.6% of the asymptomatic subjects and Haemophilus influenzae in 1.4%. The only factor independently associated with low viral detection rate in asymptomatic subjects was age ≥65 years (P = 0.04). An increased detection rate of bacteria was seen in asymptomatic subjects who were currently smoking (P

Objective: Few longitudinal studies exist on childhood exposure to indoor and outdoor air pollution and respiratory illness in China. We studied associations between indoor and outdoor environment and prevalence, onset and remission of wheeze and rhinitis among children across China. Methods: Children (3–6 y) were recruited from randomized day care centres in six cities. The main data analysis was restricted to children not moving since birth (N = 17,679). Data on wheeze, rhinitis and the home environment were assessed by a parental questionnaire. Prevalence in the first two years of life (baseline) and the last year (follow-up) was used to calculate onset and remission. Outdoor PM2.5, PM10, and NO2 at the day care centre were modelled from monitoring station data. Associations were calculated by multilevel logistic regression. Results: Prenatal NO2 was associated with decreased remission of wheeze and increased prevalence and increased onset of rhinitis. Prenatal PM2.5 was associated with increased prevalence of wheeze. Postnatal NO2 and postnatal PM10 were associated with increased prevalence and lower remission of wheeze and rhinitis. Mould, window pane condensation, renovation and cockroaches at home were associated with increased prevalence and increased onset of wheeze and rhinitis. Gas cooking was associated with increased onset of rhinitis. Children of mothers with industrial work had more wheeze. Conclusions: Outdoor PM2.5, PM10 and NO2 can increase childhood wheeze and rhinitis. Dampness and mould can increase onset and decrease remission. Crowdedness, cockroaches at home and emissions from new building materials and gas cooking can be risk factors for wheeze and rhinitis. Keywords: Asthma, Rhinitis, Dampness, PM2.5, Traffic-related air pollution (TRAP), Renovation

Introduction: Low back pain (LBP) defined as ache or pain in the lowest part of the back is a common experience among people all over the world. The lifetime prevalence is reported to be as high as 84%, and the prevalence of LBP seems to be almost the same among adolescents as among adults. The risk for having LBP later in life if you experienced LBP in adolescence is high. Material and Methods: In this cross‐sectional study of 2550 students aged 16‐20 years, we used the Standardized Nordic Questionnaire for the analysis of musculo‐skeletal symptoms. We studied gender difference, prevalence, and disability of Low back pain. We also studied differences in LBP in adolescent athletes depending on hours spent on sports or physical activity. Results: Significantly, more girls than boys had had problems sometimes during their life. Those who participated in sports reported LBP to a significantly higher extent than those who were physically inactive in their spare time. Gender and spare time sports were important risk factors for getting LBP some time in life. There was a higher risk for girls to have low back pain problems more than 30 days or daily the last year if they had had low back pain some time earlier in life. Conclusion: This study shows that low back pain (LBP) is common among Swedish adolescents, more common among girls than boys. High sport activity was associated with the risk of having LBP, length of time with LBP, and disability due to LBP.

ObjectivesTo compare short-term cardiovascular (CV) outcome in type 2 diabetes (T2D) patients without ischaemic heart disease (IHD), with IHD but no prior myocardial infarction (MI), and those with prior MI; and assess the impact on risk of age when initiating first-time glucose-lowering drug (GLD).DesignCohort study linking morbidity, mortality and medication data from Swedish national registries.ParticipantsFirst-time users of GLD during 2007–2016.OutcomesPredicted cumulative incidence for the CV outcome (MI, stroke and CV mortality) was estimated. A Cox model was developed where age at GLD start and CV risk was modelled.Results260 070 first-time GLD users were included, 221 226 (85%) had no IHD, 16 294 (6%) had stable IHD—prior MI and 22 550 (9%) had IHD+MI. T2D patients without IHD had a lower risk of CV outcome compared with the IHD populations (±prior MI), (3-year incidence 4.78% vs 5.85% and 8.04%). The difference in CV outcome was primarily driven by a relative greater MI risk among the IHD patients. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger (ConclusionsT2D patients without IHD had a lower risk of the CV outcome compared with the T2D populations with IHD, primarily driven by a greater risk of MI. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger patients had a relative greater risk compared with older patients. Our findings suggest that intense risk prevention should be the key strategy in the management of T2D patients, especially for younger patients.

Purpose: This study aimed to explore the prescription of different contraceptive methods to Swedish women with obesity and to compare the pattern of prescription and adherence to treatment between this group and normal-weight women. Materials and methods: This study included 371 women with obesity and 744 matched normal-weight women, aged 18-40. Medical records were scrutinised for the period 1 January 2010 to 31 December 2014. The retrieved variables included: background characteristics, prescribed contraceptive methods, adverse effects, duration of treatment, reason for discontinuation and bleeding pattern. Result: Progestin-only pills were mainly prescribed to women with obesity (44% vs. 20%, p = 0.001) whereas combined hormonal contraception was mainly prescribed to normal-weight women (60% vs. 21%, p amp;lt; 0.0001). Thirty-three percent vs. 25% (p = 0.003) discontinued their contraceptive method within 1 year. The most commonly declared reason for discontinuation was bleeding disturbance (14.7% vs. 9.6%, p = 0.008). Conclusion: The most commonly prescribed contraceptive method in women with obesity was progestin-only pills, but surprisingly many women with obesity were prescribed combined hormonal contraception despite current Swedish and European guidelines. Incident users with obesity were significantly more likely to discontinue their contraceptive method within the first year of the study period, compared with incident normal-weight users. Funding Agencies|county council of Ostergotland [ALF] [LIO 601741, LIO 697051]

We studied indoor sources of indoor particulate matter (PM), outdoor air pollution and antibiotic use in relation to asthma, rhinitis and eczema among pre-school children and investigated synergistic effects between PM and antibiotics use. Children (3-6y) from randomly selected day care centres in seven cities across China were included (n = 39,782). Data on ambient temperature and air pollution were collected from local monitoring stations. Data on indoor PM sources (ETS, burning of incense or mosquito coils and biomass for cooking), antibiotics use and health (doctor diagnosed asthma and rhinitis, lifetime eczema, current wheeze and current rhinitis) were assessed by a parental questionnaire. Associations were calculated by multilevel logistic regression. Asthma diagnosis was associated with outdoor temperature, NO

Objective To investigate sociodemographic and gender factors associated with suicide and suicide attempts among new users of antidepressants aged 75 and above. Design Register-based cohort study. Setting National population-based cohort of Swedish residents aged ≥75 years. Participants 185 225 patients who initiated antidepressant medication between 1 January 2007 and 31 December 2013 were followed until 31 December 2014. Main outcome measures Suicide and suicide attempts. Fine and Gray regression models were used to analyse the sociodemographic factors (age, country of birth, marital status, education level, last occupation, income and social allowance) associated with suicidal behaviours in the entire cohort and by gender. Results During follow-up, 295 suicides and 654 suicide attempts occurred. Adjusted sub-hazard ratios (aSHRs) for suicide were lower among older age groups (aSHR 0.73, 95% CI 0.53 to 0.99 for those 85–89 years; and aSHR 0.53, 95% CI 0.33 to 0.86 for those ≥90 years). A similar pattern was observed for suicide attempts. Suicide attempts were more common among those born in foreign countries (aSHR 1.58, 95% CI 1.16 to 2.15 for those born in another Nordic country; and aSHR 1.43, 95% CI 1.06 to 1.93 for those born in non-Nordic countries). In the gender-stratified analyses, being single or divorced, and born in another Nordic country was associated with a higher risk of suicide among men. Educational and occupational history and being born in a non-Nordic country influenced risk of suicidal behaviours in women. Conclusion Suicidal behaviours occurred more commonly among new users who were ‘younger’ old adults and those with foreign background, suggesting that those groups might require greater support when initiating antidepressant therapy. Our findings suggest the need for gender-specific, multifaceted approaches to the prevention of suicidal behaviours in late life.

In the past 60 years, the prevalences of asthma and allergy among children have increased around the world. Neither genetic nor outdoor environmental factors can explain this increase. We performed a cross-sectional study of 7366 children in Tianjin, China, on associations of home environment and lifestyles with asthma and allergy. The prevalences of diagnosed asthma, rhinitis and eczema among 0- to 8-year-old children in the Tianjin area were 4%, 9% and 39%. Home environment and lifestyle, together with infections, were strong risk factors. For asthma and allergy, the population attributable fraction (PAF) due to modern floors and wall coverings (i.e., laminated wooden floors and painted walls compared to tile floors and lime-coated walls) was 22%. Window condensation in winter and air conditioner use in summer, both of which are proxies for less ventilation, accounted for 7–17% of rhinitis and eczema. Cesarean delivery accounted for 10% of eczema symptoms. We developed a modern life index from appropriate home characteristics and lifestyle and food consumption habits and found it to have a clear dose–response relationship with asthma and allergy in Tianjin children. The results indicate that a “modern” home environment together with a modern lifestyle is associated with increased prevalences of asthma and allergies among children. Appropriate indoor environmental interventions and education of children’s caregivers are important in the management of childhood asthma and allergy.

This thesis examines the developmental neurotoxic effects of exposure to low-dose ionizing radiation (IR), alone or together with xenobiotics, during a critical period of neonatal brain development in mice.During mammalian brain development there is a period called the brain growth spurt (BGS), which involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to xenobiotics can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. In humans, the BGS starts during the third trimester of pregnancy and continues for approximately 2 years in the child. The present thesis has identified a defined critical period, during the BGS, when IR can induce developmental neurotoxicity in mice. The observed neurotoxicity was not dependent on sex or strain and manifested as altered neurobehaviour in the adult mouse. Furthermore, fractionated dose exposures appear to be as potent as a higher acute dose. The cholinergic system can be a target system for developmental neurotoxicity of IR, since alterations in adult mouse cholinergic system susceptibility were observed. Co-exposure to IR and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction. Furthermore, co-exposure with the environmental agent paraquat has indicated that the dopaminergic system can be a potential target. In this thesis, clinically relevant doses of IR and a sedative/anesthetic agent (ketamine) were shown to interact and exacerbate defects in adult mouse neurobehaviour, learning and memory, following neonatal exposure, at doses where the single agents did not have any impact on the measured variables. This indicates a shift in the dose-response curve for IR, towards lower doses, if exposure occurs during the neonatal brain development. In addition, co-exposed mice, showing cognitive defects, expressed elevated levels of tau protein in the cerebral cortex. Furthermore, exacerbation of neurochemical deviations were observed following co-exposure compared to irradiation alone.Further investigations of neurotoxic effects following fractionated or acute low-dose IR, modelling the clinical situation during repeated CT scans or levels of radiation deposited in non-target tissue during radiotherapy, and possible interaction effects with xenobiotics, is of great importance in the field of radioprotection.

We studied dampness and mold in China in relation to rhinitis, ocular, throat and dermal symptoms, headache and fatigue. A questionnaire study was performed in six cities including 36 541 randomized parents of young children. Seven self-reported signs of dampness were evaluated. Multilevel logistic regression models were used to calculate odds ratios (ORs). Totally, 3.1% had weekly rhinitis, 2.8% eye, 4.1% throat and 4.8% skin symptoms, 3.0% headache and 13.9% fatigue. Overall, 6.3% of the homes had mold, 11.1% damp stains, 35.3% damp bed clothing, 12.8% water damage, 45.4% window pane condensation, 11.1% mold odor, and 37.5% humid air. All dampness signs were associated with symptoms (ORs from 1.2 to 4.6; P < 0.001), including rhinitis (ORs from 1.4 to 3.2; P < 0.001), and ORs increased by number of dampness signs. The strongest associations were for mold odor (ORs from 2.3 to 4.6) and humid air (ORs from 2.8 to 4.8). Associations were stronger among men and stronger in Beijing as compared to south China. In conclusion, dampness and mold are common in Chinese homes and associated with rhinitis and ocular, throat and dermal symptoms, headache and fatigue. Men can be more sensitive to dampness and health effects of dampness can be stronger in northern China.

Background Biomass burning is associated with childhood pneumonia but few studies exist on other indoor factors. Aim To study pneumonia in relation to pre-natal and post-natal exposure among children across China. Methods Children (3–6 y) (n = 39,782) from randomized day care centres in seven cities in China. Information on pneumonia and pre-natal and post-natal exposure to home environment factors were assessed by a parental questionnaire. Life-time outdoor temperature and GDP per capita were assessed on city level. Associations were calculated by multilevel logistic regression adjusting for fourteen co-variates. Results Totally 32.0% had ever had pneumonia diagnosed by a physician. Children of farmer mothers (OR = 0.65), with breastfeeding (OR = 0.91) and living in rural (OR = 0.85) or suburban (OR = 0.90) areas had less pneumonia. Buying new furniture one year before conception (OR = 1.11) and after first year of life (OR = 1.10) increased the risk. Redecoration one year before conception (OR = 1.20), during pregnancy (OR = 1.18) and after first year of life (OR = 1.17) increased pneumonia risk. Children with mould (OR = 1.17), window pane condensation (WPC) (OR = 1.20) and mould odour (OR = 1.15) at home at birth only had a higher risk of pneumonia. Similar associations were seen for dampness and mould in the current home. Children in the oldest and newest homes had less pneumonia. Cockroaches (OR = 1.08), mosquitos or flies in the current home (OR = 1.18), an exhaust fan in the bathroom (OR = 1.10) and higher economic development level, measured as GDP per capita on city level (OR 1.11 per 10,000 RMB/year) were associated with childhood pneumonia. Conclusions Perinatal and postnatal exposure to mould, mould odour and window pane condensation at home can be early life risk factors for childhood pneumonia in China. Moreover, pre-natal and post-natal exposure to chemical emissions from new furniture and renovation could increase the risk of childhood pneumonia. Breastfeeding, farm exposure, and living in rural or suburban areas could be protective.