Mode of delivery and offspring atopic dermatitis in a Swedish nationwide study.

BACKGROUND: Atopic dermatitis is a common chronic childhood disease associated with significant morbidity and healthcare costs. There is a known association between caesarean section and asthma, but the relationship between caesarean section and offspring atopic dermatitis remains uncertain. METHODS: We conducted a register-based nationwide cohort study including children born in Sweden between January 2006 and December 2018. Data on health and socioeconomic variables were extracted from the national registers for children aged ≤5 years. Time-to-event analyses were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) adjusting for confounders and familial factors. RESULTS: 1,399,406 children were included (6,029,542 person-years at risk). Atopic dermatitis was observed in 17.2% of the 1,150,896 children born by vaginal delivery and 18.3% of the 248,510 born by caesarean section. The mean age of onset of atopic dermatitis was 2.72 years (SD 1.8). Birth by caesarean section was associated with a higher risk of atopic dermatitis (adj-HR 1.12, 95% CI: 1.10-1.14). A higher risk of atopic dermatitis was found in children born by instrumental vaginal delivery (adj-HR 1.10, 1.07-1.13); emergency caesarean section (adj-HR 1.12, 1.10-1.15), and elective caesarean section (adj-HR 1.13, 1.10-1.16) than uncomplicated vaginal delivery in children <1 year of age. Similar hazards were observed in those ≥1 year of age. In sibling control analysis, greater risks remained in children aged <1 year but not in age ≥1 year. CONCLUSIONS: In our study population, it was observed that children born by caesarean section or instrumental vaginal delivery were at higher risk of early childhood atopic dermatitis. Although familial confounding attenuates the risk in children aged ≥1 year, this was not observed in the first year of life.

Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

BACKGROUND: Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. METHODS: We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. RESULTS: The 158 patients (56.7 ± 13.6 years, 28.5% female) studied had a median CPP of 40 mmHg (IQR 35-52 mmHg). During 6 months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). CONCLUSION: A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms.

It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.

Systemic arterial pulsatility index (SAPi) predicts adverse outcomes in advanced heart failure patients.

Ventriculo-arterial (VA) coupling has been shown to have physiologic importance in heart failure (HF). We hypothesized that the systemic arterial pulsatility index (SAPi), a measure that integrates pulse pressure and a proxy for left ventricular end-diastolic pressure, would be associated with adverse outcomes in advanced HF. We evaluated the SAPi ([systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure) obtained from the final hemodynamic measurement in patients randomized to therapy guided by a pulmonary arterial catheter (PAC) and with complete data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Cox proportional hazards regression was performed for the outcomes of (a) death, transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and (b) DTxLVAD. Among 142 patients (mean age 56.8 ± 13.3 years, 30.3% female), the median SAPi was 2.57 (IQR 1.63-3.45). Increasing SAPi was associated with significant reductions in DTxLVAD (HR 0.60 per unit increase in SAPi, 95% CI 0.44-0.84) and DTxLVADHF (HR 0.81 per unit increase, 95% CI 0.70-0.95). Patients with a SAPi ≤ 2.57 had a marked increase in both outcomes, including more than twice the risk of DTxLVAD (HR 2.19, 95% CI 1.11-4.30) over 6 months. Among advanced heart failure patients with invasive hemodynamic monitoring in the ESCAPE trial, SAPi was strongly associated with adverse clinical outcomes. These findings support further investigation of the SAPi to guide treatment and prognosis in HF undergoing invasive hemodynamic monitoring.

Association of Early Life Exposure to Antibiotics With Risk of Atopic Dermatitis in Sweden.

Importance: Atopic dermatitis is associated with substantial morbidity in childhood. Further understanding of the underlying factors contributing to its onset is needed. Objective: To assess the association of exposure to antibiotics in the prenatal period and early childhood with risk of atopic dermatitis in a nationwide population in Sweden. Design, Setting, and Participants: This Swedish nationwide, register-based, prospective cohort study used data on mother-child pairs from the Swedish Medical Birth Register linked to other national registers for information on health, socioeconomic, and demographic data. Participants were followed up until an atopic dermatitis outcome, emigration, death, or the end of the study on December 31, 2015. Data for all singleton children and discordant siblings born between March 1, 2006, and December 31, 2010, were included. Data were analyzed from June 1, 2020, to October 31, 2020. Exposures: Maternal exposure to systemic antibiotics during pregnancy as well as the child's exposure to systemic antibiotics during the first year of life, as defined by a dispensed prescription in the Swedish Prescribed Drug Register. Main Outcomes and Measures: Time-to-event analyses were used to estimate the risk of outcome using attained age as a time scale. Atopic dermatitis was defined based on diagnoses in the National Patient Register and medication listed in the Swedish Prescribed Drug Register. Sibling-control analysis was performed to account for shared familial factors. Results: Among the 722 767 singleton children, the mean (SD) age was 5.8 (2.4) years and 351 589 (48.6%) were female. During the follow-up period, 153 407 children (21.2%) were exposed to antibiotics in utero and 172 405 children (23.8%) were exposed during the first year of life. The risk of atopic dermatitis among children exposed to prenatal antibiotics was greater than that among children who were not exposed (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.09-1.12). In the sibling-control analysis, no association was observed (aHR, 0.96; 95% CI; 0.92-1.00). Exposure to antibiotics during the first year of life was associated with a greater risk of atopic dermatitis (aHR, 1.52; 95% CI, 1.50-1.55), with attenuated associations in the sibling-control analysis (aHR, 1.24; 95% CI, 1.20-1.29). Conclusions and Relevance: In this cohort study, exposure to antibiotics in early life was associated with an increased risk of atopic dermatitis in the general Swedish population, but this risk was partially confounded by familial factors. Research on the ways in which antibiotic use and other shared familial factors affect other atopic diseases may be warranted.

The shared risk of diabetes between dog and cat owners and their pets: register based cohort study.

OBJECTIVE: To investigate whether dog and cat owners and their pets share a risk of developing diabetes. DESIGN: Cohort study. SETTING: Register based longitudinal study, Sweden. PARTICIPANTS: 208 980 owner-dog pairs and 123 566 owner-cat pairs identified during a baseline assessment period (1 January 2004 to 31 December 2006). MAIN OUTCOME MEASURES: Type 2 diabetes events in dog and cat owners and diabetes events in their pets, including date of diagnosis during the follow-up period (1 January 2007 to 31 December 2012). Owners with type 2 diabetes were identified by combining information from the National Patient Register, the Cause of Death Register, and the Swedish Prescribed Drug Register. Information on diabetes in the pets was extracted from veterinary care insurance data. Multi-state models were used to assess the hazard ratios with 95% confidence intervals and to adjust for possible shared risk factors, including personal and socioeconomic circumstances. RESULTS: The incidence of type 2 diabetes during follow-up was 7.7 cases per 1000 person years at risk in dog owners and 7.9 cases per 1000 person years at risk in cat owners. The incidence of diabetes in the pets was 1.3 cases per 1000 dog years at risk and 2.2 cases per 1000 cat years at risk. The crude hazard ratio for type 2 diabetes in owners of a dog with diabetes compared with owners of a dog without diabetes was 1.38 (95% confidence interval 1.10 to 1.74), with a multivariable adjusted hazard ratio of 1.32 (1.04 to 1.68). Having an owner with type 2 diabetes was associated with an increased hazard of diabetes in the dog (crude hazard ratio 1.28, 1.01 to 1.63), which was attenuated after adjusting for owner's age, with the confidence interval crossing the null (1.11, 0.87 to 1.42). No association was found between type 2 diabetes in cat owners and diabetes in their cats (crude hazard ratio 0.99, 0.74 to 1.34, and 1.00, 0.78 to 1.28, respectively). CONCLUSIONS: Data indicated that owners of a dog with diabetes were more likely to develop type 2 diabetes during follow-up than owners of a dog without diabetes. It is possible that dogs with diabetes could serve as a sentinel for shared diabetogenic health behaviours and environmental exposures.

Dog Ownership and Survival After a Major Cardiovascular Event: A Register-Based Prospective Study.

BACKGROUND: Dog ownership is associated with increased physical activity levels and increased social support, both of which could improve the outcome after a major cardiovascular event. Dog ownership may be particularly important in single-occupancy households where ownership provides substitutive companionship and motivation for physical activity. METHODS AND RESULTS: We used the Swedish National Patient Register to identify all patients aged 40 to 85 presenting with an acute myocardial infarction (n=181 696; 5.7% dog ownership) or ischemic stroke (n=154 617; 4.8% dog ownership) between January 1, 2001 and December 31, 2012. Individual information was linked across registers for cause of death, sociodemographic, and dog ownership data. We evaluated all-cause mortality and risk of recurrent hospitalization for the same cause until December 31, 2012. Models were adjusted for socioeconomic, health, and demographic factors at study inclusion such as age, marital status, the presence of children in the home, area of residence, and income, as well as all registered comorbidities and hospitalization for cardiovascular disease in the past 5 years. Dog owners had a lower risk of death after hospitalization for acute myocardial infarction during the full follow-up period of 804 137 person-years, with an adjusted hazard ratio (HR) of 0.67 (95% CI, 0.61 to 0.75) for those who lived alone, and HR of 0.85 (95% CI, 0.80 to 0.90) for those living with a partner or a child. Similarly, after an ischemic stroke, dog owners were at lower risk of death during the full follow-up of 638 219 person-years adjusted HR of 0.73 (95% CI, 0.66 to 0.80) for those who lived alone and HR of 0.88 (95% CI, 0.83 to 0.93) for those living with a partner or a child. We further found an association of dog ownership with reduced risk of hospitalization for recurrent myocardial infarction (HR, 0.93; 95% CI, 0.87 to 0.99). CONCLUSIONS: We found evidence of an association of dog ownership with a better outcome after a major cardiovascular event. Although our models are adjusted for many potential confounders, there are also unmeasured confounders such as smoking that prevent us from drawing conclusions regarding a possible causal effect.

Dog ownership and cardiovascular risk factors: a nationwide prospective register-based cohort study.

OBJECTIVE: To study the association between dog ownership and cardiovascular risk factors. DESIGN: A nationwide register-based cohort study and a cross-sectional study in a subset. SETTING: A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use. PARTICIPANTS: All Swedish residents aged 45-80 years on 1 October, 2006. MAIN OUTCOME MEASURES: Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus. RESULTS: After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45-60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status. CONCLUSIONS: In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

Indole-3 acetic acid increased risk of impaired cognitive function in patients receiving hemodialysis.

Patients receiving hemodialysis (HD) have a higher risk of cognitive impairment and dementia than the general population. The accumulation of uremic toxins in the brain causes uremic encephalopathy, however, limited data exists to elucidate the effect of protein-bound uremic toxins on cognitive function. Here we investigate the effect of indole-3 acetic acid (IAA) and hippuric acid (HA), two different protein-bound uremic toxins from amino acid derivatives, on cognitive function by Silico and in a clinical study. Prevalent HD patients were enrolled in two independent hospitals. Serum IAA and HA were measured using mass spectrometry. Cognitive performance was measured using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognitive Abilities Screening Instrument (CASI) by trained psychologists. Using silico data to predict the effect of blood-brain barrier penetration was performed. The silico data demonstrated that IAA and HA had positive blood-brain barrier penetration ability. Amongst the 230 HD patients, serum IAA was associated with poor MMSE score (ß= -0.90, 95% CI -1.61 to -0.19) and poor CASI score (ß= -3.29, 95% CI -5.69 to -0.88) in stepwise multiple linear regression analysis. In logistic regression model, Serum IAA was also associated with cognitive impairment based on MMSE definition (OR, 1.96, 95% CI 1.10, 3.5) and CASI definition (OR, 2.09, 95% CI 1.21, 3.61). There was no correlation between Serum HA levels and cognitive function status. In conclusion, IAA, not HA, was associated with cognitive impairment in HD patients. Further large scale and prospective studies are needed to confirm our findings.

Protein-bound uremic toxins are associated with cognitive function among patients undergoing maintenance hemodialysis.

Patients with chronic kidney disease have a greater risk of cognitive impairment. Cerebral uremic solute accumulation causes uremic encephalopathy; however, the association of protein-bound uremic toxins on cognitive function remains unclear. The present study aimed to investigate the association of two protein-bound uremic toxins, namely indoxyl sulfate (IS) and p-cresyl sulfate (PCS), on cognitive function in patients receiving hemodialysis (HD) for at least 90 days. Circulating free form IS and PCS were quantified by liquid chromatography/mass spectrometry. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate cognitive function. In total, 260 HD patients were recruited with a mean age of 58.1 ± 11.3 years, of which, 53.8% were men, 40% had diabetes, and 75.4% had hypertension. The analysis revealed that both free IS and free PCS were negatively associated with the CASI score and MMSE. After controlling for confounders, circulating free IS levels persisted to be negatively associated with MMSE scores [ß = -0.62, 95% confidence interval (CI): -1.16 to -0.08] and CASI scores (ß = -1.97, 95% CI: -3.78 to -0.16), mainly in the CASI domains of long-term memory, mental manipulation, language ability, and spatial construction. However, there was no correlation between free PCS and total MMSE or total CASI scores after controlling for confounders. In conclusion, circulating free form IS, but not PCS is associated with lower cognitive function test scores in HD patients. Thus, a further study is needed to evaluate whether a decrease in free IS levels can slow down cognitive decline in HD patients.

Dog ownership and the risk of cardiovascular disease and death - a nationwide cohort study.

Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

Climate variability and infectious diseases nexus: Evidence from Sweden.

Many studies on the link between climate variability and infectious diseases are based on biophysical experiments, do not account for socio-economic factors and with little focus on developed countries. This study examines the effect of climate variability and socio-economic variables on infectious diseases using data from all 21 Swedish counties. Employing static and dynamic modelling frameworks, we observe that temperature has a linear negative effect on the number of patients. The relationship between winter temperature and the number of patients is non-linear and "U" shaped in the static model. Conversely, a positive effect of precipitation on the number of patients is found, with modest heterogeneity in the effect of climate variables on the number of patients across disease classifications observed. The effect of education and number of health personnel explain the number of patients in a similar direction (negative), while population density and immigration drive up reported cases. Income explains this phenomenon non-linearly. In the dynamic setting, we found significant persistence in the number of infectious and parasitic-diseased patients, with temperature and income observed as the only significant drivers.

Zambian Women in South Africa: Insights Into Health Experiences of Labia Elongation.

Labia minora elongation consists in the manual stretching of the inner lips of the external genitalia. This practice is documented in east and southern Africa. The experiences of African women in the diaspora practicing elongation are not thoroughly understood. The purpose of this qualitative study was to explore the health harms and benefits associated with this practice of Zambian women who have migrated to Cape Town, South Africa. Twenty women and seventeen men participated in this study. Between December 2013 and May 2014, in-depth interviews and natural group discussions were conducted with the participants. The focus of this article is to report on the emic of the women related to notions of health, hygiene, and well-being. Labial elongation is perceived as a practice involving minor, short-term adverse effects that can be prevented by following some basic hygiene. Overall, personal and social value is placed on this practice because of its reported benefits for the sexual health of men and women, and for women's femininity and self-image. Further research is necessary on how female genital modifications influence Zambians' sexual preferences to inform the development of culturally appropriate health promotion interventions.

Tuberculous Pericarditis is Multibacillary and Bacterial Burden Drives High Mortality.

BACKGROUND: Tuberculous pericarditis is considered to be a paucibacillary process; the large pericardial fluid accumulation is attributed to an inflammatory response to tuberculoproteins. Mortality rates are high. We investigated the role of clinical and microbial factors predictive of tuberculous pericarditis mortality using the artificial intelligence algorithm termed classification and regression tree (CART) analysis. METHODS: Patients were prospectively enrolled and followed in the Investigation of the Management of Pericarditis (IMPI) registry. Clinical and laboratory data of 70 patients with confirmed tuberculous pericarditis, including time-to-positive (TTP) cultures from pericardial fluid, were extracted and analyzed for mortality outcomes using CART. TTP was translated to log10 colony forming units (CFUs) per mL, and compared to that obtained from sputum in some of our patients. FINDINGS: Seventy patients with proven tuberculous pericarditis were enrolled. The median patient age was 35 (range: 20-71) years. The median, follow up was for 11.97 (range: 0·03-74.73) months. The median TTP for pericardial fluid cultures was 22 (range: 4-58) days or 3.91(range: 0·5-8·96) log10CFU/mL, which overlapped with the range of 3.24-7.42 log10CFU/mL encountered in sputum, a multi-bacillary disease. The overall mortality rate was 1.43 per 100 person-months. CART identified follow-up duration of 5·23 months on directly observed therapy, a CD4 + count of ≤ 199.5/mL, and TTP ≤ 14 days (bacillary load ≥ 5.53 log10 CFU/mL) as predictive of mortality. TTP interacted with follow-up duration in a non-linear fashion. INTERPRETATION: Patients with culture confirmed tuberculous pericarditis have a high bacillary burden, and this bacterial burden drives mortality. Thus proven tuberculosis pericarditis is not a paucibacillary disease. Moreover, the severe immunosuppression suggests limited inflammation. There is a need for the design of a highly bactericidal regimen for this condition.