The feasibility and outcome of a community-based primary prevention program for cardiovascular disease in the 21st century

Objective There is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality. This study aimed to evaluate the effectiveness of a primary care CVD prevention program on mortality during a 13-year follow-up. Design A risk factor survey was sent, followed by a nurse-led lifestyle counselling to respondents with at least one CVD risk factor, and a general practitioner's (GP) appointment for high-risk persons. Screening and interventions were performed during 2005-2006. Setting A public health care centre in the town of Harjavalta, Finland. Subjects All home-dwelling 45-70-year old inhabitants without manifested CVD or diabetes. Main outcome measures All-cause and CVD mortality. Results Altogether 74% (2121/2856) inhabitants responded to the invitation. The intervention was received by 1465 individuals (52% of the invited population): 398 risk persons had an appointment with a nurse, followed by an appointment with a GP for 1067 high-risk persons. During the follow-up, 370 persons died. Mortality among the non-respondents was twofold compared to the participants'. In subjects who received the intervention, the age- and gender-adjusted hazard ratio for all-cause mortality was 0.44 (95% CI: 0.36 to 0.54) compared to the subjects who did not receive the intervention. Conclusions Reducing mortality is possible in a primary care setting by raising health awareness in the community with screening, by targeted lifestyle counselling and evidence-based preventive medication for persons at high risk for CVD. Subjects not willing to participate in health surveys have the worst prognosis.Peer reviewe

Renal hyperfiltration revisited—Role of the individual body surface area on mortality

Background: Higher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. Methods: A population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005–2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. Results: The higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. Conclusions: Higher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.Peer reviewe

New insights into smoking and urinary tract infections during pregnancy using pregnancy-pair design: A population-based register study

Introduction: Pregnancy itself predisposes to urinary tract infections (UTI). There appears to be a higher prevalence of infections and genitourinary diseases among pregnant smokers than among non-smokers. The present study is a retrospective observational register study aiming to investigate whether maternal smoking is associated with the prevalence of UTIs during pregnancy by utilizing a pregnancy-pair analysis.Material and methods: Information about pregnancies and maternal smoking was obtained from the Finnish Medical Birth Register. The study sample consisted of all singleton pregnancies (n = 723 433) of women giving birth between January 2006 and December 2018 in Finland. Information on maternal smoking was collected in three categories: (1) non-smoking; (2) quit smoking during the first trimester; and (3) continued smoking throughout the pregnancy. Information about maternal UTI diagnoses during pregnancy was received from the Hospital Discharge Register and the Medical Birth Register. UTIs were categorized as lower and upper UTIs according to the International Statistical Classification of Diseases and Related Health Problems (ICD)-10 diagnosis codes. Risks were calculated as odds ratios (OR) by logistic regression with 95% confidence intervals (CI) further adjusted for maternal characteristics (aOR). Finally, pregnancy-pair analyses were performed: mothers who had changed smoking status (no smoking/any smoking) between consecutive pregnancies (n = 27 246 pregnancy-pairs) were analyzed as one cluster and compared with non-smokers.Results: Smokers had UTIs more often compared with the non-smokers. The association was even stronger among those who continued to smoke (aOR 1.60, 95% CI 1.51-1.70) than among those who smoked only during the first trimester (aOR 1.27, 95% CI 1.18-1.37) compared with non-smokers. In pregnancy-pair analysis, smoking was associated with upper UTIs during pregnancy (OR 1.49, 95% CI 1.05-2.12) compared with non-smokers, but after the adjustments this association was attenuated (aOR 1.27, 95% CI 0.88-1.82). No association in lower UTIs was observed in the pregnancy-pair design.Conclusions: Maternal smoking was associated with a higher prevalence of UTIs during pregnancy in the standard comparison. The observed association was fully attenuated in the pregnancy-pair analysis, in which smoking was dichotomized. This study suggests that the association between maternal smoking during pregnancy and adverse maternal health effects might be more complex than previously thought.</p

Design of a prospective follow-up study on early parenthood and smoking behaviour during pregnancy in Finnish primary healthcare

Aims: The primary aim of the study is to explore different factors affecting parents' smoking behaviour, and especially how smoking may be connected with individual differences in the psychological process of becoming a parent. In the current paper, we present the study design together with basic information on the study population. Methods: The Central Satakunta Maternity and Child Health Clinic (KESALATU) Study is an ongoing prospective follow-up study in primary healthcare of the Satakunta region of southwest Finland. Families were recruited during their first maternity clinic visit between 1 September 2016 and 31 December 2019, and participation will continue until the child is 1.5 years of age. The study combines different sources and types of data: e.g. routine data obtained from primary healthcare clinic records, specific parental self-report data and data from a new exhaled carbon monoxide meter indicating maternal smoking. The data are collected using frequently repeated assessments both during pregnancy and postnatally. The methods cover the following areas of interest: family background factors (including smoking and alcohol use), self-reported parental-foetal/infant attachment and mentalization, self-reported stress, depression and quality of life. Results: 589 pregnant women and their partners were asked to participate in the study during the collection time period. The final study population consisted of 248 (42.1%) pregnant women and 160 (27.1%) partners. Conclusions: The new methods and study design have the potential to increase our understanding about the link between early parenting psychology, prenatal psychosocial risk factors and parental health behaviour.</p

Association of Early Beta-amyloid Accumulation and Neuroinflammation Measured with [11C]PBR28 in Elderly Individuals Without Dementia

OBJECTIVE: To examine whether early β-amyloid (Aβ) accumulation and metabolic risk factors are associated with neuroinflammation in elderly individuals without dementia. METHODS: We examined 54 volunteers (mean age 70.0, 56% women, 51% APOE ε4 carriers) with a TSPO-tracer [11C]PBR28 to assess neuroinflammation and with [11C]Pittsburgh compound B (PiB) to assess cerebral Aβ accumulation. [11C]PBR28 and [11C]PiB standardized uptake value ratios (SUVRs) were quantified in six regions of interests by using the cerebellar cortex as a pseudo-reference/reference region, respectively. Fasting venous glucose, insulin, and high sensitivity C-reactive protein (hs-CRP) values were determined. Homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. A subset of individuals (n=11) underwent CSF sampling, and Aβ40, Aβ42, total-tau, phospho-tau, soluble TREM2 and YKL-40 levels were measured. RESULTS: Among the whole study group, no significant association was found between [11C]PiB and [11C]PBR28 SUVR composite scores (slope 0.02, p=0.30). However, higher [11C]PiB binding was associated with higher [11C]PBR28 binding among amyloid negative ([11C]PiB composite score ≤1.5) (TSPO-genotype, age and sex adjusted slope 0.26, p=0.008) but not among amyloid positive participants (slope: -0.004, p=0.88). Higher CSF sTREM2 (rs 0.72, p=0.01) and YKL-40 (rs=0.63, p=0.04) concentrations were associated with a higher [11C]PBR28 composite score. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher [11C]PBR28 binding in brain regions where Aβ accumulation is first detected in Alzheimer's disease (AD). CONCLUSIONS: While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology

Characterisation of CART-containing neurons and cells in the porcine pancreas, gastro-intestinal tract, adrenal and thyroid glands

<p>Abstract</p> <p>Background</p> <p>The peptide CART is widely expressed in central and peripheral neurons, as well as in endocrine cells. Known peripheral sites of expression include the gastrointestinal (GI) tract, the pancreas, and the adrenal glands. In rodent pancreas CART is expressed both in islet endocrine cells and in nerve fibers, some of which innervate the islets. Recent data show that CART is a regulator of islet hormone secretion, and that CART null mutant mice have islet dysfunction. CART also effects GI motility, mainly via central routes. In addition, CART participates in the regulation of the hypothalamus-pituitary-adrenal-axis. We investigated CART expression in porcine pancreas, GI-tract, adrenal glands, and thyroid gland using immunocytochemistry.</p> <p>Results</p> <p>CART immunoreactive (IR) nerve cell bodies and fibers were numerous in pancreatic and enteric ganglia. The majority of these were also VIP IR. The finding of intrinsic CART containing neurons indicates that pancreatic and GI CART IR nerve fibers have an intrinsic origin. No CART IR endocrine cells were detected in the pancreas or in the GI tract. The adrenal medulla harboured numerous CART IR endocrine cells, most of which were adrenaline producing. In addition CART IR fibers were frequently seen in the adrenal cortex and capsule. The capsule also contained CART IR nerve cell bodies. The majority of the adrenal CART IR neuronal elements were also VIP IR. CART IR was also seen in a substantial proportion of the C-cells in the thyroid gland. The majority of these cells were also somatostatin IR, and/or 5-HT IR, and/or VIP IR.</p> <p>Conclusion</p> <p>CART is a major neuropeptide in intrinsic neurons of the porcine GI-tract and pancreas, a major constituent of adrenaline producing adrenomedullary cells, and a novel peptide of the thyroid C-cells. CART is suggested to be a regulatory peptide in the porcine pancreas, GI-tract, adrenal gland and thyroid.</p

Effect of moisture on leaf litter decomposition and its contribution to soil respiration in a temperate forest

The degree to which increased soil respiration rates following wetting is caused by plant (autotrophic) versus microbial (heterotrophic) processes, is still largely uninvestigated. Incubation studies suggest microbial processes play a role but it remains unclear whether there is a stimulation of the microbial population as a whole or an increase in the importance of specific substrates that become available with wetting of the soil. We took advantage of an ongoing manipulation of leaf litter &lt;sup&gt;14&lt;/sup&gt;C contents at the Oak Ridge Reservation, Oak Ridge, Tennessee, to (1) determine the degree to which an increase in soil respiration rates that accompanied wetting of litter and soil, following a short period of drought, could be explained by heterotrophic contributions; and (2) investigate the potential causes of increased heterotrophic respiration in incubated litter and 0–5 cm mineral soil. The contribution of leaf litter decomposition increased from 6 ± 3 mg C m&lt;sup&gt;−2&lt;/sup&gt; hr&lt;sup&gt;−1&lt;/sup&gt; during a transient drought, to 63 ± 18 mg C m&lt;sup&gt;−2&lt;/sup&gt; hr&lt;sup&gt;−1&lt;/sup&gt; immediately after water addition, corresponding to an increase in the contribution to soil respiration from 5 ± 2% to 37 ± 8%. The increased relative contribution was sufficient to explain all of the observed increase in soil respiration for this one wetting event in the late growing season. Temperature (13°C versus 25°C) and moisture (dry versus field capacity) conditions did not change the relative contributions of different decomposition substrates in incubations, suggesting that more slowly cycling C has at least the same sensitivity to decomposition as faster cycling organic C at the temperature and moisture conditions studied

Disruptive Behavior in Siblings Discordant for Exposure to Maternal Smoking during Pregnancy: a Multi-rater approach

IntroductionMaternal smoking during pregnancy (SDP) is associated with disruptive behavior. However, there is debate whether the SDP-disruptive behavior association is a potentially causal pathway or rather a spurious effect confounded by shared genetic and environmental factors.Aims and MethodsThe Missouri Mothers and Their Children Study is a sibling comparison study that includes families (n = 173) selected for sibling pairs (aged 7–16 years) discordant for SDP. Critically, the sibling comparison design is used to disentangle the effects of SDP from familial confounds on disruptive behavior. An SDP severity score was created for each child using a combination of SDP indicators (timing, duration, and amount of SDP). Multiple informants (parents and teachers) reported on disruptive behavior (i.e., DSM-IV semi-structured interview, the Child Behavior Checklist, and Teacher Report Form).ResultsThe variability in disruptive behavior was primarily a function of within-family differences (66%–100%). Consistent with prior genetically informed approaches, the SDP–disruptive behavior association was primarily explained by familial confounds (genetic and environmental). However, when using a multi-rater approach (parents and teachers), results suggest a potentially causal effect of SDP on disruptive behavior (b = 0.09, SE = 0.04, p = 0.03). The potentially causal effect of SDP remained significant in sensitivity analyses.DiscussionThese findings suggest that familial confounding likely plays a complex role in the SDP–disruptive behavior association when examining both parent and teacher reports of behavior. Importantly, the current study highlights the importance of multiple raters, reflecting a more comprehensive measure of complex behaviors (e.g., disruptive behavior) to examine the teratogenic effects of SDP.ImplicationsOur study provides additional evidence that controlling for genetic and family factors is essential when examining the effect of SDP on later behavioral problems, as it explains a portion of the association between SDP and later behavioral problems. However, we found a significant association between SDP and disruptive behavior when using a multi-rater approach that capitalizes on both parent and teacher report, suggesting that parent and teacher ratings capture a unique perspective that is important to consider when examining SDP–behavior associations.</div

The feasibility and outcome of a community-based primary prevention program for cardiovascular disease in the 21st century

Objective There is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality. This study aimed to evaluate the effectiveness of a primary care CVD prevention program on mortality during a 13-year follow-up. Design A risk factor survey was sent, followed by a nurse-led lifestyle counselling to respondents with at least one CVD risk factor, and a general practitioner's (GP) appointment for high-risk persons. Screening and interventions were performed during 2005-2006. Setting A public health care centre in the town of Harjavalta, Finland. Subjects All home-dwelling 45-70-year old inhabitants without manifested CVD or diabetes. Main outcome measures All-cause and CVD mortality. Results Altogether 74% (2121/2856) inhabitants responded to the invitation. The intervention was received by 1465 individuals (52% of the invited population): 398 risk persons had an appointment with a nurse, followed by an appointment with a GP for 1067 high-risk persons. During the follow-up, 370 persons died. Mortality among the non-respondents was twofold compared to the participants'. In subjects who received the intervention, the age- and gender-adjusted hazard ratio for all-cause mortality was 0.44 (95% CI: 0.36 to 0.54) compared to the subjects who did not receive the intervention. Conclusions Reducing mortality is possible in a primary care setting by raising health awareness in the community with screening, by targeted lifestyle counselling and evidence-based preventive medication for persons at high risk for CVD. Subjects not willing to participate in health surveys have the worst prognosis