Endocan: A biomarker for endothelial dysfunction and inflammation, linking maternal obesity and pediatric obesity in a cohort of preterm neonates.

OBJECTIVES: Numerous animal and epidemiologic studies have demonstrated a positive association between maternal obesity in pregnancy and obesity in offspring. The biologic mechanisms of this association remain under investigation. One proposed mechanism includes fetoplacental endothelial dysfunction secondary to inflammation. Endocan is a relatively new biomarker for endothelial dysfunction and inflammation. Our objectives were to examine (1) the association between maternal obesity and neonatal serum endocan at birth, and (2) the association between neonatal serum endocan at birth and pediatric obesity at 24-36 months of age. STUDY DESIGN: This was a secondary analysis of a prospective cohort of neonates born < 33 weeks gestation. Serum endocan was collected within 48 hours of birth. Serum endocan levels were compared in neonates born to obese mothers vs. those born to non-obese mothers. BMI data were retrospectively collected from cohort neonates between 24 and 36 months of age. RESULTS: The analysis included 120 mother/neonate dyads. Neonates born to obese mothers had higher median serum endocan at birth compared to neonates born to non-obese mothers (299 ng/L [205-586] vs. 251 ng/L [164-339], p = 0.045). In a linear regression modeled on neonatal serum endocan level, maternal obesity had a statistically significant positive association (p = 0.021). Higher mean serum endocan level at birth was associated with pediatric obesity between 24 and 36 months (obese vs. non-obese offspring; 574 ng/L (222) vs. 321 ng/L (166), p = 0.005). CONCLUSIONS: In our cohort of preterm neonates, elevated serum endocan at birth was associated with both maternal obesity and downstream pediatric obesity. More research is needed to understand intergenerational transmission of obesity. A large focus has been on epigenetic modification. Endothelial dysfunction and inflammation may play important roles in these pathways. Effective biomarkers, including endocan, may also serve as intermediate outcomes in future pregnancy research.

Towards an integrated blood pressure self-monitoring solution for stroke/TIA in Ireland: a mixed methods feasibility study for the TASMIN5S IRL randomised controlled trial.

BACKGROUND: Optimising blood pressure (BP) control is one of the most important modifiable risk factors in preventing subsequent stroke where the risk increases by one-third for every 10 mmHg rise in systolic BP. This study evaluated the feasibility and potential effectiveness of blood pressure self-monitoring with planned medication titration, to inform a definitive trial of the intervention, in patients with a previous stroke or transient ischaemic attack (TIA). METHODS: Patients with a history of stroke/TIA and sub-optimal BP control were invited to take part in a mixed methods feasibility study for a randomised controlled trial. Those meeting the inclusion criteria with systolic BP >130 mmHg were randomised to a self-monitoring intervention group or usual care group. The intervention involved self-monitoring BP twice a day for 3 days within a 7-day period, every month, following text message reminders. Treatment escalation, based on a pre-agreed plan by the general practitioner (GP) and patient, was initiated according to the results of these readings. Semi-structured interviews were carried out with patients and clinicians and analysed thematically. RESULTS: Of those identified, 47% (32/68) attended for assessment. Of those assessed, 15 were eligible for recruitment and were consented and randomised to the intervention or control group on a 2:1 basis. Of those randomised, 93% (14/15) completed the study and there were no adverse events. Systolic BP was lower in the intervention group at 3 months. Participants found the intervention acceptable and easy to use. GPs found it easy to incorporate into their practice activity without increasing workload. CONCLUSIONS: TASMIN5S, an integrated blood pressure self-monitoring intervention in patients with a previous stroke/TIA, is feasible and safe to deliver in primary care. A pre-agreed three-step medication titration plan was easily implemented, increased patient involvement in their care, and had no adverse effects. This feasibility study provides important information to inform a definitive trial to determine the potential effectiveness of the intervention in patients post-stroke or TIA. TRIAL REGISTRATION: ISRCTN57946500 . Registered on 12/08/2019.

Exercise Compared to Mindfulness for Physical and Mental Wellbeing in Medical Students.

Aim Physical Activity (PA) and Mindfulness-Based Stress Reduction (MBSR) both have positive effects on medical student well-being. The 'MED-WELL' programme is a curricular intervention that combines PA and education on exercise as medicine. This trial evaluates whether there is a mean difference in outcomes of participants of an exercise intervention, the 'MED-WELL' programme, versus a control group which engages in a MBSR programme. Methods All second-year medical students were voluntarily allocated into the intervention or control group. Data on overall health and well-being, sleep quality, loneliness, current level of PA, and confidence in prescribing exercise as medicine was analysed from both groups at baseline and after eight weeks. Results Within groups the intervention and control groups showed statistically significant improvements in overall well-being (p=0.010, p=0.005 respectively) and in sleep quality (p<0.001, p=0.007 respectively). The intervention group had statistically significant improvements in levels of PA (p=0.003) and confidence in prescribing exercise (p<0.001). However, there were no statistically significant differences in changes in outcome measures between groups. Conclusion This study has shown that participants in an exercise intervention, the 'MED-WELL' programme, had similar improvements in overall wellbeing and sleep quality to those in a control group who participated in a MBSR programme of the same duration.

The association between AB blood group and neonatal disease.

BACKGROUND: Numerous studies have examined the association between ABO blood groups and adult disease states, but very few have studied the neonatal population. The objective of this study was to determine the relationship between AB blood group and the occurrence of common neonatal disorders such as neutropenia at birth, sepsis, respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and patent ductus arteriosus (PDA) compared to all other blood groups. METHODS: We performed a retrospective review on 3,981 infants born at 22 0/7 to 42 6/7 weeks' gestational age and compared the relative risk of neonatal diseases in infants with AB blood group to that of infants with all other blood groups (A, B, and O). RESULTS: When compared to all other blood groups, AB infants demonstrated an increased risk for developing negative clinical outcomes. AB blood group was significantly associated with a 14-89% increased risk of neutropenia at birth, sepsis, RDS, and ROP. Risks for IVH and PDA were not significant. CONCLUSION: We hypothesize that the phenotypic expression of A and B antigens, rather than the antigens themselves, in the AB group may reveal an enhanced susceptibility to injury at the endothelial level resulting in an increased risk for disease development.

Antenatal glucocorticoid treatment is associated with diurnal cortisol regulation in term-born children.

Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few studies have examined the lasting consequences of antenatal treatment of betamethasone on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study is to examine whether antenatal exposure to betamethasone alters circadian cortisol regulation in children who were born full term. School-aged children prenatally treated with betamethasone and born at term (n=19, mean (SD)=8.1 (1.2) years old) were compared to children not treated with antenatal glucocorticoids (n=61, mean (SD)=8.2 (1.4) years old). To measure the circadian release of cortisol, saliva samples were collected at awakening; 30, 45, and 60min after awakening; and in the evening. Comparison children showed a typical diurnal cortisol pattern that peaked in the morning (the cortisol awakening response) and gradually decreased throughout the day. In contrast, children exposed to antenatal betamethasone lacked a cortisol awakening response and had a flatter diurnal slope (p's<0.01). These data suggest that antenatal glucocorticoid treatment may disrupt the circadian regulation of the HPA axis among children born at term. Because disrupted circadian regulation of cortisol has been linked to mental and somatic health problems, future research is needed to determine whether children exposed to antenatal synthetic glucocorticoids are at risk for poor mental and physical health.

Short- and long-term effects of gestational diabetes mellitus on healthcare cost: a cross-sectional comparative study in the ATLANTIC DIP cohort.

AIMS: This paper examines the association between gestational diabetes mellitus and costs of care during pregnancy and 2-5 years post pregnancy. METHODS: Healthcare utilization during pregnancy was measured for a sample of 658 women drawn from the Atlantic Diabetes in Pregnancy (ATLANTIC DIP) network. Healthcare utilization 2-5 years post pregnancy was assessed for a subsample of 348 women via a postal questionnaire. A vector of unit costs was applied to healthcare activity to calculate the costs of care at both time points. Differences in cost for women with gestational diabetes mellitus compared with those with normal glucose tolerance during the pregnancy were examined using univariate and multivariate regression analyses. RESULTS: Gestational diabetes mellitus was independently associated with an additional €817.60 during pregnancy (€1192.1 in the gestational diabetes mellitus group, €511.6 in the normal glucose tolerance group), in the form of additional delivery and neonatal care costs, and an additional €680.50 in annual healthcare costs 2-5 years after the index pregnancy (€6252.4 in the gestational diabetes mellitus group, €5434.8 in the normal glucose tolerance group). CONCLUSIONS: These results suggest that gestational diabetes mellitus is associated with increased costs of care during and post pregnancy. They provide indication of the associated cost that can be avoided or reduced by the screening, prevention and management of gestational diabetes mellitus in pregnancy. These estimates are useful for further studies that examine the cost and cost-effectiveness of such programmes.

Prevalence of depression in patients with type 2 diabetes mellitus in Irish primary care and the impact of depression on the control of diabetes.

BACKGROUND: As the Irish population ages, the management of chronic conditions in primary care is emerging as a challenge. The presence of co-morbid depression is common among such patients and may affect their response to treatment. AIMS: This study sought to determine whether the prevalence of depression is higher in patients with type 2 diabetes mellitus than in the population aged >50 in the West of Ireland, and whether depression is an independent predictor of diabetes control. METHODS: We used a cross-sectional design to examine an anonymized database of 9,698 patients aged >50 years whose medical data were collected as part of NUI Galway's CLARITY study. Glycosylated HbA1c levels were used to estimate type 2 DM control; depression was assessed using the Hospital Anxiety and Depression Scale. RESULTS: We found that while there is a higher prevalence of severe depression in patients with type 2 DM, there is no association between their diabetes control and depression after controlling for age, gender, comorbidity and GMS status. Multimorbidity is a significant predictor of depression in both diabetic and non-diabetic populations, with the odds of depression increasing as the number of co-morbidities increased. CONCLUSIONS: Patients with type 2 DM are more likely to suffer from severe depression than those without. Depression itself is not an independent predictor of diabetes control. However, it may be that the increased rates of depression observed in patients with type 2 DM are at least partially attributable to the burden of additional illnesses seen in these patients.

A prospective study of risk factors for foot ulceration: the West of Ireland Diabetes Foot Study.

BACKGROUND: This is the first study to examine risk factors for diabetic foot ulceration in Irish general practice. AIM: To determine the prevalence of established risk factors for foot ulceration in a community-based cohort, and to explore the potential for estimated glomerular filtration rate (eGFR) to act as a novel risk factor. DESIGN: A prospective observational study. METHODS: Patients with diabetes attending 12 (of 17) invited general practices were invited for foot screening. Validated clinical tests were carried out at baseline to assess for vascular and sensory impairment and foot deformity. Ulcer incidence was ascertained by patient self-report and medical record. Patients were re-assessed 18 months later. RESULTS: Of 828 invitees, 563 (68%) attended screening. On examination 23-25% had sensory dysfunction and 18-39% had evidence of vascular impairment. Using the Scottish Intercollegiate Guidelines Network risk stratification system we found the proportion at moderate and high risk of future ulceration to be 25% and 11%, respectively. At follow-up 16/383 patients (4.2%) developed a new foot ulcer (annual incidence rate of 2.6%). We observed an increasing probability of abnormal vascular and sensory test results (pedal pulse palpation, doppler waveform assessment, 10 g monofilament, vibration perception and neuropathy disability score) with declining eGFR levels. We were unable to show an independent association between new ulceration and reduced eGFR [Odds ratio 1.01; P = 0.64]. CONCLUSION: Our data show the extent of foot complications in a representative sample of diabetes patients in Ireland. Use of eGFR did not improve identification of patients at risk of foot ulceration.

Decreased survival in necrotizing enterocolitis is significantly associated with neonatal and maternal blood group: the AB isoagglutinin hypothesis.

OBJECTIVE: To determine the effect of neonatal and maternal blood group on the mortality risk from necrotizing enterocolitis (NEC). STUDY DESIGN: Retrospective chart review of all neonates admitted to the neonatal intensive care unit over 24 years. Data on birth date, gestational age, maternal/neonatal blood group, number of transfusions, and survival time (defined as date of birth to date of death/discharge) were collected on those with NEC. RESULT: 276 neonates with Bell stage II-III NEC were analyzed. AB neonates had a significantly higher risk of mortality from NEC compared with other blood groups (HR 2.87; 95% CI 1.40 to 5.89; P=0.003). Multivariate analysis showed AB blood group to be an independent risk factor for mortality from NEC. CONCLUSION: Neonatal and maternal blood groups are significantly associated with a neonate's survival from NEC. The increased mortality of AB neonates may be related to factors such as neonatal blood group antigens and/or transplacental transfer of isoagglutinins.

Patterns of fetal heart rate response at ∼30 weeks gestation predict size at birth.

There is evidence that fetal exposure to maternal stress is associated with adverse birth outcomes. Less is known about the association between fetal responses to a stressor and indicators of fetal maturity and developmental outcomes. The purpose of the present study was to determine whether fetal heart rate (FHR) patterns in response to a startling stimulus at ∼30 weeks of gestation were associated with gestational age at birth and birth weight. FHR was measured in 156 maternal-fetal dyads following a vibroacoustic stimulus. All pregnancies were singleton intrauterine pregnancies in English-speaking women who were primarily married, middle class, White and at least 18 years of age. Group-based trajectory modeling identified five groups of fetuses displaying distinctive longitudinal trajectories of FHR response to the startling stimulus. The FHR group trajectories were significantly associated with birth weight percentile (P < 0.01) even after controlling for estimated fetal weight at the time of assessment and parity, which are the known factors influencing birth weight (P < 0.01). Post hoc analyses indicated that two groups accounted for the association between FHR patterns and birth weight. The group (n = 23) with the lowest birth weight exhibited an immediate FHR deceleration followed by an immediate acceleration that does not recover. An FHR pattern characterized by immediate and fast acceleration to the peak and a slow discovery to baseline was associated with the highest birth weight. This is the first direct evidence showing that low birth weight and the resulting neurological consequences may have their origins in early fetal development.

Translating the epidemiology of psychosis into public mental health: evidence, challenges and future prospects.

Genetic and environmental factors are associated with psychosis risk, but the latter present more tangible markers for prevention. We conducted a theoretical exercise to estimate the proportion of psychotic illnesses that could be prevented if we could identify and remove all factors that lead to increased incidence associated with ethnic minority status and urbanicity. Measures of impact by population density and ethnicity were estimated from incidence rate ratios [IRR] obtained from two methodologically-similar first episode psychosis studies in four UK centres. Multilevel Poisson regression was used to estimate IRR, controlling for confounders. Population attributable risk fractions [PAR] were estimated for our study population and the population of England. We considered three outcomes; all clinically relevant ICD-10 psychotic illnesses [F10-39], non-affective psychoses [F20-29] and affective psychoses [F30-39]. One thousand and twenty-nine subjects, aged 18-64, were identified over 2.4 million person-years. Up to 22% of all psychoses in England (46.9% within our study areas) could be prevented if exposures associated with increased incidence in ethnic minority populations could be removed; this is equivalent to 66.9% within ethnic minority groups themselves. For non-affective psychoses only, PAR for population density was large and significant (27.5%); joint PAR with ethnicity was 61.7%. Effect sizes for common socio-environmental risk indicators for psychosis are large; inequalities were marked. This analysis demonstrates potential importance in another light: we need to move beyond current epidemiological approaches to elucidate exact socio-environmental factors that underpin urbanicity and ethnic minority status as markers of increased risk by incorporating gene-environment interactions that adopt a multi disciplinary perspective.

Chronic kidney disease in general practice: prevalence, diagnosis, and standards of care.

There is little prevalence data for chronic kidney disease (CKD) in Ireland and it has been suggested that rates of diagnosis of CKD in primary care are low. The aim of this cross sectional study was to examine the prevalence, diagnosis and standards of care for CKD. All patient records in three general practices in the West of Ireland were reviewed. In 2602 patients > 50 years in the community, 435 (16.7%) had chronic kidney disease defined as eGFR <60 ml/min/1.73 m2. Of these 435 individuals, only 58 (13.3%) had a diagnosis of CKD documented in their patient record. Among all patients with an eGFR <60 ml/min/1.73 m2, those with a documented diagnosis of CKD were significantly more likely to be prescribed an ACE/ARB and a lipid-lowering agent and were more likely to have had an ACR/PCR checked in the previous twelve months. Blood pressure was being appropriately monitored in the majority of patients but irrespective of eGFR level or a documented diagnosis of CKD, less than a fifth of patients had achieved a target of <130/80 mmHg. CKD is common in primary care but remains largely undiagnosed and blood pressure control remains suboptimal. A key step in improving care appears to be documenting the diagnosis which in turn appears to lead to improved standards of care and risk factor management.

Effect of prenatal glucocorticoid treatment on size at birth among infants born at term gestation.

OBJECTIVE: To determine whether prenatal treatment with a single course of glucocorticoids (GCs) affects size at birth among full-term infants independent of fetal size before GC administration or exposure to preterm labor (PTL). STUDY DESIGN: In all, 105 full-term infants were recruited into three study groups (30 GC treated; 60 controls matched for gestational age (GA) at birth and sex; and 15 PTL controls without GC exposure). Size of the infants was estimated before treatment using two-dimensional (2D) ultrasound and by direct measurement at birth. RESULTS: Length, weight and head circumference at birth were smaller among GC-treated infants compared with matched controls (P's<0.01), although fetal size did not differ before treatment (P's>0.2). Exposure to PTL did not account for this effect. CONCLUSIONS: Prenatal treatment with a single course of GCs was associated with a reduction in size at birth among infants born at term gestation. This effect cannot be explained by differences in fetal size before treatment or exposure to PTL.

The early use of minimal enteral nutrition in extremely low birth weight newborns.

OBJECTIVE: To gather information regarding the efficacy of early minimal enteral nutrition on overall feeding tolerance in extremely low birth weight infants. STUDY DESIGN: Prospective randomized controlled trial comparing the early use of minimal enteral nutrition in extremely low birth weight infants from day 2 to day 7 vs control infants. On day 8, feeding volume in both groups were advanced by 10 ml kg(-1) day(-1) until full enteral feedings were reached. Time to full feeds, number of intolerance episodes, anthropometric measurements, peak total bilirubin levels, incidence of necrotizing enterocolitis and incidence of sepsis were compared between the two groups with t-test and chi (2) test. RESULT: Eighty-four infants were enrolled in the study but only 61 infants completed the feeding protocol. No statistically significant differences were found between the groups with regards to growth patterns, feeding tolerance, mortality, length of hospital stay and incidence of sepsis and necrotizing enterocolitis. CONCLUSION: Early minimal enteral nutrition use in extremely low birth weight infants did not improve feeding tolerance.

Selection bias in enrollment to a programme aimed at the secondary prevention of ischaemic heart disease in general practice: a cohort study.

OBJECTIVE: To evaluate differences between adults who participated in a secondary prevention of ischaemic heart disease (IHD) programme and those who did not. DESIGN: Population-based cohort study. SETTING: A random selection of 12 Irish general practices. PARTICIPANTS: A total of 493 adults with IHD identified in 2000/2001. INTERVENTION: Medical records search and postal questionnaires in 2000/2001 and 2005/2006. MAIN OUTCOME MEASURES: Differences in demographic characteristics and indicators of process of care and risk factor management between participants and non-participants. RESULTS: Multiple logistic regression confirmed that female gender was associated with a reduced likelihood of participation in the secondary prevention programme [odds ratio (OR) 0.53 (95% CI: 0.32-0.87)], while an adequately controlled total cholesterol level was associated with an increased likelihood of enrollment [OR 1.82 (95% CI: 1.18-2.80)]. CONCLUSIONS: There is limited evidence that biases, which have been shown to affect participation in research, also affect participation in care programmes in everyday practice. A gender bias appears to have affected the enrollment of participants for the secondary preventive programme considered by this study, with enrollment favouring men with well-managed cholesterol. Reimbursement dependent upon patient adherence may incentivise the enrollment of adherent patients, although the influence of patient choice is unclear: the need to maintain records relating to patients who opt out of such interventions is thus highlighted.