Beyond Silence, a new contact-based education program customised for healthcare workers was not superior to standard mental health literacy training in improving mental health help-seeking or help-outreach behaviours in the workplace. The only difference was a reduction in stigmatized beliefs over time. Additional research is needed to explore the factors that lead to behaviour change.
The principles of Refinement, Replacement and Reduction (3R's) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord injury (SCI), an animal model used in rehabilitation medicine research, in order to improve the quality of experiments, avoiding unnecessary suffering. The aims of this investigation were 1- to assess acute surgical pain in mice subjected to SCI, 2- to compare the efficacy of commonly used analgesia (three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) with a combination of opioid and NSAID (one subcutaneous injection of 5 mg/kg carprofen before surgery followed by three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) and 3- to test if Infrared Thermography (IRT) could be a potential new Refinement method to easily assess thermoregulation, an important metabolic parameter. Finally, we aimed to achieve these goals without recruiting animals on purpose, but using mice already scheduled for studies on SCI. By using behaviours analysis, we found that, despite being commonly used, buprenorphine does not completely relieve acute surgical pain, whereas the combination of buprenorphine and carprofen significantly decreases pain signs by 80%. IRT technology turned out to be a very useful Refinement tool being a non invasive methods to measure animal temperature, particularly useful when rectal probe cannot be used, as in the case of SCI. We could find that temperatures constantly and significantly increased until 7 days after surgery and then slowly decreased and, finally, we could observe that in the buprenorphine and carprofen treated group, temperatures were statistically lower than in the buprenorphine-alone treated mice. To our knowledge this is the first work providing an analgesic Refinement and a description of thermoregulatory response using the IRT technology, in mice subjected to SCI.
The physiological role and the regulation of ADGRG7 are not yet elucidated. The functional involvement of this receptor was linked with different physiological process such as reduced body weight, gastrointestinal function and recently, a gene variant in ADGRG7 was observed in patients with adolescent idiopathic scoliosis. Here, we identify the <i>ADGRG7</i> as an estrogen-responsive gene under the regulation of estrogen receptor ERα in scoliotic osteoblasts and other cells lines. We found that <i>ADGRG7</i> expression was upregulated in response to estrogen (E2) in adolescent idiopathic scoliosis (AIS) cells. <i>ADGRG7</i> promoter studies indicate the presence of an ERα response half site in close vicinity of a specificity protein 1 (SP1) binding site. Mutation of the SP1 site completely abrogated the response to E2, indicating its essential requirement. ChIP confirmed the binding of SP1 and ERα to the <i>ADGRG7</i> promoter. Our results identify the <i>ADGRG7</i> gene as an estrogen-responsive gene under the control of ERα and SP1 tethered actions, suggesting a possible role of estrogens in the regulation of <i>ADGRG7</i> This article has an associated First Person interview with the first author of the paper.
MDD increased the risk of developing RA by 38%, and antidepressants may decrease this risk in these patients. Future research is necessary to confirm the underlying mechanism of MDD on the pathogenesis of RA.
The Detrended Fluctuation Analysis (DFA) is widely employed to quantify the fractal dynamics of R-R intervals (RRI). This is usually done by estimating a short- and a long-term coefficient, but it is still unclear how much the information provided by such a bi-scale DFA is independent of that of traditional spectral indices. However, more sophisticated DFA approaches have been recently proposed, including the multifractal-multiscale DFA and the DFA for magnitude and sign of RRI changes. The aim of our work is to investigate whether novel DFA approaches allow extracting the information on the nonlinear RRI dynamics that traditional spectral methods cannot retrieve.We selected 4-hour segments of beat-by-beat RRI series from a 24-hour Holter recording, one during daytime (wake), one at night (sleep) in a healthy volunteer. From the wake segment, we generated 100 surrogate series shuffling the phases but preserving the power spectrum, and then from each of the resulting RRI series, we generated the series of the sign and the series of the magnitude of successive RRI changes. We generated similar series from the sleep recording. Thus, we finally obtained 6 original beat-to-beat series to be compared with 600 surrogate series, each of 4-hour duration.The comparison between original and surrogate series showed that for this experimental setting, the traditional monofractal DFA provides the same information retrievable by the power spectrum. However, specific components of the multifractal DFA reveal information not detectable by the power spectrum, particularly in the sleep condition. Furthermore, the DFA of the magnitude of RRI changes reflects important nonlinear components. Therefore, these more sophisticated DFA approaches might effectively improve the clinical value of RRI variability analysis.
Read moreSerum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; <i>P</i><0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (<i>P</i><0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
Read moreIn September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis.
Read moreAdherence to and persistence with antidepressants is low during pregnancy and varies by medication class. Low adherence and persistence can interfere with a therapeutic effect of antidepressants, which may contribute to the worsening of depression symptoms.
Read moreCalmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.
Read more<sec> <title>Introduction</title> L’activité physique et l’exercice constituent une stratégie d’autogestion importante pour les personnes vivant avec une maladie mentale. Cette étude visait à caractériser à la fois les personnes atteintes d’un trouble de l’humeur et/ou d’anxiété qui faisaient de l’exercice ou de l’activité physique pour aider à gérer leur trouble et celles qui n’en faisaient pas, ainsi qu’à identifier les facteurs facilitant l’activité physique et l’exercice et ceux constituant un obstacle. </sec> <sec> <title>Méthodologie</title> L’Enquête sur les personnes ayant une maladie chronique au Canada – Composante des troubles de l’humeur et/ou d’anxiété de 2014 a été utilisée pour cette étude. Les répondants (n = 2 678) ont été classés en fonction de la fréquence à laquelle ils faisaient de l’exercice : (1) aucun exercice, (2) exercice une à trois fois par semaine et (3) exercice quatre fois ou plus par semaine. Nous avons pondéré toutes les estimations afin que les données soient représentatives de la population canadienne adulte vivant en logement privé dans l'une des 10 provinces et ayant déclaré avoir reçu un diagnostic de troubles de l’humeur et/ou d’anxiété. </sec> <sec> <title>Résultats</title> Sur l’ensemble des Canadiens affectés, 51,0 % ne faisaient aucun exercice pour aider à gérer leur trouble de l’humeur et/ou d’anxiété, 23,8 % en faisaient d’une à trois fois par semaine et 25,3 % en faisaient quatre fois ou plus par semaine. On a établi un lien entre, d’une part, un âge plus avancé, des niveaux de scolarité plus bas et une suffisance de revenu du ménage plus faible et, d’autre part, une fréquence plus importante de l’inactivité. Les individus vivant avec un trouble de l’humeur (avec ou sans anxiété) et ceux avec des comorbidités physiques étaient moins susceptibles de faire régulièrement de l’exercice. Les recommandations d’un médecin ou d’un autre professionnel de la santé constituaient le facteur le plus important associé à la décision de faire de de l’exercice. Les obstacles mentionnés le plus souvent à de l’exercice au moins une fois par semaine étaient un problème physique (27,3 %), un manque de temps ou un horaire trop chargé (24,1 %) et un manque de volonté ou d’autodiscipline (15,8 %). </sec> <sec> <title>Conclusion</title> Malgré les bénéfices de l’activité physique et de l’exercice pour contrer les symptômes de dépression et d’anxiété, un pourcentage important de personnes atteintes d’un trouble de l’humeur et/ou d’anxiété ne fait aucun exercice sur une base régulière, particulièrement celles atteintes de trouble de l’humeur et celles présentant des comorbidités physiques. Il est essentiel que les professionnels de la santé recommandent à leurs patients de faire une activité physique ou de l’exercice, discutent avec eux des obstacles rencontrés et les encouragent à persévérer. </sec>
Read more<b>Introduction:</b> Obstructive sleep apnea (OSA) is associated with altered acid-based balance, increased carbonic anhydrase activity and arterial standard bicarbonate (HCO<sub>3</sub>). The current study aimed to address the association between HCO<sub>3</sub> and arterial hypertension in OSA patients. We hypothesized that HCO<sub>3</sub>, as a surrogate marker of carbonic anhydrase activity, was elevated in hypertensive OSA patients compared with their normotensive counterparts. <b>Methods:</b> Subjects with a polysomnography study and arterial blood gas analysis in the European Sleep Apnea Database were selected (n=3535, 72% male, 38% hypertensives, age 52±12 years, body mass index 33.1±6.9 kg/m<sup>2</sup> and Apnea-Hypopnea Index 38±28 events/h). Patients with respiratory failure (PaO<sub>2</sub>≤8 kPa and/or PaCO<sub>2</sub>≥6.5 kPa) were excluded. Concomitant medication was determined according to ATC codes. Arterial hypertension was defined as a physician diagnosed condition with ongoing antihypertensive medication. <b>Results:</b> Mean HCO<sub>3</sub> was significantly higher in hypertensive compared with normotensive patients (24.3±2.7 vs. 23.9±2.4 mmol/l, p<0.001). In a generalized linear model, HCO<sub>3</sub> was independently associated with arterial hypertension diagnosis after controlling for sex, age, body mass index, waist-to-hip ratio, smoking, intake of diuretic medication, comorbidities, PaCO<sub>2</sub> and apnea-hypopnea index (β [95%CI] 0.06 [0.01 - 0.11], p=0.022). <b>Conclusions:</b> A higher HCO<sub>3</sub> is associated with a prevalent arterial hypertension in OSA patients. Hypertension in OSA may mechanistically be linked to more severe OSA in combination with increased carbonic anhydrase activity.
Read moreObjective: Increased home day-by-day variability of blood pressure (BP), independently from its average value, results in increased risk of target organ damage and cardiovascular events in primary and secondary cardiovascular prevention. However, the association between in-hospital day-by-day BP variability and its prognostic value in secondary cardiovascular prevention has not yet been established. Design and method: We considered 1440 consecutive cardiac patients who underwent cardiovascular rehabilitation for at least 12 days after coronary artery bypass graft (CABG), valve surgery or both. In each rehabilitation day, trained nurses measured auscultatory BP in the morning and in the afternoon at the patient bed. Systolic BP variability (SBPv) was assessed as the standard deviation of the daily measures. Logistic regression analysis was calculated with endpoints the overall mortality, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCEs). Kaplan-Meier survival curves were calculated among SBPv tertiles. Results: Mean age was 68 ± 11 years. The prevalence of male gender was 72% and of hypertension was 61%; 807 patients (56%) underwent CABG, 475 (33%) valve surgery, 158 (11%) valve surgery+CABG. Ranges of SBPv tertiles were 4.1–9.1 mmHg, 9.2–11.5 mmHg, and 11.6–24.5 mmHg. In CABG patients, 1) the Kaplan-Meier curve showed worse survival free from overall mortality (p = 0.042) and MACCEs (p = 0.006) in the highest SBPv tertile, and 2) the logistic regression analysis showed significant positive correlations of SBPv with mortality and MACCEs (see Figure), with 12%, 11% and 10% increase of relative risk of overall mortality, cardiovascular mortality, and MACCEs for each mmHg increase of SBPv (overall mortality: HR = 1.12, p = 0.002; cardiovascular mortality: HR = 1.11, p = 0.014; MACCEs: HR = 1.10, p = 0.001). Logistic regression analysis remained significant also when calculated for the coefficient of variation, thus correcting the standard deviation by the mean SBP. Multivariate analysis separately adjusted for age, gender, hypertension, mean SBP, diabetes, glomerular filtration rate, left-ventricle ejection fraction and anti-hypertensive drugs, at discharge and follow-up, confirmed the correlation between SBPv and MACCEs or overall mortality. No association between SBPv and mortality or MACCEs was found in valve-surgery patients.Conclusions: In-hospital day-by-day SBPv predicts mortality and MACCEs for CABG patients in secondary cardiovascular prevention.
Read moreGroup prenatal care, prenatal education and peer support programmes have the potential to improve social support. Prenatal interventions studies are needed to confirm these findings in higher risk groups.
Read moreIn patients with a relatively short disease duration, sacubitril/valsartan was associated with a strong favorable remodeling of the left ventricle and improvement in pulmonary circulation.
Read moreIntroductionPooling data from cohort studies can be used to increase sample size. However, individual datasets may contain variables that measure the same construct differently, posing challenges in the usefulness of combined datasets. Variable harmonization (an effort that provides comparable view of data from different studies) may address this issue.
 Objectives and ApproachThis study harmonized existing datasets from two prospective pregnancy cohort studies in Alberta Canada (All Our Families (n=3,351) and Alberta Pregnancy Outcome and Nutrition (n=2,187)). Given the comparability of the characteristics of the two cohorts and similarities of the core data elements of interest, data harmonization was justifiable. Data harmonization was performed considering multiple factors, such as complete or partial variable matching regarding question asked/responded, the response coded (value level, value definition, data type), the frequency of measurement, the pregnancy time-period of measurement, and missing values. Multiple imputation was used to address missing data resulting from the data harmonization process.
 ResultsSeveral variables such as ethnicity, income, parity, gestational age, anxiety, and depression were harmonized using different procedures. If the question asked/answered and the response recorded was the same in both datasets, no variable manipulation was done. If the response recorded was different, the response was re-categorized/re-organized to optimize comparability of data from both datasets. Missing values were created for each resulting unmatched variables and were replaced using multiple imputation if the same construct was measured in both datasets but using different ways/scales. A scale that was used in both datasets was identified as a reference standard. If the variables were measured in multiple times and/or different time-periods, variables were synchronized using pregnancy trimesters data. Finally, harmonized datasets were then combined/pooled into a single dataset (n=5,588).
 Conclusion/ImplicationsVariable harmonization is an important aspect of conducting research using multiple datasets. It provides an opportunity to increase study power through maximizing sample size, permitting more sophisticated statistical analyses, and to answer novel research questions that could not be addressed using a single study.
Read moreObjective: Evaluating the risk for cardiovascular mortality within 5 years in middle-age and older subjects, who displayed 24-hour diastolic BP variability (DBPV) greater than the systolic BP variability (SBPV).Design and method: Study population was a subgroup of Dublin Outcome Study that included 3,815 participants older than 50 years (age 65 ± 9, males 47%, hypertension 72%, diabetes 12%) not on antihypertensive medications at referral, who underwent 24-hour ambulatory BP monitoring and followed up for 5 years, of whom 315 died from cardiovascular cause (CV), including 195 from cardiac illness (CARD), and 88 from stroke (STRK). Variability was expressed by standard deviation of the BP readings. We marked the groups of participants with DBPV>SBPV and DBPV<=SBPV by the variable Index equals to 1 and 0, respectively, Odd ratio (OR) was determined using multiple logistic regression, in which the outcome was 1 for death from a specific cause, and 0 otherwise. The independent variables were Index, age, sex, body mass index (BMI), current smoking status, presence of diabetes mellitus, past cardiovascular diseases, 24-hour mean arterial pressure (MAP) and heart rate, and MAP nocturnal dipping. Results: Both groups displayed similar characteristics, but %mortality for the DBPV>SBPV group (N=165) was much higher than for the DBPV<=SBPV group (N = 3650): CV (27.9% vs 11.9%); CARD (18.2% vs 4.5%), and STRK (8.5% vs 2.0%). The odd ratios for DBPV>SBPV (see table) demonstrated high clinical and statistical significance for the tested mortality causes, and insensitivity to adjustment. For age<=50 did not display comparable association with CV death, but the small sample number did not permit a fair evaluation. Conclusions: Greater ambulatory diastolic BP variability than the systolic one for age>50 years is associated with high risk for CV death within 5 years.
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