Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.

BACKGROUND: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. METHODS: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group. RESULTS: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals. CONCLUSION: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at, http://links.lww.com/EDE/B838

Esophageal involvement in systemic sclerosis: study using high resolution manometry

Systemic sclerosis (SSc) is a chronic autoimmune fibrotic disease affecting the skin and other organs including the gastrointestinal tract. Esophagus is commonly affected in SSc and esophageal function is compromised in up to 90% of patients. Severe esophageal disease in patients with systemic sclerosis (SSc), referred as scleroderma esophagus, is characterised by ineffective or absent peristalsis along with hypotensive esophagogastric junction (hEGJ). The associations between scleroderma oesophagus and different clinical and laboratory manifestations of SSc is still controversial. Our study in fifty-four SSc patients with esophageal symptoms using high resolution manometry (HRM) and comparing the results of HRM parameters with clinical and other manifestations of the disease, showed that scleroderma esophagus was present in less than 2/3 of symptomatic patients with SSc and associated only with esophageal dilation in computed tomography. Esophageal dilation on chest CT may be a non-invasive alternative for evaluation of SSc patients with esophageal symptoms.Esophageal involvement in systemic sclerosis carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. The acute administration of buspirone in twenty SSc patients, as it was studied using HRM, showed really positive results as it increased the resting pressure of the LES, suggesting an important role of that drug in this specific group of patients. Furthermore, the longterm administration of buspirone, as it was studied in twenty two symptomatic SSc patients using HRM, showed its positive effects both in increasing the resting pressure of the LES and secondly in improving the gastroesophageal reflux disease symptoms, suggesting that buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment.Το συστηματικό σκληρόδερμα (ΣΣ) είναι ένα χρόνιο νόσημα του συνδετικού ιστού το οποίο προσβάλλει το δέρμα και άλλα συστήματα, μεταξύ των οποίων και το γαστρεντερικό σύστημα. Η προσβολή του οισοφάγου αφορά έως και το 90% των ΣΣ ασθενών. Ο «σκληροδερμικός οισοφάγος» (ΣΟ), η οισοφαγική δηλαδή προσβολή των ασθενών με ΣΣ, ο οποίος χαρακτηρίζεται από τον συνδυασμό της απουσίας περισταλτισμού στον λείο οισοφάγο και της υποτονίας του κατώτερου οισοφαγικού σφιγκτήρα (ΚΟΣ) μπορεί να συσχετισθεί με διάφορες κλινικές και εργαστηριακές παραμέτρους του ΣΣ. Η μελέτη σε πενήντα τέσσερις ΣΣ ασθενείς με συνοδά οισοφαγικά συμπτώματα των παραμέτρων της μανομετρίας υψηλής ανάλυσης (ΜΥΑ) και ειδικά του ΣΟ με κλινικά και άλλα χαρακτηριστικά της νόσου έδειξε πως ο ΣΟ παρατηρήθηκε στα 2/3 των συμπτωματικών ΣΣ ασθενών και πως συσχετίσθηκε με αυξημένη συχνότητα οισοφαγικής διάτασης στην αξονική τομογραφία (ΑΤ) θώρακος. Η παρουσία οισοφαγικής διάτασης στην ΑΤ θώρακος θα μπορούσε να αποτελέσει μία μη επεμβατική εναλλακτική για την εκτίμηση ΣΣ ασθενών με οισοφαγικά συμπτώματα.Η προσβολή του οισοφάγου στο συστηματικό σκληρόδερμα (ΣΣ) σχετίζεται με αυξημένη νοσηρότητα και αντιμετωπίζεται φαρμακευτικά με τη χρήση της δομπεριδόνης, αν και με αμφισβητούμενη αποτελεσματικότητα. Η χορήγηση από του στόματος της βουσπιρόνης, ενός μη–εκλεκτικού αγωνιστή των 5HT1A υποδοχέων, αυξάνει τον οισοφαγικό περισταλτισμό και τη λειτουργία του κατώτερου οισοφαγικού σφιγκτήρα (ΚΟΣ) σε υγιείς εθελοντές. Η εφ’άπαξ χορήγηση της βουσπιρόνης σε είκοσι ΣΣ ασθενείς, όπως μελετήθηκαν με τη χρήση της ΜΥΑ, έδειξε πολύ θετικά αποτελέσματα καθώς αύξησε σημαντικά την πίεση ηρεμίας του κατώτερου οισοφαγικού σφιγκτήρα (ΚΟΣ) υποδηλώνοντας το σημαντικό ρόλο που μπορεί να έχει αυτό το φάρμακο σε αυτή την ομάδα ασθενών. Επιπρόσθετα η μακροχρόνια χορήγηση της βουσπιρόνης, όπως μελετήθηκε σε είκοσι δύο ΣΣ ασθενείς με οισοφαγική συμπτωματολογία με τη βοήθεια της ΜΥΑ, έδειξε πως δρά θετικά στην λειτουργία του ΚΟΣ και θα μπορούσε ενδεχομένως να χορηγηθεί σε ασθενείς με ΣΣ και συμπτώματα γαστροοισοφαγικής παλινδρομικής νόσου (ΓΟΠΝ) που δεν υποχωρούν με τη λήψη ΑΑΠ

Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study

Background: Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. Aim: We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. Methods: Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. Results: Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 +/- 2.6 to 11.53 +/- 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure (+2.11 +/- 2.0 versus - 0.45 +/- 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. Conclusion: The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted

Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records

Background: Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD. Methods: We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, and heart failure) by emulating hypothetical interventions using electronic health records. We identified 138,567 individuals with 45-69 years of age without chronic disease in England from 1998 to 2016. We performed pooled logistic regression, using inverse-probability weighting to adjust for baseline and time-varying confounders. We categorized each individual into a weight loss, maintenance, or gain group. Results: Among those of normal weight, both weight loss [risk difference (RD) vs. weight maintenance = 1.5% (0.3% to 3.0%)] and gain [RD = 1.3% (0.5% to 2.2%)] were associated with increased risk for CVD compared with weight maintenance. Among overweight individuals, we observed moderately higher risk of CVD in both the weight loss [RD = 0.7% (-0.2% to 1.7%)] and the weight gain group [RD = 0.7% (-0.1% to 1.7%)], compared with maintenance. In the obese, those losing weight showed lower risk of coronary heart disease [RD = -1.4% (-2.4% to -0.6%)] but not of stroke. When we assumed that chronic disease occurred 1-3 years before the recorded date, estimates for weight loss and gain were attenuated among overweight individuals; estimates for loss were lower among obese individuals. Conclusion: Among individuals with obesity, the weight-loss group had a lower risk of coronary heart disease but not of stroke. Weight gain was associated with increased risk of CVD across BMI groups. See video abstract at,

Reporting guideline for the early-stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico evaluation, but few have yet demonstrated real benefit to patient care. Early-stage clinical evaluation is important to assess an AI system's actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use and pave the way to further large-scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multi-stakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two-round, modified Delphi process to collect and analyze expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 pre-defined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. In total, 123 experts participated in the first round of Delphi, 138 in the second round, 16 in the consensus meeting and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI-specific reporting items (made of 28 subitems) and ten generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we developed a guideline comprising key items that should be reported in early-stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings