Risk of QTc Interval Prolongation Associated With Circulating Anti‐Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

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Risk Factors for Prolonged Postoperative Ileus in Adult Patients Undergoing Elective Colorectal Surgery: An Observational Cohort Study

Reviews on Recent Clinical Trials ◽

10.2174/1574887113666180521111153 ◽

2018 ◽

Vol 13 (4) ◽

pp. 295-304 ◽

Cited By ~ 4

Author(s):

Andrea Pisani Ceretti ◽

Nirvana Maroni ◽

Marco Longhi ◽

Marco Giovenzana ◽

Roberto Santambrogio ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Colorectal Surgery ◽

Postoperative Ileus ◽

Observational Cohort Study ◽

Adult Patients ◽

Elective Colorectal Surgery ◽

Observational Cohort ◽

Prolonged Postoperative Ileus

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Neonatal Severe Hyperbilirubinemia Online Registry in Jiangsu Province: protocol for a multicentre, prospective, open, observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-040797 ◽

2021 ◽

Vol 11 (2) ◽

pp. e040797

Author(s):

Qianqian Li ◽

Xiaoyi Deng ◽

Junmei Yan ◽

Xiaofan Sun ◽

Xiaoyue Dong ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Observational Cohort Study ◽

Jiangsu Province ◽

Survival Status ◽

Bilirubin Encephalopathy ◽

Brainstem Response ◽

Observational Cohort ◽

Severe Hyperbilirubinemia

IntroductionSevere hyperbilirubinaemia in newborns can be easily complicated by acute bilirubin encephalopathy or even kernicterus, which could lead to neurological sequelae or death. However, there is no systematic study of the management of severe hyperbilirubinaemia in China. The Neonatal Severe Hyperbilirubinemia Online Registry study aims to investigate the management of jaundice before admission, risk factors and outcomes of severe hyperbilirubinaemia in a real-world setting in China.Methods and analysisThis is a prospective, multicentre, open, observational cohort study. From May 2020 to April 2023, more than 2000 patients with neonatal severe hyperbilirubinaemia from 13 tertiary hospitals in Jiangsu Province will join the study. Demographic data and treatment information will be collected from their clinical data. Management measures for jaundice before admission will be collected by the WeChat applet (called ‘Follow-up of jaundice’) after being provided by the patient’s guardian using a mobile phone. Follow-up data will include cranial MRI examination results, brainstem auditory-evoked potential or automatic auditory brainstem response, physical examination results and Griffiths Development Scales-Chinese at the corrected ages of 3–6 months and 1 and 2 years. Results and conclusions will be recorded using ‘Follow-up of jaundice.’ In-hospital outcomes, including severity of hyperbilirubinaemia (severe, extreme, hazardous), acute bilirubin encephalopathy (mild, moderate, severe) and survival status (death or survival), will be collected at discharge. Follow-up outcomes will include loss to follow-up, survival status and kernicterus (yes or no) at 2 years. The research will enhance our comprehensive knowledge of jaundice management before admission, risk factors and outcomes of severe hyperbilirubinaemia in China, which will ultimately help to reduce the incidence of neonatal severe hyperbilirubinaemia.Ethics and disseminationOur protocol has been approved by the Medical Ethics Committee of Nanjing Maternity and Child Health Care Hospital. We will present our findings at national conferences and peer-reviewed paediatrics journals.Trial registration numberNCT04251286.

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Gestational Trophoblastic Neoplasia From Genetically Confirmed Hydatidiform Moles: Prospective Observational Cohort Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001374 ◽

2018 ◽

Vol 28 (9) ◽

pp. 1772-1780 ◽

Cited By ~ 8

Author(s):

Hirokazu Usui ◽

Jia Qu ◽

Asuka Sato ◽

Zijun Pan ◽

Akira Mitsuhashi ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Laboratory Data ◽

Spontaneous Remission ◽

Observational Cohort Study ◽

Polymorphism Analysis ◽

Prospective Observational Cohort Study ◽

Gestational Trophoblastic Neoplasia ◽

Observational Cohort ◽

Hydatidiform Moles

ObjectiveThe aim of this study was to evaluate the incidence and risk factors of gestational trophoblastic neoplasia (GTN) from hydatidiform moles (HMs) cytogenetically diagnosed in a prospective cohort setting.MethodsThe prospective observational cohort study included cases of cytogenetically defined molar pregnancies, which were diagnosed by a multiplex short tandem repeat polymorphism analysis. Cases were classified as androgenetic complete HMs (CHMs), diandric monogynic triploid partial HMs (PHMs), or biparental abortion. Gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Incidences for each category, that is, CHM, PHMs, and biparental abortion, were calculated. Clinical variables (age, partner age, gravidity, parity, height, weight, BMI, and gestational age) and laboratory data (serum human chorionic gonadotropin [hCG], white blood cell count, hemoglobin, and platelet count) were compared between spontaneous remission cases and GTN cases in androgenetic CHMs.ResultsAmong 401 cases, 380 were classified as follows: 232 androgenetic CHMs, 60 diandric monogynic PHMs, and 88 biparental abortions. A total of 35 cases (15.1%) of CHMs, but only 1 case of PHM (1.7%) and no biparental abortions, exhibited progression to GTN. The hCG value before evacuation was significantly higher in GTN cases than in spontaneous remission cases (P = 0.001, Kruskal-Wallis test). Patient age was also significantly higher in GTN cases than in spontaneous remission cases (P = 0.002, Student t test).ConclusionsUnder the cohort cytogenetic diagnosis setting, the traditional risk factors for GTN after molar pregnancy, hCG value before evacuation and age, were confirmed in androgenetic CHMs. The risk of GTN was lower for PHMs than for CHMs. However, 1 patient with cytogenetic PHMs developed into GTN.

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Genetic and pharmacological relationship between P-glycoprotein and increased cardiovascular risk associated with clarithromycin prescription: An epidemiological and genomic population-based cohort study in Scotland, UK

PLoS Medicine ◽

10.1371/journal.pmed.1003372 ◽

2020 ◽

Vol 17 (11) ◽

pp. e1003372

Author(s):

Ify R. Mordi ◽

Benjamin K. Chan ◽

N. David Yanez ◽

Colin N. A. Palmer ◽

Chim C. Lang ◽

...

Keyword(s):

Cohort Study ◽

Observational Cohort Study ◽

Chronic Obstructive ◽

Antibiotic Prescribing ◽

Nucleotide Polymorphisms ◽

Major Pathway ◽

P Glycoprotein ◽

Increased Risk ◽

History Of ◽

Observational Cohort

Background There are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug–drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism. Methods and findings We conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 –AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0–14 days, 15–30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0–14 days (HR 1.31; 95% CI 1.17–1.46, p < 0.001) and 30 days to 1 year (HR 1.13; 95% CI 1.06–1.19, p < 0.001), with the association at 0–14 days modified by use of P-gp inhibitors or substrates (interaction p-value: 0.029). In the pharmacogenomic study (13,544 individuals with 44,618 discrete prescribing episodes [37,497 amoxicillin, mean age 63 years, 56% male; 7,121 clarithromycin, mean age 66 years, 47% male]), when prescribed clarithromycin, individuals with genetically determined lower P-gp activity had a significantly increased risk of CV hospitalization at 30 days to 1 year compared with heterozygotes or those homozygous for the non-P-gp–lowering allele (rs1045642 AA: HR 1.39, 95% CI 1.20–1.60, p < 0.001, GG/GA: HR 0.99, 95% CI 0.89–1.10, p = 0.85, interaction p-value < 0.001 and rs1128503 AA 1.41, 95% CI 1.18–1.70, p < 0.001, GG/GA: HR 1.04, 95% CI 0.95–1.14, p = 0.43, interaction p-value < 0.001). The main limitation of our study is its observational nature, meaning that we are unable to definitively determine causality. Conclusions In this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein.

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QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

CNS Spectrums ◽

10.1017/s1092852917000402 ◽

2017 ◽

Vol 23 (4) ◽

pp. 278-283 ◽

Cited By ~ 5

Author(s):

Anja Elliott ◽

Thibault Johan Mørk ◽

Mikkel Højlund ◽

Thomas Christensen ◽

Rasmus Jeppesen ◽

...

Keyword(s):

Small Sample Size ◽

Torsades De Pointes ◽

Small Sample ◽

Polymorphic Ventricular Tachycardia ◽

Antipsychotic Treatment ◽

Qtc Interval ◽

Qtc Prolongation ◽

Worst Case ◽

Clinical Interviews ◽

Observational Cohort

ObjectiveAntipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients.MethodsWe carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records.ResultsElectrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size.ConclusionsWe recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.

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Prevalence and risk factors of prolonged corrected QT interval in general Chinese population

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-1244-7 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Qun Ma ◽

Zhao Li ◽

Xiaofan Guo ◽

Liang Guo ◽

Shasha Yu ◽

...

Keyword(s):

Risk Factors ◽

Rural Areas ◽

Chinese Population ◽

Liaoning Province ◽

Qtc Interval ◽

Qtc Prolongation ◽

Cvd Risk ◽

Specific Risk ◽

Increased Risk ◽

General Chinese Population

Abstract Background Corrected QT (QTc) interval has been correlated with total and CVD mortality. Although much is known about the relation between prolonged QTc interval and clinical outcome, there is no information on the prevalence and specific risk factors of QTc prolongation in general Chinese population. We evaluated the prevalence of prolonged QTc interval and its risk factors in general Chinese population, aiming to fill in the gaps in the literature and provide evidence for potential CVD risk prediction and disease burden estimate in community. Methods A population-based survey was conducted on 11,209 participants over the age of 35 in rural areas of Liaoning Province from 2012 to 2013. Twelve-lead ECGs and automatic analysis were performed on all participants. Logistic regression adjustments were made by using the Bazett’s formula to correlate specific risk factors with prolonged QTc intervals (> 440 ms) for potential confounders. Results The overall prevalence of prolonged QTc interval was 31.6%. The prevalence increased significantly with age (24.1% among those aged 35–44 years; 28.3%, 45–54 years; 35.2%, 55–64 years; 43.4%, ≥65 years, P < 0.001). Participants with a history of CVD had a higher prevalence of QTc prolongation (40.7% vs. 30.0%). In the fully adjusted logistic regress model, older age, abdominal obesity, hypertension, diabetes, hypokalemia and any medicine used in the past two weeks were associated independently with increased risk for prolonged QTc interval (All P < 0.05). We found no significant differences between general obesity, hypocalcemia and hypomagnesemia with prolongation of QTc interval. Female sex showed opposite results after applying clinical diagnostic criteria, and high physical activity could reduce the risk of prolonged QTc interval. Conclusions The prevalence of prolonged QTc interval was relatively high in general Chinese population and listed relevant factors, which would help identify patients at risk in pre-clinical prevention and provide evidence for estimating potential CVD burden and making management strategies in community.

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