Eight-Row Multidetector Computed Tomography Coronary Angiography Evaluation of Significant Coronary Artery Disease in Patients with Severe Aortic Valve Stenosis

Background The aim of this study was to evaluate whether 8-row multidetector computed tomography coronary angiography (MDCT-CA) could replace invasive conventional coronary angiography (CCA) in patients with acquired severe aortic valve stenosis (AS). Coronary artery disease (CAD) diagnosis should be obtained with a noninvasive method in patients with AS undergoing valvular replacement. We evaluated the diagnostic accuracy of MDCT-CA in detecting high-grade (≥50%) stenoses in the main coronary arteries in patients with AS.Methods Twenty-three patients with acquired severe AS underwent both CCA and MDCT-CA. We calculated the total and volumetric calcium scores and evaluated the image quality of each coronary segment as assessable or nonassessable for stenosis. The images of the arteries were evaluated for the occurrence of artifacts and the presence of high-grade stenoses (≥50%) by visual estimation and comparison with that of CCA.Results Of the 322 segments screened 224 were assessable for stenosis. Heavy calcium load rendered 37 (38%) of the 98 coronary segments nonassessable.Compared to CCA, MDCT-CA had a sensitivity of 63%, a specificity of 96%, a positive predictive value of 52%, and a negative predictive value of 98% for ≥50% stenoses in the main coronary arteries.Conclusions Eight-row MDCT-CA revealed a low sensitivity in detecting significant coronary artery disease in patients with acquired severe AS. High calcium burden decreased visualization of the lumen and complicated most often a correct assessment. In this patient group, CCA should still remain the primary pre-surgical test to rule out coronary lesions requiring revascularization.     

The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico

CYP2B6 metabolizes a number of drug substrates, that are usually non-planar, neutral or weakly basic, fairly lipophilic with one or two hydrogen bond acceptors, on which it catalyses various oxidative reactions. For bupropion, cyclophosphamide, ifosfamide, pethidine, ketamine and propofol, these reactions represent major metabolic or activation pathways and for their kinetics CYP2B6 function is of considerable importance. For the rest of the substrates found, CYP2B6 contributes to overall metabolism or to a single pathway, but probably not to a materially significant extent. Among inhibitors, thiotepa, ticlopidine and clopidogrel have been characterised extensively in terms of selectivity and potency. Thiotepa is the most selective of the inhibitors, but is not useful as an in vivo inhibitor, whereas ticlopidine and clopidogrel can be used as CYP2B6-selective probes in human clinical studies. Bupropion hydroxylation is a selective, and consequently useful, in vivo probe for CYP2B6. Computational approaches are being developed to the extent that predictions on affinity of chemicals to CYP2B6 are becoming reliable enough as a first screen of new drug molecules and other chemicals. With validated in vitro and in vivo substrates (e.g. bupropion) and inhibitors (e.g. ticlopidine), it is expected that pharmacological (including pharmacogenetic) and clinical significance of CYP2B6 will be delineated more fully in the near future.     

The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism

The effect of oral contraceptives (OCs) on melatonin metabolism was studied in 29 subjects genotyped for CYP1A2 SNP g.-163C>A polymorphism. Plasma melatonin and 6-OH-melatonin concentrations were measured after a 6-mg dose of melatonin using a validated liquid chromatography/mass spectrometry method. The mean melatonin AUC and C(max) values were 4- to 5-fold higher in OC users than in non-OC users (P < .0001), whereas the weight-adjusted clearance was significantly lower in OC users (P < .0001). No significant difference in melatonin pharmacokinetics between the genotypes and no additional effect by the genotype on the OC-induced increase in melatonin exposure were evident. Melatonin exposure had no significant effect on the subjects' state of alertness. In conclusion, a significant inhibitory effect of OCs on the CYP1A2-catalyzed melatonin metabolism was seen; thereby, OC use can alter CYP1A2-phenotyping results.     

A Systematic Review and Meta-Analysis of Change in Health-Related Quality of Life for Interactive Telehealth Interventions for Patients With Asthma

ObjectivesAsthma is one of the most common major noncommunicable diseases in the world and affects individuals of all ages. Medication is used to achieve and maintain quality of life (QOL) for people with asthma. Telehealth interventions offer optimized and personalized symptom monitoring with timely treatment adjustment and the potential to increase medication adherence for individuals with asthma. This study examines and synthesizes the available data on the change in the QOL for patients with asthma who use interactive telehealth interventions, and identifies the most effective telehealth modalities used for intervention in this area.MethodsLiterature searches were conducted in 5 databases in November 2018 for studies measuring a change in QOL for patients with asthma. Study QOL outcomes, where possible, were pooled in a meta-analysis.ResultsSeventeen publications (describing 16 studies) comprising 2015 patients were included. Based on a meta-analysis, interactive telehealth interventions can improve QOL outcomes for people living with asthma, although the improved effects may be small: web portals (0.51, 95% confidence interval [CI] –0.00 to 1.03), interactive smartphone apps (0.30, 95% CI –0.16 to 0.76) and remote monitoring (standardized mean difference 0.20, 95% CI –0.11 to 0.52). Intervention delivery modalities identified include interactive web portals, smartphone apps, and remote monitoring programs.ConclusionsThe findings provide a comprehensive overview of the available literature on interactive telehealth interventions, including interactive web portals, smartphone apps, and remote monitoring programs. These findings demonstrated that a positive change in QOL can be attributed to these interventions and provide evidence for the implementation of telehealth interventions for individuals with asthma.     

Epilepsy,excess deaths and years of life lost from external causes

We systematically quantified excess mortality in epilepsy patients by cause of death using the population-attributable fraction and epilepsy-attributable years of potential life lost (YPLL) by age 75 years at ages 15 and over. We updated and undertook a re-review of mortality studies from our previous systematic review following PRISMA guidelines to identify cohort studies of general epilepsy populations reporting a relative risk (RR) of death by cause relative to the background rates in the population. Studies on epilepsy prevalence were identified through published reviews. Country-specific mortality figures were obtained from the WHO World Mortality Database. We performed a pooled analysis with the DerSimonian–Laird random effects method. In countries with very high Human Development Indices, epilepsy contributed to 0.5–1.1 % of all deaths in the total population. Among external causes, suicides (RR 2.9, 95 % confidence interval 2.2–3.8; I² 52 %) were the major contributor to YPLL, corresponding to 6.7 % and 4.2 % of excess YPLL due to epilepsy in the United States (US) and in the United Kingdom (UK) in 2010, with 541 (346–792) and 44 (28–65) excess suicide cases, respectively. Fatal accidental falls were more common, with 813 (610–1064) and 95 (71–125) excess deaths in the US and in the UK, but these caused only 2.0 % of excess YPLL as they occurred in older age groups. Suicides were the most important external cause of death in epilepsy patients in terms of excess YPLL, whereas other external causes were either more common in older ages or caused less excess deaths.     

Congenital structural anomalies in offspring of women with epilepsy--a population-based cohort study in Finland

BACKGROUND: Offspring of women with epilepsy may have an increased risk for congenital malformations, probably attributable to maternal antiepileptic medication. We conducted this population-based study to obtain valid and accurate estimates on major congenital malformations in the offspring of women with epilepsy, based on a large and representative patient cohort. METHODS: We identified all women (n = 6,535) entitled to full reimbursement for antiepileptic medication indicated for epilepsy for the first time between 1985 and 1994 from the Social Insurance Institution of Finland database. A reference cohort (n = 14,704) was identified from the Finnish Population Register Centre. Information on children born between 1993 and 2000 (patient cohort, n = 2,162; reference cohort, n = 5,413) was obtained from the Medical Birth Register. Information on children born with malformation (patient cohort, n = 116; reference cohort, n = 151) was obtained from the Finnish Register of Congenital Malformations. RESULTS: The prevalence of major malformation was 54/1,000 births among patients with epilepsy and 28/1,000 births among mothers without epilepsy, corresponding to a 2-fold overall risk for malformation in the offspring of women with epilepsy. The risk for spina bifida [odds ratio (OR) = 11.3, 95% confidence interval (CI) 2.34-108] and congenital anomalies of genital organs (OR = 8.38, 95% CI 2.15-47.4) was substantially elevated in the offspring of mothers with epilepsy. CONCLUSIONS: The absolute excess in the prevalence of major malformations was 26/1,000 births in the offspring of mothers with epilepsy in relation to the offspring of reference mothers. The highest relative risk was observed in spina bifida and congenital anomalies of genital organs. However, these malformations cover only a small proportion of all major malformations.     

Information sources used by women in Finland who use hormonal contraceptives

Objective The aim of this study was to examine information sources used by women who use hormonal contraceptives (HCs), and how information source affected women’s attitudes and perceptions in 2001 and 2007. Setting The questionnaires were distributed from university pharmacies in 12 large cities across Finland. Method The data were collected with two questionnaire surveys among women who used hormonal contraceptives in 2001 and 2007. In the 2001 survey the response rate was 53% (n = 264) and in the 2007 survey 55% (n = 436). Results The number of respondents who considered professional information sources the most important information sources was markedly bigger in 2007 than in 2001 (P = 0.005). The most common source of information concerning the benefits of hormonal contraceptives was a physician (2001: 43%, 2007: 53%). The most common source of information concerning the risks of hormonal contraceptives was friends and relatives (43%) in 2001 and physician in 2007 (35%). Only a few percent of the respondents considered a pharmacy the most important information source both the 2001 and 2007 surveys. Conclusion The importance of health care professionals as sources of information concerning hormonal contraceptives has increased. However, role of pharmacists as information source was surprisingly small. Women who use hormonal contraceptives need more information from professional sources to alleviate possible fears associated with use.     

Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.