Epidemiology of small intestinal atresia in Europe: a register-based study.

BACKGROUND: The epidemiology of congenital small intestinal atresia (SIA) has not been well studied. This study describes the presence of additional anomalies, pregnancy outcomes, total prevalence and association with maternal age in SIA cases in Europe. METHODS: Cases of SIA delivered during January 1990 to December 2006 notified to 20 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. RESULTS: In total 1133 SIA cases were reported among 5126, 164 registered births. Of 1044 singleton cases, 215 (20.6%) cases were associated with a chromosomal anomaly. Of 829 singleton SIA cases with normal karyotype, 221 (26.7%) were associated with other structural anomalies. Considering cases with normal karyotype, the total prevalence per 10 000 births was 1.6 (95% CI 1.5 to 1.7) for SIA, 0.9 (95% CI 0.8 to 1.0) for duodenal atresia and 0.7 (95% CI 0.7 to 0.8) for jejunoileal atresia (JIA). There was no significant trend in SIA, duodenal atresia or JIA prevalence over time (RR=1.0, 95% credible interval (CrI): 1.0 to 1.0 for each), but SIA and duodenal atresia prevalence varied by geographical location (p=0.03 and p=0.04, respectively). There was weak evidence of an increased risk of SIA in mothers aged less than 20 years compared with mothers aged 20 to 29 years (RR=1.3, 95% CrI: 1.0 to 1.8). CONCLUSION: This study found no evidence of a temporal trend in the prevalence of SIA, duodenal atresia or JIA, although SIA and duodenal atresia prevalence varied significantly between registers.

Hepatitis C virus infections in the Swiss HIV Cohort Study: a rapidly evolving epidemic.

BACKGROUND: Hepatitis C virus (HCV) infection has a growing impact on morbidity and mortality in patients infected with human immunodeficiency virus (HIV). We assessed trends in HCV incidence in the different HIV transmission groups in the Swiss HIV Cohort Study (SHCS). METHODS: HCV infection incidence was assessed from 1998, when routine serial HCV screening was introduced in the SHCS, until 2011. All HCV-seronegative patients with at least 1 follow-up serology were included. Incidence rates (IRs) of HCV infections were compared between men who have sex with men (MSM), injection drug users (IDU), and heterosexuals (HET). RESULTS: HCV incidence was assessed in 3333 MSM, 123 IDU, and 3078 HET with a negative HCV serology at baseline. Over 23 707 person-years (py) for MSM, 733 py for IDU, and 20 752 py for HET, 101 (3%), 41 (33%), and 25 (1%) of patients seroconverted, respectively. The IR of HCV infections in MSM increased from 0.23 (95% credible interval [CrI], .08-.54) per 100 py in 1998 to 4.09 (95% CrI, 2.57-6.18) in 2011. The IR decreased in IDU and remained <1 per 100 py in HET. In MSM, history of inconsistent condom use (adjusted hazard ratio [HR], 2.09; 95% CI, 1.33-3.29) and past syphilis (adjusted HR, 2.11; 95% confidence interval [CI], 1.39-3.20) predicted HCV seroconversion. CONCLUSIONS: In the SHCS, HCV infection incidence decreased in IDU, remained stable in HET, and increased 18-fold in MSM in the last 13 years. These observations underscore the need for improved HCV surveillance and prevention among HIV-infected MSM.

Increasing prevalence of gastroschisis in Europe 1980-2002: a phenomenon restricted to younger mothers?

Gastroschisis is an abdominal wall defect more prevalent in offspring of young mothers. It is known to be increasing in prevalence despite the general decrease in the proportion of births to young European women. We investigated whether the increase in prevalence was restricted to the high-risk younger mothers. We analysed 936 cases of gastroschisis from 25 population-based registries in 15 European countries, 1980-2002. We fitted a Bayesian Hierarchical Model which allowed us to estimate trend, to estimate which registries were significantly different from the common distribution, and to adjust simultaneously for maternal age, time (in grouped years) and the random variation between registries. The maternal age-standardised prevalence (standardised to the year 2000 European maternal age structure) increased almost fourfold from 0.54 [95% Credible Interval (CrI) 0.37, 0.75] per 10,000 births in 1980-84 to 2.12 [95% CrI 1.85, 2.40] per 10,000 births in 2000-02. The relative risk of gastroschisis for mothers <20 years of age in 1995-2002 was 7.0 [95% CrI 5.6, 8.7]. There were geographical differences within Europe, with higher rates of gastroschisis in the UK, and lower rates in Italy after adjusting for maternal age. After standardising for regional variation, our results showed that the increase in risk over time was the same for mothers of all ages--the increase for mothers <20 years was 3.96-fold compared with an increase of 3.95-fold for mothers in the other age groups. These findings indicate that the phenomenon of increasing gastroschisis prevalence is not restricted to younger mothers only.

Epidemiology of congenital diaphragmatic hernia in Europe: a register-based study.

INTRODUCTION: Published prevalence rates of congenital diaphragmatic hernia (CDH) vary. This study aims to describe the epidemiology of CDH using data from high-quality, population-based registers belonging to the European Surveillance of Congenital Anomalies (EUROCAT). METHODS: Cases of CDH delivered between 1980 and 2009 notified to 31 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. RESULTS: There were 3373 CDH cases reported among 12 155 491 registered births. Of 3131 singleton cases, 353 (10.4%) were associated with a chromosomal anomaly, genetic syndrome or microdeletion, 784 (28.2%) were associated with other major structural anomalies. The male to female ratio of CDH cases overall was 1:0.69. Total prevalence was 2.3 (95% CI 2.2 to 2.4) per 10 000 births and 1.6 (95% CI 1.6 to 1.7) for isolated CDH cases. There was a small but significant increase (relative risk (per year)=1.01, 95% credible interval 1.00-1.01; p=0.030) in the prevalence of total CDH over time but there was no significant increase for isolated cases (ie, CDH cases that did not occur with any other congenital anomaly). There was significant variation in total and isolated CDH prevalence between registers. The proportion of cases that survived to 1 week was 69.3% (1392 cases) for total CDH cases and 72.7% (1107) for isolated cases. CONCLUSIONS: This large population-based study found an increase in total CDH prevalence over time. CDH prevalence also varied significantly according to geographical location. No significant association was found with maternal age.

Hirschsprung's disease prevalence in Europe: A register based study.

BACKGROUND: Hirschsprung's disease is a congenital gut motility disorder, characterised by the absence of the enteric ganglion cells along the distal gut. The aim of this study was to describe the epidemiology of Hirschsprung's disease, including additional congenital anomalies, total prevalence, trends, and association with maternal age. METHODS: Cases of Hirschsprung's disease delivered during 1980 to 2009 notified to 31 European Surveillance of Congenital Anomaly registers formed the population-based case-series. Prevalence rates and 95% confidence intervals were calculated as the number of cases per 10,000 births. Multilevel Poisson regression was performed to investigate trends in prevalence, geographical variation and the association with maternal age. RESULTS: There were 1,322 cases of Hirschsprung's disease among 12,146,210 births. The total prevalence was 1.09 (95% confidence interval, 1.03-1.15) per 10,000 births and there was a small but significant increase in prevalence over time (relative risk = 1.01; 95% credible interval, 1.00-1.02; p = 0.004). There was evidence of geographical heterogeneity in prevalence (p < 0.001). Excluding 146 (11.0%) cases with chromosomal anomalies or genetic syndromes, there were 1,176 cases (prevalence = 0.97; 95% confidence interval, 0.91-1.03 per 10,000 births), of which 137 (11.6%) had major structural anomalies. There was no evidence of a significant increased risk of Hirschsprung's disease in cases born to women aged ≥35 years compared with those aged 25 to 29 (relative risk = 1.09; 95% credible interval, 0.91-1.31; p = 0.355). CONCLUSION: This large population-based study found evidence of a small increasing trend in Hirschsprung's disease and differences in prevalence by geographic location. There was also no evidence of an association with maternal age. Birth Defects Research (Part A), 100:695-702, 2014. © 2014 Wiley Periodicals, Inc.

Heritability and quantitative genetic divergence of serotiny, a fire-persistence plant trait.

BACKGROUND AND AIMS: Although it is well known that fire acts as a selective pressure shaping plant phenotypes, there are no quantitative estimates of the heritability of any trait related to plant persistence under recurrent fires, such as serotiny. In this study, the heritability of serotiny in Pinus halepensis is calculated, and an evaluation is made as to whether fire has left a selection signature on the level of serotiny among populations by comparing the genetic divergence of serotiny with the expected divergence of neutral molecular markers (QST-FST comparison). METHODS: A common garden of P. halepensis was used, located in inland Spain and composed of 145 open-pollinated families from 29 provenances covering the entire natural range of P. halepensis in the Iberian Peninsula and Balearic Islands. Narrow-sense heritability (h(2)) and quantitative genetic differentiation among populations for serotiny (QST) were estimated by means of an 'animal model' fitted by Bayesian inference. In order to determine whether genetic differentiation for serotiny is the result of differential natural selection, QST estimates for serotiny were compared with FST estimates obtained from allozyme data. Finally, a test was made of whether levels of serotiny in the different provenances were related to different fire regimes, using summer rainfall as a proxy for fire regime in each provenance. KEY RESULTS: Serotiny showed a significant narrow-sense heritability (h(2)) of 0·20 (credible interval 0·09-0·40). Quantitative genetic differentiation among provenances for serotiny (QST = 0·44) was significantly higher than expected under a neutral process (FST = 0·12), suggesting adaptive differentiation. A significant negative relationship was found between the serotiny level of trees in the common garden and summer rainfall of their provenance sites. CONCLUSIONS: Serotiny is a heritable trait in P. halepensis, and selection acts on it, giving rise to contrasting serotiny levels among populations depending on the fire regime, and supporting the role of fire in generating genetic divergence for adaptive traits.

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.

Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants.

BACKGROUND: Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. METHODS: We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m(2) [underweight], 18·5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), ≥40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue. FINDINGS: We used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m(2) (95% credible interval 21·3-22·1) in 1975 to 24·2 kg/m(2) (24·0-24·4) in 2014 in men, and from 22·1 kg/m(2) (21·7-22·5) in 1975 to 24·4 kg/m(2) (24·2-24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m(2) in central Africa and south Asia to 29·2 kg/m(2) (28·6-29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m(2) (21·4-22·3) in south Asia to 32·2 kg/m(2) (31·5-32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13·8% (10·5-17·4) to 8·8% (7·4-10·3) in men and from 14·6% (11·6-17·9) to 9·7% (8·3-11·1) in women. South Asia had the highest prevalence of underweight in 2014, 23·4% (17·8-29·2) in men and 24·0% (18·9-29·3) in women. Age-standardised prevalence of obesity increased from 3·2% (2·4-4·1) in 1975 to 10·8% (9·7-12·0) in 2014 in men, and from 6·4% (5·1-7·8) to 14·9% (13·6-16·1) in women. 2·3% (2·0-2·7) of the world's men and 5·0% (4·4-5·6) of women were severely obese (ie, have BMI ≥35 kg/m(2)). Globally, prevalence of morbid obesity was 0·64% (0·46-0·86) in men and 1·6% (1·3-1·9) in women. INTERPRETATION: If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia. FUNDING: Wellcome Trust, Grand Challenges Canada.

Simultaneous measurement of regional cerebral blood flow by perfusion CT and stable xenon CT: a validation study.

BACKGROUND AND PURPOSE: Knowledge of cerebral blood flow (CBF) alterations in cases of acute stroke could be valuable in the early management of these cases. Among imaging techniques affording evaluation of cerebral perfusion, perfusion CT studies involve sequential acquisition of cerebral CT sections obtained in an axial mode during the IV administration of iodinated contrast material. They are thus very easy to perform in emergency settings. Perfusion CT values of CBF have proved to be accurate in animals, and perfusion CT affords plausible values in humans. The purpose of this study was to validate perfusion CT studies of CBF by comparison with the results provided by stable xenon CT, which have been reported to be accurate, and to evaluate acquisition and processing modalities of CT data, notably the possible deconvolution methods and the selection of the reference artery. METHODS: Twelve stable xenon CT and perfusion CT cerebral examinations were performed within an interval of a few minutes in patients with various cerebrovascular diseases. CBF maps were obtained from perfusion CT data by deconvolution using singular value decomposition and least mean square methods. The CBF were compared with the stable xenon CT results in multiple regions of interest through linear regression analysis and bilateral t tests for matched variables. RESULTS: Linear regression analysis showed good correlation between perfusion CT and stable xenon CT CBF values (singular value decomposition method: R(2) = 0.79, slope = 0.87; least mean square method: R(2) = 0.67, slope = 0.83). Bilateral t tests for matched variables did not identify a significant difference between the two imaging methods (P >.1). Both deconvolution methods were equivalent (P >.1). The choice of the reference artery is a major concern and has a strong influence on the final perfusion CT CBF map. CONCLUSION: Perfusion CT studies of CBF achieved with adequate acquisition parameters and processing lead to accurate and reliable results.

Simultaneous LC-MS/MS quantification of P-glycoprotein and cytochrome P450 probe substrates and their metabolites in DBS and plasma.

BACKGROUND: An LC-MS/MS method has been developed for the simultaneous quantification of P-glycoprotein (P-gp) and cytochrome P450 (CYP) probe substrates and their Phase I metabolites in DBS and plasma. P-gp (fexofenadine) and CYP-specific substrates (caffeine for CYP1A2, bupropion for CYP2B6, flurbiprofen for CYP2C9, omeprazole for CYP2C19, dextromethorphan for CYP2D6 and midazolam for CYP3A4) and their metabolites were extracted from DBS (10 µl) using methanol. Analytes were separated on a reversed-phase LC column followed by SRM detection within a 6 min run time. RESULTS: The method was fully validated over the expected clinical concentration range for all substances tested, in both DBS and plasma. The method has been successfully applied to a PK study where healthy male volunteers received a low dose cocktail of the here described P-gp and CYP probes. Good correlation was observed between capillary DBS and venous plasma drug concentrations. CONCLUSION: Due to its low-invasiveness, simple sample collection and minimal sample preparation, DBS represents a suitable method to simultaneously monitor in vivo activities of P-gp and CYP.

Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.

The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.

Multiplex ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous quantification in human plasma of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, anidulafungin, and caspofungin.

Therapeutic drug monitoring (TDM) may contribute to optimizing the efficacy and safety of antifungal therapy because of the large variability in drug pharmacokinetics. Rapid, sensitive, and selective laboratory methods are needed for efficient TDM. Quantification of several antifungals in a single analytical run may best fulfill these requirements. We therefore developed a multiplex ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method requiring 100 μl of plasma for simultaneous quantification within 7 min of fluconazole, itraconazole, hydroxyitraconazole, posaconazole, voriconazole, voriconazole-N-oxide, caspofungin, and anidulafungin. Protein precipitation with acetonitrile was used in a single extraction procedure for eight analytes. After reverse-phase chromatographic separation, antifungals were quantified by electrospray ionization-triple-quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. Deuterated isotopic compounds of azole antifungals were used as internal standards. The method was validated based on FDA recommendations, including assessment of extraction yields, matrix effect variability (<9.2%), and analytical recovery (80.1 to 107%). The method is sensitive (lower limits of azole quantification, 0.01 to 0.1 μg/ml; those of echinocandin quantification, 0.06 to 0.1 μg/ml), accurate (intra- and interassay biases of -9.9 to +5% and -4.0 to +8.8%, respectively), and precise (intra- and interassay coefficients of variation of 1.2 to 11.1% and 1.2 to 8.9%, respectively) over clinical concentration ranges (upper limits of quantification, 5 to 50 μg/ml). Thus, we developed a simple, rapid, and robust multiplex UPLC-MS/MS assay for simultaneous quantification of plasma concentrations of six antifungals and two metabolites. This offers, by optimized and cost-effective lab resource utilization, an efficient tool for daily routine TDM aimed at maximizing the real-time efficacy and safety of different recommended single-drug antifungal regimens and combination salvage therapies, as well as a tool for clinical research.

A new, automated, four-colour interphase FISH approach for the simultaneous detection of specific aneuploidies of diagnosis and prognosis significance in high hyperdiploid ALL

In hyperdiploid acute lymphoblastic leukaemia (ALL), the simultaneous occurrence of specific aneuploidies confers a more favourable outcome than hyperdiploidy alone. Interphase (I) FISH complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in non-dividing cells. To overcome the limits of manual I-FISH, we developed an automated four-colour I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10 and 17. Parameters established for automatic nucleus selection and signal detection were evaluated (3 controls). Cut-off values were determined (10 controls, 1000 nuclei/case). Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 ALL patients (1500 nuclei/patient) were compared with those by CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed by I-FISH. I-FISH revealed numerous additional abnormal clones, ranging between 0.1 % and 31.6%, based on the large number of nuclei evaluated. Four-colour automated I-FISH permits the identification of concurrent aneuploidies of prognostic significance in hyperdiploid ALL. Large numbers of cells can be analysed rapidly by this method. Owing to its high sensitivity, the method provides a powerful tool for the detection of small abnormal clones at diagnosis and during follow up. Compared to CC, it generates a more detailed cytogenetic picture, the biological and clinical significance of which merits further evaluation. Once optimised for a given set of probes, the system can be easily adapted for other probe combinations.

Prevalence and determinants of QT interval prolongation in medical inpatients.

BACKGROUND: QT interval prolongation carries an increased risk of torsade de pointes and death. AIM: We sought to determine the prevalence of QT prolongation in medical inpatients and to identify determinants of this condition. METHODS: We enrolled consecutive patients who were admitted to the internal medicine ward and who had an electrocardiogram performed within 24 h of admission. We collected information on baseline patient characteristics and the use of QT-prolonging drugs. Two blinded readers manually measured the QT intervals. QT intervals were corrected for heart rate using the traditional Bazett formula and the linear regression-based Framingham formula. We used logistic regression to identify patient characteristics and drugs that were independently associated with QTc prolongation. RESULTS: Of 537 inpatients, 22.3% had a prolonged QTc based on the Bazett formula. The adjusted odds for QTc prolongation based on the Bazett correction were significantly higher in patients who had liver disease (OR 2.9, 95% CI: 1.5-5.6), hypokalaemia (OR 3.3, 95% CI: 1.9-5.6) and who were taking ≥1 QT-prolonging drug at admission (OR 1.7, 95% CI: 1.1-2.6). Overall, 50.8% of patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation. CONCLUSIONS: The prevalence of QTc prolongation was high among medical inpatients but depended on the method used to correct for heart rate. The use of QT-prolonging drugs, hypokalaemia and liver disease increased the risk of QTc prolongation. Many patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation, further increasing the risk of torsade de pointes and death.