Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Effective writing and dealing with reviewers. [LETTER]
- J Clin Epidemiol 2014 Apr 18.
- Detailed Analysis of the Genetic and Epigenetic Signatures of iPSC-Derived Mesodiencephalic Dopaminergic Neurons. [Journal Article]
- Stem Cell Reports 2014 Apr 8; 2(4):520-33.
Induced pluripotent stem cells (iPSCs) hold great promise for in vitro generation of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA) neurons involved in Parkinson's disease. Although iPSC-derived midbrain DA neurons have been generated, detailed genetic and epigenetic characterizations of such neurons are lacking. The goal of this study was to examine the authenticity of iPSC-derived DA neurons obtained by established protocols. We FACS purified mdDA (Pitx3 (Gfp/+) ) neurons derived from mouse iPSCs and primary mdDA (Pitx3 (Gfp/+) ) neurons to analyze and compare their genetic and epigenetic features. Although iPSC-derived DA neurons largely adopted characteristics of their in vivo counterparts, relevant deviations in global gene expression and DNA methylation were found. Hypermethylated genes, mainly involved in neurodevelopment and basic neuronal functions, consequently showed reduced expression levels. Such abnormalities should be addressed because they might affect unambiguous long-term functionality and hamper the potential of iPSC-derived DA neurons for in vitro disease modeling or cell-based therapy.
- Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism. [JOURNAL ARTICLE]
- Thromb Res 2014 Apr 4.
We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case-control study (n=2753) from Sweden.39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n=7181).It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.
- Maternal hypothyroidism in early pregnancy and infant structural congenital malformations. [Journal Article]
- J Thyroid Res 2014.:160780.
Background.The question is debated on whether maternal hypothyroidism or use of thyroxin in early pregnancy affects the risk for infant congenital malformations.
Objectives.To expand the previously published study on maternal thyroxin use in early pregnancy and the risk for congenital malformations. Methods. Data from the Swedish Medical Birth Register were used for the years 1996-2011 and infant malformations were identified from national health registers. Women with preexisting diabetes or reporting the use of thyreostatics, anticonvulsants, or antihypertensives were excluded from analysis. Risk estimates were made as odds ratios (ORs) or risk ratios (RRs) after adjustment for year of delivery, maternal age, parity, smoking, and body mass index.
Results.Among 23 259 infants whose mothers in early pregnancy used thyroxin, 730 had a major malformation; among all 1 567 736 infants, 48012 had such malformations. The adjusted OR was 1.06 (95% CI 0.98-1.14). For anal atresia the RR was 1.85 (95% CI 1.00-1.85) and for choanal atresia 3.14 (95% CI 1.26-6.47). The risk of some other malformations was also increased but statistical significance was not reached.
Conclusions.Treated maternal hypothyroidism may be a weak risk factor for infant congenital malformations but an association with a few rare conditions is possible.
- Cigarette smoking and colorectal cancer mortality among 602,242 Norwegian males and females. [Journal Article]
- Clin Epidemiol 2014.:137-45.
Colorectal cancer (CRC) is one of the main cancer types, with high incidence and mortality in Norway. We examined the association between different measures of smoking exposure and CRC mortality overall and by subsite in a large Norwegian cohort.We followed 602,242 participants from four Norwegian health surveys, aged 19-67 years at enrollment between 1972 and 2003 by linkage to the national registries through December 2007. We used Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) by smoking categories for different CRC endpoints.During a mean follow-up of 14 years, 2,333 Norwegian males and females died of CRC (60% men). Male and female ever smokers had a 20% (HR 1.23, CI 1.08-1.40 and HR 1.22, 95% CI 1.06-1.40, respectively) increased risk of death from CRC compared with sex-specific never smokers. For proximal colon cancer mortality, female ever smokers had a 50% (HR 1.49, 95% CI 1.20-1.87) increased risk compared with female never smokers. The increased risk of rectal cancer mortality was about 40% higher for male ever smokers (HR 1.43, 95% CI 1.14-1.81) compared with male never smokers. A test for heterogeneity by sex showed an increased risk of rectal cancer mortality among men which was significant for former smokers (Wald χ(2) =0.02) and an increased risk of proximal colon cancer mortality among women which was significant for ever and former smokers (Wald χ(2) =0.02 and χ(2) =0.04, respectively).Smoking is associated with increased CRC mortality in both sexes. The risk of rectal and proximal colon cancer mortality was most pronounced among male and female smokers respectively.
- Validity of maternal and infant outcomes within nationwide Medicaid data. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Apr 16.
The aim of this study is to assess the validity of preeclampsia, congenital cardiac malformations, and persistent pulmonary hypertension of the newborn (PPHN) diagnoses in the US Medicaid Analytic eXtract (MAX), a nationwide health care utilization database that may be useful for perinatal research.Using the 2000-2007 MAX, we identified more than 1 million pregnancies ending in live birth. We identified potential cases based on claims, reviewed their hospital medical records, and calculated the positive predictive values (PPVs) and 95% confidence intervals (CIs) using records as the reference.Among 183 women with any preeclampsia diagnoses, the PPV was 66.5% (53.6, 77.4%), but it increased to 94.5% (84.0, 98.3%) for inpatient preeclampsia diagnoses. The PPV for inpatient PPHN diagnoses (N = 82) was 68.3% (57.6, 77.4%), but it increased to 89.6% (CI: 77.8, 95.5%) when restricting to infants not transferred to another facility shortly after birth (N = 48). The PPV for cardiac malformations was 77.6% (65.7, 86.2%) when requiring inpatient codes on more than one date (N = 63).These PPVs are conservative, particularly when patients were transferred or received outpatient diagnoses, because we reviewed records from a single hospitalization only. PPVs improve with stringent identification criteria, at the cost of sensitivity, and can be used to correct for measurement error. Copyright © 2014 John Wiley & Sons, Ltd.
- Using a drug-safety tool to prevent competition. [Journal Article]
- N Engl J Med 2014 Apr 17; 370(16):1476-8.
- Post-approval appending of CSARs to drug package inserts: an analysis of the types of adverse reactions and time to addition. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Apr 15.
The aim of this study was to quantitatively analyze clinically significant adverse reactions (CSARs) added to drug package inserts after approval and to investigate the time to these post-approval additions as an indicator of safety-related regulatory actions.Drugs containing new active ingredients that had been approved in Japan from April 2001 to December 2010 were analyzed. We examined CSARs that had been reported in the first version of the package inserts and subsequent additions through notifications from Japan's Ministry of Health, Labour and Welfare until the end of 2011. Relative risks (RRs) for post-approval addition of CSARs were calculated for various categories of disorders. The median lengths of time to post-approval addition of CSARs were compared.A total of 238 drugs were examined. Of the 2487 CSARs associated with these drugs, 737 had been added after approval. The analysis revealed a higher likelihood for post-approval addition of CSARs for "Hepatobiliary disorders" (RR: 1.41; 95% confidence interval [CI]: 1.19-1.68), "Gastrointestinal disorders" (RR: 1.35; 95%CI: 1.10-1.66), and "Musculoskeletal and connective tissue disorders" (RR: 1.52; 95%CI: 1.11-2.07). In contrast, "Cardiac disorders" showed reduced likelihood in comparison with other disorders. For the time until post-approval addition of CSARs, "Skin and subcutaneous tissue disorders" showed the longest durations, with a median of 3020 days.Our quantitative analysis suggests that some CSARs were added more frequently to package inserts after approval and that time to post-approval additions of CSARs varied with the types of adverse drug reactions. These results can support the coherent implementation of pharmacovigilance activities. Copyright © 2014 John Wiley & Sons, Ltd.
- Notoriety bias in a database of spontaneous reports: the example of osteonecrosis of the jaw under bisphosphonate therapy in the French national pharmacovigilance database. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Apr 15.
The purpose of this study was to identify a notoriety bias in a database of spontaneous reports and its consequences on the calculation of the reporting odds ratio (ROR).We used the case/noncase methodology to calculate the ROR for bisphosphonates and osteonecrosis of the jaw (ONJ) in the French national pharmacovigilance database (from 1985 to 2013). To evaluate notoriety bias, drug-related risk factors for ONJ [as specified in the summary of product characteristics (SPC) of bisphosphonates] were systematically scanned for notifications of reports of ONJ occurring under bisphosphonate therapy. When a risk factor was present, the ONJ was considered as not due to bisphosphonates, and a second ROR was calculated under the hypothesis of maximum bias.In total, 148 cases of ONJ were reported (143 with bisphosphonates and five without). The raw ROR was 3448 (95% confidence interval 1413-8417). After analysis of the reports, only 86 had no mention of a risk factor for ONJ. The ROR under the maximum bias hypothesis was 87 (95% confidence interval 63-121). Among ONJ where chemotherapy was being administered simultaneously to bisphosphonates, 27 reports did not consider the chemotherapy to be implicated, despite seven of these occurring in cases where ONJ was mentioned in the summary of product characteristics.The existence of a notoriety bias has an impact on measures of disproportionality. The detection of pharmacovigilance signals might be delayed. It is advisable to list all drugs being taken when an adverse drug reaction occurs, and not only those known to be associated with the observed reaction. Copyright © 2014 John Wiley & Sons, Ltd.
- Normal CYP3A activity during arsenic trioxide therapy. [JOURNAL ARTICLE]
- Ann Hematol 2014 Apr 16.