Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial.

BACKGROUND: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents. METHODS: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317). RESULTS: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively. CONCLUSION: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

Serum calcium and risk of migraine: a Mendelian randomization study.

Migraine affects ∼14% of the world's population, though not all predisposing causal risk factors are known. We used electronic health records, genetic co-heritability analysis, and a two-sample Mendelian Randomization (MR) design to determine if elevated serum calcium levels were associated with risk of migraine headache. Co-morbidity was evaluated using electronic health records obtained from the PennOmics database comprising >1 million patient entries. Genetic co-heritability and causality via MR was assessed using data from the International Headache Consortium (23,285 cases, 95,425 controls) and circulating serum calcium levels (39,400 subjects). We observed co-occurrence of migraine and hypercalcaemia ICD-9 diagnoses (OR = 1.58, P = 4 × 10-13), even after inclusion of additional risk factors for migraine (OR = 1.23, P = 2 × 10-3). Second, we observed co-heritability (rg = 0.191, P = 0.03) between serum calcium and migraine headache, indicating that these traits have a genetic basis in common. Finally, we found that elevation of serum calcium levels by 1 mg/dl resulting from our genetic score was associated with an increase in risk of migraine (OR = 1.80, 95% CI: 1.31-2.46, P = 2.5 × 10-4), evidence supporting a causal hypothesis. We also present multiple MR sensitivity analyses in support of this central finding. Our results provide evidence that hypercalcaemia is comorbid with migraine headache diagnoses, and that genetically elevated serum calcium over lifetime appears to increase risk for migraine. Further studies will be required to understand the biological mechanism, pathways, and clinical implication for risk management.

MeRP: a high-throughput pipeline for Mendelian randomization analysis.

We present a Mendelian randomization (MR) pipeline (MeRP) to facilitate rapid, causal inference analysis through automating key steps in developing and analyzing genetic instruments obtained from publicly available data. Our tool uses the National Human Genome Research Institute catalog of associations to generate instrumental variable trait files and provides methods for filtering of potential confounding associations as well as linkage disequilibrium. MeRP generates estimated causal effect scores via a MR-score analysis using summary data for disease endpoints typically found in the public domain. We utilize our pipeline to develop genetic instruments for seven traits and evaluate potential causal relationships with two disease endpoints, observing two putatively causal associations between blood pressure and bone-mineral density with type 2 diabetes. Our tool emphasizes the importance of careful but systematic screening of large datasets for discovery and systematic follow-up.

Amplifying genetic logic gates.

Organisms must process information encoded via developmental and environmental signals to survive and reproduce. Researchers have also engineered synthetic genetic logic to realize simpler, independent control of biological processes. We developed a three-terminal device architecture, termed the transcriptor, that uses bacteriophage serine integrases to control the flow of RNA polymerase along DNA. Integrase-mediated inversion or deletion of DNA encoding transcription terminators or a promoter modulates transcription rates. We realized permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control signal ranges and sequential logic supporting autonomous cell-cell communication of DNA encoding distinct logic-gate states. The single-layer digital logic architecture developed here enables engineering of amplifying logic gates to control transcription rates within and across diverse organisms.

Effects of aging on generic SF-36 quality of life measurements in Hong Kong Chinese women with urinary incontinence.

BACKGROUND: To evaluate the relationship between aging, urodynamic diagnosis and generic quality of life measurement in Chinese women with urinary incontinence. METHODS: A total of 170 women presented to a university teaching hospital with urinary incontinence were recruited. The women completed the medical outcome survey, short form-36 (SF-36), immediately before they had the urodynamic investigation. The women were classified into either (1) genuine stress incontinence (n = 94) or (2) detrusor instability (n = 76). The relationships between aging, the transformed subscale scores, the population standardized component summary scores of the SF-36, and the two groups of women were studied using simultaneous multiple regression analysis. RESULTS: There was no significant difference in the age distribution between the two groups of patients (median age: 47 vs. 48, p = 0.18). However, aging causes significant impairment in the physical functioning (p < 0.001), role physical (p = 0.002) and bodily pain (p = 0.047) domains as well as the physical component scale (p < 0.001) of generic SF-36 quality of life measurements. There was no significant difference in the transformed subscale scores and the component summary scores with respect to different urodynamic diagnoses after adjustment for the effect of age. CONCLUSIONS: Aging causes significant deterioration on physical performance for Chinese women suffering from urinary incontinence. The generic SF-36 questionnaire was unable to detect a significant difference in quality of life measurement between women suffering from genuine stress incontinence and detrusor instability.

Maternal views and acceptance of antenatal HIV screening in a university teaching hospital in Hong Kong.

OBJECTIVE: To assess maternal acceptance, knowledge, attitude, perceived risks and barriers toward antenatal HIV screening. STUDY DESIGN: Prospective anonymous survey of 1,519 pregnant women recruited in a university teaching hospital RESULTS: Women demonstrated fairly good knowledge of and a positive attitude toward HIV screening. Condom usage was 61.4%, and 25.3% of women had at least 1 risk factor for HIV infection. Support for mandatory and universal screening was 31.4% and 48.8%, respectively. A total of 82.6% women agreed to HIV testing. The major reason for declining the test was that women considered themselves to be at low risk (84.3%). Women with risk factors tended to prefer more aggressive methods of antenatal testing (P < .001) and more readily accepted HIV screening (89.8% vs. 73.1%, P < .001). CONCLUSION: Given the high acceptance rate in our local population, universal offering but voluntary testing is the optimal mode of antenatal HIV screening in Hong Kong.