The Use of Hypnotics and Mortality - A Population-Based Retrospective Cohort Study

<div><p>Background</p><p>Sleep disorders, especially chronic insomnia, have become major health problem worldwide and, as a result, the use of hypnotics is steadily increasing. However, few studies with a large sample size and long-term observation have been conducted to investigate the relationship between specific hypnotics and mortality.</p><p>Methods</p><p>We conducted this retrospective cohort study using data from the National Health Insurance Research Database in Taiwan. Information from claims data including basic characteristics, the use of hypnotics, and survival from 2000 to 2009 for 1,320,322 individuals were included. The use of hypnotics was divided into groups using the defined daily dose and the cumulative length of use. Hazard ratios (HRs) were calculated from a Cox proportional hazards model, with two different matching techniques to examine the associations.</p><p>Results</p><p>Compared to the non-users, both users of benzodiazepines (HR = 1.81; 95% confidence interval [CI] = 1.78–1.85) and mixed users (HR = 1.44; 95% CI = 1.42–1.47) had a higher risk of death, whereas the users of other non-benzodiazepines users showed no differences. Zolpidem users (HR = 0.73; 95% CI = 0.71–0.75) exhibited a lower risk of mortality in the adjusted models. This pattern remained similar in both matching techniques. Secondary analysis indicated that zolpidem users had a reduced risk of major cause-specific mortality except cancer, and that this protective effect was dose-responsive, with those using for more than 1 year having the lowest risk.</p><p>Conclusions</p><p>The effects of different types of hypnotics on mortality were diverse in this large cohort with long-term follow-up based on representative claims data in Taiwan. The use of zolpidem was associated with a reduced risk of mortality.</p></div

JOP780016_Supplementary_Tables – Supplemental material for The use of antipsychotics is associated with lower mortality in patients with Alzheimer’s disease: A nationwide population-based nested case-control study in Taiwan

<p>Supplemental material, JOP780016_Supplementary_Tables for The use of antipsychotics is associated with lower mortality in patients with Alzheimer’s disease: A nationwide population-based nested case-control study in Taiwan by Che-Sheng Chu, Wan-Rung Li, Kuan-Lun Huang, Pei-Yu Su, Ching-Heng Lin and Tsuo-Hung Lan in Journal of Psychopharmacology</p

Estimated zolpidem usage from 2000 to 2009 in Taiwan.

<p>(Estimates were calculated by dividing the annual cost by the average price for a zolpidem tablet. Source: Bureau of National Health Insurance in Taiwan).</p

The cox proportion hazard regression model of stroke in OCD (n = 527).

<p>The cox proportion hazard regression model of stroke in OCD (n = 527).</p

Flow chart of the hybrid classifier, coupling ICA, SVM and IFLDA for brain MRI classification and segmentation.

<p>First, the pre-processing step included registering FLAIR and T2WI with T1WI and correcting intensity inhomogeneity correction using N3 method. Second, the entire volume data of multislice-multispectral MR image data are automatically sphered to be a new data set by using ICA to remove the first two order statistics. Third, a small set of training data, containing a 3x3 matrix (of 9 pixels) of GM, WM, CSF, and background (BG) was manually identified by operators from a specific image slice of 3D images for SVM classification of the sphered multispectral images. At the same time, all the sphered multispectral images go through skull striping with BET. Finally, the output of SVM serves as a large pool of training samples for initiation of an iterative version of FLDA,</p

The results of GM, WM and CSF quantification in the high-resolution synthetic MRI (1x1x1mm³) at various parameter settings by using SPM8 software.

<p>The results of GM, WM and CSF quantification in the high-resolution synthetic MRI (1x1x1mm³) at various parameter settings by using SPM8 software.</p

The results of GM, WM and CSF quantification in the high-resolution synthetic MRI (1x1x1mm³) at various parameter settings by using the trio-algorithm hybrid classifier.

<p>The results of GM, WM and CSF quantification in the high-resolution synthetic MRI (1x1x1mm³) at various parameter settings by using the trio-algorithm hybrid classifier.</p

The results of brain classification images from 3D multispectral-multislice MRI.

<p>Left side reveals 3D multispectral MRI of FLAIR, T1WI and T2WI and right side is the classification images. Upper, middle and lower rows show GM, WM and CSF images. (A) A 20 year old young female with 587.2 ml, 433.6 ml and 154.8 ml of GM, WM and CSF, and 49.9%, 36.9% and 13.2% of GM, WM and CSF volume fractions. (B) A 60 year old healthy male with 636.0 ml, 587.3 ml and 326.8 ml of GM, WM and CSF, and 41.0%, 37.9% and 21.1% of GM, WM and CSF volume fractions. (C) A 76 year old dementia patient with 562.3 ml, 454.3 ml and 333.1 ml of GM, WM and CSF, and 41.7%, 33.7% and 24.7% of GM, WM and CSF volume fractions.</p

A Hormone Receptor-Based Transactivator Bridges Different Binary Systems to Precisely Control Spatial-Temporal Gene Expression in <em>Drosophila</em>

<div><p>The GAL4/<em>UAS</em> gene expression system is a precise means of targeted gene expression employed to study biological phenomena in <em>Drosophila</em>. A modified GAL4/<em>UAS</em> system can be conditionally regulated using a temporal and regional gene expression targeting (TARGET) system that responds to heat shock induction. However heat shock-related temperature shifts sometimes cause unexpected physiological responses that confound behavioral analyses. We describe here the construction of a drug-inducible version of this system that takes advantage of tissue-specific GAL4 driver lines to yield either RU486-activated LexA-progesterone receptor chimeras (LexPR) or β-estradiol-activated LexA-estrogen receptor chimeras (XVE). Upon induction, these chimeras bind to a LexA operator (<em>LexAop</em>) and activate transgene expression. Using GFP expression as a marker for induction in fly brain cells, both approaches are capable of tightly and precisely modulating transgene expression in a temporal and dosage-dependent manner. Additionally, tissue-specific GAL4 drivers resulted in target gene expression that was restricted to those specific tissues. Constitutive expression of the active PKA catalytic subunit using these systems altered the sleep pattern of flies, demonstrating that both systems can regulate transgene expression that precisely mimics regulation that was previously engineered using the GeneSwitch/<em>UAS</em> system. Unlike the limited number of GeneSwitch drivers, this approach allows for the usage of the multitudinous, tissue-specific GAL4 lines for studying temporal gene regulation and tissue-specific gene expression. Together, these new inducible systems provide additional, highly valuable tools available to study gene function in <em>Drosophila</em>.</p> </div

Time-course and Dose-response Analysis of the Inducible LexPR Bridge System in Response to RU486.

<p>(A) The trans-activation of LexPR was monitored in flies (<i>Or22a</i>-Gal4/<i>UAS</i>-LexPR-attP40; +/<i>LexAop</i>-mCD8::GFP-attP2) fed various concentrations of RU486 (0, 0.5, 1, 1.5, 2, and 3 mM) for 5 days. <i>LexAop</i>-mCD8::GFP expression was observed in one of the antennal lobes of adult brains. (B) <i>LexAop</i>-mCD8::GFP expression in flies fed 1.5 mM RU486 for 1–6 days (d1–d6). (C) The inducer was removed by replacing the food with fresh food for 2–24 days ((−) d2–d24). Using 3D projections, (D) the green fluorescence intensity of single glomeruli was analyzed in 5 samples from each group of induction by different concentrations of RU486 (0, 0.5, 1, 1.5, 2, and 3 mM) for 5 days, and (E) the green fluorescence intensity of single glomeruli was analyzed from 5 samples for each group of induction for 1–6 days. Each bar represents the mean, and the error bars represent the standard error (± s.e.). Data from each panel were analyzed using Student's <i>t</i> test, and any differences between various concentrations or treatment durations are indicated: n.s. indicates no significant difference; *** indicates p<0.001; ** indicates p<0.01; and * indicates p<0.05. Scale bar, 20 µm.</p