The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.

Duration of varenicline prescription and efficacy of smoking cessation treatment: an observational study in Taiwan.

Although varenicline has had a significant effect on smoking cessation in randomized clinical trials, the dose-effect of varenicline treatment for smoking cessation in real-world settings remains unclear. This study aimed to evaluate the association between the duration of varenicline prescription and smoking cessation in Taiwan after adjusting for potential confounding effects and endogeneity bias. A total of 5106 Taiwanese participants received varenicline monotherapy for smoking cessation between March 2012 and September 2016. Multinomial logistic regression (MLR) was used to analyze the association between varenicline prescription duration and smoking cessation, stratified by the frequency of smoking clinic visits and propensity scores of early stopping of smoking cessation treatment. Compared to the reference of nonquitting, longer durations of varenicline prescription were associated with the greater likelihood of immediate and complete quitting (OR = 1.08, 95% CI = 1.02-1.14) and late quitting (OR = 1.14, 95% CI = 1.07-1.20). Among those who were more likely to continue visiting smoking clinics, longer use of varenicline was significantly associated with an increase in immediate-and-complete quitting (OR = 1.19, 95% CI = 1.15-1.23) and late quitting (OR = 1.24, 95% CI = 1.20-1.28). Varenicline prescription duration was not associated with smoking cessation among smokers who visited smoking clinics once. The relationship between varenicline prescription duration and smoking cessation was modified by the frequency of smoking clinic visits and was dependent on quitting process patterns. Encouraging smokers to continue visiting the smoking cessation clinic and use medication will help smoking cessation efforts in Taiwan.

[Using Teamwork to Reduce the Incidence of Incontinence-Associated Dermatitis].

BACKGROUND & PROBLEMS: Dermatitis associated with incontinence was the cause of 55% of the total of 386 skin lesion cases in our unit between July and December 2016 and 40.3% of the skin lesion cases in our unit during March and April 2017, indicating the importance of this issue. Our survey showed that the nurses in our unit scored an average of 78.9% on knowledge related to the prevention of incontinence-associated dermatitis and only 58.2% on knowledge related to incontinence-associated dermatitis care. The main reasons for the high incidence of incontinence-associated dermatitis included: incorrect implementation of care, no discussion with the medical team, no incontinence care standards, no continue education, lack of related equipment for preventing incontinence-associated dermatitis, unit patient characteristics, and drugs used. PURPOSE: To reduce the incidence of incontinence-associated dermatitis from 40.3% to 32.0%. RESOLUTION: A care-bundle in treating incontinence-associated dermatitis was implemented by designing an assessment flow chart for evaluating incontinence-associated dermatitis, by setting standard guidelines for incontinence-associated dermatitis care, by distributing reminder cards, special toolboxes, and by changing how the little diapers were wrapped. In-service education lessons, inter-professional collaborative practice, and regular internal audit were also executed. RESULTS: After project implementation, the knowledge score of nurses increased from 78.9% to 95.7%; the correctness of care score, as retested in November 2017, increased from 58.2% to 91.5%; and the incidence of incontinence-associated dermatitis dropped to 18.5%. These improvements achieved the goals of this project. Furthermore, the sustained effect of the project measures was confirmed, with the incidence of incontinence-associated dermatitis determined as 17.9% at three months after completion of the project. CONCLUSIONS: Formulating care procedures and cooperating with medical team personnel to provide creative care measures were shown to effectively decrease the incidence of incontinence-associated dermatitis and improve overall quality of care. The findings of this project support the revision by hospitals of regulations and procedures related to adult incontinence-associated dermatitis to provide caregivers with basis-of-care standards and uniform care procedures and standards in support of effective patient skin care regimens.

Loss of CDKL5 in Glutamatergic Neurons Disrupts Hippocampal Microcircuitry and Leads to Memory Impairment in Mice.

Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a neurodevelopmental disorder characterized by epileptic seizures, severe intellectual disability, and autistic features. Mice lacking CDKL5 display multiple behavioral abnormalities reminiscent of the disorder, but the cellular origins of these phenotypes remain unclear. Here, we find that ablating CDKL5 expression specifically from forebrain glutamatergic neurons impairs hippocampal-dependent memory in male conditional knock-out mice. Hippocampal pyramidal neurons lacking CDKL5 show decreased dendritic complexity but a trend toward increased spine density. This morphological change is accompanied by an increase in the frequency of spontaneous miniature EPSCs and interestingly, miniature IPSCs. Using voltage-sensitive dye imaging to interrogate the evoked response of the CA1 microcircuit, we find that CA1 pyramidal neurons lacking CDKL5 show hyperexcitability in their dendritic domain that is constrained by elevated inhibition in a spatially and temporally distinct manner. These results suggest a novel role for CDKL5 in the regulation of synaptic function and uncover an intriguing microcircuit mechanism underlying impaired learning and memory.SIGNIFICANCE STATEMENT Cyclin-dependent kinase-like 5 (CDKL5) deficiency is a severe neurodevelopmental disorder caused by mutations in the CDKL5 gene. Although Cdkl5 constitutive knock-out mice have recapitulated key aspects of human symptomatology, the cellular origins of CDKL5 deficiency-related phenotypes are unknown. Here, using conditional knock-out mice, we show that hippocampal-dependent learning and memory deficits in CDKL5 deficiency have origins in glutamatergic neurons of the forebrain and that loss of CDKL5 results in the enhancement of synaptic transmission and disruptions in neural circuit dynamics in a spatially and temporally specific manner. Our findings demonstrate that CDKL5 is an important regulator of synaptic function in glutamatergic neurons and serves a critical role in learning and memory.

Increased risk of avascular necrosis in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Avascular necrosis (AVN) and psoriasis have some pathogenic mechanisms and associated conditions in common. OBJECTIVE: To examine the association between psoriasis and AVN. METHODS: This study used data from the Taiwan National Health Insurance Research Database for the period 2004-2006 and identified 28,268 patients with psoriasis, who were then matched for age and sex with 113,072 controls without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Multivariate Cox proportional hazards models were used for the analysis. RESULTS: The unadjusted risk of AVN was significantly higher for patients with psoriasis than for controls (hazard ratio [HR] 2.29) and remained significant after adjustment for other risk factors (adjusted HR 1.96; 95% confidence interval 1.62-2.38). The risk for AVN increased in relation to psoriasis severity and was higher for patients with psoriasis and arthritis than for patients without arthritis. The adjusted HRs were higher for male patients than for female patients and for patients younger than 30 years compared with older patients. LIMITATIONS: We lacked information on daily tobacco use, alcohol consumption, and physical activity. CONCLUSION: The risk for AVN increased with the disease severity of psoriasis.

3D Ta/TaO x /TiO2/Ti synaptic array and linearity tuning of weight update for hardware neural network applications.

The implementation of highly anticipated hardware neural networks (HNNs) hinges largely on the successful development of a low-power, high-density, and reliable analog electronic synaptic array. In this study, we demonstrate a two-layer Ta/TaO x /TiO2/Ti cross-point synaptic array that emulates the high-density three-dimensional network architecture of human brains. Excellent uniformity and reproducibility among intralayer and interlayer cells were realized. Moreover, at least 50 analog synaptic weight states could be precisely controlled with minimal drifting during a cycling endurance test of 5000 training pulses at an operating voltage of 3 V. We also propose a new state-independent bipolar-pulse-training scheme to improve the linearity of weight updates. The improved linearity considerably enhances the fault tolerance of HNNs, thus improving the training accuracy.

Fully parallel write/read in resistive synaptic array for accelerating on-chip learning.

A neuro-inspired computing paradigm beyond the von Neumann architecture is emerging and it generally takes advantage of massive parallelism and is aimed at complex tasks that involve intelligence and learning. The cross-point array architecture with synaptic devices has been proposed for on-chip implementation of the weighted sum and weight update in the learning algorithms. In this work, forming-free, silicon-process-compatible Ta/TaOx/TiO2/Ti synaptic devices are fabricated, in which >200 levels of conductance states could be continuously tuned by identical programming pulses. In order to demonstrate the advantages of parallelism of the cross-point array architecture, a novel fully parallel write scheme is designed and experimentally demonstrated in a small-scale crossbar array to accelerate the weight update in the training process, at a speed that is independent of the array size. Compared to the conventional row-by-row write scheme, it achieves >30× speed-up and >30× improvement in energy efficiency as projected in a large-scale array. If realistic synaptic device characteristics such as device variations are taken into an array-level simulation, the proposed array architecture is able to achieve ∼95% recognition accuracy of MNIST handwritten digits, which is close to the accuracy achieved by software using the ideal sparse coding algorithm.

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice.

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, upon Cdkl5 loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role for Cdkl5 loss-of-function in neurodevelopmental disorders.