Summary
To determine denosumab’s effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing ...denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial.
Introduction
After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women.
Methods
This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses.
Results
In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (
n
= 25,059) and 1.7 per 100 person-years in the off-treatment cohort (
n
= 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52–0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population.
Conclusion
The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial.
Registration:
EnCePP registration number: EUPAS26372; registration date: 12/11/2018.
EGFR overexpression and chromosome 3p deletion are two frequent events in head and neck cancers. We previously mapped the smallest region of recurrent copy-number loss at 3p12.2-p14.1. LRIG1, a ...negative regulator of EGFR, was found at 3p14, and its copy-number loss correlated with poor clinical outcome. Inducible expression of LRIG1 in head and neck cancer TW01 cells, a line with low LRIG1 levels, suppressed cell proliferation in vitro and tumor growth in vivo. Gene expression profiling, quantitative RT-PCR, chromatin immunoprecipitation, and western blot analysis demonstrated that LRIG1 modulated extracellular matrix (ECM) remodeling and EGFR-MAPK-SPHK1 transduction pathway by suppressing expression of EGFR ligands/activators, MMPs and SPHK1. In addition, LRIG1 induction triggered cell morphology changes and integrin inactivation, which coupled with reduced SNAI2 expression. By contrast, knockdown of endogenous LRIG1 in TW06 cells, a line with normal LRIG1 levels, significantly enhanced cell proliferation, migration and invasiveness. Such tumor-promoting effects could be abolished by specific MAPK or SPHK1 inhibitors. Our data suggest LRIG1 as a tumor suppressor for head and neck cancers; LRIG1 downregulation in cancer cells enhances EGFR-MAPK-SPHK1 signaling and ECM remodeling activity, leading to malignant phenotypes of head and neck cancers.
This Letter presents a novel modeless predictive current control (PCC) based on two vectors for a synchronous reluctance motor (SynRM) drive system fed by a four-switch three-phase (FSTP) inverter. ...In each sampling period, two voltage vectors generated by the FSTP inverter are applied to emulate the operation of a six-switch three-phase inverter. Unlike model-based approaches, the proposed method is modeless, meaning that it does not require a system model or its parameters nor the capacitor voltage. For comparison purpose, both model-based and modeless PCCs are realised on a FSTP inverter-fed SynRM drive system via a 32-bit digital signal controller to contrast their current-tracking performances.
This study aimed to determine the photosynthetic performance and differences in chlorophyll fluorescence (ChlF) parameters between Eulophia dentata and its companion species Bletilla formosana and ...Saccharum spontaneum when subjected to different photosynthetic photon flux density (PPFDs). Leaf surfaces were then illuminated with 50, 100 (low PPFDs), 300, 500, 800 (moderate PPFDs); 1,000; 1,500; and 2,000 (high PPFDs) μmol m-2.s-1, and the ChlF parameters were measured during the whole process. Increasing nonphotochemical quenching of ChlF and decreasing potential quantum efficiency of PSII, actual quantum efficiency of PSII, and quantum efficiency ratio of PSII in dark recovery from 0-60 min were observed in all leaves. A significant and negative relationship was detected between energy-dependent quenching (qE) and photoinhibition percent in three species under specific PPFD conditions, whereas a significant and positive relationship was detected between photoinhibitory quenching (qI) and photoinhibition percent. The qE and qI can be easily measured in the field and provide useful ecological indexes for E. dentata species restoration, habitat creation, and monitoring.
It is unclear how the coronavirus disease 2019 (Covid-19) pandemic has affected multimorbidity incidence among those with one pre-existing chronic condition, as well as how vaccination could modify ...this association.
To examine the association of Covid-19 infection with multimorbidity incidence among people with one pre-existing chronic condition, including those with prior vaccination.
Nested case-control study.
We conducted a territory-wide nested case-control study with incidence density sampling using Hong Kong electronic health records from public healthcare facilities and mandatory Covid-19 reports. People with one listed chronic condition (based on a list of 30) who developed multimorbidity during 1 January 2020-15 November 2022 were selected as case participants and randomly matched with up to 10 people of the same age, sex and with the same first chronic condition without having developed multimorbidity at that point. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) of multimorbidity.
In total, 127 744 case participants were matched with 1 230 636 control participants. Adjusted analysis showed that there were 28%-increased odds of multimorbidity following Covid-19 confidence interval (CI) 22% to 36% but only 3% (non-significant) with prior full vaccination with BNT162b2 or CoronaVac (95% CI -2% to 7%). Similar associations were observed in men, women, older people aged 65 or more, and people aged 64 or younger.
We found a significantly elevated risk of multimorbidity following a Covid-19 episode among people with one pre-existing chronic condition. Full vaccination significantly reduced this risk increase.
Summary
Participants with physical limitation and high degree of pain had poor mental and physical health-related quality of life. In addition, the more support and exercise that the participants ...had, the more likely theywere to report better health-related quality of life.
Introduction
Osteoporosis is a public health threat worldwide. The aim of this study is to examine the effects of individual demographics, disease characteristics, and social support on health-related quality of life (HrQoL) of adults with osteoporosis. Most psychosocial studies focused on the relationships but not the specific construct of social support on HrQoL.
Methods
In a correlational design, face-to-face, structured interviews were employed to collect information. Study questionnaires included a demographic sheet, the modified Social Support Inventory, and the Short-Form 36 scales on a convenience sample of 161 individuals recruited from four outpatient centers. Using the structural equation modeling approach, all relationships among factors, mediators, and HrQoL were analyzed.
Results
The mean duration of osteoporosis was longer than 5 years. Participants who exercised more than three times per week had greater HrQoL than individuals who exercised less frequently. Participants with physical limitation and high degree of pain had poor mental and physical HrQoL. The more support that the participants perceived, the more likely they were to report better HrQoL. The best fitted structural equation modeling (SEM) model included individual demographics and physical function, and social support as significant predictors on HrQoL, with informational support and physical function acting as mediators in those relationships. Moreover, this structural model explained 35, 42, and 40 % of the variance on activity of daily living (ADL), physical, and mental health-related quality of life.
Conclusions
The more informational support that individuals have, the more likely they were to report better HrQoL. Individuals with osteoporosis who have lower pain and more exercise are considered having better HrQoL. Further longitudinal research will help clarify the direction of these relationships.
Micropillars with diameters of 3.8, 1 and 0.7
μm were fabricated from a two-phase Zr-based metallic glass using focus ion beam (FIB), and then tested in compression at strain rates from 1
×
10
−4 to ...1
×
10
−2
s
−1. The apparent yield strength of the micropillars ranges from 1992 to 2972
MPa, or 25–86% increase over that of the bulk specimens. This strength increase can be rationalized by the Weibull statistics for brittle materials.
Summary
What is known and Objective: The Department of Health (DOH) in Taiwan issued the ‘Guidelines for Benzodiazepine Use in Sedation and Hypnosis’ in March 2004, which clearly stated that ...benzodiazepines (BZDs) should not be used alone for the treatment of depression. However, the extent to which clinicians comply with the BZD guidelines was not known. This study aimed to evaluate whether sole prescribing of BZDs for major depression decreased after the implementation of the BZD guidelines.
Methods: This was a retrospective longitudinal trend analysis by analyzing the Longitudinal Health Insurance Database (LHID) from September 2002 to September 2005. The LHID contains all claims data from a random sample of 1 000 000 beneficiaries of the universal National Health Insurance programme in Taiwan. The 3‐year study period was divided equally into six periods, before and after the implementation of the guidelines respectively. For each period, the proportion of patients with major depression (ICD‐9‐CM code 296.2x, 296.3x) treated with BZDs without any concomitant antidepressant was calculated in order to conduct a trend analysis.
Results and Discussion: A total of 5463 prescriptions of BZDs solely used for major depression were observed in the entire study period. In more than 80% of the BZD prescriptions in which BZDs were used alone for major depression, they were prescribed at doses higher than one prescribed daily dose/defined daily dose and were supplied for more than 7 days. The number of outpatients with major depression ranged from 2137 to 3326 during the 12 periods. The proportion of depressed patients treated with BZDs alone per 3 months (i.e., the non‐compliance rate) fluctuated from 6·7% to 9·4% before implementation of the guidelines, and from 8·0% to 9·4% after implementation, in outpatient settings. In addition, the guideline non‐adherence rates in inpatient settings varied from 7·0% to 11·8% and from 7·8% to 12·6% before and after the implementation of the BZD guidelines respectively. Further trend analyses indicated that the implementation of the guidelines was not associated with a reduced rate of sole prescribing of BZDs for major depression in either inpatient (P = 0·083) or outpatient settings (P = 0·925).
What is new and Conclusion: The formulation and implementation of the BZD guidelines appear not to be associated with a reduced rate of sole prescribing of BZDs for major depression, and more comprehensive efforts are required.
PDF
