Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC.
To ...do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice.
Multinational population-based cohort study.
Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States.
Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription.
Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model.
A total of 527 226 new DOAC users met the inclusion criteria (apixaban,
= 281 320; dabigatran,
= 61 008; edoxaban,
= 12 722; and rivaroxaban,
= 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 95% CI, 0.70 to 0.94), edoxaban (HR, 0.77 CI, 0.66 to 0.91), or rivaroxaban (HR, 0.72 CI, 0.66 to 0.79). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 CI, 0.64 to 0.82), those receiving a reduced dose (HR, 0.68 CI, 0.61 to 0.77), and those with chronic kidney disease (HR, 0.68 CI, 0.59 to 0.77).
Residual confounding is possible.
Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials.
None.
The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.
To evaluate the association between prenatal antipsychotics exposure and the risk of birth ...and neurodevelopmental problems.
This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.
Prenatal antipsychotic exposure.
Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children.
The cohorts included 333 749 mother-child pairs for ADHD (mean SD maternal age at delivery, 31.46 5.03 years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean SD maternal age at delivery, 31.56 5.01 years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (ADHD: wHR, 0.99; 95% CI, 0.60-1.61; ASD: wHR, 1.10; 95% CI, 0.58-2.08; preterm birth: wOR, 0.93; 95% CI, 0.70-1.24; small for gestational age: wOR, 1.21; 95% CI, 0.66-2.20) and in a sibling-matched analysis (ADHD: wHR, 0.41; 95% CI, 0.04-4.93; ASD: wHR, 0.90; 95% CI, 0.40-2.01; preterm birth: wOR, 1.25; 95% CI, 0.85-1.82; small for gestational age: wOR, 0.86, 95% CI, 0.32-2.31).
In this cohort study, the findings did not suggest that prenatal antipsychotics exposure increased the risk of ADHD, ASD, or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to discontinue receipt of their regular antipsychotic treatment during pregnancy.
The combination pharmacotherapy of antiplatelet agents, lipid-modifiers, ACE inhibitors/ARBs and beta-blockers are recommended by international guidelines. However, data on effectiveness of the ...evidence-based combination pharmacotherapy (EBCP) is limited.
To determine the effect of EBCP on mortality and Cardiovascular events in patients with Coronary Heart Disease (CHD) or cerebrovascular disease.
Publications in EMBASE and Medline up to October 2018 were searched for cohort and case-control studies on EBCP for the secondary prevention of cardiovascular disease. The main outcomes were all-cause mortality and major cardiovascular events. Meta-analyses were performed based on random effects models.
21 studies were included. Comparing EBCP to either monotherapy or no therapy, the pooled risk ratios were 0.60 (95% confidence interval 0.55 to 0.66) for all-cause mortality, 0.70 (0.62 to 0.79) for vascular mortality, 0.73 (0.64 to 0.83) for myocardial infarction and 0.79 (0.68 to 0.91) for cerebrovascular events. Optimal EBCP (all 4 classes of drug prescribed) had a risk ratio for all-cause mortality of 0.50 (0.40 to 0.64). This benefit became more dilute as the number of different classes of drug comprising EBCP was decreased-for 3 classes of drug prescribed the risk ratio was 0.58 (0.49 to 0.69) and for 2 classes, the risk ratio was 0.67 (0.60 to 0.76).
EBCP reduces the risk of all-cause mortality and cardiovascular events in patients with CHD or cerebrovascular disease. The different classes of drugs comprising EBCP work in an additive manner, with optimal EBCP conferring the greatest benefit.
Background
The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and ...its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience.
Methods
We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2–12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent–child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic.
Results
The study included 29,202 individual families; of which 12,163 had children aged 2–5 years and 17,029 had children aged 6–12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers.
Conclusions
This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.
Although thousands of genetically modified mouse strains have been cryopreserved by sperm freezing, the likelihood of cryorecovery success cannot be accurately predicted using conventional sperm ...parameters. The objective of the present study was to assess the extent to which measurement of a sperm DNA fragmentation index (DFI) can predict sperm quality and fertility after cryopreservation. Using a modified TUNEL assay, we measured and correlated the DFI of frozen-thawed sperm from 83 unique mutant mouse strains with sperm count, motility and morphology. We observed a linear inverse correlation between sperm DFI and sperm morphology and motility. Further, sperm DFI was significantly higher from males with low sperm counts compared to males with normal sperm counts (P < 0.0001). Additionally, we found that viable embryos derived using sperm from males with high DFI (62.7 ± 7.2% for IVF and 73.3 ± 8.1% for ICSI) failed to litter after embryo transfer compared to embryos from males with low DFI (20.4 ± 7.9% for IVF and 28.1 ± 10.7 for ICSI). This study reveals that measurement of DFI provides a simple, informative and reliable measure of sperm quality and can accurately predict male mouse fertility.
Since the launch of Telemedicine Technologies (Wiley, 2010), the technologies surrounding telemedicine have changed immeasurably, particularly with the emerging trends of Internet-of-Things (IoT), ...digital/e-Health, and wearable, smart and assistive technologies. This second edition overhauls and expands on the original text to reflect the technical advances of the last decade. It covers applications from traditional healthcare services to remote patient monitoring and recovery, to alternative medicine and general health assessment for maintaining optimal health. This welcome update brings together a broad range of topics demonstrating how information and wireless technologies can be used in healthcare.
We herein present an overview of the upcoming 5
edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms ...will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4
edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5
edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
Aims/hypothesis
As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy.
Methods
Abundance of miR-21 was examined ...in diabetic kidneys from
db/db
mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in
db/db
mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21.
Results
In
db/db
mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with
db/m
+
mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of
db/db
mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting
Smad7
may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-β and NF-κB signalling pathways.
Conclusions/interpretation
Inhibition of miR-21 might be an effective therapy for diabetic nephropathy.
More than a third of elderly fall each year in the United States. It has been shown that the longer the lie on the floor, the poorer is the outcome of the medical intervention. To reduce delay of the ...medical intervention, we have developed an acoustic fall detection system (acoustic-FADE) that automatically detects a fall and reports it promptly to the caregiver. Acoustic-FADE consists of a circular microphone array that captures the sounds in a room. When a sound is detected, acoustic-FADE locates the source, enhances the signal, and classifies it as "fall" or "nonfall." The sound source is located using the steered response power with phase transform technique, which has been shown to be robust under noisy environments and resilient to reverberation effects. Signal enhancement is performed by the beamforming technique based on the estimated sound source location. Height information is used to increase the specificity. The mel-frequency cepstral coefficient features computed from the enhanced signal are utilized in the classification process. We have evaluated the performance of acoustic-FADE using simulated fall and nonfall sounds performed by three stunt actors trained to behave like elderly under different environmental conditions. Using a dataset consisting of 120 falls and 120 nonfalls, the acoustic-FADE achieves 100% sensitivity at a specificity of 97%.
PDF
