In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on ...dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice.
The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range IQR = 0.5-5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval CI 1.56-2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding.
In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Despite successful H. pylori (HP) eradication, some individuals remain at risk of developing gastric cancer (GC). Previous studies showed that aspirin was associated with a reduced GC risk. However, ...whether aspirin can reduce GC risk in HP-eradicated subjects remains unknown. We aimed to determine the chemopreventive effect of aspirin in HP-eradicated subjects.
We identified subjects who had received a prescription of clarithromycin-based triple therapy for HP between 2003 and 2012 from a territory-wide health care database. The observation period started from commencement of HP therapy (index date), and the follow-up was censored at the end of the study (December 2015), death, or GC diagnosis. Aspirin use was defined as use once or more often weekly. Subjects who failed HP eradication or were diagnosed with GC within 12 months of HP therapy were excluded. The hazard ratio (HR) of GC with aspirin use was calculated by Cox model with Propensity Score adjustment for age, sex, comorbidities, and concurrent medications. All statistical tests were two-sided.
The median follow-up was 7.6 years (interquartile range IQR = 5.1-10.3 years), and 169 (0.27%) out of 63 605 patients developed GC. The incidence rate of GC was 3.5 per 10 000 person-years. Aspirin use was associated with a reduced GC risk (HR = 0.30, 95% confidence interval CI = 0.15 to 0.61). The risk of GC decreased with increasing frequency, duration, and dose of aspirin (all Ptrend < .001).
Aspirin use was associated with a frequency-, dose-, and duration-dependent reduction in GC risk after HP eradication. The effect was most prominent in those who used aspirin daily or for five or more years.
This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3-5 years old and examine the relationship between MP and BMI status. A ...cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P
and P
in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.
The case‐control design is widely used in retrospective database studies, often leading to spectacular findings. However, results of these studies often cannot be replicated, and the advantage of ...this design over others is questionable. To demonstrate the shortcomings of applications of this design, we replicate two published case‐control studies. The first investigates isotretinoin and ulcerative colitis using a simple case‐control design. The second focuses on dipeptidyl peptidase‐4 inhibitors and acute pancreatitis, using a nested case‐control design. We include large sets of negative control exposures (where the true odds ratio is believed to be 1) in both studies. Both replication studies produce effect size estimates consistent with the original studies, but also generate estimates for the negative control exposures showing substantial residual bias. In contrast, applying a self‐controlled design to answer the same questions using the same data reveals far less bias. Although the case‐control design in general is not at fault, its application in retrospective database studies, where all exposure and covariate data for the entire cohort are available, is unnecessary, as other alternatives such as cohort and self‐controlled designs are available. Moreover, by focusing on cases and controls it opens the door to inappropriate comparisons between exposure groups, leading to confounding for which the design has few options to adjust for. We argue that this design should no longer be used in these types of data. At the very least, negative control exposures should be used to prove that the concerns raised here do not apply.
Background
Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti‐inflammatory drugs ...(NA‐NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA‐NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication.
Methods
Adult patients who had received clarithromycin‐based triple therapy between 2003 and 2016 were identified from a territory‐wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA‐NSAID use (≥90 days) was treated as a time‐dependent variable in a multivariable Cox model (time‐dependent analysis). Time‐independent analysis was also performed.
Results
During a median follow‐up of 8.9 years (interquartile range, 5.4‐12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA‐NSAID use was associated with a significant reduction in the risk of GC in time‐fixed analysis (adjusted hazard ratio aHR, 0.65; 95% CI, 0.47‐0.90), but not in time‐dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97‐1.87). Time‐dependent subgroup analyses also did not indicate any significant association between NA‐NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27‐2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83‐1.98).
Conclusions
NA‐NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA‐NSAIDs observed in prior studies may have been confounded by immortal time bias.
After comprehensively addressing multiple biases, the current results do not support a chemopreventive role of nonaspirin nonsteroidal anti‐inflammatory drugs in gastric cancer development among Helicobacter pylori‐eradicated patients.
Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease ...(CVD) and 10-year CVD outcomes.
A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as <40% reduction in LDL-C. We externally validated the model in a Hong Kong (HK) cohort (n = 170,904). Patients were stratified into four groups by predicted SR and 10-year CVD risk score: SR1 optimal SR & low risk; SR2 sub-optimal SR & low risk; SR3 optimal SR & high risk; SR4 sub-optimal SR & high risk; and 10-year hazard ratios (HR) determined for first major adverse cardiovascular event (MACE). Our SR model included 12 characteristics, with an area under the curve of 0.70 (95% confidence interval CI 0.70-0.71; UK) and 0.68 (95% CI 0.67-0.68; HK). HRs for MACE in predicted sub-optimal SR with low CVD risk groups (SR2 to SR1) were 1.39 (95% CI 1.35-1.43, p<0.001; UK) and 1.14 (95% CI 1.11-1.17, p<0.001; HK). In both cohorts, patients with predicted sub-optimal SR with high CVD risk (SR4 to SR3) had elevated risk of MACE (UK HR 1.36, 95% CI 1.32-1.40, p<0.001: HK HR 1.25, 95% CI 1.21-1.28, p<0.001).
Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigate macular perfusion and the systemic and ocular associations in a population-based setting.
In this cross-sectional study, 2018 adults residing in Hong Kong underwent detailed ophthalmic ...examinations after consenting to participate. Macular perfusion was measured with optical coherence tomography angiography (OCTA) using the split-spectrum amplitude decorrelation angiography algorithm. The parafoveal flow index and vessel area density were quantified using automated custom-built software.
Of the 2018 participants, the OCTA measurements were available for 1940, and 1631 (84.1%) had good quality scans. The right eyes of these 1631 participants (43.1% men) were included for final analysis. Mean age was 49.8 years (range, 18-92 years). Mean global macular vessel density was 47.3% and 55.1% for the superficial and deep retinal layers, respectively. In multivariate analysis, lower superficial vessel density remained significantly associated with lower signal strength index (SSI; P < 0.001, standardized β = 0.607) and male sex (P < 0.001, β = 0.162), and borderline associated with older age (P = 0.09, β = -0.045) and longer axial length (AL; P = 0.09, β = -0.037), while lower deep layer vessel density was significantly associated with lower SSI (P < 0.001, standardized β = 0.667), longer AL (P < 0.001, β = -0.097), and higher creatinine (P < 0.001, β = -0.072).
This large population-based study provided normative OCTA data of macular vessel density and demonstrated that a lower superficial retinal vessel density was significantly associated with lower SSI and male sex, while a lower deep layer retinal vessel density was significantly associated with lower SSI, longer AL, and higher level of creatinine. These associations must be considered when interpreting clinical quantitative OCTA data.
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