Association between Regular Hypnotic Use and Age-Related Macular Degeneration

Aspirin is widely used for relief of pain and for cardioprotective effects. Its use is of concern to ophthalmologists when ocular surgery is being considered and also in the presence of age-related macular degeneration (AMD). To examine the association of regular aspirin use with incidence of AMD. The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (N = 4926) were aged 43 to 86 years at the baseline examination. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. Incidence of early AMD, late AMD, and 2 subtypes of late AMD (neovascular AMD and pure geographic atrophy), assessed in retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. The mean duration of follow-up was 14.8 years. There were 512 incident cases of early AMD (of 6243 person-visits at risk) and 117 incident cases of late AMD (of 8621 person-visits at risk) over the course of the study. Regular aspirin use 10 years prior to retinal examination was associated with late AMD (hazard ratio [HR], 1.63 [95% CI, 1.01-2.63]; P = .05), with estimated incidence of 1.76% (95% CI, 1.17%-2.64%) in regular users and 1.03% (95% CI, 0.70%-1.51%) in nonusers. For subtypes of late AMD, regular aspirin use 10 years prior to retinal examination was significantly associated with neovascular AMD (HR, 2.20 [95% CI, 1.20-4.15]; P = .01) but not pure geographic atrophy (HR, 0.66 [95% CI, 0.25-1.95]; P = .45). Aspirin use 5 years (HR, 0.86 [95% CI, 0.71-1.05]; P = .13) or 10 years (HR, 0.86 [95% CI, 0.65-1.13]; P = .28) prior to retinal examination was not associated with incident early AMD. Among an adult cohort, aspirin use 5 years prior to observed incidence was not associated with incident early or late AMD. However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular AMD.

Prevalence and correlates of substance use among clinical nurses in Kaohsiung city.

PurposeStudies have reported mixed results on the association between benzodiazepine use and mortality. Here, we investigated whether benzodiazepine use is associated with a higher risk of 5-year all-cause mortality, and examined the association between benzodiazepine use and 5-year disease-specific mortality.Materials and MethodsIn this population-based cohort study, a nationally representative sample cohort in South Korea was examined. In 2010, benzodiazepine users were defined as individuals prescribed benzodiazepine continuously over 30 days for regular administration, and all other subjects were included in the control group. The primary endpoint was 5-year all-cause mortality, evaluated from 2011 to 2015. Propensity score (PS) matching and time-dependent Cox regression were performed for statistical analysis, which included benzodiazepine use during 2011–2015 as a time-dependent variable.ResultsA total of 822414 adult individuals were included in the final analysis, and the all-cause 5-year mortality was recorded in 20991 individuals (2.7%). The benzodiazepine group included 30837 patients and the control group comprised 791377 patients. After PS matching, 61672 individuals (30836 in each group) were included in the final analysis. After PS matching, the 5-year all-cause mortality in the benzodiazepine group was 10.0% (3082/30836), whereas that in the control group was 9.4% (2893/30836). In time-dependent Cox regression analysis of the PS-matched cohort, the benzodiazepine group showed 1.15-fold higher 5-year all-cause mortality (hazard ratio: 1.15, 95% confidence interval: 1.09–1.22; p<0.001) compared to the control group.ConclusionBenzodiazepine use was associated with increased 5-year all-cause mortality in the South Korean adult population. Further studies are needed to confirm these findings.

This Month in Gastroenterology

We sought to estimate the association between sedative hypnotic use and motor vehicle crash risk. We conducted a new user cohort study of 409 171 adults in an integrated health care system. Health plan data were linked to driver license and collision records. Participants were aged 21 years or older, licensed to drive in Washington State, had at least 1 year of continuous enrollment between 2003 and 2008, and were followed until death, disenrollment, or study end. We used proportional hazards regression to estimate the risk of crash associated with 3 sedatives. We found 5.8% of patients received new sedative prescriptions, with 11 197 person-years of exposure. New users of sedatives were associated with an increased risk of crash relative to nonuse: temazepam hazard ratio (HR) = 1.27 (95% confidence interval [CI] = 0.85, 1.91), trazodone HR = 1.91 (95% CI = 1.62, 2.25), and zolpidem HR = 2.20 (95% CI = 1.64, 2.95). These risk estimates are equivalent to blood alcohol concentration levels between 0.06% and 0.11%. New use of sedative hypnotics is associated with increased motor vehicle crash risk. Clinicians initiating sedative hypnotic treatment should consider length of treatment and counseling on driving risk.

Back to table of contents Previous article Next article Clinical and Research NewsFull AccessHigh-Dose Benzodiazepines May Increase Risk of Death in Schizophrenia PatientsMark MoranMark MoranSearch for more papers by this authorPublished Online:4 Feb 2016https://doi.org/10.1176/appi.pn.2016.1b14AbstractUse of antipsychotics or antidepressants was associated with overall mortality rates 15 to 40 percent lower compared with no use of these medications.Chronic, high-dose use of benzodiazepines among patients with schizophrenia appears to be associated with a markedly higher overall mortality rate than is seen in patients with schizophrenia who have not been exposed to benzodiazepines, according to a report in AJP in Advance (December 7, 2015).The report also found a lower overall mortality rate among patients with schizophrenia who received antipsychotics and/or antidepressants.“The results indicate that any amount of antipsychotic and antidepressant usage is associated with overall mortality rates 15 percent to 40 percent lower compared with no use of these medications,” wrote study authors Jari Tiihonen, M.D., Ph.D., and colleagues at the Karolinska Institutet in Stockholm. “In contrast, benzodiazepine exposure revealed a clear dose-response curve for mortality, where high exposure was associated with a 70 percent higher risk of death compared with no use.”The authors prospectively compared all-cause and cause-specific mortality in individuals aged 16 to 65 who had been diagnosed with schizophrenia (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. The cohort participants were identified from two nationwide Swedish health care registers.Compared with 214,670 age- and gender-matched persons from the general population, the mortality of the cohort with schizophrenia was 4.8-fold higher. The most common specific cause of death was cardiovascular disease (32.7 percent), followed by neoplasms (16.5 percent), respiratory diseases (11.0 percent), and suicide (9.5 percent). Any degree of exposure to antipsychotics or antidepressants was associated with a lower overall mortality compared with no use. The opposite was observed for benzodiazepines, and high exposure was associated with a 74 percent higher risk of death compared with no use. “The association between benzodiazepine exposure and mortality may be explained by several mechanisms,” the authors noted. “Although long-term benzodiazepine use may be a marker for more severe illness and coexisting substance abuse, it is also plausible to assume that prescribing of high doses for long periods may lead to tolerance and dose escalation. This could result in fatal interactions with concurrent use of alcohol and illicit drugs, and worsening of polysubstance dependence may result in a less healthy lifestyle in general. In addition, high-dose benzodiazepine use may also contribute to daytime sedation and proneness to accidents.”Although adverse events associated with antipsychotics have received considerable attention, the study authors emphasized that their findings suggest that patients on high doses of benzodiazepines should be monitored closely.“It is important to realize that although monitoring of patients with moderate- or high-dose antipsychotic treatment is relevant, it is essential to focus the preventive interventions on those patients who have an even higher risk of death, that is, patients not using antipsychotics and patients using high doses of benzodiazepines,” they wrote. AJP Editor Robert Freedman, M.D., cautioned that the study is not necessarily an indictment of benzodiazepines and noted that high-dose use among people with schizophrenia appears to be more common in Sweden than in the United States. “Dr. Tiihonen and colleagues fulfill the maxim that great epidemiologists raise more questions than they answer,” he told Psychiatric News. “As the authors of the study point out, regular benzodiazepine use in addition to antipsychotics likely indexes a more severely ill group of patients. “The message for clinicians is that use of benzodiazepines to avoid the toxicity of antipsychotics seems to have its own problematic consequences,” Freedman continued. “A second message is that Tiihonen and colleagues found that antidepressant use decreases mortality and should be considered as a beneficial therapeutic addition for schizophrenia.” This research was supported by Karolinska Institutet, Niuvanniemi Hospital in Kuopio, Finland, and the Sigrid Juselius Foundation. ■“Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study” can be accessed here. ISSUES NewArchived

Background: Aspirin may help to prevent dementia through its antiplatelet and anti-inflammatory effects, but findings from previous studies are mixed. Considering the length of the preclinical phase of dementia, early initiation of regular aspirin use may be more protective against dementia than later initiation. In this study, we explored the association of regular aspirin use initiated during and after midlife with the risk of dementia. Methods: Using data from 1996 to 2013 on 10,398 ARIC participants, we assessed the association of self-reported prior duration of regular aspirin use which was collected during 1996-1998 (as the baseline of this study) with incident dementia after the baseline. Dementia cases were identified based on: in-person dementia ascertainment from 2011 to 2013; the Telephone Interview for Cognitive Status (TICS) or informant interviews on dementia; and hospital discharge codes/death certificate code by surveillance through 2013. The relative hazards of dementia across categories of the duration of regular aspirin use prior to baseline (&lt;2 years, 2 to &lt;5 years, and ≥ 5 years) were compared to no regular use by Cox proportional hazard models. We adjusted for potential confounders, including demographic variables and major dementia risk factors at baseline. In sensitivity analyses, propensity score weighting was applied. Subgroup analyses were conducted by age, gender, race, APOE, and diabetes status. Results: Participants had a median age of 62 (IQR: 58, 67) at baseline. 55.8% (5,805 of 10,398) were female and 20.6% (2,147 of 10,398) were African American. Lower but non-significant relative hazards (HR) were observed among participants with regular aspirin use for &lt; 2 years (HR: 0.85; 95% CI: 0.69 to 1.04) and ≥ 5 years (HR: 0.87; 95% CI: 0.68 to 1.11), but not for the 2-5 year interval. With propensity score weighting, regular aspirin use &lt; 2 years achieved marginal significance (HR: 0.79; 95% CI: 0.63 to 0.99), while the effect of regular aspirin use ≥ 5 years changed towards null (HR: 1.04; 95%CI: 0.75 to 1.46). Without a prior hypothesis, an interaction was found for diabetes status (p = 0.016) with a significant protective association of ever regular aspirin use compared to no regular use among non-diabetic participants (HR: 0.82; 95%CI: 0.69 to 0.98). Conclusions: We found a non-significant protective association of regular aspirin use at late-middle life with onward incident dementia in a community-dwelling population. Data suggest persons with fewer comorbidities, specifically without diabetes, might be more susceptible to the preventive effect of aspirin use on dementia. Our results are subject to confounding by indication, suggesting the need for additional studies in populations which have different covariate structures than ARIC.

Regular Aspirin Use and Risk of Non-Hodgkin Lymphoma: A Prospective Analysis in the Nurses’ Health Study

Apixaban has superior effectiveness and safety compared to rivaroxaban in patients with commercial healthcare coverage: A population-based analysis in response to CVS 2022 formulary changes.

Whether metformin may reduce the risk of age-related macular degeneration (AMD) requires confirmation. This study compared the risk of AMD between ever users and never users of metformin matched on propensity score (PS) in Taiwanese patients with type 2 diabetes mellitus. We enrolled study subjects from Taiwan's National Health Insurance. A total of 423,949 patients with new onset diabetes from 1999 to 2005 were identified. After excluding ineligible patients and enrolling only patients aged between 50 and 79 years, we created 13,303 pairs of ever users and never users of metformin matched on PS. The patients were followed from 1 January 2006 to 31 December 2011. We estimated hazard ratios by Cox regression. AMD was newly diagnosed in 506 ever users and 639 never users. The respective incidence rates (per 100,000 person-years) were 778.72 and 1016.62. The hazard ratio (HR) and 95% confidence interval (CI) for ever versus never users was 0.756 (0.673-0.850). While ever users were categorized by tertiles of cumulative duration (<31.8, 31.8-63.9 and >63.9 months) and cumulative dose (<947.1, 947.1-2193.5 and >2193.5 g) of metformin, a dose-response pattern was observed. For the respective tertiles of cumulative duration, the HRs (95% CIs) were 1.131 (0.961-1.330), 0.821 (0.697-0.967) and 0.464 (0.384-0.561), while compared to never users. For the respective tertiles of cumulative dose, the HRs (95% CIs) were 1.131 (0.962-1.329), 0.739 (0.624-0.876) and 0.525 (0.438-0.629). A risk reduction among ever users was observed for all tertiles of defined daily dose but was most remarkable for the third tertile with a defined daily dose of >0.64. Subgroup analyses suggested that the benefit of metformin could be similarly observed among men and women and for age subgroups of 50-64 and 65-79 years. However, patients with diabetic retinopathy would not be significantly benefited and metformin did not seem to be preventive for exudative AMD. In general, metformin significantly reduces the risk of AMD.

Purpose/Aim: To assess whether ocular antihypertensives are associated with the development and progression of age-related macular degeneration (AMD). Materials and Methods: This retrospective, observational cohort study using healthcare claims data from a U.S. nationwide managed-care network between January 1, 2006 and December 31, 2016, included enrollees ≥40 years old with primary open-angle glaucoma with or without a diagnosis of nonexudative AMD at the index date. Hazard ratios (HR) for developing AMD or progressing from nonexudative to exudative AMD with exposure to ocular antihypertensive medications were analyzed. Results: Of 132 963 eligible enrollees, 118 174 (87.5%) had no diagnosis of AMD at baseline while 14 789 (12.5%) had adiagnosis of nonexudative AMD. Prostaglandin analog exposure had adecreased hazard of developing AMD among individuals without baseline disease (HR, 0.90; 95% CI, 0.87–0.94; p< .0001), while topical alpha2-agonist exposure demonstrated an increased hazard of AMD development (HR, 1.08; 95% CI, 1.03–1.14; p= .004). Among patients with baseline nonexudative AMD, topical carbonic anhydrase inhibitor exposure was associated with adecreased hazard of progressing to exudative disease (HR, 0.84; 95% CI, 0.71–0.99; p= .04) while topical alpha2-agonists had increased hazard (HR, 1.17; 95% CI, 1.01–1.36; p= .04). Conclusions: Certain ocular antihypertensive medications may be associated with development or progression of AMD. Their role in AMD pathogenesis should be better understood as they are considered for therapeutics in this disease.

Introduction: Aspirin is used regularly for rheumatoid pain management and cardioprotection. However, aspirin has also been associated with significant adverse events, such as cerebral and gastrointestinal bleeding. Recent findings from several observational epidemiologic studies indicate that regular aspirin use may also be associated with increased risks of some forms of age-related macular degeneration (AMD).Areas covered: In this report, we review recent findings from observational epidemiologic studies suggesting a possible adverse effect of regular aspirin use in AMD, and in particular, neovascular AMD. These findings are considered in light of the relative strengths and limitations of observational studies and randomized trials.Expert opinion: While the findings are important and warrant further investigation, the inherent limitations of observational studies, most notably uncontrolled confounding, preclude an interpretation of causality. Alternatively, the most reliable evidence with which to evaluate the effects of regular aspirin use in AMD will derive from well-designed randomized trials of sufficient size and duration. Such information is unlikely to alter current recommendations for persons at high risk of cardiovascular disease, but should help clarify the benefit-to-risk ratio of regular aspirin use in the large majority of individuals at low-to-moderate risk.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment and blindness in the United States if subretinal neovascularization is left untreated. Knowledge of the association between AMD and survival is informative for underlying mechanisms of AMD. To examine the association between AMD and risk of all-cause and specific-cause mortality in a representative US sample. This population-based prospective cohort study included 5603 participants 40 years or older who responded to the National Health and Nutrition Examination Survey (NHANES) in the 2005-2008 phase. Retinal photographs were graded as early, late, or no AMD. All analyses accounted for the complex and stratified design of NHANES with weighted data. Risks of all-cause mortality were assessed with Cox proportional hazards regression models; risks of specific-cause mortality, with Fine and Gray competing risks regression models. Time to death was counted from baseline to date of death or December 31, 2011, whichever came first. Data analysis was conducted from April 1 through 30, 2018. Age-related macular degeneration status as determined by digital fundus images. Mortality resulting from all causes and specific causes until December 31, 2011. Among the 5603 participants (52.6% female [n = 2793] and 77.1% white [n = 3017]; mean [SE] age, 56.4 [0.4] years), weighted prevalence of any AMD was 6.6%, with 386 (5.8%) having early AMD and 55 (0.8%) having late AMD. After a median follow-up of 4.5 years (interquartile range, 3.6-5.6 years), 433 (5.3%) died of all causes, of whom 361 (83.1%) had no AMD, 54 (11.5%) had signs of early AMD, 18 (5.4%) had signs of late AMD, and 72 (16.9%) had any AMD at baseline. Overall, unadjusted all-cause and specific-cause mortality rates were higher for those participants who had early, late, or any AMD compared with no AMD. However, after adjusting confounding factors, only late AMD was associated with more than a doubling of all-cause mortality (hazard ratio [HR], 2.01; 95% CI, 1.00-4.03) and more than a 3-fold higher risk of mortality due to causes other than cardiovascular disease and cancer (HR, 3.42; 95% CI, 1.38-8.49). No association was identified between AMD presence or early AMD and all-cause or specific-cause mortality. In this study's findings, only late AMD was independently associated with all-cause mortality and mortality due to causes other than cardiovascular disease and cancer, indicating that late AMD may be a marker of biological aging. Alternatively, this association may be due to unmeasured or inadequately assessed confounding factors for late AMD.

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

Postoperative delirium (PD) is an acute brain dysfunction, with a particularly high incidence after cardiovascular surgery. Pharmacist-led interventions show limited evidence in attenuating PD in cardiovascular surgery. In this retrospective cohort study, we aimed to clarify the risk factors of PD for cardiovascular surgery focused on pharmacotherapy and elucidate the effect of pharmacist-led intervention on the PD attenuation rate based on protocol-based pharmaceutical management (PBPM). This study included 142 adult patients who underwent elective valve replacement or valvuloplasty. The risk factors for PD were investigated using multivariate logistic regression analysis. Taking risk factors into consideration, a protocol was developed to discontinue benzodiazepines prescriptions by ward pharmacists, and replace with ramelteon and suvorexant if all the following factors apply: 1) number of medications ≥ 6 drugs, 2) number of doses to take ≥ 4 times, and 3) regular use of benzodiazepines or insomnia. Subsequently, the PD rate was compared during a period of two years and 6 months between the pre-PBPM (n = 39) and post-PBPM (n = 62). The PD rate for elective valve replacement or valvuloplasty was 25% (35/142). The adjusted odds ratio for polypharmacy was 3.3 (95% confidence interval: 1.2–8.9, p = 0.016), suggesting that preoperative risk assessment may be essential for patients with polypharmacy. The PD rate significantly decreased to 13% (8/62) in the post-PBPM group compared with 33% (13/39) in the pre-PBPM group (p = 0.014). There was a significant decrease in benzodiazepines use in post-PBPM compared with pre-PBPM (p = 0.026); however, the rate of ramelteon and orexin receptor antagonists use increased by PBPM introduction (p < 0.001). Although the present PBPM still requires further modification, it is simple and potentially useful for pharmacists to assess the risk of patients undergoing any elective cardiovascular surgery.