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Objectives To highlight the often overlooked role of user interface (UI) design in mitigating bias in artificial intelligence (AI)-based clinical decision support (CDS). Materials and Methods This perspective paper discusses the interdependency between AI-based algorithm development and UI design and proposes strategies for increasing the safety and efficacy of CDS. Results The role of design in biasing user behavior is well documented in behavioral economics and other disciplines. We offer an example of how UI designs play a role in how bias manifests in our machine learning-based CDS development. Discussion Much discussion on bias in AI revolves around data quality and algorithm design; less attention is given to how UI design can exacerbate or mitigate limitations of AI-based applications. Conclusion This work highlights important considerations including the role of UI design in reinforcing/mitigating bias, human factors methods for identifying issues before an application is released, and risk communication strategies. [ABSTRACT FROM AUTHOR]

Background: Although biological plausibility suggests that fluoroquinolones could lead to rhegmatogenous retinal detachment (RRD) through collagen degradation, real-world evidence on their relative risk of RRD is inconsistent, with limited information on absolute risk estimates. Objective: The study aimed to estimate the RRD risk associated with fluoroquinolones versus other antibiotics with similar indications (i.e., comparison antibiotics). Methods: We conducted a retrospective cohort study analyzing claims data from adult patients who initiated fluoroquinolones or amoxicillin/clavulanate or ampicillin/sulbactam or extended-spectrum cephalosporins using the Taiwan National Health Insurance Research Database (2009–2018) and the United States IBM MarketScan Database (2011–2020). Patients were followed for up to 90 days after cohort entry. For each country's data, after 1:1 propensity score (PS) matching, we used Cox regression models to estimate RRD risks, presented with hazard ratios (HR) with 95% confidence interval (95% CI). We used random-effects meta-analyses to derive pooled HRs across both counties. Results: Of 24,172,032 eligible patients comprising 7,944,620 insured Taiwanese (mean age [SD], 46 [18] years; 45% male) and 16,227,412 United States commercially insured individuals (mean age [SD], 47 [16] years; 40% male), 10,137,468 patients initiated fluoroquinolones, 10,203,794 initiated amoxicillin/clavulanate or ampicillin/sulbactam, and 3,830,770 initiated extended-spectrum cephalosporins. After PS matching, similar RRD incidence rates were observed between fluoroquinolones and amoxicillin/clavulanate or ampicillin/sulbactam users (0.33 [95% CI, 0.19–0.56] versus 0.35 [95% CI, 0.26–0.46] per 1,000 person-years), yielding an HR of 0.97 (95% CI, 0.76–1.23). The RRD incidence rates were also similar comparing fluoroquinolones to extended-spectrum cephalosporins (0.36 [95% CI, 0.22–0.57] versus 0.34 [95% CI, 0.22–0.50] per 1,000 person-years; HR, 1.08 [95% CI, 0.92–1.27]). The comparative safety profiles remained consistent by country, various patient characteristic (e.g., diabetes or ophthalmic conditions), type of fluoroquinolones, follow-up duration, or treatment setting. Conclusion: This large-scale study, leveraging real-world data from Taiwan and the United States, showed a low and comparable RRD risk among adults who initiated fluoroquinolones or other antibiotics with similar indications. This suggests that the RRD risk should not deter the use of fluoroquinolone when clinically indicated. [ABSTRACT FROM AUTHOR]

Background Pre-exposure prophylaxis (PrEP) effectiveness is highly dependent on medication adherence, which is associated with differential HIV risks and possibly sexually transmitted infection (STI). Methods This retrospective cohort study of PrEP users (01/01/2012–12/31/2021) used the MarketScan database of commercially insured enrollees to examine PrEP adherence trajectory groups' associations with HIV and STI acquisition risks. Distinct PrEP adherence trajectories were identified by group-based trajectory modeling among individuals who used oral PrEP. The primary outcome was HIV acquisition incidence, and secondary was STI rate, compared among trajectory groups. Inverse probability treatment weighting time-varying Cox proportional hazards models assessed HIV acquisition, and Poisson regression models assessed STI. Results Among 23 258 oral PrEP users, 4 distinct PrEP adherence patterns were identified: minimal use (10.5% of the cohort), rapidly declining (25.4%), gradually declining (24.3%), and consistently high (39.8%). Compared with the minimal use group, the gradually declining (adjusted hazard ratio [AHR], 0.53; 95% CI, 0.31–0.90) and consistently high (AHR, 0.50; 95% CI, 0.30–0.84) PrEP adherence groups showed decreased HIV incidence risks. Compared with the minimal use group, the rapidly declining (adjusted incidence rate ratio [AIRR], 1.35; 95% CI, 1.07–1.72), gradually declining (AIRR, 1.73; 95% CI, 1.38–2.18), and consistently high (AIRR, 2.06; 95% CI, 1.64–2.58) groups were associated with increased STI risk. Conclusions These findings underscore the benefits of continuing and remaining adherent to PrEP and may also inform public health strategies, clinical guidelines, and interventions aimed at maximizing the effectiveness of PrEP in reducing new HIV infections while developing targeted strategies to prevent STIs with PrEP use. [ABSTRACT FROM AUTHOR]

ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults.DesignLongitudinal cohort study.SettingHealth, Aging and Body Composition (Health ABC) Study.ParticipantsTwo thousand five participants aged 70-79 at baseline with medication and gait speed data at 1998-99, 1999-2000, 2001-02, and 2002-03.MeasurementsThe independent variables were any statin use and their standardized daily doses (low, moderate, high) and lipophilicity. The primary outcome measure was decline in gait speed of 0.1 m/s or more in the following year of statin use. Multivariable generalized estimating equations were used, adjusting for demographic characteristics, health-related behaviors, health status, and access to health care.ResultsStatin use increased from 16.2% in 1998-99 to 25.6% in 2002-03. The overall proportions of those with decline in gait speed of 0.1 m/s or more increased from 22.2% in 1998 to 23.9% in 2003. Statin use was not associated with decline in gait speed of 0.1 m/s or more (adjusted odds ratio (AOR) = 0.90, 95% confidence interval (CI) = 0.77-1.06). Similar nonsignificant trends were also seen with the use of hydrophilic or lipophilic statins. Users of low-dose statins were found to have a 22% lower risk of decline in gait speed than nonusers (AOR = 0.78, 95% CI = 0.61-0.99), which was mainly driven by the results from 1999-2000 follow-up.ConclusionThese results suggest that statin use did not increase decline in gait speed in community-dwelling older adults.

Background: Chronic cough (CC), characterized as a cough lasting >8 weeks, is a common multi-factorial syndrome in the community, especially in older adults. Methods: Using a pre-existing algorithm to identify patients with CC within the 2011–2018 Medicare beneficiaries, we examined trends in gabapentinoid use through repeated cross-sectional analyses and identified distinct utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Individuals without CC but with any respiratory conditions related to cough served as a comparator group. Results: Among patients with CC, gabapentinoid use increased from 18.6% in 2011 to 24.1% in 2018 (p = 0.002), with a similar upward trend observed in the non-CC cohort but with overall lower usage (14.7% to 18.4%; p < 0.001). Patients with CC had significantly higher burdens of respiratory and non-respiratory comorbidities, as well as greater healthcare service and medication use compared to the non-CC cohort. The GBTM analyses identified three distinct gabapentinoid utilization trajectories for CC and non-CC patients: no use (77.3% vs. 84.5%), low use (13.9% vs. 10.3%), and high use (8.8% vs. 5.2%). Conclusions: Future studies are needed to evaluate the safety and effectiveness of gabapentinoid use in patients with refractory or unexplained CC in real-world settings. [ABSTRACT FROM AUTHOR]

BackgroundRegular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive.MethodsWe analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided.ResultsAspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (

BackgroundThe impact of evidence-based guidelines and controlled trial data on use of cholesterol-lowering medications in older adults is unclear.ObjectiveTo examine whether utilization patterns of cholesterol-lowering medications in community-dwelling older adults changed following the release of the National Cholesterol Education Program Adult Treatment Panel III guidelines and results from the Prospective Study of Pravastatin in the Elderly at Risk in 2002.MethodsCommunity-dwelling elderly individuals who were enrolled in the Health, Aging and Body Composition Study in 1997-1998 were followed for up to 11 years. An interrupted time series analysis with multivariable generalized estimating equations (GEEs) was used to examine changes in level and trend in cholesterol-lowering medication use before and after 2002, adjusting for sociodemographics, health-related behaviors, and health status.ResultsCholesterol-lowering medication use increased nearly 3-fold from 14.9% in 1997-1998 to 42.6% in 2007-2008, with statins representing the most common class used (87-94%). Multivariable GEE results revealed no significant difference in the level of cholesterol-lowering medication use after 2002 (adjusted OR 0.95; 95% CI 0.89-1.02). Multivariable GEE results revealed that trend changes in the rate of increase in cholesterol-lowering medication declined after 2002 (adjusted ratio of ORs 0.92; 95% CI 0.89-0.95).ConclusionsThe use of cholesterol-lowering medication increased substantially over a decade in community-dwelling elderly individuals but was not related to a change in level or trend following the release of the guidelines and evidence-based data.

Author(s): Cheng Chen 1, Almut G. Winterstein 1,2,3, Wei-Hsuan Lo-Ciganic 1,2, Patrick J. Tighe 4, Yu-Jung Jenny Wei 1,2,* Introduction Amid the opioid epidemic in the US, the proportion of [...], Background Gabapentinoids are increasingly prescribed to manage chronic noncancer pain (CNCP) in older adults. When used concurrently with opioids, gabapentinoids may potentiate central nervous system (CNS) depression and increase the risks for fall. We aimed to investigate whether concurrent use of gabapentinoids with opioids compared with use of opioids alone is associated with an increased risk of fall-related injury among older adults with CNCP. Methods and findings We conducted a population-based cohort study using a 5% national sample of Medicare beneficiaries in the United States between 2011 and 2018. Study sample consisted of fee-for-service (FFS) beneficiaries aged [greater than or equal to]65 years with CNCP diagnosis who initiated opioids. We identified concurrent users with gabapentinoids and opioids days&apos; supply overlapping for [greater than or equal to]1 day and designated first day of concurrency as the index date. We created 2 cohorts based on whether concurrent users initiated gabapentinoids on the day of opioid initiation (Cohort 1) or after opioid initiation (Cohort 2). Each concurrent user was matched to up to 4 opioid-only users on opioid initiation date and index date using risk set sampling. We followed patients from index date to first fall-related injury event ascertained using a validated claims-based algorithm, treatment discontinuation or switching, death, Medicare disenrollment, hospitalization or nursing home admission, or end of study, whichever occurred first. In each cohort, we used propensity score (PS) weighted Cox models to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) of fall-related injury, adjusting for year of the index date, sociodemographics, types of chronic pain, comorbidities, frailty, polypharmacy, healthcare utilization, use of nonopioid medications, and opioid use on and before the index date. We identified 6,733 concurrent users and 27,092 matched opioid-only users in Cohort 1 and 5,709 concurrent users and 22,388 matched opioid-only users in Cohort 2. The incidence rate of fall-related injury was 24.5 per 100 person-years during follow-up (median, 9 days; interquartile range [IQR], 5 to 18 days) in Cohort 1 and was 18.0 per 100 person-years during follow-up (median, 9 days; IQR, 4 to 22 days) in Cohort 2. Concurrent users had similar risk of fall-related injury as opioid-only users in Cohort 1(aHR = 0.97, 95% CI 0.71 to 1.34, p = 0.874), but had higher risk for fall-related injury than opioid-only users in Cohort 2 (aHR = 1.69, 95% CI 1.17 to 2.44, p = 0.005). Limitations of this study included confounding due to unmeasured factors, unavailable information on gabapentinoids&apos; indication, potential misclassification, and limited generalizability beyond older adults insured by Medicare FFS program. Conclusions In this sample of older Medicare beneficiaries with CNCP, initiating gabapentinoids and opioids simultaneously compared with initiating opioids only was not significantly associated with risk for fall-related injury. However, addition of gabapentinoids to an existing opioid regimen was associated with increased risks for fall. Mechanisms for the observed excess risk, whether pharmacological or because of channeling of combination therapy to high-risk patients, require further investigation. Clinicians should consider the risk-benefit of combination therapy when prescribing gabapentinoids concurrently with opioids.

Background/Objectives: Concurrent opioid (OPI) and benzodiazepine (BZD) use may exacerbate injurious fall risk (e.g., falls and fractures) compared to no use or use alone. Yet, patients may need concurrent OPI-BZD use for co-occurring conditions (e.g., pain and anxiety). Therefore, we examined the association between longitudinal OPI-BZD dosing patterns and subsequent injurious fall risk. Methods: We conducted a retrospective cohort study including non-cancer fee-for-service Medicare beneficiaries initiating OPI and/or BZD in 2016–2018. We identified OPI-BZD use patterns during the 3 months following OPI and/or BZD initiation (i.e., trajectory period) using group-based multi-trajectory models. We estimated the time to first injurious falls within the 3-month post-trajectory period using inverse-probability-of-treatment-weighted Cox proportional hazards models. Results: Among 622,588 beneficiaries (age ≥ 65 = 84.6%, female = 58.1%, White = 82.7%; having injurious falls = 0.45%), we identified 13 distinct OPI-BZD trajectories: Group (A): Very-low OPI-only (early discontinuation) (44.9% of the cohort); (B): Low OPI-only (rapid decline) (15.1%); (C): Very-low OPI-only (late discontinuation) (7.7%); (D): Low OPI-only (gradual decline) (4.0%); (E): Moderate OPI-only (rapid decline) (2.3%); (F): Very-low BZD-only (late discontinuation) (11.5%); (G): Low BZD-only (rapid decline) (4.5%); (H): Low BZD-only (stable) (3.1%); (I): Moderate BZD-only (gradual decline) (2.1%); (J): Very-low OPI (rapid decline)/Very-low BZD (late discontinuation) (2.9%); (K): Very-low OPI (rapid decline)/Very-low BZD (increasing) (0.9%); (L): Very-low OPI (stable)/Low BZD (stable) (0.6%); and (M): Low OPI (gradual decline)/Low BZD (gradual decline) (0.6%). Compared with Group (A), six trajectories had an increased 3-month injurious falls risk: (C): HR = 1.78, 95% CI = 1.58–2.01; (D): HR = 2.24, 95% CI = 1.93–2.59; (E): HR = 2.60, 95% CI = 2.18–3.09; (H): HR = 2.02, 95% CI = 1.70–2.40; (L): HR = 2.73, 95% CI = 1.98–3.76; and (M): HR = 1.96, 95% CI = 1.32–2.91. Conclusions: Our findings suggest that 3-month injurious fall risk varied across OPI-BZD trajectories, highlighting the importance of considering both dose and duration when assessing injurious fall risk of OPI-BZD use among older adults. [ABSTRACT FROM AUTHOR]

We used group-based trajectory models to identify 4 distinct trajectory patterns of adherence to preexposure prophylaxis (PrEP) among 20 696 users. Only 44.5% were consistently PrEP adherent, with younger age, being female, or having substance use disorder or depression associated with early discontinuation. Public health efforts are needed to improve PrEP adherence. [ABSTRACT FROM AUTHOR]