Publications

2024

Lin, Ting-Yu, Jiun-Ling Wang, Grace Hsin-Min Wang, Yu-Yun Huang, Ming-Ching Chen, Yaa-Hui Dong, and Wei-Hsuan Lo-Ciganic. (2024) 2024. “Use of Fluoroquinolones and Risk of Rhegmatogenous Retinal Detachment: A Retrospective Cohort Study Using Two Nationwide Representative Claims Databases.”. Frontiers in Pharmacology 15: 1414221. https://doi.org/10.3389/fphar.2024.1414221.

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.

Jarlenski, Marian, Wei-Hsuan LoCiganic, Qingwen Chen, Sabnum Pudasainy, Julie M Donohue, Evan S Cole, and Elizabeth E Krans. (2024) 2024. “Association Between Buprenorphine Dose and Outcomes Among Pregnant Persons With Opioid Use Disorder.”. American Journal of Obstetrics and Gynecology. https://doi.org/10.1016/j.ajog.2024.12.001.

BACKGROUND: Opioid use disorder contributes to maternal morbidity and mortality in the United States. Little is known about how the patterns of buprenorphine dose and duration throughout pregnancy may affect neonatal and postpartum outcomes.

OBJECTIVE: To determine the associations between trajectories of buprenorphine utilization and dose during pregnancy on maternal and neonatal health outcomes.

STUDY DESIGN: Retrospective cohort study among 2925 pregnant persons with opioid use disorder, followed from the estimated start date of pregnancy through 90 days after delivery. We used administrative healthcare data from Medicaid-enrolled individuals to assess buprenorphine dose and use and maternal (postpartum buprenorphine continuation and overdose) and neonatal (low birthweight, neonatal abstinence syndrome (NAS)) outcomes. Group-based trajectory modelling was used to identify trajectories of buprenorphine dose and use during pregnancy. Weighted multivariable logistic regression assessed the association between buprenorphine trajectories and outcomes.

RESULTS: We identified 8 trajectories of buprenorphine utilization and dose during pregnancy. Regression analyses found that high doses of buprenorphine and a longer duration of buprenorphine use during pregnancy was associated with higher odds of postpartum buprenorphine continuation and reduced rates of overdose. Higher doses and longer duration of buprenorphine treatment were not associated with an increase in NAS or term low birth weight, relative to moderate or low doses or shorter treatment duration.

CONCLUSION: A longer duration and higher dose of buprenorphine treatment during pregnancy were associated with improved odds of postpartum buprenorphine continuation and were not associated with adverse neonatal outcomes.

Unigwe, Ikenna F, Amie Goodin, Wei-Hsuan Lo-Ciganic, Robert L Cook, Jennifer Janelle, and Haesuk Park. (2024) 2024. “Trajectories of Adherence to Oral Pre-Exposure Prophylaxis and Risks of HIV and Sexually Transmitted Infections.”. Open Forum Infectious Diseases 11 (10): ofae569. https://doi.org/10.1093/ofid/ofae569.

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.

Samayamuthu, Malarkodi J, Olga Kravchenko, Wei-Hsuan Lo-Ciganic, Eugene M Sadhu, Seonkyeong Yang, Shyam Visweswaran, and Vanathi Gopalakrishnan. (2024) 2024. “Trends in Postpartum Hemorrhage Prevalence and Comorbidity Burden: Insights from the ENACT Network Aggregated Electronic Health Record Data.”. Research Square. https://doi.org/10.21203/rs.3.rs-5041092/v1.

The goal of this study was to assess trends in postpartum hemorrhage (PPH), its risk factors, and maternal comorbidity burden in the United States using aggregate data from the Evolve to Next-Gen Accrual to Clinical Trials (ENACT) network. This federated network employs interactive querying of electronic health record data repositories in academic medical centers nationwide. We conducted repeated annual cross-sectional analyses to evaluate PPH occurrence and comorbidities across various ethnoracial and sociodemographic groups, starting with a large cohort of 1,287,675 unique delivery hospitalizations collected from 22 ENACT sites between 2005 and 2022. During this time, there was a statistically significant increasing trend in the prevalence of PPH, rising from 5,634 to 10,504 PPH per 100,000 deliveries (P trend <0.001). Our findings revealed a continuous upward trend in PPH rates that remained consistent among women with ≥ 1 comorbid conditions (P trend <0.001) and those with ≥ 1 maternal risk factor (P trend <0.001). This result aligns with prior studies and extends beyond the time periods previously reported. Overall, Native Hawaiian or Other Pacific Islander women had the highest PPH prevalence (  13%), followed by Asian (9.8%), American Indian or Alaska Native (8.9%), multirace (8.6%), Black or African American (8.4%) and White (7.4%) women. The top PPH risk factor identified was placenta previa or accreta, while the top comorbidity was antepartum hemorrhage / placental abruption. The most common cause of PPH, namely uterine atony, was prevalent in ENACT data. Our analysis highlights significant ethnoracial disparities and underscores the need for targeted preventative interventions.

Bell, Sigall K, Maelys J Amat, Timothy S Anderson, Mark D Aronson, James C Benneyan, Leonor Fernandez, Dru A Ricci, et al. (2024) 2024. “Do Patients Who Read Visit Notes on the Patient Portal Have a Higher Rate of ‘loop Closure’ on Diagnostic Tests and Referrals in Primary Care? A Retrospective Cohort Study.”. Journal of the American Medical Informatics Association : JAMIA 31 (3): 622-30. https://doi.org/10.1093/jamia/ocad250.

OBJECTIVES: The 2021 US Cures Act may engage patients to help reduce diagnostic errors/delays. We examined the relationship between patient portal registration with/without note reading and test/referral completion in primary care.

MATERIALS AND METHODS: Retrospective cohort study of patients with visits from January 1, 2018 to December 31, 2021, and order for (1) colonoscopy, (2) dermatology referral for concerning lesions, or (3) cardiac stress test at 2 academic primary care clinics. We examined differences in timely completion ("loop closure") of tests/referrals for (1) patients who used the portal and read ≥1 note (Portal + Notes); (2) those with a portal account but who did not read notes (Portal Account Only); and (3) those who did not register for the portal (No Portal). We estimated the predictive probability of loop closure in each group after adjusting for socio-demographic and clinical factors using multivariable logistic regression.

RESULTS: Among 12 849 tests/referrals, loop closure was more common among Portal+Note-readers compared to their counterparts for all tests/referrals (54.2% No Portal, 57.4% Portal Account Only, 61.6% Portal+Notes, P < .001). In adjusted analysis, compared to the No Portal group, the odds of loop closure were significantly higher for Portal Account Only (OR 1.2; 95% CI, 1.1-1.4), and Portal+Notes (OR 1.4; 95% CI, 1.3-1.6) groups. Beyond portal registration, note reading was independently associated with loop closure (P = .002).

DISCUSSION AND CONCLUSION: Compared to no portal registration, the odds of loop closure were 20% higher in tests/referrals for patients with a portal account, and 40% higher in tests/referrals for note readers, after controlling for sociodemographic and clinical factors. However, important safety gaps from unclosed loops remain, requiring additional engagement strategies.

Anderson, Timothy S, Brianna X Wang, Julia H Lindenberg, Shoshana J Herzig, Dylan M Berens, and Mara A Schonberg. (2024) 2024. “Older Adult and Primary Care Practitioner Perspectives on Using, Prescribing, and Deprescribing Opioids for Chronic Pain.”. JAMA Network Open 7 (3): e241342. https://doi.org/10.1001/jamanetworkopen.2024.1342.

IMPORTANCE: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations.

OBJECTIVE: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs.

MAIN OUTCOME AND MEASURES: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing.

RESULTS: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance.

CONCLUSIONS AND RELEVANCE: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

Politzer, Eran, Timothy S Anderson, John Z Ayanian, Vilsa Curto, John A Graves, Laura A Hatfield, Jeffrey Souza, Alan M Zaslavsky, and Bruce E Landon. (2024) 2024. “Primary Care Physicians In Medicare Advantage Were Less Costly, Provided Similar Quality Versus Regional Average.”. Health Affairs (Project Hope) 43 (3): 372-80. https://doi.org/10.1377/hlthaff.2023.00803.

The use of many services is lower in Medicare Advantage (MA) compared with traditional Medicare, generating cost savings for insurers, whereas the quality of ambulatory services is higher. This study examined the role of selective contracting with providers in achieving these outcomes, focusing on primary care physicians. Assessing primary care physician costliness based on the gap between observed and predicted costs for their traditional Medicare patients, we found that the average primary care physician in MA networks was $433 less costly per patient (2.9 percent of baseline) compared with the regional mean, with less costly primary care physicians included in more networks than more costly ones. Favorable selection of patients by MA primary care physicians contributed partially to this result. The quality measures of MA primary care physicians were similar to the regional mean. In contrast, primary care physicians excluded from all MA networks were $1,617 (13.8 percent) costlier than the regional mean, with lower quality. Primary care physicians in narrow networks were $212 (1.4 percent) less costly than those in wide networks, but their quality was slightly lower. These findings highlight the potential role of selective contracting in reducing costs in the MA program.

Amat, Maelys J, Timothy S Anderson, Umber Shafiq, Scot B Sternberg, Talya Salant, Leonor Fernandez, Gordon D Schiff, et al. (2024) 2024. “Low Rate of Completion of Recommended Tests and Referrals in an Academic Primary Care Practice With Resident Trainees.”. Joint Commission Journal on Quality and Patient Safety 50 (3): 177-84. https://doi.org/10.1016/j.jcjq.2023.10.005.

BACKGROUND: A frequent, preventable cause of diagnostic errors involves failure to follow up on diagnostic tests, referrals, and symptoms-termed "failure to close the diagnostic loop." This is particularly challenging in a resident practice where one third of physicians graduate annually, and rates of patient loss due to these transitions may lead to more opportunities for failure to close diagnostic loops. The aim of this study was to determine the prevalence of failure of loop closure in a resident primary care clinic compared to rates in the faculty practice and identify factors contributing to failure.

METHODS: This retrospective cohort study included all patient visits from January 1, 2018, to December 31, 2021, at two academic medical center-based primary care practices where residents and faculty practice in the same setting. The primary outcome was prevalence of failure to close the loop for (1) dermatology referrals, (2) colonoscopy, and (3) cardiac stress testing. The primary predictor was resident vs. faculty status of the ordering provider. The authors present an unadjusted analysis and the results of a multivariable logistic regression analysis incorporating all patient factors to determine their association with loop closure.

RESULTS: Of 12,282 orders for referrals and tests for the three studied areas, 1,929 (15.7%) were ordered by a resident physician. Of resident orders for all three tests, 52.9% were completed within the designated time vs. 58.4% for orders placed by attending physicians (p < 0.01). In an unadjusted analysis by test type, a similar trend was seen for colonoscopy (51.4% completion rate for residents vs. 57.5% for attending physicians, p < 0.01) and for cardiac stress testing (55.7% completion rate for residents vs. 61.2% for attending physicians), though a difference was not seen for dermatology referrals (64.2% completion rate for residents vs. 63.7% for attending physicians). In an adjusted analysis, patients with resident orders were less likely than attendings to close the loop for all test types combined (odds ratio 0.88, 95% confidence interval 0.79-0.98), with low rates of test completion for both physician groups.

CONCLUSION: Loop closure for three diagnostic interventions was low for patients in both faculty and resident primary care clinics, with lower loop closure rates in resident clinics. Failure to close diagnostic loops presents a safety challenge in primary care and is of particular concern for training programs.