Quantifying the Time to Administer Outpatient Parenteral Antimicrobial Therapy: A Missed Opportunity to Compensate for the Value of Infectious Diseases.

Outpatient parenteral antimicrobial therapy (OPAT) relies on substantial uncompensated provider time. In this study of a large academic OPAT program, the median amount of unbilled OPAT management time was 27 minutes per week, per OPAT course. These data should inform benchmarks in pursuing novel payment approaches for OPAT.

Commercial Versus Medicaid Insurance and Use of High-Priced Anticancer Treatments.

BACKGROUND: Because the markups on cancer drugs vary by payor, providers' financial incentive to use high-price drugs is differential according to each patient's insurance type. We evaluated the association between patient insurer (commercial vs Medicaid) and the use of high-priced cancer treatments. MATERIALS AND METHODS: We linked cancer registry, administrative claims, and demographic data for individuals diagnosed with cancer in North Carolina from 2004 to 2011, with either commercial or Medicaid insurance. We selected cancers with multiple FDA-approved, guideline-recommended chemotherapy options and large price differences between treatment options: advanced colorectal, lung, and head and neck cancer. The outcome was a receipt of a higher-priced option, and the exposure was insurer: commercial versus Medicaid. We estimated risk ratios (RRs) for the association between insurer and higher-priced treatment using log-binomial models with inverse probability of exposure weights. RESULTS: Of 812 patients, 209 (26%) had Medicaid. The unadjusted risk of receiving higher-priced treatment was 36% (215/603) for commercially insured and 27% (57/209) for Medicaid insured (RR: 1.31, 95% CI: 1.02-1.67). After adjustment for confounders the association was attenuated (RR: 1.15, 95% CI: 0.81-1.65). Exploratory subgroup analysis suggested that commercial insurance was associated with increased receipt of higher-priced treatment among patients treated by non-NCI-designated providers (RR: 1.53, 95% CI: 1.14-2.04). CONCLUSIONS: Individuals with Medicaid and commercial insurance received high-priced treatments in similar proportion, after accounting for differences in case mix. However, modification by provider characteristics suggests that insurance type may influence treatment selection for some patient groups. Further work is needed to determine the relationship between insurance status and newer, high-price drugs such as immune-oncology agents.

The Perceived Usability of Virtual Visits Among Black Adults' Receiving Oncology Care: A Qualitative Analysis.

BACKGROUND: With the COVID-19 pandemic came rapid uptake in virtual oncology care. During this, sociodemographic inequities in access to virtual visits (VVs) have become apparent. To better understand these issues, we conducted a qualitative study to describe the perceived usability and acceptability of VVs among Black adults diagnosed with cancer. METHODS: Adults who self-identified as Black and had a diagnosis of prostate, multiple myeloma, or head and neck cancer were recruited from 2 academic medical centers, and their community affiliates to participate in a semi-structured interview, regardless of prior VV experience. A patient and family advisory board was formed to inform all components of the study. Interviews were conducted between September 2, 2021 and February 23, 2022. Transcripts were organized topically, and themes and subthemes were determined through iterative and interpretive immersion/crystallization cycles. RESULTS: Of the 49 adults interviewed, 29 (59%) had participated in at least one VV. Three overarching themes were derived: (1) VVs felt comfortable and convenient in the right contexts; (2) the technology required for VVs with video presented new challenges, which were often resolved by an audio-only telephone call; and (3) participants reported preferring in-person visits, citing concerns regarding gaps in nonverbal communication, trusting providers, and distractions during VV. CONCLUSION: While VVs were reported to be acceptable in specific circumstances, Black adults reported preferring in-person care, in part due to a perceived lack of interpersonal connectedness. Nonetheless, retaining reimbursement for audio-only options for VVs is essential to ensure equitable access for those with less technology savvy and/or limited device/internet capabilities.

Inverse Probability Weighting to Estimate Exposure Effects on the Burden of Recurrent Outcomes in the Presence of Competing Events.

Recurrent events-outcomes that an individual can experience repeatedly over the course of follow-up-are common in epidemiologic and health services research. Studies involving recurrent events often focus on time to first occurrence or on event rates, which assume constant hazards over time. In this paper, we contextualize recurrent event parameters of interest using counterfactual theory in a causal inference framework and describe an approach for estimating a target parameter referred to as the mean cumulative count. This approach leverages inverse probability weights to control measured confounding with an existing (and underutilized) nonparametric estimator of recurrent event burden first proposed by Dong et al. in 2015. We use simulations to demonstrate the unbiased estimation of the mean cumulative count using the weighted Dong-Yasui estimator in a variety of scenarios. The weighted Dong-Yasui estimator for the mean cumulative count allows researchers to use observational data to flexibly estimate and contrast the expected number of cumulative events experienced per individual by a given time point under different exposure regimens. We provide code to ease application of this method.

Translation of a Claims-Based Frailty Index From the International Classification of Diseases, Ninth Revision, Clinical Modification to the Tenth Revision.

The Faurot frailty index (FFI) is a validated algorithm that uses enrollment and International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)-based billing information from Medicare claims data as a proxy for frailty. In October 2015, the US health-care system transitioned from the ICD-9-CM to the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Applying the Centers for Medicare and Medicaid Services General Equivalence Mappings, we translated diagnosis-based frailty indicator codes from the ICD-9-CM to the ICD-10-CM, followed by manual review. We used interrupted time-series analysis of Medicare data to assess the comparability of the pre- and posttransition FFI scores. In cohorts of beneficiaries enrolled in January 2015-2017 with 8-month frailty look-back periods, we estimated associations between the FFI and 1-year risk of aging-related outcomes (mortality, hospitalization, and admission to a skilled nursing facility). Updated indicators had similar prevalences as pretransition definitions. The median FFI scores and interquartile ranges (IQRs) for the predicted probability of frailty were similar before and after the International Classification of Diseases transition (pretransition: median, 0.034 (IQR, 0.02-0.07); posttransition: median, 0.038 (IQR, 0.02-0.09)). The updated FFI was associated with increased risks of mortality, hospitalization, and skilled nursing facility admission, similar to findings from the ICD-9-CM era. Studies of medical interventions in older adults using administrative claims should use validated indices, like the FFI, to mitigate confounding or assess effect-measure modification by frailty.

Optimizing therapeutic decision-making for off-label medicines use: A scoping review and consensus recommendations for improving practice and research.

PURPOSE: Off-label medicines use is a common and sometimes necessary practice in many populations, with important clinical, ethical and financial consequences, including potential unintended harm or lack of effectiveness. No internationally recognized guidelines exist to aid decision-makers in applying research evidence to inform off-label medicines use. We aimed to critically evaluate current evidence informing decision-making for off-label use and to develop consensus recommendations to improve future practice and research. METHODS: We conducted a scoping review to summarize the literature on available off-label use guidance, including types, extent and scientific rigor of evidence incorporated. Findings informed the development of consensus recommendations by an international multidisciplinary Expert Panel using a modified Delphi process. Our target audience includes clinicians, patients and caregivers, researchers, regulators, sponsors, health technology assessment bodies, payers and policy makers. RESULTS: We found 31 published guidance documents on therapeutic decision-making for off-label use. Of 20 guidances with general recommendations, only 35% detailed the types and quality of evidence needed and the processes for its evaluation to reach sound, ethical decisions about appropriate use. There was no globally recognized guidance. To optimize future therapeutic decision-making, we recommend: (1) seeking rigorous scientific evidence; (2) utilizing diverse expertise in evidence evaluation and synthesis; (3) using rigorous processes to formulate recommendations for appropriate use; (4) linking off-label use with timely conduct of clinically meaningful research (including real-world evidence) to address knowledge gaps quickly; and (5) fostering partnerships between clinical decision-makers, researchers, regulators, policy makers, and sponsors to facilitate cohesive implementation and evaluation of these recommendations. CONCLUSIONS: We provide comprehensive consensus recommendations to optimize therapeutic decision-making for off-label medicines use and concurrently drive clinically relevant research. Successful implementation requires appropriate funding and infrastructure support to engage necessary stakeholders and foster relevant partnerships, representing significant challenges that policy makers must urgently address.

Resistance in Enterobacterales Is Higher Among People Living With Human Immunodeficiency Virus.

BACKGROUND: Multidrug-resistant Enterobacterales (MDR-E) are important pathogens. People living with human immunodeficiency virus (HIV; PLWH) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities. METHODS: We analyzed data from 36 521 patients in a healthcare system in North Carolina who had a clinical culture with growth of an Enterobacterales species from 2000 to 2018; 440 were PLWH. We used generalized linear models to estimate prevalence ratios and differences, contrasting PLWH and people not living with HIV (PNLWH) for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models. RESULTS: The overall prevalence of MDR-E was higher among PLWH (21.5%; 95% confidence interval [CI], 18.2%-25.1%) vs PNLWH (16.5%; 95% CI, 16.2%-16.9%), with an adjusted prevalence ratio of 1.38 (95% CI, 1.14-1.65). PLWH had higher rates of antimicrobial resistance than PNLWH for all antibiotic classes analyzed, including penicillins, penicillin/beta lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PLWH than PNLWH throughout the study period based on the 5-year moving average. CONCLUSIONS: In a large clinical study population in the southeastern United States from 2000 to 2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PLWH than PNLWH. These data highlight the importance of identifying and mitigating the factors that contribute to antimicrobial resistance in PLWH, given the potential clinical consequences of these resistant pathogens.

Did the 2015 USPSTF Abnormal Blood Glucose Recommendations Change Clinician Attitudes or Behaviors? A Mixed-Method Assessment.

BACKGROUND: In 2015, the US Preventive Services Task Force (USPSTF) revised clinical recommendations to more broadly recommend abnormal blood glucose screening and more clearly recommend referral to behavioral interventions for adults with prediabetes. OBJECTIVE: To assess the effects of the 2015 USPSTF recommendation changes on abnormal blood glucose screening and referral to behavioral interventions, and to examine physicians' perceptions of the revised recommendation. DESIGN: We utilized a sequential, dependent mixed-methods triangulation design. PARTICIPANTS: A total of 33,444 patients meeting USPSTF abnormal blood glucose screening criteria within 15 health system-affiliated primary care practices and 20 primary care physicians in North Carolina. MAIN MEASURES: We assessed monthly abnormal blood glucose screening rate and monthly referral rate to behavioral interventions. To estimate trend changes in outcomes, we used segmented linear regression analysis of interrupted time-series data. We gathered physicians' perspectives on the 2015 USPSTF abnormal blood glucose recommendation including awareness of, agreement with, adoption of, and adherence to the recommendation. To analyze qualitative data, we used directed content analysis. KEY RESULTS: There was a slight significant change in trend in abnormal blood glucose screening rates post-recommendation. There was a slight, statistically significant decrease in referral rates to behavioral interventions post-recommendation. Physicians were generally unaware of the revisions to the 2015 USPSTF abnormal blood glucose recommendation; however, once the recommendations were described, physicians agreed with the screening recommendation but felt that the behavioral intervention referral recommendation was hard to implement. CONCLUSION: The 2015 USPSTF abnormal blood glucose guideline had little to no effect on abnormal blood glucose screening or referral to behavioral interventions in North Carolina practices. Potential interventions to improve these rates could include clinical decision tools embedded in the electronic health record and better referral systems for community-based diabetes prevention programs.

Trends in the use of disease-modifying therapies among reproductive-aged women with multiple sclerosis in the United States from 2010 to 2019.

PURPOSE: Multiple sclerosis (MS) is a chronic disease of the central nervous system that disproportionately affects women, with typical onset during reproductive age. Several disease-modifying therapies (DMTs) are FDA-approved to slow disease progression, but are not indicated for use during pregnancy. Our objective was to describe trends over time (2010-2019) in monthly point prevalence of DMT use among reproductive-age women, overall and by generic name. METHODS: This study used administrative claims data from the US during 2009-2019 to identify women age 15-44 with MS and continuous insurance coverage for ≥12 months. DMTs were identified using prescription fills and procedural claims for alemtuzumab, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab, ocrelizumab, and teriflunomide. Monthly prevalent use was defined as ≥1 days' supply of a DMT in the month. Age- and region-standardized monthly prevalence was estimated nonparametrically. RESULTS: Among 42 281 reproductive-aged women over 818 179 person-months, DMT use increased from a minimum monthly prevalence of 49.3% (February, 2011) to a maximum of 58.7% (April, 2019). In 2010, prevalence of injectable DMTs was 43.1% compared to 2.5% for oral DMTs; by 2014, however, oral DMTs (26.5%) surpassed injectable DMTs (23.7%) as the most common route of administration. In the most recent data available (December, 2019), the most common DMTs were dimethyl fumarate, glatiramer acetate, and fingolimod. CONCLUSIONS: DMT use among reproductive-aged women has rapidly evolved during the past decade. Collaborative treatment decision making between women with MS and clinicians may help optimize MS care and improve DMT uptake during reproductive years.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies.

BACKGROUND: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. OBJECTIVE: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. DESIGN: Active-comparator, new-user, retrospective cohort studies. SETTING: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). PARTICIPANTS: Immunocompetent adults with diverticulitis in the outpatient setting. INTERVENTION: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. MEASUREMENTS: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. RESULTS: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). LIMITATION: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. CONCLUSION: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes. PRIMARY FUNDING SOURCE: National Institutes of Health.

Standardizing Discrete-Time Hazard Ratios With a Disease Risk Score.

The disease risk score (DRS) is a summary score that is a function of a potentially large set of covariates. The DRS can be used to control for confounding by the covariates that went into estimation of the DRS and obtain a standardized estimate of an exposure's effect on disease. However, to date, literature on the DRS has not addressed analyses that focus on estimation of survival or hazard functions, which are common in epidemiologic analyses of cohort data. Here, we propose a method for standardization of hazard ratios using the DRS in longitudinal analyses of the association between a binary exposure and an outcome. This approach to handling a potentially large set of covariates through a model-based approach to standardization may provide a useful tool for cohort analyses of hazard ratios and may be particularly well-suited to settings where an exposure propensity score is difficult to model. Simulations are used in this paper to illustrate the approach, and an empirical example is provided.

Use of High-Cost Cancer Treatments in Academic and Nonacademic Practice.

BACKGROUND: Academic physicians, such as those affiliated with National Cancer Institute (NCI)-designated Comprehensive Cancer Centers, may have different practice patterns regarding the use of high-cost cancer drugs than nonacademic physicians. MATERIALS AND METHODS: For this cohort study, we linked cancer registry, administrative, and demographic data for patients with newly diagnosed cancer in North Carolina from 2004 to 2011. We selected cancer types with multiple U.S. Food and Drug Administration-approved, National Comprehensive Cancer Network-recommended treatment options and large differences in reimbursement between higher-priced and lower-priced options (stage IV colorectal, stage IV lung, and stage II-IV head-and-neck cancers). We assessed whether provider's practice setting-NCI-designated Comprehensive Cancer Center ("NCI") versus other location ("non-NCI")-was associated with use of higher-cost treatment options. We used inverse probability of exposure weighting to control for patient characteristics. RESULTS: Of 800 eligible patients, 79.6% were treated in non-NCI settings. Patients treated in non-NCI settings were more likely to receive high-cost treatment than patients treated in NCI settings (36.0% vs. 23.2%), with an unadjusted prevalence difference of 12.7% (95% confidence interval [CI], 5.1%-20.0%). After controlling for potential confounding factors, non-NCI patients remained more likely to receive high-cost treatment, although the strength of association was attenuated (adjusted prevalence difference, 9.6%; 95% CI -0.1%-18.7%). Exploratory analyses suggested potential heterogeneity across cancer type and insurance status. CONCLUSION: Use of higher-cost cancer treatments may be more common in non-NCI than NCI settings. This may reflect differential implementation of clinical evidence, local practice variation, or possibly a response to the reimbursement incentives presented by chemotherapy billing. IMPLICATIONS FOR PRACTICE: Oncology care delivery and practice patterns may vary between care settings. By comparing otherwise similar patients treated in National Cancer Institute (NCI)-designated Comprehensive Cancer Centers with those treated elsewhere, this study suggests that patients may be more likely to receive treatment with certain expensive cancer drugs if treated in the non-NCI setting. These practice differences may result in differences in patient costs and outcomes as a result of where they receive treatment.

Marginal Structural Models for Risk or Prevalence Ratios for a Point Exposure Using a Disease Risk Score.

The disease risk score is a summary score that can be used to control for confounding with a potentially large set of covariates. While less widely used than the exposure propensity score, the disease risk score approach might be useful for novel or unusual exposures, when treatment indications or exposure patterns are rapidly changing, or when more is known about the nature of how covariates cause disease than is known about factors influencing propensity for the exposure of interest. Focusing on the simple case of a binary point exposure, we describe a marginal structural model for estimation of risk (or prevalence) ratios. The proposed model incorporates the disease risk score as an offset in a regression model, and it yields an estimate of a standardized risk ratio where the target population is the exposed group. Simulations are used to illustrate the approach, and an empirical example is provided. Confounder control based on the proposed method might be a useful alternative to approaches based on the exposure propensity score, or as a complement to them.

Impact of New Medications and $4 Generic Programs on Overactive Bladder Treatment Among Older Adults in the United States, 2000-2015.

BACKGROUND: Despite several new medications being Food and Drug Administration-approved for overactive bladder (OAB) and new prescription drug payment programs, there are limited population-based data regarding OAB medication use among older adults. OBJECTIVES: To examine: (1) impacts of new medications and $4 generic programs on time trends for OAB-related medication dispensing for older adults in the United States; (2) differences by age and sex; and (3) temporal changes in OAB-related medication payments. METHODS: Using Truven Health Analytics' Medicare Supplemental Database (2000-2015), we analyzed OAB-related medication claims for 9,477,061 Medigap beneficiaries age 65-104. We estimated dispensing rates (per 1000 person-months), assessed dispensing trends using interrupted time-series methods, compared dispensing rates by age and sex, and summarized payment trends. RESULTS: From 2000 to 2015, 771,609 individuals filled 13,863,998 OAB-related prescriptions. During 2000-2007, 3 new extended-release medications became available (tolterodine, darifenacin, solifenacin), leading to increases in overall OAB-related dispensing rates by 19.1 (99% confidence interval, 17.0-21.2), a 92% increase since 2000; overall rates remained stable during 2008-2015. By 2015, the most common medications were oxybutynin (38%), solifenacin (20%), tolterodine (19%), and mirabegron (12%). Dispensing rates peaked at age 90 (rate, 53.4; 99% confidence interval, 53.1-53.7). Women had higher rates than men at all ages (average ratewomen-ratemen, 22.0). The gap between upper and lower percentiles of medication payments widened between 2008-2015; by 2015, 25% of reimbursed dispensed prescriptions had total payments exceeding $250. CONCLUSIONS: Medication-specific dispensing rates for OAB changed when new alternatives became available. Recent changes in utilization and cost of OAB medications have implications for clinical guidelines, pharmacoepidemiologic studies, and payment policies.

Left Truncation Bias to Explain the Protective Effect of Smoking on Preeclampsia: Potential, But How Plausible?

BACKGROUND: An inverse association between maternal smoking and preeclampsia has been frequently observed in epidemiologic studies for several decades. In the May 2015 issue of this journal, Lisonkova and Joseph described a simulation study suggesting that bias from left truncation might explain the inverse association. The simulations were based on strong assumptions regarding the underlying mechanisms through which bias might occur. METHODS: To examine the sensitivity of the previous authors' conclusions to these assumptions, we constructed a new Monte Carlo simulation using published estimates to frame our data-generating parameters. We estimated the association between smoking and preeclampsia across a range of scenarios that incorporated abnormal placentation and early pregnancy loss. RESULTS: Our results confirmed that the previous authors' findings are highly dependent on assumptions regarding the strength of association between abnormal placentation and preeclampsia. Thus, the bias they described may be less pronounced than was suggested. CONCLUSIONS: Under empirically derived constraints of these critical assumptions, left truncation does not appear to fully explain the inverse association between smoking and preeclampsia. Furthermore, when considering processes in which left truncation may result from the exposure, it is important to precisely describe the target population and parameter of interest before assessing potential bias. We comment on the specification of a meaningful target population when assessing maternal smoking and preeclampsia as a public health issue. We describe considerations for defining a target population in studies of perinatal exposures when those exposures cause competing events (e.g., early pregnancy loss) for primary outcomes of interest.

Incidence of opioid-managed pelvic pain after hysteroscopic sterilization versus laparoscopic sterilization, US 2005-2012.

OBJECTIVE: Compare incidence of opioid-managed pelvic pain within 12 months after hysteroscopic and laparoscopic sterilization. METHODS: Using administrative claims, we identified women aged 18-49 years without recent history of childbirth who underwent hysteroscopic or laparoscopic sterilization between 2005 and 2012. We defined the outcome as ≥2 diagnoses for pelvic pain and ≥2 prescription fills for opioids. We calculated adjusted hazard ratios (HR) using Cox models and propensity score methods (matching and inverse-probability-of-treatment-weighting [IPTW]). RESULTS: We identified 71,875 eligible women (hysteroscopic n = 26,927 [37.5%], laparoscopic n = 44,948 [62.5%]). Of those, 236 (0.88%) hysteroscopic patients and 420 (0.93%) laparoscopic patients experienced the outcome (crude HR = 0.97, 95%CI: [0.83, 1.14]). Adjusted analyses also yielded near-null results (matched HR = 1.08, 95%CI [0.90, 1.31]; IPTW HR = 0.97, 95%CI [0.80, 1.18]). While most sensitivity analyses generated results close to the null, hazard ratios estimated using propensity score matching ranged from 0.65 to 1.53. CONCLUSIONS: Among women without recent history of childbirth, we did not find compelling evidence of a clinically meaningful increase in the incidence of pelvic pain requiring opioids during the year after hysteroscopic sterilization. However, effects observed in sensitivity analyses may merit further investigation.