Real-world genomic testing and treatment patterns of newly diagnosed adult acute myeloid leukemia patients within a comprehensive health system.

BACKGROUND: We evaluated the frequency of genomic testing and treatment patterns by age category in patients with newly diagnosed (ND) acute myeloid leukemia (AML) treated in both academic- and community-based health systems within a single Midwestern State. METHODS: Retrospective analysis of data from the Indiana University Health System Enterprise Data Warehouse and two local cancer registries, of 629 patients aged ≥18 years with ND AML during 2011-2018. Primary outcome variables were, proportion of patients with genomic analysis and frequency of mutations. Chemotherapy was categorized as "standard induction" or "other chemotherapy"/targeted therapy, and hypomethylating agents. RESULTS: Overall, 13% of ND AML patients between 2011 and 2018 had evidence of a genomic sequencing report with a demonstrated increase to 37% since 2016. Genomic testing was more likely performed in patients: aged ≤60 years than >60 years (45% vs. 30%; p = 0.03), treated in academic versus community hospitals (44% vs. 26%; p = 0.01), and in chemotherapy recipients than non-therapy recipients (46% vs. 19%; p < 0.001). Most common mutations were ASXL1, NPM1, and FLT3. Patients ≥75 years had highest proportion (46%) of multiple (≥3) mutations. Overall, 31.2% of patients with AML did not receive any therapy for their disease. This subgroup was older than chemotherapy recipients (mean age: 71.4 vs. 55.7 years, p < 0.001), and was highest (66.2%) in patients ≥75 years. CONCLUSIONS: Our results highlight the unmet medical need to increase access to genomic testing to afford treatment options, particularly to older AML patients in the real-world setting, in this new era of targeted therapies.

Association between menorrhagia and risk of intrauterine device-related uterine perforation and device expulsion: results from the Association of Uterine Perforation and Expulsion of Intrauterine Device study.

BACKGROUND: Intrauterine devices are effective instruments for contraception, and 1 levonorgestrel-releasing device is also indicated for the treatment of heavy menstrual bleeding (menorrhagia). OBJECTIVE: To compare the incidence of intrauterine device expulsion and uterine perforation in women with and without a diagnosis of menorrhagia within the first 12 months before device insertion STUDY DESIGN: This was a retrospective cohort study conducted in 3 integrated healthcare systems (Kaiser Permanente Northern California, Southern California, and Washington) and a healthcare information exchange (Regenstrief Institute) in the United States using electronic health records. Nonpostpartum women aged ≤50 years with intrauterine device (eg, levonorgestrel or copper) insertions from 2001 to 2018 and without a delivery in the previous 12 months were studied in this analysis. Recent menorrhagia diagnosis (ie, recorded ≤12 months before insertion) was ascertained from the International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. The study outcomes, viz, device expulsion and device-related uterine perforation (complete or partial), were ascertained from electronic medical records and validated in the data sources. The cumulative incidence and crude incidence rates with 95% confidence intervals were estimated. Cox proportional hazards models estimated the crude and adjusted hazard ratios using propensity score overlap weighting (13-16 variables) and 95% confidence intervals. RESULTS: Among 228,834 nonpostpartum women, the mean age was 33.1 years, 44.4% of them were White, and 31,600 (13.8%) had a recent menorrhagia diagnosis. Most women had a levonorgestrel-releasing device (96.4% of those with and 78.2% of those without a menorrhagia diagnosis). Women with a menorrhagia diagnosis were likely to be older, obese, and have dysmenorrhea or fibroids. Women with a menorrhagia diagnosis had a higher intrauterine device-expulsion rate (40.01 vs 10.92 per 1000 person-years) than those without, especially evident in the first few months after insertion. Women with a menorrhagia diagnosis had a higher cumulative incidence (95% confidence interval) of expulsion (7.00% [6.70-7.32] at 1 year and 12.03% [11.52-12.55] at 5 years) vs those without (1.77% [1.70-1.84] at 1 year and 3.69% [3.56-3.83] at 5 years). The risk of expulsion was increased for women with a menorrhagia diagnosis vs for those without (adjusted hazard ratio, 2.84 [95% confidence interval, 2.66-3.03]). The perforation rate was low overall (<1/1000 person-years) but higher in women with a diagnosis of menorrhagia vs in those without (0.98 vs 0.63 per 1000 person-years). The cumulative incidence (95% confidence interval) of uterine perforation was slightly higher for women with a menorrhagia diagnosis (0.09% [0.06-0.14] at 1 year and 0.39% [0.29-0.53] at 5 years) than those without it (0.07% [0.06-0.08] at 1 year and 0.28% [0.24-0.33] at 5 years). The risk of perforation was slightly increased in women with a menorrhagia diagnosis vs in those without (adjusted hazard ratio, 1.53; 95% confidence interval, 1.10-2.13). CONCLUSION: The risk of expulsion is significantly higher in women with a recent diagnosis of menorrhagia. Patient education and counseling regarding the potential expulsion risk is recommended at insertion. The absolute risk of perforation for women with a recent diagnosis of menorrhagia is very low. The increased expulsion and perforation rates observed are likely because of causal factors of menorrhagia.

Design of the Association of Uterine Perforation and Expulsion of Intrauterine Device study: a multisite retrospective cohort study.

BACKGROUND: Intrauterine devices are effective and safe, long-acting reversible contraceptives, but the risk of uterine perforation occurs with an estimated incidence of 1 to 2 per 1000 insertions. The European Active Surveillance Study for Intrauterine Devices, a European prospective observational study that enrolled 61,448 participants (2006-2012), found that women breastfeeding at the time of device insertion or with the device inserted at ≤36 weeks after delivery had a higher risk of uterine perforation. The Association of Uterine Perforation and Expulsion of Intrauterine Device (APEX-IUD) study was a Food and Drug Administration-mandated study designed to reflect current United States clinical practice. The aims of the APEX-IUD study were to evaluate the risk of intrauterine device-related uterine perforation and device expulsion among women who were breastfeeding or within 12 months after delivery at insertion. OBJECTIVE: We aimed to describe the APEX-IUD study design, methodology, and analytical plan and present population characteristics, size of risk factor groups, and duration of follow-up. STUDY DESIGN: APEX-IUD study was a retrospective cohort study conducted in 4 organizations with access to electronic health records: Kaiser Permanente Northern California, Kaiser Permanente Southern California, Kaiser Permanente Washington, and Regenstrief Institute in Indiana. Variables were identified through structured data (eg, diagnostic, procedural, medication codes) and unstructured data (eg, clinical notes) via natural language processing. Outcomes include uterine perforation and device expulsion; potential risk factors were breastfeeding at insertion, postpartum timing of insertion, device type, and menorrhagia diagnosis in the year before insertion. Covariates include demographic characteristics, clinical characteristics, and procedure-related variables, such as difficult insertion. The first potential date of inclusion for eligible women varies by research site (from January 1, 2001 to January 1, 2010). Follow-up begins at insertion and ends at first occurrence of an outcome of interest, a censoring event (device removal or reinsertion, pregnancy, hysterectomy, sterilization, device expiration, death, disenrollment, last clinical encounter), or end of the study period (June 30, 2018). Comparisons of levels of exposure variables were made using Cox regression models with confounding adjusted by propensity score weighting using overlap weights. RESULTS: The study population includes 326,658 women with at least 1 device insertion during the study period (Kaiser Permanente Northern California, 161,442; Kaiser Permanente Southern California, 123,214; Kaiser Permanente Washington, 20,526; Regenstrief Institute, 21,476). The median duration of continuous enrollment was 90 (site medians 74-177) months. The mean age was 32 years, and the population was racially and ethnically diverse across the 4 sites. The mean body mass index was 28.5 kg/m2, and of the women included in the study, 10.0% had menorrhagia ≤12 months before insertion, 5.3% had uterine fibroids, and 10% were recent smokers; furthermore, among these women, 79.4% had levonorgestrel-releasing devices, and 19.5% had copper devices. Across sites, 97,824 women had an intrauterine device insertion at ≤52 weeks after delivery, of which 94,817 women (97%) had breastfeeding status at insertion determined; in addition, 228,834 women had intrauterine device insertion at >52 weeks after delivery or no evidence of a delivery in their health record. CONCLUSION: Combining retrospective data from multiple sites allowed for a large and diverse study population. Collaboration with clinicians in the study design and validation of outcomes ensured that the APEX-IUD study results reflect current United States clinical practice. Results from this study will provide valuable information based on real-world evidence about risk factors for intrauterine devices perforation and expulsion for clinicians.

Treatment patterns and health care costs for patients with psoriatic arthritis on biologic therapy: a retrospective cohort study.

BACKGROUND: Biologic therapies have been used in patients with psoriatic arthritis (PsA) who have been inadequately treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). OBJECTIVE: Examine treatment patterns and health care costs among patients with PsAs who initiated biologic therapy either as monotherapy or adjunctively with traditional DMARDs. METHODS: The MarketScan(®) database was used to identify adults with PsA who initiated therapy with a biologic (with first use identified as index date). Patients were required to have a 6-month pre-period with no biologic use and 1 year insurance eligibility pre- and post-index date. Cohorts of patients initiating biologic therapy either as monotherapy or adjunctively with traditional DMARDs were created. Medication use patterns including discontinuation, switching, and restarting were identified during the 1-year follow-up period. Cox proportional hazards models were conducted to compare time to discontinuation of index biologic, and logistic models were used to compare the rate of discontinuation and biologic switching between the 2 cohorts. All-cause and PsA-related costs were compared between the 2 cohorts using propensity score-adjusted bootstrapping methods. All comparisons were made after adjusting for age, sex, Charlson comorbidity index, and PsA-related total cost over 1-year pre-index date. RESULTS: Among the 3164 PsA patients identified, 67.7% initiated biologics as monotherapy and 32.3% initiated biologics adjunctively with traditional DMARDs. The number of patients on pain medications, topical medications, and traditional DMARDs was significantly lower post index date compared to pre-index date (P < 0.01), while use of antihypertensives, antidiabetics, and statins increased after patients initiated biologic therapy. In 1-year post-period, approximately half of the patients (50.9%) who initiated a biologic continued their index biologic with an average time to discontinuation of 279.8 days for all patients. Rates of discontinuation, switching, and restart were 33.1%, 9.9%, and 6.1%, respectively, for all patients. Rates of switching and restart were similar between the 2 cohorts, but a significantly lower rate of discontinuation was observed in the biologic plus traditional DMARDs cohort than the biologic monotherapy cohort. Pharmacy expenditures were higher for the biologic + DMARD cohort than the biologic-monotherapy cohort ($14,486 vs $14,062; P = 0.0348). No statistically significant differences for either all-cause or PsA-specific costs were observed across the treatment cohorts. CONCLUSIONS: Traditional DMARDs used in combination with biologic therapy appear to reduce rates of biologic therapy discontinuation.

Quality of life scores as prognostic factors of overall survival in advanced head and neck cancer: analysis of a phase III randomized trial of pemetrexed plus cisplatin versus cisplatin monotherapy.

OBJECTIVES: We examined the prognostic factors (clinical, demographic, and health-related quality of life [HRQoL]) of overall survival (OS) and progression-free survival (PFS) in patients with recurrent/metastatic head and neck cancer (HNC) who were treated with pemetrexed plus cisplatin versus cisplatin in a phase III, multinational, randomized trial. MATERIALS AND METHODS: Five subscales of the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-H&N), modified to score from 0 to 100, measured HRQoL at baseline and during treatment. Univariate and multivariate Cox proportional hazards models were used on data pooled from both treatment arms to assess the effect of baseline prognostic factors on OS and PFS. RESULTS: Of 795 patients randomized, 704 completed a baseline FACT-H&N and were included in the analysis. Age (<65 versus ⩾65; HR=0.74, 95% CI: 0.61-0.90), race (Caucasian versus non-Caucasian; HR=0.83, 95% CI: 0.70-0.98 per table), Eastern Cooperative Oncology Group performance status (ECOG PS; 0/1 versus 2; HR=0.44, 95% CI: 0.35-0.56), prior surgery/radiotherapy in the last 6months (no versus yes; HR=0.74, 95% CI: 0.61-0.90), and primary site of disease (oral cavity versus other; HR=1.37, 95% CI: 1.15-1.63) were significantly prognostic of OS in univariate models, as were baseline scores on four FACT-H&N subscales (physical well-being, emotional well-being, functional well-being, additional concerns-H&N; HRs=0.82-0.94; all P⩽0.002). In multivariate models, significant prognostic factors were age (HR=0.78); race (HR=0.76 per table); ECOG PS (HR=0.56); prior surgery/radiotherapy (HR=0.76); and baseline scores of the FACT-H&N subscales of physical well-being, social/family well-being, and additional concerns-H&N (HRs=0.89-0.94; all P⩽0.014 per table). CONCLUSIONS: The results suggest that baseline HRQoL scores are prognostic indicators of OS in recurrent/metastatic HNC in addition to other known clinical and demographic indicators. HRQoL might be considered as a stratification factor in randomized clinical trials of recurrent/metastatic HNC.