Risk Factors For Discontinuation Research Articles

Abstract PO2-17-05: Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation

Abstract Background Completion of the recommended 5-10 year course of adjuvant endocrine therapy (AET) course is low, and few risk factors for discontinuation have been identified. We examined factors associated with early AET discontinuation in a large cohort with patient-reported outcomes (PROs) and other measures routinely used in clinical care at four sites within an academic health system's multidisciplinary cancer center. Methods We examined postmenopausal women with stage I-III hormone-receptor positive breast cancer identified using the registry at an academic multidisciplinary cancer center 2014-19 who received a prescription for AET, and followed them for up to 5 years. Breast cancer extent of disease and treatments, Elixhauser comorbidity index, medication number and sociodemographic characteristics (age, race/ethnicity, insurance, area deprivation index of zip code of residence) were abstracted from the electronic health record (EHR). PRO measures included the Distress Thermometer (DT, scored 0-10) and its associated problem list (39 yes/no questions), and the Patient Health Questionnaire-9 (depression), all administered routinely as part of clinical care between diagnosis date and start of AET. If >1 PRO performed during that time, the measure closest to AET start was used. DT was dichotomized using the clinically accepted score of 4 as the threshold for severe distress, as was Patient Health Questionnaire-9 (PHQ-9) depression ( >5). AET prescription information included both prescription date from the EHR, and prescription fills assessed using an all-payer pharmacy data source. AET was defined as discontinued (d/c) when no prescription had been filled at any pharmacy for at least 90 days. We used nonparametric hypotheses test for two-samples (d/c vs. no d/c) as well as Kaplan-Meier product-limit time-to-event analyses with censoring for recurrence, death, or change of provider, and advanced machine learning to examine the association of these variables with discontinuation prior to five years. 54 curated covariates were examined in all, corresponding to a Bonferroni statistical significance p-value threshold of 0.001 to control type I error. Sensitivity analyses were performed to 1)use alternative date of DT (closest to diagnosis date) and 2)to examine d/c defined as 180 days. Results Among the cohort of 985 women (74% stage I, 25% Elixhauser comorbidity score >2), 36.9% had a DT >4, and 6.7% a PHQ-9 >5. The cohort had a median followup time of 954 days, and during followup 291 women ( 29.5) % discontinued before completion of the 5-year course or censoring for death, change to a provider outside the system or study end date in 2021. Over 40% of women who stopped filling prescriptions never had their prescriptions discontinued by their physician in the EHR. None of the examined variables including those for Distress and PL, PHQ-9 and measures of extent of disease, cancer treatments, medication number and sociodemographic characteristics were associated with early discontinuation. Results were similar in analyses using the DT date closest to diagnosis or a 180-day prescription fill gap. We also used advanced machine learning with respect to time to event discontinuation had similar results. Conclusions. Clinically available EHR data including two PRO measures were not reliable predictors of early discontinuation. However, many women who had discontinued still had orders for AET in the EHR, suggesting that their physicians were unaware that they had stopped filling prescriptions. Future work should examine whether routine monitoring of prescription fills might be enlisted to identify these women and assist with education, supportive care or other assistance to restart. Citation Format: Joan Neuner, Rodney Sparapani, Jacob Tiegs, Vaia Makris, Melinda Stolley, Sailaja Kamaraju, Bradley Crotty, Kathryn Flynn. Pharmacy fills but not baseline distress or other clinical factors can identify those at high risk for early adjuvant endocrine therapy discontinuation [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-05.

Exploring the prevalence of antidepressant medication discontinuation among pregnant veterans.

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies.

Treatment of Chronic Constipation using Elobixibat in a Real-World Setting: A Retrospective Cohort Study using an Electronic Medical Records Database in Japan

Chronic constipation is a common condition affecting people of all ages; therefore, the socioeconomic burden of chronic constipation is nonnegligible. Elobixibat (ELO), an ileal bail acid transport inhibitor, was launched in Japan in 2018. However, evidence of its use in diverse populations is limited. This study aimed to evaluate the prescription of ELO, risk factors associated with ELO discontinuation, and the continuation of stimulants or saline laxatives during ELO treatment in a real-world setting using an extensive electronic medical records database that primarily includes data from acute-care hospitals. Data of patients prescribed for ELO from April 1, 2018, to March 31, 2022, were extracted from the database. The discontinuation of ELO and stimulant or saline laxatives during ELO treatment was evaluated using the Kaplan-Meier method. The Cox proportional hazards model evaluated risk factors associated with laxative discontinuation. In total, 11,062 patients were evaluated. The rate of ELO discontinuation within 360 days of initiation was 78.7%. Hospitalized at the ELO initiation, stage 5 chronic kidney disease, and diagnosis of constipation by departments of obstetrics and gynecology or by departments of malignant neoplasm were identified as risk factors for discontinuation. Diagnosis of constipation, diabetes mellitus, Parkinson's disease, and previous laxative treatment was associated with a lower risk of ELO discontinuation. The prescription rate of stimulants and saline laxatives markedly decreased after ELO initiation; furthermore, nearly half of patients who were continuously prescribed ELO discontinued these laxatives within 360 days. The discontinuation of ELO was associated with various factors and using ELO may be beneficial in the withdrawal of concurrent stimulants and saline laxatives. These findings may help effectively manage chronic constipation.

Discontinuation of adjuvant endocrine therapy and impact on quality of life and functional status in older patients with breast cancer

PurposeSide effects are the main reason for discontinuation of adjuvant endocrine therapy in older adults. The aim of this study was to examine geriatric predictors of treatment discontinuation of adjuvant endocrine therapy within the first 2 years after initiation, and to study the association between early discontinuation and functional status and quality of life (QoL).MethodsPatients aged ≥ 70 years with stage I–III breast cancer who received adjuvant endocrine therapy were included. The primary endpoint was discontinuation of endocrine therapy within 2 years. Risk factors for discontinuation were assessed using univariate logistic regression models. Linear mixed models were used to assess QoL and functional status over time.ResultsOverall, 258 patients were included, of whom 36% discontinued therapy within 2 years after initiation. No geriatric predictive factors for treatment discontinuation were found. Tumour stage was inversely associated with early discontinuation. Patients who discontinued had a worse breast cancer-specific QoL (b = − 4.37; 95% CI − 7.96 to − 0.78; p = 0.017) over the first 2 years, in particular on the future perspective subscale (b = − 11.10; 95% CI − 18.80 to − 3.40; p = 0.005), which did not recover after discontinuation. Treatment discontinuation was not associated with functional improvement.ConclusionA large proportion of older patients discontinue adjuvant endocrine treatment within 2 years after initiation, but geriatric characteristics are not predictive of early discontinuation of treatment. Discontinuation of adjuvant endocrine therapy did not positively affect QoL and functional status, which implies that the observed poorer QoL in this group is probably not caused by adverse effects of endocrine therapy.

Risk factors for discontinuation of exclusive breast feeding within 1month: a retrospective cohort study in Japan

BackgroundWhile breastfeeding provides benefits for infants and the mother, many women either do not breastfeed or terminate breastfeeding earlier than recommended. The aim of this analysis was to identify factors associated with early discontinuation of breastfeeding in Japanese women.MethodsThis study used data from medical records of women delivering a singleton live birth between March 2017 and August 2019 in Iwase General Hospital, Fukushima Prefecture, Japan to assess cessation of breastfeeding by the 1-month postpartum appointment. Demographic (age at birth, and employment status), medical (parity, and physical and mental condition of the mother; and infant medical factors, such as sex, Apgar score, and jaundice, among other), and family factors (husband/partner, family members living at the same house, among others) in 734 women who had initiated breastfeeding during their delivery hospital stay were examined, and multiple logistic regression was used to determine significant predictors of early cessation of exclusive breastfeeding.ResultsBivariate analysis revealed that women who were primipara, unmarried, exposed to secondhand smoke, and employed; those who smoked before pregnancy; and those who had asthma were more likely to discontinue exclusive breastfeeding than other women. Infant factors associated with discontinuation were lower birthweight, earlier gestational age, neonatal intensive care unit admission, treatment for jaundice, or lower weight gain. Multivariable analysis revealed that primiparity, passive smoking before pregnancy, maternal employment, and neonatal jaundice therapy were associated with discontinuation of breastfeeding.ConclusionsIn particular, women whose partners smoked before pregnancy may need to be targeted for additional support for breastfeeding.

Retrospective Study of Mite-Specific Subcutaneous Immunotherapy in Children

To explore the clinical efficacy and influencing factors of children receiving mite-specific subcutaneous immunotherapy (SCIT). We retrospectively analyzed the data of children who had received mite SCIT for 3 years at the Desensitization Center of our hospital. We used the daily medication score (DMS) to evaluate the medication use status (the higher the score, the higher the amount of medications given and the less satisfactorily was the primary disease controlled) and we used the visual analogue scale (VAS) to evaluate clinical symptoms (the higher the score, the more severe the symptoms). Evaluation was performed after the first SCIT treatment and after treatment was given for 3 months, 4 months, 12 months, and 3 years. According to whether medication for the primary disease was stopped after 3 years, the patients were divided into two groups, the discontinued medication group (discontinued group) and the continued medication group (continued group). The general data, DMS, VAS and the decline rate of the two groups were compared, and logistic regression was performed to analyze the influencing factors of the outcome. A total of 711 children were enrolled in the study, with an average age of 8.38 years at the time of the first visit to the hospital. There were 442 males and 269 females. Skin prick test showed that 445 cases only had mite allergy, and 266 cases had mite allergy combined with other allergies. 360 cases have discontinued the medication for the primary disease after 3 years, and 351 cases had relieved symptoms, but still needed to continue with the medication. At the beginning of SCIT treatment, the DMS and VAS of the discontinued group were lower than those of the continued group ( P<0.05). Evaluations from 3 months to 3 years showed that both DMS and VAS continued to decrease compared with those from the beginning, and the decline rate of DMS and VAS of the discontinued group was higher than that of the continued group after 3 years of SCIT ( P<0.05). After 3 months of SCIT, the positive rates of nasal and ocular symptoms in the discontinued group were lower than those in the continued group ( P<0.05). After 3 years of SCIT, the positive rates of nasal, ocular, and chest symptoms in the discontinued group were lower than those in the continued group ( P<0.05). Univariate analysis combined with multivariate logistic regression showed that initial DMS>4 points and initial VAS>3.5 points were protective factors for the discontinuation of the medication for the primary disease at the end of 3 years of SCIT, while the female sex and DMS reduction rate after 12 months of treatment>50% were risk factors for discontinuation. Mite SCIT can help relieve clinical symptoms and reduce the use of medication for symptomatic treatment. Symptoms can be improved after 3 months of SCIT, with the fastest improvement shown in nasal and eye symptoms. It is not recommended to discontinue the medication for the primary disease for too much after 1 year of treatment.

Sex and Tobacco Use in Service Discontinuation in Rural Primary Care Settings

ABSTRACT Purpose Screening, brief intervention and referral to treatment in Alabama (SBIRT) integrates alcohol and substance use screenings in health care clinics in western Alabama. This study explores the relationships between sex and tobacco use with discontinuation of SBIRT services. Method Risk for alcohol and substance consumption was measured using the United States Alcohol Use Disorders Identification Test (US-AUDIT) and the Drug Abuse Screening Test (DAST-10). A convenience sample of 112 patients was utilized. A multivariable Bayesian binary regression model was estimated to determine risk factors for discontinuation. Results Overall, 64 (58.20%) individuals chose to discontinue services following their screening. Male tobacco users with positive screens for risky alcohol and/or drug use were more likely to discontinue services than non-tobacco users (aOR = 2.57, 95% CI = 1.11, 5.54). Discussion/ Conclusion SBIRT programs may need to address engagement and interventions specifically around tobacco use in relation to risky alcohol and substance use. Gender differences may reflect the need for individualized interventions.

Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding

BackgroundThis study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding.MethodsFor this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands. Eight potential prognostic baseline variables (age, body mass index, caesarean section, vaginal delivery, previous treatment, anticoagulant use, dysmenorrhea, and pictorial blood assessment score) were analyzed using univariable and multivariable regression models to estimate the risk of failure. The main outcome measure was discontinuation of the LNG-IUS within 24 months of follow up, defined as removal of the LNG-IUS or receiving an additional intervention.ResultsA total of 209 women received the LNG-IUS, 201 women were included in the analyses. 93 women (46%) discontinued LNG-IUS treatment within 24 months. Multivariable analysis showed younger age (age below 45) (adjusted RR 1.51, 95% CI 1.10–2.09, p = .012) and severe dysmenorrhea (adjusted RR 1.36, 95% CI 1.01–1.82, p = .041) to be associated with a higher risk of discontinuation.ConclusionsHigh discontinuation rates are found in women who receive an LNG-IUS to treat heavy menstrual bleeding. A younger age and severe dysmenorrhea are found to be risk factors for discontinuation of LNG-IUS treatment. These results are relevant for counselling women with heavy menstrual bleeding.

Risk Factors for Discontinuation of Treatment for Neovascular Age-Related Macular Degeneration

ABSTRACTPurpose: To investigate risk factors for treatment discontinuation for neovascular age-related macular degeneration (nAMD).Methods: Data from the Swedish Macula Register and the Skåne Healthcare Register are reported on the treatment received by 932 nAMD patients diagnosed 2013−2015. Treatment discontinuation is defined as having a termination visit or lacking a control or treatment visit during the period of 10−14 months after the diagnostic visit. The risk of treatment discontinuation during the first year is estimated using a Poisson model and a classification tree.Results: 503 eyes (50.9%) discontinued the treatment within the first year. Patients with visual acuity below 60 ETDRS letters (20/60 Snellen) at baseline, serious comorbidities, or treated at the university hospital have a 42% (95% CI 25−61%, P < 0.001), 27% (95% CI 13−43%, P = 0.001) and 30% (95% CI 15−46%, P < 0.001) increased risk to discontinue treatment compared with similar patients. Patients on ranibizumab therapy have a 45% (95% CI 28−63%, P < 0.001) increased risk for treatment discontinuation during year 1 compared with patients on aflibercept therapy. The classification tree also shows that patients on ranibizumab therapy and those with low VA at baseline are at a higher risk of terminating treatment.Conclusions: Almost half of the patients starting anti-VEGF therapy discontinue treatment during the first year. Patients with risk factors may require additional support to continue with the treatment. Aflibercept therapy could be an alternative to patients at risk of treatment discontinuation.

Tolerability of integrase inhibitors in a real-life setting.

Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit. Major outcomes were early discontinuation (≤1 year) due to any reason and more specifically due to toxicity. Incidence was calculated as number of episodes per 1000 person-years. Risk factors for discontinuation were assessed by multivariate Cox models. Early discontinuations due to any reason were 271 (raltegravir), 168 (elvitegravir) and 264 (dolutegravir) per 1000 patient-years ( P = 0.0821). Early discontinuations due to toxicity were 76 (raltegravir), 103 (elvitegravir) and 81 (dolutegravir) per 1000 patient-years ( P = 0.6792). Overall, the most common toxicities leading to discontinuation were neuropsychiatric, osteomuscular or digestive. Most frequent neuropsychiatric manifestations reported at discontinuation were insomnia, dizziness, headache and anxiety irrespective of the integrase inhibitor. Among discontinuations due to toxicity, neuropsychiatric effects were more common with dolutegravir than with raltegravir or elvitegravir ( P = 0.0046). Age (HR 1.04, 95% CI 1.02-1.07, P = 0.0007) was the only independent risk factor for early discontinuation due to toxicity. Discontinuations due to any reason tended to be less common with elvitegravir, but discontinuations due to toxicity did not differ among integrase inhibitors. Neuropsychiatric toxicity leading to drug discontinuation was more frequent with dolutegravir.

Factors associated with discontinuation of anti-retroviral therapy among adults living with HIV/AIDS in Ethiopia: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE The aim of this review is to assess the best available evidence regarding risk factors for discontinuation from anti-retroviral therapy in Ethiopia. Specifically, the review will be assessing the association between discontinuation from anti-retroviral therapy and the following: Socio-demographic and economic factors Behavioral factors Clinical factors Institutional factors INCLUSION CRITERIA Types of participants This review will consider studies reporting on HIV-positive participants aged 15 years and older who have commenced anti-retroviral therapy. Patients who have been transferred out will be excluded. Patients should have at least one follow-up time. If studies include both adult and pediatrics, and are not stratified by age (pediatrics and adults) during analysis, they will be excluded. Besides, if the studies focus on attrition (mortality or discontinuation) and are not stratified by mortality and discontinuation during analysis, the study will also be excluded. Types of exposure This review will consider studies that have examined risk factors for anti-retroviral therapy treatment discontinuation. These include socio-demographic and economic risk factors such as age, sex, income and being dependent on food supplies; behavioral risk factors such as mental status, presence of bereavement, the partner’s HIV status and fear stigma; clinical factors such as isoniazid prophylaxis provision, presence of side effects, baseline CD4 counts and regimen substitution; and institutional risk factors such as distance from the facility and waiting times. Types of outcomes This review will consider studies that include the following outcomes: anti-retroviral therapy treatment discontinuation, i.e. lost to follow up, drop out or defaulting and stopping TRUNCATED AT 250 WORDS

Abstract P1-12-04: Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes

Abstract Background: Adjuvant five-year treatment with aromatase inhibitors is standard for postmenopausal women with estrogen receptor positive breast cancer. However, aromatase inhibitor-related adverse events including joint symptoms and vasomotor symptoms have a strong impact on patients' quality of life and sometimes result in treatment discontinuation. The aim of this study is to determine risk factors for discontinuation of endocrine therapy in Japanese postmenopausal breast cancer patients treated with adjuvant anastrozole in a prospective cohort study based on patient-reported outcomes (PROs). Patients and Methods: A total of 391 postmenopausal Japanese women with estrogen receptor-positive breast cancer and treated with adjuvant anastrozole were enrolled from 28 centers in this prospective cohort study (SAVS-JP, UMIN000002455). PROs assessment was obtained at baseline, 3, 6, 9 and 12 months which included joint and vasomotor symptoms. Long-term adherence of anastrozole was obtained form 364 out of 391 patients (median follow-up: 44 months, range: 5-105months). We analyzed the relationship of discontinuation of anastrozole with joint and vasomotor symptoms induced by treatment, and patients’ characteristics. Results: Among 364 patients, 64 (17.6%) discontinued, 297 (81.6%) are ongoing and 3 (0.8%) have completed five-year anastrozole treatment. The reasons for discontinuation were recurrence: 20 (31.3%), secondary malignancies: 5 (7.8%), death from non-breast cancer: 1 (1.6%) and adverse events: 38 (59.4%). These 38 patients who stopped treatment caused by adverse events were compared with other 323 patients. Joint and vasomotor symptoms were categorized into grade 0 (no symptom or no change from baseline), grade 1+2 (mild+moderate) and grade 3 (severe). Grades of joint symptoms were significantly associated with discontinuation of anastrozole (Grade 0: 9.7%, grade 1+2: 7.8%, grade 3: 25.0%, p=0.02). Patients with longer time after menopause (16 years or longer) were significantly higher frequency of discontinuation as compared with shorter time after menopause (0-15years) (14.9% vs 8.0%, p=0.04). Univariate analysis revealed that grade 3 joint symptoms (odds ratio: 3.67, 95% confidence interval: 1.34-10.04, p=0.01) and longer time after menopause (OR: 2.01, 95%CI: 1.01-4.00, p=0.04) were significant risk factors for discontinuation. By multivariate analysis, both grade 3 joint symptoms and long time after menopause were independently associated with discontinuation. Conclusion: In the present study, we have identified that grade 3 joint symptoms and longer time after menopause were risk factors for discontinuation of adjuvant anastrozole. These data might give us useful information for counseling in patients with adjuvant aromatase inhibitors for postmenopausal Japanese women. Citation Format: Chiyomi Egawa, Shintaro Takao, Kazuhiko Yamagami, Masaru Miyashita, Masashi Baba, Shigetoshi Ichii, Muneharu Konishi, Yuichiro Kikawa, Junya Minohata, Toshitaka Okuno, Keisuke Miyauchi, Kazuyuki Wakita, Hirofumi Suwa, Takashi Hashimoto, Masayuki Nishino, Takashi Matsumoto, Toshiharu Hidaka, Yutaka Konishi, Yoko Sakoda, Akihiro Miya, Masahiro Kishimoto, Hidefumi Nishikawa, Seishi Kono, Ikuo Kokufu, Isao Sakita, Koushiro Kitatsuji, Koushi Oh, Yasuo Miyoshi. Factors influencing on discontinuation of adjuvant anastrozole in postmenopausal Japanese breast cancer patients: Results from a prospective multicenter cohort study of patient-reported outcomes [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-12-04.

FRI0542 Course of Biotherapies in A Large Cohort of Juvenile Idiopathic Arthritis at Adulthood

BackgroundFew studies focused on the course of biotherapies in juvenile idiopathic arthritis (JIA). Results of these studies showed that anti-TNFalpha drug survival was comparable to adult rheumatoid arthritis. However, these...

Predicting Discontinuation of Pegylated Interferon as a Result of Lack of Efficacy in United States Veterans With Chronic Hepatitis C on Dual Therapy.

Many patients with chronic hepatitis C virus (HCV) being treated with pegylated interferon (peg-IFN) plus ribavirin (RBV) do not respond to therapy and do not clear the virus. Standard of care during the era of dual therapy was to discontinue the patient's therapy based on insufficient decreases in viral load after 12 and/or 24 weeks on therapy. We identified patient characteristics that were significant predictors of discontinuation as a result of lack of efficacy (LOE) in a national database of US veterans with genotypes 1 and 4. We identified US veterans who received care at Veterans Affairs medical centers in 2004-2009 and who had lab-confirmed HCV diagnoses and initiated therapy with peg-IFN plus RBV. Patients who discontinued therapy early were classified as either LOE or non-LOE discontinuers based on pharmacy refill patterns and laboratory response data. Predictors of LOE discontinuation were identified using univariate and multivariable Cox proportional hazards modeling. Of 321 238 HCV patients with an ICD-9 diagnosis code, 31 215 (9.7%) initiated dual therapy with peg-IFN plus RBV, and 10 333 (3.2%) met all inclusion criteria and were included in the analysis. Overall, 13.6% of the cohort was classified as LOE. Significant predictors of LOE discontinuation included treatment for drug abuse (hazard ratio [HR] = 2.18), age >65 years (HR = 1.75), antiretroviral therapy for HIV (HR = 1.48), black race (HR = 1.47), platelet count >100/mm3 (HR = 1.46), and drug therapy for insomnia (HR = 1.40). We identified risk factors for discontinuation caused by LOE. Future work should focus on determining whether these characteristics are also predictive of triple-therapy LOE discontinuations.

Long-Term Adherence to Antimuscarinic Therapy in Everyday Practice: A Systematic Review

Antimuscarinic drug treatment is known to have side effects and, consequently, poor adherence in therapeutic regimens. In this systematic review we study the long-term (greater than 6 months) adherence to antimuscarinic drugs in daily clinical practice, and identify factors contributing to poor adherence and persistence. This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed using PubMed® and Embase™ using synonyms for incontinence, overactive bladder and antimuscarinics combined with synonyms for medication adherence. We chose to include only pharmaceutical database studies (using prescription/insurance claim data) and patient self-report studies, using established pharmacoepidemiological parameters such as persistence rate and medication possession rate. A total of 1,245 titles were screened, of which 102 abstracts were assessed. Fourteen studies were ultimately included, comprising 190,279 unique patients (mean age 69.5 years). Regardless of which specific antimuscarinic drug is studied, persistence rates are usually poor. Considering all drugs together, median persistence rates were 12.0% to 39.4% (with an outlier of 75.5%) at 12 months, 8.0% to 15.0% at 18 months and 6.0% to 12.0% at 24 months. At 36 months persistence rates ranged from 0.0% (darifenacin) to 16.0% (trospium). Mean reported medication possession rates were also low, with a mean of 0.37 at 12 months. Risk factors for discontinuation were identified, with the most important being younger age group, use of oxybutynin and use of immediate release formulations. Improvement in adherence and persistence with antimuscarinic medication should be an important goal in the development of new drugs for overactive bladder and urinary incontinence.

Predictors of Early Treatment Discontinuation Among Patients With Genotype 1 Hepatitis C and Implications for Viral Eradication

A significant proportion of patients with hepatitis C virus (HCV) infection discontinue antiviral treatment prematurely. Risk factors for discontinuation before 48 weeks among patients with genotype 1 HCV vary over the course of therapy. We investigated the rates and risk factors for treatment discontinuation within 12 weeks, 12-24 weeks, and 24-48 weeks. We retrospectively evaluated data from all Veterans Affairs (VA) patients with genotype 1 HCV who initiated pegylated interferon and ribavirin therapy from 2002-2007 (n = 11,019). We accounted for appropriate discontinuation because of viral nonresponse. Overall, 53% of patients completed at least 38.4 weeks of therapy (80% of the projected 48 weeks), 16.5% discontinued early in the setting of viral nonresponse, and 30.9% discontinued despite viral response or in the absence of virologic data. Cirrhosis, diabetes, pretreatment substance use disorder, hemoglobin, and lack of hematopoietic growth factor use independently predicted discontinuation before 12 weeks (P < .05 for all). Among patients with documented early virologic responses, higher baseline levels of creatinine, depression, and lack of growth factor use predicted discontinuation from 12-24 weeks. No factors independently predicted discontinuation from 24-48 weeks among patients responding to treatment at 24 weeks. Early discontinuation of antiviral therapy is common. Use of growth factors was the strongest independent predictor of treatment retention before 24 weeks and should be evaluated prospectively. Early interventions may also be warranted for other risk factors for early discontinuation, such as pre-existing substance use, depression, cirrhosis, or diabetes.

"Risk Factors for Discontinuation of Norplant Implant Use Due to Menstrual Problems."

The objective of the analysis reported here was to examine risk factors for early discontinuation of Norplant implant use due to perceived menstrual problems. Cox's proportional hazard regression model was used to calculate adjusted hazard ratios that would reflect the relationship of selected subject characteristics to the risk of early discontinuation due to perceived menstrual problems. Approximately 13% of the study population discontinued for perceived menstrual problems. At the end of year 2, the gross cumulative life table discontinuation rate for perceived menstrual problems was 9.4 per 100 women and it rose to 16.4 per 100 women at the end of year 5. Women in this study were significantly more likely to discontinue Norplant implant use due to perceived menstrual problems if they had a higher eduction level (>12 years), had used no contraceptives in the month before Norplant implant insertion, or had a relatively long average duration of menstrual flow at admission. Identifying potential risk factors such as these may help providers to counsel and prepare women to use the Norplant implant method.

Risk factors for discontinuation of Norplant implant use due to menstrual problems.

The objective of the analysis reported here was to examine risk factors for early discontinuation of Norplant implant use due to perceived menstrual problems. Cox's proportional hazard regression model was used to calculate adjusted hazard ratios that would reflect the relationship of selected subject characteristics to the risk of early discontinuation due to perceived menstrual problems. Approximately 13% of the study population discontinued for perceived menstrual problems. At the end of year 2, the gross cumulative life table discontinuation rate for perceived menstrual problems was 9.4 per 100 women and it rose to 16.4 per 100 women at the end of year 5. Women in this study were significantly more likely to discontinue Norplant implant use due to perceived menstrual problems if they had a higher education level (> 12 years), had used no contraceptives in the month before Norplant implant insertion, or had a relatively long average duration of menstrual flow at admission. identifying potential risk factors such as these may help providers to counsel and prepare women to use the Norplant implant method.