Background/Objectives: Among sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients. Methods: This was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2–63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives. Results: Of 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078–1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2–12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications. Conclusions: The majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

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This study is the first to determine the prevalence of NSAID TD and the factors that were associated with its occurrence in South Korea. These results may help prevent TD and improve appropriate medication use.

BACKGROUND: Individuals with sickle cell disease (SCD) suffer from recurrent catastrophic pain crises that are often managed by opioid analgesics. Being adherent to hydroxyurea has been associated with decreased health care resource use for pain; however, evidence of its association with opioid use is limited. OBJECTIVE:To determine if adherence to hydroxyurea is associated with opioid use among patients with SCD. METHODS: This retrospective study usedTexas Medicaid data from September 1, 2011, to August 31, 2016 (study period). The index date was the date of hydroxyurea initiation. Patients who were aged 2-63 years at the index date, had ≥ 1 inpatient or ≥ 2 outpatient SCD diagnoses during the study period, had ≥ 1 hydroxyurea prescription during the identification period (September 1, 2011-August 31, 2015, had no diagnosis of other indications for hydroxyurea during the study period, and were continuously enrolled for at least 12 months after the index date were included. Hydroxyurea adherence was measured using medication possession ratio (MPR). The study outcomes (measured 1-year post-index) were ( a) opioid use; (b) number of opioid prescriptions; (c) strong opioid use (morphine, hydromorphone, fentanyl, and methadone); (d) number of strong opioid prescriptions; (e) high-dose opioid use (≥ 50 mg morphine milligram equivalent [MME]); and (f) days supply for opioid prescriptions. Covariates included demographic (age and gender) and clinical (vaso-occlusive crisis [VOC], avascular necrosis, iron overload, acute chest syndrome, and blood transfusion) characteristics. Descriptive, bivariate (chi-square and Wilcoxon-Mann-Whitney tests), multiple logistic regression, and negative binomial regression analyses were performed. RESULTS: 1,146 patients (18.3 [12.3] years) met the inclusion criteria. Of these, 19.6% were adherent to hydroxyurea (defined as What is already known about this subject • Patients with sickle cell disease (SCD) suffer from recurrent catastrophic pain crises, and practice guidelines recommend opioid analgesics for pain management.

Although new pharmaceutical therapy options have recently become available, hydroxyurea is still the most commonly used and affordable treatment option for sickle cell disease (SCD). This study aimed to update the evidence on hydroxyurea adherence and its association with clinical and economic outcomes among individuals with SCD. This retrospective study used Texas Medicaid claims data from 09/2011–08/2016. Individuals were included if they had ≥1 inpatient or ≥2 outpatient SCD diagnoses, had ≥1 hydroxyurea prescription, were 2–63 years of age, and were continuously enrolled in Texas Medicaid between 6 months before and 1 year after the first hydroxyurea prescription fill date (index date). Hydroxyurea adherence (Medication Possession Ratio; MPR), vaso‐occlusive crisis (VOC)‐related outcomes, healthcare utilization and expenditures (SCD‐related and all‐cause) during the 1 year following the index date were measured. Bivariate and multivariable analyses were used to address the study objectives. Among 1035 included individuals (age: 18.8 ± 12.5 years, female: 52.1%), 20.9% were adherent to hydroxyurea (defined as MPR≥0.8). After adjustment for demographic and clinical characteristics, compared to being non‐adherent, adhering to hydroxyurea was significantly associated with: a lower risk (Odds Ratio [OR] = 0.480, p = .0007) and hazard rate (Hazard Ratio [HR] = 0.748, p = .0005) of a VOC event, fewer VOC events (Incidence Rate Ratio [IRR] = 0.767, p = .0009), fewer VOC‐related hospital days (IRR = 0.593, p = .0003), fewer all‐cause and SCD‐related hospitalizations (IRR = 0.712, p = .0008; IRR = 0.707, p = .0008, respectively) and emergency department visits (IRR = 0.768, p = .0037; IRR = 0.746, p = .0041, respectively), and lower SCD‐related total healthcare expenditures (IRR = 0.796, p = .0266). Efforts to increase adherence to hydroxyurea could improve clinical and economic outcomes among individuals with SCD.