Real-world Duration of Use and Dosing Frequency of Daratumumab in Patients With Multiple Myeloma in the United States.

Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as a combination therapy for newly diagnosed multiple myeloma (MM) and as monotherapy and combination therapy for relapsed or refractory MM cases. We assessed the length of DARA use across lines of therapy and the probabilities of treatment discontinuation in patients with MM in the real-world. We used the deidentified Clinformatics Data Mart database from Optum to identify patients with MM (n=2124) who received DARA-containing treatment between November 1, 2015 and March 31, 2021 in the United States. Patients were excluded if they had received a stem cell transplant. The duration of DARA use was defined as the time interval between the first initiation and discontinuation of DARA as a time-to-event outcome using the Kaplan-Meier method. A gap of more than 60 days between 2 consequent DARA claim dates was defined as DARA discontinuation. The median duration of continuous DARA use was 16.6 months. By 24 months, 33.1% of patients remained on DARA treatment. In a subgroup analysis of patients with 12 months or more continuous insurance coverage (n=1246), the median length of DARA use was 24.7 months; by 24 months, 51.8% remained on DARA treatment. The dose adherence ratios (observed DARA doses relative to the label) were close to 1.0, particularly among patients with longer follow-up, indicating that real-world DARA dosing frequency was similar to that on the approved label. In summary, this real-world analysis reported that the median duration of continuous DARA use is 16.6 months, with high dosing adherence in patients who have MM.

Management of infection among Medicare beneficiaries with HIV/AIDS: risk of diabetes with protease inhibitors and associated racial disparities using big data approach.

Association between protease inhibitors (PI) and Type II diabetes mellitus (T2DM) in human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients is largely debated. This study examined the odds of developing T2DM among HIV/AIDS Medicare beneficiaries treated with PI and possible racial disparities in the odds. We performed a nested casecontrol study of Medicare database 2013-2017. We included HIV/AIDS positive beneficiaries who were enrolled continuously in Medicare Part A/B with no previous history of T2DM. PI-users were matched to non-PI users and non-anti-retroviral therapies (ART) users using a1:1 greedy propensity score (PS) matching . Multivariablee logistic regressions were performed to assess the odds of developing T2DM. The analysis included 2,353 HIV/AIDS beneficiaries. Matched samples were generated for PI vs. non-PI groups (n = 484) and PI vs. non-ART groups (n = 490). Compared to the non-PI group, the odds of developing T2DM were higher in PI-users (AOR: 1.76; 95% CI: 1.17-2.64), in Caucasian PI-users (AOR: 1.81; 95% CI: 1.02-3.22) and in African-American PI-users (AOR: 1.86; 95% CI: 1.03-3.36). Compared to the non-ART group, the odds of developing T2DM were higher in PI-users (AOR: 1.87; 95% CI: 1.25-2.81), in Caucasian PI-users (AOR: 1.96; 95% CI: 1.14-3.39) and in African-American PI-users (AOR: 2.05; 95% CI: 1.03-4.09). The use of PI is associated with higher odds of T2DM; odds were higher among African-Americans than Caucasians.

Economic impact of comorbid diabetes and associated racial disparities in managing Medicare beneficiaries with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).

Clinical management of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is progressing to include chronic/metabolic complications, which may impose a significant economic burden on beneficiaries and Medicare. We assessed the national economic impact of comorbid Type-II Diabetes Mellitus (T2DM) on HIV/AIDS patients and potential raical disparities. This study was a cross-sectional study of Medicare database 2013-2017. Analytical sample included HIV/AIDS positive beneficiaries continuously enrolled in Part A/B. Total medical costs, prescription costs, inpatient costs, outpatient costs, out-of-pocket (OOP) costs, and Medicare costs were assessed from Medicare claims. Generalized linear models with log-link and gamma distribution were used to examine the impact of T2DM on different costs. A total of 2,509 eligible HIV/AIDS positive beneficiaries were identified of which 19.9% (n=498) had T2DM. After adjusting for covariates, T2DM beneficiaries had higher inpatient costs: 63.34% (95% CI: 42.73%-86.94%), outpatient costs: 50.26% (95% CI: 30.70%-72.75%), Medicare costs: 27.95% (95% CI: 13.81%-43.84%), OOP costs: 59.15% (95% CI: 40.02%-80.92%), and total medical costs: 27.83% (95% CI: 14.27%-43.00%) than non-T2DM beneficiaries. Incremental costs were higher among African Americans than Caucasians. Comorbid T2DM mposes a significant economic burden on HIV/AIDS patients and Medicare, which is higheramong African Americans.

The impact of statin use prior to intensive care unit admission on critically ill patients with sepsis.

OBJECTIVE: To evaluate the impact of pre-intensive care unit admission (pre-ICU) statin use on all-cause in-hospital mortality and ICU length of stay (LOS). DESIGN: Retrospective cohort study. SETTING: Adult ICUs at tertiary hospitals. PATIENTS: Adult critically ill patients diagnosed with sepsis admitted to the ICUs. INTERVENTION: The exposure was pre-ICU statin prescription (statin users); unexposed represented absence of pre-ICU prescription (non-users). MEASUREMENT AND MAIN RESULTS: We used the 2001-2012 Medical Information Mart for Intensive Care-III (MIMIC-III) database to determine average treatment effect (ATE) of pre-ICU statin use on 30-day ICU mortality, ICU LOS, and 30-day in-hospital mortality using the Augmented Inverse Propensity Weighted technique (AIPW), after adjusting for confounding factors (age, race, health insurance, corticosteroids use, vital signs, laboratory tests, and Sequential Organ Failure Assessment score (SOFA). We measured 30-day ICU mortality as deaths within 30 days of admission to the ICU, and ICU LOS was measured in fractional days. A 30-day in-hospital mortality was measured as death within 30 days of hospital admission. A total of 8200 patients with sepsis were identified; 19.8% (1623) were statin users, and 80.2% (6577) were non-users. Most were Caucasian, aged 80 years and above, and male. After adjusting for confounding factors, pre-ICU statin use decreased 30-day ICU mortality (ATE, -0.026; 95% confidence interval [CI], -0.048 to -0.009); ICU LOS (ATE, -0.369; 95% Cl, -0.849 to -0.096); and 30-day in-hospital mortality (ATE, -0.039; 95% CI, -0.084 to -0.026) on average compared with non-statin use, respectively. In a stratified analysis, the result for ICU LOS (ATE, -0.526; 95% CI, -0.879 to -0.241) and 30-day in-hospital mortality (ATE, -0.023; 95% CI, -0.048 to -0.002) was consistent among patients admitted to the medical ICU. CONCLUSIONS: Among patients with sepsis admitted to the medical ICU, pre-ICU statin use is causally associated with a decrease in 30-day ICU mortality, ICU LOS, and 30-day in-hospital mortality compared to non-use. This study adds to the totality of evidence on the pleiotropic effect of statin use in patients with sepsis.

Evaluation of Severe Myalgia Induced by Continuous-Infusion Bumetanide in Patients with Acute Heart Failure.

STUDY OBJECTIVES: Continuous intravenous (IV) infusion bumetanide has been associated with severe myalgia in case reports, and the package labeling lists a reported incidence of 0.2% for severe myalgia. The primary objective of this study was to quantify the incidence of bumetanide infusion-induced severe myalgia in patients with acute heart failure (AHF). Secondary objectives were to assess a dose-response relationship between bumetanide infusion rate and occurrence of myalgia and to investigate potential risk factors associated with bumetanide-induced myalgia. DESIGN: Retrospective analysis. SETTING: Large academic medical center. PATIENTS: Adults hospitalized with AHF who required bumetanide (≥ 0.5 mg/hr [464 patients]) or furosemide (≥ 20 mg/hr [197 patients]) by continuous IV infusion between September 2015 and May 2017. MEASUREMENTS AND MAIN RESULTS: The incidence of severe myalgia with IV furosemide infusion was assessed to measure confounding by indication bias. Electronic medical records were used to identify patients exposed to bumetanide 0.25-mg/ml or furosemide 2-mg/ml continuous IV infusions. We defined severe myalgia as a diffuse myalgia with a physician's documented suspicion of bumetanide- or furosemide-induced myalgia unresponsive to electrolyte repletion and necessitating a change to alternative diuretics. The incidence of severe myalgia during bumetanide therapy was 5.8%, with the incidence increasing with higher bumetanide infusion rates: 2.6% for an infusion rate ≤ 1 mg/hour and 10.3% for a rate > 1 mg/hour (p=0.0005). In the multivariate logistic regression analysis, a bumetanide infusion rate > 1 mg/hour was independently associated (odds ratio 4.8, 95% confidence interval 1.94-12.02, p=0.0007) with severe myalgia compared to that with a rate ≤ 1 mg/hour. No patients receiving furosemide continuous IV infusion experienced severe myalgia, although infusion rates were lower in potency than bumetanide infusion rates. CONCLUSION: The incidence of severe myalgia in patients with AHF receiving bumetanide infusion was 5.8%, 29-fold higher than incidence rate listed in the package labeling. Patients receiving infusion rates > 1 mg/hour were 4-fold more likely to experience bumetanide-induced severe myalgia than those receiving rates ≤ 1 mg/hour.

Correlates of reported modern contraceptive use among postpartum HIV-positive women in rural Nigeria: an analysis from the MoMent prospective cohort study.

BACKGROUND: Nigeria has an annual population of ~ 200,000 women who are both pregnant and HIV-positive. High unmet need for family planning in this population could lead to unintended pregnancies, along with the increased risk of mother-to-child transmission of HIV (MTCT). To identify modifiable barriers and facilitators in effective family planning, we examined correlates of modern contraceptive use among HIV-positive women enrolled in the MoMent prevention of MTCT (PMTCT) implementation research study in rural North-Central Nigeria. METHODS: In this prospective cohort study, HIV-positive pregnant women were enrolled at 20 Primary Healthcare Centers and followed up to 12 months postpartum. Baseline socio-demographic, clinical and obstetric data were collected at enrollment. Participants were to receive routine family planning counselling from healthcare workers during postnatal visits. Analysis utilized baseline data linked to available family planning information collected from each woman at the first postpartum visit. Multivariate logistic regression was performed to determine factors associated with modern contraceptive use. RESULTS: Out of 497 women enrolled, family planning data was available for 399 (80.3%) women, of whom 349 (87.5%) received family planning counselling, and 321 (80.5%) were 30 years old or less. Two-thirds (268, 67.2%) of the cohort analyzed had 1-2 children at baseline; 24.8% (n = 99) had 3-4 children, and 8.0% (n = 32) had > 4 children. Approximately half (199, 49.9%) of the women reported no modern contraceptive use in the postpartum period. Male condoms (116, 29.1%) were the most reported method of contraception; other methods reported included oral hormones (71, 17.8%) and intrauterine devices (13, 3.2%). Only disclosure of HIV status to male partner or relative (aOR = 2.0, 95% CI: 1.2-3.3; p = 0.01) and receipt of family planning counselling (aOR = 2.3, 95% CI: 1.1-4.8; p = 0.03) were positively associated with reported modern contraceptive use. Age, marital or educational status, religious affiliation, employment status, gravidity and parity were non-correlates. CONCLUSIONS: Family planning counselling and disclosure of HIV status are modifiable positive predictors of contraceptive use among our cohort of postpartum HIV-positive women in rural Nigeria. Rates of unintended pregnancy and concomitant risk of MTCT could be significantly reduced through strategies that facilitate these correlates. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov registration number: NCT 01936753; registered September 3, 2013.

Evaluation of dika wax-soybean oil-based artesunate-loaded lipospheres: in vitro-in vivo correlation studies.

OBJECTIVES: To formulate and evaluate artesunate-loaded lipospheres and study the in vitro-in vivo correlations (IV-IVC). MATERIALS AND METHODS: Lipospheres were formulated by melt homogenisation using structured lipid matrices consisting of (1:3 and 1:6) soybean oil and dika wax and were characterised in vitro and in vivo. RESULTS: The small angle X-ray diffraction (SAXD) results of the lipid matrices showed prominent reflection at 2θ = 2.49°, d = 3.55 Å while, wide angle X-ray diffraction (WAXD) showed prominent reflection at 2θ = 20.83°, d = 0.42 Å. Lipospheres had maximum encapsulation efficiency of 80%, showed no significant decrease in pH with time (p < 0.05), and had sustained release properties. The ratio of the area under the curve (AUC) of the lipospheres and the tablets gave bioavailability enhancement factor of 2.108. CONCLUSION: Artesunate-loaded lipospheres could be used orally or parenterally once daily, for the treatment of malaria.