What Is Valued Most by Patients With Type 2 Diabetes Mellitus When Selecting Second-Line Antihyperglycemic Medications in China

Objective: To estimate patient preferences for second-line antihyperglycemic medications in China.Methods: A face to face survey with the best-worst scaling (BWS) choices was administered in patients with diagnosed type 2 diabetes mellitus (T2DM). Study participants were asked to indicate which attribute they valued most and which attribute they valued least in 11 choice sets, each of which consisted of five alternatives out of 11 antihyperglycemic medication-specific attributes (treatment efficacy, weight change, hypoglycemic events, gastrointestinal side effects, cardiovascular health, urinary tract infection and genital infection side effects, edema, mode of administration, bone fracture, dosing frequency and out-of-pocket cost). A counting approach, a conditional logit model, and K-means clustering were used to estimate the relative importance of items and preference heterogeneity.Results: A total of 362 participants were included with a mean age of 63.6 (standard deviation: 11.8) years. There were 56.4% of participants were women, and 56.3% being diagnosed with diabetes for at least 5 years. Efficacy, cardiovascular health and hypoglycemic events were valued most, while dosing frequency, mode of administration and bone fracture were valued least. The K-means clustering further showed preference heterogeneity in out-of-pocket cost across the participants.Conclusion: Our study suggests that treatment efficacy, cardiovascular health and hypoglycemic events are valued most by Chinese patients with T2DM when selecting second-line antihyperglycemic medications. The study improves the understanding of patients’ preferences for second-line antihyperglycemic medications in China.

The Difference in Contributing Factors and Costs Associated with Outpatient Refusal to Accept Cardiovascular Medications or Analgesics During Dispensing Process.

Background: Study looking into cardiovascular disorders (CVD) medicines or analgesics cost-saving activities during dispensing process is lacking. Aim: To determine differences in factors and costs associated with refused CVD medicines or analgesics during dispensing process Method: This study was approved by Medical Research and Ethics Committee (MREC) (Registration number: NMRR-20-177-53153(IIR)). Participants receiving CVD medicines or analgesics during dispensing process were recruited via convenience sampling technique between February and March 2020 at the Specialist Pharmacy Department of Jerantut Hospital, Malaysia. Refusal to medications and its reasons were asked based on the questionnaire developed by the researchers. Results: Overall, 175 patients participated in this survey and CVD drugs contributed toward 58.9% of the refused medicines. Those who refused CVD drugs and analgesics were significantly different in terms of gender, medications dosing frequency, refusal reasons namely side effects, medications use, intentionally skipping dose and skipping the dose when feeling well. No associations were found between forgetfulness and age with refusal to CVD drugs or painkillers. Those who refused CVD medicines had a significantly higher total daily medicines, total daily pill burden, and total number of medicines refused per prescription compared to those who refused analgesics. Cost of CVD medicines refused per prescription was significantly higher compared to analgesics, median Ringgit Malaysia (RM) 10.50 (IQR, RM 15.00) versus median RM 6.00 (IQR, 15.00), P=0.01. Conclusion: Refusal to CVD medicines and analgesics was associated with several medication’s and patient’s factors. However, higher cost-saving was observed in those refusing CVD medicines. Keywords: cardiovascular disease, analgesics, dispensing, wastage

Correlation between Serum Zinc Levels and Levodopa in Parkinson’s Disease

Long-term intake of potential zinc-chelating drugs may cause zinc deficiency. We postulated that zinc deficiency in Parkinson’s disease (PD) patients was related to the intake of drugs such as levodopa. We investigated the relationship between zinc levels and levodopa administration period, dosage, and symptoms of zinc deficiency in PD patients. We measured serum zinc levels and analyzed correlations between serum zinc levels, the levodopa oral administration period, dosage, dosing frequency, and zinc deficiency symptoms including taste disorders. Data analyses were performed using Spearman’s rank correlation coefficient. The mean serum zinc level was 60.5 ± 11.6 μg/dL. The mean administration period for levodopa was 8.0 ± 5.5 years, mean administration frequency 3.4 ± 0.9 times/d, and mean administration dose 420.6 ± 237.1 mg/d. Negative correlations between zinc levels and levodopa dosage and dosing frequency were found. Multiple regression analysis showed a significant correlation with the frequency of levodopa (β = −0.360, p = 0.007). No significant change in clinical symptoms was observed after zinc administration, but anxiety tended to improve. Our results indicated that frequent levodopa administration strongly influenced serum zinc levels which may have alleviating effects on psychiatric symptoms; therefore, preventing zinc deficiency can be important during PD treatment.

Reduced Dosing Frequency Following a Switch to Rix-FP for the Treatment of Hemophilia B: Results from the Athn 2 Study

Introduction: The approval of extended half-life recombinant factor IX (rFIX) replacement products has expanded the range of therapeutic options available for the treatment of hemophilia B. Compared with standard half-life FIX, these products allow for extended dosing intervals while maintaining appropriate bleed control. One such extended half-life product is rIX-FP (IDELVION; CSL Behring), a recombinant fusion protein linking rFIX with recombinant albumin, offering the possibility of dosing up to every 21 days in adults. The ATHN 2: Factor Switching Study provides information on patient outcomes following a switch from a previous FIX product to rIX-FP. Methods: ATHN 2 was a factor-switching study sponsored by the American Thrombosis and Hemostasis Network (ATHN) conducted in participants across the US hemophilia treatment center (HTC) network. This was a multi-center, longitudinal, observational study with two arms: a prospective arm following participants for up to one year after switching factor replacement product, and a retrospective arm including participants who have switched products within the 50 weeks prior to enrollment with retrospective and/or prospective assessment for up to one year. Male and female children and adults (≥2 years) with FIX clotting activity ≤5% of normal who had previously been treated with plasma-derived or recombinant FIX for at least 50 exposure days were eligible for inclusion. Treatment was administered at the discretion of the participant's hemophilia caregiver. Data was collected at study/clinic visits, or via a telephone interview conducted every three months. Baseline demographic data was collected for all participants. The prescribed dosing frequency for each participant was collected before and after the switch to rIX-FP, including dosing frequency taken from the first and last treatment records taken during the study following the switch. Participants were also asked to rank their satisfaction with rIX-FP upon the completion or early termination of the study. Results: A total of 41 participants were included in this analysis; 27 in the prospective arm and 14 in the retrospective arm. The mean (SD) age across all participants was 22.5 (17.1) years, ranging from 2 to 71 years. The median age was 18 years old and most participants had severe hemophilia B (FIX activity <1%; n=26, 63%). Prior to the switch to rIX-FP, 76% (n=31) of participants were receiving prophylaxis and 24% (n=10) received episodic treatment. The majority of participants (62%) receiving prophylaxis were treated twice a week (Table 1). Following the treatment switch, 93% of participants were initially assigned to a once-weekly or less frequent dosing regimen. This proportion remained stable over the course of the study, with 89% of participants on once-weekly or less frequent prophylaxis by the time of the last record taken. Among 23 participants with complete data on their prophylaxis dose interval before and after treatment switch, 70% of the participants were able to extend their dose frequency and maintain the extended dose frequency through the study. Thirty-seven participants responded to the satisfaction survey, with the majority (n=33, 89%) being somewhat or very satisfied with rIX-FP treatment. Conclusions: Switching to rIX-FP allowed participants to extend their prophylaxis dosing interval and a majority of participants were able to maintain the extended dose interval through the study period. In addition, a majority of participants were satisfied with rIX-FP treatment, altogether suggesting that extended half-life factor replacement with rIX-FP offers a valuable treatment option for hemophilia B. Figure 1 Figure 1. Disclosures Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Chrisentery-Singleton: Biomarin: Speakers Bureau; Kedrion: Consultancy; Takeda: Consultancy, Speakers Bureau; Spark: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Hema Biologics: Consultancy; Grifols: Consultancy; Genentech: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Desai: CSL Behring: Current Employment. von Drygalski: Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Patel: CSL Behring: Current Employment. Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Catalyst Biosciences: Consultancy. Sidinio: Biomarin: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Catalyst: Consultancy. Wang: Bayer: Consultancy; Biomarin: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Hema Biologics: Consultancy; Novo Nordisk: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Neufeld: Pfizer: Consultancy; Chiesi: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Octapharma: Consultancy, Research Funding; Acceleron Pharma: Consultancy; Baxter: Consultancy; Shire: Consultancy; Takeda: Consultancy; CSL: Consultancy; Biogen: Consultancy; Novo Nordisk: Consultancy; Bristol Myers-Squibb: Consultancy; ATHN: Research Funding; Celgene: Research Funding.

Impact of Dosing Frequency of Oral Oncolytics on Refill Adherence Among Patients with Hematological Malignancies

Background : With advances in oral oncolytics for hematologic malignancies, it is important to consider dosing frequency and treatment (tx) adherence, as prior data have shown poor adherence to oral cancer medications may result in inferior tx outcomes (Huang WC, Expert Rev Anticancer Ther, 2016; Muluneh B, J Oncol Pract, 2018). There is limited evidence regarding the impact of dosing frequency on tx adherence among patients with hematological malignancies treated with oral oncolytics. The objective of this study was to characterize real-world demographic and clinical characteristics, and compare refill adherence, among patients with hematological malignancies receiving once-daily (QD) versus twice-daily (BID) oral oncolytics. Methods : This retrospective cohort study used multi-year (2012-2020) commercial claims data from Optum's de-identified Clinformatics ® Data Mart Database and included adults (≥18 yr) with a diagnosis of a hematological malignancy identified using ICD-9-CM and ICD-10-CM codes. The exposure of interest was receipt of an oral oncolytic, and the date of the first observed oral oncolytic (QD or BID) was considered the index date. All patients were required to have continuous health plan enrollment for ≥6 mo prior and ≥6 mo after the index date. The 6-mo period prior to the index date was considered the baseline period for determining patient demographics, clinical characteristics, and prior medication use. To minimize the effect of the differences in observable baseline patient characteristics between the QD and BID groups on refill adherence, 1:1 propensity score (PS) matching was used. Tx refill adherence to QD and BID oral oncolytics was measured using two established metrics: proportion of days covered (PDC) and medication possession ratio (MPR). PDC, a conservative measure of refill adherence, was considered for primary analysis as it measures total days of drug coverage within a pre-specified follow-up period; whereas MPR which was included for sensitivity analysis, measures total drug supplied within the pre-specified follow-up period. PDC and MPR were measured at pre-defined time periods of 3 and 6 mo, and from the index date until the end of the follow-up period (variable-length follow-up). Patients with drug coverage for ≥80% (PDC or MPR ≥0.8) of pre-defined time periods were considered tx refill adherent. Results: The study identified 5,874 adults with hematological malignancies, of whom 4,938 (84.1%) received QD oral oncolytics and 936 (15.9%) received BID oral oncolytics. Before 1:1 PS matching, there were significant differences between the two groups in terms of mean age (67.5 yr QD vs 61.6 yr BID, P<0.001), insurance type (Medicare, 65.4% QD vs 46.8% BID, P<0.001), being previously untreated (67.6% QD vs 63.7% BID, P=0.019), and Charlson's comorbidity score (mean: 1.61 QD vs 1.44 BID, P<0.001). After 1:1 PS matching, demographics, baseline comorbidities, cancer histology, and line of therapy were well-balanced. The matched cohort comprised 936 patients receiving QD oral oncolytics and 936 patients receiving BID oral oncolytics. Table 1 summarizes refill adherence among patients with hematological malignancies receiving QD versus BID oral oncolytics. The proportion of patients with ≥80% of drug coverage during follow-up was higher for QD versus BID recipients at 3 mo: numerically higher by PDC (70.8% vs 66.9%, P=0.065) and statistically significantly higher by MPR (72% vs 67.8%, P=0.049). The proportion of adherent patients was significantly higher for QD vs BID for both PDC and MPR at 6 mo (PDC: 62% vs 56.8%, P=0.024; MPR: 62.7% vs 57.5%, P=0.021) and at variable-length follow-up (PDC: 82.4% QD vs 77.7% BID, P=0.011; MPR: 84.9% QD vs 80.9%, P=0.020). These results suggest QD dosing is associated with improved tx adherence to oral hematological oncolytics compared to BID dosing. Conclusions: This study demonstrates significantly higher refill adherence in patients receiving QD versus BID oral hematological oncolytics at 6 mo and variable-length follow-up, highlighting the potential benefit of dosing convenience in improving adherence to oral oncolytics in the real-world setting. As suboptimal tx adherence may result in reduced tx effectiveness, real-world characterization of refill adherence rates of oral oncolytics can better inform on tx effectiveness outside of a controlled clinical trial environment. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Kebede: Pharmacyclics LLC, an AbbVie Company: Consultancy; ObsEva: Other. Rege: Pharmacyclics LLC, an AbbVie Company (paid to institution): Consultancy. Volodarsky: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Osei-Bonsu: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

Complications and dosing frequency of 5% imiquimod for genital warts in a young man

A clinical decision report using: Fife KH, Ferenczy A, Douglas JM Jr, et al. Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day. Sex Transm Dis. 2001;28(4):226-231. https://doi.org/10.1097/00007435-200104000-00007 for a patient with genital warts and an unstable social support network.

Preparation and Evaluation of Captopril Oral Floating Controlled Release Formulations

Aim: Dosing frequency is a major hurdle in geriatrics with frequent drug administration. In such cases, oral controlled release floating formulations are helpful which causes reduction in dosing frequency and fluctuation of drug levels in plasma. The main aim of the current research was to prepare Captopril floating controlled release formulations in order to achieve extended gastric retention in the upper GIT. Methodology: Captopril tablets were prepared using different concentrations of poly ethylene oxide water soluble resin (PEO WSR) 303 (5% to 30%) by direct compression technique. Captopril formulations CSP1 and CSP6 were formulated using PEO WSR 303. Pre and post compression parameters were evaluated. Dissolution studies were performed for the prepared tablets using 0.1N hydrochloric acid as dissolution medium. Results: The dissolution studies showed controlled drug release up to 12h. The formulation CSP5 prepared using 25% w/w of PEO WSR 303 showed maximum drug release of 97.97% at 12h. Almost similar drug release profile was also observed for CSP6 which was prepared using 30%w/w PEO WSR 303. These two formulations were further added with various concentrations of sodium bicarbonate (5% to 15%) and citric acid (2.5% to 10%) which enhanced floating of drug in Gastro intestinal tract (GIT). Formulation CSP8 containing 10% of sodium bicarbonate with 25% PEO WSR 303 showed less buoyancy lag time and prolonged drug release. Formulation CSP15 showed very less buoyancy lag time of 5sec. Characterization studies like Fourier Transform Infra Red spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) were also carried out. Conclusion: The prepared Captopril floating tablets could be an alternative formulation for prolonged drug release.