Pill Burden Research Articles

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening. We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. Our study included all PA patients with hypokalemia diagnosed between 2001 and 2022. Delayed diagnosis was defined as duration of hypokalemia of more than 1 year from first occurrence to first evaluation by a PA specialist. Patients were reassessed post adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 years (range, 2.4-7.5 years). Patients with delayed diagnosis were older, had longer duration of HT, higher pill burden, lower renal function, and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidemia, and less severe hypokalemia (serum potassium >3.0 mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%) (P < .05). Sixty of 118 (50.8%) nondelayed, and 39 of 122 (32.0%) patients with delayed diagnosis, underwent surgery. Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in HT guidelines, and efforts to improve awareness of PA among primary care physicians, are urgently needed.

Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis.

Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis. We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year. The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p &lt; 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p &lt; 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p &lt; 0.0001 vs. baseline). Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.

Bioequivalence of 240mg Apalutamide Tablets and Preparation in Aqueous Food Vehicles for Alternative Administration.

A 240-mg single tablet has been developed with the focus of reducing the pill burden of the apalutamide daily dose of 240mg (4×60-mg tablets). An open-label, randomized, single-dose phase 1 study with a 2-sequence and 2-period crossover design in healthy men determined the bioequivalence of a 240-mg single tablet versus the currently available 4×60-mg tablets (Part 1, N = 74) and assessed effect of a high-fat meal (Part 2, N = 21) on apalutamide maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-72h). The 90% confidence interval of geometric mean ratios for Cmax and AUC0-72h fell between 80% and 125% for both Part 1 and Part 2. No new safety concerns with the 240-mg single tablet were observed. To support the use of different food vehicles as well as nasogastric (NG) tubes for alternative administration, we conducted in vitro compatibility studies to evaluate the purity, dose, and stability of 240-mg tablets dispersed in applesauce/yogurt/orange juice/green tea as well as in NG tubes (polyurethane/silicone/polyvinyl chloride). The studies confirmed the alternative administrations do not affect the purity, dose-accuracy, or stability of apalutamide. The apalutamide 240-mg tablet is bioequivalent to 4×60-mg tablets and compatible with the tested food vehicles and NG tubes.

Retrospective analysis of the biopharmaceutics characteristics of solid oral Modified-Release drug products in approved US FDA NDAs designated as Extended-Release or Delayed-Release formulations

BackgroundModified Release (MR) orally administered drugs products [Extended-Release (ER) and Delayed-Release (DR)] differ from Immediate-Release (IR) drug products in their drug release site and/or rate to offer therapeutic advantages. It is important to understand the biopharmaceutics factors that determine how a drug works in the gastrointestinal tract and the various pharmacokinetic properties that determine a drug’s rate of absorption and release in the human body. To better understand the biopharmaceutics characteristics of ER and DR drug products, this study retrospectively analyzed submissions approved by the US Food and Drug Administration (FDA), from 2001 to 2021, and their corresponding review documents. This review work is expected to enhance the readers’ understanding regarding the biopharmaceutics properties that supported approval of these products’ ER claims, as per 21 CFR 320.25(f), and DR claims. MethodsA comprehensive search was conducted using the FDA’s internal New Drug Application (NDA) database for ER and DR oral drug products approved between 2001 and 2021. The search yielded 87 ER applications (23 ER capsules and 64 ER tablets) and 21 DR applications (10 DR capsules, 11 DR tablets) for which electronic records were accessible. These products were analyzed for overall drug product design, dosing frequency compared to the reference (if applicable), degree of fluctuation, dissolution method, and alcohol dose-dumping. ResultsOut of 87 total applications for ER drug products that were assessed, 62% of the ER tablets contained a polymer matrix formulation, and hypromellose (HPMC) was used in 50% of these products. 52% of the ER capsules consisted of polymer beads while about half of the DR drug products contained a non-bead formulation with a combination of polymers. The majority of ER drug products were found to have a reduction in dosing frequency and a decrease in the degree of fluctuation when compared to the IR reference product. The 13 ER drug products that exhibited an increase in degree of fluctuation exhibited general and pharmacodynamic benefits, such as reduced dosing frequency and reduced pill burden. The majority of DR formulations were developed to prevent drug degradation in the stomach, followed by to decrease potential stomach irritation, and lastly for localized release in the colon. The majority of ER drug products had 1:1 ratios of dissolution duration compared to dosing frequency (i.e., the majority of ER drug products had a dissolution duration of 24 h and were dosed every 24 h while those with a dissolution duration of 12 h were dosed every 12 h). The majority of ER applications had single-stage dissolution methods while most DR drug products used biphasic dissolution methods. All of the DR dissolution methods incorporated an acid stage of 2 h and a buffer stage with various timeframes. 53% the DR drug products had a ratio of dissolution duration to dosing frequency of 1:4 (e.g. a dissolution duration of 2 h to a dosing frequency of 8 h) or 1:8 (e.g. a dissolution duration of 2 h to a dosing frequency of 16 h). Of the ER tablets and DR drug products, 72% exhibited no alcohol dose-dumping under in vitro testing conditions. ER capsules, however, did not yield similar results—most of which exhibited alcohol induced dose-dumping. Alcohol dose dumping was mitigated by either in vivo studies or warnings on the drug product label. ConclusionThe results of this study help the reader understand the design, characteristics, and pharmacological advantages of the ER and DR drug products for patient benefit; as well as the regulations governing the FDA’s assessment of ER claims.

Influence of the new dispersible fixed-dose combination anti-Tuberculosis drug on treatment adherence among children with Tuberculosis in Osun State, Nigeria.

The dispersible fixed-dose combination drug has been recommended as the mainstay of treatment for TB in children. However, more needs to be known about its effect on treatment. This study aimed to assess the effectiveness of the formulation on treatment adherence among children with TB. A historical cohort design was used to assess and compare adherences of old loose non-dispersible and new dispersible fixed-dose anti-TB drugs, using a convergent parallel mixed-method approach for data collection. Determinants of treatment adherence were assessed using binary logistic regression. The proportion of children with good treatment adherence was higher in the new dispersible formulation group (82 [64.6%]) relative to the proportion among the loose non-dispersible formulation group (29 [23.4%]). Reports of forgetfulness, travelling and pill burden were significantly higher among those with poor adherence in the loose non-dispersible formulation group. Significant predictors of treatment adherence were acceptability (adjusted OR [AOR]=4.1, p=0.013, 95% CI 1.342 to 12.756), travelling from treatment areas (AOR=8.9, p=0.002, 95% CI 2.211 to 35.771) and forgetfulness (AOR=74.0, p<0.001, 95% CI 23.319 to 234.725). The determinants of treatment adherence are multifactorial. In addition to ensuring universal access to the drug, flexible referral in case of travelling and ensuring treatment partners' participation to minimise forgetfulness to take pills, are essential.

Efficacy and safety of perindopril/indapamide/amlodipine single-pill combination in essential hypertension

Abstract Background In hypertensive patients uncontrolled with dual therapy, perindopril, indapamide and amlodipine triple therapy form one of the core drug treatments recommended by the latest European (ESC/ESH 2018) and International (ISH 2020) Guidelines, ideally used as single-pill combination (SPC) to improve adherence to treatment. Purpose To assess efficacy and safety of the SPC of Perindopril arginine 5 mg/Indapamide 1.25 mg/Amlodipine 5 mg (P5/I1.25/A5) compared to the free combination of Perindopril tert-butylamine 4 mg/Indapamide 1.25 mg (P4/I1.25) plus Amlodipine 5 mg (P4/I1.25 +A5) and of the titration to higher doses up to P10/I.2.5/A10 for SPC and P8/I.2.5+A10 for free combination, in patients with essential uncontrolled hypertension. Methods A randomized, double-blind, controlled, 7-month phase III study in hypertensive Asian patients uncontrolled with dual therapy (Systolic Blood Pressure (SBP) ≥140 and &amp;lt;180mmHg and Diastolic Blood Pressure (DBP) ≥90 and &amp;lt;110 mmHg). After a 1-month run-in period on P4/I1.25, patients were randomized to a 6-month parallel group period to receive the triple therapy either as SPC (P5/I1.25/A5) or as free combination (P4/I1.25+A5), potentially up-titrated to higher doses after 2 and 4 months if BP remained uncontrolled. Results 532 patients (mean SBP/DBP 150.4/97.2 mmHg, mean age 56 years) were randomized to receive SPC or free combination. After 2 months of randomized treatment, a large decrease in office SBP/DBP was observed in both the SPC (-15.0/-8.6mmHg) and the free combination group (-14.5/-8.7mmHg). The SBP-lowering effect of the SPC was shown to be non-inferior to the free combination (study primary endpoint, p&amp;lt;0.001). In patients uncontrolled on SPC after 2 and 4 months, titration to P10/I2.5/A5 then to P10/I2.5/A10 (in 46.1 and 17.6% patients in SPC group, respectively) led to additional SBP/DBP decrease (-9.0/-5.9 mmHg and -6.1/-3.6 mmHg, respectively). After 6 months, 64.4% of patients reached BP control. ABPM data corroborated these findings. Similar results were observed in the free combination group. Over the 6-month randomized period, treatments were well tolerated, even at the highest doses of the SPC. The most frequently reported treatment-related adverse events were those already described for indapamide, perindopril and amlodipine, i.e., hyperuricemia, hypokalemia and cough, and were observed with a similar frequency in both groups. Peripheral edema and hypotension or orthostatic hypotension remained low. Conclusion Perindopril/Indapamide/Amlodipine SPC is as effective and safe as the free combination in hypertensive patients uncontrolled with dual therapy of Perindopril/Indapamide. The uptitration to higher dosages of the triple-drug SPC provided additional benefit on BP lowering and BP control without increasing pill burden.

Rationale and Design of the Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT): A Pilot Study

Cancer therapeutics-related cardiac dysfunction (CTRCD) is a well-recognised complication of cancer treatment. Treatment of CTRCD involves cardioprotective therapy (CPT) which can lead to a recovery of CTRCD with normalisation of the left ventricular ejection fraction (LVEF). As a result, there are potentially millions of cancer survivors with recovered CTRCD on CPT. Cardioprotective therapy can be associated with an undesirable long-term pill burden, financial costs, and side effects. Cancer survivorship is anticipated to increase significantly by the end of this decade. To date, there is no evidence of the safety of stopping CPT in this setting. This study seeks to evaluate the hypothesis that ceasing cardioprotective medication is a feasible and safe option without significant impact on LVEF in low-risk patients who have recovered from CTRCD. We will perform a multicentre prospective open-label randomised controlled trial with blinded endpoint (PROBE) of supervised CPT cessation compared to continuing CPT (control). The primary study end point is the change in LVEF by cardiac magnetic resonance imaging at 6 months of enrolment between the two groups. Secondary end points include changes in quality-of-life questionnaires, other cardiac imaging parameters, and recurrence of heart failure. Cessation Of Pharmacotherapy In Recovered Chemotherapy-induced cardioToxicity (COP-RCT) is one of the first studies currently underway to evaluate the safety of ceasing CPT in recovered CTRCD. The results will inform clinical practice in this evidence-free zone.

Abstract 14501: Process Evaluation of a Double Blind Randomized Controlled Trial to Assess the Efficacy and Safety of a Quadruple Ultra-Low-Dose Treatment for Hypertension Within a Federally Qualified Health Center Network (QUARTET USA)

Introduction: This explanatory sequential mixed-methods process evaluation of the QUARTET USA clinical trial (NCT03640312) explores patient and health professional perceptions about the use of low-dose quadruple therapy (LDQT) as a novel strategy for hypertension management. Methods: Sixty-two patients took part in the trial. Survey data were collected from patients to understand their beliefs about blood pressure medications and treatment satisfaction with LDQT. A sub-sample of 13 English and Spanish patients and 11 health professionals, recruited via purposive sampling, took part in semi-structured qualitative interviews. Data collection took place between August 2019 and July 2022. Quantitative data were analyzed using descriptive statistics and cross-tabulations, and the qualitative data were analyzed using thematic analysis. Common themes from the two sets of findings were integrated. Results: 54.3% of patients believed in the necessity of their blood pressure medicines and 40.6% were concerned about the side effects and long-term effects of their medications. At trial completion, 80.4% of the patients were satisfied with the LDQT, 96.4% were certain the benefits of taking LDQT outweighed the disadvantages, and all participants reported that it was convenient to take. Both patients and health professionals found LDQT acceptable because it facilitated patients’ blood pressure control and medication adherence, and reduced patients’ perceived pill burden and adverse reactions. Health professionals stated that a limitation of LDQT was the inability to titrate the dose and that health insurance coverage and inclusion of LDQT in national hypertension guidelines could increase its widespread use. Conclusions: The LDQT strategy was acceptable to patients and health professionals for hypertension treatment. While LDQT therapy generally improved and maintained patients’ blood pressure control, medication adherence, and had a good safety profile, the limitation of its titration inflexibility and medication cost were raised by health professionals. Making LDQT therapy flexible by introducing stepped care combinations and ensuring health insurance coverage could increase its widespread implementation and scale-up.

Long-term safety and decrease of pill burden by tenapanor therapy: a phase 3 open-label study in hemodialysis patients with hyperphosphatemia

Phosphate binders (PBs) generally have a high pill burden. Tenapanor selectively inhibits sodium/hydrogen exchanger isoform 3, reducing intestinal phosphate absorption. Tenapanor is a novel drug administered as a small tablet, twice daily. This multicenter, open-label, single-arm, phase 3 study aimed to evaluate the long-term safety of tenapanor and its efficacy in decreasing PB pill burden. Tenapanor 5 mg twice daily was administered to hemodialysis patients with serum phosphorus level 3.5–7.0 mg/dl at baseline; the dose could be increased up to 30 mg twice daily. Patients could also switch from PBs. The primary endpoint was safety during 52-week administration. The key secondary endpoint was a ≥ 30% reduction in the total pill number of daily PBs and tenapanor from baseline. Of 212 patients starting treatment, 154 completed the study. Diarrhea was the most frequent adverse event, occurring in 135 patients (63.7%); most events were classified as mild (74.8%). No clinically significant changes occurred other than serum phosphorus level. At Week 52/discontinuation, 158/204 patients (77.5%) achieved the key secondary endpoint. Complete switching from PBs to tenapanor was achieved in 50–76 patients (26.7%–41.5%), and 80 patients (51.9%) at Week 8–12 and Week 50, respectively. Serum phosphorus remained generally stable within the target range (3.5–6.0 mg/dl). These findings suggest the long-term safety and tolerability of tenapanor. Tenapanor could reduce or eliminate PB pill burden while controlling serum phosphorus levels.Trial registration: NCT04771780

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD).The treatment for SHPT includessynthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT.The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

A Predictive Model for Identifying Low Medication Adherence Among Patients with Cirrhosis.

This study aims to identify the novel risk predictors of low medication adherence of cirrhosis patients in a large cohort and construct an applicable predictive model to provide clinicians with a simple and precise personalized prediction tool. Patients with cirrhosis were recruited from the inpatient populations at the Department of Infectious Diseases of Tangdu Hospital. Patients who did not meet the inclusion criteria were excluded. The primary outcome was medication adherence, which was analyzed by the medication possession ratio (MPR). Potential predictive factors, including demographics, the severity of cirrhosis, knowledge of disease and medical treatment, social support, self-care agency and pill burdens, were collected by questionnaires. Predictive factors were selected by univariable and multivariable logistic regression analysis. Then, a nomogram was constructed. The decision curve analysis (DCA), clinical application curve analysis, ROC curve analysis, Brier score and mean squared error (MSE) score were utilized to assess the performance of the model. In addition, the bootstrapping method was used for internal validation. Among the enrolled patients (460), most had good or moderate (344, 74.78%) medical adherence. The main risk factors for non-adherence include young age (≤50 years), low education level, low income, short duration of disease (<10 years), low Child-Plush class, poor knowledge of disease and medical treatment, poor social support, low self-care agency and high pill burden. The nomogram comprised these factors showed good calibration and good discrimination (AUC = 0.938, 95% CI = 0.918-0.956; Brier score = 0.14). In addition, the MSE value was 0.03, indicating no overfitting. This study identified predictive factors regarding low medication adherence among patients with cirrhosis, and a predictive nomogram was constructed. This model could help clinicians identify patients with a high risk of low medication adherence and intervention measures can be taken in time.

Predictors of maternal and fetal outcome in severely anemic pregnant mothers: A sequential mixed methods study.

Severe anemia in pregnancy increases maternal and neonatal morbidity and mortality in the antenatal period. To find out the maternal and fetal outcomes in severely anemic pregnant women and explore the reason for the persistence of severe anemia in pregnant women. Sequential explanatory mixed method study (Quan-Qual) was conducted in the Government Women and Children Hospital for a period of 1 and half years. Most of the people were from rural backgrounds and belonging to low socioeconomic status have been registered. Quantitative data were collected from 125 severe anemic cases; a consecutive sampling technique was applied. In-depth interviews were conducted among purposively selected severe anemic patients (n = 15) who were vocal and willing to explore the reason for the persistence of anemia. The interviews were conducted till the point of saturation. Ethical principles were adhered throughout the study. Quantitative data were anlyzed using SPSS software. Manual content analysis was done for qualitative data. Among 125 severe anemic patients, 12.8% patients had preterm labour, about 23.2% had inadequate lactation, and 13.6% had a puerperal febrile illness. It was found 41.6% of neonates had respiratory distress and 33.6% had the refusal of feeds. When compared to vaginal delivery, women undergoing cesarean section have 3.2 times (95% confidence interval 1.39-7.32) higher odds of developing maternal complications. Nagelkerke's R2 value for the model was 11.1%. Five broad categories namely Family centric nature, Lack of awareness, Pill burden, Food Fads, and Myths related to iron intake emerged from the study. Complications can occur in mothers and neonates if anemia is not corrected in early trimester.

Investigating the ability to adhere to cardiometabolic medications with different properties: a retrospective cohort study of >500 000 patients in the USA

ObjectivePoor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been...

Successful Multidrug-Resistant Tuberculosis Treatment Without HIV Viral Suppression: A Missed Opportunity.

Coinfection with multidrug-resistant tuberculosis (MDR-TB) and HIV is common, but few published studies examine how undergoing MDR-TB treatment affects HIV disease indicators. Using data from a nested, retrospective cohort of people with HIV (PWH) and successful MDR-TB treatment outcomes, we built multivariable regression models to explore correlates of HIV viral suppression at MDR-TB treatment completion. Among 531 PWH successfully treated for MDR-TB, mean age was 37.4 years (SD 10.2, interquartile range 30-43), 270 (50.8%) were male, 395 (74.4%) were virally suppressed at MDR-TB outcome, and 259 (48.8%) took bedaquiline. Older age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI]: 1.01 to 1.06) increased odds of viral suppression, while having a prior TB episode (aOR 0.45, 95% CI: 0.31 to 0.64), having a detectable viral load at MDR-TB treatment initiation (aOR 0.17, 95% CI: 0.09 to 0.30), living in a township (aOR 0.49, 95% CI: 0.28 to 0.87), and being changed from efavirenz-based antiretroviral therapy (ART) to a protease inhibitor due to bedaquiline usage (aOR 0.19, 95% CI: 0.04 to 0.82) or not having an ART change while on bedaquiline (aOR 0.29, 95% CI: 0.11 to 0.75) lowered odds of viral suppression. Changing from efavirenz to nevirapine due to bedaquiline usage did not significantly affect odds of viral suppression (aOR 0.41, 95% CI: 0.16 to 1.04). Increased pill burden and adverse treatment effects did not significantly affect HIV viral suppression while switching ART to a protease inhibitor to accommodate bedaquiline or not changing ART while taking bedaquiline did, suggesting that PWH and MDR-TB may benefit from additional support if they must switch ART.

Tenapanor Effect on Decrease in Phosphate Binder Pill Burden for Hyperphosphatemia in Japanese Patients Undergoing Hemodialysis: A Phase 3 Long-Term Study

Tenapanor Effect on Decrease in Phosphate Binder Pill Burden for Hyperphosphatemia in Japanese Patients Undergoing Hemodialysis: A Phase 3 Long-Term Study

Prevalence of polypharmacy among older adults in Ethiopia: a systematic review and meta-analysis

Polypharmacy is a significant concern for older adults. Taking multiple medicines to prevent and treat comorbidities is very common in older adults, potentially leading to polypharmacy. Polypharmacy is associated with the development of geriatric syndromes, including cognitive impairment, delirium, falls, frailty, urinary incontinence, and weight loss. The prevalence of polypharmacy varies according to the literature. There is a paucity of data regarding the prevalence of polypharmacy among older adults. Therefore, this study aimed to estimate the pooled prevalence of polypharmacy among older adults in Ethiopia. A comprehensive search of databases, including PubMed, MEDLINE, EMBASE, Hinari, Cumulative Index to Nursing and Allied Health Literature, International Scientific Indexing, Cochrane library and Web of Science, and Google Scholar, was conducted. STATA statistical software (version 17) was used to analyze the data. Forest plot and I2 heterogeneity test were computed to examine the existence of heterogeneity. Subgroup analysis and sensitivity analysis were done to explore the source of heterogeneity. Publication bias was evaluated by using funnel plots and Egger’s test. A random effect model was used to determine the pooled prevalence of polypharmacy. After reviewing 123 studies, 13 studies with a total of 3547 older adults fulfilled the inclusion criteria and were included in this meta-analysis. The result from 13 studies revealed that the pooled prevalence of polypharmacy among older adults in Ethiopia was 37.10% (95CI: 28.28–45.91). A Subgroup Meta-analysis showed that the heterogeneity level was slightly lower among studies done in Oromia region (I2 = 46.62, P-value = 0.154). Higher pooled polypharmacy prevalence was found among older adults with cardiovascular disorders (42.7%) and admitted patients (51.4%). In general, it was found that the pooled prevalence of polypharmacy among older adults in Ethiopia was high. More than one in three older adults take five or more medications at a time. Thus, intervention focusing on rational geriatric pharmacotherapy is significant to prevent unnecessary pill burden, adverse drug events, medical costs, geriatric morbidity, and mortality. Furthermore, enhancing pharmacist roles towards medication therapy management and safety monitoring in older adults is also indicated.

Patterns and factors associated with SSRI medication adherence: a retrospective study using pharmacy claims data

Abstract Objectives To assess the patterns and risk factors associated with selective serotonin reuptake inhibitor (SSRI) medication adherence among enrollees of a multiple employer welfare beneficiary association operating in Florida. Methods This study used a pharmacy claims database for beneficiaries of the Independent Colleges and Universities Benefits Association. The sample of 2541 patients were enrollees who filled two or more consecutive SSRI prescriptions during the analysis period 2015–20. Adherence was measured as the proportion of days covered by a medication. Multiple logistic regression analysis was used to explore the relationship between sociodemographic, healthcare access, and clinical and medication-related factors and adherence. Key findings Adherence was associated with higher odds of being female [odds ratio (OR): 1.2, 95% confidence interval (CI): 0.995–1.464, P &amp;lt; .10] and higher pill burden (OR: 1.3, CI: 1.021–1.642, P&amp;lt; 0.05). Patients using only retail pharmacies (OR: 0.356, CI: 0.196–0.645, P &amp;lt; .01), having any out-of-pocket costs (OR: 0.552, CI: 0.348–0.875, P &amp;lt; .50), changing the prescriber over the duration of the treatment (OR: 0.708, CI: 0.589–0.851, P &amp;lt; .01), taking antihypertensive (OR: 0.708, CI: 0.5077–0.988, P &amp;lt; 0.50), and asthma (OR: 0.609, CI: 0.450–0.826, P &amp;lt; .01) medications were less likely to be adherent. Prescriber specialty was not found to be associated with adherence. Conclusion These findings can inform policymakers and healthcare insurance companies on barriers to medication access and recommend strategies to eliminate these barriers and design interventions to improve the adherence of groups at risk for nonadherence. Healthcare providers can identify patients who are less likely to be adherent and customize counseling interventions for these patients.

Proof-of-Concept in Developing a 45% Drug Loaded Amorphous Nanoparticle Formulation

Amorphous solid dispersion (ASD) is an enabling approach utilized to deliver poorly soluble compounds. ASDs can spontaneously generate drug-rich amorphous nanoparticles upon dissolution, which can act as a reservoir for maintaining supersaturation during oral absorption. But, conventional ASDs are often limited in drug loadings to < 20 %. For indications where the dose is high, this can translate into a significant pill burden. The aim of this research was to develop a high drug loading (DL) amorphous nanoparticle (ANP) formulation that can release the drug-rich nanoparticles into solution upon contact with aqueous environment. Nanoparticles were directly engineered using solvent/anti-solvent precipitation. The obtained nanoparticle suspension was then concentrated followed by solidification to a re-dispersible amorphous dosage form using spray drying or lyophilization. The impact of process variables was studied using dynamic light scattering (DLS), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). It was observed that spray drying led to a non-re-dispersible formulation. Sucrose and trehalose containing lyocakes resulted in re-dispersible formulations. The trehalose containing lyocakes, in a dog study, gave comparable performance to the reference tablet in the fasted state but lower area under the curve (AUC) in fed state.

Patient Preference Trade-offs for Next-Generation Kidney Replacement Therapies.

Next-generation implantable and wearable KRTs may revolutionize the lives of patients undergoing dialysis by providing more frequent and/or prolonged therapy along with greater mobility compared with in-center hemodialysis. Medical device innovators would benefit from patient input to inform product design and development. Our objective was to determine key risk/benefit considerations for patients with kidney failure and test how these trade-offs could drive patient treatment choices. We developed a choice-based conjoint discrete choice instrument and surveyed 498 patients with kidney failure. The choice-based conjoint instrument consisted of nine attributes of risk and benefit pertinent across KRT modalities. Attributes were derived from literature reviews, patient/clinician interviews, and pilot testing. The risk attributes were serious infection, death within 5 years, permanent device failure, surgical requirements, and follow-up requirements. The benefit attributes were fewer diet restrictions, improved mobility, pill burden, and fatigue. We created a random, full-profile, balanced overlap design with 14 choice pairs plus five fixed tasks to test validity. We used a mixed-effects regression model with attribute levels as independent predictor variables and choice decisions as dependent variables. All variables were significantly important to patient choice preferences, except follow-up requirements. For each 1% higher risk of death within 5 years, preference utility was lower by 2.22 ( β =-2.22; 95% confidence interval [CI], -2.52 to -1.91), while for each 1% higher risk of serious infection, utility was lower by 1.38 ( β =-1.46; 95% CI, -1.77 to -1.00) according to comparisons of the β coefficients. Patients were willing to trade a 1% infection risk and 0.5% risk of death to gain complete mobility and freedom from in-center hemodialysis ( β =1.46; 95% CI, 1.27 to 1.64). Despite an aversion to even a 1% higher risk of death within 5 years, serious infection, and permanent device rejection, patients with kidney failure suggested that they would trade these risks for the benefit of complete mobility.

SAT087 Maternally Inherited Diabetes And Deafness: Support For SGLT2 Inhibitor Use

Abstract Disclosure: S. Pandya: None. K. Selk: None. Introduction: Maternally inherited diabetes and deafness (MIDD) is a rare genetic disease resulting from a mitochondrial mutation. There is a wide phenotypic expression secondary to heteroplasmy. The clinical manifestations of MIDD are hyperglycemia, sensorineural hearing loss, maculopathy, cardiac conduction defects, myopathy/poor exercise tolerance, and neuropathy. Diabetes mellitus generally occurs during the third decade of life, and there tends to be rapid progression to insulin therapy with reported earlier onset of microvascular complications. Here we present a case of MIDD successfully treated long-term with empagliflozin and linagliptin. Clinical Case: A 36-year-old male with sensorineural hearing loss presented with a 20-pound unintentional weight loss, polyphagia, and polydipsia. His blood glucose level was 300 mg/dL and HbA1c was 14.3%. His mother carried a diagnosis of type 2 diabetes mellitus and his grandmother had latent autoimmune diabetes of adulthood. Prior to presenting to endocrinology, he had been started on metformin, glipizide, and linagliptin with ongoing poor glycemic control. Given his presentation, family history, and lean habitus with BMI of 20, he was assessed for possible autoimmune diabetes. Testing for glutamic acid decarboxylase 65-kilodalton isoform antibody (GAD65), islet cell antibody, tyrosine phosphatase-related islet antigen 2 (IA2), and zinc transporter 8 antibody (ZNT8) was unrevealing. A C-peptide level was detectable but &amp;lt;1 ng/mL. His sulfonylurea was discontinued, and he was started on basal insulin with a dramatic improvement in his glycemic control. He was later able to discontinue insulin therapy. However, given poor exercise tolerance and his known hearing loss, he was seen by genetics where he underwent testing and was found to have a m.3243 A&amp;gt;G mutation in MT-TL1 gene making the diagnosis of MIDD. Metformin was discontinued due to a possible risk of lactic acidosis and sitagliptin was initiated. Due to hyperglycemia, empagliflozin was added and he was later transitioned to empagliflozin-linagliptin to reduce his pill burden. He has continued to have a1c levels of 6.5% or less for the last 3 years and periodic C-peptide measurements have been &amp;gt;1 ng/mL. Conclusion: Given MIDD is a rare form of monogenic diabetes, treatment tends to be individualized with many transitioning to insulin early in their disease course. Given the reported increased risk for microvascular complications, sodium-glucose cotransporter-2 (SGLT2) inhibitors are an attractive therapeutic agent. However, there is little literature on the use of these agents in MIDD and there is concern about the risk for diabetic ketoacidosis given insulin use is required by many afflicted individuals. This case highlights the safety of long-term empagliflozin in a patient with MIDD. Presentation: Saturday, June 17, 2023