High Pill Burden Research Articles

Facilitators and barriers to initiating and completing tuberculosis preventive treatment among children and adolescents living with HIV in Uganda: a qualitative study of adolescents, caretakers and health workers

IntroductionPeople living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.MethodsWe conducted a qualitative study from February 2022 to March 2023, at three paediatric and adolescent HIV treatment centers in Uganda. In-depth interviews were conducted at TPT initiation and after completion for purposively selected health workers, adolescents aged 10–19 years living with HIV, and caretakers of children aged below 18years.ResultsThe desire to avoid TB disease, previous TB treatment, encouragement from family members, and ministry of health policies emerged as key facilitators for the children and adolescents to initiate TPT. Barriers to TPT initiation included; TB and HIV-related stigma, busy carer and adolescent work schedules, reduced social support from parents and family, history of drug side effects, high pill burden and fatigue, and perception of not being ill. TPT completion was enabled by combined TPT and ART refill visits, delivery of ART and TPT within the community, and continuous education and counseling from health workers. Reported barriers to TPT completion included TB and HIV-related stigma, long waiting time. Non-disclosure of HIV status by caretakers to CALHIV and fear of side effects was cited by health workers as a barrier to starting TPT. Facilitators of TPT initiation and completion reported by healthcare workers included patient and caretaker health education, counselling about benefits of TPT and risk of TB disease, having same appointment for TPT and ART refill to reduce patient waiting time, adolescent-friendly services, and appointment reminder phone calls.ConclusionThe facilitators and barriers of TPT initiation and completion among CALHIV span from individual, to health system and structural factors. Health education about benefits of TPT and risk of TB, social support, adolescent-friendly services, and joint appointments for TPT and ART refill are major facilitators of TPT initiation and completion among CALHIV in Uganda.

#1579 The effectiveness and safety of sucroferric oxyhydroxide in the treatment of hyperphosphatemia in dialysis patients: a systematic review

Abstract Background and Aims Hyperphosphatemia is an independent prognostic factor for mortality in dialysis patients. The most widely used phosphate binders are sevelamer and lanthanum carbonate. Poor compliance may be due to high pill burden and gastrointestinal adverse reactions. Some previous studies on sucroferric oxyhydroxide showed a potential reduction of phosphorus levels and pill burden. This study aims to determine the effectiveness and safety profile of sucroferric oxyhydroxide in the control of hyperphosphatemia in dialysis-dependent patients. Method A systematic search was conducted in the Cochrane Library, MEDLINE, TRIP Database, and ClinicalTrials.gov until Jan 8, 2024. All randomized controlled trials on the use of sucroferric oxyhydroxide for the treatment of hyperphosphatemia in adult dialysis patients were included. The comparator groups considered were sevelamer or lanthanum. The outcomes of interest were post-treatment serum phosphorus level, the change of serum phosphorus level from baseline, hemoglobin level, ferritin level, transferrin saturation level, adverse events, serious adverse events, and all-cause mortality. Two authors independently searched for articles, screened the articles for inclusion, and appraised the articles using the REVMAN risk of bias table. The GRADE was used to assess the certainty of evidence. In case of a disagreement, the two authors discussed until a consensus was reached. If a consensus was not reached, an independent third-party reviewer was consulted. Meta-analysis was conducted using Review Manager 5.4.1 software. Results We included 7 RCTs represented by 11 records and a total of 2031 adult dialysis patients with hyperphosphatemia. The usual dose of sucroferric oxyhydroxide is 750 mg-3000 mg/day. Sucroferric oxyhydroxide reduces serum phosphorus levels comparable to that of sevelamer (MD = −0.03 mmol/L, 95% CI −0.10 to 0.03, I2 49%) and of lanthanum (MD = −0.02 mmol/L, 95% CI −0.36 to 33, I2 0%). The decrease in serum phosphorus level from the baseline is also comparable with sevelamer (MD = −0.06 mmol/L, 95% CI −0.13 to 0.00, I2 59%). Sucroferric oxyhydroxide significantly reduces the daily number of tablet intake (MD = −7.09 tablets/day, 95% CI −10.45 to −3.73, p-value < 0.0001, I2 = 99%) compared to sevelamer. The use of sucroferric oxyhydroxide shows significantly higher hemoglobin level (MD = 1.15; 95% CI 0.92 to 1.39, p-value < 0.0001, I2 = 0%), higher transferrin saturation level (MD = 8.33; 95% CI 6.06 to 10.59, p-value < 0.0001, I2 = 0%) and higher ferritin level (MD = 64.16; 95% CI 31.64 to 96.68, p-value 0.0001) compared with the use of sevelamer. Pooled analysis on sucroferric oxyhydroxide showed no significant differences in adverse events (RR = 1.05, 95% CI 0.95 to 1.17, I2 = 47%); serious adverse events (RR = 1.11, 95% CI 0.84 to 1.47, I2 = 0%) and all-cause mortality (RR = 0.94; 95% CI 0.38 to 2.31, I2 = 0%) compared to sevelamer. The most common adverse events reported were nausea, diarrhea, abdominal discomfort, fecal discoloration, and hyperphosphatemia. Conclusion Sucroferric oxyhydroxide is comparable with sevelamer and lanthanum in decreasing serum phosphorus levels. It is also associated with higher hemoglobin, ferritin, and transferrin saturation levels compared with the sevelamer group. Since there are no significant differences in the risks of adverse events, serious adverse events, and all-cause mortality, the decrease in pill burden with sucroferric oxyhydroxide may help improve patient compliance.

Adherence to Medications in Patients with Ischaemic Heart Disease in Oman.

This study aimed to evaluate the level of adherence to medication among patients with ischaemic heart disease (IHD) in Oman and assess the related factors. This cross-sectional questionnaire-based study among patients with IHD attending the outpatient clinic at Sultan Qaboos University Hospital, Muscat, Oman, was performed between January and December 2021. A total of 105 patients (mean age = 49.9 ± 11.1 years, 78.1% male) were recruited. Most of the patients (80%) reported taking the medications by themselves; 77 (73.3%) patients said that over the preceding 2 weeks, they had missed at least 3 doses of their medication. The reasons for missing the medications included forgetting (100%), having to take too many tablets (57%), feeling that the tablets are not effective (48%) and having to take the tablets too often each day (23%). The factors responsible for patients failing to take medications could not be identified. Medication adherence was low among patients with IHD in Oman, with high pill burden being the most common reason for non-adherence. Physicians must bear this in mind when reviewing patients.

Prodrugs as empowering tools in drug discovery and development: recent strategic applications of drug delivery solutions to mitigate challenges associated with lead compounds and drug candidates.

The delivery of a drug to a specific organ or tissue at an efficacious concentration is the pharmacokinetic (PK) hallmark of promoting effective pharmacological action at a target site with an acceptable safety profile. Sub-optimal pharmaceutical or ADME profiles of drug candidates, which can often be a function of inherently poor physicochemical properties, pose significant challenges to drug discovery and development teams and may contribute to high compound attrition rates. Medicinal chemists have exploited prodrugs as an informed strategy to productively enhance the profiles of new chemical entities by optimizing the physicochemical, biopharmaceutical, and pharmacokinetic properties as well as selectively delivering a molecule to the site of action as a means of addressing a range of limitations. While discovery scientists have traditionally employed prodrugs to improve solubility and membrane permeability, the growing sophistication of prodrug technologies has enabled a significant expansion of their scope and applications as an empowering tool to mitigate a broad range of drug delivery challenges. Prodrugs have emerged as successful solutions to resolve non-linear exposure, inadequate exposure to support toxicological studies, pH-dependent absorption, high pill burden, formulation challenges, lack of feasibility of developing solid and liquid dosage forms, first-pass metabolism, high dosing frequency translating to reduced patient compliance and poor site-specific drug delivery. During the period 2012-2022, the US Food and Drug Administration (FDA) approved 50 prodrugs, which amounts to 13% of approved small molecule drugs, reflecting both the importance and success of implementing prodrug approaches in the pursuit of developing safe and effective drugs to address unmet medical needs.

Cannabis Use, Perspectives, and Experiences Among Patients Receiving Hemodialysis: A Descriptive Patient Survey.

Patients with chronic kidney disease experience high burden of symptoms, negatively affecting their quality of life. Medication therapy is often initiated to address these symptoms but is limited by variable efficacy and high pill burden. There is interest among clinicians and patients to explore cannabis and cannabinoids as an alternative treatment to manage symptoms related to kidney disease. The objectives were to characterize cannabis use among patients receiving maintenance hemodialysis (HD), to describe patient perspectives on cannabis, and to explore patient experiences with their kidney health care team related to cannabis. This was a descriptive, cross-sectional paper-based patient survey. Patients receiving maintenance HD at Toronto General Hospital in the ambulatory setting between July and August 2020 were included. A 33-item questionnaire was developed to address the study questions based on existing cannabis questionnaires and input from kidney specialist physicians, pharmacists, kidney nurse practitioners, and patients. The questionnaire was distributed to patients during their in-center HD session. Patients who chose to participate in the study completed the questionnaire and returned it to the study team. In total, there were 52 respondents, of which 11 (21%) reported cannabis use in the preceding 3 months, and 23 (44%) reported historical cannabis use. Baseline characteristics were similar between those who used cannabis and those who did not, with a possible trend of cannabis users being younger. The most commonly reported reasons for using cannabis were recreation and symptom management. Those who reported using cannabis for symptom management were doing so without medical authorization or documentation. Common symptoms that cannabis was used to self-treat were insomnia, anxiety, and/or non-neuropathic pain. Dried flower was the most common type of product used, and smoking was the most common route. Care gaps and opportunities to improve patient care related to cannabis use were identified, related to monitoring and management of adverse effects, management of drug interactions, harm reduction strategies, informed decision-making, and prescriber education. The overall participation rate was low, at approximately 17%, possibly related to the COVID-19 pandemic, lack of interest, or fear of revealing cannabis use. Non-response bias is a possible limitation as this was a voluntary survey. The questionnaire was limited to multiple-choice and Likert scale questions, therefore limiting the depth of patient responses. Our study showed that cannabis use among patients receiving HD is common and comparable with the general population. Patients may be using cannabis to self-manage symptoms related to kidney disease, without the involvement of the health care team. Multiple opportunities to improve patient care related to cannabis use were identified.

A Cross-Sectional Survey of Fixed-Dose Combination Antihypertensive Medicine Prescribing in Twenty-Four Countries, Including Qualitative Insights.

Treatment inertia, non-adherence and non-persistence to medical treatment contribute to poor blood pressure (BP) control worldwide. Fixed dose combination (FDC) antihypertensive medicines simplify prescribing patterns and improve adherence. The aim of this study was to identify factors associated with prescribing FDC antihypertensive medicines and to understand if these factors differ among doctors worldwide. A cross-sectional survey was conducted online from June 2023 to January 2024 to recruit doctors. We collaborated with an international network of researchers and clinicians identified through institutional connections. A passive snowballing recruitment strategy was employed, where network members forwarded the survey link to their clinical colleagues. The survey instrument, developed through a literature review, interviews with academic and clinical researchers, and pilot testing, assessed participants perspectives on prescribing FDC antihypertensive medicines for hypertension. Participants rated their level of agreement (5-point Likert scale) with statements representing six barriers and four facilitators to FDC use. Data from 191 surveys were available for analysis. 25% (n = 47) of participants worked in high-income countries, 38% (n = 73) in upper-middle income, 25% (n = 48) in lower-middle income, 6% (n = 10) in low-income countries. Forty percent (n = 70) of participants were between 36-45 years of age; two thirds were male. Cost was reported as a barrier to prescribing FDC antihypertensive medicines [51% (n = 87) agreeing or strongly agreeing], followed by doctors' confidence in BP measured in clinic [40%, (n = 70)], access [37%, (n = 67)], appointment duration [35%, (n = 61)], concerns about side-effects [(21%, n = 37)], and non-adherence [12%, (n = 21)]. Facilitators to FDC antihypertensive polypills prescribing were clinician facing, such as access to educational supports [79%, (n = 143)], more BP measurement data [67%, (n = 120)], a clinical nudge in health records [61%, (n = 109)] and patient-facing including improved patient health literacy [49%, (n = 88)]. The levels of agreement and strong agreement across all barriers and facilitators were similar for participants working in higher or lower income countries. Across all countries, participants rated FDC antihypertensive medications highly valuable for managing patients with non-adherence, (82% reported high or very high value), for patients with high pill burden (80%). Cost and access were the most common barriers to prescribing FDCs across high- and low-income countries. While greater educational support for clinicians was perceived as the leading potential facilitator of FDC use, this seems unlikely to be effective without addressing access.

Her2 positive metastatic breast cancer treated with low dose lapatinib in a resource-constrained setting in South India: a retrospective audit.

Despite the development of newer anti-Her2 agents, access to these medicines is still restricted with lapatinib being widely used as a second-line agent in Her2-positive metastatic breast cancer. However, lapatinib at approved doses of 1,250 to 1,500 mg/day contributes to a high pill burden and financial toxicity. In a population that has an average national per capita income of only USD 2238.1, lapatinib alone contributes to a financial burden of USD 6153.56 per year (approximately USD 500 per month). A concept of 'value meal' has been suggested - the higher bioavailability of lapatinib with the meal being exploited to reduce its administered dose. This concept was utilised in a resource-constrained tertiary care center in South India and we report the outcomes. In our institution, consecutive patients with Her2 positive metastatic breast cancer from 1 January 2014 to 31 December 2020 who could not afford trastuzumab, lapatinib or any other anti-Her2 agent were offered low-dose lapatinib, 500 mg daily with meal. We conducted a retrospective cohort study of the safety and efficacy of this regimen. Among the 47 patients who received low-dose lapatinib, the majority had de novo metastatic disease (57.4%) and multiple visceral metastases (48.9%). The median number of lines of treatment before lapatinib was one. The disease control rate with lapatinib was 61.7%. The median progression-free survival was 7 months (95% CI: 5.6-8.4 months). The median duration of response was 4.5 months, ranging from 1.3 to 45.8 months. Only eleven patients (23.4%) experienced toxicity, mainly dermatological, with grade 3 in only one (2.1%) and no grade 4 toxicities. Low-dose lapatinib is a regimen that offers an acceptable disease control rate. This strategy requires further exploration, particularly for the benefit of resource-limited areas.

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.

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

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.

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.

Association between phosphate binder pill burden and mortality risk in patients on maintenance hemodialysis: a single-center cohort study with 7-year follow-up of 513 patients.

Dialysis patients often take multiple oral medications, leading to a high pill burden. Phosphate binders (PBs) account for a large proportion of this daily pill burden (DPB). The relationship between DPB and mortality risk remains unclear, and we hypothesized that this relationship might be influenced by the proportion of PBs to all medications. We divided DPB into those derived from PBs and non-PB drugs and analyzed the association with mortality risk over a 7-year period in 513 chronic hemodialysis patients using a baseline model. The median (interquartile range) DPB from all drugs was 15.8 (11.2-21.0) pills/day/patient, and the median ratio of PB pills to all drug pills was 29.3 (13.7-45.9)% at baseline. During a median observation period of 5.2years, 161 patients (31.4%) died. Kaplan-Meier analysis showed no significant difference in all-cause mortality between PB users and non-users. However, a significant survival advantage was observed in the highest tertile of DPB from PBs compared to the lowest tertile. Conversely, the highest tertile of DPB from non-PB drugs was associated with worse survival. Consequently, the highest tertile of the ratio of PBs to all pills was associated with better survival. This association remained significant even after adjusting for patient characteristics in the Cox proportional hazards model. However, when serum nutritional parameters were included as covariates, the significant association disappeared. Dialysis patients prescribed a higher rate of PB pills to all medications exhibited a lower mortality risk, possibly due to their better nutritional status.

Evaluation of Medication Adherence in Chronic Kidney Disease Patients with and without Hemodialysis

Abstract Background: Poor long-term adherence and persistence to pharmacological therapy is widely acknowledged as one of the primary clinical difficulties in the management of chronic diseases such as chronic kidney disease (CKD). The present study was aimed to measure treatment adherence using the Morisky Medication Adherence Scale (MMAS)-8 questionnaire in CKD patients with or without hemodialysis. Methodology: It was a cross-sectional study conducted in 120 clinically stable CKD patients with Stage 3 onward with or without hemodialysis. The sociodemographic and clinical characteristics of participants were collected in a predesigned format. Individual participants were scheduled for interviews and asked to complete inventory questionnaires. Medication adherence was assessed using a validated diagnostic tool MMAS-8 questionnaire. Results: Out of 120 individuals, the average number of medicines prescribed per prescription was 5.63 ± 2.22 and 4.65 ± 1.72 in the dialysis and nondialysis groups, respectively. Patients on dialysis had a higher pill burden than nondialysis patients, with more than three-fourths (78.3%) of them taking more than five medications every prescription. Low, moderate, and good adherence were reported in 61.7% (n = 37) versus 26.7% (n = 16), 33.3% (n = 20) versus 71.7% (n = 43), and 5% (n = 3) versus 1.6% (n = 1) of patients with and without dialysis, respectively, in MMAS-8. The most often reported nonadherence behaviors were forgetting to take medications, forgetting to pack medications while traveling, and feeling pressured to follow a treatment plan. There was an association between the dialysis and nondialysis groups in education level, employment, and pill load among patients with low adherence. Conclusion: Majority of the respondents (more than 90%) reported low-to-moderate adherence in both dialysis and nondialysis populations. Physicians and all other health-care professionals should work together to reduce the obstacles to good adherence by enhancing communication, reducing the burden of taking a lot of pills, and, if possible, by occasionally checking on patient adherence when there is suspicion of poor adherence.

Optimizing Antiretroviral Therapy in Heavily ART-Experienced Patients with Multi-Class Resistant HIV-1 Using Proviral DNA Genotypic Resistance Testing

Resistance to multiple antiretroviral drugs among people living with HIV (PLWH) can result in a high pill burden, causing toxicity and drug interactions. Thus, the goal is to simplify treatment regimens while maintaining effectiveness. However, former resistance analysis data may not be current or complete. The use of proviral DNA genotyping may assist in selecting appropriate treatment options. A retrospective study was carried out on individuals belonging to the Cologne HIV cohort with a resistance history to two or more antiretroviral (ARV) classes and on non-standard antiretroviral therapy (ART). Patients required former viral RNA and a recent proviral DNA resistance test to be available prior to the switch to ART. Potential discrepancies between resistance test results obtained through RNA and proviral DNA methods and the consequent virological and clinical outcomes following ART adjustments were analyzed. Out of 1250 patients, 35 were eligible for inclusion in this study. The median length of known HIV infection was 27 years, and the median duration of ART was 22 years. Of the 35 participants, 16 had received all five ARV classes. Based on proviral DNA genotyping results, ART was simplified in 17 patients. At the last follow-up examination after changing therapy, 15 patients had HIV RNA &lt;50 copies/mL (median 202 days, range 21–636). The mean number of pills per day decreased from eight to three, and the median intake frequency decreased from two to one time/day (ranges 1–2). Our study supports the use of proviral DNA genotyping as a safe strategy for switching to simplified ART regimens. However, the lack of extensive research on the advantages of proviral DNA genotyping makes it challenging to fully assess its benefits in terms of treatment selection.

CO156 Impact of Long-Acting Modality on the Management of the Parkinson's Disease

Parkinson’s Disease (PD) is a chronic, progressive, neuro-degenerative disorder that predominantly affects the ability to perform common, daily activities and characterized by both motor and non-motor symptoms. In 2016, PD accounted for approximately 6 million prevalent cases, 0.2 million deaths and 3.2 million DALYs (Disability adjusted life years) globally. PD management have plethora of therapies with high pill burden causing non-adherence (NA). Due to NA and lack of targeted therapies the burden of disease is increasing significantly.

Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis

Children deserve simple, short, safe, and effective treatment for rifampicin-resistant tuberculosis

Physiologically-based pharmacokinetic/pharmacodynamic modeling to predict tumor growth inhibition and the efficacious dose of selective estrogen receptor degraders in humans.

GDC-9545 (giredestrant) is a highly potent, nonsteroidal, oral selective estrogen receptor antagonist and degrader that is being developed as a best-in-class drug candidate for early-stage and advanced drug-resistant breast cancer. GDC-9545 was designed to improve the poor absorption and metabolism of its predecessor GDC-0927, for which development was halted due to a high pill burden. This study aimed to develop physiologically-based pharmacokinetic/pharmacodynamic (PBPK-PD) models to characterize the relationships between oral exposure of GDC-9545 and GDC-0927 and tumor regression in HCI-013 tumor-bearing mice, and to translate these PK-PD relationships to a projected human efficacious dose by integrating clinical PK data. PBPK and Simeoni tumor growth inhibition (TGI) models were developed using the animal and human Simcyp V20 Simulator (Certara) and adequately described each compound's systemic drug concentrations and antitumor activity in the dose-ranging xenograft experiments in mice. The established PK-PD relationship was translated to a human efficacious dose by substituting mouse PK for human PK. PBPK input values for human clearance were predicted using allometry and in vitro in vivo extrapolation approaches and human volume of distribution was predicted from simple allometry or tissue composition equations. The integrated human PBPK-PD model was used to simulate TGI at clinically relevant doses. Translating the murine PBPK-PD relationship to a human efficacious dose projected a much lower efficacious dose for GDC-9545 than GDC-0927. Additional sensitivity analysis of key parameters in the PK-PD model demonstrated that the lower efficacious dose of GDC-9545 is a result of improvements in clearance and absorption. The presented PBPK-PD methodology can be applied to support lead optimization and clinical development of many drug candidates in discovery or early development programs.

An Insight into Advances in Developing Nanotechnology Based Therapeutics, Drug Delivery, Diagnostics and Vaccines: Multidimensional Applications in Tuberculosis Disease Management.

Tuberculosis (TB), one of the deadliest contagious diseases, is a major concern worldwide. Long-term treatment, a high pill burden, limited compliance, and strict administration schedules are all variables that contribute to the development of MDR and XDR tuberculosis patients. The rise of multidrug-resistant strains and a scarcity of anti-TB medications pose a threat to TB control in the future. As a result, a strong and effective system is required to overcome technological limitations and improve the efficacy of therapeutic medications, which is still a huge problem for pharmacological technology. Nanotechnology offers an interesting opportunity for accurate identification of mycobacterial strains and improved medication treatment possibilities for tuberculosis. Nano medicine in tuberculosis is an emerging research field that provides the possibility of efficient medication delivery using nanoparticles and a decrease in drug dosages and adverse effects to boost patient compliance with therapy and recovery. Due to their fascinating characteristics, this strategy is useful in overcoming the abnormalities associated with traditional therapy and leads to some optimization of the therapeutic impact. It also decreases the dosing frequency and eliminates the problem of low compliance. To develop modern diagnosis techniques, upgraded treatment, and possible prevention of tuberculosis, the nanoparticle-based tests have demonstrated considerable advances. The literature search was conducted using Scopus, PubMed, Google Scholar, and Elsevier databases only. This article examines the possibility of employing nanotechnology for TB diagnosis, nanotechnology-based medicine delivery systems, and prevention for the successful elimination of TB illnesses.

Pill-burden and its association with treatment burden among patients with advanced stages of chronic kidney disease

IntroductionChronic kidney disease (CKD) is associated with multimorbidity and high treatment burden. Pill-burden is one component of the overall treatment burden. However, little is known about its magnitude and contribution to the overall treatment burden among patients with advanced stages of CKD. This study aimed to quantify the magnitude of pill-burden in dialysis-dependent vs. non-dialysis-dependent advanced-stage CKD patients and its association with treatment burden. MethodsThis was a cross-sectional study for the assessment of pill-burden and treatment burden among non-dialysis and hemodialysis (HD)-dependent CKD patients. Pill-burden was quantified as “number of pills/patient/week” through electronic medical record, while treatment burden was assessed using the “Treatment Burden Questionnaire (TBQ)”. Furthermore, oral and parenteral medication burden was also quantified. Data were analyzed using both descriptive and inferential analysis, including Mann – Whitney U test and two-way between groups analysis of variance (ANOVA). ResultsAmong the 280 patients included in the analysis, the median (IQR) number of prescribed chronic medications was 12 (5.7) oral and 3 (2) parenteral medications. The median (IQR) pill-burden was 112 (55) pills/week. HD patients experienced higher pill-burden than non-dialysis patients [122 (61) vs. 109 (33) pills/week]; however, this difference did not reach statistical significance (p = 0.81). The most commonly prescribed oral medications were vitamin D (90.4%), sevelamer carbonate (65%), cinacalcet (67.5%), and statins (67.1%). Overall, patients who had high pill-burden (≥112 pills/week) had significantly higher perceived treatment burden compared to low pill-burden patients (<112 pills/week) [47(36.2) vs. 38.5(36.7); p = 0.0085]. However, two-way ANOVA showed that dialysis status is the significant contributor to the treatment-burden in the high overall pill-burden group (p < 0.01), the high oral-medication-burden group (p < 0.01), and the high parenteral-medication-burden group (p = 0.004). ConclusionsPatients with advanced CKD experienced a high pill-burden, which increases the treatment burden; however, the dialysis status of the patient is the main factor affecting the overall treatment burden. Future intervention studies should target this population with an aim to reduce polypharmacy, pill-burden, and treatment burden, which may ultimately improve CKD patients’ quality of life.

Innovative Therapeutic Approaches Based on Nanotechnology for the Treatment and Management of Tuberculosis.

Tuberculosis (TB), derived from bacterium named Mycobacterium tuberculosis, has become one of the worst infectious and contagious illnesses in the world after HIV/AIDS. Long-term therapy, a high pill burden, lack of compliance, and strict management regimens are disadvantageswhich resulted in the extensively drug-resistant (XDR) along with multidrug-resistant (MDR) in the treatment of TB. One of the main thrust areas for the current scenario is the development of innovative intervention tools for early diagnosis and therapeutics towards Mycobacterium tuberculosis (MTB). This review discusses various nanotherapeutic agents that have been developed for MTB diagnostics, anti-TB drugs and vaccine. Undoubtedly, the concept of employing nanoparticles (NPs) has strong potential in this therapy and offers impressive outcomes to conquer the disease. Nanocarriers with different types were designed for drug delivery applications via various administration methods. Controlling and maintaining the drug release might be an example of the benefits of utilizing a drug-loaded NP in TB therapy over conventional drug therapy. Furthermore, the drug-encapsulated NP is able to lessen dosage regimen and can resolve the problems of insufficient compliance. Over the past decade, NPs were developed in both diagnostic and therapeutic methods, while on the other hand, the therapeutic system has increased. These "theranostic" NPs were designed for nuclear imaging, optical imaging, ultrasound, imaging with magnetic resonance and the computed tomography, which includes both single-photon computed tomography and positron emission tomography. More specifically, the current manuscript focuses on the status of therapeutic and diagnostic approaches in the treatment of TB.