Simple Regimen Research Articles

Assessment of swallowability and acceptability of scored darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) tablets in HIV-1-infected children aged ≥6 to

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) fixed-dose combination (FDC) was developed as a once-daily, complete antiretroviral (ARV) regimen therapy to address the need for simplified protease inhibitor-based ARV regimens. This study assessed the swallowability and acceptability for long-term use of scored placebo tablets matching the D/C/F/TAF FDC tablets in children living with HIV-1. This study (NCT04006704) was a Phase 1, open-label, randomized, single-dose, 2-period, 2-sequence crossover study in children living with HIV-1, aged ≥6 to <12years and weighing ≥25 to <40kg, on a stable ARV regimen for ≥3months. Participants were asked to swallow whole (size, 21 × 11 × 7mm) and split matching placebo D/C/F/TAF tablets. Swallowability of the matching placebo D/C/F/TAF tablets (primary endpoint) was assessed by observers. Acceptability of taking matching placebo D/C/F/TAF tablets and current ARVs was evaluated by participants using a 3-point questionnaire. Participants rated the acceptability for long-term daily use of the placebo D/C/F/TAF tablets, and observers assessed how easily caregivers could split a scored tablet by hand, using 3-point questionnaires. Among the 24 participants who enrolled and completed the study, 95.8% (23/24) were able to swallow the whole and split matching placebo D/C/F/TAF tablets after 1 or 2 attempts. Most participants (>70%) rated the acceptability of tablets for long-term daily use as acceptable or good to take. Breaking the tablets was considered easy or OK by 79.2% (19/24) of caregivers. Scored D/C/F/TAF FDC tablets are swallowable - with whole favoured over split - and considered at least acceptable for long-term daily intake in children living with HIV-1 aged ≥6 to <12years. ClinicalTrials.gov Identifier: NCT04006704.

A pragmatic randomized controlled trial to evaluate the efficacy and safety of an oral short-course regimen including bedaquiline for the treatment of patients with multidrug-resistant tuberculosis in China: study protocol for PROSPECT

IntroductionThe lack of safe, effective, and simple short-course regimens (SCRs) for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment has significantly impeded TB control efforts in China.MethodsThis phase 4, randomized, open-label, controlled, non-inferiority trial aims to assess the efficacy and safety of a 9-month all-oral SCR containing bedaquiline (BDQ) versus an all-oral SCR without BDQ for adult MDR-TB patients (18–65 years) in China. The trial design mainly mirrors that of the “Evaluation of a Standardized Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB” (STREAM) stage 2 study, while also incorporating programmatic data from South Africa and the 2019 consensus recommendations of Chinese MDR/RR-TB treatment experts. Experimental arm participants will receive a modified STREAM regimen C that replaces three group C drugs, ethambutol (EMB), pyrazinamide (PZA), and prothionamide (PTO), with two group B drugs, linezolid (LZD) and cycloserine (CS), while omitting high-dose isoniazid (INH) for confirmed INH-resistant cases. BDQ duration will be extended from 6 to 9 months for participants with Mycobacterium tuberculosis-positive sputum cultures at week 16. The control arm will receive a modified STREAM regimen B without high-dose INH and injectable kanamycin (KM) that incorporates experimental arm LZD and CS dosages, treatment durations, and administration methods. LZD (600 mg) will be given daily for ≥ 24 weeks as guided by observed benefits and harm. The primary outcome measures the proportion of participants with favorable treatment outcomes at treatment completion (week 40), while the same measurement taken at 48 weeks post-treatment completion is the secondary outcome. Assuming an α = 0.025 significance level (one-sided test), 80% power, 15% non-inferiority margin, and 10% lost to follow-up rate, each arm requires 106 participants (212 total) to demonstrate non-inferiority.DiscussionPROSPECT aims to assess the safety and efficacy of a BDQ-containing SCR MDR-TB treatment at seventeen sites across China, while also providing high-quality data to guide SCRs administration under the direction of the China National Tuberculosis Program for MDR-TB. Additionally, PROSPECT will explore the potential benefits of extending the administration of the 9-month BDQ-containing SCR for participants without sputum conversion by week 16.Trial registrationClinicalTrials.gov NCT05306223. Prospectively registered on 16 March 2022 at https://clinicaltrials.gov/ct2/show/NCT05306223?term=NCT05306223&draw=1&rank=1 {2}.

Simplifying medication regimens for residents of aged care facilities: Pharmacist and physician use of a structured five-step medication simplification tool

BackgroundPharmacist-led medication regimen simplification using a structured approach can reduce unnecessary medication regimen complexity in residential aged care facilities (RACFs), but no studies have investigated simplification by different health professionals, nor the extent to which simplification is recommended during comprehensive medication reviews. ObjectivesTo compare medication regimen simplification opportunities identified by pharmacists, general medical practitioners (GPs), and geriatricians and to determine if pharmacists identified simplification opportunities during routinely conducted comprehensive medication reviews in RACFs for these same residents. MethodsThree pharmacists, three GPs and three geriatricians independently applied the Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) to medication data for 83 residents taking medications at least twice daily. Interrater agreement was calculated using Fleiss's kappa. Pharmacist medication review reports for the same 83 residents were then examined to identify if the pharmacists conducting these reviews had recommended any of the simplification strategies. ResultsOverall, 77 residents (92.8 %) taking medications at least twice daily could have their medication regimen simplified by at least one health professional. Pharmacists independently simplified 53.0–77.1 % of medication regimens (Κ = 0.60, 95%CI 0.46–0.75, indicating substantial agreement), while GPs simplified 74.7–89.2 % (Κ = 0.44, 95%CI 0.24–0.64, moderate agreement) and geriatricians simplified 41.0–66.3 % (Κ = 0.30, 95%CI 0.16–0.44, fair agreement). No simplification recommendations were included in the reports previously prepared by pharmacists as part of the comprehensive medication reviews undertaken for these residents. ConclusionPharmacists, GPs, and geriatricians can all identify medication regimen simplification opportunities, although these opportunities differ within and between professional groups. Although opportunities to simplify medication regimens during comprehensive medication reviews exist, simplification is not currently routinely recommended by pharmacists performing these reviews in Australian RACFs.

Impact of coordinated care on adherence to antihypertensive medicines among adults experiencing polypharmacy in Australia.

Adherence to antihypertensives is key for blood pressure control. Most people with hypertension have several comorbidities and require multiple medicines, leading to complex care pathways. Strategies for coordinating medicine use can improve adherence, but cumulative benefits of multiple strategies are unknown. Using dispensing claims for a 10% sample of eligible Australians, we identified adult users of antihypertensives during July 2018-June 2019 who experienced polypharmacy (≥5 unique medicines). We measured medicine use reflecting coordinated medicine management in 3 months before and including first observed dispensing, including: use of simple regimens for each cardiovascular medicine; prescriber continuity; and coordination of dispensings at the pharmacy. We measured adherence (proportion of days covered) to antihypertensive medicines in the following 12 months, and used logistic regression to assess independent associations and interactions of adherence with these measures of care. We identified 202 708 people, of which two-thirds (66.6%) had simple cardiovascular medicine regimens (one tablet per day for each medicine), two-thirds (63.3%) were prescribed >75% of medicines from the same prescriber, and two-thirds (65.5%) filled >50% of their medicine on the same day. One-third (28.4%) of people experienced all three measures of coordinated care. Although all measures were significantly associated with higher adherence, adherence was greatest among people experiencing all three measures (odds ratio = 1.63; 95% confidence interval: 1.55-1.72). This interaction was driven primarily by effects of prescriber continuity and dispensing coordination. Coordinating both prescribing and dispensing of medicines can improve adherence to antihypertensives, which supports strategies consolidating both prescribing and supply of patients' medicines.

Simplifying treatment from double-inhaler to single-inhaler triple therapy in patients with chronic obstructive pulmonary disease

A clinical decision report using: Ferguson GT, Brown N, Compton C, et al. Once-daily single-inhaler versus twice-daily multiple-inhaler triple therapy in patients with COPD: lung function and health status results from two replicate randomized controlled trials. Respir Res. 2020;21(1):131. https://doi.org/10.1186/s12931-020-01360-w for a patient requesting a simplified therapeutic regimen with equal efficacy for chronic obstructive pulmonary disease (COPD) management.

Comparative Efficacy and Safety of Standard and Biweekly Trifluridine/Tipiracil Regimen in Patients With Colorectal Cancer.

Trifluridine/tipiracil (FTD/TPI) is used to treat metastatic colorectal cancer (mCRC). Since the standard regimen of FTD/TPI features a complex dosing schedule and frequently results in severe hematological toxicities, a simplified regimen has emerged, in which FTD/TPI is orally administered biweekly. However, the survival benefits and potential adverse events associated with the biweekly FTD/TPI regimen have not been fully evaluated in previous reports. Therefore, in this study, the differences in efficacy and safety between the standard and biweekly FTD/TPI regimens were retrospectively investigated in patients with mCRC. Data from 90 patients who received FTD/TPI for mCRC were extracted from the electronic medical records at the Osaka University Hospital. According to the inclusion and exclusion criteria, 85 of the 90 patients were enrolled in the study. We compared patient characteristics, overall survival (OS), progression-free survival (PFS), and adverse events between the standard (n=56) and biweekly groups (n=29). The biweekly group exhibited prolonged OS and PFS compared to patients in the standard group. Multivariate analysis for OS and PFS demonstrated that the biweekly regimen was the only significant factor that affected OS, and not PFS (HR=0.561, p=0.049). Kaplan-Meier analysis indicated that neutropenia (grade ≥3) in the biweekly group was significantly prolonged compared to the standard group (p=0.012). However, there were no significant differences in adverse events between the two groups (p>0.999). The biweekly FTD/TPI regimen, compared to the standard regimen, should enhance both OS and PFS in patients with mCRC without escalating any adverse event.

Tofacitinib pharmacokinetics in children and adolescents with juvenile idiopathic arthritis.

These analyses characterized tofacitinib pharmacokinetics (PKs) in children and adolescents with juvenile idiopathic arthritis (JIA). Data were pooled from phase I (NCT01513902), phase III (NCT02592434), and open-label, long-term extension (NCT01500551) studies of tofacitinib tablet/solution (weight-based doses administered twice daily [b.i.d.]) in patients with JIA aged 2 to less than 18 years. Population PK modeling used a nonlinear mixed-effects approach, with covariates identified using stepwise forward-inclusion backward-deletion procedures. Simulations were performed to derive dosing recommendations for children and adolescents with JIA. Two hundred forty-six pediatric patients were included in the population PK model. A one-compartment model with first-order elimination and absorption with body weight as a covariate for oral clearance and apparent volume of distribution sufficiently described the data. Oral solution was associated with comparable average concentration (Cavg) and slightly higher (113.9%) maximum concentration (Cmax) versus tablet, which was confirmed by a subsequent randomized, open-label, bioavailability study conducted in healthy adult participants (n = 12) by demonstrating adjusted geometric mean ratios (90% confidence interval) between oral solution and tablet of 1.04 (1.00-1.09) and 1.10 (1.00-1.21) for area under the curve extrapolated to infinity and Cmax, respectively (NCT04111614). A dosing regimen of 3.2 mg b.i.d. solution in patients 10 to less than 20 kg, 4 mg b.i.d. solution in patients 20 to less than 40 kg, and 5 mg b.i.d. tablet/solution in patients greater than or equal to 40 kg, irrespective of age, was proposed to achieve constant Cavg across weight groups. In summary, population PK characterization informed a simplified tofacitinib dosing regimen that has been implemented in pediatric patients with JIA.

Microparticles and multi-unit systems for advanced drug delivery

Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy with favorable pharmacokinetics and patient centricity. On the other hand, the above advantages are served by high and well reproducible quality attributes of the medicinal product where even flexible design and controlled processability offer success as well as possible longer product life-cycle for the manufacturers. Moreover, the specific demands of patients can be taken into account, including simplified dosing regimens, flexible dosage, drug combinations, palatability, and ease of swallowing.In the more than 70 years since the first modified-release formulation appeared on the market, many new formulations have been marketed and many publications have appeared in the literature. More unique and newer pharmaceutical technologies and excipients have become available for producing tailor-made particles with micrometer dimensions and beyond. All these have contributed to the fact that the sub-units (e.g. minitablets, pellets, microspheres) that make up a multiparticulate system can vary widely in composition and properties. Some units have mucoadhesive properties and others can float to contribute to a suitable release profile that can be designed for the multiparticulate formula as a whole. Nowadays, there are some available formulations on the market, which are able to release the active substance even for several months (3 or 6 months depending on the type of treatment).In this review, the latest developments in technologies that have been used for a long time are presented, as well as innovative solutions such as the applicability of 3D printing to produce subunits of multiparticulate systems. Furthermore, the diversity of multiparticulate systems, different routes of administration are also presented, touching the ones which are capable of carrying the active substance as well as the relevant, commercially available multiparticle-based medical devices. The versatility in size from 1 µm and multiplicity of formulation technologies promise a solid foundation for the future applications of dosage form design and development.

#317 : The Clinical Outcome of Ovarian Stimulation Undergoing Intrauterine Insemination with Follitropin Delta in Indonesian Women

Background and Aims: Intrauterine insemination (IUI) has been widely used as a common treatment for infertile couples due to its simplicity and low cost. Numerous studies have shown that IUI cycles with controlled ovarian stimulation (COS) result in higher pregnancy rates compared to those without COS. Follitropin delta, a novel recombinant FSH (rFSH) can be used for controlled ovarian stimulation in women undergoing assisted reproductive technologies (ART) and was dosed individually based on serum anti-Müllerian hormone (AMH) concentration and body weight. In this study, we used a simplified dosage equivalent method. The aim of this study was to compare the efficacy and safety of follitropin delta in its simplified dosage equivalent regimen with follitropin alfa in a conventional dose regimen in Indonesian women undergoing intrauterine insemination. Method: A single-center, retrospective observational study from January 2020 to December 2022 was performed in 228 IUI cycles in Halim Fertility Center, Indonesia. Controlled Ovarian Stimulation was performed during IUI cycles and divided into two groups: group I received follitropin delta with a simplified dosage equivalent regimen, and group II received follitropin alfa with a conventional dose. The baseline characteristics, cycle parameters, and IUI outcomes of both groups were compared. Results: Our study included 228 IUI cycles with the follitropin delta group (114 IUI cycles) and the follitropin alfa group (114 IUI cycles). The clinical pregnancy rate was higher in the follitropin delta than the follitropin alfa but there was no significant difference between the groups (p&gt;0.05). The multiple pregnancy rate and Ovarian Hyperstimulation Syndrome (OHSS) rates were lower in follitropin delta than follitropin alfa but there was no significant difference between the groups (p&gt;0.05). Conclusion: Follitropin delta with a simplified dosage equivalent regimen showed higher efficacy and similar safety compared with follitropin alfa in conventional dosing regimen in Indonesian women undergoing Intrauterine insemination.

OP93 The Cost Effectiveness Of Antiretroviral Therapy Adherence Interventions In HIV/AIDS Patients: A Systematic Review Of Decision Analytic Models

IntroductionPeople living with HIV/AIDS (PLWHA) frequently struggle to maintain optimal adherence to antiretrovirals (ARVs). Different adherence-improving interventions have been developed and examined through decision analytic model-based health technology assessments. Therefore, we aimed to conduct a systematic review of all decision analytic models developed to improve adherence in PLWHA.MethodsThe review protocol was registered on Prospero (CRD42022270039) and relevant studies published from inception to 23 October 2022 were identified through searches of the following databases: PubMed, Embase, the National Health Service Economic Evaluation Database, PsycINFO, the Health Economic Evaluations Database, and EconLit. Studies were included if they were modeling works of full economic evaluations, including cost-effectiveness analyses (CEA), cost-utility analyses, cost-benefit analyses, and cost-consequence analyses. The primary outcome was the cost effectiveness of adherence interventions reported as the incremental cost per additional quality-adjusted life-year (QALY). Study quality was assessed with the Quality of Health Economics Studies instrument. Due to the heterogeneity of the data, a permutation matrix was used for quantitative data synthesis rather than a meta-analysis.ResultsThe 15 studies identified were conducted in North America (8/15), Africa (4/15), and Europe (3/15). The time horizon was one year in one study, ten years in one study, 20 years in three studies, and a lifetime horizon in ten studies. The types of interventions were smartphone-based (5/15), nurse involved (2/15), directly observed therapy (2/15), case manager involved (1/15), simplification of regimens (1/15), Link4Health (1/15), and others (3/15) that involved multicomponent intervention. The interventions gained higher QALYs with cost savings in all 15 studies and gained QALYs at a higher cost at an acceptable incremental cost-effectiveness ratio in 80 percent (12/15) of studies. The studies were of fair (13%) to high quality (87%).ConclusionsThis study is the first systematic review of decision analytic model-based CEAs of adherence interventions in the management of PLWHA. Most of the identified studies recently published good quality cost-effectiveness analyses with an adequate timeframe.

Inhaler Adherence in COPD: A Crucial Step Towards the Correct Treatment.

COPD is a typical example of chronic disease. As such, treatment adherence tends to be as low as between 30% and 50%, with specific issues in COPD due to the use of inhaled therapies. Decreased adherence in COPD is associated with worse outcomes, with increased risk for exacerbations and long-term mortality. Factors that impact adherence are multiple, some related to patient, some related to clinicians and finally some related to healthcare system. Among clinician factors, prescription of simplified treatment regimens delivered by an inhaler adapted to the patient's characteristics is crucial. Although it has been observed a huge improvement in the design and usability of inhaler devices for COPD in the last two centuries, there is still a clear gap in this field. Smart inhalers as well as simplified treatment regimens could improve adherence and therefore improve long-term outcomes in COPD.

Retrospective Evaluation of a Dexamethasone Sparing Antiemetic Regimen: An Antiemetic Prophylaxis Study on NEPA (Netupitant Plus Palonosetron) for Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Cancer Patients.

Background Corticosteroids, specifically dexamethasone (DEX), have been extensively utilized for the prevention of chemotherapy-induced nausea and vomiting (CINV). However, their usage is associated with a range of adverse events. In contrast, the combination of NetupitantPlus Palonosetron (NEPA) with a single dose of DEX provides comparable efficacy in preventing CINV over a five-day period following chemotherapy administration. This regimen offers the advantage of reducing the need for additional doses of DEX, particularly in the high-risk setting of HEC (Highly emetic chemotherapy). Objective To evaluate dexamethasone sparing anti-emetic regimen (single dose dexamethasone with NEPA) for prophylaxis of CINV in patients receiving HEC. Methodology This is a retrospective, observational, real-world, single-center study including data of 69 patients who received high-dose emetogenic chemotherapy and were administered DEX (8 or 12 mg) on day 1, with no dose ofDEX on days 2, 3, and 4, combined with an oral combination of tablet netupitant 300 mg and palonosetron 0.5 mg. NEPA was taken orally an hour prior to the start of the HEC cycle. The primary efficacy endpoint was complete response (CR) which is defined as no nausea, emesis, or no rescue medication during the Acute (< 24 hours) and Delayed Phase (25-120 hours) of chemotherapy. Results The overall CR achieved in the acute and delayed phase for vomiting is 100% at all four follow-ups. The CR achieved in the acute phase is 95.7% whereas 98.6% of patients showed CR in the delayed phase respectively. No patient required any rescue medication. No acute and delayed phase of vomiting was reported. Conclusion A simplified regimen of NEPA plus single-dose DEX offers effective CINV prevention throughout five days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting chemotherapy.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients.

This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1year after switching indicated a difference of 3.27±1.10mmol/L vs . 3.40±1.59mmol/L in triglyceride ( P =0.014), 4.82±0.74mmol/L vs . 4.88±0.72mmol/L in total cholesterol ( P =0.038), 3.09±0.70mmol/L vs . 3.18±0.66mmol/L in low-density lipoprotein ( P <0.001), and 0.99±0.11mmol/L vs . 0.95±0.10mmol/L in high-density lipoprotein ( P <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P <0.001). The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Diagnosis and management of cryptococcal meningitis in HIV-infected adults.

Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.

Feasibility and Implementation of an out-of-Pocket Cost Calculator for Pre-Treatment Financial Counselling in Cancer Patients

Introduction Public healthcare in Singapore is funded by a combination of subsidies, insurance, which includes national basic coverage (MediShield, MSL) and optional private coverage, pensions (MediSave, MSV) and out of pocket (OOP) costs. In Sep 2022, spiraling cancer costs led to a shift in national policy with the introduction of a Cancer Drug List (CDL) of cost-effective treatments. OOP costs are now determined by multiple factors such as subsidy status, financial resources, insurance claim limits, residency status, drug subsidy tier, therapeutic indication, dose and cost. To simplify this complex manual process, we developed ChemoCalc, a digital calculator for individualized OOP estimates. We hypothesize that it will increase OOP cost estimate accuracy, improve efficiency and have high uptake. Methods The study was performed in a Singapore tertiary cancer center. ChemoCalc was developed with a multi-disciplinary team comprising physicians, pharmacists, operations administrators, patient service associates and medical social workers. Data sources were consolidated and hierarchical logic determined for calculating regimen and patient-specific OOP cost. Data sources included the CDL, hospital formulary, chemotherapy protocols, chemotherapy facility fees and various national subsidy schemes. These were encoded into an algorithm by a third-party developer. The user interface and experience (UI/UX) was envisioned by the team with iterations based on feasibility testing. FCs were trained on using ChemoCalc and data was collected pre and post-ChemoCalc implementation. Feasibility outcomes were demand, acceptability, practicality and integration (the extent to which ChemoCalc could be deployed in a secure hospital IT environment). These were assessed through employee focus groups (FG). Reporting officers were not present during the FG. Implementation outcomes were adoption (percentage of eligible users using ChemoCalc for FC), engagement (percentage of returning users), efficiency (median time taken to perform FC) and accuracy (percentage of bills which are within ±10% of the FC estimate). For accuracy, 10 bills were randomly selected each month and compared against the pre-treatment FC. Results Prior to the development of ChemoCalc, the demand for automated FC was identified through employee engagement. ChemoCalc (Figure 1) was developed and iterated from Aug - Sep 2022. Feasibility assessment identified that simplicity underscored a good UI/UX. To reduce UI clutter and improve ease-of-use, an algorithm was encoded to ensure that only variables relevant to a particular regimen need to be entered (Figure 2). All data fields were accessible via the hospital electronic medical record. The final version of ChemoCalc was deemed acceptable and practical by FG. It was integrated into the hospital environment seamlessly and accessible from all hospital computers and personal mobile devices. Data collection for implementation outcomes took place from 1 Oct 2022 to 31 Mar 2023. ChemoCalc was used by 72 different members of staff from all job groups. On average, the prices of 2,484 regimens (mean 11 regimens per patient) were generated each month, with a total of 17,385 price estimates generated. 91% of price estimates were for subsidized patients and 9% for private patients. For staff performing FC, the adoption and engagement rate was 100%. ChemoCalc improved efficiency for the FC process with an accuracy of 95% (baseline 35%, 270% increase). Time spent computing OOP reduced from a median of 8 min (range 4.5 - 13) to 44 seconds (range 15 - 20) for simple regimens, and 23 min (range 15.5 - 44) to 1 min (range 0.3 - 1.3) for complex regimens respectively. Due to the convenience and simplicity, there was 100% uptake for pre-treatment FC, as staff have been able to process more FC requests and spend more time addressing patients' financial concerns. It has also allowed patients to compare costs of different treatment regimens. Conclusion The implementation of ChemoCalc was successful with 100% adoption rate and significantly improved efficiency and accuracy. ChemoCalc's algorithm can easily be adjusted to accommodate country- or institution-specific reimbursements for implementation elsewhere. Further studies are required to investigate if pre-treatment FC addresses financial toxicity or influences healthcare costs.

Functional insulin aspart/insulin degludec-based microneedles for promoting postprandial glycemic control.

Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are transdermal delivery devices that may allow diabetic patients to easily deploy transdermal insulin therapy while considerably reducing injection pain. In this study, we investigated the combination of dissolving MNs with IAsp or IDeg therapy as an alternative to daily multiple insulin injections, aiming to improve glycemic control and patient compliance. Mechanical properties of the MNs, structural stability of insulin encapsulated in the MNs, and transdermal application characteristics were studied to assess the practicality of insulin-loaded MNs for diabetes therapy. In vivo experiments conducted on diabetic rats demonstrated that the IAsp- and IDeg-loaded MNs have comparable blood glucose control abilities to that of subcutaneous injections. In addition, the therapeutic properties of insulin-loaded MNs under diverse dietary conditions and application strategies were further investigated to provide new information to support future clinical trials. Taken together, the proposed MNs have the potential to improve balances between glycemic control, hypoglycemia risk, and convenience, providing patients with simpler regimens. STATEMENT OF SIGNIFICANCE: 1. The fabricated functional insulin-loaded dissolving microneedles closely matched the glucose rise that occurs in response to meals, demonstrating promising alternatives for multiple daily insulin injections. 2. The hypoglycemic properties of insulin microneedles were investigated under diverse dietary conditions and application strategies, yielding new information to support future clinical trials. 3. Molecular dynamics simulations were utilized to study the interactions between the insulin and microneedle matrix materials, providing a strategy for theoretically understanding drug stability as well as the release mechanism of drug-loaded microneedles.

Pneumococcal Vaccination Recommendation and Completion Rates Among Patients With Inflammatory Bowel Disease and Barriers to Vaccination.

Guidelines for inflammatory bowel disease (IBD) patients receiving immunosuppression encouraged both the pneumococcal polysaccharide vaccine (PPSV23) and the pneumococcal conjugate vaccine (PCV13). We aimed to evaluate which pneumococcal vaccines are recommended and administered, and to understand provider and IBD patient knowledge regarding pneumococcal vaccinations. We performed a retrospective, cross-sectional analysis of 357 adult IBD patients on immunosuppression in our health care system. Patient demographics and clinical characteristics were collected. The primary outcome was rate of documented vaccinations recommended by providers; the secondary outcome was rate of receipt of the vaccines. We identified factors associated with receipt of any pneumococcal vaccine through multivariable logistic regression. We also performed provider and IBD patient surveys to understand provider and patient knowledge regarding pneumococcal vaccines. We used χ 2 and Fisher exact tests to assess survey responses. Fifty seven percent of IBD patients had any pneumococcal vaccination recommended and 35% had recommendations for both PPSV23 and PCV13. Forty percent received any pneumococcal vaccine and 18% received both vaccines. In multivariable analyses, increasing age (adjusted odds ratio: 1.03, 95% CI: 1.01-1.05) was associated with receipt of any pneumococcal vaccine, after adjusting for gender, race, insurance, disease activity, and time seen in our gastroenterology clinics. In the survey study, on average, 59% of providers correctly answered questions regarding pneumococcal vaccination indications. In our health care system, while recommendation for any pneumococcal vaccination was >50%, receipt of both PPSV23 and PCV13 was low. Simplified vaccine regimens (ie, PCV20) will likely improve vaccination rates.

Simplified regimens for AIDS-related cryptococcal meningitis - improving its access in Africa.

Simplified regimens for AIDS-related cryptococcal meningitis - improving its access in Africa.

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes

PurposeTo assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial.MethodsOriginally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed.ResultsFifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (−0.8 ± 1.1%, −0.7 ± 1.1%, and −1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (−1.2 ± 1.0%, −1.2 ± 1.1%, and −1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower.ConclusionSimplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes.Clinical trial registrationClinical trial registration no. NCT04196231, clinicaltrials.gov.

Simplification of Complex Insulin Regimens with IdegLira in People with Type2 Diabetes: Literature Review and Clinical Recommendations.

This study developed a simple algorithm based on clinical results described in medical literature and which allows one to simplify complex insulin regimes with IdegLira to avoid adverse events related to the complexity of some insulin treatments. We conducted a systematic review of the literature that allowed us to identify studies that evaluated the clinical result of simplifying complex insulin regimes. The authors reviewed the common factors these simpler regimes had, including the type of patients who used them. We found nine clinical studies published between 2017 and 2022, eight performed in Europe and one in Latin America. The monitoring time of the studies ranged between 3 and 18months. The size of the study populations was between 61 and 611 patients (the latter was in five countries). In all studies, HbA1c decreased by 0.6-1.7% and the weight decreased by 0.1-3.11kg. On the basis of the findings of these studies, we made some recommendations for clinical practice to simplify treatment. The results of these studies support an algorithm that simplifies the treatment of complex insulin regimens.