Characterizing long-acting injectable antiretroviral therapy eligibility and initiation at a safety net academic medical center in the southeastern United States.

Background: Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) extends dosing intervals from daily to every 8 weeks. Equitable implementation requires anticipating and addressing barriers to use. We described LAI-CAB/RPV eligibility and initiation among persons with HIV (PWH) receiving care at a Southeastern US academic medical center. Methods: We included PWH ≥18 years, in care 01/01/2020-12/31/2021, and participating in the UNC CFAR HIV Clinical Cohort. We characterized LAI-CAB/RPV eligibility, compared those with and without recent detectable viral load (VL), and described clinical outcomes on LAI-CAB/RPV. Results: Among 1672 PWH, 425 (25.4%) had LAI-CAB/RPV drug-resistance. Among 1238 LAI-eligible PWH, 8.9% had detectable VL. Median age was 53 (interquartile range 40, 61), 54.6% were non-Hispanic Black, and 73.6% male. Over one-third lived >50 miles from clinic, one-fifth were uninsured, and 7.4% reported hazardous alcohol use. Gaps in care (prior 12-month) were more common among PWH with detectable VL versus suppressed (23.1% vs 13.9%, p = 0.03). 6/47 initiated LAI-CAB/RPV had detectable VL prior to injection; >95% sustained suppression and those with detectable VL had a rapid decline in viremia. Conclusions: Three-quarters of PWH were eligible for LAI-CAB/RPV, but equitable implementation may require addressing challenges such as distance to care, inconsistent care engagement, and other comorbid conditions, particularly for PWH with viremia.

Atorvastatin-Loaded Dissolving Microarray Patches for Long-Acting Microdepot Delivery: Comparison of Nanoparticle and Microparticle Drug Formulations.

The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia. The MP-loaded D-MAPs exhibited an average drug loading of 5.15 ± 0.4 mg of ATR per patch, surpassing the 2.4 ± 0.11 mg/patch observed with NC-loaded D-MAPs. Skin deposition studies demonstrated the superior performance of MP D-MAPs, which delivered 2.0 ± 0.33 mg of ATR per 0.75 cm2 patch within 24 h, representing 38.76% of the initial amount of drug loaded. In contrast, NC D-MAPs delivered approximately 0.89 ± 0.12 mg of ATR per 0.75 cm2 patch at 24 h, equivalent to 38.42 ± 5.13% of the initial ATR loaded. Due to their favorable results, MP D-MAPs were chosen for an in vivo study using Sprague-Dawley rats. The findings demonstrated the capacity of D-MAPs to deliver and attain therapeutically relevant ATR concentrations (>20 ng/mL) for 14 days after a single 24-h application. This study is the first to successfully demonstrate the long-acting transdermal delivery of ATR using MP-loaded D-MAPs after a 24-h single-dose application. The innovative D-MAP system, particularly when loaded with MP, arises as a promising, minimally invasive, long-acting substitute for ATR delivery. This technology has the potential to improve patient compliance and therapeutic outcomes while also significantly advancing the field of transdermal drug delivery.

Impact of Demographics and Insurance Coverage on Schizophrenia Treatment and Healthcare Resource Utilization Within an Integrated Healthcare System.

Purpose: Little is known about the impact of health disparities on antipsychotic treatment and healthcare resource utilization (HRU) among patients with schizophrenia. The objective of this analysis is to examine treatment patterns and HRU by age, race/ethnicity, and insurance coverage among patients with schizophrenia in an integrated delivery network (IDN). Patients and Methods: This cross-sectional study used electronic health record data from MedStar Health, an IDN in the Baltimore-Washington, DC, area. Patients were aged ≥18 years and had ≥2 outpatient encounters or ≥1 hospitalization with a diagnosis of schizophrenia between January 1, 2017 and March 31, 2021. Outcomes assessed included oral antipsychotic prescriptions, long-acting injectable antipsychotic (LAI) utilization, hospitalizations, emergency department (ED) visits, and outpatient visits. Analyses compared subgroups based on age, race/ethnicity (non-Hispanic Black, non-Hispanic White, and other), and type of insurance coverage at index (Medicare, Medicaid, and other) during 12 months of follow-up. Results: A total of 78.1% of patients had ≥1 prescription for an antipsychotic and 69.1% received ≥1 second-generation antipsychotic. Second-generation long-acting injectables (SGA LAI) were utilized by 9.0% of patients, with the elderly and Medicaid beneficiaries having the lowest SGA LAI utilization. Overall, 61.7% of patients had ≥1 hospitalization, 56.4% had ≥1 outpatient visit, and 50.5% had ≥1 ED visit. Hospitalizations and ED visits were most common in those 18 to 24 years of age and in Medicaid beneficiaries, whereas outpatient visits were more common for the elderly and Medicare beneficiaries. Conclusion: At the population level, the results indicate widespread underprescription/underutilization of antipsychotics that have been shown to improve clinical and economic outcomes in patients with schizophrenia, particularly SGA LAI. Within specific subpopulations, disparities in treatment selection and HRU were observed, suggesting the need for increased attention to at-risk groups to ensure consistent quality of care regardless of age, race/ethnicity, or insurance coverage.

Long-acting muscarinic antagonist and long-acting ß2-agonist combination for the treatment of maintenance therapy-naïve patients with chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count <300 cells/µL) patients. In randomized controlled trials (RCTs), LAMA/LABA combination therapy improved lung function, St. George's Respiratory Questionnaire (SGRQ) total score, and Transitional Dyspnea Index (TDI) focal score and reduced the use of rescue medications, exacerbation risk, and risk of first clinically important deterioration (CID), compared with LAMA or LABA monotherapy. However, there is limited evidence regarding the efficacy and safety of LAMA/LABA combination therapy versus LAMA or LABA monotherapy in maintenance therapy-naïve patients. This review discusses the rationale for the early initiation of LAMA/LABA combination therapy in maintenance therapy-naïve patients with COPD. In post hoc analyses of pooled data from RCTs, compared with LAMA or LABA monotherapy, LAMA/LABA combination therapy improved lung function and quality of life and reduced COPD symptoms, risk of first moderate/severe exacerbation, risk of first CID, and use of rescue medication, with no new safety signals. In a real-world study, patients initiating LAMA/LABA had significantly reduced risk of COPD-related inpatient admissions and rate of on-treatment COPD-related inpatient admissions over 12 months than those initiating LAMA. Consequently, LAMA/LABA combination therapy could be considered the treatment of choice in maintenance therapy-naïve patients with COPD, as recommended by the GOLD 2024 report.

Long-acting bronchodilator combination therapy for the treatment of maintenance therapy­naïve patients with chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease (COPD) is a common lung disease that makes it hard to breathe and is a leading cause of death and disability worldwide. This disease tends to worsen lung function from an early stage, especially in people who only have mild or moderate symptoms. To help stop the loss of lung function and maintain the quality of life for patients with COPD, two main types of long-lasting inhaler medications are used: one type focuses on relaxing the muscles around the airways, and the other type helps open the airways making it easier to breathe. Some medications combine these two types of action and are approved for long-term management of COPD. However, there is not much information on the effectiveness and safety of these combination medications in patients who have never taken long-lasting COPD medication before. Current health guidelines suggest starting these combination medications in patients who are likely to see their symptoms get worse quickly, and who do not have a high level of a specific type of white blood cell. In this review, we discuss the evidence for starting these combination treatments early in patients who have never used long-lasting COPD medications before. There is no strong evidence yet that shows starting treatment early benefits patients with newly diagnosed COPD. However, about 30% of patients in clinical trials designed to study the effectiveness of these combination medications, had never received any long-lasting treatment before. After-the-fact analyses of these patients showed that these combination medications could reduce symptoms such as breathlessness, improve lung function, enhance quality of life, lessen the need for emergency medications, and decrease the risk of severe symptom flare-ups. Overall, the evidence supports using these combination inhaler medications as the first choice of treatment for patients with moderate COPD symptoms who have not previously been treated with long-lasting inhalers.

Menstrual management using the etonogestrel implant in individuals with intellectual disabilities in Joinville, Brazil.

OBJECTIVE: This study aimed to describe the use of etonogestrel (ENG) implants for menstrual management (i.e., management of bleeding and symptoms associated with menstruation) in individuals with intellectual disabilities. METHODS: This study retrospectively analyzed a cohort of individuals with intellectual disabilities who began using ENG implants between 2003 and 2018, in Joinville, Brazil. We collected sociodemographic, clinical, and reproductive data from the medical records, along with information related to ENG implant use. RESULTS: In total, 369 implants were placed in 130 individuals with intellectual disabilities. The median age at the first implant was 20 (interquartile range [IQR], 17-26) years, and 43.8% of the patients were adolescents. By December 2018, 90 patients had received two or more subsequent implants. The median duration of current ENG implant use was 19 (IQR, 12.8-22) months. More than 40% of the patients had comorbidities, with epilepsy being the most common. During the use of the current implant, 80% of the patients had a favorable bleeding profile (no bleeding or ≤1 bleeding episode per month), and 53.8% (70/130) had no bleeding within 3 months before their last medical visit. Among patients experiencing dysmenorrhea and premenstrual syndrome (PMS), 79% (64/81) and 82% (54/66) reported complete improvement, respectively. The premature implant removal rate was 8.9% (33/369). Unfavorable bleeding was the main reason for premature implant removal (20 out 33 removals). CONCLUSIONS: ENG implants might be a suitable option for individuals with intellectual disabilities who require management of menstrual bleeding and symptoms associated with menstruation. Most patients had a favorable bleeding profile and experienced significant improvements in dysmenorrhea and PMS, contributing to the high continuation rates of ENG implants.

In vitro and in vivo evaluation of in situ forming polyester implants for the extended release of carvedilol.

Polyester based in situ forming implants (ISFIs) are injectable long-acting drug delivery systems that offer a wide range of unique advantages. As a result of these advantages, two relatively high molecular weight, ester terminated grades of poly (D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) were evaluated for their ability (i) to form ISFIs loaded with carvedilol, and (ii) to control its release both in vitro and in vivo. At a polymeric concentration of 40% w/w, implant solutions were syringeable, injectable, and able to encapsulate carvedilol to a high degree (encapsulated drug% > 97%). When visualized using scanning electron microscopy (SEM), implants were found to have a dense thin surface atop porous sublayers. As for their in vitro evaluation, PLGA and PLA implants were able to maintain drug release over the course of 49 and 84 days, respectively. On the other hand, in vivo drug release from both implants was almost identical and lasted for only 42 days. This may be due to the overriding effect of the similar host environment at the injection site that diminished the effect of polymeric physiochemistry on phase inversion and drug release. Lastly, while the polymer-free drug/NMP solution completely released its drug content within the initial half hour in vitro, the formulation extended drug release in vivo. This could be due to a yet to be investigated interaction between carvedilol and NMP under in vivo conditions. These results cement the significance of formulating carvedilol loaded ISFIs for the management of chronic conditions.

Immediate versus delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to conduct a meta-analysis of randomized trials comparing the immediate versus delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events. DATA SOURCES: Cochrane Central, Embase, PubMed and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation. STUDY ELIGIBILITY CRITERIA: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated relative risks (RR) with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random effects model was employed in the R software. Moreover, we assessed the risk of bias of selected RCTs using version 2 of the Cochrane Risk of Bias Assessment Tool. RESULTS: We included 24 randomized trials comprising 2,507 participants, of whom 1,293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (RR 0.16; 95% CI 0.04-0.71; P = 0.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (RR 1.23; 95% CI 1.09-1.37; P < 0.01). CONCLUSIONS: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women.

Post pregnancy family planning in Latin America and the Caribbean analysis and strengths in training on immediate contraception post obstetric event by CLAP/PAHO.

Virtual courses developed by the Pan American Health Organization (PAHO) on family planning and immediate contraception post obstetric event (ICPOE) were launched in 2021 as training actions on ICPOE in the region. A total of 89,899 people enrolled in these courses; 36,494 (40.7%) of them enrolled in the course on ICPOE, and almost 60% of participants from Latin America passed the course. Moreover, 37% of participants were nurses, and 36% were physicians; most participants were from 20 to 39 years old. Eighty per cent completed the course in a week, and 89% had finished it by the 15th day. Students who passed the course expressed high overall satisfaction (95%), with ease of taking the course at home (63%) and at the workplace (33%) identified most frequently. Furthermore, practice training sessions (including simulation models) were conducted with 165 candidates to be trainers, physicians, and obstetricians. Approved trainers came from the Dominican Republic, Honduras, Bolivia, and Paraguay. CONCLUSION: There was evidence of the need for ICPOE training, and the innovative virtual courses developed by PAHO.

Enhanced long-acting simvastatin delivery via effervescent powder-carrying hollow microneedles and nanocrystal-loaded microneedles.

Hyperlipidemia and its associated cardiovascular complications are the major causes of mortality and disability worldwide. Simvastatin (SIM) is one of the most commonly prescribed lipid-lowering drugs for the treatment of hyperlipidemia by competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. However, the extensive first-pass metabolism leading to low oral bioavailability and frequent daily doses may lead to poor patient compliance and adverse effects caused by plasma fluctuations. To overcome these challenges, this work purposed two microneedle (MN) delivery strategies for the potential enhancement of SIM delivery. Firstly, nanocrystal (NC) formulations of SIM were investigated, followed by incorporation into a trilayer dissolving microneedle (DMN) design. Furthermore, a novel effervescent powder-carrying MN (EMN) design was developed to enhance intradermal delivery by incorporating the effervescent agents into the drug powder. Both MN approaches exhibited significantly improved permeation and in-skin deposition ability in the Franz cell study, with the ex vivo delivery efficiency of 64.33 ± 6.17 % and 40.11 ± 4.53 % for EMNs and DMNs, respectively. Most importantly, in vivo studies using a female Sprague-Dawley rat model confirmed the successful delivery of SIM from NCs-loaded DMNs (Cmax = 287.39 ± 106.82 ng/mL) and EMNs (Cmax = 203.05 ± 17.07 ng/mL) and maintain therapeutically relevant plasma concentrations for 15 days following a single application. The enhanced bioavailabilities of DMNs and EMNs were 24.28 % and 103.82 %, respectively, which were both significantly higher than that of conventional oral administration.

The Langmuir-Blodgett trough (Langmuir film balance) can be used to understand the stabilizer concentrations in aqueous nano- and microsuspensions.

Aqueous suspensions of poorly soluble, crystalline drug particles in the sub-micron range hold the ability to regulate the drug release for a defined period of time after e.g., intramuscular, or subcutaneous administration, working as an eminent formulation strategy for the preparation of long-acting injectables. Aqueous suspensions are typically prepared by top-down approaches, e.g., wet bead media milling or high-pressure homogenization, containing the active pharmaceutical compound and surfactants and/or polymers for stabilization purposes. Currently, the screening of proper stabilizers and adequate stabilizer concentration during formulation investigations is based on a trial-and-error approach with variations in combinations, concentrations, and/or ratios. To obtain a more efficient methodology during formulation screening, the present study investigated the correlation between the surface activity of two different surfactants, i.e., poloxamer 188 and polysorbate 20, by drop profile tensiometry and Langmuir trough monolayer, and the obtained sizes of cinnarizine particles as a tool to predict the optimal surfactant concentration to prepare physical stable nano- and microsuspensions. The obtained results demonstrated that the molecular area determined as the area per surfactant molecule measured in the Langmuir trough combined with the specific surface area of the prepared suspensions could be used to predict the suitable concentration of the surfactant based upon short-term stress stability data. The results further showed that higher concentrations of poloxamer 188 were necessary to stabilize the suspensions when compared to the needed concentration of polysorbate 20. In addition, it was observed that there was a need for a slightly higher surfactant concentration when the suspensions were milled with the smallest bead size of 0.5 mm instead of larger sizes of bead (0.8 and 1.0 mm), which could not be accounted for by differences in specific surface area.

Healthcare utilization and economics evaluation of paliperidone palmitate once-monthly in schizophrenia: a one-year, real-world, and retrospective mirror image study in China.

Background: Investigation and analysis of the changes in healthcare resources and burden of schizophrenia in the real world before and after switching from oral antipsychotics (OAPs) to paliperidone palmitate once-monthly (PP1M) could provide evidence to clinicians and patients for choosing treatment modality and data support for health policy optimization. Methods: The first dosage of PP1M was set as mirror point, and patients with mirror point between January 2020 and June 2022 were recruited in the study. The differences in treatment patterns, healthcare resource utilization, and costs within one year before and after the mirror point were compared. Results: A total of 72 patients transitioning from OAPs to PP1M (mean age, 35.33 years; 43.06% female) were included in the study. Of the 72 patients, the application of PP1M resulted in a significant reduction in the hospitalization times, emergency room visits, and direct medical costs (P < 0.001), while the pharmacy cost and total cost increased by 222.57% (P < 0.001) and 16.35% (P < 0.001), respectively; PP1M accounted for 88.48% of the pharmacy cost. For patients with ≥1 hospitalization during the OAPs phase (n = 25), the number of hospitalizations, hospitalization days and hospitalization expenses decreased by more than 90% (P < 0.001). Total one-year expenses decreased by 37.67% (P < 0.001), and pharmacy expenses increased by 185.21% (P < 0.001). For patients with no hospitalizations during the OAPs phase (n = 47), emergency and outpatient visits decreased by 70% (P < 0.001) and 30.27% (P < 0.05), respectively, while the total cost increased by 117.56% (P < 0.001), and the pharmacy cost increased by 260.15% (P < 0.001) after initiation of PP1M treatment. Conclusion: After the transition to PP1M, the number of hospitalizations and outpatient and emergency department visits reduced, and healthcare resources were conserved. Switching to PP1M may be more economically beneficial for patients with prior hospitalizations while on OAP regimens. The high price of PP1M might be an obstacle to its widespread use.

Virological History Predicts Non-sustained Viral Suppression with Long-Acting Cabotegravir and Rilpivirine Therapy, independent of Pharmacokinetic Parameters.

BACKGROUND: This study aimed to investigate factors contributing to non-sustained viral suppression, including intermittent viremia and persistent low-level viremia, during cabotegravir (CAB) plus rilpivirine (RPV) long-acting (LA) injectable therapy, with a focus on pharmacokinetics (PK). METHODS: A prospective cohort study was conducted on people with HIV (PWH) transitioning from stable oral antiretroviral therapy (ART) to bimonthly CAB+RPV LA. Standardized follow-up included close monitoring through blood sampling for plasma HIV-1 viral load (VL) and multiple plasma drug concentrations measurements to analyze the connection between PK parameters and virologic outcomes. RESULTS: Among 173 patients with a median (IQR) follow-up of 11.1(7.1-13.2) months and 789 pre-dose measurements, 38.7% experienced VL≥20 copies/mL, and 16.2% had levels ≥50 copies/mL. Intermittent viremia occurred in 34.7% of patients, and persistent low-level viremia in 4%. Virological failure developed in two cases. Predictors of non-sustained viral suppression included VL at HIV diagnosis [AHR: 1.49 per log10 VL, 95% CI: 1.04-2.12, P =.027], detectable viremia on oral ART [AHR: 2.45, 95% CI: 1.29-4.65, P =.006], and the level of viral suppression at transition [AHR: 0.38, 95% CI: 0.19-0.75, P =.004]. We found a significant association between low trough concentrations of CAB and RPV and episodes of detectable viremia exceeding 50 copies/mL. However, none of the assessed PK covariates predicted non-sustained viral suppression in multivariable models. CONCLUSION: Non-sustained viral suppression in PWH transitioning from stable oral ART to CAB+RPV LA was linked to pre-existing factors before transition. Higher VL pre-ART and incomplete suppression on oral therapy increased the risk, independent of PK parameters.

Effects of structured contraceptive counseling in young women: Secondary analyses of a cluster randomized controlled trial (the LOWE trial).

INTRODUCTION: Unwanted pregnancy constitutes a huge health issue. Long-acting reversible contraception (LARC) are the most effective methods for preventing unwanted pregnancy, especially among young women. This study evaluates the intervention effect of structured contraceptive counseling on the choice, initiation, and use of LARC in young women. MATERIAL AND METHODS: This is a secondary analysis of women aged 18-25, enrolled in a multicenter cluster randomized controlled trial performed in abortion, youth, and maternal health clinics across the Stockholm County in Sweden. Clinics were randomized (1:1) to provide structured contraceptive counseling (intervention) or standard counseling (control). Surveys were administered at the clinic visit and follow-ups at 3, 6, and 12 months. Primary outcome focused on the choice of LARC among women 18-25 years of age. Secondary outcomes included initiation, and use of LARC at 3 and 12 months, satisfaction with the counseling received and information on extended use of combined hormonal contraceptives. The study was registered at Clinicaltrials.gov (NCT03269357). RESULTS: From September 2017 to May 2019, 770 women aged 18-25 years from 28 clinics/clusters were recruited. There was a significant intervention effect on LARC choice (aOR 5.96, 95% CI 3.25-10.94), initiation (aOR 4.43, 95% CI 2.32-8.46), and use at 12 months (aOR 2.21, 95% CI 1.31-3.73). The odds of LARC choice at pre-booked visits were higher and more women received information about extended-use regimen for short-acting reversible contraception in the intervention group compared to the control group. The intervention package was well received, but with higher satisfaction at pre-booked compared to drop-in visits. CONCLUSIONS: Our study demonstrates that comprehensive structured contraceptive counseling significantly increases LARC choice, initiation and use, with high satisfaction among young participants, especially at pre-booked visits. The results highlight an approach that merits implementation to increase quality of care in contraceptive services, to enhance reproductive health for adolescents and young adults.

Long-Acting Injectable Antipsychotic Medication Use in Youth: A Systematic Review of the Literature Along with MedWatch Safety Data and Prescriber Attitudes.

Objectives: Long-acting injectable (LAI) antipsychotic medications are being prescribed to children and adolescents along a broad age range from 2 to 17 years old. However, there is no U.S. Food and Drug Administration (FDA) approved indication for the use of any LAI in a pediatric population. The goal of this article is to perform a systematic literature review regarding the use of LAIs in a pediatric population, to obtain pediatric LAI safety data, and to survey prescriber attitudes regarding LAI use in youth. Methods: A search for relevant articles between June 1986 and June 2021 was conducted. Safety data were obtained from FDA MedWatch postmarketing adverse event reports regarding LAI use in children and adolescents. A survey of practicing Child and Adolescent Psychiatrists in Wisconsin was done regarding the use of LAIs in youth. Results: The predominant reasons for LAI use in youth were illness severity and treatment noncompliance. Twenty-six of 30 identified studies and reports favored LAI use in youth, but were of low to very low quality. Overall, 587 FDA MedWatch reports between June 1986 and June 2021 were identified. Most adverse events occurred in modest numbers. Extrapyramidal symptoms accounted for 18% of all MedWatch reports, neuroleptic malignant syndrome accounted for 3% of all reports, and deaths accounted for 2% of all reports. The concern for safety was reflected in prescriber survey results along with a recognition that LAIs can be helpful to target severe psychiatric symptoms and address treatment noncompliance. Conclusions: No randomized controlled studies were found. Identified published studies and reports were of low to very low quality. However, it appeared reasonable that the use of LAIs in a select group of pediatric patients can be helpful to target severe psychiatric symptoms and to enhance treatment compliance.

The pathway to delivering injectable CAB for HIV prevention: strategies from global PrEP leaders leveraging an adapted version of the Intervention Scalability Assessment Tool (ISAT).

BACKGROUND: Longer-acting cabotegravir (CAB) is a novel, safe, and efficacious pre-exposure prophylaxis (PrEP) for HIV prevention. As we near a time for CAB scale-up, the experience of global leaders in PrEP research and implementation can be leveraged to identify optimal strategies for scaling and integrating CAB into existing PrEP infrastructure worldwide. METHODS: We recruited leaders of HIV prevention clinical trials and large PrEP programs through a combination of purposive and snowball sampling for participation in individual interviews. We conducted interviews using a semi-structured guide that compared CAB to oral PrEP and sought perspectives on barriers and strategies for CAB scale-up. Interviews were conducted virtually, audio recorded, and transcribed. We used thematic analysis, grounded in an adapted version of the Intervention Scalability Assessment Tool (ISAT), to identify critical elements for optimizing delivery of CAB. RESULTS: From October 2021 to April 2022, we interviewed 30 participants with extensive experience in PrEP research, care, and programming. Participants worked in all seven WHO regions and reported a median of 20 years working in HIV and 10 years in PrEP. Participants agreed that CAB was efficacious and discrete, therefore having the potential to address current concerns about oral PrEP adherence and stigma. Participants indicated direct and indirect costs for provider training, expansion of existing medical infrastructure, and the current medication cost of CAB as major concerns for roll out. The true cost to the end-user and health system were unknown. There were some conflicting strategies on how to best address product targeting, presentation of efficacy, and timing of product availability with scale-up. Some thought that targeting CAB for the general population could normalize PrEP and decrease stigma, while others thought that prioritizing key populations could optimize impact by targeting those with highest risk. Overall, participants emphasized that to ensure successful CAB scale-up, communities and stakeholders must be involved at every stage of planning and implementation. CONCLUSIONS: Our evaluation found that although there is a clear and urgent need for additional HIV PrEP options beyond daily oral PrEP, CAB scale-up must be thoughtful, flexible, and based in lessons learned from oral PrEP rollout.

Preventing recurrence of endometriosis-related pain by means of long-acting progestogen therapy: the PRE-EMPT RCT.

Background: Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Recurrence of symptoms following an operation is common. Although hormonal treatment can reduce this risk, there is uncertainty about the best option. Objectives: To evaluate the clinical and cost-effectiveness of long-acting progestogen therapy compared with the combined oral contraceptive pill in preventing recurrence of endometriosis-related pain and quality of life. Design: A multicentre, open, randomised trial with parallel economic evaluation. The final design was informed by a pilot study, qualitative exploration of women's lived experience of endometriosis and a pretrial economic model. Setting: Thirty-four United Kingdom hospitals. Participants: Women of reproductive age undergoing conservative surgery for endometriosis. Interventions: Long-acting progestogen reversible contraceptive (either 150 mg depot medroxyprogesterone acetate or 52 mg levonorgestrel-releasing intrauterine system) or combined oral contraceptive pill (30 µg ethinylestradiol, 150 µg levonorgestrel). Main outcome measures: The primary outcome was the pain domain of the Endometriosis Health Profile-30 questionnaire at 36 months post randomisation. The economic evaluation estimated the cost per quality-adjusted life-years gained. Results: Four hundred and five women were randomised to receive either long-acting reversible contraceptive (N = 205) or combined oral contraceptive pill (N = 200). Pain scores improved in both groups (24 and 23 points on average) compared with preoperative values but there was no difference between the two (adjusted mean difference: -0.8, 95% confidence interval -5.7 to 4.2; p = 0.76). The long-acting reversible contraceptive group underwent fewer surgical procedures or second-line treatments compared with the combined oral contraceptive group (73 vs. 97; hazard ratio 0.67, 95% confidence interval 0.44 to 1.00). The mean adjusted quality-adjusted life-year difference between two arms was 0.043 (95% confidence interval -0.069 to 0.152) in favour of the combined oral contraceptive pill, although this cost an additional £533 (95% confidence interval 52 to 983) per woman. Limitations: Limitations include the absence of a no-treatment group and the fact that many women changed treatments over the 3 years of follow-up. Use of telephone follow-up to collect primary outcome data in those who failed to return questionnaires resulted in missing data for secondary outcomes. The COVID pandemic may have affected rates of further surgical treatment. Conclusions: At 36 months, women allocated to either intervention had comparable levels of pain, with both groups showing around a 40% improvement from presurgical levels. Although the combined oral contraceptive was cost-effective at a threshold of £20,000 per quality-adjusted life-year, the difference between the two was marginal and lower rates of repeat surgery might make long-acting reversible contraceptives preferable to some women. Future work: Future research needs to focus on evaluating newer hormonal preparations, a more holistic approach to symptom suppression and identification of biomarkers to diagnose endometriosis and its recurrence. Trial registration: This trial is registered as ISRCTN97865475. https://doi.org/10.1186/ISRCTN97865475. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/114/01) and is published in full in Health Technology Assessment; Vol. 28, No. 55. See the NIHR Funding and Awards website for further award information. The NIHR recognises that people have diverse gender identities, and in this report, the word 'woman' is used to describe patients or individuals whose sex assigned at birth was female, whether they identify as female, male or non-binary.

Endometriosis is a condition where cells similar to ones that line the womb are found elsewhere in the body. Endometriosis affects 1 in 10 women, many of whom have surgery for persistent pain. Unfortunately, symptoms often return and some women will need repeat operations. Hormonal contraceptives can prevent the return of endometriosis-related pain: either long-acting reversible contraceptives (injections or a coil, fitted inside the womb) or the combined oral contraceptive pill (often called 'the pill'). We do not know which is the best option. The aim of this trial was to find out which of these two hormone treatments was more effective in terms of symptom relief, avoidance of further surgery and costs. Four hundred and five women with endometriosis, who were not intending to get pregnant, participated in a clinical trial. Half of the participants took long-acting reversible contraceptives, and the other half took the pill for 3 years following endometriosis surgery. The choice of treatment was made at random by a computer to ensure a fair comparison, although those allocated to the long-acting contraceptive could choose between injections or the coil. Participants completed questionnaires about their symptoms and life quality at intervals up to 3 years. Both treatments were equally good at reducing pain but more women using the pill had repeat operations. The pill was a little more costly overall but associated with a slightly higher quality of life. Both treatments are equally effective in reducing pain up to 3 years after surgery for endometriosis. The differences in costs are small and the choice of treatment should be based on personal preference.

The association between socio-economic deprivation and receipt of long-acting reversible contraception at a single clinic visit.

OBJECTIVES: To determine the relationship between area deprivation index (ADI) and obtaining single-visit long-acting reversible contraception (LARC). STUDY DESIGN: We utilized Poisson regression to determine the association between area deprivation and single-visit LARC insertion within a state-wide healthcare system between 2019-2021. RESULTS: Among our cohort (N = 4417), 68.60% of patients desiring LARC obtained single-visit LARC. Participants living in high deprivation areas were less likely to receive single-visit LARC (aRR 0.72, 95% CI 0.65-0.80). CONCLUSIONS: Living in areas of high deprivation is independently negatively associated with obtaining a single-visit LARC. IMPLICATIONS: While access to single-visit LARC should be universally improved, reducing barriers for patientswith a higher ADI may help limit inequities in reproductive healthcare.

Perspectives and Preferences of People with Type 2 Diabetes for the Attributes of Weekly Insulin.

INTRODUCTION: Daily insulin administration can be burdensome for people with type 2 diabetes (PwT2D) and can impact treatment adherence. This study investigated preferences for once-weekly, long-acting basal insulin for treatment of PwT2D. METHODS: An online discrete-choice experiment was administered to PwT2D in the USA. Qualitative interviews informed the selection of six attributes: reduction in A1c level after 6 months, amount of time spent in optimal blood sugar range each day, number of serious low blood sugar events, number of nighttime low blood sugar events, change in weight because of the insulin over 6 months, and frequency of administration. Each participant completed eight questions offering a choice between two long-acting insulins; questions varied according to an experimental design. A fixed treatment choice question asked about preferences for daily versus weekly insulin, holding other treatment features constant. Data were analyzed using random-parameters logit models, and heterogeneity was explored through subgroup analyses. RESULTS: Four hundred sixty-six PwT2D completed the survey (mean age, 57; mean A1c, 7.5%; 59.0% female); 33.3% of these were currently on a basal/bolus regimen, 34.3% used basal only, and 32.4% were insulin naive. Respondents placed the most importance on avoiding a 10-pound weight change and equal importance on the largest change in the number of serious and nighttime low blood sugar events per year and achieving the longest time in range included in the choice questions. There was significant heterogeneity in preferences by experience: insulin-naive respondents had stronger preferences for scheduled and flexible weekly insulin over daily insulin; 67.6% preferred flexible weekly over daily insulin, all else being equal. CONCLUSION: PwT2D valued insulin efficacy and reducing treatment-related adverse events, with heterogeneity in the relative importance of administration frequency. All else being equal, respondents preferred weekly over daily basal insulin. These findings provide insights into the preferences of PwT2D considering weekly long-acting insulin.

Advances in insulin: a review of icodec as a novel once-weekly treatment for type 2 diabetes.

Type 2 diabetes (T2D) is a chronic condition that requires not only a team-based approach but also substantial self-management by those affected. Patient-clinician barriers such as lack of educational resources, hesitancy in initiation of therapy, concerns over treatment-related side effects, frequency of dosing, and the establishment of treatment goals, can prevent a patient from achieving optimal glycemic management. Recently, advances in diabetes technology and insulin formulations have helped to address some of these concerns. Insulin icodec, the first once-weekly basal insulin analog, has demonstrated efficacy and safety comparable to traditional basal insulin formulations. Since clinicians and patients may benefit from a once-weekly therapy, this review sought to evaluate the potential clinical implications of insulin icodec. A literature search was performed using PubMed, Google Scholar, and ClinicalTrials.gov up to 31 January 2024. Key search terms such as once-weekly basal insulin, icodec, and ONWARDS were utilized to compile relevant publications. Further, studies involving patients living with T2D on once-weekly insulin icodec compared with once-daily basal insulin were considered for this review. Findings from this review suggest insulin icodec can offer a reduced dosing frequency that may improve medication adherence, provide effective glycemic management, and a comparable safety profile to existing basal insulins. In summary, insulin icodec may help to remove patient-clinician barriers associated with suboptimal glycemic management with its once-weekly dosing schedule. Clinicians can further support a patient's ability to self-manage the disease through continued monitoring and guidance on the use of icodec.

Type 2 diabetes can be a challenging illness to manage since patients and clinicians often encounter obstacles such as limited access to educational resources, concerns about starting treatment, worries about side effects, and inconvenient dosing schedules. While recent advancements in diabetes technology and insulin formulations have helped, there's still a need for more information to ease concerns about treatment. Insulin icodec, an insulin taken just once a week, has shown to be just as effective and safe as traditional daily insulins. Since both clinicians and patients may benefit from the use of a once-weekly therapy, we evaluated the possible impact of insulin icodec on clinical practice and patient outcomes. To do this, researchers collected and read scientific articles published online on or before 31 January 2024. Key search terms were used during the online search. After a review of the articles, the authors found that insulin icodec could not only simplify treatment by reducing the number of injections needed but also control blood sugar as effectively as existing insulin options. In summary, insulin icodec has the potential to address many of the challenges associated with managing type 2 diabetes, offering a simpler dosing schedule that could improve adherence and overall blood sugar. Continued support and guidance from clinicians and interdisciplinary team members can further enhance a patient's ability to manage their diabetes effectively with insulin icodec.

Single inhaler combination inhaled corticosteroid-formoterol as both maintenance and reliever (SMART) compared with a step up of treatment with fixed-dose inhaled corticosteroid-long-acting ß2-agonist maintenance with a short-acting ß2-agonist as reliever in adolescents and adults with poorly controlled asthma in Colombia: a cost-utility analysis.

OBJECTIVE: The aim of the present study was to determine the cost-utility of single inhaler combination inhaled corticosteroid and a long-acting ß2-agonist (ICS/LABAs) as both maintenance and reliever (SMART) compared with a step-up maintenance treatment with a fixed medium to high dose of ICS combined with LABA and a short-acting ß2-agonist (SABA) as reliever (ICS-LABA maintenance plus SABA) among patients aged 12 years or more with poorly controlled asthma in Colombia. METHODS: A Markov-type model was developed to estimate the costs and health outcomes of a simulated cohort of patients aged 12 years or more with uncontrolled asthma treated for 12 months. The main effectiveness data were obtained from a recent meta-analysis. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). RESULTS: The base-case analysis showed that the budesonide/formoterol (BUD/FORM) SMART strategy was associated with lower overall treatment costs (US $3,062.37 vs. $4,462.02 average cost per patient over 12 months) and the greatest gain in QALYs (0.8511 vs. 0.8258 QALYs on average per patient over 12 months) compared with ICS-LABA maintenance plus SABA at step 4, thus leading to dominance. CONCLUSIONS: In patients aged 12 years or more with uncontrolled asthma at GINA step 3 or 4, the BUD/FORM SMART strategy at either step 3 or 4 is cost-effective compared with the ICS-LABA maintenance plus SABA at step 4 strategy, because it shows a greater gain in QALYs at lower total treatment costs.