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Discontinuation of buprenorphine as a medication for opioid use disorder (MOUD) necessitates careful tapering to reduce opioid withdrawal and relapse. With a half-life of 43-60 days, buprenorphine extended-release formulation (BUP-XR) may provide gradual taper, facilitating successful treatment discontinuation. This study sought to understand experiences with stopping BUP-XR as described on social media. Reddit records (March 2018 to August 2022) were evaluated for the presence of referents to BUP-XR using parallel criteria based on predefined keywords and subreddit context. The keyword-based search identified records mentioning \"Sublocade\" (or similar search strings) regardless of subreddit. The subreddit context-based criteria identified records that were created within the r/Sublocade subreddit. Records that included reference to BUP-XR were further evaluated for mentions of treatment cessation using predefined keywords. A 50% randomized sample was then selected for qualitative analysis by a single experienced subject matter expert. Records were manually coded to validate references to BUP-XR and MOUD cessation and were evaluated for additional predefined constructs related to opioid craving and withdrawal, BUP-XR and other MOUD treatment details, and other nonmedical opioid use. Emergent constructs related to cessation-related knowledge, attitudes, behaviors, and experiences were also identified as part of the data coding and annotation process. Of 6082 total, 3041 records were coded and analyzed; most (n=2692, 97.4%) referenced BUP-XR, of which, 43.8% (n=1179) referenced cessation of BUP-XR as MOUD. Many individuals shared information about prior use of MOUD, primarily transmucosal buprenorphine (185 records/63 authors), including the use of BUP-XR to taper off buprenorphine. Individuals provided details of their BUP-XR treatment experiences before and following cessation. Only 102 (8.7%) records mentioned opioid withdrawal; 1 record mentioned craving. Withdrawal experiences with BUP-XR were generally described as less intense than other drugs, although at least mild withdrawal was seen as an inevitable part of cessation. Thematic analysis revealed discussions of polypharmacy with transmucosal buprenorphine and the importance of personalized treatment and patient agency. There was nuanced discussion of treatment cessation using BUP-XR on Reddit, with individuals describing detailed courses of treatment and treatment experiences. Few records mentioned opioid withdrawal, and when discussed, withdrawal experiences during cessation of BUP-XR were generally described as less intense than withdrawal experiences with other drugs. These results suggest that social media, such as Reddit, can be leveraged to explore perspectives on treatment and recovery among individuals with opioid use disorder. Overall, this study provides insights into real-world patient experiences with cessation of BUP-XR and is consistent with prior case series; however, more research is needed to understand the course of opioid use disorder following cessation of BUP-XR as well as other MOUD.

Delayed‐release and extended‐release methylphenidate hydrochloride (JORNAY PM®) is a novel capsule formulation of methylphenidate hydrochloride, used to treat attention deficit hyperactivity disorder in patients 6 years and older. In this paper, we develop a Level A in vitro‐in vivo correlation (IVIVC) model for extended‐release methylphenidate hydrochloride to support post‐approval manufacturing changes by evaluating a point‐to‐point correlation between the fraction of drug dissolved in vitro and the fraction of drug absorbed in vivo. Dissolution data from an in vitro study of three different release formulations: fast, medium, and slow, and pharmacokinetic data from two in vivo studies were used to develop an IVIVC model using a convolution‐based approach. The time‐course of the drug concentration resulting from an arbitrary dose was considered as a function of the in vivo drug absorption and the disposition and elimination processes defined by the unit impulse response function using the convolution integral. An IVIVC was incorporated in the model due to the temporal difference seen in the scatterplots of the estimated fraction of drug absorbed in vivo and the fraction of drug dissolved in vitro and Levy plots. Finally, the IVIVC model was subjected to evaluation of internal predictability. This IVIVC model can be used to predict in vivo profiles for different in vitro profiles of extended‐release methylphenidate hydrochloride.

Purpose: To discuss new therapeutic strategies for chemotherapy-induced nausea and vomiting (CINV) involving 5-hydroxytryptamine type 3 (5HT3)-receptor antagonists (RAs). Summary: CINV remains poorly controlled in patients receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC); nausea and delayed-phase CINV (24–120 hours after chemotherapy) are the most difficult to control. National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO) antiemesis-guideline recommendations for HEC include a four-drug regimen (5HT3 RA, neurokinin 1 [NK1] RA, dexamethasone, and olanzapine). For some MEC regimens, a three-drug regimen (5HT3 RA, NK1 RA, and dexamethasone) is recommended. While 5HT3 RAs have dramatically improved CINV in the acute phase (0–24 hours after chemotherapy), their efficacy declines in the delayed phase. Newer formulations have been developed to extend 5HT3-RA efficacy into the delayed phase. Granisetron extended-release subcutaneous (GERSC), the most recently approved 5HT3 RA, provides slow, controlled release of therapeutic granisetron concentrations for ≥5 days. GERSC is included in the NCCN and ASCO guidelines for MEC and HEC, with NCCN-preferred status for MEC in the absence of an NK1 RA. Efficacy and safety of 5HT3 RAs in the context of guideline-recommended antiemetic therapy are reviewed. Conclusion: Recent updates in antiemetic guidelines and the development of newer antiemetics should help mitigate CINV, this dreaded side effect of chemotherapy. GERSC, the most recently approved 5HT3-RA formulation, is indicated for use with other antiemetics to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of MEC and anthracycline–cyclophosphamide combination-chemotherapy regimens.

Introduction Attention‐deficit/hyperactivity disorder (ADHD) is associated with impairments related to peer relations (PR) and social activities (SA). The objective of this post hoc analysis was to assess the degree to which viloxazine extended‐release (viloxazine ER; viloxazine extended‐release capsules; Qelbree®) improves clinical assessments of PR and SA in children and adolescents with ADHD. Methods Data were used from four Phase III placebo‐controlled trials of 100 to 600 mg/day of viloxazine ER (N = 1354; 6–17 years of age). PR and SA were measured with the Peer Relations content scale of the Conners 3rd Edition Parent Short Form's Peer Relation content scale (C3PS‐PR) and the Social Activities domain of the Weiss Functional Impairment Rating Scale‐Parent Report's (WFIRS‐P‐SA) at baseline and end of study. ADHD symptoms were assessed weekly with the ADHD Rating Scale, 5th Edition. The analyses relied on the general linear mixed model with the subject as a random effect. Results Improvement in C3PS‐PR (p = .0035) and WFIRS‐P‐SA (p = .0029) scores were significantly greater in subjects treated with viloxazine ER compared with placebo. When using measures of clinically meaningful response, the C3PS‐PR responder rate was significantly higher for viloxazine ER (19.2%) compared with placebo (14.1%) and the difference was statistically significant (p = .0311); the Number Needed to Treat (NNT) was 19.6. The WFIRS‐P‐SA responder rate was significantly higher for viloxazine ER (43.2%) compared with placebo (28.5%) and the difference was statistically significant (p < .0001); the NNT was 6.8. The standardized mean difference effect size for both PR and SA was 0.09. Conclusions Viloxazine ER significantly reduces the impairment of PR and SA in children and adolescents with ADHD. Although its effects on PR and SA are modest, many ADHD patients can be expected to achieve clinically meaningful improvements in PR and SA with viloxazine ER treatment for longer than 6 weeks. KEY POINTS Children and adolescents with attention‐deficit/hyperactivity disorder (ADHD) commonly experience deficits associated with peer relations (PR) and social activities (SA). Viloxazine extended‐release (viloxazine ER) is approved for the treatment of ADHD in children and adolescents. In a post hoc analysis of pooled data from four pediatric, Phase III, placebo‐controlled trials, viloxazine ER significantly improved the outcome in assessments of both PR and SA in children and adolescents with ADHD.

Advances in nanomedicine have become indispensable for targeted drug delivery, early detection, and increasingly personalized approaches to cancer treatment. Nanoparticle-based drug-delivery systems have overcome some of the limitations associated with traditional cancer-therapy administration, such as reduced drug solubility, chemoresistance, systemic toxicity, narrow therapeutic indices, and poor oral bioavailability. Advances in the field of nanomedicine include \"smart\" drug delivery, or multiple levels of targeting, and extended-release drug-delivery systems that provide additional methods of overcoming these limitations. More recently, the idea of combining smart drug delivery with extended-release has emerged in hopes of developing highly efficient nanoparticles with improved delivery, bioavailability, and safety profiles. Although functionalized and extended-release drug-delivery systems have been studied extensively, there remain gaps in the literature concerning their application in cancer treatment. We aim to provide an overview of smart and extended-release drug-delivery systems for the delivery of cancer therapies, as well as to introduce innovative advancements in nanoparticle design incorporating these principles. With the growing need for increasingly personalized medicine in cancer treatment, smart extended-release nanoparticles have the potential to enhance chemotherapy delivery, patient adherence, and treatment outcomes in cancer patients.

Patients with glycogen storage disease type Ia (GSDIa) are prone to hypoglycemia. Uncooked cornstarch (CS) is the treatment, but maintaining nighttime blood glucose levels is still difficult. The study enrolled patients with GSDIa to investigate the benefits of bedtime extended release CS (ER-CS, Glycosade®) versus regular CS. The daytime CS schedule was not altered. A 7-day continuous glucose monitoring (CGM) was performed at the baseline and 12 weeks after using ER-CS. Biochemical profile, sleep quality (Pittsburgh Sleep Quality Index, PSQI), and quality of life (SF-36 questionnaire) were measured at the baseline and 24 weeks after using ER-CS. Nine patients (9 to 33 years of age) were enrolled. Compared with the baseline (80.0 ± 6.33 mg/dL), the 12-week evaluations revealed higher mean morning glucose levels (86.5 ± 8.26 mg/dL, p = 0.015). Twenty-four weeks after the use of bedtime ER-CS, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both decreased (from 69.3 ± 77.8 to 41.1 ± 40.4 U/L and from 78.8 ± 99.6 to 37.8 ± 28.81 U/L, respectively, p = 0.013 for both analyses), and sleep and fasting time both elongated (from 7.8 ± 0.87 to 8.6 ± 1.02 h and from 6.5 ± 1.22 to 7.6 ± 1.02 h, respectively, p = 0.011 for both analyses). The mean PSQI score in the five adult patients decreased significantly (from 5.8 ± 1.29 to 3.0 ± 1.71, p = 0.042). This study provides evidence of clinically meaningful improvements by shifting only bedtime regular CS to ER-CS in patients with GSDIa. As ER-CS is considerably more expensive than regular CS, this approach presents a cost-effective alternative.

High intra-patient variability (IPV) of tacrolimus levels is associated with poor long-term outcome after transplantation. We aimed to evaluate whether the number of regularly prescribed medications is associated with the tacrolimus IPV. We have studied 152 kidney transplant recipients (KTRs) with mean post-transplant time of 6.0 ± 3.1 years. The coefficient of variation (CV) as a measure of IPV was calculated in each individual patient. Data concerning the type and number of currently prescribed medications were collected. The participants were divided into four groups, based on the number of regularly prescribed drugs (≤3, 4–6, 7–9, ≥10 drugs, respectively). There was an increasing trend for median CV, proportional to the increasing number of medications [group 1: 0.11 (interquartile range, 0.08–0.14), group 2: 0.14 (0.01–0.17), group 3: 0.17 (0.14–0.23), group 4: 0.17 (0.15–0.30); p value for trend = 0.001]. Stepwise backward multivariate regression analysis revealed that the number of medications [partial correlation coefficient (rpartial) = 0.503, p < 0.001] independently influenced the tacrolimus IPV. Concomitant steroid or diuretics use increased IPV only in Advagraf-treated KTRs, whereas proton-pump inhibitor or statin use increased IPV in the Prograf group but not in the Advagraf group. A large number of concomitant medications significantly increases the tacrolimus IPV in stable KTRs.

The poly(ADP‐ribose) polymerase‐1/2 inhibitor veliparib is active against tumors deficient in homologous DNA damage repair. The pharmacokinetics and safety of veliparib extended‐release (ER) were evaluated in patients with advanced solid tumors. This phase I study assessed veliparib‐ER up to 800 mg once daily or 600 mg twice daily. Dose‐limiting toxicities (DLTs), recommended phase II dose (RP2D), and maximum tolerated dose (MTD) were assessed in cycle 1 and safety/tolerability during continuous administration (28‐day cycles). Seventy‐one patients (n = 53 ovarian, n = 17 breast, n = 1 prostate carcinoma) received veliparib; 50 had deleterious breast cancer susceptibility (BRCA) gene mutations. Single‐dose veliparib‐ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration‐time curve compared with veliparib immediate‐release (IR). Three patients experienced DLTs (grade 2: asthenia; grade 3: nausea/vomiting, seizure). RP2D and MTD for veliparib‐ER were 400 mg BID. The most frequent adverse events (AEs) were nausea (78.9%) and vomiting (50.7%). The most common grade 3/4 treatment‐related AEs were as follows: thrombocytopenia (7.0%), nausea, and anemia (4.2% each). Overall, 12 (27.3%) patients with ovarian and 10 (62.5%) patients with breast carcinoma had a partial response. Veliparib‐ER, versus veliparib‐IR, exhibited an improved pharmacokinetic profile and was well tolerated in patients with ovarian and BRCA‐mutated breast cancers. Veliparib is active against tumors deficient in homologous DNA damage repair. This phase I study assessed the pharmacokinetics and safety of veliparib extended‐release (ER) versus veliparib immediate‐release (IR) in patients with advanced solid tumors. Veliparib‐ER, versus veliparib‐IR, exhibited an improved pharmacokinetic profile and was well tolerated in patients with ovarian and breast cancer susceptibility gene‐mutated breast cancers.

This retrospective analysis evaluated chemotherapy-induced nausea and vomiting (CINV)-related hydration needs with palonosetron or granisetron extended-release subcutaneous (GERSC), approved in 2016 for CINV prevention. At a community practice, CINV-related hydration per chemotherapy cycle was determined following highly (HEC) or moderately emetogenic chemotherapy (MEC) and a guideline-recommended antiemetic regimen: neurokinin 1 receptor antagonist, dexamethasone and either palonosetron only, GERSC only, or palonosetron switched to GERSC. Palonosetron-only patients (n = 93) had a significantly higher mean (standard deviation) hydration rate (0.9 [1.1]) than GERSC-only patients (n = 91) (0.3 [0.6]) (p < 0.0001). Switched patients' (n = 48) hydration rates were significantly higher in the HEC subgroup with palonosetron (0.7 [1.2]) versus GERSC (0.5 [1.0]) (p = 0.028). GERSC in a three-drug antiemetic regimen may reduce hydration needs following HEC or MEC.

HLD200 is the first evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) designed to delay initial release of MPH and provide treatment effects throughout the day and into the evening for individuals with attention-deficit/hyperactivity disorder (ADHD). Because DR/ER-MPH is uniquely absorbed in the colon, it cannot be substituted for other ADHD medications on a milligram-per-milligram basis. To provide clinicians with a target dose range for DR/ER-MPH when transitioning patients from a prior ADHD medication, dose conversion ratios (DCRs) between prior medication doses and optimized doses of DR/ER-MPH were determined post hoc from a pivotal Phase III study of children (aged 6–12 years) with ADHD. DR/ER-MPH doses were optimized over a 6-week open-label period. DCRs were calculated between optimized doses of DR/ER-MPH at week 6 and prior stable doses of ADHD medication. Mean DCRs ranged from 1.8 to 4.3 for optimized DR/ER-MPH dose versus previous stable dose for individuals taking an extended-release stimulant monotherapy. DCRs for those taking an immediate-release stimulant monotherapy ranged from 4.7 to 6.0. In a Phase III trial of children with ADHD, optimized doses of DR/ER-MPH were higher than doses of prior ADHD medications, but the adverse event profile was consistent with that of other MPHs. Higher DCRs compared with those predicted by bioavailability differences are consistent with a predicted dose-dependent duration of effect for DR/ER-MPH: with increasing doses, absorption is extended but with an attenuated increase in Cmax compared with MPH formulations absorbed in the upper bowel. These data may help guide clinicians to optimize DR/ER-MPH doses. ClinicalTrials.gov identifier: NCT02493777.