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Simple Summary: Carbon dots (CDs) are carbon-based nanomaterials with versatile applications, including fluorescence imaging, drug and gene transport, drug delivery, medical diagnosis, and biosensing. In this study, we successfully synthesized various CDs without significantly impacting the cell viability of cancer cells, which suggests the potential for future bioimaging and drug delivery applications. These findings contribute to advancing the potential of CDs in various biomedical research contexts. Backgroung: The rising complexity and associated side effects of cancer treatments highlight the need for safer and more effective therapeutic agents. Carbon-based nanomaterials such as CDs have been gaining prominence for their unique characteristics, opening avenues for diverse applications such as fluorescence imaging, drug and gene transport, controlled drug delivery, medical diagnosis, and biosensing. Despite promising advancements in research, it remains imperative to scrutinize the properties and potential cytotoxicity of newly developed CDs, ensuring their viability for these applications. Methods: We synthesized four N-doped CDs through a hydrothermal method. Cell viability assays were conducted on A549 and UM-UC-5 cancer cells at a range of concentrations and incubation times, both individually and with the chemotherapeutic agent 5-fluorouracil (5-FU). Results: The obtained results suggest that the newly developed CDs exhibit suitability for applications such as bioimaging, as no significant impact on cell viability was observed for CDs alone. [ABSTRACT FROM AUTHOR]

Hypoparathyroidism is a disease characterized by inadequate or absent parathyroid hormone (PTH) levels. It manifests with hypocalcemia, hyperphosphatemia, and elevated urinary fractional excretion of calcium. The conventional therapy with calcium supplementation and active vitamin D analogs is limited by the pill burden, unstable calcium concentrations, and significant renal and bone complications. Hence, the development of replacement therapies utilizing PTH or PTH-related receptor modulators has emerged as a promising therapeutic avenue. rhPTH (1-84) (NATPARA®) is a once-daily injection of full-length recombinant human parathyroid hormone that was initially approved by the U.S. Food and Drug Administration(FDA) in 2015 for hypoparathyroidism. However, it was recalled from the U.S. market in 2019, and its production will cease globally by the end of 2024. TransCon™ PTH, known as palopegteriparatide, utilizes an innovative technology to provide a sustained release of PTH (1-34) prodrug. It has received approval from the European Medicines Agency and is currently undergoing FDA review. Eneboparatide is a PTH receptor 1 agonist, designed to stimulate a specific receptor configuration. Encaleret is a negative allosteric modulator of the calcium-sensing receptor and rescues the secretion of naive PTH inAutosomal Dominant Hypocalcemia type 1. MBX 2109 is an investigational once-weekly PTH prodrug that addresses thefrequent administration challenge. EB612, the tablet form of PTH(1-34), is the first oral hormone replacement treatment for hypoparathyroidism. Recent developments in the management of chronic hypoparathyroidism hold promise as a therapeutic approach to restore physiological function, manage symptoms, and prevent associated complications. [ABSTRACT FROM AUTHOR]

Long Acting Injectable (LAI) therapy to treat HIV is an alternative to daily oral medications. The success of early roll-out of LAI to eligible patients requires a better understanding of patients' awareness and interest in this novel therapy. We administered an electronic survey to patients attending an urban HIV clinic in the US South. Eligible participants were 18 + years old with a most recent HIV-1 viral load < 200 copies/ml, without any evidence of genotypic resistance to LAI components or chronic hepatitis B. Survey recipients were asked about current treatment, engagement in care, and knowledge of LAI. Between January-April 2023, 480 patients were screened; 319 were eligible, and 155 (49%) completed the survey. The majority (119, 77%) were aware of, and 87 (56%) were interested in LAI. In regression analysis, only age was associated with interest in LAI (OR 0.95, 95% CI 0.92,0.99). Among proposed benefits of injectables, ease of travel without pills, lack of daily pill-taking, and fewer medication interactions were most appealing. Among proposed concerns with injectables, higher cost and insurance coverage of the new medicine were most worrisome. A large majority of people with HIV (PWH) are aware of the newest treatment available, and just over half of our sample expressed interest in LAI. Older age was associated with lower interest in LAI. LAI is appealing for its convenience, privacy, and avoidance of drug interactions, while the increased costs associated with LAI need to be addressed. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco. Methods: The study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty. Results: According to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings. Conclusions: The model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations. [ABSTRACT FROM AUTHOR]

Background: Insomnia is more common as people age. Several common hypnotics used to treat insomnia often do not adequately alleviate sleep issues in older adults and may be associated with negative residual effects such as an increased risk of falls, cognitive impairment, automobile accidents, and lack of response to auditory stimuli. The objective of these analyses of three clinical studies was to investigate the efficacy and safety of the dual orexin-receptor antagonist lemborexant (LEM) in older adults. Methods: Study E2006-G000-304 (Study 304; NCT02783729) was a randomized, double-blind, placebo (PBO)-controlled, active-comparator trial where subjects with insomnia disorder received LEM 5 mg (LEM5), LEM 10 mg (LEM10), zolpidem tartrate extended-release 6.25 mg (ZOL), or PBO for 30 days. In crossover Study E2006-E044-106 (Study 106; NCT02583451), healthy subjects (good sleepers) received LEM 2.5 mg, LEM5, LEM10, or PBO for eight nights or zopiclone on days 1 and 8 (and PBO on days 2–7). In crossover Study E2006-A001-108 (Study 108; NCT03008447), healthy subjects received a single dose of LEM5, LEM10, PBO, or ZOL. Sleep assessments included polysomnography-based latency to persistent sleep (LPS), wake after sleep onset (WASO), WASO in the second half of the night (WASO2H), sleep efficiency, postural stability, middle-of-the-night and next-day cognitive performance, middle-of-the-night auditory awakening threshold and return-to-sleep latency, and driving performance. Results: Overall, 453 of 1006 (45%; Study 304), 24 of 48 (50%; Study 106), and 28 of 56 (50%; Study 108) subjects were aged ≥ 65 years. In Study 304, LEM decreased (improved) LPS, WASO, and WASO2H from baseline more than ZOL and PBO; subjects treated with LEM had greater increases in sleep efficiency (improved) than with ZOL or PBO. In both Studies 304 and 108, postural stability was not impaired at waketime in subjects who received LEM compared with PBO. At waketime, LEM did not impair memory compared with PBO. In Study 108, following middle-of-the-night awakening, LEM and ZOL did not affect subjects' ability to awaken to auditory stimuli; LEM did not affect tests of memory and attention. In Study 106, LEM did not impair next-day driving performance in healthy elderly compared with PBO. LEM was well tolerated in subjects aged ≥ 65 years. Conclusions: LEM provided benefits on sleep variables without next-morning residual effects in subjects aged ≥ 65 years, supporting LEM as a treatment option for older adults with insomnia. Trial Registration Numbers and Dates of Registration: Study 304: ClinicalTrials.gov identifier, NCT02783729, date of registration, 26 May 2016. Study 106: ClinicalTrials.gov identifier, NCT02583451, date of registration, 22 October 2015. Study 108: ClinicalTrials.gov identifier, NCT03008447, date of registration, 2 January 2017. Plain Language Summary: The prevalence of insomnia increases with age; however, some hypnotics used for treating insomnia do not adequately resolve sleep problems in older adults and may be associated with adverse residual effects. Specifically, some hypnotics pose safety concerns in this population of patients who are generally more vulnerable to treatment-related effects, including increasing the risk of falls, risks of cognitive impairment, automobile accidents, and unresponsiveness to auditory stimuli. Safer and more effective insomnia medications are needed to reduce sleep problems with improved side-effect profiles. This analysis of lemborexant clinical studies conducted in adult subjects at least 65 years old found the drug to be effective without impairing memory, attention or balance the following day compared with placebo. These subjects were normal sleepers (for age) or had insomnia disorder. Furthermore, lemborexant was not associated with impaired ability to drive the next morning or awaken to loud middle-of-the-night sounds. Lemborexant was well tolerated in these older adults, similar to findings for adults aged at least 18 years. These findings indicate that lemborexant may be an appropriate treatment option for insomnia in older adults. [ABSTRACT FROM AUTHOR]

In the current work, the efficacy of sago starch as potential biopolymer‐blends with sodium alginate in the designing of sustained drug‐releasing particles for oral delivery is investigated, where calcium alginate‐sago starch particles are prepared via ionic gelation process employing calcium chloride as ionic cross‐linker. These particles showed the aceclofenac loading of 16.94 ± 0.94–18.92 ± 1.17%, aceclofenac encapsulation efficiency of 84.72 ± 1.94–94.59 ± 3.53%, and average particle‐size of 1.11 ± 0.09–1.32 ± 0.11 mm. FESEM analysis indicated spherical‐shaped particles with rough surfaces. FTIR and P‐XRD analyses demonstrated absence of any kinds of interactions in‐between drug‐polymers within particles and the encapsulated aceclofenac present within these polymeric particles is in the amorphous state. All these formulated polymeric particles demonstrated sustained in vitro aceclofenac releasing profile over 12 h and pH‐responsive performance of in vitro swelling. These kinds of sustained drug‐releasing sago starch‐based particles can be advantageous to facilitate reduction of dosing interval and improved oral bioavailability with enhanced patient compliance. [ABSTRACT FROM AUTHOR]

The U.S. Food and Drug Administration (FDA) approved the etonogestrel contraceptive implant for 3 years of use. Evidence suggests that it may be used for up to 5 years for pregnancy prevention, also known as extended use. We conducted a national cross-sectional survey among a group of reproductive health clinicians. We developed an online survey using the Consolidated Framework for Implementation Research (CFIR) and distributed it through e-mail listservs and social media groups from May to June 2021. We analyzed results using multivariable logistical regression. Among the 300 respondents, 195 (65.0%) reported that they always offer extended use, and 50 (16.7%) reported that they sometimes offer extended use. Fifty-five respondents (18.3%) reported that they never offer extended use. After adjusting for age, gender, and clinical setting, we found that complex family planning sub-specialists (adjusted odds ratio [aOR] = 9.32; 95% confidence interval [CI] [1.81, 48.03]) and family medicine physicians (aOR = 4.37, 95% CI [1.58, 12.10]) were significantly more likely to recommend extended use compared with general obstetrics and gynecology (OBGYN) physicians. Clinicians from private practices or health maintenance organizations were significantly less likely to offer extended use than those from academic centers (aOR = 0.19, 95% CI [0.07, 0.51]; aOR = 0.06, 95% CI [0.01, 0.31]). The most common barriers to offering extended use were concerns about pregnancy risk, bleeding, and lack of FDA approval past 3 years. Meanwhile, clinicians identified strong published evidence supporting extended use as a key facilitator for offering it, and they perceived that prior counseling on extended use from a past clinician was a key facilitator for patients to adopt it. One-third of clinicians in this study did not consistently offer extended use of the contraceptive implant. An opportunity exists to expand access to extended use by focusing on education interventions for clinicians and seeking FDA approval for 5 years of use. [ABSTRACT FROM AUTHOR]

Purpose: Niacin (nicotinic acid), known for its lipid-modifying effects, has been explored for its potential anti-inflammatory properties and potential to affect adipokines secretion from adipose tissue. The aim of this systematic review and meta-analysis was to assess the effects of niacin on inflammatory markers and adipokines. Methods: A comprehensive search was conducted across five databases: PubMed, Scopus, Cochrane Library, Embase, and ISI Web of Science. Randomized controlled trials exploring the effects of niacin on inflammatory markers (CRP, IL-6, TNF-α) and adipokines (Adiponectin, Leptin) were included. Pooled effect sizes were analysed using a random-effects model, and additional procedures including subgroup analyses, sensitivity analysis and dose-response analysis were also performed. Results: From an initial 1279 articles, fifteen randomized controlled trials (RCTs) were included. Niacin administration demonstrated a notable reduction in CRP levels (SMD: -0.88, 95% CI: -1.46 to -0.30, p = 0.003). Subgroup analyses confirmed CRP reductions in trials with intervention durations ≤ 24 weeks, doses ≤ 1000 mg/day, and elevated baseline CRP levels (> 3 mg/l). The meta-analysis of IL-6 and TNF-α revealed significant TNF-α reductions, while IL-6 reduction did not reach statistical significance. Niacin administration also substantially elevated Adiponectin (SMD: 3.52, 95% CI: 0.95 to 6.1, p = 0.007) and Leptin (SMD: 1.90, 95% CI: 0.03 to 3.77, p = 0.04) levels. Conclusion: Niacin treatment is associated with significant reductions in CRP and TNF-α levels, suggesting potential anti-inflammatory effects. Additionally, niacin positively influences adipokines, increasing Adiponectin and Leptin levels. These findings provide insights for future research and clinical applications targeting inflammation and metabolic dysregulation. [ABSTRACT FROM AUTHOR]

Enterically coated (ENT) or delayed-release (DEL) capsules may lessen gastrointestinal symptoms (GIS) following acute sodium citrate (SC) ingestion, although the effects on blood acid-base balance are undetermined. Fourteen active males ingested 0.4 g.kg−1 body mass (BM) SC, within gelatine (GEL), DEL and ENT capsules or 0.07 g.kg−1 BM sodium chloride control (CON). Blood acid-base balance and GIS were measured for 4 h. Ingestion form had no significant effect on total GIS experienced (GEL: 2 ± 7; DEL: 1 ± 8; ENT: 1 ± 4 AU). Most (7/14) participants experienced zero symptoms throughout. Peak GIS typically emerged ≤100 min post-ingestion, with a similar time to reach peak GIS between ingestion form (GEL: 36 ± 70; DEL: 13 ± 28; ENT: 15 ± 33 AU). Blood [HCO3−] was significantly higher with ENT versus GEL (ENT: 29.0 ± 0.8; GEL: 28.5 ± 1.1 mmol.L−1, P = 0.037). Acute ingestion of a reduced SC dose elicited minimal GIS, producing significant changes in blood [HCO3−] from rest, irrespective of ingestion form (GEL: 6.0 ± 0.9; DEL: 5.1 ± 1.0; ENT: 6.2 ± 0.8 mmol.L−1). The necessity of individualized ingestion strategies is also challenged, with sustained increases in blood [HCO3−] of ≥4 mmol.L−1 for up to 153 min highlighted. If commencing exercise at peak alkalosis augments subsequent performance above starting at a standardized time point where HCO3− is still elevated remains unclear. [ABSTRACT FROM AUTHOR]

pH-responsive hydrogel antibacterial microspheres were prepared by complex coacervation method and used as drug carriers to load the antibiotic substitute potassium diformate (KDF). The results showed that the three-dimensional network structure of the composite hydrogel was formed among the polysaccharide components, and Zeolite A loaded with KDF was uniformly dispersed in it. The results of drug release behavior and kinetics in vitro showed that the drug release rate was higher and the release mechanism followed the Ritger-Peppas model, which indicated that the antibacterial microspheres had a good pH response. In vitro, the carrier showed broad-spectrum antibacterial activity, good biocompatibility, and degradability. Sodium carboxymethylcellulose and pectin synergistic by hydrogen bonding, potassium dicarboxylate-loaded Zeolite A is filled in a three-dimensional hydrogel network, and chitosan quaternary ammonium salts coat the outer layer. [ABSTRACT FROM AUTHOR]

The continuous production of mature blood cell lineages is maintained by hematopoietic stem cells but they are highly susceptible to damage by ionizing radiation (IR) that induces death. Thus, devising therapeutic strategies that can mitigate hematopoietic toxicity caused by IR would benefit acute radiation syndrome (ARS) victims and patients receiving radiotherapy. Herein, we describe the preparation of an injectable hydrogel formulation based on Arg‐Gly‐Asp‐alginate (RGD‐Alg) and Laponite using a simple mixing method that ensured a slow and sustained release of interleukin‐12 (IL‐12) (RGD‐Alg/Laponite@IL‐12). The local administration of RGD‐Alg/Laponite@IL‐12 increased survival rates and promoted the hematopoietic recovery of mice who had received sublethal‐dose irradiation. Local intra‐bone marrow (intra‐BM) injection of RGD‐Alg/Laponite@IL‐12 hydrogel effectively stimulated IL12 receptor‐phosphoinositide 3‐kinase/protein kinase B (IL‐12R‐PI3K/AKT) signaling axis, which promoted proliferation and hematopoietic growth factors secretion of BM mesenchymal stem/stromal cells. This signaling axis facilitates the repair of the hematopoietic microenvironment and plays a pivotal role in hematopoietic reconstitution. In conclusion, we describe a biomaterial‐sustained release of IL‐12 for the treatment of irradiated hematopoietic injury and provide a new therapeutic strategy for hematopoietic ARS. [ABSTRACT FROM AUTHOR]

Background and aim: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use. Design, setting and participants: This was a population-based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada. All individuals with at least one OAT dispensation in BC between 1 January 2014 and 31 August 2021 took part. Measurements: To assess changes in OAT prescribing practices over time, we calculated initiation doses, dose titration intervals, maintenance doses and take-home dosing intervals stratified by medication [methadone, buprenorphine--naloxone and slow-release oral morphine (SROM)] according to recommended guidelines. Findings: A total of 265 410 OAT episodes (57.5% on methadone, 34.5% on buprenorphine--naloxone and 8.0% on SROM) were initiated during the study period. Compared with the guideline recommendation, observed initiation doses were higher among all medications from 2014 (2017 for SROM) to 2021 (buprenorphine--naloxone: 14-29%; methadone: 53-66%; SROM: 26-55%). Titration intervals were shorter for all medications, consistent with guidelines for buprenorphine--naloxone (26-49%), but shorter than recommended for methadone or SROM (28-51% and 12-41%, respectively). Higher maintenance dosing was observed for methadone (68-78%) and SROM (3-21%). Take-home allowances extending beyond the recommended guideline length increased across medications (buprenorphine--naloxone: 18-35%; methadone: 50-64%; SROM: 34-39%). Changes in prescribing patterns were similar for first-time OAT initiators. Conclusion: In British Columbia, Canada, from 2014 to 2021, prescribers of opioid agonist treatment (OAT) appeared to initiate both new and experienced OAT clients at higher doses than guideline recommendations, titrate them more rapidly and maintain clients at higher doses. Take-home dose allowances also gradually increased. [ABSTRACT FROM AUTHOR]

Objectives: In June 2020, modified‐release paracetamol (paracetamol‐MR) preparations were up‐scheduled from schedule‐2 (available in pharmacy) to schedule‐3 (available by request to a pharmacist only). The present study aims to ascertain whether up‐scheduling affected the frequency of paracetamol‐MR overdoses. Methods: This is a retrospective cohort study of two data sets from 1 June 2017 to 31 May 2022. Monash Health data were extracted using the diagnosis of paracetamol overdose coding and electronic medical records data. Calls regarding paracetamol‐MR overdoses to Victorian Poisons Information Centre (VPIC) were extracted from the Poisons centre call database. We used a quasi‐experimental research design with interrupted time series analysis to evaluate the immediate impact and change in trend of poisoning‐related calls and ED presentations before and after June 2020. The change in proportion of paracetamol‐MR cases in both databases was analysed using the Χ2 test. Results: The proportion of paracetamol‐MR cases in both data sets did not change. From Monash Health, there was no level change in monthly paracetamol‐MR overdose‐related presentations following re‐scheduling (rate ratio [RR] = 1.08, 95% confidence interval [CI] = 0.57–2.01). There was no change in monthly paracetamol‐MR overdose‐related calls to VPIC following re‐scheduling (RR = 1.05, 95% CI = 0.96–1.14). Conclusion: The proportion of paracetamol‐MR overdoses did not decrease after the up‐scheduling to S3. Similarly, the frequency of overdoses by month remained similar. Further limitations on access to paracetamol products may need to be considered. [ABSTRACT FROM AUTHOR]

Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P =.63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Despite promising results regarding using long-acting cardioplegia in the adult population, little data exists specifically for operations requiring prolonged aortic cross-clamp needing additional doses. In this pilot study, we evaluated the outcomes of patients undergoing surgery with prolonged cross-clamp time based on four different redosing compositions. Methods: During the period from January 2019 until June 2022, 288 patients undergoing cardiac surgery with an expected cross-clamp time over 60 min were prospectively randomized regarding the type of the cardioplegia used: Group 1 (N = 150)- single-dose del Nido antegrade cardioplegia and Group 2 (N = 138)- single-dose Histidine-Tryptophane-Ketoglutarate (HTK) antegrade cardioplegia. In patients with ischemic time over 60 min, needing a redosing were further analyzed separately in four subgroups: (A) Cold whole blood (CWB) (4:1) (N = 95); (A1: DN-CWB; A2: HTK-CWB) and (B) St Thomas Solution (N = 92) (B1: DN-St Thomas; B2: HTK-St Thomas. Control groups were C1 (DN redosed by DN) and C2 (HTK by HTK). Results: Troponin levels in A1 and B1 groups were significantly lower than in DN-control. Respiratory support time and incidence of atrial fibrillation were significantly lower in Group A1 versus DN-control. Conclusions: Long-acting cardioplegic techniques are becoming widely utilized in the adult population, with minimal data on redosing methods/compositions for prolonged cases. Due to the small patient population, further investigation is needed to delineate optimal redosing methods, but this report brings to attention the initial success of multiple strategies. [ABSTRACT FROM AUTHOR]

Objective: Maintaining appropriate salivary levels of an active ingredient is challenging. Intraoral trays can be used to deliver medications for localized treatment. Based on previous successful daytime studies with a slow-release sirolimus varnish, the aim was to optimize intraoral appliances/trays for overnight use to deliver slow-release medications in a manner that maintains therapeutic salivary levels of the active ingredient to treat oral conditions. Method and materials: An acrylic tray appliance containing 0.5 mg of sirolimus in a sustained-release varnish was placed on six anterior teeth for 12 hours, in ten healthy volunteers. Whole unstimulated saliva was collected at 1, 2, 10, and 12 hours after application. Blood was collected at the time of recruitment to confirm eligibility, and 12 hours after device removal to measure sirolimus levels. Drug levels in the blood and saliva were analyzed. Slow- and fast-release formulations, varnish position (buccal, palatal, or lingual), and tray placement (mandibular or maxillary) were qualitatively compared. Participants evaluated the varnish and tray. Results: Moderate concentrations of sirolimus were detected in the saliva when the fast-release formulation was used. The highest levels were from the mandibular tray with lingual varnish application. Sialometry of all participants was within normal range, and the highest drug levels were detected when low flow was measured. No traces of the medication were found in the blood. Conclusions: Salivary concentrations of medications applied to an intraoral appliance are affected by the placement in the maxilla or mandible, varnish formulation, location of varnish, and salivation rate. These results may help optimize medication release following application to various oral devices. [ABSTRACT FROM AUTHOR]

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is efficacious in preventing HIV among men-who-have-sex-with-men (MSM) and will be soon available in Europe. This study investigated the intention and preference to use LAI-PrEP among MSM in the Netherlands by employing a diffusion of innovation approach. This study had a cross-sectional design nested within a cohort study established in 2017 to understand oral PrEP use among MSM. 309 MSM completed the survey on their awareness, interest, intention, and preference for LAI-PrEP in June 2022. Among them, 83% showed high/very-high interest in, and 63% showed high/very-high intention to use LAI-PrEP. A repeated innovator effect from the early adopters to LAI-PrEP was not observed. Early adopters did not show increased intention to use LAI-PrEP compared to other MSM subgroups, but neither did PrEP-naïve nor PrEP-discontinued MSM. However, among the 218 current oral PrEP users, suboptimal adherence was associated with preference for LAI-PrEP but not with intention to use it. In conclusion, our findings indicated that an effective, available, and affordable LAI-PrEP would be welcomed in the Netherlands, but that its introduction may not significantly expand PrEP coverage. However, the introduction of LAI-PrEP in the Netherlands could prove beneficial to MSM with suboptimal adherence to oral PrEP. [ABSTRACT FROM AUTHOR]

Background: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. Methods: This was a double‐blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in‐hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3‐point reduction in the MDAS. Results: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p‐value 0.42, a non‐significant difference. A post‐hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p‐value = 0.033, Wilcoxon Rank Sum test). Conclusions: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied. [ABSTRACT FROM AUTHOR]

Opioid agonist therapy is first line in the management of opioid use disorder (OUD). Many guidelines support buprenorphine as the optimal treatment due to its preferred safety profile. Extended-release buprenorphine (BUP-XR) is a weekly or monthly subcutaneously administered formulation of buprenorphine. Emerging research has explored the use of BUP-XR in a variety of patient populations to guide clinicians in determining which patients may or may not benefit from BUP-XR. We conducted a literature review in Medline, PsycInfo and Embase to capture the literature to date on BUP-XR. Abstracts were reviewed, and papers which guided selection of individuals who would or would not benefit from BUP-XR were included. Our search returned 359 articles, and 31 met inclusion criteria. Special populations who may benefit from BUP-XR include individuals experiencing homelessness, incarceration, and medical or psychiatric comorbidity, while caution should be used around pregnancy. Patient preference and patient-centered outcomes were recurring considerations to guide the selection of BUP-XR. Extended-release buprenorphine formulations represent a relatively new tool for managing OUD and may specifically benefit patients undergoing transitions in care. Further research on the comparative effectiveness of extended-release versus daily-dosing formulations and in other populations of interest is needed. [ABSTRACT FROM AUTHOR]

In this study, a new gastro-floating sustained-release tablet (GFT) with a combination of Etoricoxib (ET) and Famotidine (FM) was successfully developed. GFTs were prepared by using a combination of hydrophilic swellable natural/semi-synthetic polymers as a controlled-release layer. Through a 24 full factorial statistical experimental design, the effects of formulation factors on the release of GFTs were conducted. The ideal floating tablet (FT) comprised konjac-gum (150 mg), guar-gum (26.57 mg), xanthan-gum (54.17 mg), and HPMC-K15-M (69.25 mg). The ideal FT exhibited a high swelling index (SI) (297.7%) and rapid FLT (around 50 s) in 0.1 N HCl as well as controlled release of ET (22.43% in 1 h and 77.47% in 8 h) and FM (24.89% in 1 h and 93.82% in 8 h) with the absence of any drug-excipient interactions. The AUC0∼72 (ng h/mL) of ET and FM in the GFTs were approximately double-fold of the market, respectively. The relative bioavailability was (207.48 ± 12.02% and 208.51 ± 13.11%) compared with commercial tablets. The X-ray imaging showed a promising buoyancy ability for approximately 8 h. These findings revealed the successful preparation of the sustained-release floating tablet with improved dual drug delivery. [ABSTRACT FROM AUTHOR]

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Background: Periodontal diseases may benefit more from topical treatments with nanoparticles rather than systemic treatments due to advantages such as higher stability and controlled release profile. This study investigated the preparation and characterization of thermosensitive gel formulations containing clindamycin-loaded niosomes and solid lipid nanoparticles (SLNs) loaded with fluconazole (FLZ), as well as their in vitro antibacterial and antifungal effects in the treatment of common microorganisms that cause periodontal diseases. Methods: This study loaded niosomes and SLNs with clindamycin and FLZ, respectively, and assessed their loading efficiency, particle size, and zeta potential. The particles were characterized using a variety of methods such as differential scanning calorimetry (DSC), dynamic light scattering (DLS), and Transmission Electron Microscopy (TEM). Thermosensitive gels were formulated by combining these particles and their viscosity, gelation temperature, in-vitro release profile, as well as antibacterial and antifungal effects were evaluated. Results: Both types of these nanoparticles were found to be spherical (TEM) with a mean particle size of 243.03 nm in niosomes and 171.97 nm in SLNs (DLS), and respective zeta potentials of -23.3 and -15. The loading rate was 98% in niosomes and 51% in SLNs. The release profiles of niosomal formulations were slower than those of the SLNs. Both formulations allowed the release of the drug by first-order kinetic. Additionally, the gel formulation presented a slower release of both drugs compared to niosomes and SLNs suspensions. Conclusion: Thermosensitive gels containing clindamycin-loaded niosomes and/or FLZ-SLNs were found to effectively fight the periodontitis-causing bacteria and fungi. [ABSTRACT FROM AUTHOR]

Long-acting injectable antiretroviral therapy (LAI-ART) can offer people living with HIV (PLWH) a promising alternative to daily oral therapy. This article highlights the issues, challenges and conditions related to introducing LAI-ART into the social lives of PLWH and HIV-care practices in Senegal. Semi-structured interviews were conducted with 42 PLWH in two hospital care units in Dakar and with 13 healthcare providers and 6 peer educators. Interviews were transcribed, thematically coded and analysed using a cross-sectional approach. We found three key issues. First, simplifying living with HIV: PLWH respondents perceive LAI-ART as an opportunity to ease the burden associated with taking tablets. This enthusiasm may however be qualified by an ambivalent relationship with injections and is subject to certain conditions. Second, certain constraints linked to the medicalisation of care are to be anticipated, including the obligation to go to the hospital every two months for injections. These findings foreshadow the new management work for medical follow-up expected to fall on PLWH and caregivers. Third, the challenges of introducing LAI-ART in Senegal are to ensure adequate organisation of care and supply and sustainability of the program. These results clarify how to implement programs to introduce LAI-ART into real life in the West African context. [ABSTRACT FROM AUTHOR]

Long-acting injectable HIV pre-exposure prophylaxis (LAI-PrEP) could help overcome multilevel challenges to HIV prevention for people who inject drugs (PWID), including those in the binational San Diego-Tijuana metroplex. Yet, general PrEP awareness and interest in LAI-PrEP remain underexplored among PWID. From 2020 to 2021, 562 HIV-negative PWID in San Diego and Tijuana completed surveys assessing general PrEP awareness and interest in oral and LAI-PrEP. Modified Poisson regression examined factors associated with general PrEP awareness. Multinomial logistic regression assessed factors associated with interest in both oral and LAI-PrEP, oral PrEP only, LAI-PrEP only, or neither. General PrEP awareness was low (18%) and associated with experiencing unsheltered homelessness (adjusted prevalence ratio [APR] = 1.50, 95% confidence interval [CI]: 0.96–2.33), past 6-month fentanyl injection (APR = 1.53, 95% CI: 1.04–2.25), and transactional sex (APR = 1.71, 95% CI: 1.06–2.76). Interest in oral PrEP only was most common (44%), followed by LAI-PrEP only (25%) and neither (16%). Compared to the odds of being interested in LAI-PrEP only, the odds of being interested in oral PrEP only were lower among those who were stopped by police (AOR = 0.38, 95% CI: 0.22–0.65), reported past 6-month fentanyl injection (AOR = 0.33, 95% CI: 0.20–0.56), polydrug use (AOR = 0.48, 95% CI: 0.27–0.86), injecting multiple times daily (AOR = 0.26, 95% CI: 0.14–0.46), receptive syringe use (AOR = 0.30, 95% CI: 0.19–0.49), and higher perceived HIV risk (AOR = 0.24, 95% CI: 0.15–0.39). Interest in LAI-PrEP was more common among PWID reporting social and structural factors that could interfere with oral PrEP adherence, suggesting LAI-PrEP implementation could increase PrEP coverage among those most vulnerable to HIV. [ABSTRACT FROM AUTHOR]

This review attempted to ascertain the rationale for the formulation of sustainedrelease local anesthetics and summarize the various formulation approaches designed to date to achieve sustained and localized local analgesic effects. The incidence of pain, which is the concern of patients as well as health care professionals, is increasing due to accidents, surgical procedures, and other diseases. Local anesthetics can be used for the management of moderate to severe acute and chronic pain. They also allow regional analgesia, in situations where the cause and source of the pain are limited to a particular site or region, without the need for loss of consciousness or systemic administration of other analgesics thereby decreasing the risk of potential toxicities. Though they have an interesting antipain efficacy, the short duration of action of local anesthetics makes the need for their multiple injections or opioid adjuvants mandatory. To overcome this problem, different formulations are being designed that help achieve prolonged analgesia with a single dose of administration. Combination with adjuvants, liposomal formulations, lipid-based nanoparticles, thermo-responsive nanogels, microspheres, microcapsules, complexation with multivalent counterions and HP-β-CD, lipid-based nanoparticles, and bio-adhesive films, and polymeric matrices are among the approaches. Further safety studies are required to ensure the safe and effective utilization of sustained-release local anesthetics. Moreover, the release kinetics of the various formulations should be adequately established. [ABSTRACT FROM AUTHOR]

X‐linked nephrogenic diabetes insipidus (X‐NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type‐2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP‐intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3‐adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3‐AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X‐NDI. Here we demonstrate that the β3‐AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X‐NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow‐release preparation, promoted a sustained antidiuretic effect, reducing the 24 h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X‐NDI mice. Taken together, these data suggest that human β3‐AR agonists might represent an effective possible treatment strategy for X‐NDI. [ABSTRACT FROM AUTHOR]

Enrofloxacin is a special antibacterial agent for animals and is a synthetic third-generation fluoroquinolone broad-spectrum antibacterial agent. It has excellent antibacterial effects and is widely used in clinical practice. However, the solubility of enrofloxacin is extremely low and this has greatly limited its clinical use. We assessed progress in overcoming this deficiency by tracking pharmaceutical alterations to enrofloxacin in vivo delivery systems. We used the keywords 'enrofloxacin', 'pharmaceuticals' and 'preparations' to assess relevant literature sources collected in CNKI, Wanfang, Vepsa, China Patent Information Network, PubMed, Web of Science and other domestic and foreign databases from 2010 to 2022 to summarize the research progress of enrofloxacin pharmaceutics. A total of 62 valid literature were retrieved and we found that pharmaceutic technologies successfully were able to increase enrofloxacin solubility, palatability, bioavailability and half-life. The continuous development and promotion of new drug formulations and new materials will give enrofloxacin preparations broad application prospects in veterinary medicine. [ABSTRACT FROM AUTHOR]

Prevention and treatment of HIV infection continues to evolve. Adherence to both preventives and antiretroviral therapy is important to efficacy in preventing infection and producing viral suppression. Long-acting options are now available which may help optimize outcomes. [ABSTRACT FROM AUTHOR]

This investigation used a tubular microreactor to produce Vildagliptin (VLG) loaded ethyl cellulose (EC) nanoparticles (NPs) for sustained delivery of a drug. A central composite design was used to quantify the influence of independent variables on the desired responses. The independent factors selected to achieve the desired entrapment efficiency and sustained drug release were EC concentration and sodium lauryl sulfate concentration. On the other hand, the dependent variables chosen for assessment were particle size (Y1) and encapsulation efficiency (Y2). The nanoparticles produced were analyzed, which included particle size measurement, transmission electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, encapsulation efficiency (EE) determination, and in vitro drug release study. The optimized samples TEM investigation verified the nanoparticles' spherical shape and particle size distribution, ranging from 160 to 250 nm. The entrapment efficiency (EE) fell within the range of 63–87%. In the in-vitro drug release study, VLG-loaded EC nanoparticles exhibited sustained release over 12 h. Applying various kinetic equations to the in-vitro drug release data demonstrated that the drug release mechanism involved diffusion. This comprehensive study concluded that the VLG-EC-NPs achieved optimal particle size, EE, and desirable level of sustained drug release. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of fixed-dose combinations (FDC) of triple-drug dapagliflozin, sitagliptin, and metformin (DSM) compared with FDC of two-drug sitagliptin and metformin (SM), in Indian adult patients with type 2 diabetes (T2D). Methods: A multicentric, randomized, double-blind, active-controlled, Phase 3 study (CTRI/2021/10/037461) was conducted on 274 Indian adult patients with T2D. Patients were randomized (1:1) to receive either an FDC of triple-drug (n = 137) dapagliflozin propanediol 10 mg, sitagliptin phosphate 100 mg, and metformin hydrochloride 1000 mg extended-release (DSM) or FDC of two-drug (n = 137) sitagliptin phosphate 100 mg and metformin hydrochloride 1000 mg sustained-release (SM), for 16 weeks. The primary endpoint was a change in HbA1c, while the secondary endpoints were changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body weight, and safety. Results: Both DSM and SM FDCs reduced HbA1c significantly (-1.45% and -1.00%, respectively, both p < 0.0001), however, HbA1c lowering was superior with DSM (∆ -0.45%; p = 0.0005) compared to SM, at week 16. Similarly, both DSM and SM FDCs reduced FPG and PPG significantly, however, FPG (∆ -12.4 mg/dl; p = 0.003) and PPG reduction (∆ -18.45 mg/dl; p = 0.01) were significantly superior to DSM compared to SM, respectively. No significant reduction in body weight was observed between the two arms. Both FDCs were well tolerated. Conclusion: FDC of DSM was superior to SM in reducing HbA1c, FPG, and PPG in Indian adults with T2D. Both triple and dual FDCs had optimal safety profiles. [ABSTRACT FROM AUTHOR]

Exogenous melatonin can be helpful for treatment of some sleep disorders. However, immediate-release formulations are rapidly absorbed and cleared from the body making it difficult to provide coverage for an entire sleep period. Extended-release melatonin formulations can better mimic the naturally occurring melatonin profile and increase efficacy, but few studies have reported on their pharmacokinetics. To assess the pharmacokinetics of extended-release melatonin, we conducted a randomized, double-blind, crossover study of extended-release melatonin (4 mg) compared to immediate-release melatonin (4 mg) in 18 healthy adults, ages 18–65 years. Participants received immediate-release or extended-release melatonin in clinic after an 8 h fast, and blood samples were taken over a 10-h period. After a 7-day washout period, the same procedures were repeated with the melatonin form not previously received. Extended-release melatonin had a longer time to peak concentration (1.56 vs 0.6 h) and elimination half-life (1.63 vs 0.95 h) compared with immediate-release melatonin. Maximum concentration was lower for extended-release melatonin compared with immediate-release melatonin (7581 pg/mL vs 13120 pg/mL). Extended-release melatonin raised melatonin levels in as little as 15 min and sustained elevated melatonin levels (>300 pg/mL) for 6 h before falling below 50 pg/mL by 9 h. No clinically relevant adverse events were observed, and safety parameters remained within normal ranges for both formulations. The pharmacokinetic profile of this extended-release melatonin formulation suggests that it could be used for future efficacy studies of melatonin and sleep outcomes. This trial is registered at ClinicalTrials.gov, NCT04067791. [ABSTRACT FROM AUTHOR]

This study aimed to develop a tablet that shows a drug release profile similar to the tofacitinib sustained-release tablet (Xeljanz XR®; OROS™) using hot melt extrusion technology. Tofacitinib citrate was selected as the drug. HPMCAS, HPMCP, and Kollidon VA64 were used as thermoplastic polymers to prepare a hot-melt extrudate. The extrudate was obtained from a twin screw extruder and pelletizer. The granules were compressed using a single punch press machine and then coated. TGA, DSC, XRD, FT-IR, and SEM were performed on the hot melt extrudate to understand its physicochemical properties. Dissolution tests were performed using the paddle method (USP Apparatus II). The results showed that the crystallinity state of tofacitinib changed to amorphous after the hot melt extrusion process; however, no chemical change was observed. The drug release profile was similar to that of Xeljanz XR®, which has an initial lag time owing to its OROS™ formulation; a coating process was performed to obtain a similar drug release profile. The lag time was controlled by adjusting the thickness of the coating layer. Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR®. [ABSTRACT FROM AUTHOR]

In 2012, the Federal Drug Administration approved daily oral pre-exposure prophylaxis (PrEP) for HIV prevention in adults. Longer acting injectable PrEP (LA PrEP) has been approved and other formulations are in development. A successful LA PrEP rollout requires examining potential facilitators and barriers to PrEP uptake. Given that transgender and gender expansive (TGE) individuals experience more social vulnerability and higher levels of medical mistrust compared to other populations, examining the role of these two factors in LA PrEP uptake is important. This study, PrEP for ALL, is a community-based participatory research project in Texas that engaged TGE community members and organizational partners through a community advisory board. In total, 482 TGE individuals were recruited and responded to all relevant questions in an online survey, including their intentions to use three formulations: a monthly oral pill, a bimonthly intramuscular injection, and an annual subdermal implant. Multiple regression analysis was used to examine the influence of social vulnerability and medical mistrust on intention to use each LA PrEP formulation adjusting for other relevant factors. Findings suggest that individuals with higher levels of social vulnerability had greater intentions to use the monthly oral pill (β = 0.12, p = 0.009), the bimonthly intramuscular injection (β = 0.18, p < 0.001), and annual subdermal implant (β = 0.17, p < 0.001), whereas medical mistrust reduced intentions to use the bimonthly intramuscular injection (β = −0.18, p < 0.001) and annual subdermal implant (β = −0.11, p = 0.021). Improvements in gender-affirming clinical care are needed along with LA PrEP formulations that allow for greater autonomy and reduced clinical contact. Clinical Trial Registration number: NCT05044286. [ABSTRACT FROM AUTHOR]

The article focuses on the treatment of pediatric renal tubular acidosis (RTA) using the prolonged-release alkali formulation Sibnayal®, highlighting its effectiveness and tolerability in a clinical setting. It reports that while the efficacy is comparable to standard treatments, Sibnayal® is preferred by many patients, especially school-aged children, due to its ease of administration.

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol. [ABSTRACT FROM AUTHOR]

Objective: To investigate the predictive value of obstetric findings when using dinoprostone (prostaglandin E2 [PGE2]) vaginal inserts for cervical ripening, and to assess the optimal cervical‐ripening method between PGE2 vaginal insert and/or cervical dilators. Methods: This prospective observational study enrolled pregnant women who underwent cervical ripening for labor induction in 37–41 week' gestation in 2020. In evaluation 1, optimal obstetric findings predictive of rapid cervical ripening using PGE2 were assessed. In evaluation 2, the duration from PGE2 administration to labor onset and perinatal outcomes were compared between cases in which only PGE2 was used and cases that were treated with PGE2 after mechanical cervical dilators (Dilapan®) for extremely immature cervical ripening (uterine cervical os <2 cm). Results: In evaluation 1, uterine dilatation before the use of a PGE2 vaginal insert was mostly correlated with the time from PGE2 administration to labor onset (r = −0.428, p < 0.001). When the uterine cervical os dilatation was ≥2 cm, a shorter time‐to‐labor onset was found. In addition, os dilatation, effacement, and station at the time of PGE2 vaginal insert removal also significantly progressed. In evaluation 2, the median duration from PGE2 administration to labor onset was 1740 min in cases where only PGE2 was used, and 610 min in those where PGE2 was used after mechanical cervical dilators (p = 0.011). Conclusion: PGE2 vaginal inserts are relatively effective when the uterine cervical os is ≥2 cm in diameter. However, in cases of extremely immature cervical‐ripening, it was feasible to use PGE2 vaginal inserts before mechanical cervical dilatation. [ABSTRACT FROM AUTHOR]

Background: Chronic breathlessness adversely impacts people with chronic obstructive pulmonary disease and their caregivers (family and friends), who may, in turn, experience significant burden due to their caregiving role. Sustained-release morphine may reduce chronic breathlessness in some patients, which may have an impact on caregivers' perceived burden. Aim: To explore the impact on caregiver burden of active treatment of people with chronic breathlessness (modified Medical Research Council (mMRC) ⩾ 3) and chronic obstructive pulmonary disease (COPD) with regular, low-dose, sustained-release morphine within a multi-site, double-blind, randomised, placebo-controlled trial. Design: Exploratory analysis of self-reported caregiver burden at baseline and end of week 3 in a randomised, double-blind, placebo-controlled study. Caregiver measures included: demographics and perceived burden (Zarit Burden Interview 12-item short-form questionnaire). Patient measures included: worst breathlessness and FitBitR-measures. Setting/participants: All consenting caregivers of trial patient participants in a multi-site study recruiting from palliative care and respiratory services. Results: Caregivers (n = 49; 59% women; median age 68 years [IQR 50–75]) reported median baseline caregiver burden 12 [IQR 5–17], with 53% reporting high burden (⩾13). Eighty-four percent of caregivers reported no change in burden. In people whose worst breathlessness improved, caregiver burden moved in the same direction, though the correlation was not significant (rs = 0.25, p = 0.17). Conversely, caregiver burden worsened as patients' minutes lightly active increased, with the correlation being significant (rs = 0.56, p = 0.04). Conclusions: Caregivers reported high levels of caregiver burden, but patients' response to treatment in terms of their symptom and function may influence change in caregiver burden over a three-week period. [ABSTRACT FROM AUTHOR]

Present study aimed compared pharmacokinetic profile of sustained-release CaffXtend® capsules (SR-Caffeine) with immediate-release caffeine capsules (IR-Caffeine), and the effect of SR-caffeine on memory, motivation, concentration, and attention. This open-label, randomized, single-dose, two-treatment, two-sequence, two-period, two-way crossover oral bioavailability study block randomized (1:1) healthy subjects (N = 15) to receive SR-Caffeine (200 mg) and IR-Caffeine (200 mg). Blood samples were collected at 0.25, 0.50, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36 and 48 h in each period. Primary study outcome included comparing relative bioavailability of SR-Caffeine 200 mg and IR-Caffeine 200 mg under fasting conditions, and changes in caffeine research visual analogue scale (Caff-VAS) scores ('relaxed', 'alert', 'jittery', 'tired', 'tense', 'headache', 'overall mood' and 'mentally fatigued') were also evaluated. Fifteen subjects completed the study. Mean tmax was 4.08 ± 2.13h for SR-Caffeine compared to 0.83 ± 0.39h for IR-Caffeine, (p < 0.0001). Similarly, mean t½ was 7.07 ± 3.48h for SR-Caffeine compared to 5.78 ± 2.11h for IR-Caffeine (p = 0.04189). However, total exposure was similar for SR-Caffeine and IR-Caffeine (90% CI: 89.89-120.50% to 94.49-123.82% for geometric least square mean of ln-transformed AUC0-t and AUC0-∞). In the Caff-VAS evaluation, the SR-Caffeine group showed significantly better scores for 'jitteriness', 'tiredness', 'alertness' and 'overall mood' for 8-12 h than the IR-Caffeine group. No adverse events were reported. Results demonstrated sustained release of caffeine over 24 h from SR-Caffeine as compared to IR-Caffeine, which showed significant improvements in the scores for 'relaxed', 'alertness' and 'overall mood' and significantly lower scores for the parameters-'jittery' and 'tired' for extended period. [ABSTRACT FROM AUTHOR]

Background: Watson's Theory Human Care (THC) is effective in the nursing care process, but its use is limited in individuals with bipolar disorder. Aim: It was aimed to use THC in the nursing approach of an individual diagnosed with bipolar disorder who was admitted to a psychiatry clinic. Method: The data of the case were collected between 01.07.2023 and 02.08.2023 in the closed psychiatry clinic of a mental health hospital serving in the Black Sea region of Turkiye. Interviews with the case were made according to THC and the nursing process was reported according to THC. In order to share the data about the individual, permission was obtained by making a statement to him and his name was not mentioned in the study. Results: The patient, who came to the clinic with complaints of grandiose delusions, suspicions and sudden anger, and was admitted to the clinic with the diagnosis of bipolar affective disorder, also has a history of kidney transplantation. An approach focused on trust and compassion was adopted with the case, and the interpersonal relations and care process were managed with the remedial methods in THC. In the care process, nursing interventions were implemented by adopting a holistic approach with a compassionate, sincere and safe interaction based on the 10 healing factors in the THC, and the results were evaluated. Conclusion: In the current case, the use of THC brings with it various limitations, while providing interaction-oriented and systematic nursing care with a holistic approach. It is recommended to increase the research conducted by nursing students and psychiatric nurses with other disciplines based on THC in individuals with bipolar disorder who are treated in closed psychiatry clinics. [ABSTRACT FROM AUTHOR]

Microbial biofilms are a major hindrance in the wound healing process, prolonging the inflammatory response phase, thus making them a target in treatment. The aim of this study is to assess the antibacterial properties of commercially available wound dressings, of various material composition and antibacterial agents, towards multiple in vitro microbial and biofilm models. A variety of in vitro microbial and biofilm models were utilised to evaluate the ability of wound dressing materials to sequester microbes, prevent dissemination and manage bioburden. Sequestering and dissemination models were used to evaluate the ability of wound dressing materials to prevent the biofilm‐forming bacterium, Pseudomonas aeruginosa, from migrating through dressing materials over a 24–72 h challenge period. Additionally, Centre for Disease Control (CDC) Bioreactor and Drip Flow models were used to evaluate antibacterial killing efficacy towards established P. aeruginosa and Staphylococcus aureus biofilms using more challenging, wound‐like models. Controlled‐release iodine foam and silver‐impregnated carboxymethylcellulose (CMC) wound dressing materials demonstrated potent biofilm management properties in comparison to a methylene blue and gentian violet‐containing foam dressing. Both the iodine‐containing foam and silver‐impregnated CMC materials effectively prevented viable P. aeruginosa dissemination for up to 72 h. In addition, the controlled‐release iodine foam and silver‐impregnated CMC materials reduced P. aeruginosa bioburden in the Drip Flow model. The controlled‐release iodine foam demonstrated superiority in the CDC Bioreactor model, as both the silver‐ and iodine‐containing materials reduced S. aureus to the limit of detection, but P. aeruginosa growth was only completely reduced by controlled‐release iodine foam dressing materials. The data generated within the in vitro biofilm models supports the clinical data available in the public domain for the implementation of iodine foam dressings for effective biofilm management and control in wound care. [ABSTRACT FROM AUTHOR]

Objective While postpartum depot medroxyprogesterone acetate (DMPA) is a highly effective form of contraception, some data suggest an association with depressive symptoms. Our objective was to evaluate the relationship between receipt of DMPA in the immediate postpartum period and postpartum depressive symptoms. Study Design This retrospective cohort study included all women who received prenatal and postpartum care at academic obstetric clinics affiliated with a tertiary care institution between January 1, 2008 and December 31, 2014. All women were counseled on contraception prior to hospital discharge. DMPA was available in the hospital pharmacy, and its utilization was documented in the electronic health record. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for postpartum depression for all women at all postpartum visits. A score of 10 or greater was categorized as positive. Bivariable and multivariable analyses were used to identify the association between immediate postpartum DMPA use and a positive postpartum depression screen. Results Of the 5,073 women who met inclusion criteria, 410 (8.1%) received DMPA prior to hospital discharge. Compared with women who did not receive DMPA, women who received DMPA prior to hospital discharge were younger, more likely to identify as Black race or Latinx ethnicity, and more likely to be publicly insured. Clinical characteristics also differed. Women who received DMPA were more likely to be obese and to have experienced prenatal depressive symptoms, been diagnosed with a hypertensive disorder of pregnancy, delivered preterm, and delivered vaginally. Receipt of immediate postpartum DMPA was not associated with having a positive screen for postpartum depression in bivariable (5.4 vs. 6.0%, p = 0.29) or multivariable (adjusted odds ratio 0.94, confidence interval 0.53–1.68) analyses. Conclusion Receipt of postpartum DMPA is not associated with a positive postpartum PHQ-9 screen. Concerns about precipitating postpartum depression should not preclude the utilization of DMPA as a contraceptive agent. Key Points Contraception is an important issue for obstetricians to address with postpartum patients. Concerns have been raised over the relationship between DMPA and depression. Our study shows that DMPA is not associated with a positive postpartum depression screen. [ABSTRACT FROM AUTHOR]

Nirsevimab (Beyfortus™), a long-acting monoclonal antibody targeting the respiratory syncytial virus (RSV) fusion (F) protein, is the first prophylactic monoclonal antibody against RSV to be licensed for use in all infants in their first RSV season, and thus presents a highly valuable tool in the fight against RSV disease in children. Additionally, in the USA and Canada, nirsevimab is licensed for use in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Data from randomized, double-blind, placebo-controlled clinical trials show that a single intramuscular dose of nirsevimab is efficacious in reducing the incidence of medically attended RSV lower respiratory tract (LRT) disease in healthy term and preterm infants through at least 150 days in their first RSV season. Pharmacokinetic data also support the efficacy of nirsevimab in infants at higher risk of severe RSV disease, including in the second RSV season with a second nirsevimab dose. Nirsevimab has an extended serum half-life, resulting in a duration of protection from a single dose which can cover a full typical RSV season. Nirsevimab is well tolerated, with low rates of reactogenicity, and can be administered concomitantly with childhood vaccines. Plain Language Summary: Respiratory syncytial virus (RSV) is a significant cause of infant morbidity and mortality worldwide, and prevention strategies involving vaccines or monoclonal antibodies against RSV have been global health priorities. The monoclonal antibody palivizumab has been licensed for 25 years; however, its use in children is restricted to a small subset of infants at increased risk of severe RSV disease, and five monthly doses are necessary to cover the RSV season. Nirsevimab (Beyfortus™) is a long-acting monoclonal antibody designed to provide protection against RSV through the RSV season from a single dose. Based on clinical trial data, nirsevimab, administered as a single intramuscular injection, reduces the incidence of medically attended RSV lower respiratory tract disease in infants through the RSV season. Nirsevimab is well tolerated, with low rates of adverse reactions. As the first monoclonal antibody for the prevention of RSV disease to be licensed for use in all infants in their first RSV season, nirsevimab represents an important advance in the fight against RSV. [ABSTRACT FROM AUTHOR]

A new sustained-release (SR) pregabalin tablet, YHD1119, was formulated for once-daily dosing. In the current study, we aimed to evaluate the pharmacokinetics of YHD1119 tablets in patients with reduced renal function. Subjects were grouped by creatinine clearance: > 60 mL/min/1.73m² (Cohort A) and 30-60 mL/min/1.73m² (Cohort B). Eight subjects in Cohort A received a YHD1119 75 mg tablet (Y75T) and a YHD1119 150 mg tablet (Y150T) in each period, and eight subjects in Cohort B received a Y75T. Non-compartment analysis and population pharmacokinetic analysis using a one-compartment model with first-order elimination and first-order absorption with lag time were performed. Sixteen subjects completed the study. The geometric mean ratio (GMR) (90% confidence intervals [CI]) for maximum concentration (Cmax), and area under the concentration-time profile from 0 to the last measurable time (AUClast) after Y75T of Cohort B to those of Y75T of Cohort A were 1.2273 (1.0245-1.4701), and 2.4146 (1.8142-3.2138), respectively. The GMR (90% CI) for Cmax, and AUClast after Y75T of Cohort B to those of Y150T of Cohort A were 0.6476 (0.5229-0.8021), and 1.1471 (0.8418-1.5632), respectively. Simulated steady-steady pregabalin concentrations after once-daily Y75T dosing in subjects with eGFR 45 mL/min/1.73 m² were within the range of steady-state concentrations simulated after once-daily Y150T dosing in subjects with eGFR 90 mL/min/1.73 m². The total pregabalin exposure of Y75T in patients with moderate renal impairment was comparable with that of Y150T in subjects with near-normal renal function. [ABSTRACT FROM AUTHOR]

Lyotropic liquid crystals (LLCs) are liquids that have crystalline structures. LLCs as drug delivery systems that can deliver hydrophobic, hydrophilic, and amphiphilic agents. Due to their unique phases and structures, LLCs can protect both small molecules and biologics from the gastrointestinal tract's harsh environment, thus making LLCs attractive as carriers for oral drug delivery. In this review, we discuss the advantages of LLCs and LLCs as oral formulations targeting intestinal lymphatic transport. In oral LLC formulations, the relationship between the micelle compositions and the resulting LLC structures as well as intestinal transport and absorption were determined. In addition, we further demonstrated approaches for the enhancement of intestinal lymphatic transport: (1) lipid-based LLCs promoting chylomicron secretion and (2) the design of LLC nanoparticles with M cell-triggered ligands for targeting the M cell pathway. In this review, we introduce LLC drug delivery systems and their characteristics. Our review focuses on recent approaches using oral LLC drug delivery strategies targeting the intestinal lymphatic system to enhance drug bioavailability. [ABSTRACT FROM AUTHOR]

As the opioid overdose epidemic escalates, there is an urgent need for treatment innovations to address both patient and clinician barriers when initiating buprenorphine in the emergency department (ED). These include insurance status, logistical challenges such as the ability to fill a prescription and transportation, concerns regarding diversion, and availability of urgent referral sites. Extended‐release buprenorphine (XR‐BUP) preparations such as a new 7‐day injectable could potentially solve some of these issues. We describe the pharmacokinetics of a new 7‐day XR‐BUP formulation and the feasibility of its use in the ED setting. We report our early experiences with this medication (investigational drug CAM2038), in the context of an ongoing clinical trial entitled Emergency Department‐Initiated BUP VAlidaTION (ED INNOVATION), to inform emergency clinicians as they consider incorporating this medication into their practice. The medication was approved by the European Medicines Agency in 2018 and the U.S. Food and Drug Administration in 2023 for those 18 years or older for the treatment of moderate to severe opioid use disorder (OUD). We report our experience with approximately 800 ED patients with OUD who received the 7‐day XR‐BUP preparation in the ED between June 2020 and July 2023. [ABSTRACT FROM AUTHOR]

Corneal disorders and diseases are prevalent in the field of clinical ophthalmology. Fungal keratitis, one of the major factors leading to visual impairment and blindness worldwide, presents significant challenges for traditional topical eye drop treatments. The objective of this study was to create biocompatible 3D-crosslinked hydrogels for drug delivery to the cornea, intending to enhance the bioavailability of ophthalmic drugs. Firstly, a series of flexible and porous hydrogels were synthesized (free-radical polymerization), characterized, and evaluated. The materials were prepared by the free-radical polymerization reaction of 1-vinyl-2-pyrrolidinone (also known as N-vinylpyrrolidone or NVP) and 1,6-hexanediol dimethacrylate (crosslinker) in the presence of polyethylene glycol 1000 (PEG-1000) as the porogen. After the physicochemical characterization of these materials, the chosen hydrogel demonstrated outstanding cytocompatibility in vitro. Subsequently, the selected porous hydrogels could be loaded with voriconazole, an antifungal medication. The procedure was adapted to realize a loading of 175 mg voriconazole per ring, which slightly exceeds the amount of voriconazole that is instilled into the eye via drop therapy (a single eye drop corresponds with approximately 100 mg voriconazole). The voriconazole-loaded rings exhibited a stable zero-order release pattern over the first two hours, which points to a significantly improved bioavailability of the drug. Ex vivo experiments using the established porcine eye model provided confirmation of a 10-fold increase in drug penetration into the cornea (after 2 h of application of the hydrogel ring, 35.8 ± 3.2% of the original dose is retrieved from the cornea, which compares with 3.9 ± 1% of the original dose in the case of eye drop therapy). These innovative hydrogel rods and rings show great potential for improving the bioavailability of ophthalmic drugs, which could potentially lead to reduced hospitalization durations and treatment expenses. [ABSTRACT FROM AUTHOR]

Background: Nephropathic cystinosis is a rare lysosomal storage disorder in which accumulation of cystine and formation of crystals particularly impair kidney function and gradually lead to multi-organ dysfunction. Lifelong therapy with the aminothiol cysteamine can delay the development of kidney failure and the need for transplant. The purpose of our long-term study was to explore the effects of transitioning from immediate release (IR) to extended release (ER) formulation in Norwegian patients in routine clinical care. Methods: We retrospectively analysed data on efficacy and safety in 10 paediatric and adult patients. Data were obtained from up to 6 years before and 6 years after transitioning from IR- to ER-cysteamine. Results: Mean white blood cell (WBC) cystine levels remained comparable between the different treatment periods (1.19 versus 1.38 nmol hemicystine/mg protein) although most patients under ER-cysteamine underwent dose reductions. For the non-transplanted patients, the mean estimated glomerular filtration rate (eGFR) change/year was more pronounced during ER-treatment (− 3.39 versus − 6.80 ml/min/1.73 m2/year) possibly influenced by individual events, such as tubulointerstitial nephritis and colitis. Growth measured by Z-height score tended to develop positively. Four of seven patients reported improvement of halitosis, one reported unchanged and two reported worsened symptoms. Most adverse drug reactions (ADRs) were of mild severity. One patient developed two serious ADRs and switched back to IR-formulation. Conclusions: The results from this long-term retrospective study indicate that switching from IR- to ER-cysteamine was feasible and well tolerated under routine clinical practice. ER-cysteamine allowed satisfactory disease control over the long period considered. [ABSTRACT FROM AUTHOR]

To address the medication requirements of different populations, efforts have been made to develop sustained-release formulations of andrographolide. In this study, andrographolide tablets (3D-AGT) and encapsulating agents (3D-AGE) were created using a semi-solid extrusion (SSE) 3D printer with varying release rates. Sodium alginate and chitosan were utilized as excipients to produce a hexagonal 3D-AGT with a diameter of 10.00 mm and a height of 3.00 mm. The 3D-AGE was then assembled by combining the upper layer and the ground floor loaded with andrographolide. Both formulations exhibited smooth surfaces and uniform internal composition. FT-IR analysis confirmed that the chemical structures of andrographolide and the excipients remained intact throughout the printing process. The drug loading capacity of 3D-AGT preparations, formulated with four different excipient ratios, exceeded 85%. Additionally, two 3D-AGE preparations (10 and 20 mg) were successfully loaded with the drug. In vitro drug release tests demonstrated that both 3D-AGT and 3D-AGE preparations exhibited satisfactory drug release performance. However, the proportions of excipients and drug loading had minimal impact on the cumulative drug dissolution effect. In terms of antibacterial activity against Escherichia coli, both preparations displayed antibacterial rates of nearly 85% or higher in vitro. Furthermore, the average results from nine volunteers indicated that 3D-AGE effectively masked the bitter taste of andrographolide. This study suggested that the release rate of andrographolide could be regulated using SSE 3D printing through careful structural design and adjustment of printing parameters, thus providing a novel approach for personalized traditional Chinese medicine preparations. [ABSTRACT FROM AUTHOR]

Asthma is an inflammatory condition which leads to narrowed and hyperresponsive airways. In recent times, the standard approach to managing asthma has been to use an inhaled corticosteroid (ICS, the preventer) to dampen down the inflammation and a short-acting bronchodilator (the reliever) to open up the airways if the person with asthma needed symptom relief. If the preventer inhaler is doing its job, the reliever should not be needed more than three times per week. The British Thoracic Society/Scottish Intercollegiate Guidelines Network guidelines currently reflect this approach (BTS/SIGN, 2019), but later this year these guidelines will be updated based on a collaboration with the National Institute for Health and Care Excellence (NICE). NICE previously published its own asthma guidelines, which were controversial in terms of their recommendations, with a focus on using preventer therapy if a reliever was needed three times a week or more, rather than prioritising the use of anti-inflammatory treatment for an inflammatory condition. It will be interesting to see what the joint recommendations will be. In the meantime, many clinicians with an interest in asthma management are looking to the Global Initiative for Asthma recommendations for a fresh approach to asthma management (GINA, 2023). [ABSTRACT FROM AUTHOR]