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Background: The introduction of CDK 4/6 inhibitors for breast cancer patients has contributed to increased ambulatory patient visits for oncologists. The Medication Assessment by Pharmacist program aims to evaluate the impact of oncology pharmacists performing medication assessment follow-up visits. Methods: Breast cancer patients on a CDK 4/6 inhibitor deemed suitable by their oncologist for pharmacist assessment could be booked for a pharmacist medication assessment appointment at alternate treatment cycles. Results: Between February 2019 to November 2021, 29 of 128 patients (22.7%) were selected for 46 total Medication Assessment by Pharmacist visits resulting in 920 min of clinic time savings for physicians. There were similar rates of adhering to provincial protocols for scheduling visits (99% vs. 96%, p = 0.12) and monitoring investigations (98% vs. 98%, p = 0.96) between those enrolled in Medication Assessment by Pharmacist or not. Surveys completed by medical oncologists and pharmacists demonstrated that nine of nine oncologists felt Medication Assessment by Pharmacist reduced workload and wanted Medication Assessment by Pharmacist expanded to additional oncology drugs. Pharmacist-completed surveys revealed that nine of nine pharmacists felt Medication Assessment by Pharmacist increased job satisfaction, and allowed further application of clinical skills. All agreed that patients were receptive to meeting with pharmacists. According to survey results, 33% of oncologists versus 100% of pharmacists routinely asked about medication adherence, new medications or supplements. Conclusion: Integrating pharmacists into a shared care model reduces ambulatory patient visits for oncologists without deviating from provincial protocol guidelines for monitoring and visits for patients on CDK 4/6 inhibitors. Leveraging the medication expertise of pharmacists also increases the frequency of addressing medication adherence and concurrent therapies. Medication Assessment by Pharmacist may be an effective strategy in alleviating projected shortages of oncology providers. [ABSTRACT FROM AUTHOR]

To evaluate the factors associated with poor medication adherence in patients with DM and HTN in Peru. A cross-sectional study. We analyzed data from the Peruvian Demographic and Family Health Survey from 2014 to 2019. Adjusted prevalence ratios (aPR) and their respective 95% confidence intervals (CI) were estimated to determine the factors associated with poor medication adherence. We included 15,184 participants with a known diagnosis of DM and HTN. The frequency of poor medication adherence was 37.1%, with 36.7% among individuals with HTN and 29.2% among individuals with DM. Those belonging to age groups above 30 years (aPR: 0.77; 95% CI: 0.74–0.80, for the group ≥ 60 years) had a lower frequency of poor medication adherence. Meanwhile, being male (aPR: 1.03; 95% CI: 1.01–1.05), lacking health insurance (aPR: 1.08; 95% CI: 1.05–1.10), belonging to lower wealth quintiles (aPR: 1.12; 95% CI: 1.08–1.17, for the first quintile), and living in the mountain region (aPR: 1.09; 95% CI: 1.06–1.12) were associated with a higher frequency of poor medication adherence. These findings were consistent when stratifying by the type of disease. This study showed that poor medication adherence is common in patients with HTN and DM in Peru and is associated with sociodemographic factors, highlighting the importance of public health approaches to improve adherence. [ABSTRACT FROM AUTHOR]

Purpose: To explore patients' willingness to have medication adherence measured using different methods and evaluate the feasibility and validity of their combination (i.e., pill counts, a medication diary and a questionnaire assessing adherence two months post-discharge). Methods: (1) A cross-sectional evaluation of the willingness of patients with polypharmacy to have their medication adherence measured post-discharge. (2) Medication adherence was monitored during two months using pill counts based on preserved medication packages and a diary in which patients registered their adherence-related problems. During a home visit, the Probabilistic Medication Adherence Scale (ProMAS) and a questionnaire on feasibility were administered. Results: A total of 144 participants completed the questionnaire at discharge. The majority was willing to communicate truthfully about their adherence (97%) and to share adherence-related information with healthcare providers (99%). More participants were willing to preserve medication packages (76%) than to complete a medication diary (67%) during two months. Most participants reported that preserving medication packages (91%), completing the diary (99%) and the ProMAS (99%) were no effort to them. According to the majority of participants (60%), pill counts most accurately reflected medication adherence, followed by the diary (39%) and ProMAS (1%). Medication adherence measured by pill counts correlated significantly with ProMAS scores, but not with the number of diary-reported problems. However, adherence measured by the medication diary and ProMAS correlated significantly. Conclusion: Combining tools for measuring adherence seems feasible and can provide insight into the accordance of patients' actual medication use with their prescribed regimen, but also into problems contributing to non-adherence. [ABSTRACT FROM AUTHOR]

Objective: Statin treatment compliance and achieving target levels differ between populations. This study aimed to determine the status of achieving the lipid targets and evaluate patients' compliance to statin treatment in type 2 diabetic patients with dyslipidemia. Method: This cross-sectional study included type 2 diabetes mellitus (T2DM) patients with dyslipidemia who applied for treatment at our polyclinics. Statin compliance was evaluated using the Modified Morisky Adherence Scale (MMAS-8) through a face-to-face interview. Cardiovascular (CV) risk was calculated according to the 2019 ESC (European Society of Cardiology) criteria by evaluating the patients' individual risk factors. LDL targets were determined according to risk categories with the same criteria. Results: A total of 504 patients (F/M: 274/230) were included. The serum LDL levels were 102.6 ± 39.2 mg/dL. Of the patients, 56.1% were under statin treatment. CV risk was very high in 73.6% of patients. LDL levels were significantly lower in users than in non-users (91.2 ± 26.0, 117.3 ± 38.4, p < 0.0001). The rate of reaching the LDL target was 14.8% in statin users. Treatment compliance was low for 40.6% of statin users. Discontinuation of statin treatment due to side effects was 15.7% (n = 14). N = 49 patients willingly discontinued statin treatment. They reported that 40.8% considered the treatment unnecessary. Conclusion: It was observed that 56.1% of type 2 diabetic patients were on statin therapy. A small percentage of them 14.8% (n = 42) reached the LDL target. Statin non-compliance and a lack of awareness of the statin treatment are the main reasons for high LDL levels in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Three Diels-Alder type adducts (1-3) along with their precursors, including one 2-arylbenzofuran (4) and one stilbene (5), were isolated from the MeOH extract of M. alba var. shalun root cultures. Among them, 1 is a new Diels-Alder type adduct named morushalunin D. The molecular structures of 1-5 were elucidated based on spectroscopic data and comparison with the literatures. Cytotoxic properties of compounds 1-5 were evaluated against murine leukemia P-388 cells. Morushalunin D (1), mulberrofuran T (2), sorocein A (3), moracin M (4), and oxyresveratrol (5) were active, significantly inhibiting the growth of P-388 cells with IC50 values of 0.5, 1.0, 0.6, 2.0, and 3.3 μg/ml, respectively. [ABSTRACT FROM AUTHOR]

We conducted a parallel-group randomized controlled trial in three HIV clinics in Mexico to evaluate a user-centred habit-formation intervention to improve ART adherence among MSM living with HIV. We randomized 74 participants to the intervention group and 77 to the control group. We measured adherence at one, four, and ten months through medication possession ratio and self-reported adherence. Additionally, we measured viral load, CD4 cell count, major depression disorder symptoms, and alcohol and substance use disorder at baseline, fourth and tenth months. We found no statistically significant effect on adherence between groups. However, the intervention demonstrated positive results in major depression disorder symptoms (21% vs. 6%, p = 0.008) and substance use disorder (11% vs. 1%, p = 0.018) in the fourth month. The latter is relevant because, in addition to its direct benefit, it might also improve the chances of maintaining adequate adherence in the long term. This trial was retrospectively registered at ClinicalTrials.gov (trial number NCT03410680) on 8 January 2018. Trial registration: ClinicalTrials.gov identifier: NCT03410680. [ABSTRACT FROM AUTHOR]

Simple Summary: This review article delves into the expanding role of 3D culture models in advancing breast cancer biology comprehension and enhancing drug response predictions, with an emphasis on triple-negative breast cancer (TNBC). It highlights the indispensable contribution of advanced technologies like patient-derived organoids and multi-omics analyses in unraveling tumor biology intricacies and drug sensitivity patterns, thereby fostering the creation of personalized therapeutic approaches. Additionally, it underscores the necessity of understanding the clinical translation for optimal model selection in TNBC therapy development, while acknowledging the impact of differences in cell culture models and culture conditions on drug response disparities. Advancements in cell culturing techniques have allowed the development of three-dimensional (3D) cell culture models sourced directly from patients' tissues and tumors, faithfully replicating the native tissue environment. These models provide a more clinically relevant platform for studying disease progression and treatment responses compared to traditional two-dimensional (2D) models. Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) emerge as innovative 3D cancer models capable of accurately mimicking the tumor's unique features, enhancing our understanding of tumor complexities, and predicting clinical outcomes. Triple-negative breast cancer (TNBC) poses significant clinical challenges due to its aggressive nature, propensity for early metastasis, and limited treatment options. TNBC PDOs and PDXOs have significantly contributed to the comprehension of TNBC, providing novel insights into its underlying mechanism and identifying potential therapeutic targets. This review explores the transformative role of various 3D cancer models in elucidating TNBC pathogenesis and guiding novel therapeutic strategies. It also provides an overview of diverse 3D cell culture models, derived from cell lines and tumors, highlighting their advantages and culturing challenges. Finally, it delves into live-cell imaging techniques, endpoint assays, and alternative cell culture media and methodologies, such as scaffold-free and scaffold-based systems, essential for advancing 3D cancer model research and development. [ABSTRACT FROM AUTHOR]

We used group-based trajectory models to identify 4 distinct trajectory patterns of adherence to preexposure prophylaxis (PrEP) among 20 696 users. Only 44.5% were consistently PrEP adherent, with younger age, being female, or having substance use disorder or depression associated with early discontinuation. Public health efforts are needed to improve PrEP adherence. [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1–9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1–2 and 4–9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1–9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07–14.3). The expression of TLRs 1–6 and 8–9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1–2 and 4–9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors. [ABSTRACT FROM AUTHOR]

The article explores the use of re-randomization tests as a sensitivity analysis in two multicenter randomized controlled trials (RCTs) evaluating a new vaccine. The tests were conducted to confirm the results of the primary analyses, which used analysis of covariance (ANCOVA). The authors recommend pre-specifying re-randomization tests in RCTs with dynamic covariate-adaptive randomization and highlight the importance of considering methodological and computational aspects. The article also references three additional articles that discuss the significance of randomization in clinical trials and the potential challenges that can arise when it is not properly implemented. These articles offer valuable insights and perspectives for researchers studying clinical trials and experimental design. [Extracted from the article]

Background: Checkpoint inhibition has emerged as an effective treatment strategy for a variety of cancers, including in older adults. However, older patients with cancer represent a heterogenous group as they can vary widely in frailty, cognition, and physical status. Objective: This study aims to investigate the association between clinical frailty and immune-related treatment toxicity, hospitalization, and treatment discontinuation due to immune-related treatment toxicity in older patients treated with checkpoint inhibitors. Methods: Patients aged 70 years and older treated with checkpoint inhibitors were selected from the TENT study, IMAGINE study, and "Tolerability and safety of immunotherapy study". Clinical frailty was assessed by the Geriatric-8 test score and World Health Organization (WHO) status. Outcomes were grades 3–5 toxicity, hospitalization, and treatment discontinuation due to toxicity during treatment. Results: Of 99 patients included, 22% had comorbidities. While 33% of the patients were considered frail based on an abnormal Geriatric-8 test score of < 15, physical impairments were considered absent in 51% (WHO score of 0) and mild in 40% (WHO score of 1). Despite the limited sample size of the cohort, consistent trends were observed with patients with an abnormal Geriatric-8 test score of < 15 or a higher WHO score of 1 for having higher odds of toxicity [odds ratio (OR) 2.32 (95% CI 0.41–13.02); OR 1.33 (95% CI 0.45–4.17)], treatment discontinuation due to immune-related treatment toxicity [OR 2.25 (95% CI 0.61–8.31); OR 2.18 (95% CI 0.7–6.73)], and hospitalization due to immune-related treatment toxicity [OR 3.72 (95% CI 0.39–35.4); OR 1.31 (95% CI 0.35–4.9)]. Moreover, in a sub-analysis, we observed that the treatment discontinuation due to immune-related treatment toxicity occurred often in patients with grade 1–2 toxicity as well. Conclusions: Although not statistically significant, in older patients treated with immunotherapy in a real-life population with cancer, we observed consistent trends towards increased toxicity, hospitalization, and treatment discontinuation with increasing frailty. Larger studies are needed to confirm these exploratory results. Moreover, older patients with a lower toxicity grade 1–2 experienced early treatment discontinuation frequently, suggesting a lower tolerance of toxicity. [ABSTRACT FROM AUTHOR]

Simple Summary: The study investigates the effects of curcumin in native conditions and after irradiation with 450 nm light on the energy metabolism, redox balance, and cellular growth of head and neck cancer cells and human primary fibroblasts. Although curcumin in native conditions already shows an anti-cancer effect, affecting energy metabolism and limiting the growth of tumor cells and cells that inhabit the surrounding microenvironment, irradiation with 450 nm light (photodynamic) enhances its effect by acting on antioxidant defenses. This study, therefore, opens up new perspectives on specific wavelengths of light that appear to be able to improve the drug's action on cancer growth and proliferation, offering hope for better patient outcomes in the future. Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting FoF1-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm2, continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W—450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin's effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between missed CMS Star Ratings quality measures for medication adherence over 3 years for diabetes, hypertension, and hyperlipidemia medications (9 measures) and health care utilization and relative costs. STUDY DESIGN: Retrospective cohort study. METHODS: The study examined eligible patients who qualified for the diabetes, statin, and renin-angiotensin system antagonist medication adherence measures in 2018, 2019, and 2020 and were continuously enrolled in a Medicare Advantage prescription drug plan from 2017 through 2021. Atotal of 103,900 patients were divided into 4 groups based on the number of adherence measures missed (3 medication classes over 3 years): (1) missed 0 measures, (2) missed 1measure, (3) missed 2 or 3 measures, and (4) missed 4 or more measures. To achieve a quality measure, patients had to meet the Pharmacy Quality Alliance 80% threshold of proportion of days covered during the calendar year. RESULTS: The mean age of the cohort was 71.1 years, and 49.9% were female. Compared with patients who missed 0 of 9 adherence measures, those who missed 1 measure, 2 or 3 measures, and 4 or more measures experienced 12% to 26%, 22% to 42%, and 24% to 50% increased risks, respectively, of all-cause and diabetes-related inpatient stays and all-cause and diabetes-related emergency department visits (allPvalues<.01). Additionally, patients who missed 1, 2 or 3, and 4 or more adherence measures experienced 14%, 19%, and 20% higher monthly medical costs, respectively. CONCLUSIONS: Missing Star Ratings quality measures for medication adherence was associated with an increased likelihood of health care resource utilization and increased costs for patients taking medications to treat diabetes, hypertension, and hyperlipidemia. [ABSTRACT FROM AUTHOR]

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to outline the use of population and disease registries for clinical trial pre-screening. Materials and methods: The search was conducted in the time period of January 2014 to December 2022 in three databases: MEDLINE, Embase, and Web of Science Core Collection. References were screened using the Rayyan software, firstly based on titles and abstracts only, and secondly through full text review. Quality of the included studies was assessed using the List of Included Studies and quality Assurance in Review tool, enabling inclusion of publications of only moderate to high quality. Results: The search originally identified 1430 citations, but only 24 studies were included, reporting the use of population and/or disease registries for trial pre-screening. Nine disease domains were represented, with 54% of studies using registries based in the USA, and 62.5% of the studies using national registries. Half of the studies reported usage for drug trials, and over 478,679 patients were identified through registries in this review. Main advantages of the pre-screening methodology were reduced financial burden and time reduction. Discussion and conclusion: The use of registries for trial pre-screening increases reproducibility of the pre-screening process across trials and sites, allowing for implementation and improvement of a quality assurance process. Pre-screening strategies seem under-reported, and we encourage more trials to use and describe their pre-screening processes, as there is a need for standardized methodological guidelines. [ABSTRACT FROM AUTHOR]

Background: Leptomeningeal metastasis (LM) of small cell lung cancer (SCLC) is a highly detrimental occurrence associated with severe neurological disorders, lacking effective treatment currently. Proteolysis-targeting chimeric molecules (PROTACs) may provide new therapeutic avenues for treatment of podophyllotoxin derivatives-resistant SCLC with LM, warranting further exploration. Methods: The SCLC cell line H128 expressing luciferase were mutated by MNNG to generate H128-Mut cell line. After subcutaneous inoculation of H128-Mut into nude mice, H128-LM and H128-BPM (brain parenchymal metastasis) cell lines were primarily cultured from LM and BPM tissues individually, and employed to in vitro drug testing. The SCLC-LM mouse model was established by inoculating H128-LM into nude mice via carotid artery and subjected to in vivo drug testing. RNA-seq and immunoblotting were conducted to uncover the molecular targets for LM. Results: The SCLC-LM mouse model was successfully established, confirmed by in vivo live imaging and histological examination. The upregulated genes included EZH2, SLC44A4, VEGFA, etc. in both BPM and LM cells, while SLC44A4 was particularly upregulated in LM cells. When combined with PROTAC EZH2 degrader-1, the drug sensitivity of cisplatin, etoposide (VP16), and teniposide (VM26) for H128-LM was significantly increased in vitro. The in vivo drug trials with SCLC-LM mouse model demonstrated that PROTAC EZH2 degrader-1 plus VM26 or cisplatin/ VP16 inhibited H128-LM tumour significantly compared to VM26 or cisplatin/ VP16 alone (P < 0.01). Conclusion: The SCLC-LM model effectively simulates the pathophysiological process of SCLC metastasis to the leptomeninges. PROTAC EZH2 degrader-1 overcomes chemoresistance in SCLC, suggesting its potential therapeutic value for SCLC LM. [ABSTRACT FROM AUTHOR]

Background/Aims: Mirikizumab is a p19-directed anti-interleukin-23 antibody with potential efficacy against ulcerative colitis (UC). We evaluated the efficacy and safety of mirikizumab in a Japanese subpopulation with moderately to severely active UC from the LUCENT-1 and LUCENT-2 studies. Methods: LUCENT-1 and LUCENT-2 were phase 3, randomized, double-blind, placebo-controlled trials of mirikizumab therapy in adults with moderately to severely active UC. LUCENT-1 was a 12-week induction trial where patients were randomized 3:1 to receive intravenous mirikizumab 300 mg or placebo every 4 weeks (Q4W). Patients achieving a clinical response with mirikizumab following the induction study were re-randomized 2:1 to double-blind treatment with either mirikizumab 200 mg or placebo subcutaneously Q4W during the 40-week maintenance study. The primary outcomes were clinical remission at week 12 of LUCENT-1 and week 40 of LUCENT-2. Results: A total of 137 patients enrolled in Japan were randomized to mirikizumab (n = 102) or placebo (n = 35). Compared with placebo, patients who received mirikizumab showed numerically higher clinical remission at week 12 of induction (32.4% [n = 33] vs. 2.9% [n = 1]) and at week 40 of maintenance (48.9% [n = 23] vs. 28.0% [n = 7]). A greater number of patients achieved key secondary endpoints in the mirikizumab group compared with placebo. The frequency of treatment-emergent adverse events was similar across mirikizumab and placebo groups. Efficacy and safety results observed in the Japanese subpopulation were generally consistent with those in the overall population. Conclusions: Mirikizumab induction and maintenance treatments were effective in Japanese patients with moderately to severely active UC. No new safety concerns were identified. [ABSTRACT FROM AUTHOR]

Background: The Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program aims to improve the cardiovascular health of women aged 40–64 years with low incomes, and who are uninsured or underinsured. The objective is to examine WISEWOMAN participants with hypertension who had high blood pressure (BP) improvement from January 2014 to June 2018, by race and ethnicity. Also examined was participation in WISEWOMAN Healthy Behavior Support Services (HBSS) and adherence to antihypertensive medication. Materials and Methods: WISEWOMAN data from January 2014 to June 2018 were analyzed by race and ethnicity. BP improvement was defined as at least a 5 mm Hg decrease in systolic or diastolic BP values from baseline screening to rescreening. The prevalence of HBSS participation and antihypertensive medication adherence were calculated among hypertensive women with BP improvement. Results: Approximately 64.2% (4,984) of WISEWOMAN participants with hypertension had at least a 5 mm Hg BP improvement. These improvements were consistent across each race and ethnicity (p = 0.56) in the study. Nearly 70% of women who had BP improvement attended at least one HBSS. Hispanic women (80.1%) had the highest HBSS attendance percentage compared to non-Hispanic Black women (64.1%) and non-Hispanic White women (63.8%; p < 0.001). About 80% of women with BP improvement reported being adherent to antihypertensive medication in the previous 7 days. Conclusions: The proportion of women achieving BP improvement in the WISEWOMAN program was consistent across race and ethnicity. In addition, women with BP improvement reported adherence to antihypertensive medication and participation in HBSS. [ABSTRACT FROM AUTHOR]

Based on computer-aided drug design (CADD), the active groups of the known active small molecule compounds that can bind to EGFR target protein were analyzed through the molecular docking method. Then, 12 novel asiatic acid derivatives were synthesized by introducing active groups at ring A and C-28 positions of asiatic acid. The structures of these novel compounds were determined by NMR and MS. Furthermore, the anti-tumor activities of these derivatives on human lung cancer cells (A549) and human breast cancer cells (MCF-7) were evaluated by MTT assay. In conclusion, compounds I4 and II3 have stronger anti-cancer activity than parent compounds, the activities were stronger than gefitinib and comparable to afatinib, which may be potential candidate compounds for tumor therapy. [ABSTRACT FROM AUTHOR]

The clinical importance of adhering to the regimen in tuberculosis patients has been widely investigated, but most studies were conducted in controlled settings and in limited populations. We aimed to measure the level of real-world adherence during intensive phase and investigate the predictors and the risk of mortality and health outcomes of intensive phase non-adherence in tuberculosis patients. We conducted a nationwide cohort study by linking the Korean National Tuberculosis Surveillance System and the National Health Information Database. We included all incident drug-susceptible tuberculosis patients who initiated the regimens recommended by the World Health Organization from 2013 to 2018. Adherence was measured using the proportion of days covered (poor [<50%], moderate [50%–79%], and high [≥80%]). We used logistic regression model to assess predictors and the Cox proportional hazard model to evaluate the risk of mortality and health outcomes with intensive phase non-adherence. Of 46,818 patients, there were 8% and 11% with poor and moderate adherent groups, respectively. Age ≥45 years, insulin use, and history of renal failure were predictors of non-adherence. Compared with high adherent group, poor and moderate adherent groups were associated with a substantial risk of mortality (poor: hazard ratio, 2.14 [95% confidence interval, 1.95–2.34]; moderate: 1.76 [1.62–1.92]). Similar trends were observed for health outcomes. Stratified analyses showed a higher risk of mortality in patients with medical aid, low income, and history of renal failure, systematic corticosteroids, and immunomodulators. Non-adherence during intensive phase increased mortality risk by twofold, underscoring targeted intervention for high-risk population, including advanced diabetes, and immunocompromised patients. [ABSTRACT FROM AUTHOR]

Haloperidol, the first butyrophenone neuroleptic, was created in Europe by Janssen Pharmaceuticals in 1958 and was introduced swiftly throughout the continent with great enthusiasm. On September 15, 1959, at Janssen's headquarters in Belgium, teams from around Europe praised the effectiveness of haloperidol. In the United States, on the contrary, its introduction was a tremendous failure, plagued by accusations of inefficacy and patent disputes. A clinical trial in Manhattan has been blamed for this commercial failure. The results of the Manhattan trial were seen as radically different from the results obtained in continental Europe. This divide would have considerable impact not only with regard to haloperidol's path on both sides of the Atlantic, but also possibly on the practical experience and theoretical construction of psychiatry. This article tries to reconstruct the story of that trial based mainly on published papers and interviews. Exploring how societal changes and issues of gender and race shaped this process, this investigation attempts to understand and contextualize different possible reasons for this Atlantic rift. [ABSTRACT FROM AUTHOR]

Hepatitis B virus reactivation (HBVr) during and after immunosuppressive/immunomodulatory (IS/IM) therapy is associated with significant morbidity and mortality, including hepatic decompensation and acute liver failure. The risk of HBVr with IS/IM has been heterogeneous and often unpredictable. As a result, patients with active or previous HBV infection are often excluded from clinical drug trials of such agents. Thorough screening for HBV infection, antiviral prophylaxis, and careful monitoring for HBVr have proven to be effective in reducing the rate of HBVr and improving its outcome in the context of IS/IM. Therefore, safe enrollment and management of certain HBV-marker–positive patients in clinical trials is possible. There is a great, unmet need for consistent, evidence-based recommendations for best practices pertaining to enrollment, monitoring, and management of HBVr in clinical trial participants receiving IS/IM. The aim of these consensus guidelines is to provide a step-by-step blueprint to safely enroll, monitor and manage the patient with inactive chronic or resolved HBV in IS/IM clinical trials from the time of screening through to the end of post-treatment follow up. [ABSTRACT FROM AUTHOR]

In Southern and Eastern Africa, initiation of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention has been high among adolescent girls and young women (AGYW) offered PrEP. However, persistence and prevention-effective use of PrEP among this critical group continues to be a challenge. We conducted a qualitative sub-study of AGYW from the Community PrEP Study in Eastern Cape Province, South Africa who had high rates of pick up for monthly PrEP refills over two years, but differing levels of PrEP adherence based on tenofovir-diphosphate (TFV-DP) measurements in dried blood spots (DBS). Contrasting 22 AGYW with low versus high levels of TFV-DP in DBS, we qualitatively explored factors which influenced PrEP persistence vs. non-persistence, unique patterns of PrEP use (e.g., discarding or stockpiling), and participant recommendations for improving AGYW prevention-effective use of PrEP in the future. Results showed that PrEP misconceptions and mistrust among participants' social networks negatively influenced adherence. In comparison, supportive families and/or partners and personal trust that PrEP works positively influenced adherence. Those with low adherence described being motivated to come to the site for other study benefits (e.g., reimbursement money, snacks, sanitary pads) and discarding PrEP to avoid stigma associated with being seen with pills. Future PrEP implementation strategies should focus on involving families and partners in PrEP support for AGYW and minimizing PrEP stigma at a community level. Trial registration NCT03977181. Retrospectively registered on June 6, 2019. [ABSTRACT FROM AUTHOR]

Women with HIV (WWH) face increased difficulties maintaining adherence to antiretroviral therapy (ART) due to a variety of demographic and psychosocial factors. To navigate the complexities of ART regimens, use of strategies to maintain adherence is recommended. Research in this area, however, has largely focused on adherence interventions, and few studies have examined self-reported preferences for adherence strategies. The purpose and objectives of this study were to explore the use of ART self-management strategies among a diverse sample of WWH, examine demographic and psychosocial differences in strategy use, and assess the association between strategies and ART adherence. The current study presents secondary data of 560 WWH enrolled in the Miami-Dade County Ryan White Program. Participants responded to questionnaire items assessing demographic and psychosocial characteristics, use of adherence strategies, and ART adherence during the past month. Principal component analysis identified four categories among the individual strategies and multivariable binomial logistic regression assessed adherence while controlling for individual-level factors. The majority of WWH reported optimal ART adherence, and nearly all used multiple individual strategies. The number of individual strategies used and preferences for strategy types were associated with various demographic and psychosocial characteristics. Adjusting for demographic and psychosocial characteristics, optimal ART adherence during the past month was associated with the use of four or more individual strategies. When conducting regular assessments of adherence, it may be beneficial to also assess use of adherence strategies and to discuss with WWH how using multiple strategies contributes to better adherence. [ABSTRACT FROM AUTHOR]

Background: Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. Objective: The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. Methods: The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. Results: Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage‐dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1‐EAAT2. Conclusion: In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease. [ABSTRACT FROM AUTHOR]

The three decades of experience with piezoelectric devices applied in the field of bioanalytical chemistry are shared. After introduction to principles and suitable measuring approaches, active and passive methods based on oscillators and impedance analysis, respectively, the focus is directed towards biosensing approaches. Immunosensing examples are provided, followed by other affinity sensing approaches based on hybridization of nucleic acids, aptamers, monitoring of enzyme activities, and detection of pathogenic microbes. The combination of piezosensors with cell lines and testing of drugs is highlighted, including mechanically active cells. The combination of piezosensors with other measuring techniques providing original hybrid devices is briefly discussed. [ABSTRACT FROM AUTHOR]

Background: Individuals with schizophrenia require prolonged antipsychotic medication treatment. But more than 50% of individuals with schizophrenia experience adverse medication experiences during their antipsychotic treatments. Such individuals often adjust or discontinue medication, leading to disease relapse and impaired social functioning. Psychiatric nurses should pay close attention to the medication experiences of individuals with schizophrenia. This research explore the relationship between medication burden and medication experience, as well as the mediating effect of medication belief in stable patients with schizophrenia. Methods: A convenience sample of hospitalized stable patients with schizophrenia were selected from Daqing Third Hospital and Baiyupao Hospital from September 2023 to December 2023. A survey was conducted with them using a questionnaire consisting of general information questionnaire, The Subjective Well-being Under Neuroleptic Treatment Scale(SWN), The Living with Medicines Questionnaire(LMQ), Beliefs about Medicines Questionnaire-Specific (BMQ-Specific). Pearson correlation analysis was used to explore the correlation between LMQ, BMQ-Specific and SWN scores, and multiple linear regression analysis was used to explore the influencing factors of medication experience in patients with schizophrenia. AMOS 24.0 was used to construct the structural equation modeling(SEM), and the mediation effect of the SEM was tested using Bootstrap method. Results: According to the sample size calculation requirements of structural equation model, a total of 300 samples were required in this study, and 400 effective questionnaires were actually collected in this study, which met the sample size requirements for constructing structural equation models. Bootstrap test showed that the mediation effect was significant. The total effect of medication burden on medication experience was significant (Z=-12.146, 95%CI (-0.577, -0.417), P < 0.001). The indirect effect of medication burden on medication experience, that is, the mediating effect of medication belief was significant (Z=-4.839, 95%CI (-0.217, -0.096), P < 0.001). The direct effect of medication burden on medication experience was significant (Z=-7.565, 95%CI (-0.437, -0.257), P < 0.001). This model belongs to partial mediation model. Conclusions: Psychiatric nurses can enhance the patients' medication experience by reducing medication burden and strengthening medication beliefs. Therefore, the results also provide theoretical references and decision-making foundations for psychiatric nursing professionals to develop appropriate management strategies for individuals with schizophrenia. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cell carcinoma (RCC) is common, affecting over 400,000 patients globally each year. In limited stage disease and where surgery is a feasible therapeutic option, event free survival rates are high. In contrast, locally advanced disease is associated with frequent relapse, and up to 30% of patients present with metastatic disease. Standard of care treatments for metastatic disease include tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI), but clinical responses are variable and generally not durable. Novel cell-based immunotherapy approaches such as Chimeric Antigen Receptor T-cells (CAR-T) and T-cell receptor engineered T-cells (TCR-T) have shown efficacy in some blood cancers and are currently under evaluation in solid tumours including RCC. Here, we review the landscape of cellular immunotherapy for RCC in the context of currently available therapies and outline how advanced engineering solutions may further enhance this therapeutic approach. Renal cell carcinoma (RCC) affects over 400,000 patients globally each year, and 30% of patients present with metastatic disease. Current standard of care therapy for metastatic RCC involve TKIs and ICIs, including combinatorial strategies, but this offers only modest clinical benefit. Novel treatment approaches are warranted, and cell-based immunotherapies for RCC hold significant promise. These are currently being tested in the pre-clinical setting and in early phase clinical trials. Here, we review the landscape of cellular immunotherapy for RCC in the context of currently available therapies, with a particular focus on defining the current best antigenic targets, the range of cell therapy products being explored in RCC, and how advanced engineering solutions may further enhance these therapies in the RCC space. [ABSTRACT FROM AUTHOR]

Mexico is the third Latin American country with the most children and adolescents living with human immunodeficiency virus (ALHIV). There is a lack of information on the characteristics of this population. We aimed to describe the social and mental health characteristics of Mexican ALHIV. A census was conducted of all adolescent patients with HIV at a pediatric hospital (n = 47; mean age 14.39, S.D. = 3.65) and their caregivers. We collected data on socio-demographic characteristics, family, intelligence, mental health, adverse life events, substance use, treatment, knowledge of Antiretroviral Treatment (ART) and HIV, and biomarkers. Most cases were transmitted vertically and self-reported ART adherence was above 90%. Some obstacles to adherence were medicine discomfort, believing that they did not need it, and forgetfulness. The vulnerabilities were intellectual disability, adverse life events, possible mental health problems, and little knowledge of their illness and treatment. These findings suggest the importance of interventions to improve the perception and knowledge of HIV and ART to increase ART adherence. [ABSTRACT FROM AUTHOR]

As an important part of medical science, Traditional Chinese Medicine (TCM) attracts much public attention due to its multi-target and multi-pathway characteristics in treating diseases. However, the limitations of traditional research methods pose a dilemma for the evaluation of clinical efficacy, the discovery of active ingredients and the elucidation of the mechanism of action. Therefore, innovative approaches that are in line with the characteristics of TCM theory and clinical practice are urgently needed. Chinmendomics, a newly emerging strategy for evaluating the efficacy of TCM, is proposed. This strategy combines systems biology, serum pharmacochemistry of TCM and bioinformatics to evaluate the efficacy of TCM with a holistic view by accurately identifying syndrome biomarkers and monitoring their complex metabolic processes intervened by TCM, and finding the agents associated with the metabolic course of pharmacodynamic biomarkers by constructing a bioinformatics-based correlation network model to further reveal the interaction between agents and pharmacodynamic targets. In this article, we review the recent progress of Chinmedomics to promote its application in the modernisation and internationalisation of TCM. [ABSTRACT FROM AUTHOR]

Objectives: For drugs reimbursed with limited evidence of patient benefits, confirmatory evidence of overall survival (OS) and quality of life (QoL) benefits is important. For QoL data to serve as valuable input to patients and decision-makers, it must be measured and analyzed using appropriate methods. We aimed to assess the measurement and analyses of post-reimbursement QoL data for cancer drugs introduced in Swedish healthcare with limited evidence at the time of reimbursement. Methods: We reviewed any published post-reimbursement trial data on QoL for cancer drugs reimbursed in Sweden between 2010 and 2020 with limited evidence of improvement in QoL and OS benefits at the time of reimbursement. We extracted information on the instruments used, frequency of measurement, extent of missing data, statistical approaches, and the use of pre-registration and study protocols. Results: Out of 22 drugs satisfying our inclusion criteria, we identified published QoL data for 12 drugs in 22 studies covering multiple cancer types. The most frequently used QoL instruments were EORTC QLQ-C30 and EQ-5D-3/5L. We identified three areas needing improvement in QoL measurement and analysis: (i) motivation for the frequency of measurements, (ii) handling of the substantial missing data problem, and (iii) inclusion and adherence to QoL analyses in clinical trial pre-registration and study protocols. Conclusions: Our review shows that the measurements and analysis of QoL data in our sample of cancer trials covering drugs initially reimbursed without any confirmed QoL or OS evidence have significant room for improvement. The increasing use of QoL assessments must be accompanied by a stricter adherence to best-practice guidelines to provide valuable input to patients and decision-makers. [ABSTRACT FROM AUTHOR]

Background: Harms, also known as adverse events (AEs), are recorded and monitored in randomised controlled trials (RCTs) to ensure participants' safety. Harms are recorded poorly or inconsistently in RCTs of Behaviour Change Interventions (BCI); however, limited guidance exists on how to record harms in BCI trials. This qualitative study explored experiences and perspectives from multi-disciplinary trial experts on recording harms in BCI trials. Methods: Data were collected through fifteen in-depth semi-structured qualitative interviews and three focus groups with thirty-two participants who work in the delivery and oversight of clinical trials. Participants included multi-disciplinary staff from eight CTUs, Chief investigators, and patient and public representatives. Interviews and focus group recordings were transcribed verbatim and thematic analysis was used to analyse the transcripts. Results: Five themes were identified, namely perception and understanding of harm, proportionate reporting and plausibility, the need for a multi-disciplinary approach, language of BCI harms and complex harms for complex interventions. Participants strongly believed harms should be recorded in BCI trials; however, making decisions on "how and what to record as harms" was difficult. Recording irrelevant harms placed a high burden on trial staff and participants, drained trial resources and was perceived as for little purpose. Participants believed proportionate recording was required that focused on events with a strong plausible link to the intervention. Multi-disciplinary trial team input was essential for identifying and collecting harms; however, this was difficult in practice due to lack of knowledge on harms from BCIs, lack of input or difference in opinion. The medical language of harms was recognised as a poor fit for BCI trial harms but was familiar and established within internal processes. Future guidance on this topic would be welcomed and could include summarised literature. Conclusions: Recording harms or adverse events in behaviour change intervention trials is complex and challenging; multi-disciplinary experts in trial design and implementation welcome forthcoming guidance on this topic. Issues include the high burden of recording irrelevant harms and use of definitions originally designed for drug trials. Proportionate recording of harms focused on events with a strong plausible link to the intervention and multi-disciplinary team input into decision making are essential. [ABSTRACT FROM AUTHOR]

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/ kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies [ABSTRACT FROM AUTHOR]

Effective medication management practice (MMP) improves compliance of chronic conditions management and reduces medication error for better clinical outcomes. This is important for stroke survivors with multiple comorbidities and post-stroke complications. This study aimed to determine appropriateness of home MMP and its associated factors among post stroke patients. This was a cross-sectional, single-centre study involving 120 stroke patients of a primary care medical centre in Kuala Lumpur between January and March 2021. The assessment of MMP appropriateness relied on scores obtained through a set of questions administered via face-to-face, online or telephone interview. The mean age of participants was 65.1 (SD 11.7) years. 55.8% of participants had inappropriate home MMP; where the majority did not update their medication list (86.3%), did not memorise the medication's name (75%), and did not return the leftover medication to the pharmacy (63.3%). Female gender (AOR: 2.74, 95% CI: 1.18-6.35, p-value: 0.019), household income (> RM4850) (AOR: 2.82, 95% CI: 1.03-7.69, p-value: 0.043), and number of clinic appointments (>2) (AOR: 5.27, 95% CI: 1.44-19.24, p-value: 0.012) were significantly correlated with better home MMP. The MMP among post-stroke patients was poor. Better home MMP were associated with female gender, higher socioeconomic status, and more frequent clinic appointments. Concerted health education should be provided, particularly focusing on medication management to improve home MMP in post-stroke patients and ultimately improving their overall health outcomes. [ABSTRACT FROM AUTHOR]

Background: Erenumab is a monoclonal antibody that targets the calcitonin gene‐related peptide (CGRP) receptor and is approved for the preventative treatment of migraine in adults. CGRP is involved in the regulation of vasomotor tone under physiologic and pathologic conditions, including hypertension. While there has not been evidence of hypertension in preclinical models or clinical trials, post‐marketing data suggest erenumab may be associated with hypertension. This led to a warning in the United States Food and Drug Administration prescribing information for erenumab. Objective: To determine the frequency of worsening blood pressure (BP) after initiation of erenumab in patients with migraine and how this is associated with hypertension. Methods: This is an observational retrospective cohort study evaluating patients at a tertiary headache or neurology department. Systolic and diastolic BPs were compared between the initial visit prior to initiation of erenumab, and follow‐up visit while on erenumab. Worsening BP was defined as moving from a lower stage to a higher stage of BP, as defined by the American Heart Association. Serious adverse vascular events were also recorded. Results: A total of 335 patients were included in the final analysis (mean [SD] age of 45.7 [14.40] years, 83.9% [281/335] female). At baseline, 20.9% (70/335) of patients had a prior diagnosis of hypertension. The median (interquartile range) time to follow‐up appointment from initial appointment was 20.5 (13.3–35.3) weeks. The mean (SD) BP at baseline was systolic 124.7 (15) mmHg and diastolic 77 (11) mmHg, and at follow‐up was systolic 124.0 (15) mmHg and diastolic 77.8 (9) mmHg. Overall, 23.3% (78/335) of all patients had worsening BP, whereas 13/225 (3.9%) patients had improvement in their BP. Patients with atrial fibrillation were more likely to develop worsening BP (odds ratio, 4.9, 95% confidence interval 1.12–21.4; p = 0.035). There was no association between worsening BP and pre‐existing hypertension, sex, body mass index, or age. One patient had non‐ST elevation myocardial infarction attributed to a hypertensive emergency while on erenumab. Conclusion: We found that 23.3% of patients initiated on erenumab may have developed worsening BP, suggesting the need for BP monitoring in patients initiated on erenumab. Plain Language Summary: This study aimed to determine how often blood pressure (BP) increases in patients with migraine after initiation of erenumab, a migraine preventative treatment. We compared patients' BP before starting erenumab versus while on erenumab. We found that nearly a quarter of patients developed higher BP, suggesting the need for BP monitoring in patients taking erenumab. [ABSTRACT FROM AUTHOR]

Background: Poor adherence to inhaled corticosteroids (ICS) is a significant challenge in pediatric asthma, contributing to health inequities. Text-message reminders for ICS therapy are an evidence-based approach that improves pediatric asthma medication adherence, yet has not been widely adopted into practice, partly due to lack of (1) participant input on design and implementation and (2) use of sustainable community linkages. Remote Asthma Link™ (RAL) seeks to fill this gap as a school-linked text-message intervention wherein parents of children with poorly controlled asthma received daily, 2-way text-message reminders for preventive inhaler use. Responses were shared with school nurses who conducted remote check-ins with families. Enrolled children, largely from underserved backgrounds, experienced improvements in medication adherence and asthma health outcomes. While initial results were promising, we have yet to elicit participant input to refine the protocol for more widespread implementation. Objective: Examine participant perspectives on barriers and facilitators of RAL implementation. Methods: Semistructured interviews were conducted May–June 2022 with intervention participants: 10 parents, 7 school nurses, and 4 pediatric providers (n = 21) until thematic saturation was reached. Interview transcripts were coded using thematic analysis. Results: Several facilitators for RAL implementation were identified, including ease of use and accessibility, personal connection to the school nurse, and receipt of a visual notification for habit formation. Barriers included challenges with school nurses reaching parents, poor understanding of program expectations, and lack of reimbursement structure. Participant-proposed solutions to barriers included utilizing alternate communication methods (eg, social media), educational sessions, and meeting with payors to consider reimbursement models. Conclusion: RAL is a school-linked text-message intervention demonstrating promise in improving outcomes and equity in asthma care. Key implementation facilitators, barriers, and proposed solutions will inform protocol adaptations to promote successful implementation of this and other text-message interventions into clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Adjuvant chemotherapy (AC) with S1 is beneficial for pancreatic cancer, but the completion rate of S1 remains at 70%. Additionally, there are no useful indicators for achieving completion of S1. Therefore, we have assumed that studying the C-reactive protein-to-albumin ratio as an indicator based on nutritional status may be useful in predicting this. When this indicator proves effective, we believe that more cases can complete the treatment by improving nutrition or adjusting the dosage before starting AC. Adjuvant chemotherapy (AC) with S-1 after radical surgery for resectable pancreatic cancer (PC) has shown a significant survival advantage over surgery alone. Consequently, ensuring that patients receive a consistent, uninterrupted S-1 regimen is of paramount importance. This study aimed to investigate whether the C-reactive protein-to-albumin ratio (CAR) could predict S-1 AC completion in PC patients without dropout due to adverse events (AEs). We retrospectively enrolled 95 patients who underwent radical pancreatectomy and S-1 AC for PC between January 2010 and December 2022. A statistical analysis was conducted to explore the correlation of predictive markers with S-1 completion, defined as continuous oral administration for 6 months. Among the 95 enrolled patients, 66 (69.5%) completed S-1, and 29 (30.5%) failed. Receiver operating characteristic curve analysis revealed 0.05 as the optimal CAR threshold to predict S-1 completion. Univariate and multivariate analyses further validated that a CAR ≥ 0.05 was independently correlated with S-1 completion (p < 0.001 and p = 0.006, respectively). Furthermore, a significant association was established between a higher CAR at initiation of oral administration and acceptable recurrence-free and overall survival (p = 0.003 and p < 0.001, respectively). CAR ≥ 0.05 serves as a predictive marker for difficulty in completing S-1 treatment as AC for PC due to AEs. [ABSTRACT FROM AUTHOR]

Objective: Administrative requirements could disrupt sustained Supplemental Nutrition Assistance Program (SNAP) participation among income‐eligible individuals. To meet their food needs, low‐income individuals without consistent SNAP benefits may compromise on medication use, posing a risk to their health. The objective of this study is to examine the association of SNAP participation duration in a given year with cost‐related medication nonadherence (CRN) and emergency department (ED) use in income‐eligible individuals. Design: Cross‐sectional. Sample: Non‐elderly and elderly adults who used prescription medications and participated in SNAP the previous year in 2016–2018 National Health Interview Survey. Subsamples included individuals with specific chronic conditions. Measurements: CRN and ED usage. Results: SNAP participation for <12 months in the previous year was related to increased CRN and ED use in nonelderly adults taking prescription medication, as well as in those with hypertension, cardiovascular disease and asthma. Further, <12‐month SNAP participation was associated with greater odds of having at least one ED visit in nonelderly and elderly adults. Conclusions: Sustained SNAP participation could help income‐eligible individuals better adhere to their prescribed medications and reduce health complications requiring ED visits. Findings suggest the importance of addressing SNAP participation gaps among income‐eligible individuals in health care settings. [ABSTRACT FROM AUTHOR]

Background: There are few studies that examine relationships between cognitive function, illness perceptions, and medication adherence after heart transplantation, limiting the development of effective adherence-promoting interventions. Objective: The purpose of this study was to describe relationships between cognitive function, illness perceptions, and medication adherence among heart transplant recipients. Methods: A cross-sectional, observational design was used. Measures included the telephone-Montreal Cognitive Assessment (t-MoCA©), Patient Health Questionnaire-9, Brief Test of Adult Cognition by Telephone, Basel Assessment of Adherence to Immunosuppressive Medications Scale, and the Brief Illness Perceptions Questionnaire. Descriptive statistics, point-biserial correlations, Pearson's correlations, and logistic regression were used to describe relationships. Results: Of the 35 participants (mean age: 61 years [SD: 10.3], 71.4% male, 71.4% white), 31.4% (n = 11) were classified as nonadherent to their immunosuppression medications. Higher immediate word recall, indicating better episodic memory (memory for autobiographical and recent events), and higher illness coherence scores were associated with not missing doses of medication. Higher t-MoCA© total scores, indicating normal cognitive function, and lower depression scores were associated with taking medications on time. More than 22% (n = 8) of participants scored less than 19 on the t-MoCA©, an indication of mild cognitive impairment. Conclusion: Cognitive impairment may be more common among heart transplant recipients than what is currently recognized, and specific domains of cognitive function were related to medication adherence after transplantation in this study. Future studies should include longitudinal evaluations of cognitive function, depression, and medication adherence. Consideration of these relationships is needed when designing adherence-promoting interventions for this population. [ABSTRACT FROM AUTHOR]

The article discusses a post hoc secondary analysis of a Phase II/III clinical trial for progressive supranuclear palsy (PSP), revealing that patients prescribed benzodiazepine derivatives experienced a more rapid worsening of PSP Rating Scale scores.

Introduction: Abnormal lipid metabolism, one of the hallmarks in cancer, has gradually emerged as a novel target for cancer treatment. As organelles that store and release excess lipids, lipid droplets (LDs) resemble "gears" and facilitate cancer development in the body. Aim: This review discusses the life cycle of LDs, the relationship between abnormal LDs and cancer hallmarks, and the application of LDs in theragnostic and clinical contexts to provide a contemporary understanding of the role of LDs in cancer. Methods: A systematic literature search was conducted in PubMed and SPORTDiscus. Retrieve and summarize clinical trials of drugs that target proteins associated with LD formation using the Clinical Trials website. Create a schematic diagram of lipid droplets in the tumor microenvironment using Adobe Illustrator. Conclusion: As one of the top ten hallmarks of cancer, abnormal lipid metabolism caused by excessive generation of LDs interrelates with other hallmarks. The crosstalk between excessive LDs and intracellular free fatty acids (FFAs) promotes an inflammatory environment that supports tumor growth. Moreover, LDs contribute to cancer metastasis and cell death resistance in vivo. Statins, as HMGCR inhibitors, are promising to be the pioneering commercially available anti‐cancer drugs that target LD formation. [ABSTRACT FROM AUTHOR]

Background: Anti‐myelin‐associated glycoprotein (MAG) neuropathy is a debilitating demyelinating polyneuropathy with no approved therapies. Our primary objective was to ascertain lenalidomide safety and maximum tolerated dose (MTD) in anti‐MAG neuropathy. Methods: This phase 1b, open‐label, single‐arm, dose‐finding trial was conducted from 2019 through 2022. The original design included a dose‐escalation/extension phase followed by a dose‐expansion phase. Three doses of lenalidomide were evaluated: 10, 15, and 25 mg. The main outcome was the MTD. Results: Eleven patients enrolled (10 men), with a mean age of 67.6 years (SD = 6.18, range 58–77 years) and mean disease duration of 8.5 years (SD = 10.9, range 1–40 years). The study terminated early due to higher‐than‐expected non‐dose‐limiting toxicity venous thromboembolism (VTE) events. The calculated MTD was 25 mg (posterior mean of toxicity probability was 0.01 with a 95% credible interval of 0.00, 0.06), but a recommended phase 2 dose of 15 mg was advised. For secondary exploratory outcomes, only EQ‐5D (−0.95, 95% CI −1.81 to −0.09) and total IgM (−162 mg/dL, 95% CI −298 to −26) showed signs of improvement by month 12. Conclusions: Lenalidomide was associated with higher‐than‐expected VTE events in anti‐MAG neuropathy patients, despite a calculated MTD of 25 mg. A recommended phase 2 dose of 15 mg was advised. Lenalidomide did not improve disability or impairment at 12 months, although this study was not powered for efficacy. The risks of long term lenalidomide may outweigh benefit for patients with anti‐MAG neuropathy. Any future efficacy study should address VTE risk, as current myeloma guidelines appear inadequate. Trial Registration: Lenalidomide in Anti‐MAG Neuropathy: Phase 1b Study, ClinicalTrials.gov Identifier: NCT03701711, https://clinicaltrials.gov/ct2/show/NCT03701711. First submitted October 10, 2018. First patient enrolled in January 2019. [ABSTRACT FROM AUTHOR]

Lumasiran (Oxlumo®), a first-in-class synthetic, double-stranded, ribonucleic acid (RNA) interference molecule targeting glycolate oxidase through silencing HAO1 mRNA, is approved in several countries for patients of any age and stage of kidney function with primary hyperoxaluria type 1 (PH1). Approval was based on results from the phase III ILLUMINATE trials. In the double-blind, placebo-controlled, ILLUMINATE-A trial, subcutaneous lumasiran was significantly more effective than placebo in reducing 24-h urinary oxalate excretion in patients aged ≥ 6 years with PH1; this effect was sustained for ≥ 36 months in ongoing longer-term analyses. In the single-arm ILLUMINATE-B trial, lumasiran reduced urinary oxalate:creatinine ratios and plasma oxalate levels in patients aged < 6 years with PH1. In the single-arm ILLUMINATE-C trial, lumasiran reduced plasma oxalate levels in patients with PH1 receiving dialysis as well as those not receiving dialysis. In secondary and exploratory analyses of these trials, nephrocalcinosis grade, kidney stone event rates and estimated glomerular filtration rates were either stable or improved with lumasiran. Lumasiran had an acceptable tolerability profile that remained consistent in longer-term analyses; the most common adverse events were mild and transient injection-site reactions. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1. Plain Language Summary: Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that leads to excess oxalate in urine or plasma requiring removal by the kidneys. This overproduction is damaging and can lead to kidney failure. Management of PH1 is typically not curative, eventually ending in kidney and/or liver transplantation. Lumasiran (Oxlumo®) is the first medicine to be approved in several countries for use in patients with PH1, regardless of their age or level of kidney function. It reduces liver oxalate production, lessening damage to the kidneys and potentially reducing the need for organ transplantation. In clinical trials, lumasiran was effective in reducing oxalate levels (in urine and/or plasma) in patients of all ages with PH1, and irrespective of whether they were receiving dialysis or not. Lumasiran either improved or stabilized the severity of calcium deposition in the kidneys, number of kidney stone events and kidney function. Lumasiran had an acceptable tolerability profile; the most common side effects were mild injection-site reactions that resolved quickly. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage (sICH), the most prevalent and lethal subtype of stroke, is characterized by spontaneous hemorrhage in the brain parenchyma. Presently, there are no effective methods for preventing and treating sICH. The existing sICH animal models can be broadly categorized into three classes: (1) induced intracerebral hemorrhage models, including autologous blood injection model, collagenase injection model, microballoon inflation model, and hyperglycemia-induced sICH hematoma expansion model; (2) spontaneous hypertensive intracerebral hemorrhage models mainly include stroke-prone spontaneously hypertensive rats (SHRsp) and stroke-prone renovascular hypertensive rats (RHRsp); (3) gene-modified models encompassing transgenic hypertensive intracerebral hemorrhage, transgenic cerebral amyloid angiopathy, arteriovenous malformation-related, cerebral cavernous malformation-related and collagen-related genetically modified animal models for sICH. These models contribute not only to unraveling the pathogenesis of sICH and exploring preventive or therapeutic interventions, but also serve as invaluable tools for conducting preclinical drug trials to advance novel treatments. This guide comprehensively reviews sICH pathogenesis, delineates the superiority and inferiority of different species of modeling animals, explains the modeling principles and techniques for various sICH animal models, elucidates the technical details of animal model production, summarizes the pathophysiological mechanism simulated by the models and their clinical relevance, outlines the neurobehavioral evaluation methodologies for sICH animal models, compares the advantages and disadvantages of various models, and suggests their applicable research areas. Additionally, it underscores critical considerations in the design of preclinical drug trials for sICH. [ABSTRACT FROM AUTHOR]

Few studies have been conducted to explore medication non-adherence in persons with schizophrenia (PWS) and its influencing factors in rural China. This study aimed to investigate the medication non-adherence and its influencing factors among PWS in rural China. A total of 269 PWS and their family caregivers in Xinjin district, Chengdu, China were investigated on medication adherence and related factors. Logistic regression was employed to identify the influencing factors. The results showed that 37.6% of PWS had medication non-adherence. PWS living with family caregivers had significantly lower rate of medication non-adherence (34.7%) than those not living with family caregivers (60.0%) (p < 0.01). Family caregivers' affiliate stigma of mental illness, knowledge of mental illness and self-esteem were significantly related to patients' medication non-adherence (p < 0.05). PWS' employment status, living with family caregiver, present mental status and social support were significantly related to medication adherence. This study shows medication non-adherence is severe among PWS in rural China. Both patient- and family-related factors affect patients' medication adherence seriously. Except improving patients' treatment and mental status, development of family caregiving, social support network and intervention on reducing stigma of mental illness should be crucial for enhancing PWS' medication adherence. [ABSTRACT FROM AUTHOR]

Background: Cellulitis is a common acute skin and soft tissue infection that causes substantial morbidity and healthcare costs. Aims: To audit the impact on cellulitis management, regimen tolerability and outcomes of switching from outpatient parenteral antimicrobial therapy (OPAT) using intravenous (i.v.) cefazolin once daily plus probenecid to oral beta‐lactam therapy (OBLT) using oral flucloxacillin plus probenecid. Methods: We undertook a retrospective audit on cellulitis management, regimen tolerability and outcomes at the Dunedin Public Hospital Emergency Department (ED) before and after a change of the local outpatient cellulitis treatment pathway from OPAT using i.v. cefazolin once daily plus probenecid to OBLT using oral flucloxacillin plus probenecid. Results: OPAT was used in 97/123 (78.9%) patients with cellulitis before compared to 1/70 (1.4%) after the pathway change (odds ratio (OR), 0.04, P < 0.01). OBLT was used in 26/123 (21.1%) patients with cellulitis before and 69/70 (98.6%) after (OR, 218.8, P < 0.01). Antimicrobial change due to intolerance occurred in 4/123 (3.2%) patients with cellulitis before and 4/70 (5.7%) after (OR, 1.8, P, not significant (NS)) the pathway change. Inpatient admission within 28 days occurred in 15/123 (12.2%) cellulitis patients before and 9/70 (12.9%) after (OR, 1.1, P, NS) the pathway change. Conclusions: Implementation of a change in outpatient cellulitis treatment pathway resulted in a significant change in prescribing practice. Our findings suggest that OBLT was both tolerable and had similar outcomes to OPAT. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the last two decades, there has been a major shift in cancer research models. What was once dominated by genetically engineered mice models and fast-growing immortalized cancer cell lines has given way to a number of patient-derived models of cancer (PDMCs) that may be more representative of human disease. However, the complexities of these patient-derived models, both in vitro and in vivo systems, influence both data interpretation and interoperability. To address these challenges, the PDMC Consortium within the National Cancer Institute undertook this review describing the past, present, and future use of PDMCs while providing example vignettes with practical recommendations from the collective experience of the consortium members. For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab. [ABSTRACT FROM AUTHOR]