J Natl Cancer Inst. 2023 Jul 12:djad135. doi: 10.1093/jnci/djad135. Online ahead of print.

ABSTRACT

BACKGROUND: Recently several new treatment regimens have been approved for treating metastatic hormone-sensitive prostate cancer (mHSPC), building on androgen deprivation therapy (ADT) alone. These include docetaxel-ADT (DA), Abiraterone Acetate-Prednisone-ADT (AAP), Apalutamide-ADT (AAT), Enzalutamide-ADT (ET), Darolutamide-Docetaxel-ADT (DAD) and Abiraterone- Prednisone-ADT-Docetaxel (AAD). There are no validated predictive biomarkers for choosing a specific regimen. The goal of this study was to conduct a health economic outcome evaluation to determine the optimal treatment from the US public sector (VA).

METHODS: We developed a partitioned survival model in which mHSPC patients transitioned between three health states (progression free, progressive disease to castrate resistance state, and death) at monthly intervals based on Weibull survival model estimated from published Kaplan-Meier curves using a Bayesian network meta-analysis of seven clinical trials (7,208 patients). The effectiveness outcome in our model was quality-adjusted life-years (QALYs). Cost input parameters included initial and subsequent treatment costs and costs for terminal care and for managing grade 3+ drug related adverse events, and were obtained from the Federal Supply Schedule and published literature.

RESULTS: Average 10-year costs ranged from $34,349 (ADT) to $658,928 (DAD) and mean QALYs ranged from 3.25 (ADT) to 4.57 (ET). Treatment strategies DA, EAD, AAT, and DAD were eliminated due to dominance (ie, they were more costly and less effective than other strategies). Of the remaining strategies, AAP was the most cost-effective strategy at a willingness-to-pay threshold of $100,000/QALY (ICER = $21,247/QALY).

CONCLUSIONS: Our simulation model found AAP to be an optimal first-line treatment for mHSPC from a public (VA) payer perspective.

PMID:37436697 | DOI:10.1093/jnci/djad135

Endocrinol Metab (Seoul). 2023 Jul 12. doi: 10.3803/EnM.2023.1684. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service.

METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months.

RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. Conclusion: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

PMID:37435663 | DOI:10.3803/EnM.2023.1684

Nutrients. 2023 May 2;15(9):2172. doi: 10.3390/nu15092172.

ABSTRACT

Despite the frequent changes in household composition in Sub-Saharan Africa, the literature on the household division process is sparse, with no evidence of its effect on food security. This paper addresses the topic in Malawi, where the fission process is evident and malnutrition is a severe problem. Using the Integrated Household Panel Dataset, this study applies the difference-in-difference model with the propensity score matching technique to compare matched groups of households that did and did not split between 2010 and 2013. The results suggest that coping strategies adopted by poor households and life course events determine household fission in Malawi, a process that benefits household food security in the short term. On average, the food consumption score is 3.74 units higher among households that split between 2010 and 2013 compared to the matched households that did not. However, the household division might have long-run adverse effects on food insecurity, especially for poor households due to the adoption of coping strategies that might compromise their human capital and income-generating activities. Therefore, this process warrants attention for the more accurate understanding, design, and evaluation of food security interventions.

PMID:37432382 | PMC:PMC10181379 | DOI:10.3390/nu15092172

Drug Ther Bull. 2023 Jul 11:dtb-2023-000038. doi: 10.1136/dtb.2023.000038. Online ahead of print.

NO ABSTRACT

PMID:37433645 | DOI:10.1136/dtb.2023.000038

BMJ Open. 2023 Jul 11;13(7):e070185. doi: 10.1136/bmjopen-2022-070185.

ABSTRACT

INTRODUCTION: Parkinson's disease is one of the most common neurodegenerative diseases. Deep brain stimulation (DBS) can improve motor symptoms in patients with middle and late Parkinson's disease, reduce the use of levodopa, and thus reduce drug-related side effects. Postoperative delirium can significantly reduce the short-term and long-term quality of life in elderly patients, which can be alleviated by dexmedetomidine (DEX). However, whether prophylactic DEX could reduce the incidence of postoperative delirium in patients with Parkinson's disease was still unknown.

METHODS AND ANALYSIS: This is a single-centre, randomised, double-blinded, placebo-controlled group trial. A total of 292 patients aged 60 years and above elected for DBS will be stratified according to DBS procedure, subthalamic nucleus or globus pallidus interna, then randomly allocated to the DEX group or the placebo control group with a 1:1 ratio, respectively. In the DEX group, patients will be injected with the DEX continuously with an electronic pump at a rate of 0.1 µg/kg/hour for 48 hours at the beginning of general anaesthesia induction. In the control group, normal saline will be administered at the same rate for patients as in the DEX group. The primary endpoint is the incidence of postoperative delirium within 5 days after surgery. Postoperative delirium is assessed by the combination of the Richmond Anxiety Scale and the Confusion Assessment Method (CAM) for the intensive care unit or the 3-minute diagnostic interview for CAM as applicable. The secondary endpoints include the incidence of adverse events and non-delirium complications, the length of stay in the intensive care unit and hospital and all-cause 30-day mortality after the operation.

ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of Beijing Tiantan Hospital of Capital Medical University (KY2022-003-03). The results of this study will be disseminated through presentation at scientific conferences and publication in scientific journals.

TRIAL REGISTRATION NUMBER: NCT05197439.

PMID:37433729 | DOI:10.1136/bmjopen-2022-070185

JAMA. 2023 Jul 11;330(2):152-160. doi: 10.1001/jama.2023.10042.

ABSTRACT

IMPORTANCE: Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal.

OBJECTIVE: To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo.

DESIGN, SETTING, AND PARTICIPANTS: A 3-group, double-blind, placebo-controlled, randomized trial (ORCA-2) compared 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo, with follow-up to 24 weeks, among 810 adults who smoked cigarettes daily and wanted to quit. It was conducted at 17 US sites from October 2020 to December 2021.

INTERVENTIONS: Participants were randomized (1:1:1) to cytisinicline, 3 mg, 3 times daily for 12 weeks (n = 270); cytisinicline, 3 mg, 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks (n = 269); or placebo 3 times daily for 12 weeks (n = 271). All participants received behavioral support.

MAIN OUTCOMES AND MEASURES: Biochemically verified continuous smoking abstinence for the last 4 weeks of cytisinicline treatment vs placebo (primary) and from end of treatment to 24 weeks (secondary).

RESULTS: Of 810 randomized participants (mean age, 52.5 years; 54.6% female; mean of 19.4 cigarettes smoked daily), 618 (76.3%) completed the trial. For the 6-week course of cytisinicline vs placebo, continuous abstinence rates were 25.3% vs 4.4% during weeks 3 to 6 (odds ratio [OR], 8.0 [95% CI, 3.9-16.3]; P < .001) and 8.9% vs 2.6% during weeks 3 to 24 (OR, 3.7 [95% CI, 1.5-10.2]; P = .002). For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; P < .001) and 21.1% vs 4.8% during weeks 9 to 24 (OR, 5.3 [95% CI, 2.8-11.1]; P < .001). Nausea, abnormal dreams, and insomnia occurred in less than 10% of each group. Sixteen participants (2.9%) discontinued cytisinicline due to an adverse event. No drug-related serious adverse events occurred.

CONCLUSIONS AND RELEVANCE: Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering new nicotine dependence treatment options.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04576949.

PMID:37432430 | DOI:10.1001/jama.2023.10042

BMC Public Health. 2023 Jul 10;23(1):1317. doi: 10.1186/s12889-023-16259-6.

ABSTRACT

BACKGROUND: Despite having an effective community-based Directly Observed Therapy Short-course (DOTS) strategy for tuberculosis (TB) care, treatment adherence has been a major challenge in many developing countries including Ghana. Poor adherence results in discontinuity of treatment and leads to adverse treatment outcomes which pose an increased risk of drug resistance. This study explored barriers to TB treatment adherence and recommended potential patient-centered strategies to improve treatment adherence in two high-burden TB settings in the Ashanti region of Ghana.

METHODS: The study was conducted among TB patients who defaulted on treatment in the Obuasi Municipal and Obuasi East districts in the Ashanti region. A qualitative phenomenology approach was used to explore the barriers to TB treatment adherence. Purposive sampling was adopted to select study participants with different sociodemographic backgrounds and experiences with TB care. Eligible participants were selected by reviewing the medical records of patients from health facility TB registers (2019-2021). Sixty-one (61) TB patients met the eligibility criteria and were contacted via phone call. Out of the 61 patients, 20 were successfully reached and consented to participate. In-depth interviews were conducted with participants using a semi-structured interview guide. All interviews were audio recorded and transcribed verbatim. The transcripts were imported into Atlas.ti version 8.4 software and analyzed using thematic content analysis.

RESULTS: Food insecurity, cost of transportation to the treatment center, lack of family support, income insecurity, long distance to the treatment center, insufficient knowledge about TB, side effect of drugs, improvement in health after the intensive phase of the treatment regimen, and difficulty in accessing public transportation were the main co-occurring barriers to treatment adherence among the TB patients.

CONCLUSION: The main barriers to TB treatment adherence identified in this study reveal major implementation gaps in the TB programme including gaps related to social support, food security, income security, knowledge, and proximity to treatment centers. Hence, to improve treatment adherence there is a need for the government and the National Tuberculosis Programme (NTP) to collaborate with different sectors to provide comprehensive health education, social and financial support as well as food aid to TB patients.

PMID:37430295 | DOI:10.1186/s12889-023-16259-6

Reg Anesth Pain Med. 2023 Jul 9:rapm-2023-104666. doi: 10.1136/rapm-2023-104666. Online ahead of print.

ABSTRACT

BACKGROUND/IMPORTANCE: Despite over 30 years of use by pediatric anesthesiologists, standardized dosing rates, dosing characteristics, and cases of toxicity of truncal nerve catheters are poorly described.

OBJECTIVE: We reviewed the literature to characterize dosing and toxicity of paravertebral and transversus abdominis plane catheters in children (less than 18 years).

EVIDENCE REVIEW: We searched for reports of ropivacaine or bupivacaine infusions in the paravertebral and transversus abdominis space intended for 24 hours or more of use in pediatric patients. We evaluated bolus dosing, infusion dosing, and cumulative 24-hour dosing in patients over and under 6 months. We also identified cases of local anesthetic systemic toxicity and toxic blood levels.

FINDINGS: Following screening, we extracted data from 46 papers with 945 patients.Bolus dosing was 2.5 mg/kg (median, range 0.6-5.0; n=466) and 1.25 mg/kg (median, range 0.5-2.5; n=294) for ropivacaine and bupivacaine, respectively. Infusion dosing was 0.5 mg/kg/hour (median, range 0.2-0.68; n=521) and 0.33 mg/kg/hour (median, range 0.1-1.0; n=423) for ropivacaine and bupivacaine, respectively, consistent with a dose equivalence of 1.5:1.0. A single case of toxicity was reported, and pharmacokinetic studies reported at least five cases with serum levels above the toxic threshold.

CONCLUSIONS: Bolus doses of bupivacaine and ropivacaine frequently comport with expert recommendations. Infusions in patients under 6 months used doses associated with toxicity and toxicity occurred at a rate consistent with single-shot blocks. Pediatric patients would benefit from specific recommendations about ropivacaine and bupivacaine dosing, including age-based dosing, breakthrough dosing, and intermittent bolus dosing.

PMID:37429620 | DOI:10.1136/rapm-2023-104666

Int J Clin Pharm. 2023 Jul 10. doi: 10.1007/s11096-023-01611-y. Online ahead of print.

ABSTRACT

BACKGROUND: Fighter pilots are a specific population in which any adverse drug reaction can unpredictably interact with aeronautical constraints and thus compromise flight safety. This issue has not been evaluated in risk assessments.

AIM: To provide a semi-quantitative assessment of the risk to flight safety of self-medication in fighter pilots.

METHOD: A cross-sectional survey that aimed at identifying the determinants of self-medication in fighter pilots was conducted. All medications consumed within 8 h preceding a flight were listed. A modified Failure Mode and Effects Analysis was performed, and any adverse drug reaction reported in the French marketing authorization document of a drug was considered a failure mode. The frequency of occurrence and severity were evaluated using specific scales to assign each to three risk criticality categories: acceptable, tolerable, and unacceptable.

RESULTS: Between March and November 2020, the responses of 170 fighter pilots were analyzed, for an overall return rate of approximately 34%. Among them, 78 reported 140 self-medication events within 8 h preceding a flight. Thirty-nine drug trade names (48 different international nonproprietary names) were listed, from which 694 potential adverse drug reactions were identified. The risk criticality was considered unacceptable, tolerable and acceptable for 37, 325 and 332 adverse drug reactions, respectively. Thus, the risk criticality was considered unacceptable, tolerable and acceptable for 17, 17, and 5 drugs, respectively.

CONCLUSION: This analysis suggests that the overall risk to flight safety of the current practice of self-medication in fighter pilots may be considered at least tolerable, or even unacceptable.

PMID:37430120 | DOI:10.1007/s11096-023-01611-y

HCA Healthc J Med. 2022 Dec 30;3(6):343-348. doi: 10.36518/2689-0216.1384. eCollection 2022.

ABSTRACT

Description Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially life-threatening disorder characterized by uncontrolled and spontaneous clot formation throughout the body. Known secondary causes of TTP include malignancy, bone marrow transplantation, pregnancy, various medications, and HIV infection. TTP in the setting of COVID-19 vaccination is rare and not well reported. Reported cases have been confined primarily to the AstraZeneca and Johnson and Johnson COVID-19 Vaccines. TTP in the setting of Pfizer BNT-162b2 vaccination has only recently been reported. We present a patient with no obvious risk factors for TTP who presented with acute altered mental status and was found to have objective evidence of TTP. To our knowledge, there are very few reported cases of TTP in the setting of a recent Pfizer COVID-19 vaccination.

PMID:37427316 | PMC:PMC10327936 | DOI:10.36518/2689-0216.1384

HCA Healthc J Med. 2022 Dec 30;3(6):349-354. doi: 10.36518/2689-0216.1452. eCollection 2022.

ABSTRACT

Description Anaphylaxis is a rare but serious adverse reaction that can occur following mRNA-based vaccination against coronavirus (COVID-19). This is a case of a geriatric patient presenting with hypotension and an urticarial rash with bullous lesions following a syncopal episode with incontinence. She received the second dose of the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine three days prior, and first developed the skin abnormalities the morning after receiving the vaccine. She had no past history of anaphylaxis or allergies to vaccinations. Her presentation met the diagnostic criteria for anaphylaxis, according to the World Allergy Organization: she had acute onset illness involving the skin and was hypotensive with symptoms suggestive of end-organ dysfunction. The latest literature published on anaphylaxis to mRNA-based COVID-19 vaccination indicates that this is an extremely rare complication. From December 14, 2020, to January 18, 2021, 9 943 247 doses of the Pfizer-BioNTech vaccine and 7 581 429 doses of the Moderna vaccine were administered in the United States. Sixty-six of these patients met anaphylaxis criteria. Of these cases, 47 received the Pfizer vaccine and 19 received the Moderna vaccine. Unfortunately, the mechanisms of these adverse reactions remain poorly understood, although it is postulated that particular vaccine components such as polyethylene glycol or polysorbate 80 may be the underlying triggers. This case demonstrates the importance of recognizing anaphylactic signs and symptoms, as well as proper patient education about the benefits and potential, albeit rare, adverse effects, of vaccination.

PMID:37427315 | PMC:PMC10327935 | DOI:10.36518/2689-0216.1452

HCA Healthc J Med. 2020 Dec 29;1(6):459-461. doi: 10.36518/2689-0216.1206. eCollection 2020.

ABSTRACT

Description Health care professionals hold the responsibility of reporting any adverse drug reactions in order to learn about new therapy and how best to safely care for our patients. The information derived from case publications and FDA MedWatch reports are essential to accumulate information and increase awareness for the possible risks of new drugs.

PMID:37427052 | PMC:PMC10324794 | DOI:10.36518/2689-0216.1206

Front Pharmacol. 2023 Jun 22;14:1183514. doi: 10.3389/fphar.2023.1183514. eCollection 2023.

ABSTRACT

Background: Clinical trials have shown that the use of trastuzumab deruxtecan (DS-8201) alone is expected to provide novel therapeutic options for HER2-low/positive patients. Nevertheless, there are some variations in the efficacy of trial results, with potential risks at the safety level. Most DS-8201 trials in HER2 advanced breast cancer (ABC) have been conducted in the form of small-sample nonrandomized controlled studies, resulting in a lack of validated indicators to evaluate the efficacy and safety of DS-8201. Thus, this meta-analysis aimed to pool the results of various trials of DS-8201 alone to explore the efficacy and safety of DS-8201 in patients with HER2-low/positive advanced breast cancer. Methods: Relevant studies were searched in seven databases, including Embase, PubMed, Web of Science, Cochrane Library, CNKI, VIP database and WanFang data, to collect single-arm studies on DS-8201 for HER2-low/positive ABC. MINORS was adopted for quality assessment and STATA 16.0 for data analysis. Results: Ten studies involving 1,108 patients were included in this meta-analysis. As for the tumor response rate, the pooled ORR and DCR of all studies reached 57% (95% CI: 47%-67%) and 92% (95% CI: 89%-96%) respectively, and the pooled ORRs of the HER2-low expression group and the HER2-positive expression group were 46% (95% CI: 35%-56%) and 64% (95% CI: 54%-74%). Only the low expression group achieved median survival time, with a pooled median PFS and median OS of 9.24 (95% CI: 7.54-10.94) months and 23.87 (95% CI: 21.56-26.17) months, respectively. The most common treatment-related adverse events from DS-8201 were nausea (all grades: 62%; ≥ grade III: 5%), fatigue (all grade: 44%; ≥ grade III: 6%), and alopecia (all grades: 38%; ≥ grade III: 0.5%). Drug-related interstitial lung disease or pneumonitis occurred in 13% of the 1,108 patients, with only a 1% incidence of AE ≥ grade III. Conclusion: The present study suggests that DS-8201 is effective and safe in the treatment of ABC with low or positive HER2 expression, providing additional relevant information for its clinical application. However, further strengthening of the pairs is needed, as well as more clinical studies to support individualized treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023390316.

PMID:37426807 | PMC:PMC10324614 | DOI:10.3389/fphar.2023.1183514

HCA Healthc J Med. 2020 Oct 29;1(5):283-288. doi: 10.36518/2689-0216.1040. eCollection 2020.

ABSTRACT

Description Perampanel (Fycompa) is a newer anti-epileptic drug believed to exert its effects in the central nervous system by inhibiting post-synaptic glutamate receptors. However, the precise therapeutic mechanism is unknown. The most common neuropsychiatric side effect is affective dysregulation; there are also reports of psychosis. We describe a 32 year old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, after Perampanel was added to his antiepileptic medications. Perampanel administration was temporarily withheld, and subsequently on restarting, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between Perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.

PMID:37426610 | PMC:PMC10324743 | DOI:10.36518/2689-0216.1040

Clin Psychopharmacol Neurosci. 2023 Aug 31;21(3):534-543. doi: 10.9758/cpn.22.1014.

ABSTRACT

OBJECTIVE: COVID-19 has gravely affected patients with psychiatric conditions. Potential interactions may occur between psychotropic medications and medications used in treatment of COVID-19. This study aimed to compare the online databases in terms of the quality of drug-drug interaction related information available on them.

METHODS: 216 drug interactions which included fifty-four psychotropic medication interactions with four COVID-19 drugs across six databases were analyzed by four authors independently. The overall grading of the databases was done on Likert scale independently by the authors using the parameters of ease of understanding for consumers and professionals, level of completeness, discussion on level of evidence and the number of available drugs, congruity with other databases and the mean score was tabulated.

RESULTS: Drugbank and Lexicomp had maximum discrepancy. The safety profile of Hydroxychloroquine was the best (eighteen moderate/severe psychotropic medication reactions) while Ritonavir has worst profile with thirty-nine medications. Drugbank had the highest SCOPE score (1.00) for completeness and covid19druginteractions.com had least (0.81). Overall, Liverpool© Drug Interaction Group and Lexicomp scored the highest (23/30 each) and were the best interaction checker software closely followed by Drugs.com (22/30). Medscape and WebMD were the poorest interaction checker databases.

CONCLUSION: There is significant variability in the available online databases. Liverpool© Drug Interaction Group and Lexicomp were the most reliable sources for healthcare workers whereas for patients, Drugs.com was the easiest to understand (as it segregates the needs of general consumers and professionals distinctly to explain the interaction).

PMID:37424421 | DOI:10.9758/cpn.22.1014

Drug Ther Bull. 2023 Jul 9:dtb-2023-000036. doi: 10.1136/dtb.2023.000036. Online ahead of print.

NO ABSTRACT

PMID:37423715 | DOI:10.1136/dtb.2023.000036

Colloids Surf B Biointerfaces. 2023 Jul 4;228:113440. doi: 10.1016/j.colsurfb.2023.113440. Online ahead of print.

ABSTRACT

Wound healing remains a considerable challenge due to its complex inflammatory microenvironment. Developing novel wound dressing materials with superior wound repair capabilities is highly required. However, conventional dressing hydrogels for wound healing are often limited by their complex cross-linking, high treatment costs, and drug-related side effects. In this study, we report a novel dressing hydrogel constructed only by the self-assembly of chlorogenic acid (CA). Molecular dynamic simulation studies revealed the formation of CA hydrogel was mainly through non-covalent interactions, such as π-π and hydrogen bond. Meanwhile, CA hydrogel exhibited superior self-healing, injectability, and biocompatibility properties, making it a promising candidate for wound treatment. As expected, in vitro experiments demonstrated that CA hydrogel possessed remarkable anti-inflammatory activity, and its ability to promote the generation of microvessels in HUVEC cells, as well as the promotion of microvessel formation in HUVEC cells and proliferation of HaCAT cells. Subsequent in vivo investigation further demonstrated that CA hydrogel accelerated wound healing in rats through regulating macrophage polarization. Mechanistically, the CA hydrogel treatment enhanced the closure rate, collagen deposition, and re-epithelialization while simultaneously suppressing the secretion of pro-inflammatory cytokines and increasing the production of CD31 and VEGF during the wound healing process. Our findings indicate that this multifunctional CA hydrogel is a promising candidate for wound healing, particularly in cases of impaired angiogenesis and inflammatory responses.

PMID:37421764 | DOI:10.1016/j.colsurfb.2023.113440

Mol Pharm. 2023 Jul 8. doi: 10.1021/acs.molpharmaceut.3c00196. Online ahead of print.

ABSTRACT

The free-state solution behaviors of small molecules profoundly affect their respective properties. It is becoming more obvious that compounds can adopt a three-phase equilibrium when placed in an aqueous solution, among soluble-lone molecule form, self-assembled aggregate form (nano-entities), and solid precipitate form. Recently, correlations have emerged between the existence of self-assemblies into drug nano-entities and unintended side effects. This report describes our pilot study involving a selection of drugs and dyes to explore if there may be a correlation between the existence of drug nano-entities and immune responses. We first implement practical strategies for detecting the drug self-assemblies using a combination of nuclear magnetic resonance (NMR), dynamic light scattering (DLS), transmission electron microscopy (TEM), and confocal microscopy. We then used enzyme-linked immunosorbent assays (ELISA) to monitor the modulation of immune responses on two cellular models, murine macrophage and human neutrophils, upon exposure to the drugs and dyes. The results suggest that exposure to some aggregates correlated with an increase in IL-8 and TNF-α in these model systems. Given this pilot study, further correlations merit pursuing on a larger scale given the importance and potential impact of drug-induced immune-related side effects.

PMID:37421372 | DOI:10.1021/acs.molpharmaceut.3c00196

Hum Vaccin Immunother. 2023 Aug 1;19(2):2228164. doi: 10.1080/21645515.2023.2228164. Epub 2023 Jul 7.

ABSTRACT

As of August 2021, less than 5% of the total population in Afghanistan has been fully vaccinated against COVID-19. Concerns remain regarding low uptake of the vaccine due to several factors. This study was conducted to understand the perception of the public on COVID-19 and its vaccines in Afghanistan. This was a formative study using qualitative method that included FGDs with vaccination target groups and KIIs, using interview guides in local languages in 12 provinces with 300 participants during May-June 2021. Verbatim transcripts were created, and a deductive thematic analysis was conducted with transcripts after the key themes and sub-themes were developed and reviewed. Totally 24 FGDs with male and female COVID-19 high-risk groups, 12 KIIs with EPI managers, and 12 KIIs with prison heads were conducted. Key themes included awareness and perception about COVID-19, its vaccination, motivators for getting vaccinated, barriers for not getting vaccinated, and sources of information. Awareness about the COVID-19 was high in urban areas compared to rural areas. Almost 60% of the participants considered the COVID-19 vaccine effective. However, participants expressed their concerns regarding rumors and misconceptions on content, source, effectiveness, and side effects of the vaccine in their communities. Based on the study results, many participants expressed accurate knowledge about the COVID-19 disease and its vaccines. Significant barriers including misinformation, conspiracy theories, and fear of side effects persist. Collaboration between stakeholders and increasing awareness and engagement of communities about the benefits and effectiveness of the vaccines should be considered crucial.

PMID:37417006 | PMC:PMC10339775 | DOI:10.1080/21645515.2023.2228164

Subst Abuse Treat Prev Policy. 2023 Jul 7;18(1):42. doi: 10.1186/s13011-023-00544-z.

ABSTRACT

BACKGROUND: Encephalopathy can occur from a non-fatal toxic drug event (overdose) which results in a partial or complete loss of oxygen to the brain, or due to long-term substance use issues. It can be categorized as a non-traumatic acquired brain injury or toxic encephalopathy. In the context of the drug toxicity crisis in British Columbia (BC), Canada, measuring the co-occurrence of encephalopathy and drug toxicity is challenging due to lack of standardized screening. We aimed to estimate the prevalence of encephalopathy among people who experienced a toxic drug event and examine the association between toxic drug events and encephalopathy.

METHODS: Using a 20% random sample of BC residents from administrative health data, we conducted a cross-sectional analysis. Toxic drug events were identified using the BC Provincial Overdose Cohort definition and encephalopathy was identified using ICD codes from hospitalization, emergency department, and primary care records between January 1st 2015 and December 31st 2019. Unadjusted and adjusted log-binomial regression models were employed to estimate the risk of encephalopathy among people who had a toxic drug event compared to people who did not experience a toxic drug event.

RESULTS: Among people with encephalopathy, 14.6% (n = 54) had one or more drug toxicity events between 2015 and 2019. After adjusting for sex, age, and mental illness, people who experienced drug toxicity were 15.3 times (95% CI = 11.3, 20.7) more likely to have encephalopathy compared to people who did not experience a drug toxicity event. People who were 40 years and older, male, and had a mental illness were at increased risk of encephalopathy.

CONCLUSIONS: There is a need for collaboration between community members, health care providers, and key stakeholders to develop a standardized approach to define, screen, and detect neurocognitive injury related to drug toxicity.

PMID:37420239 | PMC:PMC10329314 | DOI:10.1186/s13011-023-00544-z