Eur Respir J. 2023 Sep 9;62(3):2300198. doi: 10.1183/13993003.00198-2023. Print 2023 Sep.

ABSTRACT

BACKGROUND: Current guidelines recommend 20-40 mg·day-1 of oral prednisolone for treating pulmonary sarcoidosis. Whether the higher dose (40 mg·day-1) can improve outcomes remains unknown.

METHODS: We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day-1 initial dose) or low-dose (20 mg·day-1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL) scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale.

FINDINGS: We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the high-dose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the 18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19 (44.2%) in the low-dose group (p=0.75). The mean time to relapse/treatment failure was similar between the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores did not differ between the study groups.

INTERPRETATION: High-dose prednisolone was not superior to a lower dose in improving outcomes or the HRQoL in sarcoidosis and was associated with similar adverse effects.

PMID:37690784 | DOI:10.1183/13993003.00198-2023

BMC Womens Health. 2023 Sep 9;23(1):478. doi: 10.1186/s12905-023-02630-7.

ABSTRACT

INTRODUCTION: In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients' experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi.

METHODS: Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient's perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction.

RESULTS: Most women in both groups were well versed on DTG's potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures.

CONCLUSION: DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.

PMID:37689628 | PMC:PMC10492391 | DOI:10.1186/s12905-023-02630-7

Ned Tijdschr Geneeskd. 2023 Aug 30;167:D7604.

ABSTRACT

BACKGROUND: Oral nicotine pouches are pouches that contain varying amounts of nicotine. The use of nicotine pouches by adolescents has increased since 2020. Subsequently, there has been an increase in the amount of reports of nicotine intoxications. Acute nicotine intoxications have a biphasic clinical course, during which the initial symptoms may include agitation, tachycardia and vomiting. When large enough doses are used more serious symptoms may emerge. As well as the acute side effects, studies have shown that the use of oral nicotine pouches with tobacco is associated with a younger age at which cigarette smoking is initiated.

PATIENT DESCRIPTION: A 9 year-old boy presented at the Emergency Department with symptoms of nausea, dizziness and shivering following the oral use of one nicotine pouch. Aside from tachycardia the physical examinations showed no abnormalities. The patient was diagnosed with an acute nicotine intoxication and was admitted to the paediatric department for 24 hours.

CONCLUSION: Oral nicotine pouches are commonly used by adolescents. Aside from the addictive nature of nicotine, it is important that clinicians are aware of the symptoms of acute and late-phase intoxications.

PMID:37688459

Molecules. 2023 Aug 24;28(17):6229. doi: 10.3390/molecules28176229.

ABSTRACT

Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant adverse effects. (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells.

PMID:37687058 | PMC:PMC10488497 | DOI:10.3390/molecules28176229

Nutrients. 2023 Aug 30;15(17):3788. doi: 10.3390/nu15173788.

ABSTRACT

Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N = 620) seeking better sleep were randomly assigned to receive one of three study products. Sleep A (contained lower (0.35 mg THC and higher levels of botanicals (75 mg each hops oil and valerian oil), Sleep B (contained higher THC (0.85 mg) and lower botanicals (20 mg each hops oil and valerian oil) or placebo) for 4 weeks. Sleep disturbance was assessed at baseline and weekly using NIH's Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.

PMID:37686820 | PMC:PMC10490534 | DOI:10.3390/nu15173788

Int J Mol Sci. 2023 Sep 2;24(17):13614. doi: 10.3390/ijms241713614.

ABSTRACT

Prostate cancer is the second most common cancer for men and a major health issue. Despite treatments, a lot of side effects are observed. Photodynamic therapy is a non-invasive method that uses photosensitizers and light to induce cell death through the intramolecular generation of reactive oxygen species, having almost no side effects. However, some of the PSs used in PDT show inherent low solubility in biological media, and accordingly, functionalization or vectorization is needed to ensure internalization. To this end, we have used arene-ruthenium cages in order to deliver PSs to cancer cells. These metalla-assemblies can host PSs inside their cavity or be constructed with PS building blocks. In this study, we wanted to determine if the addition of metals (Mg, Co, Zn) in the center of these PSs plays a role. Our results show that most of the compounds induce cytotoxic effects on DU 145 and PC-3 human prostate cancer cells. Localization by fluorescence confirms the internalization of the assemblies in the cytoplasm. An analysis of apoptotic processes shows a cleavage of pro-caspase-3 and poly-ADP-ribose polymerase, thus leading to a strong induction of DNA fragmentation. Finally, the presence of metals in the PS decreases PDT's effect and can even annihilate it.

PMID:37686420 | PMC:PMC10488040 | DOI:10.3390/ijms241713614

Int J Mol Sci. 2023 Sep 1;24(17):13562. doi: 10.3390/ijms241713562.

ABSTRACT

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696-0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine (p < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injury.

PMID:37686369 | PMC:PMC10487599 | DOI:10.3390/ijms241713562

Int J Mol Sci. 2023 Aug 31;24(17):13497. doi: 10.3390/ijms241713497.

ABSTRACT

Transcription factors (TFs) have been shown to play a key role in the occurrence and development of tumors, including triple-negative breast cancer (TNBC), with a worse prognosis. Machine learning is widely used for establishing prediction models and screening key tumor drivers. Current studies lack TF integration in TNBC, so targeted research on TF prognostic models and targeted drugs is beneficial to improve clinical translational application. The purpose of this study was to use the Least Absolute Shrinkage and Selection Operator to build a prognostic TFs model after cohort normalization based on housekeeping gene expression levels. Potential targeted drugs were then screened on the basis of molecular docking, and a multi-drug combination strategy was used for both in vivo and in vitro experimental studies. The machine learning model of TFs built by E2F8, FOXM1, and MYBL2 has broad applicability, with an AUC value of up to 0.877 at one year. As a high-risk clinical factor, its abnormal disorder may lead to upregulation of the activity of pathways related to cell proliferation. This model can also be used to predict the adverse effects of immunotherapy in patients with TNBC. Molecular docking was used to screen three drugs that target TFs: Trichostatin A (TSA), Doxorubicin (DOX), and Calcitriol. In vitro and in vivo experiments showed that TSA + DOX was able to effectively reduce DOX dosage, and TSA + DOX + Calcitriol may be able to effectively reduce the toxic side effects of DOX on the heart. In conclusion, the machine learning model based on three TFs provides new biomarkers for clinical and prognostic diagnosis of TNBC, and the combination targeted drug strategy offers a novel research perspective for TNBC treatment.

PMID:37686305 | PMC:PMC10487460 | DOI:10.3390/ijms241713497

Int J Mol Sci. 2023 Aug 31;24(17):13498. doi: 10.3390/ijms241713498.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) are a significant cause of mortality, and pharmacogenomics (PGx) offers the potential to optimize therapeutic efficacy while minimizing ADRs. However, there is a lack of data on the Croatian population, highlighting the need for investigating the most common alleles, genotypes, and phenotypes to establish national guidelines for drug use.

METHODS: A single-center retrospective cross-sectional study was performed to examine the allele, genotype, and phenotype frequencies of drug-metabolizing enzymes, receptors, and other proteins in a random sample of 522 patients from Croatia using a 28-gene PGx panel.

RESULTS: Allele frequencies, genotypes, and phenotypes for the investigated genes were determined. No statistically significant differences were found between the Croatian and European populations for most analyzed genes. The most common genotypes observed in the patients resulted in normal metabolism rates. However, some genes showed higher frequencies of altered metabolism rates.

CONCLUSIONS: This study provides insights into the allele, genotype, and phenotype frequencies of drug-metabolizing enzymes, receptors, and other associated proteins in the Croatian population. The findings contribute to optimizing drug use guidelines, potentially reducing ADRs, and improving therapeutic efficacy. Further research is needed to tailor population-specific interventions based on these findings and their long-term benefits.

PMID:37686303 | PMC:PMC10487565 | DOI:10.3390/ijms241713498

Int J Mol Sci. 2023 Aug 30;24(17):13459. doi: 10.3390/ijms241713459.

ABSTRACT

Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.

PMID:37686266 | PMC:PMC10487921 | DOI:10.3390/ijms241713459

Int J Mol Sci. 2023 Aug 30;24(17):13424. doi: 10.3390/ijms241713424.

ABSTRACT

Cyclophosphamide causes side effects in cancer patients, including hepatotoxicity. Probiotics have recently emerged as potential approaches for the administration of many diseases. This study aimed to evaluate the protective effects of Lactiplantibacillus plantarum P101 against cyclophosphamide-induced liver injury and elucidate the underlying mechanism. In this study, Lactiplantibacillus plantarum P101 or Lactobacillus rhamnosus GG were pre-administered to mice with varying duration (1 week, 2 weeks, and 3 weeks) before being intraperitoneally injected with cyclophosphamide at a dose of 30 mg/kg/day for 7 days to induce liver injury. Results demonstrated that cyclophosphamide-induced liver injury was characterized by histopathological disorders, including irregular central venous shape and hepatic vascular rupture, as well as a severe inflammation response and oxidative stress. The administration of probiotics for 3 weeks exerted the most significant improvements in alleviating liver injury, oxidative stress, and inflammation when compared to the shorter intervention duration. Notably, Lactiplantibacillus plantarum P101 exhibited more pronounced effects than Lactobacillus rhamnosus GG. Furthermore, Lactiplantibacillus plantarum P101 enhanced the antioxidant defense system by activating the Nrf2/ARE signaling pathway, ultimately alleviating hepatotoxicity and hepatocyte apoptosis. In conclusion, this study highlighted the potential of Lactiplantibacillus plantarum P101 to alleviate cyclophosphamide-induced hepatotoxicity.

PMID:37686229 | PMC:PMC10488115 | DOI:10.3390/ijms241713424

Sci Rep. 2023 Sep 8;13(1):14865. doi: 10.1038/s41598-023-41899-4.

ABSTRACT

In-vivo toxicity assessment is an important step prior to clinical development and is still the main source of data for overall risk assessment of a new molecular entity (NCE). All in-vivo studies are performed according to regulatory requirements and many efforts have been exerted to minimize these studies in accordance with the (Replacement, Reduction and Refinement) 3Rs principle. Many aspects of in-vivo toxicology packages can be optimized to reduce animal use, including the number of studies performed as well as study durations, which is the main focus of this analysis. We performed a statistical comparison of adverse findings observed in 116 short-term versus 78 long-term in-house or in-house sponsored Contract Research Organizations (CRO) studies, in order to explore the possibility of using only short-term studies as a prediction tool for the longer-term effects. All the data analyzed in this study was manually extracted from the toxicology reports (in PDF formats) to construct the dataset. Annotation of treatment related findings was one of the challenges faced during this work. A specific focus was therefore put on the summary and conclusion sections of the reports since they contain expert assessments on whether the findings were considered adverse or were attributed to other reasons. Our analysis showed a general good concordance between short-term and long-term toxicity findings for large molecules and the majority of small molecules. Less concordance was seen for certain body organs, which can be named as "target organ systems' findings". While this work supports the minimization of long-term studies, a larger-scale effort would be needed to provide more evidence. We therefore present the steps performed in this study as an open-source R workflow for the Comparison of Short-term and Long-term Toxicity studies (CSL-Tox). The dataset used in the work is provided to allow researchers to reproduce such analysis, re-evaluate the statistical tools used and promote large-scale application of this study. Important aspects of animal research reproducibility are highlighted in this work, specifically, the necessity of a reproducible adverse effects reporting system and utilization of the controlled terminologies in-vivo toxicology reports and finally the importance of open-source analytical workflows that can be assessed by other scientists in the field of preclinical toxicology.

PMID:37684321 | PMC:PMC10491674 | DOI:10.1038/s41598-023-41899-4

Nat Commun. 2023 Sep 8;14(1):5529. doi: 10.1038/s41467-023-41066-3.

ABSTRACT

Immune checkpoint inhibitors cause side effects ranging from autoimmune endocrine disorders to severe cardiotoxicity. Periodic Fasting mimicking diet (FMD) cycles are emerging as promising enhancers of a wide range of cancer therapies including immunotherapy. Here, either FMD cycles alone or in combination with anti-OX40/anti-PD-L1 are much more effective than immune checkpoint inhibitors alone in delaying melanoma growth in mice. FMD cycles in combination with anti-OX40/anti-PD-L1 also show a trend for increased effects against a lung cancer model. As importantly, the cardiac fibrosis, necrosis and hypertrophy caused by immune checkpoint inhibitors are prevented/reversed by FMD treatment in both cancer models whereas immune infiltration of CD3+ and CD8+ cells in myocardial tissues and systemic and myocardial markers of oxidative stress and inflammation are reduced. These results indicate that FMD cycles in combination with immunotherapy can delay cancer growth while reducing side effects including cardiotoxicity.

PMID:37684243 | PMC:PMC10491752 | DOI:10.1038/s41467-023-41066-3

Prim Care Companion CNS Disord. 2023 Sep 5;25(5):22cr03448. doi: 10.4088/PCC.22cr03448.

NO ABSTRACT

PMID:37683621 | DOI:10.4088/PCC.22cr03448

Medicine (Baltimore). 2023 Sep 8;102(36):e34965. doi: 10.1097/MD.0000000000034965.

ABSTRACT

RATIONALE: Acute lymphoblastic leukemia (ALL) represents approximately 1-quarter of all new cases of childhood cancer. Although overall survival following diagnosis has improved in recent years, the toxicity of chemotherapy remains a concern.

PATIENT CONCERNS: We describe an 11-year-old male patient diagnosed with T-cell precursor ALL who developed compounded complications during the induction phase of chemotherapy. Patient was hospitalized in the Department of Pediatric Hematology, Oncology, and Transplantology of the Medical University of Lublin, Poland. The patient's induction therapy was started according to the AIEOP-BFM ALL 2017 protocol IAp (International Collaborative Treatment Protocol for Children and Adolescents with Acute Lymphoblastic Leukemia).

DIAGNOSES: Patient developed compounded complications such as cholecystitis, hepatotoxicity, pancreatitis and myelosuppression.

INTERVENTIONS: The patient was treated with leukapheresis, received a broad-spectrum antibiotic, potassium supplementation and hepatoprotective treatment and laparotomy cholecystectomy.

OUTCOMES: In the available literature, there is a limited amount of similar clinical cases with multiple complications in pediatric patients with ALL. Toxicities cause delays in the treatment of the underlying disease.

LESSONS: In children with acute lymphoblastic leukemia, there are side effects during the treatment such as cholecystitis and pancreatitis. Complications during treatment require a quick response and modification of disease management. Abdominal ultrasound performed before treatment makes it possible to observe the dynamics of lesions. Genetic mutation analysis could allow us to more precisely respond to the possible susceptibility to and appearance of complications after the use of a given chemotherapeutic agent.

PMID:37682188 | PMC:PMC10489477 | DOI:10.1097/MD.0000000000034965

Medicine (Baltimore). 2023 Sep 8;102(36):e35138. doi: 10.1097/MD.0000000000035138.

ABSTRACT

BACKGROUND: This study compared the effectiveness of nalmefene and fentanyl in reducing the incidence and severity of etomidate-induced myoclonus.

METHODS: One hundred fifty patients were randomized to receive 0.25ug/kg of nalmefene, 1ug/kg of fentanyl, or the same volume of normal saline 3 minutes prior to etomidate-induced anesthesia. The primary observational indexes were the severity level and incidence of etomidate-induced myoclonus, and the secondary observational index included blood pressure, heart rate, and the incidence of adverse effects from anesthesia induction to resuscitation, such as cough, chest wall rigidity, dizziness, nausea, pain after awakening, and intraoperative awareness.

RESULTS: The incidence of myoclonus was significantly lower in the nalmefene group (8.0%) than in the fentanyl group (32.0%) (P = .003) and in the normal saline group (72.0%) (P = .000). The severity level of myoclonus in the nalmefene group was significantly lower than the fentanyl group (P = .001) and normal saline group (P = .000). Meanwhile, the incidences of cough and chest wall rigidity during anesthesia induction were significantly lower in the nalmefene group compared with the fentanyl group (P = .003, P = .027). There were no statistically significant differences in heart rate and mean arterial pressure among the 3 gruops (P > .05). There was no difference in the incidence of adverse effects among the 3 groups during recovery from anesthesia (P > .05).

CONCLUSION: Intravenous injection of 0.25ug/kg of nalmefene 3 minutes prior to etomidate is more effective in preventing etomidate-induced myoclonus during general anesthesia than 1ug/kg of fentanyl.

PMID:37682124 | PMC:PMC10489433 | DOI:10.1097/MD.0000000000035138

Cells. 2023 Aug 25;12(17):2147. doi: 10.3390/cells12172147.

ABSTRACT

In the emerging era of cancer immunotherapy, immune checkpoint blockades (ICBs) and adoptive cell transfer therapies (ACTs) have gained significant attention. However, their therapeutic efficacies are limited due to the presence of cold type tumors, immunosuppressive tumor microenvironment, and immune-related side effects. On the other hand, dendritic cell (DC)-based vaccines have been suggested as a new cancer immunotherapy regimen that can address the limitations encountered by ICBs and ACTs. Despite the success of the first generation of DC-based vaccines, represented by the first FDA-approved DC-based therapeutic cancer vaccine Provenge, several challenges remain unsolved. Therefore, new DC vaccine strategies have been actively investigated. This review addresses the limitations of the currently most adopted classical DC vaccine and evaluates new generations of DC vaccines in detail, including biomaterial-based, immunogenic cell death-inducing, mRNA-pulsed, DC small extracellular vesicle (sEV)-based, and tumor sEV-based DC vaccines. These innovative DC vaccines are envisioned to provide a significant breakthrough in cancer immunotherapy landscape and are expected to be supported by further preclinical and clinical studies.

PMID:37681880 | PMC:PMC10486560 | DOI:10.3390/cells12172147

Int J Environ Res Public Health. 2023 Aug 23;20(17):6628. doi: 10.3390/ijerph20176628.

ABSTRACT

BACKGROUND: There have been multiple reported pharmacy initiatives to reduce opioid misuse and accidental overdose to address our nation's public health crisis. To date, there has not been a description in the literature of a community pharmacy follow-up initiative for dispensed opioids.

METHODS: A follow-up program was designed and implemented in community pharmacies as part of a previously developed opioid overdose and misuse prevention program (ONE Program). Five to twelve days after the dispensing of an opioid, pharmacy technicians called the patient to follow up on opioid safety topics. Pharmacy technicians used a questionnaire to inquire about medication disposal plans, if the patient was taking the medication more than prescribed, medication side effects, and if the patient needed a pharmacist consultation. The results from that questionnaire were documented.

RESULTS: During the first 18 months of the follow-up program, 1789 phone calls were completed. Of those contacted, 40% were still using their opioid medication, and over 10% were experiencing side effects which triggered a pharmacist consult. Patients were reminded of proper medication disposal methods, and most patients (78%) desired to dispose of unused medication at the pharmacy medication disposal box.

CONCLUSIONS: Follow-up phone calls post-opioid medication dispensing were shown to add value to a previously established opioid misuse and accidental overdose prevention program and allowed for the fulfillment of the Pharmacist Patient Care Process.

PMID:37681768 | PMC:PMC10487139 | DOI:10.3390/ijerph20176628

Medicine (Baltimore). 2023 Sep 8;102(36):e34983. doi: 10.1097/MD.0000000000034983.

ABSTRACT

BACKGROUND: To assess the safety and efficacy of sorafenib and sunitinib as first-line treatments for metastatic renal cell carcinoma (mRCC), to provide evidence-based support for clinical decision-making regarding rational drug use.

METHODS: Until May 10, 2023, a comprehensive search was conducted across PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang databases to identify clinical studies comparing sorafenib with sunitinib as first-line treatment for mRCC. The literature was screened, data extracted, and quality evaluated independently by 2 researchers. Meta-analysis was conducted using Revman5.4 software.

RESULTS: A total of 3741 patients were enrolled in 20 studies. The meta-analysis results indicated that there were no significant differences in the 2- and 5-year progression-free survival (PFS) and overall survival (OS) rates between the sorafenib and sunitinib groups (P > .05). The disease control rate (DCR) was comparable between the 2 groups (P > .05), while the objective response rate (ORR) was higher in the sunitinib group (P = .03). However, subgroup analysis revealed no significant differences in ORR, DCR, 2- and 5-year PFS, and OS rates between sorafenib and sunitinib among both Asian populations as well as European and American populations (P > .05). In terms of drug-related adverse events, the incidence of grade ≥ 3 hypertension, leukopenia, neutropenia, thrombocytopenia, anemia, nausea and vomiting were significantly lower in the sorafenib group compared to the sunitinib group (P < .05).

CONCLUSION: In the first-line treatment of mRCC, sorafenib exhibits comparable efficacy to sunitinib but with lower toxicity.

PMID:37682147 | DOI:10.1097/MD.0000000000034983

Heliyon. 2023 Aug 27;9(9):e19441. doi: 10.1016/j.heliyon.2023.e19441. eCollection 2023 Sep.

ABSTRACT

Adverse drug events constitute a major challenge for the success of clinical trials. Several computational strategies have been suggested to estimate the risk of adverse drug events in preclinical drug development. While these approaches have demonstrated high utility in practice, they are at the same time limited to specific information sources. Thus, many current computational approaches neglect a wealth of information which results from the integration of different data sources, such as biological protein function, gene expression, chemical compound structure, cell-based imaging and others. In this work we propose an integrative and explainable multi-modal Graph Machine Learning approach (MultiGML), which fuses knowledge graphs with multiple further data modalities to predict drug related adverse events and general drug target-phenotype associations. MultiGML demonstrates excellent prediction performance compared to alternative algorithms, including various traditional knowledge graph embedding techniques. MultiGML distinguishes itself from alternative techniques by providing in-depth explanations of model predictions, which point towards biological mechanisms associated with predictions of an adverse drug event. Hence, MultiGML could be a versatile tool to support decision making in preclinical drug development.

PMID:37681175 | PMC:PMC10481305 | DOI:10.1016/j.heliyon.2023.e19441