Cutis. 2022 Sep;110(3):E19-E20. doi: 10.12788/cutis.0632.

NO ABSTRACT

PMID:36446123 | DOI:10.12788/cutis.0632

Cutis. 2022 Oct;110(4):201-206. doi: 10.12788/cutis.0627.

ABSTRACT

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.

PMID:36446101 | DOI:10.12788/cutis.0627

Oncology (Williston Park). 2022 Nov 8;36(11):658-663. doi: 10.46883/2022.25920978.

ABSTRACT

Small studies have demonstrated the benefit of integrative oncology (IO) therapies in patients with breast cancer; however, referral patterns and timing of therapies are unknown. This study describes the referral pattern and utilization of IO services by young women with breast cancer. A retrospective review identified female patients, 40 years or younger, with a breast cancer diagnosis between 2014 and 2019, and a documented IO consultation. Patient demographics, cancer characteristics, treatments, reasons for seeking and timing of IO consultation, and IO treatment modalities were analyzed. The IO program treated 64 young women with a median age of 38.6 years. Clinical staging was primarily IA (27%), IIA (34%), or IIB (27%), and 64% of patients were clinically node negative with no evidence of metastasis. Women utilized the IO program for recurrence risk reduction and for treatment-related adverse effects (TRAEs), most commonly vasomotor complaints (44%). Therapies utilized were acupuncture (36%), healing touch (28%), oncology massage (30%), and other (75%; music therapy, therapeutic art, spiritual care, meditation, t'ai chi, yoga, and nutrition), which were commonly initiated during treatment (69%). Our data suggest that young women utilize IO services to reduce their future cancer risk and TRAEs, but they are often referred after standard cancer care treatments have begun. Future studies could examine the optimal timing for IO intervention.

PMID:36445978 | DOI:10.46883/2022.25920978

Cochrane Database Syst Rev. 2022 Nov 29;11(11):CD012053. doi: 10.1002/14651858.CD012053.pub2.

ABSTRACT

BACKGROUND: Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction or cessation of treatment, which have an impact on survival. Coriolus versicolor (Trametes versicolor or 'Turkey Tail') mushroom and its extracts have been used by cancer patients to help with adverse effects.

OBJECTIVES: To assess the effects of adjunctive Coriolus versicolor (Trametes versicolor) and its extracts on adverse effects and on survival during colorectal cancer treatment (chemotherapy and radiotherapy) compared with no adjunctive treatment.

SEARCH METHODS: We searched databases including CENTRAL, MEDLINE, Embase, AMED and CINAHL, Chinese and Japanese databases, and trials registers to 12th April 2022 without restriction of language or publication status. We screened reference lists and attempted to contact researchers in the field to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating the efficacy and safety of Coriolus versicolor and its extracts in adult participants with a confirmed diagnosis of colorectal cancer, in addition to conventional treatment. Interventions included any preparation of Coriolus versicolor (raw, decoction, capsule, tablet, tincture, extract, injection), any part of the fungus (cap, stem, mycelium or whole), in any dose or regimen. Outcomes included adverse events rates, survival, disease progression and recurrence, response rates and quality of life.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We evaluated the overall certainty of evidence using the GRADE approach.

MAIN RESULTS: We included seven parallel RCTs (1569 participants). Six studies (1516 participants) were conducted in Japan and one study (53 participants) in China. Studies included both male and female participants with colorectal cancer (five studies), colon cancer (one study) or rectal cancer (one study). Participants were diagnosed with cancer ranging from stage II to stage IV. Coriolus was used in the form of an extract in all seven studies and was generally used after curative resection, although in one study it was used preoperatively. Duration of treatment with the extract varied between four weeks and three years. Chemotherapeutic regimens in six studies consisted of an oral fluoropyrimidine which was preceded by weekly intravenous 5-Fluorouracil (5-FU) in one study, by mitomycin C in two studies, and which was combined with folinic acid (Leucovorin) in two studies and with radiotherapy preoperatively in one study. XELOX (oxaliplatin intravenous infusion and capecitabine) was used in the remaining study. We found very low-certainty evidence of little to no effect of adjunctive treatment with Coriolus (in the form of an extract, polysaccharide-Krestin, PSK) on withdrawal from treatment due to adverse events (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.45 to 2.34; 703 participants; 3 studies;). We are uncertain whether adjunctive Coriolus versicolor and its extracts compared to usual care alone resulted in a difference in adverse events including neutropenia (RR 0.41, 95% CI 0.24 to 0.71; 133 participants; 3 studies; very low certainty), oral cavity disorders such as oral dryness and mucositis (RR 0.37, 95% CI 0.13 to 1.03; 1022 participants; 5 studies; very low certainty), nausea (RR 0.73, 95% CI 0.44 to 1.22; 969 participants; 4 studies; very low certainty), diarrhoea (RR 0.77, 95% CI 0.32 to 1.86; 1022 participants; 5 studies; very low certainty), and fatigue (RR 0.76; 95% CI 0.33 to 1.78; 133 participants; 3 studies; very low certainty). We found low-certainty evidence of a small effect of adjunctive Coriolus on improved survival at five years compared with no adjunctive care (RR 1.08, 95% CI 1.01 to 1.15; 1094 participants; 3 studies; number needed to benefit (NNTB) = 16 (95% Cl 9 to 70). The effect at earlier time points was unclear.

AUTHORS' CONCLUSIONS: Due to the very low certainty of evidence, we were uncertain about the effect of adjunctive Coriolus (in the form of an extract PSK) on adverse events resulting from conventional chemotherapy for colorectal cancer. This includes effects on withdrawal of treatment due to adverse events and on specific adverse outcomes such as neutropenia and nausea. The uncertainty in the evidence also means that it was unclear whether any adverse events were due to the chemotherapy or to the extract itself. While there was low-certainty evidence of a small effect on overall survival at five years, the influence of reduced adverse effects on this could not be determined. In addition, chemotherapy regimens used in assessing this outcome do not reflect current preferred practice.

PMID:36445793 | PMC:PMC9707730 | DOI:10.1002/14651858.CD012053.pub2

JAMA Netw Open. 2022 Nov 1;5(11):e2244141. doi: 10.1001/jamanetworkopen.2022.44141.

ABSTRACT

IMPORTANCE: Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available.

OBJECTIVE: To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients.

DESIGN, SETTING, AND PARTICIPANTS: This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022.

EXPOSURES: Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy.

MAIN OUTCOMES AND MEASURES: Clinical characteristics and outcomes were ascertained through manual record review.

RESULTS: Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities.

CONCLUSIONS AND RELEVANCE: In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

PMID:36445705 | DOI:10.1001/jamanetworkopen.2022.44141

J Cutan Pathol. 2022 Dec;49(12):1051-1059. doi: 10.1111/cup.14306. Epub 2022 Aug 18.

ABSTRACT

BACKGROUND: Categorization of biopsy specimens into inflammatory reaction patterns is central to dermatopathologic assessment. Mixed inflammatory patterns are poorly characterized and may represent clinicopathologic challenges. The purpose of this study was to identify clinical and histopathologic findings associated with the mixed spongiotic-interface dermatitis (SID) histopathologic pattern.

METHODS: Fifty-one institutional biopsy specimens of SID were identified over a 2-year period by retrospective natural language search. Histopathologic and clinical features were identified.

RESULTS: The most common histopathologic features associated with SID were mild spongiosis (51%), focal vacuolar interface change (72%), lymphocytic exocytosis (92%), and superficial-dermal lymphocytic infiltrate (94%) with variable eosinophils (61%). Clinically, 80% of subjects presented with a symmetric morbilliform eruption. Polypharmacy (94%), immunosuppression (47%), and history of malignancy (47%) were common. The most common diagnoses were drug reaction (37%), possible drug reaction (12%), and viral exanthem (12%). Drug reaction with eosinophilia and systemic symptoms represented 25% of all confirmed cutaneous adverse drug reactions (CADR). Average time from drug initiation to symptom initiation was 20 days (SD: 22.3, range: 0-90); median disease duration was 25.5 days. Spongiotic vesicles and Langerhans cells were less common in patients with a strong clinicopathologic diagnosis of drug reaction compared to non-drug eruptions (p = 0.04).

CONCLUSIONS: The mixed SID pattern is commonly encountered in CADR but may represent a more subacute course, implying consideration for inciting medication(s) started before the typical 7- to 14-day window.

PMID:36445270 | PMC:PMC9709294 | DOI:10.1111/cup.14306

Alzheimers Res Ther. 2022 Nov 29;14(1):178. doi: 10.1186/s13195-022-01110-8.

ABSTRACT

BACKGROUND: This review describes the research and development process of gantenerumab, a fully human anti-amyloid monoclonal antibody in development to treat early symptomatic and asymptomatic Alzheimer's disease (AD). Anti-amyloid monoclonal antibodies can substantially reverse amyloid plaque pathology and may modify the course of the disease by slowing or stopping its clinical progression. Several molecules targeting amyloid have failed in clinical development due to drug-related factors (e.g., treatment-limiting adverse events, low potency, poor brain penetration), study design/methodological issues (e.g., disease stage, lack of AD pathology confirmation), and other factors. The US Food and Drug Administration's approval of aducanumab, an anti-amyloid monoclonal antibody as the first potential disease-modifying therapy for AD, signaled the value of more than 20 years of drug development, adding to the available therapies the first nominal success since cholinesterase inhibitors and memantine were approved. BODY: Here, we review over 2 decades of gantenerumab development in the context of scientific discoveries in the broader AD field. Key learnings from the field were incorporated into the gantenerumab phase 3 program, including confirmed amyloid positivity as an entry criterion, an enriched clinical trial population to ensure measurable clinical decline, data-driven exposure-response models to inform a safe and efficacious dosing regimen, and the use of several blood-based biomarkers. Subcutaneous formulation for more pragmatic implementation was prioritized as a key feature from the beginning of the gantenerumab development program.

CONCLUSION: The results from the gantenerumab phase 3 programs are expected by the end of 2022 and will add critical information to the collective knowledge on the search for effective AD treatments.

PMID:36447240 | DOI:10.1186/s13195-022-01110-8

Drug Ther Bull. 2022 Nov 29:dtb-2022-000067. doi: 10.1136/dtb.2022.000067. Online ahead of print.

ABSTRACT

Overview of: Carbone F, Van den Houte K, Besard L, et al Diet or medication in primary care patients with IBS: the DOMINO study - a randomised trial supported by the Belgian Health Care Knowledge Centre (KCE Trials Programme) and the Rome Foundation Research Institute. Gut 2022;71:2226-32.

PMID:36446551 | DOI:10.1136/dtb.2022.000067

BMJ Open. 2022 Nov 28;12(11):e063921. doi: 10.1136/bmjopen-2022-063921.

ABSTRACT

INTRODUCTION: Here, we provide a feasible, well-designed protocol of a randomised controlled trial for the assessment of the effects of a home-based multidisciplinary intervention on the severity of skin adverse drug reactions and health-related indicators in patients with non-small cell lung cancer (NSCLC) under epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy.

METHODS AND ANALYSIS: The study will be a two-group, parallel randomised controlled trial conducted at patients' homes by a multidisciplinary team in Zhengzhou in Henan Province, China. Patients with NSCLC who received EGFR-TKI therapy and experienced adverse skin reactions will be randomised and receive either ordinary care or home-based multidisciplinary interventions. The intervention will be divided into an intensive stage (6 weeks) and a maintenance stage (6 weeks) with baseline and follow-up assessment. Interventions in the intensive stage will include general interventions such as health education, follow-up, behaviour guide and social support and targeted interventions such as skill training, coping with adverse drug reaction and problem-solving. The measures that will be carried out in maintenance stage are continuous interventions consisted of an intensive intervention. The multidisciplinary team will be responsible for managing skin adverse drug reactions as required at patients' homes. Data collection and analysis will be performed by researchers at baseline, the end of the sixth week of intervention and the third month after the intervention. The primary outcome is the degree of skin adverse drug reactions, while the secondary outcomes, for example, self-management ability, quality of life, outpatient visits and health economics indicators, will also be presented.

ETHICS AND DISSEMINATION: This study was reviewed and approved by the Ethics Committee of Zhengzhou University (No. ZZUIRB-2020-97). Findings will be available to patients, clinicians, nurses, pharmacists, community medical staff, funders and health policymakers through peer-reviewed publications, social media and patient support groups.

TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry (ChiCTR2000040643).

PMID:36442902 | DOI:10.1136/bmjopen-2022-063921

BMJ Open. 2022 Nov 28;12(11):e050590. doi: 10.1136/bmjopen-2021-050590.

ABSTRACT

INTRODUCTION: Novel therapies such as small protein molecule inhibitors and immunotherapies are tested in early phase trials before moving to later phase trials and ultimately standard practice. A key aim of these clinical trials is to define a toxicity profile, however, the emphasis is often on safety with measurements of organ toxicity. Other subjective side effects can be under-reported because they are not measured formally within the trial protocols. The concern from clinical practice is that cognitive toxicity is poorly studied and may be under-reported in this context. This could lead to toxicity profiles of new treatments not being fully described and patients with unmet need in terms of acknowledgement and support of symptoms. This protocol outlines a framework of an exploratory study with feasibility aspects to investigate the impact and experience of cognitive changes for patients on phase I trials.

METHODS AND ANALYSIS: This is a mixed-methods study, combining quantitative and qualitative approaches. The sample is 30 patients with advanced cancer who are participating in phase I trials of novel therapies in the early clinical trials unit of a specialist cancer centre. A test battery of validated cognitive assessments will be taken alongside patient reported outcome measures at three time points from baseline, day eight and day 28 post start of treatment. At day 28, a semi-structured interview will be conducted and the narrative thematically analysed. Results will be integrated to offer a comprehensive description of cognitive function in this patient group.

ETHICS AND DISSEMINATION: The study has received full HRA and ethical approval. It is the first study to introduce formal cognitive assessments in a cancer phase I trial context. The study has the potential to highlight previously unreported side effects and more importantly unmet need in terms of care for patients who are participating in the trials.

PMID:36442900 | DOI:10.1136/bmjopen-2021-050590

Oncotarget. 2022 Nov 17;13:1259-1270. doi: 10.18632/oncotarget.28310.

ABSTRACT

PURPOSE/OBJECTIVES: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. APOE genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of APOE genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that APOE genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention.

MATERIALS AND METHODS: Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50-75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments.

RESULTS: Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline (p = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention (p = 0.013) and after 6 months of follow up (p = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not.

CONCLUSIONS: APOE genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

PMID:36441715 | DOI:10.18632/oncotarget.28310

Front Immunol. 2022 Nov 10;13:1016730. doi: 10.3389/fimmu.2022.1016730. eCollection 2022.

ABSTRACT

Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and mechanisms. These reactions are classified into allergic drug hypersensitivity reactions and non-allergic drug hypersensitivity reactions. At present, the hapten theory, pharmacological interaction with immune receptors (p-i) concept, altered peptide repertoire model, and altered T-cell receptor (TCR) repertoire model have been proposed to explain how small molecule drugs or their metabolites induce allergic drug hypersensitivity reactions. Meanwhile, direct activation of mast cells, provoking the complement system, stimulating or inhibiting inflammatory reaction-related enzymes, accumulating bradykinin, and/or triggering vascular hyperpermeability are considered as the main factors causing non-allergic drug hypersensitivity reactions. To date, many investigations have been performed to explore the underlying mechanisms involved in drug hypersensitivity reactions and to search for predictive and preventive methods in both clinical and non-clinical trials. However, validated methods for predicting and diagnosing hypersensitivity reactions to small molecule drugs and deeper insight into the relevant underlying mechanisms are still limited.

PMID:36439170 | PMC:PMC9684170 | DOI:10.3389/fimmu.2022.1016730

Front Immunol. 2022 Nov 10;13:953210. doi: 10.3389/fimmu.2022.953210. eCollection 2022.

ABSTRACT

BACKGROUND: To conduct a meta-analysis with the aim of comparing the outcomes of antiviral prophylaxis and preemptive therapy for the prevention of cytomegalovirus (CMV) infection in liver transplant (LT) recipients.

METHODS: We searched databases for qualified studies up until March 2022. Finally, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.

RESULTS: With a total of 1834 LT patients, the pooled incidence of CMV infection and CMV disease in the overall LT recipients using antiviral prophylaxis and preemptive therapy were 24.7% vs. 40.4% and 6.4% vs. 9.4%, respectively. Our meta-analysis exhibited a significant reduction in the incidence of CMV infection due to antiviral prophylaxis when compared to preemptive therapy in the high-risk group (OR: 6.67, 95% CI: 1.73, 25.66; p = 0.006). In contrast, there was a significant reduction in the incidence of late-onset of CMV disease in preemptive therapy compared to antiviral prophylaxis in the high-risk group (OR: 0.29, 95% CI: 0.12, 0.74; p = 0.009). However, the incidence of CMV disease, allograft rejection, graft loss, drug related adverse effects, opportunistic infections and mortality did not differ significantly between both the interventions (all p> 0.05).

CONCLUSIONS: We found the use of antiviral prophylaxis, compared with preemptive therapy, is superior in controlling CMV infection and prolonging the time to CMV disease in LT recipients without an increased risk of opportunistic infections, allograft rejection, graft loss, drug related adverse effects, development of drug resistance, and mortality.

PMID:36439159 | PMC:PMC9685424 | DOI:10.3389/fimmu.2022.953210

BMJ Open Gastroenterol. 2022 Nov;9(1):e001001. doi: 10.1136/bmjgast-2022-001001.

ABSTRACT

OBJECTIVE: This study aimed to evaluate the safety and tolerability of OP-724, a CREB-binding protein/β-catenin inhibitor, in patients with advanced primary biliary cholangitis (PBC).

DESIGN: An open-label, non-randomised, phase 1 trial was conducted at two hospitals in Japan. Patients with advanced PBC classified as stage III or higher according to the Scheuer classification by liver biopsy between 4 September 2019 and 21 September 2021 were enrolled. Seven patients received intravenous OP-724 infusions at escalating dosages of 280 and 380 mg/m2/4 hours two times weekly for 12 weeks. The primary endpoint was the incidence of serious adverse events (SAEs). The secondary endpoints were the incidence of AEs and the improvement in the modified Histological Activity Index (mHAI) score.

RESULTS: Seven patients (median age, 68 years) were enrolled. Of these seven patients, five completed twelve cycles of treatment, one discontinued prematurely for personal reasons in the 280 mg/m2/4 hours cohort, and one in the 380 mg/m2/4 hours cohort was withdrawn from the study due to drug-induced liver injury (grade 2). Consequently, the recommended dosage was determined to be 280 mg/m2/4 hours. SAEs did not occur. The most common AEs were abdominal discomfort (29%) and abnormal hepatic function (43%). OP-724 treatment was associated with histological improvements in the fibrosis stage (2/5 (40%)) and mHAI score (3/5 (60%)) on histological analysis.

CONCLUSION: Administration of intravenous OP-724 infusion at a dosage of 280 mg/m2/4 hours two times weekly for 12 weeks was well tolerated by patients with advanced PBC. However, further evaluation of antifibrotic effects in patients with PBC is warranted.

TRIAL REGISTRATION NUMBER: NCT04047160.

PMID:36442892 | DOI:10.1136/bmjgast-2022-001001

Front Pharmacol. 2022 Nov 9;13:1008946. doi: 10.3389/fphar.2022.1008946. eCollection 2022.

ABSTRACT

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom's relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan-Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03-3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference -0.13, 95% CI -0.27-0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients. Clinical Trial Registration: https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020].

PMID:36438822 | PMC:PMC9682103 | DOI:10.3389/fphar.2022.1008946

Psychiatry Clin Neurosci. 2022 Nov 27. doi: 10.1111/pcn.13511. Online ahead of print.

ABSTRACT

INTRODUCTION: Impulse control disorders (e.g., pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on D3-receptor agonism, and switching to alternatives with different pharmacologic mechanisms represents a common management strategy. Nonetheless, treatment failure is common and gaining pathophysiological insights is needed.

AIM: We aimed to identify targets potentially contributing to pathologic impulsivity.

METHOD: We performed a pharmacovigilance-pharmacodynamic study on dopamine agonists and antipsychotics using the Food and Drug Administration Adverse Event Reporting System (January 2004-December 2021). We estimated disproportionate reporting using the Bayesian information component. Using online public databases (IUPHAR, ChEMBL, PDSP, DrugBank), we calculated drug occupancies. To identify the targets potentially contributing to impulsivity, we fitted univariate regression models interpolating information components and occupancies within dopamine agonists and antipsychotics. Sensitivity analyses were performed to check for the robustness of the results.

RESULTS: Among 19,887 reports of impulsivity, 5,898 recorded an antipsychotic, and 3,100 a dopamine agonist. The more robust signals concerned aripiprazole (N=3,091; median information component [95% confidence interval] = 4.51[4.45-4.55]) and brexpiprazole (229; 4.00[3.78-4.16]) for antipsychotics, pergolide (105; 5.82[5.50-6.06]) and pramipexole (2009; 5.43[5.36-5.48]) for dopamine agonists. Robust, significant positive associations between drug occupancy and impulsivity reporting were found for D3 within dopamine agonists (beta=1.52; p-value=0.047) and 5-HT1a within antipsychotics (1.92, 0.029).

CONCLUSION: Our results supported the role of D3-receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5-HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug-induced impulsivity. This article is protected by copyright. All rights reserved.

PMID:36436204 | DOI:10.1111/pcn.13511

BMC Public Health. 2022 Nov 25;22(1):2182. doi: 10.1186/s12889-022-14573-z.

ABSTRACT

PURPOSE: To determine the prevalence and associated factors of self-reported medication information needs among medication users in a general population aged 40 years and above - The Tromsø Study.

METHODS: Cross-sectional study of medication users (n = 10,231) among participants in the Tromsø Study, a descriptive analysis of questionnaire data and multivariable logistic regression (n = 9,194).

RESULTS: Sixteen percent of medication users expressed a need for more information about own medications. Overall, medication users agreed to a higher degree to have received information from the GP compared to the pharmacy. Concerned medication users and those disagreeing to have received information about side effects had the highest odds for needing more information (OR 5.07, 95% CI 4.43-5.81) and (OR 2.21, 95% CI 1.83-2.68), respectively. Medication users who used heart medications (e.g., nitroglycerin, antiarrhythmics, anticoagulants) (OR 1.71, 95% CI 1.46-2.01), medication for hypothyroidism (OR 1.36, 95% CI 1.13-1.64) or had moderately health anxiety had expressed need for medication information. Whereas medication users with lower education, those that never used internet to search for health advice, and medication users who disagreed to have received information about reason-for-use were associated with lower odds (OR 0.75, 95% CI 0.62-0.91), (OR 0.85, 95% CI 0.74-0.98) and (OR 0.68, 95% CI 0.53-0.88), respectively.

CONCLUSION: This study demonstrated that there is need for more information about own medications in a general population aged 40 years and above and shed light on several characteristics of medication users with expressed information need which is important when tailoring the right information to the right person.

PMID:36434564 | DOI:10.1186/s12889-022-14573-z

Nutrients. 2022 Nov 9;14(22):4723. doi: 10.3390/nu14224723.

ABSTRACT

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.

PMID:36432410 | DOI:10.3390/nu14224723

Molecules. 2022 Nov 16;27(22):7926. doi: 10.3390/molecules27227926.

ABSTRACT

Globally, plastics are used in various products. Concerns regarding the human body's exposure to plastics and environmental pollution have increased with increased plastic use. Microplastics can be detected in the atmosphere, leading to potential human health risks through inhalation; however, the toxic effects of microplastic inhalation are poorly understood. In this study, we examined the pulmonary toxicity of polystyrene (PS), polypropylene (PP), and polyvinyl chloride (PVC) in C57BL/6, BALB/c, and ICR mice strains. Mice were intratracheally instilled with 5 mg/kg of PS, PP, or PVC daily for two weeks. PS stimulation increased inflammatory cells in the bronchoalveolar lavage fluid (BALF) of C57BL/6 and ICR mice. Histopathological analysis of PS-instilled C57BL/6 and PP-instilled ICR mice showed inflammatory cell infiltration. PS increased the NLR family pyrin domain containing 3 (NLRP3) inflammasome components in the lung tissue of C57BL/6 and ICR mice, while PS-instilled BALB/c mice remained unchanged. PS stimulation increased inflammatory cytokines, including IL-1β and IL-6, in BALF of C57BL/6 mice. PP-instilled ICR mice showed increased NLRP3, ASC, and Caspase-1 in the lung tissue compared to the control groups and increased IL-1β levels in BALF. These results could provide baseline data for understanding the pulmonary toxicity of microplastic inhalation.

PMID:36432032 | DOI:10.3390/molecules27227926

Int J Mol Sci. 2022 Nov 17;23(22):14207. doi: 10.3390/ijms232214207.

ABSTRACT

Asthma is a common inflammatory disease of the lungs. The prevalence of asthma is increasing worldwide, and the tendency indicates that the number of asthma sufferers will soar in the coming years for several reasons, in particular, the lifestyles we have adopted that expose us to risk factors. Salbutamol is the first selective short-acting β2-agonist (SABA) used as an alternative reliever in the treatment of asthma. Its therapeutic effect is based on its potent smooth muscle relaxant properties, which allow the inhibition of bronchial smooth muscle contraction and subsequent bronchodilation. Salbutamol can be administered orally, intravenously (IV), intramuscularly (IM), subcutaneously, or by inhalation. For this reason, the pharmacokinetic (PK) parameters-absorption, distribution, metabolism, and elimination-are highly diverse and, consequently, the efficacy and adverse effects also differ between each formulation. Here, we review the pharmacological profile of different salbutamol formulations, focusing on their efficacy and adverse effects for its original application, asthma.

PMID:36430683 | DOI:10.3390/ijms232214207