Ital J Dermatol Venerol. 2023 Feb;158(1):26-31. doi: 10.23736/S2784-8671.23.07479-0.

ABSTRACT

BACKGROUND: Despite its favorable long-term safety profile, side effects during dimethyl fumarate (DMF) treatment for psoriasis are not uncommon and may lead to treatment suspension. The association between side effects, especially gastrointestinal, and dietary habits has not yet been specifically addressed.

METHODS: This observational, cross-sectional study aimed to assess the dietary habits of patients with moderate-to-severe plaque psoriasis in treatment with DMF who attended three Italian psoriasis clinics. Demographic and clinical data, including any side effects, were collected from the patients' medical records. A self-administered questionnaire recorded and scored: 1) if meals are eaten regularly or not; 2) daily intake at meals of fatty foods, milk and dairy products, alcohol, fruit and vegetables; and 3) in the case of side effects, the time between eating and their onset.

RESULTS: We included 53 patients in treatment with DMF at a daily dose of 232.4±194.1 mg for 38±29.8 weeks. Thirty-eight (71.7%) reported side effects, namely flushing (60.5%), diarrhea (44.7%), gastralgia (29%) and nausea (15.8%). Overweight seemed associated with the occurrence of side effects. In 47.4% of subjects, side effects appeared within 2 hours of having a meal. Daily fat intake appeared to protect against side effects, albeit without statistical significance; skipping meals was correlated with their onset in subjects complaining of diarrhea.

CONCLUSIONS: Finding some correlation between dietary habits and occurrence of side effects during DMF treatment requires further investigation with the aim of developing possible strategies to improve its tolerability and retention rate.

PMID:36939500 | DOI:10.23736/S2784-8671.23.07479-0

Expert Opin Drug Saf. 2023 Mar 20. doi: 10.1080/14740338.2023.2193391. Online ahead of print.

ABSTRACT

OBJECTIVES: Taxane-related neurotoxicity is a frequent clinical problem but lacks postmarketing data regarding neurological disorders. This study aimed to evaluate the potential association between neurological adverse events and several taxane-derived drugs via the Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: Disproportionality analysis was applied to data mining of the suspected cases of neurological disorders after using different taxanes based on the FAERS data from January 2017 and December 2021. We also investigated the times to onset, fatality, and hospitalization proportions of taxane-related neurotoxicity.

RESULTS: In total, 3,940 cases were screened out, which were more prevalent in elderly patients and females. Peripheral neuropathy was a common adverse event among all taxanes with relatively strong association. Generally, the median time to neurological adverse effect onset was 27 days (interquartile range, 11.0~78.0 days) following taxane regimens, and the majority of cases were detected within the first 30 days. Among cases of neurological adverse events treated with taxane, the fatality and hospitalization proportions were 6.13% and 28.63%, respectively.

CONCLUSION: By analyzing the FAERS data, we provided a detailed profile of neurotoxicity and different taxanes in detail in terms of clinical characteristics, time to onset, and patient outcomes.

PMID:36939004 | DOI:10.1080/14740338.2023.2193391

Front Pharmacol. 2023 Mar 3;14:1077607. doi: 10.3389/fphar.2023.1077607. eCollection 2023.

ABSTRACT

Background: Drug-induced parkinsonism (DIP) is the most prevalent neurological side effect of antipsychotics in the Chinese population. Early prevention, recognition, and treatment of DIP are important for the improvement of treatment outcomes and medication adherence of schizophrenia patients. However, the risk factors of DIP and the impact on the clinical syndromes of schizophrenia remain unknown. Aim: The goal of this study was to explore the risk factors, clinical correlates, and social functions of DIP in Chinese schizophrenia patients. Methods: A cross-sectional analysis of a multicenter, observational, real-world, prospective cohort study of the Chinese schizophrenia population with a baseline assessment was conducted from the year 2012 to 2018. Participants were recruited from four mental health centers in Shanghai and totaled 969 subjects. Sociodemographic data, drug treatment, and clinical variables were compared between the DIP group and the non-DIP group. Variables that correlated with the induction of DIP, and with p≤ 0.1, were included in the binary logistic model for analyzing the risk factors of DIP. First generation antipsychotics (FGA)/second generation antipsychotics (SGA) model and high and low/medium D2 receptor antipsychotics were analyzed respectively to control the bias of co-linearity. All risk factors derived from the a forementioned models and clinical variables with p≤ 0.1 were included in the multivariate analysis of clinical correlates and social function of DIP patients. The Positive and Negative Syndrome Scale (PANSS) model and the personal and social performance (PSP) model were analyzed separately to control for co-linearity bias. Results: Age (OR = 1.03, p< 0.001), high D2 receptor antagonist antipsychotic dose (OR = 1.08, p = 0.032), and valproate dose (OR = 1.01, p = 0.001) were the risk factors of DIP. FGA doses were not a significant contributor to the induction of DIP. Psychiatric symptoms, including more severe negative symptoms (OR = 1.09, p< 0.001), lower cognition status (OR = 1.08, p = 0.033), and lower excited symptoms (OR = 0.91, p = 0.002), were significantly correlated with DIP induction. Social dysfunction, including reduction in socially useful activities (OR = 1.27, p = 0.004), lower self-care capabilities (OR = 1.53, p< 0.001), and milder disturbing and aggressive behavior (OR = 0.65, p< 0.001), were significantly correlated with induction of DIP. Valproate dose was significantly correlated with social dysfunction (OR = 1.01, p = 0.001) and psychiatric symptoms (OR = 1.01, p = 0.004) of DIP patients. Age may be a profound factor that affects not only the induction of DIP but also the severity of psychiatric symptoms (OR = 1.02, p< 0.001) and social functions (OR = 1.02, p< 0.001) of schizophrenia patients with DIP. Conclusion: Age, high D2 receptor antagonist antipsychotic dose, and valproate dose are risk factors for DIP, and DIP is significantly correlated with psychiatric symptoms and social performance of Chinese schizophrenia patients. The rational application or discontinuation of valproate is necessary. Old age is related to psychotic symptoms and social adaption in Chinese schizophrenic patients, and early intervention and treatment of DIP can improve the prognosis and social performance of schizophrenia patients. Clinical Trial Registration: Identifier: NCT02640911.

PMID:36937864 | PMC:PMC10020528 | DOI:10.3389/fphar.2023.1077607

Iran J Pharm Res. 2022 Sep 26;21(1):e130124. doi: 10.5812/ijpr-130124. eCollection 2022 Dec.

ABSTRACT

BACKGROUND: The prevalence of drug poisoning is on the rise in Iran due to the increased public access to drugs. A national drug poisoning registry system is a suitable tool for better management, control, and prevention of drug poisoning.

OBJECTIVES: This study aimed to propose a national drug poisoning registry model for Iran.

METHODS: This was an applied research conducted in two major phases. In the first phase, all sources pertaining to drug poisoning registries were reviewed, and a national drug poisoning registry model was proposed. In the second phase, this model was validated and finalized using a researcher-made questionnaire and through a two-stage Delphi technique.

RESULTS: The focus of national drug poisoning activities and registry management reached the 100% consensus of experts at the Drug and Poison Information Center of the Food and Drug Organization (Ministry of Health and Medical Education). Goals, data sources, registry system structure, data set, standards, data exchange, registry features, and processes of the proposed model also achieved unanimous expert consensus.

CONCLUSIONS: Given the importance of a national drug poisoning registry in gathering, storing, analyzing, and reporting the data of patients, it is essential to provide a framework for evaluating and controlling drug poisoning and for generating valuable data for decision-making. The model proposed herein can offer the information infrastructure for designing and implementing such a system.

PMID:36937211 | PMC:PMC10016136 | DOI:10.5812/ijpr-130124

J Pak Med Assoc. 2023 Mar;73(3):737. doi: 10.47391/JPMA.746.

NO ABSTRACT

PMID:36932804 | DOI:10.47391/JPMA.746

J Pak Med Assoc. 2023 Mar;73(3):674-676. doi: 10.47391/JPMA.4993.

ABSTRACT

Hepatitis C virus infection is one of the main causes of chronic liver disease worldwide. The highly efficacious direct-acting antiviral (DAA) drugs licensed for therapy have revolutionised the treatment and are reported to have few side effects. Sofosbuvir is a pan-genotypic DAA that acts by inhibition of the hepatitis C NS5B polymerase. It has shown high efficacy in combination with several other drugs with low toxicity, a high resistance barrier, and minimal drug interactions with other hepatitis C DAA drugs. We describe a first of its kind case from Pakistan with visual disturbances caused by Sofosbuvir. A temporal relationship was observed between the treatment initiation and the onset of visual disturbances. The aim of this case report is to draw attention to the unanticipated side effects of this relatively new class of drug that have not been reported previously.

PMID:36932780 | DOI:10.47391/JPMA.4993

J Pak Med Assoc. 2023 Mar;73(3):500-504. doi: 10.47391/JPMA.5512.

ABSTRACT

OBJECTIVE: To evaluate children with suspected or definite hypervitaminosis D with respect to prevalence, clinical manifestations and pharmacological aspects.

METHODS: The retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised medical records from January 1 to December 31, 2018, of children aged <18 years with 25-hydroxyvitamin D levels >50ng/ml. Clinical and pharmacological data was retrieved. Data was analysed using SPSS 23.

RESULTS: Of the 118,149 subjects visiting the clinical laboratory during the study period, children tested for serum 25-hydroxyvitamin D levels were 16,316(13.8%) who had a median age of 9.78 years (interquartile range: 10.2 years). Children who registered for consultation were 2720(16.6%), and, out of them, 602(22%) had serum 25-hydroxyvitamin D >50ng/ml. The median 25-hydroxyvitamin D levels and age were 70.1ng/ml (interquartile range: 100ng/ml) and 3.1 years (interquartile range: 17.93 years), respectively, and 345(57.3%) of them were boys. Children supplemented with vitamin D were 197(33.1%) and 193(97.9%) of them were prescribed by physicians. Mega-doses were taken by 68(34.17%), while the remaining had used various combinations in syrup or tablet forms. Commonly prescribed mega-doses were 600,000IU 30((44.1%) and 200,000IU 31(45.5%) injections of vitamin D. The primary indications were pains/aches in 51(25.8%) cases, developmental delay 50(25.3%), and vitamin D deficiency 49(24.8%). The main symptoms of hypervitaminosis D or toxicity were abdominal pain 27(13.7%) and constipation 31(15.7%).

CONCLUSIONS: Children should be given vitamin D supplements with caution as prolonged supplementation and repeated mega-doses can result in toxicity which may cause serious consequences.

PMID:36932749 | DOI:10.47391/JPMA.5512

Medicine (Baltimore). 2023 Mar 17;102(11):e33236. doi: 10.1097/MD.0000000000033236.

ABSTRACT

Due to the urgency of controlling the coronavirus disease 2019 pandemic, coronavirus disease 2019 messenger ribonucleic acid (mRNA) vaccines have been expeditiously approved and introduced in several countries without sufficient evaluation for adverse events. We analyzed adverse events among Korean healthcare workers who received all 3 doses of the BNT162b2 mRNA vaccine. This survey was conducted among hospital workers of Inha University Hospital who had received the BNT162b2 mRNA vaccine for their first, second, third rounds, and using a diary card. The surveyed adverse events included local (redness, edema, and injection site pain) and systemic (fever, fatigue, headache, chill, myalgia, arthralgia, vomiting, diarrhea, pruritis, and urticaria) side effects and were divided into 5 grades (Grade 0 = none - Grade 4 = critical). Based on adverse events reported at least once after any of the 3 doses, the most common systemic adverse reactions were chills and headache (respectively, 62.6%, 62.4%), followed by myalgia (55.3%), arthralgia (53.4%), fatigue (51.6%), pruritus (38.1%), and fever (36.5%). The frequency and duration of adverse events were significantly greater in women (P < .05) than men. Except for redness, pruritus, urticaria, and most adverse reactions had a higher rate of occurrence after the third dose in subjects who also had reactions with the second dose. However, grade 4 adverse events did occur with the third dose in some patients, even if there were no side effects with the first and second doses. Adverse events experienced with the first and second doses of the BNT162b2 mRNA vaccine in Korean healthcare workers increased the incidence of adverse events at the time of the third dose. On the other hand, grade 4 adverse events could still occur with the third dose even though there were no side effects with the first and second doses.

PMID:36930126 | PMC:PMC10018524 | DOI:10.1097/MD.0000000000033236

Medicine (Baltimore). 2023 Mar 17;102(11):e33273. doi: 10.1097/MD.0000000000033273.

ABSTRACT

BACKGROUND: Preventing contrast-induced acute kidney injury (CI-AKI) is critical because of its association with poor clinical outcomes, including extended hospital stays and increased mortality. The effects of probucol on preventing CI-AKI have been controversial. Therefore, this systematic review and meta-analysis evaluated the influence of probucol combined with hydration on the CI-AKI risk in patients with coronary heart disease undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI).

METHODS: We retrieved data from the following databases from their inception to May 29, 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database (Sinomed), Wanfang Database, and Chinese Scientific Journal Database. The methodological quality of the trials was assessed following the Cochrane Handbook guidelines, and Review Manager 5.3 and Stata 14.0 software were used for the data analysis.

RESULTS: We included 14 trials comprising 3306 patients in the analysis. All included trials reported the CI-AKI incidence rate (the primary outcome). Probucol with hydration significantly reduced the CI-AKI incidence compared to hydration alone (odds ratio [OR]: 0.33, 95% confidence interval [CI]: 0.25-0.44, P < .001). Subgroup analyses were performed based on the contrast medium type (iso-osmolality vs low-osmolality contrast medium [LOCM]) and volume (less than or more than 200 mL); the effects of probucol with hydration versus hydration-only on CI-AKI were comparable within each subgroup. Additionally, the serum creatinine (Scr) concentration 24 hours, 48 hours, and 72 hours and the estimated glomerular filtration rate (eGFR) 72 hours after contrast exposure were better in the probucol with hydration group than the hydration-only group. Finally, major clinical adverse events and adverse drug reactions were comparable between the probucol with hydration and hydration-only groups.

CONCLUSION: Probucol with hydration decreases the CI-AKI incidence compared to hydration only in patients with coronary heart disease undergoing CAG or PCI. However, more high-quality, large-sample, multicenter randomized trials are needed to confirm this conclusion.

PMID:36930109 | PMC:PMC10019121 | DOI:10.1097/MD.0000000000033273

Oncoimmunology. 2023 Mar 8;12(1):2188719. doi: 10.1080/2162402X.2023.2188719. eCollection 2023.

ABSTRACT

Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management. Here, we conducted a multi-institution analysis of all patients with stage III/IV melanoma who developed RirAEs after being treated with ICIs (anti-PD-1/L1, anti-CTLA-4, and combination PD-1/CTLA-4 blockade) at three institutions (Vanderbilt University Medical Center, Massachusetts General Hospital, and Melanoma Institute of Australia). RirAEs were defined as those occurring in approximately <1% of patients treated with anti-PD-1 or <2% with combination. Of 2834 patients who received ICIs, 82 developed RirAEs and were more common with combination PD-1/CTLA-4 blockade (4.6%) vs. anti-PD-1/L1 agents (2.8%). Overall median time from ICI start to RirAE was 86 days (interquartile range 42-235 days) with significantly earlier onset in combination therapy (p < 0.001). The spectrum of RirAEs spanned across several organ systems. Most RirAEs were grade 2 (57 [41.3%]) and grade 3 (40 [29.0%]) with relatively few grade 4 (11 [8.0%]) or 5 (5 [3.6%]) events. Steroid re-escalation (21.4%) or additional immunosuppression (13.8%) were commonly required. RirAE recurrence occurred in 22.6% with ICI rechallenge; 37.1% had new irAEs with rechallenge. In conclusion, RirAEs associated with ICIs in melanoma patients occurred, in aggregate, in 2-5% of patients treated with anti-PD-1-based therapy. Steroid re-escalation and alternative immunosuppression use were frequently required but fatal irAEs were fairly uncommon.

PMID:36926262 | PMC:PMC10012911 | DOI:10.1080/2162402X.2023.2188719

Muscle Nerve. 2023 Mar 16. doi: 10.1002/mus.27819. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: Expanded access protocols (EAPs) are a Food and Drug Administration (FDA)-regulated pathway for granting access to investigational products (IPs) to individuals with serious diseases who are ineligible for clinical trials. There is limited information about the use of EAPs in ALS; the aim of this report is to share the design, operational features, and costs of an EAP program for ALS.

METHODS: The program was launched in 2018 at a single center. In alignment with FDA guidance, protocols were designed as individual (single participant) or intermediate size. Inclusion criteria were broad (e.g., no restrictions due to long disease duration or low vital capacity). Safety information was collected in all EAPs. Selected biomarkers were collected in nine of the EAPs.

RESULTS: From July 2018 through February 2022, 17 EAPs were submitted for FDA and institutional review board (IRB) approval. The mean time from submission to approval from the FDA and IRB were 24 days and 37 days, respectively. A total of 164 participants were enrolled and, of these, 77 participants were still receiving IP as of February 2022. The mean duration of participation in an EAP was 12.6 months. No drug-related serious adverse events were reported from any of the EAPs. Average site cost was $613.47 per participant per month, not including IP costs.

CONCLUSION: EAPs provide a framework through which access to IP can be safely provided to people with ALS who do not qualify for clinical trials. Site resources are needed to launch and maintain these programs. This article is protected by copyright. All rights reserved.

PMID:36929648 | DOI:10.1002/mus.27819

ANZ J Surg. 2023 Mar 16. doi: 10.1111/ans.18361. Online ahead of print.

ABSTRACT

BACKGROUND: Multimodal therapy (MMT) for analgesia following joint arthroplasty continues to reduce cost and the requirement of strong opioids post-operatively. Tramadol immediate release is an important MMT component providing synergistic pain relief via dual μ-opioid agonism and serotonin and noradrenaline reuptake inhibition. Case reports have shown tramadol when combined with antidepressants cause serotonin syndrome, but this has yet to be demonstrated in larger studies. We undertook a pilot study assessing the functional outcomes and incidence of side effects associated with tramadol in lower limb arthroplasty patients with a focus on those taking concomitant antidepressants.

METHODS: Primary and revision hip and knee arthroplasties performed in 2018-2019 by a senior surgeon were included (n = 364). Patient records were assessed to determine pain scores, length of hospitalization, prescription of tramadol and antidepressants, self-reported side effects and previous adverse reactions associated with tramadol.

RESULTS: Nine-five percentage of patients had been prescribed tramadol, and 16% had concurrent prescription of tramadol and one or more antidepressants. The total rate of adverse effects associated with tramadol before and during the study was 7% (n = 25) including two cases of concomitant tramadol and antidepressant use. For patients on tramadol, median 2-week post-operative pain score was 1.5 (IQR 1-2.5) out of 10 and hospitalization length was 1 (IQR 1-2) days.

CONCLUSION: Tramadol immediate release appears to be well tolerated among our patient population with no significantly increased prevalence of side effects when co-administered with low and moderate dose antidepressants.

PMID:36929136 | DOI:10.1111/ans.18361

Reg Anesth Pain Med. 2023 Mar 16:rapm-2023-104398. doi: 10.1136/rapm-2023-104398. Online ahead of print.

ABSTRACT

INTRODUCTION: The addition of adjuvants to short-acting local anesthetics (LA) is common practice in clinical routine to speed up block onset and decrease pain on injection. In a previous study, we observed the development of microscopic crystal precipitations after bupivacaine or ropivacaine were mixed with adjuvants; this follow-up study is intended to clarify whether crystallization (A) also occurs in short-acting or intermediate-acting LA-adjuvant mixtures, (B) changes over time, and (C) is associated with the solutions' pH.

METHODS: Lidocaine 2%, prilocaine 2%, mepivacaine 2%, procaine 2% and chloroprocaine 2% were individually mixed with clonidine, dexamethasone, dexmedetomidine, epinephrine, fentanyl, morphine or sodium bicarbonate 8.4% in clinically established ratios. For each mixture, we measured initial pH and recorded crystallization patterns at 0, 15, 30 and 60 min using a standardized, semiquantitative light microscopy approach.

RESULTS: Lidocaine 2% and mepivacaine 2% plus sodium bicarbonate 8.4%, and mepivacaine 2% plus dexamethasone developed delayed grade 5 crystallization over 1 hour. Prilocaine-based, procaine-based and chloroprocaine-based mixtures showed much less pronounced crystallization, with a maximum of grade 2. Initial pH and grade of crystallization showed weak monotonic relationships at time points t0, t15 and t30 (ρ=-0.17, 0.31 and 0.32, (all p>0.05)) and a moderate relationship time point t60 (ρ=0.57 (p=0.0003)) CONCLUSIONS: Our study revealed high grades of crystallization in lidocaine/mepivacaine-bicarbonate and mepivacaine-dexamethasone mixtures, although these were previously considered safe for local, perineural or neuraxial use. Our findings cast particular doubt on the safety of preparing these formulations for later use.

PMID:36928300 | DOI:10.1136/rapm-2023-104398

Ned Tijdschr Geneeskd. 2023 Mar 8;167:D7402.

ABSTRACT

Statins are effective drugs that can reduce the risk of new cardiovascular events. Although in randomized, placebo-controlled trials statins are associated with a low risk of mild muscle complaints such as myalgia, in daily practice up to 30% of patients report complaints attributed to statin use. Two recent studies have shown statin-associated muscle complaints are mainly related to the nocebo effect. The nocebo effect is a decrease in benefit and/or a new onset or worsening of adverse effects due to an expectation of harm associated with the treatment. Statins face reputational challenges due to a vast amount of negative attention on the internet. We need to address the nocebo effect by managing the perception of statins and provide patients with objective information about statin treatment, reduce the negative expectations, and placing discussion about the likelihood of adverse effects into the context of treatment benefit.

PMID:36920298

Tidsskr Nor Laegeforen. 2023 Mar 13;143(4). doi: 10.4045/tidsskr.22.0758. Print 2023 Mar 14.

NO ABSTRACT

PMID:36919290 | DOI:10.4045/tidsskr.22.0758

BMC Public Health. 2023 Mar 14;23(1):488. doi: 10.1186/s12889-023-15346-y.

ABSTRACT

BACKGROUND: Although patients frequently use patient information leaflets (PILs) to obtain information about medicine, their confidence in using it may be diminished after reading it. This study aimed to assess the public perception of PIL's quality and the perceived impact of its use on medication adherence.

METHODS: A community-based cross-sectional study of 1,138 adult individuals in Saudi Arabia, April-May 2020, was conducted via Survey Monkey using an anonymous validated e-questionnaire. Data were collected on personal characteristics, PIL readership and preferences, perception towards PIL quality and impact of its use on taking medication, and reasons for not reading PIL. In addition, logistic regression analysis was performed to identify the significant predictors of reading PIL. Significance was considered at p < 0.05.

RESULTS: Nearly all participants (91.1%) reported reading PIL. The more read PIL's sections were directions of use (52.7%) and side effects (30.3%). Female gender (OR = 5.64, 95%CI: 3.53,9.02), age over 40 years (OR = 2.80, 95%CI: 1.69,4.64), and secondary education or more (OR = 1.74, 95%CI: 1.06,2.85) were the significant predictors of reading PIL. The majority of PIL readers reported their preference for verbal information (65.8%), hard copy presentation (77%), adding graphics (71.1%), and concise content of PIL (68.8%). In addition, most participants reported PIL always/usually adds to their knowledge of medicines (70.6%) and said that PIL reading positively impacted their medication adherence (64.9%). For only 8.8%, PIL reading negatively impacted their adherence, primarily because of reading information on medicine's side effects and complications (74.4%). More than one-half of participants perceived the PIL quality as good/excellent in terms of; font size (51.3%), language comprehensiveness (64.9%), paper quality (68.0%), and general appearance (64.9%). Getting sufficient information from doctors and pharmacists was the main reason for not reading the PIL (59.2%). Most participants (92.5%) agreed on standardizing how information is displayed in the PIL among all PILs of all companies.

CONCLUSION: PIL is read by nearly all the study sample, especially females, older, and educated subjects. It was perceived as beneficial in upgrading medication adherence. Effective designing of PILs should focus on patients' literacy level and age. Standardization of the PIL structure in all pharmaceutical companies is recommended.

PMID:36918823 | DOI:10.1186/s12889-023-15346-y

BMC Bioinformatics. 2023 Mar 14;24(1):93. doi: 10.1186/s12859-023-05212-4.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDIs) prediction is vital for pharmacology and clinical application to avoid adverse drug reactions on patients. It is challenging because DDIs are related to multiple factors, such as genes, drug molecular structure, diseases, biological processes, side effects, etc. It is a crucial technology for Knowledge graph to present multi-relation among entities. Recently some existing graph-based computation models have been proposed for DDIs prediction and get good performance. However, there are still some challenges in the knowledge graph representation, which can extract rich latent features from drug knowledge graph (KG).

RESULTS: In this work, we propose a novel multi-view feature representation and fusion (MuFRF) architecture to realize DDIs prediction. It consists of two views of feature representation and a multi-level latent feature fusion. For the feature representation from the graph view and KG view, we use graph isomorphism network to map drug molecular structures and use RotatE to implement the vector representation on bio-medical knowledge graph, respectively. We design concatenate-level and scalar-level strategies in the multi-level latent feature fusion to capture latent features from drug molecular structure information and semantic features from bio-medical KG. And the multi-head attention mechanism achieves the optimization of features on binary and multi-class classification tasks. We evaluate our proposed method based on two open datasets in the experiments. Experiments indicate that MuFRF outperforms the classic and state-of-the-art models.

CONCLUSIONS: Our proposed model can fully exploit and integrate the latent feature from the drug molecular structure graph (graph view) and rich bio-medical knowledge graph (KG view). We find that a multi-view feature representation and fusion model can accurately predict DDIs. It may contribute to providing with some guidance for research and validation for discovering novel DDIs.

PMID:36918766 | DOI:10.1186/s12859-023-05212-4

Sci Transl Med. 2023 Mar 15;15(687):eabn2110. doi: 10.1126/scitranslmed.abn2110. Epub 2023 Mar 15.

ABSTRACT

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

PMID:36921036 | DOI:10.1126/scitranslmed.abn2110

J Ethnopharmacol. 2023 Jun 12;309:116383. doi: 10.1016/j.jep.2023.116383. Epub 2023 Mar 12.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The use of herbal medicines for prophylaxis, prevention, and treatment of various ailments is rising throughout the world because they are thought to be safer than allopathic treatments, which they are. However, several investigations have documented the toxicity and adverse drug reactions (ADR) of certain formulations and botanicals if not consumed wisely.

AIM OF THE STUDY: The goal of the current study is to address herbal medication pharmacovigilance (PV) modeling and related considerations for improved patient safety. Also, focus is laid on the comprehensive and critical analysis of the current state of PV for herbal medications at the national and international levels.

MATERIALS AND METHODS: Targeted review also known as focused literature review methodology was utilized for exploring the data from various scientific platforms such as Science Direct, Wiley Online Library, Springer, PubMed, Google Scholar using "pharmacovigilance, herbal medicine, traditional medicine, ADR, under reporting, herb toxicity, herb interactions" as keywords along with standard literature pertaining to herbal medicines that is published by the WHO and other international and national organizations etc. The botanical names mentioned in the present article were authenticated using World Flora Online database.

RESULTS: The historical developments paving the way for PV in regulatory setup were also discussed, along with various criteria's for monitoring herbal medicine, ADR of herbs, phytoconstituents, and traditional medicines, herb-drug interactions, modes of reporting ADR, databases for reporting ADR's, provisions of PV in regulatory framework of different nations, challenges and way forward in PV are discussed in detail advocating a robust drug safety ecosystem for herbal medicines.

CONCLUSION: Despite recent efforts to encourage the reporting of suspected ADRs linked to herbal medicines, such as expanding the programme and adding community pharmacists and other healthcare professionals as recognized reporters, the number of herbal ADR reports received by the regulatory bodies remains comparatively low. Since users often do not seek professional advice or report if they have side effects, under-reporting, is anticipated to be significant for herbal medications. There are inadequate quality control methods, poor regulatory oversight considering herbs used in food and botanicals, and unregulated distribution channels. In addition, botanical identity, traceability of herbs, ecological concerns, over-the-counter (OTC) herbal medicines, patient-physicians barriers requires special focus by the regulatory bodies for improved global safety of herbal medicines.

PMID:36918049 | DOI:10.1016/j.jep.2023.116383

J Oral Facial Pain Headache. 2023 Winter;37(1):27-34. doi: 10.11607/ofph.3163.

ABSTRACT

Aims: To present a review of the mechanisms of action, available clinical data, and safety profiles of novel migraine therapeutics to inform practice. Methods: PubMed, Medline, and Google Scholar were searched for randomized controlled trials (24 publications), review articles (15 publications), and other pertinent literature (16 publications) discussing the novel migraine therapeutics available between the years 2010 and 2021. All publications were reviewed to assess the mechanism of action, relevant clinical data, and side effect profile for each novel treatment. Therapeutic gain was also recorded in studies that included a placebo arm. Results: A total of 55 studies were included in the final analysis. In the preventive treatment of migraine, novel medications target calcitonin gene-related peptide (CGRP) and fall into either the monoclonal anti-CGRP or gepant class. For the acute treatment of migraine, novel medications fall into either the ditan or gepant class. Several medical devices have been developed for the acute and preventive treatment of migraine. Conclusion: Novel therapeutics are available for both the prevention and acute treatment of migraine headaches. These new medications and neuromodulatory devices appear overall to be safe and effective in the management of migraine headaches.

PMID:36917235 | DOI:10.11607/ofph.3163