Wanlong Lin

Background: Traditional pharmacy management, which relies on paper- and computer-based methods, is often inefficient and inflexible. There is an urgent need to develop support tools to address these challenges. The WeChat mini-program has been applied in multiple fields because it is readily accessible within the WeChat ecosystem. Its use in pharmacy management may support more accessible and flexible workflows. Objective: To develop and evaluate a WeChat mini-program-based Mobile Pharmacy Management Assistance System. Methods: A Pharmacy Collaboration Team consisting of front-line pharmacists, pharmacy administrators, and one informatics pharmacist was established to collect functional requirements through group discussions. The system was developed as a WeChat mini-program and implemented in routine pharmacy-management practice. After the 3-month implementation period, participating pharmacists were invited to complete a questionnaire. The questionnaire included the System Usability Scale, self-reported experience ratings comparing paper-based, computer-based, and mobile management modes, and open-ended feedback. Experience ratings were summarized using medians and interquartile ranges. Differences among the three paired management modes were analyzed using the Friedman test with Bonferroni correction. Results: The final version of the system consisted of six modules: shift handovers, drug knowledge base, medication-error recording and analysis, drug-expiry reminders, damaged-drug recording, and medication consultations. Twenty-eight participants were invited to participate, and 27 completed valid questionnaires. The mean System Usability Scale score was 79.54 with a standard deviation of 11.33. The mobile-based mode received higher ratings for accessibility, work data sharing, and update frequency. The most frequently selected liked feature was the convenience of access anytime and anywhere, whereas the least appreciated feature was the limited interface size on mobile devices. Conclusions: This single-center exploratory evaluation supports the feasibility and preliminary usability of a WeChat mini-program-based mobile pharmacy management assistance system developed through a multi-role Pharmacy Collaboration Team. The system showed potential advantages in selected self-reported user-experience dimensions among pharmacists. However, the findings should be interpreted as preliminary evidence based on perceived user experience. Larger multicenter studies using objective workflow, data-quality, and medication-management outcomes are needed to evaluate its practical impact further.

Background Many women are exposed to antiseizure medications (ASMs) during pregnancy, raising concerns about pregnancy and offspring health risks. The current safety data remain insufficient, necessitating further investigation. Methods Using data from the FDA Adverse Event Reporting System (2010–2023), this study employed both the Reporting Odds Ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) for disproportionality analysis of pregnancy and offspring toxicity related to maternal ASM exposure. In addition, we performed signal adjustment by excluding polytherapy cases, and drug–drug interaction (DDI) signals of two ASMs were identified using Ω Shrinkage measures and Chi-square tests. Results 3,459 mothers were exposed to 23 ASMs, resulting in 10,910 adverse events. 59 malformation signals, 27 adverse perinatal outcome signals, and 35 dysplasia signals were identified. Among traditional ASMs, valproic acid (VPA) and carbamazepine (CBZ) exhibited the highest number of signals, while levetiracetam (LEV), lamotrigine (LTG), lacosamide, gabapentin, and topiramate (TPM) predominated among newer ASMs. Signals for cardiac malformations, adverse neurodevelopment, and adverse offspring growth outcomes were widespread, with the strongest signals for specific outcomes observed for zonisamide [ROR = 14.82, 95% CI: 5.43–40.41], gabapentin [ROR = 52.52, 95% CI: 15.68–175.95], and brivaracetam [ROR = 22.96, 95% CI: 8.42–62.61], respectively. Six DDI signals displayed ≥ 3, including LTG + LEV/VPA associated with malformation, CBZ + lacosamide/LTG, and VPA + clonazepam associated with fetal loss. Conclusions The potential risks associated with LEV and LTG surpass expectations, warranting further evaluation, particularly in combination therapy. In addition, ASMs with widespread signals, such as VPA, CBZ, TPM, and lacosamide, warrant heightened attention.

Background The relationship between antidepressants, depression, and the incidence of postpartum hemorrhage (PPH) has been reported in observational studies, but the causal link between these factors remains unknown. Clarifying this relationship is important for treating depression during pregnancy and managing PPH. Objective We aimed to assess the causal relationship between antidepressants, depression, and PPH using a two-sample Mendelian randomization method. Methods Single nucleotide polymorphisms were identified from publicly available genetics summary databases (FinnGen database, access date: 28 December, 2023, version R9, phenocode: ANTIDEPRESSANTS, 195,321 participants; the genome-wide association studies [GWAS] catalog, access date: 3 April, 2024, GWAS ID: ebi-a-GCST90016607; Integrative Epidemiological Unit database, access date: 3 April, 2024, GWAS ID: ieu-a-1187) as alternative exposure factors for antidepressants and depression. Subsequently, inverse variance weighting, Mendelian randomization-Egger regression, weighted median, simple method, and weighted method were employed for Mendelian randomization analyses, and the results were validated for pleiotropy, heterogeneity, and sensitivity. Results The analyses employed three sets of genetic tools, comprising two sets of 9 and 32 single nucleotide polymorphisms that are strongly associated with depression and another set of 26 single nucleotide polymorphisms that are associated with antidepressants. The inverse variance weighting indicated that antidepressants are associated with PPH (odds ratio = 1.36, 95% confidence interval 1.10–1.69, p = 0.005). Conversely, none of the five methods of Mendelian randomization analysis identified an effect of depression on PPH. Conclusions This Mendelian randomization analysis indicated that antidepressant use is associated with PPH. However, the evidence does not support a causal relationship between depression and PPH.

Background: Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce.Objectives: To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health.Materials and methods: Data from the FDA adverse event reporting system (FAERS) were analyzed (2010–2022). Disproportionality analyses were used to identify signals of each drug‐adverse event pair associated with paternal drug exposure in a different hierarchical manner.Results: Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam‐small for dates baby and finasteride‐cryptorchidism were particularly significant (reporting odds ratio, ROR > 800, N > 10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept‐skeletal dysplasia, and tacrolimus‐talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti‐tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin.Conclusions: This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases—abortion, diazepam—small for date baby, finasteride—cryptorchidism, etoposide and cisplatin‐13 trisomy.

Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder. Although prior studies have investigated the metabolomes of SMA in various contexts, there is a gap in research on cerebrospinal fluid (CSF) metabolomics compared to healthy controls. CSF metabolomics can provide insights into central nervous system function and patient outcomes. This study aims to investigate CSF metabolite profiles in untreated SMA patients to enhance our understanding of SMA metabolic dysregulation. Methods: This case control study included 15 SMA patients and 14 control subjects. CSF samples were collected, and untargeted metabolomics was conducted to detect metabolites in SMA and control groups. Results: A total of 118 metabolites abundance were significantly changed between the SMA and control groups. Of those, 27 metabolites with variable importance for the projection (VIP) ≥ 1.5 were identified. The top 5 differential metabolites were N-acetylneuraminic acid (VIP = 2.38, Fold change = 0.43, P = 5.49 × 10^–5), 2,3-dihydroxyindole (VIP = 2.33, Fold change = 0.39, P = 1.81 × 10^–4), lumichrome (VIP = 2.30, Fold change = 0.48, P = 7.90 × 10^–5), arachidic acid (VIP = 2.23, Fold change = 10.79, P = 6.50 × 10^–6), and 10-hydroxydecanoic acid (VIP = 2.23, Fold change = 0.60, P = 1.44 × 10^–4). Cluster analysis demonstrated that the differentially metabolites predominantly clustered within two main categories: protein and amino acid metabolism, and lipid metabolism. Conclusions: The findings highlight the complexity of SMA, with widespread effects on multiple metabolic pathways, particularly in amino acid and lipid metabolism. N-acetylneuraminic acid may be a potential treatment for functional improvement in SMA. The exact mechanisms and potential therapeutic targets associated with metabolic dysregulation in SMA require further investigation.

Background and Objective Spinal muscular atrophy (SMA) is a genetic disorder with limited treatment options. It is crucial to have a comprehensive understanding of drug safety in order to make informed clinical drug selections for patients with SMA. Assessing the safety profiles of therapeutic drugs for SMA has been challenging due to the limited number of patients included in clinical trials. This study aims to investigate and compare the potential safety concerns associated with three leading SMA therapeutic drugs: nusinersen, risdiplam, and onasemnogene abeparvovec. Methods The FDA Adverse Event Reporting System database was used to analyze drug safety, and a case (SMA drug)/noncase (all other drugs in the database) approach was employed to estimate safety signals through disproportionality analysis and reporting odds ratio (ROR). Veen analysis was conducted to compare and select the idiosyncratic adverse events (AEs) associated with each drug. Results The study included 5324 cases of nusinersen, 1184 cases of risdiplam, and 1277 cases of onasemnogene abeparvovec. Venn analysis revealed 27 common AEs among the three drugs, including cardiac, gastrointestinal, metabolism, musculoskeletal, renal, respiratory disorders, and infections. Additionally, 196 AEs exclusively found in nusinersen included post lumbar puncture syndrome [ROR (95% CI) = 6120.91 (5057.01–7408.64), n = 372], procedural pain [ROR (95% CI) = 54.86 (48.13–62.54), n = 234], idiopathic intracranial hypertension [ROR (95% CI) = 6.12 (2.29–16.33), n = 4], and hypokalemia [ROR (95% CI) = 2.02 (1.24–3.31), n = 16]. Additionally, transient deafness was identified as an unexpected and rare, yet severe, AE for nusinersen [ROR (95% CI) = 23.32 (8.71–62.44), n = 4]. Risdiplam exhibited 50 AEs exclusively, with notable idiosyncratic AEs including diarrhea [ROR (95% CI) = 4.55 (3.79–5.46), n = 121], fatigue [ROR (95% CI) = 2.03 (1.6–2.57), n = 70], photosensitivity reaction [ROR (95% CI) = 9.50 (4.25–21.13), n = 6], rash [ROR (95% CI) = 1.90 (1.36–2.67), n = 34], and [ROR (95% CI) = 4.3 (1.93–9.58), n = 6] in comparison with the other two drugs. Moreover, ileus [ROR (95% CI) = 11.11 (4.14–29.51), n = 4], gastrointestinal hemorrhage [ROR (95% CI) = 2.55 (1.15–5.69), n = 6], and hypoglycemic unconsciousness [ROR (95% CI) = 153.58 (62.98–374.54), n = 5] were rare but severe AEs associated with risdiplam. Onasemnogene abeparvovec had 143 exclusively identified AEs, with significant high signals for troponin I increase [ROR (95% CI) = 627.1 (492.2–798.99), n = 78], troponin T increase [ROR (95% CI) = 233.98 (153.29–357.15), n = 23], blood lactate dehydrogenase increase [ROR (95% CI) = 39.81 (28.88–54.87), n = 38], and transaminases increase [ROR (95% CI) = 36.88 (29.24–46.52), n = 73]. Conclusions This study highlights the importance of monitoring injection-related injuries and transient deafness events in patients treated with nusinersen. For onasemnogene abeparvovec, careful monitoring for renal impairment, liver injury, and myocardial damage is necessary. Risdiplam requires attention to the potential risk of rare but severe gastrointestinal damage events and hypoglycemia. Importantly, risdiplam exhibited lower liver and renal toxicity, making it a potential consideration for patients with liver or renal insufficiency or for combined use with other drugs that possess high liver or renal toxicity. These findings can be a reference for drug selection and further prospective studies.

Aim: Nirmatrelvir as a new 3CL protease inhibitor for treating COVID-19 drug of antiviral drug, the potential side effects have not yet been fully studied yet. The aim of this study was to identify potential risk of Nirmatrelvir by analyzing post-marketing safety data based on the largest publicly available worldwide pharmacovigilance database. Methods: We analyzed Nirmatrelvir adverse events to detect and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. Case/non-case approach were used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for AEs with ≥4 counts. Results: Total of 26846 cases were included. Disease recurrence [ROR(95%CI)=413.2(395.6-431.59)], dysgeusia [ROR(95%CI)=110.84(106.04-115.85)], anosmia [ROR(95%CI)=15.21(12.76-18.11)], ageusia [ROR(95%CI)=9.80(8.50-11.3)] and urticaria [ROR(95%CI)=1.91(1.69-2.17)] were the main safety signals. In addition, abdominal pain upper and skin toxicity were two specific safety signals of Nirmatrelvir. In pregnant population, a significant increased ROR was found in life-threatening [ROR(95%CI)=5.12(1.38-19.00)]. Conclusion: We identified that disease recurrence, dysgeusia, abdominal pain upper and skin toxicity were the main and specific safety signals of Nirmatrelvir. Clinician and pharmacist should pay attention on these AEs. Notably, a potential risk of Nirmatrelvir in pregnant population should be alerted.