A 10-year retrospective study of antibacterial-induced thrombocytopenia in a women and children hospital using China Hospital Pharmacovigilance System and Visual Basic for Applications.

AIMS: We aimed to investigate antibacterial-induced thrombocytopenia using the China Hospital Pharmacovigilance System (CHPS) in conjunction with Visual Basic for Applications (VBA). METHODS: Between September 2011 and December 2022, a 2-phase workflow was employed to identify antibacterial-induced thrombocytopenia, including preliminary screening in phase (I) conducted by CHPS algorithms and causality assessment by trained pharmacists in phase (II) using VBA. The incidence of thrombocytopenia in each antibacterial was calculated, and comparisons were performed between paediatric and adult patients. RESULTS: CHPS algorithms identified 4080 cases from 485 238 admissions (including 223 735 admissions receiving at least 1 antibacterial treatment). After ruling out cases with chemotherapy and abnormal platelet count at admission, 3832 cases were available. Using VBA, pharmacists identified 1039 cases (1246 antibacterial treatments, 28 agents) as potential thrombocytopenia instances (κ = 0.89), with an incidence of 0.46%. All antibacterial treatments correlated temporally with thrombocytopenia. Carbapenems (meropenem 1.77%), glycopeptides (vancomycin 1.55%) and lincosamides (clindamycin 0.44%) were prominent causal groups. The highest incidences of thrombocytopenia in the cephalosporins and penicillins groups were ceftazidime (2.04%) and piperacillin/tazobactam (1.24%), respectively. Among all antibacterial treatments, clindamycin showed the shortest time to onset (TTO), and erythromycin showed the longest TTO. Paediatric patients exhibited a longer TTO (61 vs. 29 h), extended time to nadir (83 vs. 37 h), lower platelet nadir count values (110 vs. 92 × 109/L), and a higher severe case proportion (12.37 vs. 3.86%) when compared with adults. CONCLUSION: Different antibacterial agents exhibit varying incidences of thrombocytopenia, with notable disparities between adults and children in the characteristics of thrombocytopenia.

Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND AND OBJECTIVES: Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. METHODS: A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. RESULTS: Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. CONCLUSION: Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.

Randomized controlled trial of an app for cancer pain management.

PURPOSE: The primary objective of this investigation was to devise a mobile application for self-management of cancer-related discomfort, with the overarching goal of enhancing patients' overall well-being. Would the utilization of the self-management application result in an amelioration of life quality compared to conventional follow-up procedures? METHODS: Modules were meticulously devised with the collaborative expertise of oncology pain specialists employing the Delphi technique. Reliability of the consultation was assessed using Cronbach's α. After developing the app, a prospective randomized controlled study was conducted to evaluate the app's effect on participants' quality of life. The trial group used the app; the control group received a follow-up telephone consultation. Assessments of quality of life were conducted both at baseline and following a 4-week intervention period. RESULTS: After two rounds of Delphi expert consultation, the functional modules of Pain Guardian were determined to include five functional modules, including pain self-measurement (real-time dynamic recording of pain by patients), patient reminders (reminders of outbreaks of pain disposal, medication, and review), uploading of examination reports, online consultation, health education, and other functional modules. Cronbach's α was 0.81. Overall, 96 patients (including esophageal, gastric, colorectal, nasopharyngeal, pulmonary, pancreatic, breast, ovarian, uterine, bone, thoracic, bladder, cervical, soft tissue sarcoma, mediastinal, and lymphoma) with cancer pain were divided into the trial and control groups. There were no significant differences in basic information and quality of life at baseline between groups. After 4 weeks of intervention, quality of life was significantly higher in the trial group than in the control group. Patients' satisfaction with the app was high (93.7%). CONCLUSIONS: The primary obstacle encountered in the development of applications for managing cancer-related discomfort lies in the sensitive nature of the subject matter, potentially leading to patient apprehension regarding application usage for pain management. Consequently, meticulous attention to user preferences and anticipations is imperative, necessitating the creation of an application characterized by user-friendliness and medical efficacy. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR1800016066; http://www.chictr.org.cn/showproj.aspx?proj=27153 . Date of Registration: 2018-05-09.

Post-marketing safety concerns with nirmatrelvir: A disproportionality analysis of spontaneous reports submitted to the FDA Adverse Event Reporting System.

AIMS: Nirmatrelvir is an antiviral drug with a novel mechanism of action, targeting the 3-CL protease, and is used in the treatment of COVID-19. However, the potential side effects have not yet been fully studied. The aim of this study was to identify potential safety signals of nirmatrelvir by analysing post-marketing safety data based on the largest publicly available worldwide pharmacovigilance database. METHODS: We analysed nirmatrelvir adverse events to identify and characterize relevant safety signals based on the FDA Adverse Event Reporting System database in 2022. The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered 4 or more. RESULTS: A total of 26 846 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 the pregnant population, there was a significant increased ROR for life-threatening conditions (ROR [95% CI] = 8.00 [1.77-36.20]). CONCLUSIONS: Our study identified that the main and specific safety signals of nirmatrelvir were disease recurrence, dysgeusia, abdominal pain upper and skin toxicity. Clinicians and pharmacists should be vigilant of these AEs, although differentiating between COVID-19 symptoms and AEs can be challenging. Notably, a potential safety concern of nirmatrelvir should be a warning based on a small number of events in the pregnant population. However, the available data are insufficient, and further continued pharmacovigilance and surveillance is needed to fully understand this issue.

Metabolites of organophosphate ester flame retardants in urine from Shanghai, China.

The metabolites of nine organophosphate ester (OPE) flame retardants were measured in 180 urine samples collected from a population (including adults and children) in western Shanghai, China, using liquid chromatography-tandem spectrometry (LC-MS/MS). The total urinary concentrations of nine OPE metabolites ranged 100-23800 pg/mL, with a geometric mean (GM) value of 1450 pg/mL. The concentrations of alkyl-OPE metabolites (879 pg/mL) were approximately an order of magnitude higher than those of aryl-OPE (53.7 pg/mL) and chlorinated-OPE metabolites (52.7 pg/mL). Diphenyl phosphate (DPHP), diethyl phosphate (DEP), di-n-butyl phosphate (DNBP), bis(2-ethylhexyl) phosphate (BEHP), and bis(2-butoxyethyl) phosphate (BBOEP) were the dominant OPE metabolites found in urine. The results showed that an increase in age was associated with a significant decrease in urinary DPHP (r = -0.278, p < 0.01) and DNBP (r = -0.314, p < 0.01) concentrations. The highest concentrations of DPHP (GM = 80.7 pg/mL) and DNBP (GM = 16.9 pg/mL) were found in urine from people living in homes that were less than 10 years old. The urinary DNBP concentration was significantly associated with self-reported symptoms of allergy. Our result establishes baseline value for OPE exposure in a population in China for comparison in future studies.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

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.

Comparative analysis of adverse events associated with CDK4/6 inhibitors based on FDA's adverse event reporting system: a case control pharmacovigilance study.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors marked a milestone in the breast cancer treatment. Due to the potential impact of adverse effects on treatment decisions and patient outcomes, careful consideration of the varying toxicities of CDK4/6 inhibitors is crucial, as three inhibitors-palbociclib, abemaciclib, and ribociclib-have been approved with differences in adverse event profiles. However, limitations in clinical trials call for urgent real-world safety studies to evaluate and compare the risk of adverse events (AEs) among these CDK4/6 inhibitors. Therefore, this study aimed to analyze AEs of CDK4/6 inhibitors and provide insights for clinical drug selection, using real world database. METHODS: The AEs of CDK4/6 inhibitors in the FDA Adverse Event Reporting System (2015-2022) were analyzed. Four disproportionality methods were used to detect safety signals: reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Neural Network Propagation, and Multi-Item Gamma Poisson Shrinker. Venn analysis was used to compare and select common and specific AEs. RESULTS: This study included 73,042 patients treated with palbociclib, 25,142 with ribociclib, and 7563 with abemaciclib. All three inhibitors had 27 common AEs. Palbociclib exhibited the highest ROR for hematologic toxicities, while ribociclib showed the highest ROR for macrocytosis, nail disorders, and hepatic lesions. Abemaciclib displayed the highest ROR for mucosal toxicity. Common signals for both palbociclib and ribociclib included hematologic toxicities, decreased immune responsiveness, and aphthous ulcers. Myelosuppression, oral pain, and pseudocirrhosis were common signals for palbociclib and abemaciclib. Anemia, hepatotoxicity, and pneumonitis were observed as common signals for ribociclib and abemaciclib. Furthermore, specific AEs associated with palbociclib included fatigue, alopecia, and stomatitis. For ribociclib, specific AEs included electrocardiogram QT prolongation, thrombocytopenia, and decreased hemoglobin. Abemaciclib was specifically linked to diarrhea, vomiting, and interstitial lung disease. CONCLUSION: Our analysis revealed that palbociclib showed a higher risk of hematologic toxicity. Ribociclib showed higher risks of hepatotoxicity, nephrotoxicity, and QT prolongation. Abemaciclib showed higher risks of hepatotoxicity, gastrointestinal effects, interstitial lung disease, and thrombosis. These findings provide valuable insights for CDK4/6 inhibitor selection.

Assessing safety concerns of interstitial lung disease associated with antibody-drug conjugates: a real-world pharmacovigilance evaluation of the FDA adverse event reporting system.

BACKGROUND: Antibody-drug conjugates have revolutionized cancer therapy due to their selectivity and efficacy. However, concerns have been raised regarding the potential effects of trastuzumab deruxtecan in interstitial lung diseases. AIM: This study aimed to investigate the safety signals and time to onset of antibody-drug conjugates induced interstitial lung disease. METHOD: We utilized the FDA Adverse Event Reporting System database (2004-2022) to identify interstitial lung disease safety signals in 13 FDA-approved antibody-drug conjugates. Disproportionality analysis was conducted to estimate the reporting odds ratios for interstitial lung disease. RESULTS: Seven antibody-drug conjugates exhibited safety signals of interstitial lung disease: trastuzumab deruxtecan [reporting odds ratio, ROR (95% confidence intervals, CI) = 64.15 (57.07-72.10)], enfortumab vedotin [ROR (95% CI) = 5.24 (3.25-8.43)], trastuzumab emtansine [ROR (95% CI) = 3.62 (2.90-4.53)], brentuximab vedotin [ROR (95% CI) = 3.22 (2.49-4.17)], polatuzumab vedotin [ROR (95% CI) = 2.56 (1.59-4.12)], gemtuzumab ozogamicin [ROR (95% CI) = 2.53 (1.70-3.78)], and inotuzumab ozogamicin [ROR (95% CI) = 2.33 (1.21-4.49)]. Five antibody-drug conjugates with limited reports were excluded from further analysis: belantamab mafodotin, loncastuximab tesirine, mirvetuximab sorafenib, tisotumab vedotin, and moxetumomab pasudotox. Japan and the United States were the primary reporting countries. CONCLUSION: This real-world study highlights high safety signals of interstitial lung disease associated with antibody-drug conjugates. Clinicians should be aware of these safety concerns and risk factors and implement early identification measures for their patients. Future research should prioritize comprehensively exploring the relationship between antibody-drug conjugates and lung diseases.

Dysregulation of cerebrospinal fluid metabolism profiles in spinal muscular atrophy patients: a case control study.

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.

Prevalence of metabolic syndrome among urban community residents in China.

BACKGROUND: Metabolic risk factors and abnormalities such as obesity and hypertension are rapidly rising among the Chinese population following China's tremendous economic growth and widespread westernization of lifestyle in recent decades. Limited information is available about the current burden of metabolic syndrome (MetS) in China. METHODS: We analyzed data on metabolic risk factors among 22,457 adults aged ≥ 32 years participating in the "Zhabei Health 2020" survey (2009-2010), a cross-sectional study of a representative sample of community residents in Zhabei District. We defined MetS using Chinese-specific cut-off points for central obesity according to consensus criteria recently endorsed by several international and national organizations in defining MetS in different populations worldwide. We used a multiple logistic regression model to assess the associations of potential risk factors with MetS. RESULTS: The unadjusted prevalence of the MetS was 35.1% for men and 32.5% for women according to the consensus criteria for Chinese. The prevalence increased progressively from 12.1% among participants aged 32-45 years to 45.4% among those aged ≥ 75 years. Age, smoking, family history of diabetes, and education are significantly associated with risk of MetS. CONCLUSIONS: The MetS is highly prevalent and has reached epidemic proportion in Chinese urban adult community residents.

[Kaiqiao Jieyin acupuncture combined with repetitive transcranial magnetic stimulation for post-stroke aphasia: a randomized controlled trial].

OBJECTIVE: To observe the effect of Kaiqiao Jieyin acupuncture (acupuncture for opening orifices and relieving aphasia) combined with repetitive transcranial magnetic stimulation (rTMS) on language ability and daily life communication ability in patients with post-stroke aphasia (PSA). METHODS: Fifty-six patients with PSA were randomly divided into an observation group and a control group, 28 cases in each group. Both groups received routine symptomatic treatment. The control group was treated with speech rehabilitation training and rTMS. On the basis of the treatment in the control group, the observation group was treated with Kaiqiao Jieyin acupuncture at the speech area Ⅰ, Fengchi (GB 20), Tongli (HT 5), Lianquan (CV 23), Panglianquan (Extra), etc. Panglianquan (Extra) on both sides were connected to electroacupuncture, with intermittent wave, 2 Hz in frequency. The above treatment was performed once a day for 5 consecutive days, followed by 2 days of rest for 2 weeks. The scores of western aphasia battery (WAB, including scores of spontaneous speech, auditory comprehension, repetition, naming and score of aphasia quotient [AQ]) and communication abilities in daily living (CADL) in the two groups were compared before and after treatment. RESULTS: After treatment, the spontaneous speech, auditory comprehension, repetition, naming scores and AQ scores in both groups were higher than those before treatment (P<0.05), and the increase in the observation group was greater than the control group (P<0.05). The CADL scores of the two groups were higher than those before treatment (P<0.05). CONCLUSION: Kaiqiao Jieyin acupuncture combined with rTMS can improve the language ability and daily life communication ability of PSA patients.

Differences in Hypersensitivity Reactions to Iodinated Contrast Media: Analysis of the US Food and Drug Administration Adverse Event Reporting System Database.

BACKGROUND: A comparative hypersensitivity risk profile of frequently used iodinated contrast media (ICM) may be required for their safer use. OBJECTIVE: To explore the association between hypersensitivity reactions (HSRs) and specific ICM and characterize the spectrum of ICM-related HSRs. METHODS: We performed a disproportionality analysis and proportionality test to assess the safety profile of ICM-related HSRs and compare the frequency ratio of specific HSRs in diverse age, sex, and country subgroups. We used reports downloaded from the US Food and Drug Administration Adverse Event Reporting System and data on the national use of individual ICM for this analysis. RESULTS: A total of 11,343,365 adverse event reports were collected from the first quarter of 2013 to the first quarter of 2021, among which 5,432 cases were identified as ICM-induced HSRs. All of the studied ICMs were associated with overreporting frequencies of HSRs, in which iomeprol showed the highest reporting odds ratio (ROR) of 24.75 (95% CI, 19.61-31.24). Iopromide (ROR = 22.29; 95% CI, 20.18-24.62) and ioversol (ROR = 20.85; 95% CI, 18.54-23.44) were more likely to cause angioedema than other ICMs, particularly in the group aged 45 to 64 years. Iomeprol was associated with the largest disproportionality for severe cutaneous adverse reactions (ROR = 127.90; 95% CI, 103.32-159.88), whereas iodixanol exhibited maximal incidence when total use cases were considered. Regarding anaphylactic shock, iopamidol presented the highest disproportionality (ROR = 31.11; 95% CI, 27.15-35.65), especially in males or seniors aged greater than 65 years, whereas iopromide resulted in the maximum frequency in China and the United States. CONCLUSIONS: Different ICMs exhibited diverse profiles regarding HSRs, which could be further affected by age, sex, or geographic area. Prospective studies are required for patient safety.

Safety Concerns with Nusinersen, Risdiplam, and Onasemnogene Abeparvovec in Spinal Muscular Atrophy: A Real-World Pharmacovigilance Study.

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.

The assessment of interhemispheric imbalance using functional near-infrared spectroscopic and transcranial magnetic stimulation for predicting motor outcome after stroke.

Objective: To investigate changes in interhemispheric imbalance of cortical excitability during motor recovery after stroke and to clarify the relationship between motor function recovery and alterations in interhemispheric imbalance, with the aim to establish more effective neuromodulation strategies. Methods: Thirty-one patients underwent assessments of resting motor threshold (RMT) using transcranial magnetic stimulation (TMS); the cortical activity of the primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA) using functional near-infrared spectroscopy (fNIRS); as well as motor function using upper extremity Fugl-Meyer (FMA-UE). The laterality index (LI) of RMT and fNIRS were also calculated. All indicators were measured at baseline(T1) and 1 month later(T2). Correlations between motor function outcome and TMS and fNIRS metrics at baseline were analyzed using bivariate correlation. Results: All the motor function (FMA-UE1, FMA-UE2, FMA-d2) and LI-RMT (LI-RMT1 and LI-RMT2) had a moderate negative correlation. The higher the corticospinal excitability of the affected hemisphere, the better the motor outcome of the upper extremity, especially in the distal upper extremity (r = -0.366, p = 0.043; r = -0.393, p = 0.029). The greater the activation of the SMA of the unaffected hemisphere, the better the motor outcome, especially in the distal upper extremity (r = -0.356, p = 0.049; r = -0.367, p = 0.042). There was a significant moderate positive correlation observed between LI-RMT2 and LI-SMA1 (r = 0.422, p = 0.018). The improvement in motor function was most significant when both LI-RMT1 and LI-SMA1 were lower. Besides, in patients dominated by unaffected hemisphere corticospinal excitability during motor recovery, LI-(M1 + SMA + PMC)2 exhibited a significant moderate positive association with the proximal upper extremity function 1 month later (r = 0.642, p = 0.007). Conclusion: The combination of both TMS and fNIRS can infer the prognosis of motor function to some extent. Which can infer the role of both hemispheres in recovery and may contribute to the development of effective individualized neuromodulation strategies.

Case report: High-frequency repetitive transcranial magnetic stimulation for treatment of hereditary spastic paraplegia type 11.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders that currently have no cure. HSP type 11 (SPG11-HSP) is a complex form carrying mutations in the SPG11 gene. Neuropathological studies demonstrate that motor deficits in these patients are mainly attributed to axonal degeneration of the corticospinal tract (CST). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that can induce central nervous system plasticity and promote neurological recovery by modulating the excitability of cortical neuronal cells. Although rTMS is expected to be a therapeutic tool for neurodegenerative diseases, no previous studies have applied rTMS to treat motor symptoms in SPG11-HSP. Here, we report a case of SPG11-HSP with lower extremity spasticity and gait instability, which were improved by applying high-frequency rTMS (HF-rTMS) at the primary motor cortex (M1). Clinical and physiological features were measured throughout the treatment, including the Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), the timed up and go (TUG) test and the 10-meter walk test time (10 MWT). The structure and excitability of the CST were assessed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS), respectively. After treatment, the patient gained 17 points of BBS, along with a gradual decrease in MAS scores of the bilateral lower extremity. In addition, the TUG test and 10 MWT improved to varying degrees. TMS assessment showed increased motor evoked potential (MEP) amplitude, decreased resting motor threshold (RMT), decreased central motor conduction time (CMCT), and decreased difference in the cortical silent period (CSP) between bilateral hemispheres. Using the DTI technique, we observed increased fractional anisotropy (FA) values and decreased mean diffusivity (MD) and radial diffusivity (RD) values in the CST. It suggests that applying HF-rTMS over the bilateral leg area of M1 (M1-LEG) is beneficial for SPG11-HSP. In this study, we demonstrate the potential of rTMS to promote neurological recovery from both functional and structural perspectives. It may provide a clinical rationale for using rTMS in the rehabilitation of HSP patients.

Optimal exposure targets for vancomycin in the treatment of neonatal coagulase-negative Staphylococcus infection: A retrospective study based on electronic medical records.

BACKGROUND: The currently advocated ratio of area under the curve (AUC) over 24 h to minimum inhibitory concentration (AUC/MIC) > 400 and AUC < 600 mg h/L as the therapeutic drug monitoring (TDM) target of vancomycin is based on data from multiple observational studies in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. It may not be applicable to newborns with coagulase-negative Staphylococcus (CoNS) infection. We conducted a retrospective study to identify the optimal exposure targets for vancomycin in the treatment of neonatal CoNS infection. METHODS: Based on the inclusion and exclusion criteria, serum vancomycin concentration, demographics, clinical data, and related laboratory data of newborns who received vancomycin intravenous infusion from June 1, 2016 to February 1, 2021 were collected retrospectively. The AUC was calculated using the maximum a posteriori Bayesian (MAPB) method. The vancomycin exposure threshold of AUC/MIC for efficacy and AUC for toxicity (acute kidney injury, AKI) were determined based on receiver operating characteristic (ROC) curve analysis. The correlation between vancomycin exposure and both clinical effect and nephrotoxicity was analyzed using logistic multivariate regression. RESULTS: In total, 153 patients and 245 vancomycin concentrations (160 trough and 85 peak concentrations) were included. The ROC curve analysis showed that the exposure thresholds of AUC/MIC for clinical efficacy and AUC for nephrotoxicity were 281 and 602 mg h/L, respectively. The multivariate regression analysis showed that AUC/MIC > 280 was a predictor of efficacy (OR: 13.960, 95% CI: 1.891-103.078, P < 0.05) and AUC > 600 mg h/L was associated with AKI (OR: 9.008, 95% CI: 2.706-29.983, P < 0.05). The vancomycin AUC/MIC threshold for treating neonatal CoNS infection with vancomycin is lower than the currently advocated AUC/MIC >400. CONCLUSION: The optimal exposure targets for vancomycin in neonatal CoNS infection were AUC/MIC > 280 and AUC < 600 mg h/L.

Prognostic Value of Two Polymorphisms, rs1045642 and rs1128503, in ABCB1 Following Taxane-based Chemotherapy: A Meta-Analysis.

OBJECTIVE: Genetic polymorphisms can influence the chemotherapeutic response; however, previous studies have produced conflicting results, and have failed to identify the most relevant polymorphisms for predicting the response to treatment in patients with cancer. The present meta-analysis was conducted to determine the correlation between two polymorphisms (rs1045642 and rs1128503) in ATP-binding cassette transporter B subfamily member 1 (ABCB1), which is associated with multidrug resistance, and the survival of patients treated with taxane-containing chemotherapy. METHODS: Several databases, including PubMed and Embase, were used to retrieve articles evaluating the association between the ABCB1 rs1045642 and rs1128503 polymorphisms and survival, published prior to August 2019. The meta-analysis was conducted using R software to determine the pooled hazard ratio (HR) and 95% confidence intervals (95% CIs). RESULTS: Fifteen studies involving 3320 patients were included in the meta-analysis. The effect of the rs1128503 polymorphism on progression-free survival remained significant in the heterozygote (HR 0.81; 95% CI: 0.67-0.98) and homozygote (HR 0.71; 95% CI: 0.58-0.88) models. The TT genotype rs1128503 was associated with better overall survival (HR 0.72; 95% CI: 0.53-0.97). CONCLUSION: Carriers of the rs1128503 T allele of ABCB1 showed a survival benefit after taxane-containing chemotherapy.

Evaluation of a medication error monitoring system to reduce the incidence of medication errors in a clinical setting.

BACKGROUND: Medication errors have significant health and economic consequences. Monitoring medication errors by implementing monitoring systems proved in the USA and European countries since 1990s to be an effective method for error detection, leading to improved safety at all levels of health care. Currently, China does not have a universal medication error monitoring system. OBJECTIVE: To evaluate the effectiveness of the Medication Error Monitoring System for the reduction of medication errors in Xiamen Maternity and Child Care Hospital. METHODS: Between January-June 2014, the Medication Error Monitoring System developed by Xiamen Maternity and Child Care Hospital was employed to monitor medication errors through error reporting by physicians and pharmacists. The errors collected by this system were then thoroughly assessed and addressed by specific improvements including more frequent training, introducing computerised prescribing systems and a bar-coding medicine dispensing system. Data collected from January-June 2015, was then compared with the data collected in 2014 to determine whether medication errors had been reduced. RESULTS: Between 2014 and 2015, the total medication errors in prescribing and dispensing were reduced by approximately 27%. Compared with 2014, there was a marked reduction in the number of errors due to misdiagnoses and inappropriate usage/dosage in 2015, while the number of data entry errors increased and became the most common cause of medication error. The success rate of pharmacy interventions increased from 95.25% to 96.88%, albeit modest. However, across all medication errors in the stage of prescribing and dispensing, non-human-related errors significantly decreased from 44.25% in 2014 to 37.94% in 2015 with apvalue of 0.021. CONCLUSION: The Medication Error Monitoring System is effective at monitoring medication error data, leading to a reduction in reported medication errors. Better training for hospital staff including doctors and pharmacists will be critical to reduce human-related medication errors in the hospital.

Clinical and experimental study of oxaliplatin in treating human gastric carcinoma.

AIM: To evaluate the therapeutic effectiveness of oxaliplatin on human gastric carcinoma and to explore its mechanisms. METHODS: Twenty-two cases of stage IV gastric carcinoma received 4-6 (mean 4.6) cycles of first line combined chemotherapy with oxaliplatin (oxaliplatin 85 mg/m(2), iv, gtt, 1 h, d 1; leukovorin 200 mg/m(2), iv, gtt, 1 h, d 1 and d 2; 5-FU 300 mg/m(2),iv, d 1 and d 2, 5-FU, continuous iv, gtt, 48 h; 1 cycle/2 wk). Response rate, progression-free survival (PFS), total survival time, toxic side effects were evaluated. The inhibitory effect of oxaliplatin on human gastric cell line SGC-7901 was detected and IC(50) was calculated by MTT. Transmission electron microscopy, flow cytometry and TUNEL were performed to evaluate the apoptosis of cell line induced by the drug. The expression of Caspase-3 m-RNA was detected by RT-PCR. AC-DEVD-CHO, a Caspase-3 specific inhibitor, was used to elucidate the role of activated Caspase-3 in the process of apoptosis induced by oxaliplatin. RESULTS: Total response (complete and partial) occurred in 9 (40.9%) patients. Mean PFS was 4.2 mo and mean total survival time was 7.2 mo. Cumulative neurotoxicity (all grade I-II), vomiting and diarrhea, myelosuppression appeared in 93.5%, 20%, 32.9% patients, respectively. IC(50) was calculated to be 0.71 mg/L by MTT assay. A maximal inhibitory rate reached 85.3%. Apoptosis index was elevated after incubated with 1 mmol/L oxaliplatin for 30 min, but without statistic significance (P>0.05). However it could be detected at a much higher degree both by flowcytometry and by TUNEL with a statistical significance (68.47+/-7.92% and 8.23+/-2.67%, respectively, P<0.05) after incubated with 1 mmol/L oxaliplatin for 2 d. By means of RT-PCR, we detected an enhancement of Caspase-3 m-RNA expression induced by oxaliplatin which was also in positive correlation with the apoptotic level. AC-DEVD-CHO, a Caspase-3 specific inhibitor, could significantly inhibit and delay apoptosis induced by oxaliplatin. CONCLUSION: Oxaliplatin is effective and well-tolerated in patients with advanced gastric carcinoma. Oxaliplatin could significantly inhibit the growth of human gastric cell line SGC-7901. The induction of Caspase-3 m-RNA expression, activation of Caspase-3 and promotion of apoptosis may be some of the therapeutic mechanisms of oxaliplatin on gastric carcinoma. Annexin-V-fluorescein labeling flow cytometry is much more sensitive than TUNEL in detecting early stage apoptosis.