Efficacy and tolerability of magnesium sulfate in children with infantile epileptic spasms syndrome: A systematic review and meta-analysis.

Peginterferon plus ribavirin versus interferon plus ribavirin for chronic hepatitis C.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

Infantile Epileptic Spasms Syndrome (IESS) is the most common epilepsy syndrome in children with trisomy 21. First-line standard treatments for IESS include adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin. Among children with trisomy 21 and IESS, treatment with ACTH or oral corticosteroids may yield higher response rates compared with vigabatrin. However, supporting data are largely from single-center, retrospective cohort studies. Leveraging the multi-center, prospective National Infantile Spasms Consortium (NISC) database, we evaluated the efficacy of first-line (standard) treatments for IESS in children with trisomy 21. We assessed clinical spasms remission at two weeks, clinical spasms remission at three months, and improvement of EEG (resolution of hypsarrhythmia) three months after initiation of treatment. Thirty four of 644 (5.3%) children with IESS were diagnosed with trisomy 21. In all children with trisomy 21, epileptic spasms was their presenting seizure type. Twenty of 34 (59%) children were initially treated with ACTH, nine (26%) with oral corticosteroids, and five (15%) with vigabatrin. Baseline demographics did not vary among treatment groups. The overall clinical remission rate after two weeks of treatment was 53% including 13 of 20 (65%) receiving ACTH, three of nine (33%) receiving oral corticosteroids, and two of five (40%) receiving vigabatrin (p = 0.24). The continued clinical response rate at three months was 32% including 8 of 20 (40%) receiving ACTH, two of nine (22%) receiving oral corticosteroids, and one of five (20%) receiving vigabatrin. Thirty of the 34 (88%) children presented with hypsarrhythmia (88%). EEG improvement at three months was better for children treated with ACTH (74%) or oral corticosteroids (83%) than vigabatrin (20%; p = 0.048). Adjustment for time from epileptic spasms onset to treatment did not alter results. In our cohort, epileptic spasms were the first presenting seizure type in all children with trisomy 21. Among first-line standard treatment options, ACTH may have superior efficacy for clinical and electrographic outcomes for IESS in children with trisomy 21.

Programmed cell death receptor-1 and its ligand-1 (PD-1/PD-L1) inhibitors have been applied to many cancers, but the difference of treatment-related adverse events (AEs) across cancer types remains unknown. We performed a meta-analysis and systemic review to compare the incidences of commonly reported all-grade AEs across cancer types and found that the most frequent AEs were fatigue, rash/pruritus, loss of appetite/nausea and diarrhea. However, each cancer type also had its higher incidences of AEs involving a relevant system, such as melanoma with epidermal AEs (rash, diarrhea and enterocolitis), lung cancer with dyspnea and pneumonitis, digestive system cancers with amylase and lipase elevation; and renal cell and urothelial cancer with kidney injury (creatinine elevation and proteinuria). However, the incidence of hepatitis did not follow the pattern to show a difference. We did another comparison between PD-1 and PD-L1 inhibitors in lung cancer and urothelial cancer respectively, and found that the risk of most AEs did not differ much, except for more hypothyroidism in PD-1 inhibitors, and more kidney injury in PD-L1 inhibitors. Besides possible immunological mechanisms for treatment-related AEs, the influence of previous radiotherapy and the clinical characteristics of the diseases themselves should also be considered and is worth further investigation. With the result of this meta-analysis, clinicians could estimate the risk of certain AE in certain cancer type, to make treatment options and to customize monitor strategies.

ObjectiveDue to the conflicting evidence and expected regional therapeutic variations for cost‐effectiveness in children with infantile epileptic spasms syndrome (IESS), this study assessed treatment effectiveness, safety, Health‐Related Quality of Life (HRQoL), and performed a cost‐effectiveness analysis (CEA) for hormonal therapies in Indian children with IESS.MethodsThis prospective observational study was conducted at a referral pediatrics center in North India. Children with IESS (aged 3–18 months), who were prescribed either a synthetic form of adrenocorticotrophic hormone (ACTH) or oral prednisolone, were included and compared for cessation of epileptic spasms (ES), treatment‐emergent adverse events (TEAEs), HRQoL (assessed through Hi‐QUALIN), and cost‐effectiveness using a decision‐tree model. Incremental cost effectiveness ratio (ICER) and number needed to treat were calculated. One‐way sensitivity analyses predicted the impact of each variable on the cost‐effectiveness (CE) model using a Tornado diagram.ResultsOf 93 children with IESS [73 (79%) boys; mean age (SD) = 10.1 (3.7) months; median (IQR) daily burden of ES: 27.8 (14.0, 61.9)], 55 (59%) were initiated on ACTH, while the rest on oral prednisolone (38 [41%]). After 2 weeks of treatment, ES cessation was achieved in 29/55 (53%) on ACTH and 13/38 (34%) on oral prednisolone. Additionally, an insignificantly different incidence of TEAEs was reported in the ACTH group (23/55 [42%]) compared with the oral prednisolone group (19/38 [50%]). Children aged 3–12 months showed statistically significant improvement in overall HRQoL scores at 2 weeks of treatment (p < 0.01). Using a decision tree model, CEA showed higher ICER (ICER: 122 185 INR; ~1468.90 USD and QALY: 331 643 INR; ~3987.0 USD) for ACTH than oral prednisolone, suggesting caregiver or parents need to spend at least 122 185 INR for one in five children on ACTH to be ES free compared with prednisolone.SignificanceThis analysis suggests ACTH was more cost‐effective than oral prednisolone for managing IESS from the Indian patient's perspective. ACTH was also a cost‐effective option for short‐term quality of life outcomes.Plain Language SummaryThis study looked at two first‐line treatment options, that is, ACTH and oral prednisolone, for infantile epileptic spasms syndrome (IESS) at a referral pediatric center in North India. We found that ACTH was more effective than oral prednisolone for epileptic spasm cessation and improved health‐related quality of life in the short term. Although ACTH costs more, it was found to be a cost‐effective option. These findings can help families and clinicians make better treatment choices based on both health benefits and costs.

Objective: To analyze the clinical characteristics, genetic features and prognosis of infantile epileptic spasms syndrome (IESS) associated with mitochondrial gene variants. Methods: A case-series study was conducted, including 18 children diagnosed with mitochondrial gene variant-associated IESS at the Department of Pediatrics, Xiangya Hospital of Central South University from June 2016 to June 2025. General data, clinical manifestations, laboratory findings and treatment outcomes were systematically analyzed. Results: Among the 18 children, 11 were boys, 7 were girls, the age of seizure onset was 6 (3, 9) months. Elevated lactate level was found in 7 children. Neuroimaging of magnetic resonance imaging revealed cerebral atrophy in 10 cases, and basal ganglia, thalamic, or midbrain lesions in 3 cases. Genetic testing identified 12 pathogenic genes, including mitochondrial protein synthesis-related genes: AFG3L2 (4 cases), PARS2 (3 cases), RARS2 (1 case), MIPEP (1 case), and PTCD3 (1 case); respiratory chain enzyme complex-related genes: FOXRED1 (2 cases), NDUFS7 (1 case), MT-ND1 (1 case), and MT-ATP6 (1 case); and other mitochondrial-related genes: POLG (1 case), COQ4 (1 case), and PDHA1 (1 case). ACTH or prednisone therapy was administered in 14 children, with 5 achieving spasm control for ≥28 d spasm freedom and resolution of hypsarrhythmia on electroencephalogram. Ketogenic diet therapy was used in 4 children, and effective in 1 case with the PDHA1 gene variant. Fourteen patients exhibited drug-resistant epilepsy requiring ≥2 antiseizure medications. At a follow-up of 3.0 (1.5, 4.3) years, 3 children died. Among 12 children ≥3 years of age, modified Rankin scale (mRS) scores demonstrated 1 case with favorable outcomes (mRS ≤2 score) and 11 with poor outcomes (mRS >2 score). Conclusions Mitochondrial gene variants in IESS mainly involve mitochondrial respiratory chain enzyme complexes and protein synthesis pathways, typically manifesting as drug-resistant epilepsy with poor prognosis. Elevated lactate levels combined with cerebral atrophy or basal ganglia lesions may aid diagnosis.

Nutritional vitamin B12 deficiency-associated Infantile epileptic spasms syndrome: Clinico-neurophysiological presentation, response to treatment, and neurodevelopmental outcome

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Use of Combination Premedication Prior to Motixafortide Administration Reduced Severity and Frequency of AEs in the Phase 3 Genesis Trial - a Single Center Analysis

Comparative Safety of Atorvastatin 80 mg Versus 10 mg Derived from Analysis of 49 Completed Trials in 14,236 Patients

To compare the clinical efficacy and safety of adrenocorticotropic hormone (ACTH) combined with topiramate versus topiramate monotherapy in treating Infantile Epileptic Spasm Syndrome (IESS), and to explore the risk factors for relapse. This retrospective cohort study included 185 IESS pediatric patients treated at Yan'an People's Hospital between April 2018 and January 2024. Patients were divided into a control group (n=95, topiramate monotherapy) and an observation group (n=90, ACTH combined with topiramate) based on their treatment regimen. Propensity score matching (PSM) was employed to balance baseline differences. Outcomes compared between the groups included spasm control rates, electroencephalogram (EEG) improvement, changes in functional scores, and incidence of adverse reaction. Multivariate logistic regression was used to identify independent risk factors for relapses. The observation group demonstrated significantly higher rates of complete spasm control (75.56% vs. 50.53%) and complete EEG improvement (76.67% vs. 54.74%) compared to the control group (P<0.01). Post-treatment, the observation group showed more significant improvements in developmental quotient (DQ), motor index (MI), and Kramer scores (P<0.01). Multivariate analysis identified structural etiology (OR=3.12), monotherapy (OR=2.54), and higher Kramer scores (OR=1.45) as independent risk factors for relapse (all P<0.01). The incidence of adverse reactions did not differ significantly between groups (34.44% vs. 29.47%, P=0.468). ACTH combined with topiramate offers superior efficacy for spasm control, EEG improvement, and neurological function recovery compared to topiramate monotherapy, without increasing adverse reactions. Structural etiology, monotherapy, and Kramer scores are independent predictors for relapse.

Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

The aim of the study was to investigate the frequency and severity of adverse events (AEs) and laboratory abnormalities of interest over 96 weeks of treatment with etravirine or placebo in the pooled TMC125 DUET (Demonstrate Undetectable viral load in patients Experienced with ARV Therapy) trials. Treatment-experienced, HIV-1-infected patients randomly received etravirine 200 mg twice a day (bid) or placebo, plus a background regimen. The frequency and severity of neuropsychiatric, rash, hepatic and lipid AEs were analysed; frequencies were also adjusted for total patient-years of exposure (PYE). A total of 599 and 604 patients received etravirine and placebo, respectively (median treatment duration 96.0 and 69.6 weeks, respectively). There was no significant difference between the treatment groups in the frequency of neuropsychiatric AEs. However, a significant difference in the frequency of rash was observed (20.5% vs. 11.8%, respectively; P < 0.0001); rash was generally mild to moderate in severity; the rate of discontinuation because of rash was low (2.2% vs. 0% in the etravirine and placebo groups, respectively). The frequency of hepatic AEs was low and similar between the treatment groups (8.7% vs. 7.1%, respectively; P = 0.3370); hepatic enzyme levels did not increase over time. Lipid-related laboratory abnormalities and changes over time in lipid levels were generally comparable between treatment groups. Adjusting for treatment exposure, the frequency of AEs remained similar between treatment groups, with the exception of rash [13.7 vs. 9.3 per 100 PYE; relative risk (95% confidence interval) 1.48 (1.02-1.95)]. The frequency of AEs of interest was generally similar between the treatment groups, both overall and when adjusted for treatment exposure, with the exception of rash which was more frequent in the etravirine group.

Denosumab in patients with giant-cell tumour of bone: a multicentre, open-label, phase 2 study.

Background: 6-year analysis of adverse events (AE) in a preoperative autologous deposit (PAD) program. Patients and Methods: This analysis was performed in 28,244 patients who underwent major bone and joint surgery from 1989 to 1994 and who took part in our PAD program. Patients were included into the PAD program if eligible for elective surgery with supposed blood loss requiring blood transfusion. Patient’s physical status was rated according to the ASA score. Blood or plasma volume donated was replaced routinely, mostly with polygeline. Monitoring during donation included ECG (lead II) and noninvasive blood pressure recording. Oxygen (2 l/min) was applied via nasal sponges. AE were rated as mild (grade I), moderate (grade II), severe (grade III), and fatal (grade IV). All AE happening in the blood bank were taken into account; additionally, all grade III and grade IV AE occurring within 24 h after PAD were considered, independent of a relationship between PAD and AE. AE were analyzed in relation to age and ASA status of the patients. Data were evaluated using descriptive statistics, chi-square test, and Spearman rank correlation; statistical significance was considered for p < 0.05. Results: 28,244 patients underwent 50,542 PAD sessions and donated a total of 132,093 autologous units. A total of 588 AE happened; i.e. in 2.08% of all participating patients and in 1.17% of all donations (not units obtained!). With increasing ASA score, i.e. with worsening of the patient’s physical status, the frequencies of mild and moderate AE decreased. 65.9% (n = 388) of all AE were considered as mild, 33.2% (n = 195) were rated as moderate, 0.51% (n = 3) were graded as severe, and 0.34% (n = 2) were fatal. No overall relation between patients’ age and frequency of AE could be demonstrated. However, patients over 70 years (21.1%) accounted for 30.7% of AE (p < 0.05). The rate of AE associated with autologous plasmapheresis was 3.4-times higher than that associated with autologous blood donation. With one exception, all severe and fatal AE were found in patients over 70 years with ASA score III and a history of cardio- or cerebrovascular diseases. All these patients had undergone autologous plasmapheresis. Conclusion: The overall frequency of AE in our PAD program was not higher than that reported for homologous programs. However, severe and fatal AE exclusively happened in patients who underwent autologous plasmapheresis. Therefore, in elderly patients and in those with concomitant cardio- or cerebrovascular diseases the indication for participation in a PAD/autologous plasmapheresis program has to be made very cautiously and by weighing pros and cons.