PLoS One. 2024 Oct 21;19(10):e0308213. doi: 10.1371/journal.pone.0308213. eCollection 2024.

ABSTRACT

INTRODUCTION: A patient's perceived sensitivity to medicines (PSM) might influence the reported side effects of a treatment. The experience of side effects can result in personal and structural costs (such as nonadherence). Research on nocebo mechanisms and the workings of side effect reporting has been disproportionally smaller compared to the emerging evidence of the individual and clinical impact of the matter. In this study, we explored and re-examined the association between PSM and reported side effects within a specific population (chronic low back pain patients receiving acupuncture treatment), including possible mediating variables (i.e., gender, medical and nonmedical care utilization, optimism, pessimism, anxiety, depression and treatment expectation).

METHODS: We conducted a secondary analysis of a randomized controlled trial that examined the influence of treatment outcome expectations in chronic low back pain (CLBP) patients. All measures in the analysis were self-assessments. We explored the association between PSM, reported side effects and personal characteristics using correlational and regression analyses.

RESULTS: Our sample consisted of 152 CLBP patients (65.8% female), the mean age was 39.5 years (SD = 12.5). We found positive correlations between PSM and reported side effects (r = 0.24; p < 0.01) and between PSM and anxiety (r = 0.21; p < 0.05). However, the subsequent regression analyses did not confirm a mediating or moderating effect of anxiety between PSM and reported side effects.

CONCLUSION: We confirmed and extended earlier research on PSM. Our study involved a specific pain population receiving a nonpharmacological intervention. Our results highlight the importance of targeting PSM and anxiety within a treatment to take measures to mitigate the prevalence of side effects.

PMID:39432475 | DOI:10.1371/journal.pone.0308213

Ther Adv Drug Saf. 2024 Oct 16;15:20420986241285929. doi: 10.1177/20420986241285929. eCollection 2024.

ABSTRACT

BACKGROUND: As prostaglandin medications, crucial in glaucoma treatment, become more widely used, their local adverse events are increasingly observed.

OBJECTIVES: To evaluate the common adverse events of four clinically commonly used prostaglandin F (FP) receptor agonists in the treatment of glaucoma in the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

DESIGN: We screened and analyzed the generic and brand names of latanoprost, bimatoprost, travoprost, and tafluprost in the FAERS database and summarized and cleaned the baseline information of subjects receiving the above-mentioned drugs.

METHODS: Perform descriptive statistical analysis on the baseline information of subjects using the drugs. Conduct disproportionality analysis of drug-related adverse events. The criteria for positive signals of adverse events are established by simultaneously meeting the thresholds set by four methods: the ratio of reported odds, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker. Additionally, assess the cumulative risk curves for drug-induced time of the aforementioned drugs and use one-way ANOVA to compare differences in drug-induced time across different groups.

RESULTS: The study included 1567 latanoprost, 1517 bimatoprost, 696 travoprost, and 82 tafluprost subjects. Adverse events mainly affected eye disorders, with significant issues in iris hyperpigmentation, ocular pemphigoid, corneal endothelial cell loss, periorbital fat atrophy, corneal irritation, eyelash growth, and ocular hyperemia. The time to onset varied among drugs, with latanoprost showing the longest (mean days = 344.37) and bimatoprost the shortest duration (mean days = 155.65; p < 0.001).

CONCLUSION: Although signal detection analysis based on the FAERS database cannot establish a definitive causal relationship, our study found that FP receptor agonists used in glaucoma can cause various adverse events. Assessing their clinical suitability and potential side effects is crucial for providing personalized treatment and ensuring medication safety.

PMID:39429679 | PMC:PMC11487502 | DOI:10.1177/20420986241285929

Cureus. 2024 Sep 19;16(9):e69689. doi: 10.7759/cureus.69689. eCollection 2024 Sep.

ABSTRACT

In clinical practice, tetracycline antimicrobial agents often lead to adverse events with drug fever and leukemoid reaction (LR) being rare occurrences. Here, we present a case of tigecycline-induced LR in a burn patient, which we believe is the first reported case of tigecycline-induced drug fever and LR globally in a burn patient and second overall.

PMID:39429433 | PMC:PMC11489805 | DOI:10.7759/cureus.69689

Chem Biol Interact. 2024 Oct 17:111282. doi: 10.1016/j.cbi.2024.111282. Online ahead of print.

ABSTRACT

This review examines how various medications can trigger inflammation throughout the body. It explores causes, ranging from common pain relievers like NSAIDs to chemotherapy drugs. The review also highlights potential treatments, including established medications and promising new therapies. Physicians and patients can work together to reduce this risk by understanding these causes and implementing preventive measures, such as monitoring for side effects and using alternative medications when possible. Drug-induced inflammation can be categorized into four types based on the immune response involved. Symptoms vary by type and affected organ. Common symptoms include fever, malaise, joint pain, rash, and swelling. Diagnosis involves blood tests, imaging, and biopsies. Treatment primarily involves discontinuing the suspected drug and providing supportive care. The development of new drugs and therapies has made diagnosis challenging. However, recent advances in biomarkers and genetic risk assessment techniques are improving diagnosis and risk assessment of drug-induced liver injury. Preventive measures for drug-induced inflammation include monitoring for side effects, using alternative medications, developing new drug delivery methods, exploring new anti-inflammatory drugs, being aware of rare side effects, and understanding the underlying mechanisms.

PMID:39426657 | DOI:10.1016/j.cbi.2024.111282

Lancet Neurol. 2024 Nov;23(11):1133-1146. doi: 10.1016/S1474-4422(24)00373-9.

ABSTRACT

BACKGROUND: Fasudil is a small molecule inhibitor of Rho-associated kinase (ROCK) and is approved for the treatment of subarachnoid haemorrhage. In preclinical studies, fasudil has been shown to attenuate neurodegeneration, modulate neuroinflammation, and foster axonal regeneration. We aimed to investigate the safety, tolerability, and efficacy of fasudil in patients with amyotrophic lateral sclerosis.

METHODS: ROCK-ALS was a phase 2, randomised, double-blind, placebo-controlled trial conducted at 19 amyotrophic lateral sclerosis centres in Germany, France, and Switzerland. Individuals (aged 18-80 years) with at least probable amyotrophic lateral sclerosis (as per the revised El Escorial criteria), a disease duration of 6-24 months, and a slow vital capacity greater than 65% of predicted normal were eligible for inclusion. Patients were randomly assigned (1:1:1) to receive 30 mg (15 mg twice daily) or 60 mg (30 mg twice daily) fasudil or matched placebo intravenously for 20 days over a 4-week period. Follow-up assessments were performed at 45, 90, and 180 days after treatment initiation. The co-primary endpoints were safety until day 180 (defined as the proportion without drug-related serious adverse events) and tolerability during the treatment period (defined as the proportion who did not discontinue treatment due to suspected drug-related adverse events). The primary analyses were carried out in the intention-to-treat population, which included all participants who entered the treatment phase. This trial is registered at ClinicalTrials.gov (NCT03792490) and Eudra-CT (2017-003676-31) and is now completed.

FINDINGS: Between Feb 20, 2019, and April 20, 2022, 120 participants were enrolled and randomised; two individuals assigned fasudil 30 mg withdrew consent before the baseline visit. Thus, the intention-to-treat population comprised 35 in the fasudil 30 mg group, 39 in the fasudil 60 mg group, and 44 in the placebo group. The estimated proportion without a drug-related serious adverse event was 1·00 (95% CI 0·91 to 1·00) with placebo, 1·00 (0·89 to 1·00) with fasudil 30 mg, and 1·00 (0·90 to 1·00) with fasudil 60 mg; the difference in proportions was 0·00 (95% CI -0·11 to 0·10; p>0·99) for fasudil 30 mg versus placebo and 0·00 (-0·10 to 0·10; p>0·99) for fasudil 60 mg versus placebo. Treatment tolerability (the estimated proportion who did not discontinue) was 0·93 (95% CI 0·81 to 0·99) with placebo, 1·00 (0·90 to 1·00) with fasudil 30 mg, and 0·90 (0·76 to 0·97) with fasudil 60 mg; the difference in proportions was 0·07 (95% CI -0·05 to 0·20; p=0·25) for fasudil 30 mg versus placebo, and -0·03 (-0·18 to 0·10; p=0·70) for fasudil 60 mg versus placebo. Eight deaths occurred: two in the placebo group, four in the fasudil 30 mg group, and two in the fasudil 60 mg group. The most common serious adverse events were respiratory failure (seven events), gastrostomy (five events), pneumonia (four events), and dysphagia (four events). No serious adverse events or deaths were attributed to study treatment. Adverse events, which were mainly related to disease progression, occurred in 139 participants in the placebo group, 108 in the fasudil 30 mg group, and 105 in the fasudil 60 mg group.

INTERPRETATION: Fasudil was well tolerated and safe in people with amyotrophic lateral sclerosis. The effect of fasudil on efficacy outcomes should be explored in larger clinical trials with a longer treatment duration, oral administration, and potentially higher dose of the trial drug.

FUNDING: Framework of the E-Rare Joint Transnational Call 2016 "Clinical research for new therapeutic uses of already existing molecules (repurposing) in rare diseases".

PMID:39424560 | DOI:10.1016/S1474-4422(24)00373-9

Farm Hosp. 2024 Oct 17:S1130-6343(24)00155-7. doi: 10.1016/j.farma.2024.09.006. Online ahead of print.

ABSTRACT

OBJECTIVE: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy.

METHOD: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival, and overall survival. Safety was measured as percentage of patients with adverse effects and severity.

RESULTS: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2-4.5), including autologous haematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%), and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95% CI: 0-49.1), median overall survival was not reached. At the study cut-off date, 5 patients had died (38.5%), 4 were in complete remission without active treatment (30.8%), and 4 were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, 2 suffered treatment delays (thrombocytopenia and hypertransaminemia), and 1 changed the regimen to monthly (pulmonary toxicity).

CONCLUSIONS: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed favourable effectiveness data in the study sample, expressed as objective response rate of 46.2% and a clinical benefit rate of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature.

PMID:39424522 | DOI:10.1016/j.farma.2024.09.006

Mult Scler Relat Disord. 2024 Oct 11;92:105939. doi: 10.1016/j.msard.2024.105939. Online ahead of print.

ABSTRACT

BACKGROUND: Ocrelizumab (OCR) effectively modifies the disease course in multiple sclerosis (MS) patients but may cause a preinfusion "wearing-off phenomenon" (WoP). This study explored the prevalence, timing, and severity of this phenomenon in MS patients using the OCR, as well as the associated symptoms and treatment satisfaction.

METHODS: We conducted a prospective multicenter study across 11 MS centers involving MS patients aged 18-70 years who had received at least two OCR doses. The study employed a questionnaire addressing demographic, clinical, and radiological data; symptom progression; and treatment satisfaction.

RESULTS: Of the 409 patients included in the study, 406 participated. A significant portion experienced varying degrees of WoP: 39.2% sometimes, 25.9% usually, and 14.3% always, with 55.9% noting symptom onset over four weeks prior to their next dose. Common symptoms included fatigue, walking difficulties, and pain. Subgroup analysis of 334 patients revealed that 78.1% of patients experienced these effects, which correlated with shorter disease durations, a longer delay between the two doses before the last dose, and a greater rate of relapse (P>0.05).

CONCLUSION: The WoP of the OCR is prevalent and significant among MS patients and is influenced by the dosing interval, disease duration, and relapse rate. These insights underscore the need for personalized treatment schedules and more research into factors affecting MS management.

PMID:39423725 | DOI:10.1016/j.msard.2024.105939

Res Pract Thromb Haemost. 2024 Sep 5;8(7):102565. doi: 10.1016/j.rpth.2024.102565. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: Persons with acquired hemophilia A are often older and suffer from comorbidity or frailty. Little is known about the impact on clinically relevant outcomes of acquired hemophilia A.

OBJECTIVES: To assess the relevance of age, physical performance status, comorbidity, and concomitant medication on the risk of bleeding and other outcomes.

METHODS: Post hoc analysis of data from the GTH-AHA-EMI study that used emicizumab for bleed protection and withheld immunosuppressive treatment during the early phase of management. Primary endpoint was the rate of clinically relevant new bleeding (CRNB) during the first 12 weeks of emicizumab prophylaxis.

RESULTS: Forty-seven patients were enrolled. Median age was 76 years; performance status (World Health Organization performance status [WHO-PS]) was 3 or worse in 41%; Charlson comorbidity index (CCI) was 5 or higher in 63%; antithrombotic drugs were reported in 34%. Rate of CRNB during 12 weeks of emicizumab prophylaxis was similar across subgroups of age, sex, WHO-PS, CCI, baseline factor VIII activity, and inhibitor titer. Patients with CRNB during the study had more severe anemia already at baseline. However, persistent severe anemia in week 4 was not related to risk of bleeding beyond this time. CRNB was associated with injury from falling in 7 of 14 patients. Adverse events grade 3 or higher were not related to baseline CCI or age but were more frequent in patients with poor WHO-PS.

CONCLUSION: Emicizumab provided bleed protection regardless of age and comorbidity. Clinical baseline characteristics did not predict breakthrough bleeding under emicizumab. Poor WHO-PS at baseline was associated with severe adverse events during the study.

PMID:39420971 | PMC:PMC11480235 | DOI:10.1016/j.rpth.2024.102565

Pharmacoepidemiol Drug Saf. 2024 Oct;33(10):e70037. doi: 10.1002/pds.70037.

ABSTRACT

BACKGROUND AND OBJECTIVES: This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy.

METHODS: Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).

RESULTS: The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease.

DISCUSSION: Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

PMID:39420647 | DOI:10.1002/pds.70037

BMC Emerg Med. 2024 Oct 17;24(1):197. doi: 10.1186/s12873-024-01102-x.

ABSTRACT

BACKGROUND: The prevalence of emergency department (ED) visits among the elderly is high and increasing. While emergency services for the elderly involve many factors, drug-related problems (DRPs) that can worsen patient conditions are less frequently discussed. This study investigates the prevalence of preventable drug-related ED visits (DREDp) and the characteristics of DRPs in elderly ED patients through a comprehensive medication review.

METHODS: A cross-sectional study was conducted at a non-trauma ED of a university-affiliated tertiary-care hospital. All adult patients aged 60 years and older who were on medications and visited the ED were included. A clinical pharmacist conducted comprehensive medication reviews for each patient. Patients were classified as experiencing drug-related ED visits (DRED) if their primary reason for the visit was associated with a DRP, as determined by both the physician and pharmacist. DRPs attributed to medication errors were categorized as preventable, while other DRPs were assessed for preventability using modified Schumock and Thornton criteria.

RESULTS: The study involved 351 patients with a mean age of 75.5 years (SD 9.3) and an equal male-to-female ratio of ED visits. The median number of comorbidities was five (IQR 3-6), with about half of the patients taking ten or more medications. The interdisciplinary team classified 43 patients (12.3%) as DREDp, accounting for 58.1% of the 74 (21.1%) drug-related ED visits. All medication errors categorized as causing harm (level E and higher) occurred within the DREDp group, constituting approximately half of all DREDp (22 cases, 51.2%). Approximately two-thirds of drug-related ED visits were associated with adverse drug events (ADEs), predominantly involving antithrombotics, oral hypoglycemic agents, and antineoplastics. Multivariable analysis identified that ED visits involving potentially inappropriate medications (PIMs) according to the STOPP criteria and the presence of multiple comorbidities (six or more concurrent diseases) were significantly associated with DREDp.

CONCLUSIONS: About one in ten elderly patients visited the ED due to preventable DRPs. The majority of DRPs leading to ED visits were ADEs. Both the prescription of PIMs and the presence of multiple comorbidities were significantly associated with DREDp.

PMID:39420250 | DOI:10.1186/s12873-024-01102-x

Eur Radiol. 2024 Oct 18. doi: 10.1007/s00330-024-11114-7. Online ahead of print.

ABSTRACT

OBJECTIVES: To systematically review and meta-analyze the recurrent rate of iodinated contrast medium (ICM)-associated adverse drug reactions (ADRs) and the preventive effect of using alternative ICM lacking a common carbamoyl side chain.

MATERIALS AND METHODS: A systematic literature search was conducted in the MEDLINE and EMBASE databases to identify studies that investigated the recurrence rate of ICM-associated ADRs or hypersensitivity reactions (HSRs). Studies that included patients who subsequently underwent contrast-enhanced computed tomography scans after their index reactions were included, while studies with overlapping cohorts were excluded. The first search was conducted on November 10, 2023. The pooled recurrence rate of ICM-associated ADR was determined using the DerSimonian-Laird random-effects model. Subgroup analyses were also conducted based on the substitution of ICM, with particular consideration given to the N-(2,3-dihydroxypropyl) carbamoyl side chain.

RESULTS: A total of ten original articles were included in the analysis, collectively spanning from June 2001 to March 2021. The pooled recurrence rate of ICM-associated ADR was not significantly different from that of ICM-associated HSR (16.6% [95% CI, 7.8-31.9%] vs. 15.5% [95% CI, 10.8-21.8%], p = 0.87). In the subgroup analyses, the pooled odds ratio for ICM-associated recurrent ADR when using a different ICM compared with using the same ICM was 0.31 (95% CI, 0.21-0.45), which means a 69% reduction. Moreover, the pooled odds ratio for ICM-associated recurrent ADR when substituting ICMs with different side chains compared with substituting with common side chains was 0.65 (95% CI, 0.52-0.82), which means an additional 35% reduction.

CONCLUSION: Substituting with an alternative ICM led to a 69% reduction in recurrent ADRs, with an additional 35% reduction observed when using ICM lacking a common carbamoyl side chain.

KEY POINTS: Question No standardized guidelines exist for replacing previously used iodinated contrast medium (ICM) to prevent recurrent adverse reactions. Findings Using alternative contrast medium with a different carbamoyl side chain prevents adverse drug reactions effectively. Clinical relevance This study advocates using alternative ICM without a common carbamoyl side chain to prevent recurrent adverse drug reactions in patients with a history of such events.

PMID:39419863 | DOI:10.1007/s00330-024-11114-7

Eur J Hosp Pharm. 2024 Oct 17:ejhpharm-2024-004188. doi: 10.1136/ejhpharm-2024-004188. Online ahead of print.

ABSTRACT

Neutropenia is a rare complication of drug therapy and is usually underdiagnosed. Cefoperazone/sulbactam is a combination of broad-spectrum antibacterial agents. Data on cefoperazone/sulbactam-induced neutropenia are limited. Herein, we report the case of a 35 year-old female patient who was admitted to the hospital due to an appendiceal abscess. After anti-infective treatment with cefoperazone/sulbactam, the patient developed neutropenia on day 4. After discontinuing treatment with cefoperazone/sulbactam, the patient's white blood cells and neutrophils gradually returned to normal. Hence, clinicians should monitor changes in neutrophil count during cefoperazone/sulbactam therapy and provide timely treatment.

PMID:39419595 | DOI:10.1136/ejhpharm-2024-004188

Open Forum Infect Dis. 2024 Sep 26;11(10):ofae560. doi: 10.1093/ofid/ofae560. eCollection 2024 Oct.

ABSTRACT

BACKGROUND: In TANGO and SALSA, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior to continuing a baseline regimen among adults who were treatment experienced, although few switched from bictegravir (B) / emtricitabine (F) / tenofovir alafenamide (TAF). Here, we present the efficacy and safety of switching to DTG/3TC as compared with continuing with B/F/TAF among adults with virologic suppression.

METHODS: DYAD is an open-label clinical trial that randomized adults with HIV-1 RNA <50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or maintain B/F/TAF. The primary end point is the proportion with HIV-1 RNA ≥50 copies/mL at week 48 (Food and Drug Administration Snapshot algorithm, intention-to-treat exposed population, 6% noninferiority margin).

RESULTS: Overall, 222 adults were randomized (16% women, 51% aged ≥50 years, 28% Black). At week 48, 6 (4%) with DTG/3TC and 5 (7%) with B/F/TAF had HIV-1 RNA ≥50 copies/mL (treatment difference, -2.8%; 95% CI, -11.4% to 3.1%), meeting noninferiority criteria. Through week 48, 18 participants (12 with DTG/3TC, 6 with B/F/TAF) met confirmed virologic withdrawal (CVW) criteria, and 2 of 18 had resistance: 1 with B/F/TAF developed M184M/I and G140G/S at week 12, and 1 with DTG/3TC had M184V at week 12. One participant with DTG/3TC and non-CVW developed M184V and K65R at week 12. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 2 (3%) and 0 participants with B/F/TAF, respectively.

CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing B/F/TAF among adults with virologic suppression at week 48. Drug-related AEs and withdrawals were higher in the DTG/3TC arm, which is likely consistent with the open-label nature of this switch study.

PMID:39416993 | PMC:PMC11482008 | DOI:10.1093/ofid/ofae560

Adv Ther. 2024 Oct 16. doi: 10.1007/s12325-024-02991-x. Online ahead of print.

ABSTRACT

INTRODUCTION: This phase 3 study assessed the efficacy, safety, and pharmacokinetics of the 6-month prolonged release (PR) formulation in Chinese children with central precocious puberty (CPP).

METHODS: In this open-label study (NCT05029622), Chinese children (girls < 9 years, boys < 10 years) received two doses of triptorelin pamoate 22.5 mg (day 1 and month 6). Primary endpoint was the proportion at month 6 with luteinizing hormone (LH) suppression (stimulated peak LH ≤ 5 IU/L after gonadotropin-releasing hormone stimulation). Secondary endpoints included safety assessments, hormone level changes, and clinical parameters from baseline.

RESULTS: Overall, 66 children completed the study (93.9% girls; median age 8.0 [range 5-9] years). At month 6, all patients had LH suppression; this was maintained at month 12 in 98.5% of patients. Mean basal and peak LH and follicle-stimulating hormone levels were suppressed throughout follow-up. All patients at months 3 to 12 had sex hormone suppression to prepubertal levels. Stable or reduced breast development was seen for 98.4% and 93.5% of girls at month 6 and 12, respectively; all boys had regression or stable genital development until month 12. Compared with baseline (9.82 cm/year), mean growth velocity was 5.88 cm/year at month 6 and 5.17 cm/year at month 12. Mean bone age/chronological age ratio decreased from 1.27 at baseline to 1.23 and 1.21 at month 6 and 12, respectively. In girls, 64.5% showed decreased uterine length at month 6 and 12 versus baseline, while 75.0% of boys showed stable testicular volume versus baseline. Thirteen patients (19.7%) had 22 drug-related treatment emergent adverse events (TEAEs); no grade ≥ 3 TEAEs were reported.

CONCLUSION: The efficacy and safety profile of triptorelin 6-month PR in Chinese children with CPP was consistent with data previously reported in non-Chinese children with CPP, supporting this as a viable treatment option for Chinese children with CPP.

TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov identifier, NCT05029622.

PMID:39412628 | DOI:10.1007/s12325-024-02991-x

J Clin Med. 2024 Oct 2;13(19):5879. doi: 10.3390/jcm13195879.

ABSTRACT

Background: Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator, which was demonstrated to reduce serum triglyceride levels with few drug-related adverse events in several clinical studies, as well as phase II and III clinical trials. One of the limitations of this medicine was the requirement of twice-daily oral administration, resulting in reduced medication adherence, particularly in elderly patients, who are rather good targets for this medicine. Recently, a once-daily extended-release (XR) tablet has been introduced. Given an improvement in medication adherence, the therapeutic efficacy of pemafibrate may be enhanced. Methods: Patients with hypertriglyceridemia, in whom conventional twice-daily immediate-release (IR) pemafibrate was converted to pemafibrate XR between 2023 and 2024, were eligible. Each type of tablet was prescribed for three months, respectively. A dose change was not attempted. The serum triglyceride levels were compared between 3 months pre-conversion and 3 months post-conversion using a Friedman test and a post hoc Wilcoxon signed-rank test. Results: A total of 46 patients were included. The median age was 62 years, and 29 were men. IR was continued for 698 (280, 1183) days before the conversion. During the last 3-month IR therapy, serum triglyceride levels remained unchanged from 171 (138, 239) mg/dL to 181 (123, 245) mg/dL (p = 0.78). Following the conversion, no patients had drug-related adverse events, and all patients completed 3-month XR therapy. At three months after the conversion, the serum triglyceride levels decreased significantly from 181 (123, 245) mg/dL to 146 (107, 184) mg/dL (p < 0.001). Conclusions: Pemafibrate XR might be a more promising medication than conventional IR in improving hypertriglyceridemia, probably due to improved medication adherence.

PMID:39407939 | DOI:10.3390/jcm13195879

Pharmazie. 2024 Oct 1;79(9):209-214. doi: 10.1691/ph.2024.4540.

ABSTRACT

Background: Of all adverse drug reactions, 35-45% are due to medication errors and would therefore be preventable. Thus, it is essential to implement effective strategies to prevent medication errors. However, it remains unclear whether medication reviews provide an additional benefit compared to medication reconciliation regarding medication safety. Aim: The present study aimed to evaluate whether medication reconciliation and medication reviews affect the incidence of preventable adverse drug reactions in elderly patients. Method: Non-elective patients 65 years and above admitted to the hospital, taking at least one high-risk drug, were eligible for participation in a three-armed randomized controlled trial. One group went through the medication reconciliation process, a second group received a comprehensive medication review, including medication reconciliation, and the third group did not receive any pharmaceutical intervention (control group). The incidence of preventable adverse drug reactions during hospitalization was set as the primary endpoint. The severity of the preventable adverse drug reactions and the number and clinical relevance of drug-related problems and discrepancies were defined as secondary endpoints. Results: In 207 patients, 74 preventable adverse drug reactions were detected. Neither medication reconciliation nor medication reviews showed a significant impact on the incidence of preventable adverse drug reactions compared to the control group. However, medication reviews significantly reduced the severity of preventable adverse drug reactions (p=0.017). Conclusion: The current study results suggest that medication reviews may have an impact on a clinically relevant outcome by reducing the severity of preventable adverse drug reactions. A significant impact of medication reconciliation on clinically relevant outcomes could not be demonstrated. Based on the results of this study, when deciding on a pharmaceutical intervention comprehensive medication reviews should be preferred over sole medication reconciliation whenever possible.

PMID:39407421 | DOI:10.1691/ph.2024.4540

BMC Public Health. 2024 Oct 15;24(1):2837. doi: 10.1186/s12889-024-20353-8.

ABSTRACT

BACKGROUND: To prevent the recurrence of Adverse Drug Events (ADEs), particularly drug allergies, it is essential to avoid re-exposure to causative drugs. Awareness of previous ADEs is crucial for patients because they can share accurate information with healthcare providers (HCPs). This study aims to assess users' willingness to share ADE information and evaluate the factors related to this willingness by utilizing a prospective ADE information-sharing system currently under consideration in South Korea.

METHODS: In September 2023, a self-administered questionnaire was collected from a sex-, age-, and regionally stratified nationwide convenience sample of adults recruited through a commercial panel in South Korea. Factors contributing to the willingness to share ADE information and create electronic ADE cards (e-ADE cards) were investigated using multivariate logistic regression analysis.

RESULTS: Among the 1,000 respondents, 458 (45.8%) were willing to share ADE information, and 521 (52.1%) were willing to create e-ADE cards. The willingness to share personal ADE information and create e-ADE cards was positively associated with the perceived benefits of sharing ADE, trust in HCPs and positive experiences. Notably, older adult patients demonstrated a higher willingness to share information and use e-ADE cards, with rates of 56% and 62%, respectively.

CONCLUSIONS: Our findings indicate that the approach to sharing personal ADE information should be distinct from that of sharing comprehensive health information. Notably, users are likely to willingly disclose their personal information even if they are not anonymized, owing to the significant perceived benefits of sharing. The findings of this study can enhance awareness about sharing personal ADE information and contribute to the successful establishment of an ADE information-sharing system, thereby improving the patient safety environment.

PMID:39407197 | DOI:10.1186/s12889-024-20353-8

BMC Geriatr. 2024 Oct 15;24(1):841. doi: 10.1186/s12877-024-05449-5.

ABSTRACT

BACKGROUND: This study aimed to systematically evaluate interventions and effects that promote involvement in medication safety among older people with chronic diseases and to provide new ideas and references for developing standardized and effective intervention strategies to improve patient involvement in medication safety.

METHODS: A comprehensive literature search across twelve databases was conducted using both computerized and manual methods. The search was limited to studies designated as randomized controlled trials or quasi-experimental studies and was conducted from the time of each database's inception until September 2023. Two researchers independently carried out qualitative analyses, which included screening the literature, extracting the data, and assessing the quality of the selected studies.

RESULTS: This study included five studies involving a total of 388 participants, with interventions aimed at enhancing patient involvement in medication safety, including interactive health education, motivational interviewing, and medication reconciliation. However, direct evidence confirming the positive impact of these interventions in promoting medication safety behaviors among older people with chronic diseases is still lacking.

CONCLUSIONS: Patient involvement in medication safety behaviors is essential for promoting healthy aging. Medication education, motivational interviewing, and medication reconciliation may improve the willingness and ability of older people to participate. However, limitations in the methodological quality of current studies prevent drawing definitive conclusions, highlighting the urgent need for more high-quality research.

TRIAL REGISTRATION: PROSPERO number CRD42023494924.

PMID:39407167 | DOI:10.1186/s12877-024-05449-5

J Cyst Fibros. 2024 Oct 14:S1569-1993(24)01788-0. doi: 10.1016/j.jcf.2024.09.020. Online ahead of print.

ABSTRACT

BACKGROUND: A highly effective therapy involving elexacaftor, tezacaftor, and ivacaftor (ETI) for cystic fibrosis (CF) patients has recently raised safety concerns regarding potential psychiatric disorders. The manuscript reports cases of suicide attempts in patients receiving ETI and investigates putative causality using the WHO spontaneous reporting database.

METHODS: First, four cases of suicide attempts/self-injury are described. Second, a disproportionality analysis was conducted using spontaneous reports collected in Vigibase through the standardised MedDRA Query (narrow version) "Suicide/Self-injury" and ETI exposure. Reporting Odds Ratio (ROR) was calculated for the main and subgroup (i/suicide attempt, ii/suicidal ideation) analyses. Sensitivity analyses were performed with variations in exposure, to ivacaftor/lumacaftor to assess the intrinsic psychiatric risk of CF patients, and paracetamol as a positive control for suicide attempt and a negative one for suicidal ideation. Exposure to reduced-dose ETI was studied to evaluate the dose-gradient effect.

RESULTS: Four cases of suicide attempt/self-injury occurred 3 to 13 months after ETI initiation in CF patients and were reported to the Bordeaux Pharmacovigilance centre. Aside, in Vigibase, ETI is associated with an increased likelihood of reporting suicidal behaviour (ROR 2.5, 95 % CI[2.1; 2.8]). A signal of disproportionate reporting was found for the subgroup of suicide attempts (1.4, 95 % CI[1.2; 1.8]), unlike ivacaftor/lumacaftor, which was associated only with the risk of reporting suicidal ideation. Significant ROR values were also found for reduced-dose ETI for all psychiatric effects studied except suicide attempt.

CONCLUSIONS: ETI exposure is related with increased reporting of suicidal behaviour. A potential dose-dependent effect merits further investigation.

PMID:39406576 | DOI:10.1016/j.jcf.2024.09.020

Ter Arkh. 2024 Sep 14;96(8):836-845. doi: 10.26442/00403660.2024.08.202841.

ABSTRACT

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

PMID:39404730 | DOI:10.26442/00403660.2024.08.202841