Br J Cancer. 2024 May 7. doi: 10.1038/s41416-024-02701-y. Online ahead of print.

ABSTRACT

BACKGROUND: Gut microbiome modulation to boost antitumor immune responses is under investigation.

METHODS: ROMA-2 evaluated the microbial ecosystem therapeutic (MET)-4 oral consortia, a mixture of cultured human stool-derived immune-responsiveness associated bacteria, given with chemoradiation (CRT) in HPV-related oropharyngeal cancer patients. Co-primary endpoints were safety and changes in stool cumulative MET-4 taxa relative abundance (RA) by 16SRNA sequencing. Stools and plasma were collected pre/post-MET-4 intervention for microbiome and metabolome analysis.

RESULTS: Twenty-nine patients received ≥1 dose of MET-4 and were evaluable for safety: drug-related adverse events (AEs) occurred in 13/29 patients: all grade 1-2 except one grade 3 (diarrhea). MET-4 was discontinued early in 7/29 patients due to CRT-induced toxicity, and in 1/29 due to MET-4 AEs. Twenty patients were evaluable for ecological endpoints: there was no increase in stool MET-4 RA post-intervention but trended to increase in stage III patients (p = 0.06). MET-4 RA was higher in stage III vs I-II patients at week 4 (p = 0.03) and 2-month follow-up (p = 0.01), which correlated with changes in plasma and stool targeted metabolomics.

CONCLUSIONS: ROMA-2 did not meet its primary ecologic endpoint, as no engraftment was observed in the overall cohort. Exploratory findings of engraftment in stage III patients warrants further investigation of microbiome interventions in this subgroup.

PMID:38714747 | DOI:10.1038/s41416-024-02701-y

Gut Liver. 2024 May 7. doi: 10.5009/gnl230494. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: : Ursodeoxycholic acid (UDCA) is the only well-established and widely used agent for dissolving gallstones. Epidemiological and animal studies have suggested potential therapeutic benefits of n-3 polyunsaturated fatty acids (PUFA) for dissolving cholesterol gallstones. We evaluated whether adding PUFA to UDCA improves gallstone dissolution in patients with cholesterol gallstones.

METHODS: : This randomized, prospective, preliminary clinical trial compared the efficacy and safety of UDCA plus PUFA combination therapy (combination group) with those of UDCA monotherapy (monotherapy group). The inclusion criteria were a gallstone diameter ≤15 mm on ultrasonography, radiolucent stones on plain X-ray, and no to mild symptoms. Gallstone dissolution rates, response rates, and adverse events were evaluated.

RESULTS: : Of the 59 screened patients, 45 patients completed treatment (24 and 21 in the monotherapy and combination groups, respectively). The gallstone dissolution rate tended to be higher in the combination group than in the monotherapy group (45.7% vs 9.9%, p=0.070). The radiological response rate was also significantly higher in the combination group (90.5% vs 41.7%, p=0.007). In both groups, dissolution and response rates were higher in patients with gallbladder sludge than in those with distinct stones. Four adverse events (two in each group) were observed, none of which were study drug-related or led to drug discontinuation. The incidence of these adverse events was similar in both groups (combination vs monotherapy: 9.5% vs 8.3%, p=0.890).

CONCLUSIONS: : UDCA plus PUFA therapy dissolves cholesterol gallstones more effectively than UDCA monotherapy, without significant complications. Further prospective, large-scale studies of this combination therapy are warranted.

PMID:38712398 | DOI:10.5009/gnl230494

Cureus. 2024 Apr 6;16(4):e57722. doi: 10.7759/cureus.57722. eCollection 2024 Apr.

ABSTRACT

Urticarial vasculitis (UV) is a type of small-vessel vasculitis, which is rarely associated with anti-tumor necrosis factor (TNF)-alpha medication. We describe a 72-year-old woman with multiple comorbidities on several medications, including an adalimumab biosimilar for Hurley stage II recalcitrant hidradenitis suppurativa (HS), who presented with new-onset severe angioedema and a rash with urticarial wheals that covered most of her body surface area. The diagnosis of drug-induced UV is supported by both the history of adalimumab biosimilar use and the histopathology result. The patient responded successfully to a course of doxycycline administered for three months, which was preceded by corticosteroid dosages, both orally and intravenously, to reduce inflammation. The given case highlights the correlation between a distinct dermatologic autoimmune manifestation and TNF-targeted therapy, demonstrating the importance for dermatologists to be aware of the potential side effects of adalimumab biosimilars in order to manage them effectively.

PMID:38711695 | PMC:PMC11073587 | DOI:10.7759/cureus.57722

J Neurogastroenterol Motil. 2024 May 4. doi: 10.5056/jnm23150. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD.

METHODS: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean (NDI-K), and gastroesophageal reflux disease-health-related quality of life (GERD-HRQL). The main outcome was satisfactory symptom relief rates at 8 weeks.

RESULTS: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study.

CONCLUSION: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

PMID:38710534 | DOI:10.5056/jnm23150

J Natl Cancer Inst. 2024 May 6:djae098. doi: 10.1093/jnci/djae098. Online ahead of print.

ABSTRACT

BACKGROUND: Camonsertib is a selective oral inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase with demonstrated efficacy in tumors with DNA damage response gene deficiencies. On-target anemia is the main drug-related toxicity typically manifesting after the period of dose-limiting toxicity evaluation. Thus dose/schedule optimization requires extended follow-up to assess prolonged treatment effects.

METHODS: Long-term safety/tolerability and antitumor efficacy of three camonsertib monotherapy dose levels/schedules were assessed in the TRESR study dose-optimization phase: 160 mg once daily (QD) 3 days on/4 off (160 3/4; the preliminary recommended phase II dose [RP2D]) and two step-down groups of 120 mg QD 3/4 (120 3/4) and 160 mg QD 3/4, 2 weeks on/1 off (160 3/4, 2/1w). Safety endpoints included incidence of treatment-related adverse events (TRAEs), dose modifications, and transfusions. Efficacy endpoints included overall response rate, clinical benefit rate, progression-free survival, and circulating-tumor-DNA (ctDNA)-based molecular response rate.

RESULTS: The analysis included 119 patients: 160 3/4 (n = 67), 120 3/4 (n = 25), and 160 3/4, 2/1w (n = 27) treated up to 117.1 weeks as of the data cutoff. The risk of developing grade 3 anemia was significantly lower in the 160 3/4, 2/1w group compared with the preliminary RP2D group (HR = 0.23, 2-sided P = .02), translating to reduced transfusion and dose reduction requirements. The intermittent weekly schedule did not compromise antitumor activity.

CONCLUSION: The 160 3/4, 2/1w dose was established as an optimized regimen for future camonsertib monotherapy studies offering significantly reduced anemia incidence without any compromise to efficacy.

PMID:38710487 | DOI:10.1093/jnci/djae098

Lancet Oncol. 2024 May 3:S1470-2045(24)00140-2. doi: 10.1016/S1470-2045(24)00140-2. Online ahead of print.

ABSTRACT

BACKGROUND: Trastuzumab deruxtecan is a HER2-directed antibody-drug conjugate approved by the US Food and Drug Administration and the European Medicines Agency for HER2-mutant non-small-cell lung cancer. Few treatment options exist for patients with HER2-mutant solid tumours beyond lung cancers. We investigated trastuzumab deruxtecan in metastatic solid tumours with specific activating HER2 mutations.

METHODS: In this open-label, phase 2, basket study done in 29 centres in Asia, Europe, and North America, we investigated trastuzumab deruxtecan (5·4 mg/kg every 3 weeks by intravenous infusion) in patients aged 18 years or older with unresectable or metastatic solid tumours with specific activating HER2 mutations, an Eastern Cooperative Oncology Group performance status of 0 or 1, and disease progression following previous treatment (previous HER2-targeted therapy was permitted) or with no satisfactory alternative treatment options. The primary endpoint was confirmed objective response rate by independent central review. Anti-tumour activity and safety were analysed in all patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT04639219, and is active but no longer recruiting.

FINDINGS: Between Dec 30, 2020, and Jan 25, 2023, 102 patients (62 [61%] female and 40 [39%] male; median age 66·5 years [IQR 58-72]; 51 [50%] White, two [2%] Black or African American, 38 [37%] Asian, and 11 [11%] did not have race information reported) with solid tumours with activating HER2 mutations received trastuzumab deruxtecan and were included in the anti-tumour activity and safety analyses sets. Patients had a median of three (IQR 2-4) previous treatment regimens. The median duration of follow-up was 8·61 months (IQR 3·71-12·68). The objective response rate by independent central review was 29·4% (95% CI 20·8-39·3; 30 of 102 patients). 52 (51%) patients had a treatment-emergent adverse event of grade 3 or worse; the most common events (in ≥5% of patients) were anaemia (16 [16%]) and neutrophil count decreased (eight [8%]). Drug-related treatment-emergent serious adverse events occurred in ten (10%) patients. Adjudicated drug-related interstitial lung disease or pneumonitis of any grade occurred in 11 patients (11%; three grade 1, five grade 2, one grade 3, and two grade 5); there were two (2%) cases of fatal adjudicated drug-related interstitial lung disease or pneumonitis.

INTERPRETATION: Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations, with no new safety signals. Prespecified HER2 mutations might be targeted by HER2-directed antibody-drug conjugates and our findings support further investigation of trastuzumab deruxtecan in the pan-tumour setting.

FUNDING: AstraZeneca and Daiichi Sankyo.

PMID:38710187 | DOI:10.1016/S1470-2045(24)00140-2

Pharmaceut Med. 2024 May;38(3):251-259. doi: 10.1007/s40290-024-00524-z. Epub 2024 May 6.

ABSTRACT

INTRODUCTION: Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment.

OBJECTIVE: The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria.

METHODS: This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019 to 30th October 2020 and the comparison period was 1st November 2020 to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal-Wallis test was used to test for differences in medians between groups.

RESULTS: Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal-Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App.

CONCLUSION: Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients.

PMID:38705932 | DOI:10.1007/s40290-024-00524-z

Res Social Adm Pharm. 2024 May 1:S1551-7411(24)00155-4. doi: 10.1016/j.sapharm.2024.04.018. Online ahead of print.

ABSTRACT

BACKGROUND: Geriatric Oncology is a specialty where a multidisciplinary approach can address the unmet needs of older adults with cancer. Older adults are at increased risk of adverse drug events (ADE) due to age-related changes in pharmacokinetics and pharmacodynamics, increasing treatment complexity, and medication burden.

OBJECTIVES: To review the literature to determine the incidence of unplanned hospitalisation due to ADE for all medications, both systemic anticancer therapy (SACT) and non-SACT medications.

METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search included the following databases: PubMed, CINAHL, and Embase. A manual search of Scopus was then performed. Study quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, Mixed Methods Appraisal Tool (MMAT) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework.

RESULTS: Overall, three studies were included. One observational study reported 19 % of unplanned hospital admissions due to ADE in patients aged ≥70 years with cancer. The first retrospective study reported 24 % of unplanned hospital admissions are due to ADE in patients aged ≥70 years with cancer, and the second retrospective study reported 26 % of patients with metastatic melanoma treated with immune checkpoint inhibitors had an unplanned hospital admission due to an ADE.

CONCLUSION: There is a paucity of studies assessing unplanned hospitalisation due to ADE in older adults with cancer. Future studies are needed and should account for the reporting of potential ADE relative to supportive care, ancillary medications, and indeed chronic medications used to treat long-standing comorbidities.

PMID:38705819 | DOI:10.1016/j.sapharm.2024.04.018

Vaccine. 2024 May 31;42(15):3486-3492. doi: 10.1016/j.vaccine.2024.04.051. Epub 2024 May 3.

ABSTRACT

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years.

METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status.

RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively.

CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

PMID:38704258 | DOI:10.1016/j.vaccine.2024.04.051

Compr Psychiatry. 2024 Apr 15;133:152486. doi: 10.1016/j.comppsych.2024.152486. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the long-term safety and tolerability of off-label high-dose serotonin reuptake inhibitors (OLHD-SRIs) in the treatment of obsessive-compulsive disorder (OCD).

METHODS: A retrospective longitudinal study was performed on 105 randomly selected outpatients diagnosed with OCD and were treated with OLHD-SRIs for at least 6 months. Patients received sertraline >200 mg/day, escitalopram >20 mg/day, fluvoxamine >300 mg/day, and fluoxetine >60 mg/day, combined with exposure and response prevention therapy. Patients were divided into three dosing groups: sertraline equivalent dose (SED) ≤ 200 mg/day (n = 26, 24.7%), 201-400 mg/day (n = 51, 48.5%) and 401-650 mg/day (n = 28, 26.6%). Safety and tolerability were assessed with an electrocardiogram, blood biochemistry, complete blood count, and side-effects monitoring.

RESULTS: SED ranged from 100 to 650 mg/day and the mean duration of OLHD-SRI treatment was 20.8 months. The most common side-effects reported were sexual dysfunction (n = 36, 34%), weight gain (n = 28, 27%), sedation (n = 27, 26%), hyperhidrosis (n = 20, 19%), and tremor (n = 11, 10%). Abnormal ECG was documented in one patient, and another patient experienced a first-time seizure, whereas elevated liver enzymes were seen in 4.8% of the sample (n = 5). None of the patients had serotonin syndrome or drug-induced liver injury. Side-effects did not differ among the three dosing groups.

CONCLUSION: OLHD-SRIs appear to be safe and well tolerated in OCD patients in SED ≤ 650 mg/day doses and the side-effects did not differ between the three dosing groups.

PMID:38703743 | DOI:10.1016/j.comppsych.2024.152486

Methods. 2024 Jun;226:164-175. doi: 10.1016/j.ymeth.2024.04.020. Epub 2024 May 1.

ABSTRACT

Ensuring the safety and efficacy of chemical compounds is crucial in small-molecule drug development. In the later stages of drug development, toxic compounds pose a significant challenge, losing valuable resources and time. Early and accurate prediction of compound toxicity using deep learning models offers a promising solution to mitigate these risks during drug discovery. In this study, we present the development of several deep-learning models aimed at evaluating different types of compound toxicity, including acute toxicity, carcinogenicity, hERG_cardiotoxicity (the human ether-a-go-go related gene caused cardiotoxicity), hepatotoxicity, and mutagenicity. To address the inherent variations in data size, label type, and distribution across different types of toxicity, we employed diverse training strategies. Our first approach involved utilizing a graph convolutional network (GCN) regression model to predict acute toxicity, which achieved notable performance with Pearson R 0.76, 0.74, and 0.65 for intraperitoneal, intravenous, and oral administration routes, respectively. Furthermore, we trained multiple GCN binary classification models, each tailored to a specific type of toxicity. These models exhibited high area under the curve (AUC) scores, with an impressive AUC of 0.69, 0.77, 0.88, and 0.79 for predicting carcinogenicity, hERG_cardiotoxicity, mutagenicity, and hepatotoxicity, respectively. Additionally, we have used the approved drug dataset to determine the appropriate threshold value for the prediction score in model usage. We integrated these models into a virtual screening pipeline to assess their effectiveness in identifying potential low-toxicity drug candidates. Our findings indicate that this deep learning approach has the potential to significantly reduce the cost and risk associated with drug development by expediting the selection of compounds with low toxicity profiles. Therefore, the models developed in this study hold promise as critical tools for early drug candidate screening and selection.

PMID:38702021 | DOI:10.1016/j.ymeth.2024.04.020

J Med Internet Res. 2024 May 3;26:e48572. doi: 10.2196/48572.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs), which are the phenotypic manifestations of clinical drug toxicity in humans, are a major concern in precision clinical medicine. A comprehensive evaluation of ADRs is helpful for unbiased supervision of marketed drugs and for discovering new drugs with high success rates.

OBJECTIVE: In current practice, drug safety evaluation is often oversimplified to the occurrence or nonoccurrence of ADRs. Given the limitations of current qualitative methods, there is an urgent need for a quantitative evaluation model to improve pharmacovigilance and the accurate assessment of drug safety.

METHODS: In this study, we developed a mathematical model, namely the Adverse Drug Reaction Classification System (ADReCS) severity-grading model, for the quantitative characterization of ADR severity, a crucial feature for evaluating the impact of ADRs on human health. The model was constructed by mining millions of real-world historical adverse drug event reports. A new parameter called Severity_score was introduced to measure the severity of ADRs, and upper and lower score boundaries were determined for 5 severity grades.

RESULTS: The ADReCS severity-grading model exhibited excellent consistency (99.22%) with the expert-grading system, the Common Terminology Criteria for Adverse Events. Hence, we graded the severity of 6277 standard ADRs for 129,407 drug-ADR pairs. Moreover, we calculated the occurrence rates of 6272 distinct ADRs for 127,763 drug-ADR pairs in large patient populations by mining real-world medication prescriptions. With the quantitative features, we demonstrated example applications in systematically elucidating ADR mechanisms and thereby discovered a list of drugs with improper dosages.

CONCLUSIONS: In summary, this study represents the first comprehensive determination of both ADR severity grades and ADR frequencies. This endeavor establishes a strong foundation for future artificial intelligence applications in discovering new drugs with high efficacy and low toxicity. It also heralds a paradigm shift in clinical toxicity research, moving from qualitative description to quantitative evaluation.

PMID:38700923 | DOI:10.2196/48572

Expert Opin Drug Saf. 2024 May 3. doi: 10.1080/14740338.2024.2351451. Online ahead of print.

ABSTRACT

OBJECTIVE: Elagolix is approved for the treatment of moderate-to-severe pain associated with endometriosis. However, the long-term safety of elagolix in a large sample of real-world patients is unknown.

METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) reports were collected and analyzed for the first quarter of 2019 through the second quarter of 2023. Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms, were employed in data mining to quantify the signals of elagolix-related adverse events (AEs).

RESULTS: A total of 112 elagolix-induced AE signals were detected in 17 system organ classes (SOCs) that simultaneously met the thresholds of 4 algorithms. After removing the non-drug-related AE signals, we detected several AE signals such as hot flushes, bone pain, suicidal ideation, depression, and increased liver enzymes, which were known during the clinical trial phase. In addition to this, we detected several unexpected important adverse events that were not mentioned in the drug insert, including cystitis interstitial, parosmia, and epiploic appendagitis. The median onset time of elagolix-associated AEs was 28.5 days. The majority of cases occurred within 1 month after initiation of elagolix treatment.

CONCLUSION: Our study provides a comprehensive picture of the safety of elagolix in the post-marketing setting, while also identifying potential new AE signals. These findings emphasize the importance of continued monitoring of the potential risks of elagolix.

PMID:38700323 | DOI:10.1080/14740338.2024.2351451

Vet Rec. 2024 May 4;194(9):324. doi: 10.1002/vetr.4212.

NO ABSTRACT

PMID:38700205 | DOI:10.1002/vetr.4212

Lancet Child Adolesc Health. 2024 Jun;8(6):389-390. doi: 10.1016/S2352-4642(24)00106-8. Epub 2024 Apr 30.

NO ABSTRACT

PMID:38697176 | DOI:10.1016/S2352-4642(24)00106-8

Lancet Child Adolesc Health. 2024 Jun;8(6):422-432. doi: 10.1016/S2352-4642(24)00078-6. Epub 2024 Apr 30.

ABSTRACT

BACKGROUND: Rare and severe adverse events can occur in children with inflammatory bowel disease (IBD), and the relationship with disease or drug treatment is often uncertain. We aimed to establish a method of reporting adverse events of interest in children with IBD, allowing for estimates of incidence rates with comparison between different regions, and, if possible, to compare with published data on rates of adverse events in children overall.

METHODS: For this analysis, we used data from the Paediatric Inflammatory Bowel Disease Network for Safety, Efficacy and Treatment and Quality improvement of care (PIBD-SETQuality) Safety Registry, which collects data on multiple rare and severe adverse events in children younger than 19 years with IBD. Overall, the registry collected data on ten prespecified rare and severe adverse events in children with IBD, as established by a panel of paediatric IBD experts, via reports from paediatric gastroenterologists at participating hospitals between Nov 1, 2016, and March 31, 2023. Reporting physicians, who could only be paediatric gastroenterologists or IBD nurses reporting on behalf of paediatric gastroenterologists, were recruited through invitations sent to both national and international IBD networks and at conferences. Once per month, participating paediatric gastroenterologists received an email with an anonymous and unique link to an online survey asking them to report whether any of ten rare and severe adverse events had occurred in a patient in their paediatric-IBD population in the previous month. Prevalent or retrospective rare and severe adverse events were excluded, as were events occurring in children with an unconfirmed diagnosis of IBD or for whom inflammatory colitis was part of a monogenic immunodeficiency disorder. Duplicates and events that did not meet the definitions and criteria were excluded. Physicians could also report other, non-categorised adverse events if they considered them rare and severe. In case of no response, up to two reminders were sent for each per-month survey. Annual denominator data surveys were sent to obtain the total number of person-years for the estimation of incidence rates, which were calculated via Poisson regression models.

FINDINGS: Responses were gathered from 220 paediatric gastroenterologists from 167 centres. 121 centres were in Europe, 23 centres were in North America, 17 centres were in Asia, and six centres were in Oceania. Combined, the total population with paediatric IBD consisted of an estimated 30 193 children with 114 528 person-years of follow-up. 451 adverse events were initially reported. After excluding and reorganising adverse events, 402 were eligible; 261 (65%) were categorised and 141 (35%) were non-categorised. The most frequently reported adverse events were venous-thromboembolic events (n=66), renal failure (n=43), opportunistic infections (n=42), and cancer (n=33). Haemophagocytic lymphohistiocytosis (n=4) and liver failure (n=3) were the least frequently reported adverse events. Incidence rates per 10 000 person-years were 5·50 (95% CI 4·25-6·97) for venous-thromboembolic events, 3·75 (2·74-4·99) for renal failure, 3·67 (2·67-4·89) for opportunistic infection, and 2·88 (2·01-3·98) for cancer. Of 66 venous-thromboembolic events, 31 (47%) involved cerebral venous sinus thrombosis at an incidence rate of 2·71 (95% CI 1·86-3·77).

INTERPRETATION: The PIBD-SETQuality Safety Registry enabled us to identify incidence rates of rare and severe adverse events in children with IBD. Our findings can guide physicians and enhance awareness of the incidence of adverse events in children with IBD that are considered to be rare.

FUNDING: EU Horizon 2020 Research and Innovation Programme.

PMID:38697175 | DOI:10.1016/S2352-4642(24)00078-6

Eur J Hosp Pharm. 2024 May 2:ejhpharm-2023-004023. doi: 10.1136/ejhpharm-2023-004023. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to assess and compare the occurrence of 3-HIT in people living with HIV (PLWH) and seronegative patients. Additionally, the study investigated whether HIV infection could serve as a predictor of the presence of 3-HIT.

METHODS: A cross-sectional study was conducted between December 2022 and January 2023 to compare PLWH with a group of seronegative patients with chronic diseases attending an outpatient hospital pharmacy service. The 3-HIT concept encompasses the simultaneous presence of non-adherence to concomitant treatment (NAC), drug-drug interactions (DDIs), and high pharmacotherapeutic complexity in polymedicated patients. The assessment of 3-HIT compliance included NAC, evaluated using both the Morisky-Green questionnaire and electronic pharmacy dispensing records. DDIs were analysed using the Liverpool University and Micromedex databases. Pharmacotherapeutic complexity was measured using the Medication Regimen Complexity Index (MRCI) tool. Logistic regression analysis was performed to identify independent factors related to 3-HIT. Additionally, an explanatory logistic model was created to investigate whether HIV infection, along with other adjustment variables, could predict compliance with the 3-HIT concept.

RESULTS: The study included 145 patients: 75 PLWH and 70 seronegative patients. The median age was 40 versus 39 years, respectively (p=0.22). Seronegative patients exhibited a higher prevalence of NAC (p<0.01). HIV infection was identified as a protective factor in the context of DDIs (p<0.01). Male sex (p<0.01) and age (p=0.01) were identified as being associated with an MRCI ≥11.25 points. A higher prevalence of 3-HIT was observed in seronegative patients (18.7% vs 48.6%, p<0.01). However, the developed regression model identified HIV infection as a risk factor associated with an increased likelihood of 3-HIT (OR 4.00, 95% CI 1.88 to 8.52, p<0.01).

CONCLUSIONS: The 3-HIT concept exhibited a high prevalence among seronegative patients with chronic diseases, with HIV infection identified as a predicted risk factor for NAC and the development of 3-HIT.

PMID:38697803 | DOI:10.1136/ejhpharm-2023-004023

Drug Ther Bull. 2024 May 2:dtb-2024-000029. doi: 10.1136/dtb.2024.000029. Online ahead of print.

NO ABSTRACT

PMID:38697797 | DOI:10.1136/dtb.2024.000029

Drug Ther Bull. 2024 May 2:dtb-2024-000030. doi: 10.1136/dtb.2024.000030. Online ahead of print.

NO ABSTRACT

PMID:38697796 | DOI:10.1136/dtb.2024.000030

BMC Cancer. 2024 May 2;24(1):552. doi: 10.1186/s12885-024-12291-w.

ABSTRACT

BACKGROUND: Patients with hematological malignancies often require multidrug therapy using a variety of antineoplastic agents and supportive care medications. This increases the risk of drug-related problems (DRPs). Determining DRPs in patients hospitalized in hematology services is important for patients to achieve their drug treatment goals and prevent adverse effects. This study aims to identify DRPs by the clinical pharmacist in the multidisciplinary team in patients hospitalized in the hematology service of a university hospital in Turkey.

METHODS: This study was conducted prospectively between December 2022 and May 2023 in the hematology service of Suleyman Demirel University Research and Application Hospital in Isparta, Turkey. DRPs were determined using the Pharmaceutical Care Network Europe (PCNE) 9.1 Turkish version.

RESULTS: This study included 140 patients. Older age, longer hospital stay, presence of acute lymphoblastic leukemia, presence of comorbidities, higher number of medications used, and polypharmacy rate were statistically significantly higher in the DRP group than in the non-DRP group (p < 0.05). According to multivariate logistic regression analysis, the probability of DRP in patients with polypharmacy was statistically significant 7.921 times (95% CI: 3.033-20.689) higher than in patients without polypharmacy (p < 0.001).Every 5-day increase in the length of hospital stay increased the likelihood of DRP at a statistically significant level (OR = 1.476, 95% CI: 1.125-1.938 p = 0.005). In this study, at least one DRP was detected in 69 (49.3%) patients and the total number of DRPs was 152. Possible or actual adverse drug events (96.7%) were the most common DRPs. The most important cause of DRPs was drug choice (94.7%), and the highest frequency within its subcategories was the combination of inappropriate drugs (93.4%).

CONCLUSIONS: This study shows the importance of including a clinical pharmacist in a multidisciplinary team in identifying and preventing DRPs in the hematology service.

PMID:38698336 | DOI:10.1186/s12885-024-12291-w