Pharmacoepidemiol Drug Saf. 2024 Sep;33(9):e70003. doi: 10.1002/pds.70003.

ABSTRACT

PURPOSE: Removing medicines from market may benefit public health by preventing adverse drug reactions (ADRs), which should be quantified. This study's aim was to identify a model to quantify the impact of medicines' marketing authorisation (MA) withdrawal and revocation in terms of preventing morbidity and mortality.

METHODS: MA withdrawals and revocations for safety reasons in France, Germany and/or the United Kingdom between July 2012 and December 2016 were identified for prescription medicines. Annual exposure was estimated for each medicine, using IQVIA Medical Research Data (IMRD)-France, IMRD-Germany and IMRD-UK primary care electronic health record databases. European Medicines Agency records provided reasons for regulatory action for each medicine. Absolute risks of ADRs which led to MA withdrawal were estimated for patients exposed to each medicine by systematic review of quantitative research. Public health impact, expressed as annual number of ADRs avoided, was estimated by modelling exposure and ADR risk.

RESULTS: Four MA withdrawals and two revocations met study inclusion criteria. Each product's usage decreased following MA withdrawal or revocation. Absolute risk for ADRs was 0.1%-41.25%. To estimate impact of each withdrawal or revocation, its average annual exposure within each IMRD population was multiplied by the absolute risk to give the crude number of ADRs prevented annually due to regulatory action.

CONCLUSIONS: This model quantifies the public health impact of MA withdrawal and revocation in terms of serious morbidity, resulting from eliminated or reduced usage of medicines. This method can be applied to products in other settings to quantify the impact of other pharmacovigilance actions.

PMID:39212104 | DOI:10.1002/pds.70003

JMIR Public Health Surveill. 2024 Aug 29;10:e63808. doi: 10.2196/63808.

ABSTRACT

BACKGROUND: Herbal medicines (HMs) are extensively used by consumers/patients worldwide. However, their safety profiles are often poorly reported and characterized. Previous studies have documented adverse events (AEs) associated with HMs, such as hepatotoxicity, renal failure, and allergic reactions. However, the prevalence rate of AEs related to HMs has been reported to be low. To date, no systematic review and meta-analysis has comprehensively analyzed the AEs of HMs using published data acquired from pharmacovigilance (PV) databases.

OBJECTIVE: This study aimed to (1) estimate the reporting rate of the AEs of HMs using PV databases and (2) assess the detailed data provided in AE reports.

METHODS: In this systematic review and meta-analysis, MEDLINE/PubMed, SCOPUS, EMBASE, and CINAHL were systematically searched for relevant studies (until December 2023). The DerSimonian-Laird random effects model was used for pooling the data, and subgroup analyses, the meta-regression model, and sensitivity analysis were used to explore the source of heterogeneity. Crombie's checklist was used to evaluate the risk of bias (ROB) of the included studies.

RESULTS: In total, 26 studies met the eligibility criteria. The reporting rate of the AEs of HMs ranged considerably, from 0.03% to 29.84%, with a median overall pooled estimate of 1.42% (IQR 1.12%-1.72%). Subgroup analyses combined with the meta-regression model revealed that the reporting rate of the AEs of HMs was associated with the source of the reporter (P=.01). None of the included studies provided full details of suspected herbal products, only the main ingredients were disclosed, and other potentially harmful components were not listed.

CONCLUSIONS: This systematic review and meta-analysis highlighted risks related to HMs, with a wide range of reporting rates, depending on the source of the reporter. Continuous efforts are necessary to standardize consumer reporting systems in terms of the reporting form, education, and follow-up strategy to improve data quality assurance, aiming to enhance the reliability and utility of PV data for monitoring the safety of HMs. Achieving effective monitoring and reporting of these AEs necessitates collaborative efforts from diverse stakeholders, including patients/consumers, manufacturers, physicians, complementary practitioners, sellers/distributors, and health authorities.

TRIAL REGISTRATION: PROSPERO (Prospective International Register of Systematic Reviews) CRD42021276492.

PMID:39208414 | DOI:10.2196/63808

PLoS One. 2024 Aug 29;19(8):e0309362. doi: 10.1371/journal.pone.0309362. eCollection 2024.

ABSTRACT

BACKGROUND: Drug, medicament, and biological substance poisoning, adverse effects, and underdosing are significant public health concerns. Gaining insight into the patterns and trends in hospitalizations caused by these occurrences is essential for the development of preventative initiatives, optimization of treatment regimens, and improvement of patient safety. The aim of this study is to examine the trend of hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019.

METHODS: This is an ecological descriptive study that examined hospitalisation related to poisoning by, adverse effect of and underdosing of drugs, medicaments and biological substances in Australia between 1998 and 2019. A nationwide hospital admissions database was used for this study.

RESULTS: Between 1998 and 2019, a total of 683,869 hospital admission episodes were recorded in Australia. The overall annual number of hospital admissions for various reasons increased by 20.5% from 29,854 in 1998 to 35,960 in 2019, representing a decrease in hospital admission rate of 10.6% [from 158.69 (95% CI 156.90-160.49) in 1998 to 141.91 (95% CI 140.44-143.37) in 2019 per 100,000 persons, trend test, p<0.05]. Overnight-stay admissions accounted for 69.2% of the total number of hospital admissions, and 30.8% were same-day admissions. Rates of same-day hospital admission decreased by 13.3% [from 50.55 (95%CI 49.54-51.57) in 1998 to 43.81 (95%CI 43.00-44.63) in 2019 per 100,000 persons]. Rates of overnight-stay hospital admission decreased by 11.1% [from 108.14 (95%CI 106.66-109.63) in 1998 to 96.17 (95%CI 94.96-97.38) in 2019 per 100,000 persons]. Admissions related to antiepileptic, sedative-hypnotic and antiparkinsonism drugs was the most prevalent hospital admissions type accounting for 26.8%. Females were responsible for 418,751 hospital admission episodes, representing 61.5% of the total number of hospital admission.

CONCLUSION: This study found that while the overall annual number of admissions increased, the rate of admission decreased over the same period. The most common reasons for admissions were antiepileptic, sedative-hypnotic, and anti-parkinsonism drugs. The study also noted increases in admissions related to anaesthetics, therapeutic gases, hormones, and their synthetic substitutes. These findings suggest a concerning rise in the suboptimal use of these medications. In order to combat the increasing incidence of this type of admissions, it is imperative to strengthen public awareness initiatives on medicine safety and abuse.

PMID:39208193 | DOI:10.1371/journal.pone.0309362

Clin Endosc. 2024 Aug 29. doi: 10.5946/ce.2024.003. Online ahead of print.

ABSTRACT

The use of immune checkpoint inhibitors (ICIs) for the treatment of various malignancies is increasing. Immune-related adverse events can occur after ICI administration, with gastrointestinal adverse events constituting a significant proportion of these events. When ICI-related diarrhea/colitis is suspected, endoscopic evaluation is recommended to differentiate it from other etiologies and assess the severity of colitis. The distribution of intestinal inflammation in ICI-related colitis demonstrates a high frequency of extensive colitis (23-86%). However, isolated right-sided colitis (3-8%) and ileitis (2-16%) are less prevalent. Endoscopic findings vary and predominantly encompass features indicative of inflammatory bowel disease, including aphthae, ulcers, diffuse or patchy erythema, mucosal edema, loss of vascular pattern, and friability. The presence of ulcers and extensive intestinal inflammation are associated with a reduced response to treatment. Microscopic inflammation can be observed even in endoscopically normal mucosa, underscoring the need for biopsies of seemingly normal mucosa. Histological findings present with acute/chronic inflammation and occasionally exhibit characteristics observed in inflammatory bowel disease, microscopic colitis, or ischemic colitis. The first-line therapeutic choice for ICI-related diarrhea/colitis with a common terminology criteria for adverse events grade of 2 or above is corticosteroids, whereas infliximab and vedolizumab are recommended for refractory cases.

PMID:39206499 | DOI:10.5946/ce.2024.003

Glob Pediatr Health. 2024 Aug 27;11:2333794X241273171. doi: 10.1177/2333794X241273171. eCollection 2024.

ABSTRACT

Objective. Children's vulnerability to drug-related side effects has been highlighted in several studies. However, there is no consensus on the risk factors associated with these side effects. This study aimed to investigate risk factors associated with drug-related side effects in children. Methods. This scoping review was conducted across multiple databases. The search strategy was created with a focus on drug-related side effects, as they are more predictable based on the pre-determined risk factors. Data were collected, and reported narratively. Results. The demographic, health, hospital, and drug-related risk factors may cause drug-related side effects in children. Among them, low age, sex, polypharmacy, length of hospitalization, and medications used for comorbidities may increase the risk. Conclusion. While most of the risk factors might be similar in adults and children, their impact might be different in these 2 groups. Therefore, future studies should identify more details about the impact of the risk factors in children.

PMID:39205860 | PMC:PMC11350535 | DOI:10.1177/2333794X241273171

Liver Int. 2024 Sep;44(9):2469-2476. doi: 10.1111/liv.16014. Epub 2024 Jun 22.

ABSTRACT

BACKGROUND & AIMS: The benefits of prophylactic antibiotics in patients with alcohol-associated hepatitis (AH) receiving steroids remain unclear. We aimed to assess the clinical impact of prophylactic antibiotics in AH patients receiving steroids.

METHODS: We systematically reviewed four electronic databases from inception to 30 November 2023. Pooled estimates were analysed using random-effects models. The primary outcome was 90-day survival. Secondary outcomes included infection at days 30 and 90 days, hepatorenal syndrome (HRS), acute kidney injury (AKI), hepatic encephalopathy (HE) and drug-related adverse events (AE). Trial sequential analyses were performed for the primary outcome of 90-day mortality.

RESULTS: We screened 419 articles and included six eligible studies (four RCTs and two matched cohort studies) with a total of 510 patients. Compared to standard medical treatment (SMT), prophylactic antibiotics were associated with a lower risk of infection at 30 days (OR: 0.35, 95%CI: 0.20-0.59, I 2 = 0%), infection at 90 days (OR: 0.26, 95%CI: 0.10-0.67, I 2 = 0%) and a lower rate of HE (OR: 0.32, 95%CI: 0.12-0.87, I 2 = 0%). However, prophylactic antibiotics did not improve 90-day survival, sepsis-related mortality, HRS, or AKI. The risks of drug-related AE and fungal infections were similar in patients with AH who received prophylactic antibiotics or SMT. Using trial sequential analysis, the minimum sample size required to detect a 15% relative risk reduction in 90 days mortality with prophylactic antibiotics was 1171.

CONCLUSIONS: In hospitalized AH patients receiving steroid therapy, prophylactic antibiotics reduced the risk of infection and HE, but did not improve survival or prevent AKI compared to SMT.

PMID:39205440 | DOI:10.1111/liv.16014

Pharmaceuticals (Basel). 2024 Aug 22;17(8):1099. doi: 10.3390/ph17081099.

ABSTRACT

Specific drugs are well known to have the capacity to induce Parkinson-like symptoms. Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Pharmaceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with the associated drug trends and characteristics. Our findings indicate that similar to Parkinson's disease, age-related differences affect the onset of these reported events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, the side effects can vary depending on the site of action. These insights underline the importance of the swift identification of the drugs suspected of causing these events and the implementation of measures to reduce their side effects.

PMID:39204204 | DOI:10.3390/ph17081099

J Clin Med. 2024 Aug 18;13(16):4869. doi: 10.3390/jcm13164869.

ABSTRACT

Introduction: Adverse drug reactions are a significant problem in modern society, stemming from the increase in prescribed medications, over-the-counter drugs, and overall polypharmacy. Glomerular disorders are one of the frequently reported renal conditions associated with medication use. VigiBase is a significant tool for evaluating events associated with drug use, and, to the authors' knowledge, no study has yet assessed this database to identify the primary medications associated with glomerular disorders. Materials and Methods: We collected data from VigiBase for 54 years and evaluated data based on global frequencies, disproportionality (IC025 values), nephrotoxic potential, and physiopathological mechanisms. Results: Over the evaluation period, 33.932.051 spontaneous notifications of adverse drug reactions reported in VigiBase were assessed, from which 106.775 notifications of drug-associated glomerular disorders were extracted. The isolated medications were classified as 'potential nephrotoxins' (47.0%), with 40% of the medications lacking scientific references to report any association with the development of glomerular disorders. Among the evaluated medications, Inotersen (IC025 of 8.3), Penicillamine (IC025 6.8), Bevacizumab (IC025 5.9) and Lenvatinib (IC025 5.4) were identified as having the strongest association with these glomerular disorders. For medications classified as 'non-nephrotoxic', a high disproportionality index was observed, suggesting drugs that might be considered as new potential nephrotoxins. Conclusions: Drug-induced glomerular disorders were significantly associated with medications that had no established nephrotoxic role but demonstrated a high disproportionality index in VigiBase. These newly alleged nephrotoxic drugs warrant further evaluation in dedicated studies to assess their true nephrotoxic potential.

PMID:39201010 | DOI:10.3390/jcm13164869

Korean J Radiol. 2024 Sep;25(9):824-832. doi: 10.3348/kjr.2024.0248.

ABSTRACT

OBJECTIVE: To determine the preventive effect of changing gadolinium-based contrast agents (GBCAs) to reduce the recurrence of GBCA-associated acute adverse drug reactions (ADRs).

MATERIALS AND METHODS: This retrospective, observational, single-center study-conducted between January 2016 and December 2021-included 238743 consecutive GBCA-enhanced MRI examinations. We focused on a subgroup of patients who experienced acute GBCA-associated ADRs during any of these examinations and subsequently underwent follow-up GBCA-enhanced MRI examinations up until July 2023. The follow-up examinations involved either the same (non-change group) or different (change group) GBCAs compared to the ones that initially caused the acute ADR. Baseline participant characteristics, generic profile of the GBCAs, administration of premedication, history of prior ADR to iodinated contrast media, and symptoms of GBCA-associated acute ADRs were retrospectively analyzed. Multivariable logistic regression with generalized estimating equations and propensity score matching were used.

RESULTS: A total of 1042 instances of acute ADRs (0.44%; 95% confidence interval [CI]: 0.41%-0.46%) were reported. Three-hundred and seventy-three patients underwent GBCA-enhanced MRI examinations after experiencing GBCA-associated acute ADRs within the study period; 31.9% (119/373) reexperienced acute ADRs at any of the follow-up examinations. The ADR recurrence was significantly lower in the GBCA change group than in the non-change group according to multivariable logistic regression (adjusted odds ratio [OR]: 0.35; 95% CI: 0.13-0.90; P = 0.03) and analysis with propensity score matching (14.3% [6/42] vs. 36.9% [31/84], respectively; OR: 0.32, 95% CI: 0.11-0.94; P = 0.04). A history of an ADR to iodinated contrast media (OR: 1.14, 95% CI: 0.68-1.90; P = 0.62) and premedication (adjusted OR: 2.09, 95% CI: 0.93-4.68; P = 0.07) were not significantly associated with GBCA-associated acute ADR recurrence. A separate analysis for recurrent allergic-like hypersensitivity reactions demonstrated similar results (adjusted OR: 0.20, 95% CI: 0.06-0.65; P < 0.01).

CONCLUSION: Changing GBCAs may reduce the risk of GBCA-associated acute ADR recurrence.

PMID:39197827 | DOI:10.3348/kjr.2024.0248

J Gerontol Nurs. 2024 Sep;50(9):7-11. doi: 10.3928/00989134-20240809-03. Epub 2024 Sep 1.

ABSTRACT

PURPOSE: To define prescribing cascades (PCs) and provide tools to identify PCs, including the most common PCs described in the literature. PCs lead to the accumulation of medications prescribed to older adults, disproportionately affecting those who often have additional health care complexities, such as multiple chronic conditions and multiple transitions of care.

METHOD: Review of recent research efforts to identify and describe evolving clinical practice interventions to detect and reverse PCs.

RESULTS: Clinicians can contribute to mitigating PCs through better understanding of how PCs occur in practice. Armed with this knowledge, clinical team members can implement proposed strategies and techniques to engage in primary and secondary prevention of PCs.

CONCLUSION: Ultimately, PCs are a culprit of preventable medication harm. Several tools are presented, which are initiated through maintaining a high index of suspicion for PCs in the evaluation of a new symptom presentation by older patients. [Journal of Gerontological Nursing, 50(9), 7-11.].

PMID:39194326 | DOI:10.3928/00989134-20240809-03

J Pharm Health Care Sci. 2024 Aug 27;10(1):52. doi: 10.1186/s40780-024-00373-7.

ABSTRACT

BACKGROUND: Interstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD. Furthermore, the factors that lead the attending physician to suspect ICI-induced ILD (ICI-ILD) remain unclear. This study aimed to investigate the ICI-ILD detection based on subjective symptoms and their relationship with disease severity in patients receiving anti-PD-1/PD-L1 antibody.

METHODS: This was a retrospective observational study. We enrolled the patients who received anti-PD-1/PD-L1 antibody at Kyoto University Hospital between September 2014 and April 2021. Patients who developed ICI-ILD were stratified into two distinct groups based on factors that triggered the suspicion of ILD development. The "Subjective symptoms" group was defined as patients in whom ILD was detected based on subjective symptoms. Conversely, the "Routine examinations" group was defined as patients in whom ILD was suspected based on scheduled routine examinations. The severity of ILD in each group was assessed and its association with changes in the respiratory symptoms was examined.

RESULTS: Of 926 patients who received anti-PD-1/PD-L1 antibody, 51 patients (5.5%) developed ICI-ILD. The incidence of ICI-ILD in patients with lung cancer was significantly higher than that in patients with other cancers (P < 0.001). Among the patients with ICI-ILD, 27 patients (52.9%) were classified into the "Subjective symptoms" group. The "Subjective symptoms" group exhibited a significantly higher proportion of Grade 3-5 ICI-ILD cases than the "Routine examinations" group (76.2% vs. 23.8%, P = 0.010). At the last visit, before the suspected onset of ILD, 21 of the 27 patients (77.8%) had no symptoms or no change in the respiratory symptoms.

CONCLUSION: Subjective symptoms triggered the suspicion of Grade 3-5 ICI-ILD. Enhanced monitoring and patient education could be essential for the early detection of ICI-ILD because ILD may develop rapidly. Our findings might help to manage ICI-ILD in clinical practice.

PMID:39192314 | DOI:10.1186/s40780-024-00373-7

J Transl Med. 2024 Aug 27;22(1):789. doi: 10.1186/s12967-024-05439-6.

ABSTRACT

BACKGROUND: Kidneys are at risk from drug-induced toxicity, with a significant proportion of acute kidney injury (AKI) linked to medications, particularly cisplatin. Existing cytoprotective drugs for cisplatin-AKI carry side effects, prompting a search for better biological therapies. Mesenchymal Stem Cells (MSCs) are under consideration given their regenerative properties, yet their clinical application has not achieved their full potential, mainly due to variability in the source of MSC tested. In addition, translating treatments from rodent models to humans remains challenging due to a lack of standardized dosing and understanding potential differential responses to cisplatin between animal strains.

METHOD: In the current study, we performed a time-course analysis of the effect of cisplatin across different mouse strains and evaluated gender related differences to create a robust preclinical model that could then be used to explore the therapeutic efficacy of different sources of MSCs for their ability to reverse AKI.

RESULT: Our data indicated that different mouse strains produce differential responses to the same cisplatin dosing regimen. Despite this, we did not observe any gender-related bias towards cisplatin nephrotoxicity. Furthermore, our time-course analysis identified that cisplatin-induced inflammation was driven by a strong CXCL1 response, which was used as a putative biomarker to evaluate the comparative therapeutic efficacy of different MSC sources in reversing AKI. Our data indicates that UC-MSCs have a stronger anti-inflammatory effect compared to BM-MSCs and AD-MSCs, which helped to ameliorate cisplatin-AKI.

CONCLUSION: Overall, our data underscores the importance of using an optimized preclinical model of cisplatin-AKI to test different therapies. We identified CXCL1 as a potential biomarker of cisplatin-AKI and identified the superior efficacy of UC-MSCs in mitigating cisplatin-AKI.

PMID:39192240 | DOI:10.1186/s12967-024-05439-6

In Vivo. 2024 Sep-Oct;38(5):2098-2106. doi: 10.21873/invivo.13671.

ABSTRACT

BACKGROUND/AIM: Genomic variants can predispose individuals to adverse drug effects (ADEs), implying the potential for personalised therapy based on genetic data to prevent them. However, existing pharmacogenomic databases lack a comprehensive list of such variants due to irregular updates and incomplete literature coverage. To facilitate the assessment of the feasibility of using pharmacogenetic testing on a larger scale and identify existing gaps in the literature, this study sought to compile a comprehensive list of genomic variants associated with ADEs, with a focus on serious ADEs.

PATIENTS AND METHODS: To identify relevant pharmacogenetic studies within randomised controlled trials (RCTs), post-hoc studies of RCTs and meta-analyses, two literature searches were performed across multiple databases. The compiled list of variants associated with ADEs was refined to create a set of variant-drug pairs significantly associated with serious ADEs.

RESULTS: We identified 254 RCTs/post-hoc studies and 207 meta-analyses investigating variants associated with ADEs. Among the 254 RCTs/post-hoc studies identified, 24 meta-analyses were conducted. Among these, only G6PD A- showed a significant association with severe anaemia in patients receiving artemisinin-based treatment for malaria.

CONCLUSION: This systematic review provides a comprehensive list of variants associated with ADEs and a set of variant-drug pairs significantly associated with serious ADEs. These resources serve as valuable references for regulatory agencies, researchers, and healthcare professionals. This study, however, underscores the need for improved indexing and standardised definitions of ADE seriousness in the literature.

PMID:39187310 | DOI:10.21873/invivo.13671

Lupus. 2024 Aug 26:9612033241279071. doi: 10.1177/09612033241279071. Online ahead of print.

ABSTRACT

OBJECTIVE: Systemic lupus erythematosus (SLE) constitutes an autoimmune disorder with potential involvement of the gastrointestinal system (GIS). Our objective was to assess the gastrointestinal (GI) manifestations in patients diagnosed with childhood onset SLE.

METHODS: The study cohort consisted of 123 patients with childhood onset-SLE and GIS involvement from 16 referral departments of pediatric rheumatology. All participants met the Systemic Lupus International Collaborating Clinics criteria.

RESULTS: Out of 123 patients, 78 (63.4%) exhibited GIS involvement at the initial SLE diagnosis, whereas the remaining 45 (36.6%) developed GI symptoms after a median duration of 12 (3-140) months. Eighty-two (66.7%) individuals experienced symptoms related to the GI tract, whereas the remaining patients received a diagnosis of GI involvement through laboratory assessments. The predominant initial GIS involvement symptom was abdominal pain, observed in 77 (62.6%) patients, followed by elevated hepatic transaminases in 70 (56.9%), hepatomegaly in 40 (32.5%), diarrhea in 26 (21.1%), and jaundice in 11 (8.9%) patients. The GIS involvement was associated with SLE in 82 (78.6%), while it resulted from drug-related adverse events in 35 (28.5%) patients or comorbidities in 6 (0.5%) patients.

CONCLUSION: GIS involvement should be considered in all childhood onset-SLE patients, especially in the presence of suggestive symptoms or elevated hepatic transaminases. It is also crucial to consider SLE in the differential diagnosis of GIS manifestations in children. Apart from GIS involvement directly associated with SLE, adverse events of drugs should be kept in mind.

PMID:39186467 | DOI:10.1177/09612033241279071

Front Med (Lausanne). 2024 Aug 7;11:1370481. doi: 10.3389/fmed.2024.1370481. eCollection 2024.

ABSTRACT

BACKGROUND: The purpose of this network meta-analysis (NMA) was to evaluate the efficacy of intravenous opioid μ-receptor analgesics in shortening the duration of mechanical ventilation (MV) in ICU patients.

METHODS: Randomized controlled trials comparing the efficacy of remifentanil, sufentanil, morphine, and fentanyl on the duration of MV in ICU patients were searched in Embase, Cochrane, Pubmed, and Web of Science electronic databases. The primary outcome was MV duration. The Bayesian random-effects framework was used to evaluate relative efficacy.

RESULTS: In total 20 studies were included in this NMA involving 3,442 patients. Remifentanil was not associated with a reduction in the duration of MV compared with fentanyl (mean difference (MD) -0.16; 95% credible interval (CrI): -4.75 ~ 5.63) and morphine (MD 3.84; 95% CrI: -0.29 ~ 10.68). The secondary outcomes showed that, compared with remifentanil, sufentanil can prolong the duration of extubation. No regimen significantly shortened the ICU length of stay and improved the ICU mortality, efficacy, safety, and drug-related adverse events.

CONCLUSION: Among these analgesics, remifentanil did not appear to be associated with a reduction in MV duration. Clinicians should carefully titrate the analgesia of MV patients to prevent a potentially prolonged duration of MV due to excessive or inadequate analgesic therapy.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, CRD42021232604.

PMID:39185471 | PMC:PMC11342801 | DOI:10.3389/fmed.2024.1370481

Clin Ther. 2024 Aug 24:S0149-2918(24)00211-X. doi: 10.1016/j.clinthera.2024.07.012. Online ahead of print.

ABSTRACT

PURPOSE: Cardiac implantable electronic device (CIED) infections are increasingly common. Gram-positive bacteria such as coagulase negative staphylococci and Staphylococcus aureus are the most commonly involved pathogens. The aim of this study was to describe the characteristics and outcome of patients with CIED infections who underwent device removal and were empirically treated with high dose (8-12 mg/kg daily) daptomycin (DAP) in combination with ceftriaxone (CRO).

METHODS: Retrospective, single center study including patients admitted at IRCCS San Raffaele Hospital (Milan, Italy), from June 2011 to June 2021, who underwent device removal for CIED infection and were empirically treated with DAP/CRO.

FINDINGS: Overall, 147 patients were included in this study. Median duration of therapy was 16 days (IQR 14-26). Empirical treatment with DAP/CRO was confirmed as definitive treatment in 140 patients (95.2%). In 7 (4.8%) patients DAP/CRO were discontinued according to the definite microbiological isolates: Corynebacterium spp. (4), Pseudomonas aeruginosa (2), Enterobacter cloacae (1). Ten patients (6.8%) underwent treatment simplification to narrow-spectrum antibiotics. One patient (0.6%) interrupted DAP-CRO due to pancytopenia. 6-month follow-up was available for 123/147 patients (83.7%): 9 patients recurred with a CIED infection (7.3%), and 9 died (7.3%).

IMPLICATIONS: In our 10-year experience, high-dose DAP in combination with CRO represented a good option for empirical therapy of CIED infections. DAP-CRO combination was safe and effective, showing no significant drug-related adverse events and low rates of 6-month recurrence and mortality.

PMID:39183124 | DOI:10.1016/j.clinthera.2024.07.012

Lancet. 2024 Aug 24;404(10454):764-772. doi: 10.1016/S0140-6736(24)01357-6.

ABSTRACT

BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza.

METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450.

FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies.

INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans.

FUNDING: World Health Organization.

PMID:39181596 | DOI:10.1016/S0140-6736(24)01357-6

BMC Health Serv Res. 2024 Aug 23;24(1):975. doi: 10.1186/s12913-024-11346-9.

ABSTRACT

OBJECTIVE: To perform a cost study of pharmacist-led medication reviews in patients with an acute hospitalization for adverse drug events.

METHOD: Emergency department pharmacists performed medication reviews in patients hospitalized after visiting the emergency department for an adverse drug event (ADE). Control patients were hospitalized after an emergency department visit not related to an ADE and received usual care. The costs of the intervention were labour costs of the junior emergency department pharmacist and the cost savings consisted of costs of medication that was stopped or reduced during six months after the intervention. Sensitivity analyses were performed to evaluate different scenarios.

RESULTS: In the intervention group (n = 104) 113 medication changes led to stopping or reducing medication, accounting for averted costs of €22,850. In the control group (n = 112) 39 medication changes led to stopping or reducing medication, accounting for averted costs of €299. The mean labour costs of the intervention were €138 per patient, resulting in saved costs of €61 per patient per six months. Sensitivity analyses showed that if the intervention would be performed by a senior clinical pharmacist, there are no cost savings (€-21), if parts of the intervention would be executed by pharmacy technicians (e.g. administrative tasks), cost savings would be augmented to €87, if outliers in costs associated with medication reduction would be excluded, there are no cost savings (€-35) and if the costs of reduced medication were extrapolated to one year, cost savings would be €260.

CONCLUSION: In this study, medication reviews by junior emergency department pharmacists in patients hospitalized after an emergency department visit for an ADE lead to a cost reduction over a six month period.

TRIAL REGISTRATION: The main study is registered on the ISRCTN registry with trial ID ISRCTN12506329 on 06-03-2022.

PMID:39180043 | DOI:10.1186/s12913-024-11346-9

Stud Health Technol Inform. 2024 Aug 22;316:873-874. doi: 10.3233/SHTI240550.

ABSTRACT

Artificial Intelligence (AI), particularly Machine Learning (ML), has gained attention for its potential in various domains. However, approaches integrating symbolic AI with ML on Knowledge Graphs have not gained significant focus yet. We argue that exploiting RDF/OWL semantics while conducting ML could provide useful insights. We present a use case using signaling pathways from the Reactome database to explore drug safety. Promising outcomes suggest the need for further investigation and collaboration with domain experts.

PMID:39176931 | DOI:10.3233/SHTI240550

Stud Health Technol Inform. 2024 Aug 22;316:803-807. doi: 10.3233/SHTI240533.

ABSTRACT

Causal Deep/Machine Learning (CDL/CML) is an emerging Artificial Intelligence (AI) paradigm. The combination of causal inference and AI could mine explainable causal relationships between data features, providing useful insights for various applications, e.g. Pharmacovigilance (PV) signal detection upon Real-World Data. The objective of this study is to demonstrate the use of CDL for potential PV signal validation using Electronic Health Records as input data source.

PMID:39176914 | DOI:10.3233/SHTI240533