BMC Med Inform Decis Mak. 2024 Jul 4;24(1):188. doi: 10.1186/s12911-024-02596-y.

ABSTRACT

BACKGROUND: Medication errors and associated adverse drug events (ADE) are a major cause of morbidity and mortality worldwide. In recent years, the prevention of medication errors has become a high priority in healthcare systems. In order to improve medication safety, computerized Clinical Decision Support Systems (CDSS) are increasingly being integrated into the medication process. Accordingly, a growing number of studies have investigated the medication safety-related effectiveness of CDSS. However, the outcome measures used are heterogeneous, leading to unclear evidence. The primary aim of this study is to summarize and categorize the outcomes used in interventional studies evaluating the effects of CDSS on medication safety in primary and long-term care.

METHODS: We systematically searched PubMed, Embase, CINAHL, and Cochrane Library for interventional studies evaluating the effects of CDSS targeting medication safety and patient-related outcomes. We extracted methodological characteristics, outcomes and empirical findings from the included studies. Outcomes were assigned to three main categories: process-related, harm-related, and cost-related. Risk of bias was assessed using the Evidence Project risk of bias tool.

RESULTS: Thirty-two studies met the inclusion criteria. Almost all studies (n = 31) used process-related outcomes, followed by harm-related outcomes (n = 11). Only three studies used cost-related outcomes. Most studies used outcomes from only one category and no study used outcomes from all three categories. The definition and operationalization of outcomes varied widely between the included studies, even within outcome categories. Overall, evidence on CDSS effectiveness was mixed. A significant intervention effect was demonstrated by nine of fifteen studies with process-related primary outcomes (60%) but only one out of five studies with harm-related primary outcomes (20%). The included studies faced a number of methodological problems that limit the comparability and generalizability of their results.

CONCLUSIONS: Evidence on the effectiveness of CDSS is currently inconclusive due in part to inconsistent outcome definitions and methodological problems in the literature. Additional high-quality studies are therefore needed to provide a comprehensive account of CDSS effectiveness. These studies should follow established methodological guidelines and recommendations and use a comprehensive set of harm-, process- and cost-related outcomes with agreed-upon and consistent definitions.

PROSPERO REGISTRATION: CRD42023464746.

PMID:38965569 | DOI:10.1186/s12911-024-02596-y

Eur J Hosp Pharm. 2024 Jul 4:ejhpharm-2024-004209. doi: 10.1136/ejhpharm-2024-004209. Online ahead of print.

ABSTRACT

Thrombotic microangiopathy is a serious condition that can be precipitated by exposure to certain medications. Although rare, it is life threatening and requires a high index of clinical suspicion, appropriate laboratory testing and immediate cessation of the offending agent. We present a case of a 75-year-old man with a history of ischaemic heart disease treated with clopidogrel and aspirin. One month after initiating the treatment he developed microangiopathic haemolytic anaemia and thrombocytopenia. Extensive clinical and laboratory investigations suggested thrombotic microangiopathy secondary to clopidogrel. The drug was immediately discontinued and treatment with intravenous corticosteroids was started. Within a week the patient's laboratory parameters normalised, indicating successful recovery. This case highlights the role of early detection and immediate discontinuation of suspected medication in the effective management of clopidogrel-induced thrombotic microangiopathy. Healthcare professionals should consider drug-induced thrombotic microangiopathy as a possible diagnosis in patients receiving clopidogrel who present with thrombocytopenia and microangiopathic haemolytic anaemia.

PMID:38964832 | DOI:10.1136/ejhpharm-2024-004209

Eur J Hosp Pharm. 2024 Jul 4:ejhpharm-2024-004222. doi: 10.1136/ejhpharm-2024-004222. Online ahead of print.

ABSTRACT

OBJECTIVES: Preoperative medication errors can be prevented by screening patients through a preoperative pharmaceutical care consultation. The aim of this study was to analyse the cost-effectiveness of implementing such a consultation and to determine which patients would benefit most.

METHODS: A retrospective study was conducted that included all patients who underwent a preoperative pharmacy consultation between 2016 and 2020. During this consultation, two part-time pharmacists reviewed patients' appropriate preoperative chronic medication management. All prevented errors were collected and classified by therapeutic group and type of error. A team of pharmacists and anaesthetists assigned to each prevented medication error a probability of causing an adverse event 'p', following the methodology of Nesbit et al by establishing five different 'p' values: 0, 0.01, 0.1, 0.4, and 0.6. 'p' = 1 was not considered. The cost of an adverse event was determined to be between €4124 and €6946 according to current literature, and a sensitivity analysis was performed by increasing the interval by 20% above and below. The cost of employing two part-time specialist pharmacists was estimated to be €59 142. Savings per medication error prevented were calculated as (€4124 OR €6946) × 'p'. Total savings were the sum of all costs associated with prevented medication errors. Patients on chronic medications who were in therapeutic groups with a 0.6 probability of an adverse event or who were in therapeutic groups responsible for 50% of the prevented adverse events were considered prioritisable.

RESULTS: 3105 patients attended the consultation and 1179 medication errors were prevented, corresponding to 300 adverse events. 42.2% of the errors had a 'p' of 0.4. The costs avoided by this consultation ranged from €1 237 200 to €2 083 800, while the cost of its implementation was €295 710. The cost-effectiveness ratio was between €4.2 and €7.0 saved per euro invested. In the sensitivity analysis, the ratios ranged from €3.3 to €8.5 per euro invested. Fifteen different therapeutic groups accounted for 90% of the medication errors prevented. The therapeutic groups 'Agents acting on the renin-angiotensin system', 'Antidiabetics, non-insulin (excluding SGLT2)' and 'Antithrombotics: low molecular weight heparins' were responsible for 56% of the prevented adverse events. The therapeutic groups 'Antidiabetics: rapid-acting insulin' and 'Antithrombotic agents: vitamin K antagonists, low-molecular-weight heparins, or direct oral anticoagulants' had a 'p' of 0.6. Therefore, patients in six therapeutic groups should be prioritised for preoperative pharmacy counselling.

CONCLUSIONS: The implementation of preoperative pharmaceutical care consultations in Spain has proven to be cost-effective. Incorporating the probability of a medication error causing an adverse event allowed the prioritisation of patients for these consultations. Patients taking anticoagulants, oral antidiabetics, rapid-acting insulins, and agents acting on the renin-angiotensin system benefited the most. This study could serve as a basis for implementing such consultations in other hospitals, as they are effective in reducing the cost of medication errors in surgical patients.

PMID:38964831 | DOI:10.1136/ejhpharm-2024-004222

J Immunother Cancer. 2024 Jul 4;12(7):e008591. doi: 10.1136/jitc-2023-008591.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, improving outcomes for many patients. However, toxicities termed immune-related adverse events (irAEs) are limitations of these revolutionary treatments. These irAEs may resolve with treatment or ICI cessation (acute) or persist many months beyond therapy cessation (chronic). Acute irAEs were the first to be recognized and are thus more well studied. However, chronic irAEs have been highlighted in recent years and are becoming a topic of more intensive investigation. These chronic irAEs have been noted to affect many different organ systems, including endocrine, rheumatologic, gastrointestinal, dermatologic, neurologic, and cardiovascular systems. In this review, we discuss current knowledge surrounding the frequency, time course, and risk factors associated with chronic irAEs affecting various organ systems, treatment approaches, and future directions.

PMID:38964785 | DOI:10.1136/jitc-2023-008591

Cureus. 2024 Jun 3;16(6):e61562. doi: 10.7759/cureus.61562. eCollection 2024 Jun.

ABSTRACT

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

PMID:38962632 | PMC:PMC11220731 | DOI:10.7759/cureus.61562

Cureus. 2024 Jun 2;16(6):e61551. doi: 10.7759/cureus.61551. eCollection 2024 Jun.

ABSTRACT

Introduction Mechanical low back pain frequently originates from the lumbar facet joint (LFJ). Axial low back discomfort can result from osteoarthritis in the LFJ. Depending on the severity of LFJ degeneration, the effect of intra-articular (IA) LFJ corticosteroid injection may vary. For LFJ discomfort, IA block with steroids and local anaesthetics has also been utilised, with varying degrees of success. The main objective of this study was to assess the efficacy of IA steroid injections dexamethasone vs. triamcinolone acetonide for the treatment of LFJ syndrome and to compare functional outcome in terms of Visual Analog Scale (VAS) score, Modified Oswestry Disability Index (MODI) score, and short-form McGill Pain Questionnaire between the two groups. Methodology Dexamethasone 8 mg or triamcinolone acetonide 40 mg was given intra-articularly to 27 patients comprising group A and 33 patients comprising group B, respectively (total 60 patients). Before intervention and at one, three, and six months, observation was conducted using the VAS score, short-form McGill pain questionnaire, and MODI score. Results There was a significant difference between both the groups after the procedure with pain alleviation and functional improvement, more in the group that received triamcinolone acetonide. A significant difference was observed in all three parameters that assessed pain with differences more pronounced at six months. Conclusion Pain reduction and clinical outcomes were better among the group that received triamcinolone acetonide. Injection of a steroid alone is associated with its own side effects. When a lumbar transforaminal epidural injection is used to treat radiculopathy in the lumbar area, particulate medication (triamcinolone) is more effective than non-particulate medication (dexamethasone) with no known drug-related complications.

PMID:38962603 | PMC:PMC11220230 | DOI:10.7759/cureus.61551

Cureus. 2024 Jun 3;16(6):e61559. doi: 10.7759/cureus.61559. eCollection 2024 Jun.

ABSTRACT

Yawning is a normal physiological process that occurs naturally in all human beings in different settings, such as hunger, drowsiness, or stress. It is typically harmless, but abnormal yawning can be seen in many medical conditions. In psychiatry, it frequently occurs in disorders like depression, insomnia, and anxiety due to disturbed sleep. It has also been observed as an adverse reaction of some drugs, like escitalopram, a selective serotonin reuptake inhibitor. Escitalopram is a widely prescribed, well-tolerated antidepressant and antianxiety drug that can induce a range of side effects, one of which is excessive yawning. Its excessive occurrence can be distressing for patients, affecting their socio-occupational functioning. Clinically, differentiating yawning induced by escitalopram treatment from that in depression can be a diagnostic hurdle. Awareness and recognition of this lesser known side effect can improve patient outcomes by allowing for timely adjustments and easing the discomfort.

PMID:38962587 | PMC:PMC11221399 | DOI:10.7759/cureus.61559

Acta Clin Belg. 2024 Jul 3:1-8. doi: 10.1080/17843286.2024.2376304. Online ahead of print.

ABSTRACT

Patients with hepatoblastoma featuring carcinoma characteristics have better outcomes after liver transplantation, than after chemotherapy and resection. Possibly this should be extrapolated to aggressive subtypes of hepatocellular carcinomas in non-cirrhotic livers, where early liver transplantation might also be indicated. However, the risks associated with liver transplantation and immunosuppressive treatment after liver transplantation are once again demonstrated by this case of a 32-year-old women with a negative personal and familial history of liver diseases. She underwent transplantation (DBD) for a hepatocellular carcinoma with stem cell features (HCC-HS; an aggressive 'hepatoblast subtype' of hepatocellular carcinoma) after chemotherapeutical downstaging techniques failed to sufficiently downstage the tumor. Despite being on conventional immunosuppressive regimens (tacrolimus and mycophenolate mofetil with initial corticosteroids tapered), this patient still developed two severe rejection episodes, one of which necessitated retransplantation (DCD). Both episodes were preceded by alterations in tacrolimus trough levels, either intentionally, when tacrolimus was reduced within a nephroprotective regimen, or unintentionally, when rifampicin, a CYP3A4 inducer, significantly lowered the trough levels. Together, these episodes stress the importance of therapeutic drug monitoring of tacrolimus. Furthermore, the patient experienced an everolimus-linked drug-induced thrombotic microangiopathy, underwent multiple ERCPs for an anastomotic stricture and only one and a half year after the first liver transplantation she already suffers from long-term immunosuppressive-related side effects such as impaired glucose tolerance, hypertension and a potential cardiomyopathy. At present, she is still alive and experienced no recurrence of her primary tumor. Her case underscores the significant challenges in post-liver transplantation care.

PMID:38961614 | DOI:10.1080/17843286.2024.2376304

Int J Urol. 2024 Jul 3. doi: 10.1111/iju.15524. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of dose-dense gemcitabine and cisplatin (ddGC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC).

METHODS: Patients with locally advanced MIBC (cT2aN0M0-cT4N1M0) who received ddGC between December 2017 and December 2023 were included. Regimens of ddGC with pegfilgrastim were administered every 2 weeks for 4 cycles, followed by radical cystectomy. The pathological complete response (CR) (pT0N0) and objective response (OR) (<pT2N0) rates were evaluated in patients who underwent radical cystectomy. Tolerability was assessed using relative dose intensity (RDI). Adverse events (AEs) were documented according to the Common Terminology Criteria for Adverse Events in all patients who received ddGC. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method.

RESULTS: A total of 45 patients (cT2N0, 60%; cT3N0, 22%; cT4N0, 9%; and cTanyN1, 9%) were included. Of the 41 who underwent cystectomy, 38 (92.7%) completed all planned cycles, with a median RDI of 0.96 (interquartile range [IQR], 0.89-1.00). Overall, CR and OR were achieved in 12 (29.3%) and 17 (41.5%) patients, respectively, increasing to 32.4% and 45.9%, respectively, in cN0 patients. Severe AEs (grade ≥ 3) were observed in eight patients (17.8%), including four hematological toxicities. At a median follow-up of 31 months, 2-year DFS and OS were 70.8% and 89.2%, respectively.

CONCLUSION: Neoadjuvant ddGC demonstrated good tolerability, efficacy, and safety, suggesting its potential as a treatment option for MIBC.

PMID:38961545 | DOI:10.1111/iju.15524

Reg Anesth Pain Med. 2024 Jul 2:rapm-2024-105530. doi: 10.1136/rapm-2024-105530. Online ahead of print.

ABSTRACT

BACKGROUND: Dexamethasone palmitate (DEP), a prodrug of dexamethasone (DEX), is a synthetic corticosteroid medication distinguished by the inclusion of a fatty acid component known as palmitate. This study introduces DEP as a novel therapeutic option for spinal epidural injection, aiming to provide safer and longer-lasting pain relief as an alternative to for patients with spinal stenosis.

METHODS: 40 rats were randomly divided into four groups: those receiving epidural administration of normal saline (NS), and DEP in the lumbar spinal stenosis (LSS) model, and non-model rats receiving epidural NS administration. Paw withdrawal thresholds to mechanical stimulation and motor function (neurogenic intermittent claudication) were observed for up to 21 days. Hematology and blood chemistry analyses were performed 1 week after drug therapy. Tissue samples were collected for steroid pathology examination to evaluate adhesion degree, perineural area inflammation, and chromatolysis in the dorsal root ganglion (DRG), and adrenal gland.

RESULTS: The DEX and DEP groups demonstrated significant recovery from mechanical allodynia and motor dysfunction after 2 weeks of drug therapy (p<0.001). However, by the third week, the effect of DEX started to diminish while the effect of DEP persisted. Furthermore, the DEP group exhibited reduced fibrosis and less chromatolysis than the NS group. No steroid overdose or toxin was observed in any group.

CONCLUSION: The epidural administration of DEP demonstrated therapeutic efficacy in reducing allodynia and hyperalgesia resulting from chronic DRG compression, thus offering prolonged pain relief. These findings underscore the potential of DEP as a promising treatment alternative for pain associated with LSS, serving as a viable substitute for .

PMID:38960590 | DOI:10.1136/rapm-2024-105530

Eur J Hosp Pharm. 2024 Jul 2:ejhpharm-2024-004266. doi: 10.1136/ejhpharm-2024-004266. Online ahead of print.

ABSTRACT

INTRODUCTION: Invasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on how effective antifungal prophylaxis is against Candida spp infections and limited guidance on the prevention of Aspergillus spp infections. This systematic review and meta-analysis will assess the literature to see if antifungal prophylaxis reduces the incidence of IFI after heart transplant in adults.

METHODS AND ANALYSIS: This systematic review protocol follows the Preferred Reporting Items for Systematic reviews and Meta Analysis guidelines. A systematic search of the Cochrane Library, Web of Science, Scopus, Embase, MEDLINE, and Proquest databases will be undertaken. Reference lists of retrieved publications and conference abstracts will also be searched. Title, abstract and full-text screening will be undertaken by two reviewers. Discrepancies will be resolved by a third reviewer. Studies with paediatric patients, multi-organ transplants, or patients with a second heart transplant will be excluded, along with those who do not have clear definitions and diagnostic criteria for IFI. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool and the Risk of Bias in Non-randomised Studies of Interventions tool. A meta-analysis will be carried out, but if studies are not deemed to be sufficiently similar, only a narrative synthesis will be undertaken.

ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review as primary data will not be collected. The results of the review will be disseminated through publication in an academic journal and scientific conferences.

PROSPERO REGISTRATION NUMBER: CRD42024516588.

PMID:38960452 | DOI:10.1136/ejhpharm-2024-004266

Curr Med Res Opin. 2024 Jul 3:1-16. doi: 10.1080/03007995.2024.2373883. Online ahead of print.

ABSTRACT

Objective: To compare the safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD.Methods: In the absence of head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) were used to compare rates of adverse events reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER. Pooled patient-level data from two centanafadine trials (NCT03605680, NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e., above the 99th percentile).Results: Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: -11.95), initial insomnia (-11.10), decreased appetite (-8.05), anxiety (-5.39), palpitations (-5.25), and feeling jittery (-4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER.Conclusion: In this anchored MAIC, centanafadine had a better safety profile and possibly lower efficacy than methylphenidate hydrochloride ER. While the safety results were robust across analyses, there was no difference in efficacy between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern.

PMID:38958732 | DOI:10.1080/03007995.2024.2373883

Hum Vaccin Immunother. 2024 Dec 31;20(1):2372884. doi: 10.1080/21645515.2024.2372884. Epub 2024 Jul 3.

ABSTRACT

To fully understand the safety of DTaP-IPV/Hib vaccination, we evaluated the differences between DTaP-IPV/Hib co-administration and separate administration of the DTaP, IPV and Hib vaccines (DTaP+IPV+Hib) based on adverse events following immunization (AEFI). All AEFI reported in Hebei Province, China, between 2020 and 2022 were included in this study. The risk difference (RD%), relative risk (RR), and Chi-square value were used to compare the differences in reported rates of AEFI between the DTaP-IPV/Hib and DTaP+IPV+Hib groups. From 2020 to 2022, 130 AEFI cases were reported in Hebei Province after DTaP-IPV/Hib vaccination, corresponding to an AEFI reported rate of 66.9/million doses, which was significantly lower than that for DTaP+IPV+Hib (9836 AEFI with a reported rate of 637.8/million doses). The overall reported rate of non-severe AEFI for DTaP+IPV+Hib vaccines was 9.5 times that of DTaP-IPV/Hib vaccination [95% confidence interval (CI): 8.0, 11.3]. Meanwhile, the reported rate of AEFI among infants aged 0-1 y was 9.8 times higher for DTaP+IPV+Hib than for DTaP-IPV/Hib (95% CI: 8.2, 11.7). DTaP+IPV+Hib vaccination also resulted in higher risks of high fever, localized redness and swelling, localized induration, and allergic rash compared with DTaP-IPV/Hib vaccination. The risk of AEFI, which were mostly mild reaction, was higher after vaccination with DTaP+IPV+Hib than after DTaP-IPV/Hib vaccination.

PMID:38957938 | DOI:10.1080/21645515.2024.2372884

Front Psychiatry. 2024 Jun 18;15:1414622. doi: 10.3389/fpsyt.2024.1414622. eCollection 2024.

ABSTRACT

3,4-Methylenedioxymethamphetamine (MDMA) is being investigated in controlled clinical trials for use as an adjunct medication treatment for post-traumatic stress disorder. MDMA is metabolized by N-demethylation, primarily by CYP2D6, to its main inactive metabolite, 4-hydroxy-3-methoxymethamphetamine. It is also metabolized to a lesser extent by CYP1A2, CYP2B6, and CYP3A4 to its active metabolite, 3,4-methylenedioxyamphetamine. Considering the extensive hepatic metabolism and excretion, MDMA use in psychiatry raises concerns over drug-induced liver injury (DILI), a rare but dangerous event. Majority of the drugs withdrawn from the market for liver injury caused death or transplantation at frequencies under 0.01%. Unfortunately, markers for liver injury were not measured in most published clinical trials. At the same time, no visible DILI-related symptoms and adverse events were observed. Idiosyncratic DILI cases are rarely registered during clinical trials due to their rare nature. In this study, we surveyed a larger, over 1,500, and a more diverse set of reports from the FDA Adverse Event Reporting System and found 23 cases of hepatic injury and hepatic failure, in which MDMA was reported to be taken in addition to one or more substances. Interestingly, 22 out of 23 cases had one or more listed drugs with a known DILI concern based on the FDA's DILIrank dataset. Furthermore, only one report had MDMA listed as the primary suspect. Considering the nearly 20 million doses of MDMA used annually, this single report is insufficient for establishing a significant association with DILI.

PMID:38957734 | PMC:PMC11217510 | DOI:10.3389/fpsyt.2024.1414622

Drugs Aging. 2024 Jul;41(7):583-600. doi: 10.1007/s40266-024-01121-0. Epub 2024 Jul 2.

ABSTRACT

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.

PMID:38954400 | DOI:10.1007/s40266-024-01121-0

Eur J Cancer. 2024 Jun 29;207:114196. doi: 10.1016/j.ejca.2024.114196. Online ahead of print.

ABSTRACT

INTRODUCTION: The prognosis of patients with advanced biliary tract cancer (BTC) is still poor, and new strategies improving patients' outcome are needed. In our trial we investigated safety and activity of nab-paclitaxel in combination with gemcitabine and oxaliplatin as first-line systemic treatment for patients with advanced BTC.

METHODS: In this investigator-initiated, multicenter, dose-escalation, single-arm phase I/II trial, patients were accrued into cohorts of 3 patients and dose escalation was performed following the standard 3 + 3 rule. Primary endpoint was the proportion of patients free from progression at 6 months. Secondary endpoints included safety and tolerability of the combination; progression-free survival (PFS); overall survival (OS); objective response rate (ORR); duration of response.

RESULTS: Between July 2017 and December 2020, 67 patients were treated. Among the 10 patients in the phase I, no dose-limiting toxicity was observed, and dose level 2 was defined as recommended phase II dose for the phase II part. At data cutoff, the 6-month PFS rate was 49.1 % (95 % CI 40.8-57.5 %) with 28 patients out of 57 free from progression or death at 6 months. Median PFS was 6.3 months (95 % CI 3.6-10.1) and median OS was 12.4 months (95 % CI 8-23). ORR was 20.89 %. Most common grade 3 and grade 1-2 drug-related adverse events were neutropenia and peripheral neuropathy, respectively.

CONCLUSION: Triple chemotherapy demonstrated a favorable safety profile. However, the study did not meet its primary endpoint. Future studies will clarify the benefit of chemotherapy combinations in different settings. This trial is registered with ClinicalTrials.gov, NCT03943043.

PMID:38954899 | DOI:10.1016/j.ejca.2024.114196

Zhonghua Jie He He Hu Xi Za Zhi. 2024 Jul 12;47(7):638-646. doi: 10.3760/cma.j.cn112147-20240229-00117.

ABSTRACT

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

PMID:38955749 | DOI:10.3760/cma.j.cn112147-20240229-00117

Zhonghua Jie He He Hu Xi Za Zhi. 2024 Jul 12;47(7):632-637. doi: 10.3760/cma.j.cn112147-20231124-00339.

ABSTRACT

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

PMID:38955748 | DOI:10.3760/cma.j.cn112147-20231124-00339

Am J Clin Oncol. 2024 Jul 2. doi: 10.1097/COC.0000000000001126. Online ahead of print.

ABSTRACT

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population.

METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data.

RESULTS: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis.

CONCLUSIONS: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.

PMID:38951994 | DOI:10.1097/COC.0000000000001126

J Am Med Dir Assoc. 2024 Jun 29:105118. doi: 10.1016/j.jamda.2024.105118. Online ahead of print.

ABSTRACT

OBJECTIVES: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants.

DESIGN: A 3-round Delphi study.

SETTING AND PARTICIPANTS: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries.

METHODS: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms.

RESULTS: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth.

CONCLUSIONS AND IMPLICATIONS: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs.

PMID:38950588 | DOI:10.1016/j.jamda.2024.105118