Drug-induced Adverse Events

Comparative pharmacovigilance assessment of adverse events associated with the use of hydroxyurea, L-glutamine, voxelotor, and crizanlizumab in sickle cell disease

Sat, 2023-11-11 06:00

Am J Hematol. 2023 Nov 11. doi: 10.1002/ajh.27153. Online ahead of print.

ABSTRACT

Using disproportionality analysis, this study compared the adverse events (AEs) associated with the use of the new agents (e.g., L-glutamine, voxelotor, and crizanlizumab) to the commonly used medication, hydroxyurea, in sickle cell disease. We found that the most frequent drug-related AEs observed in this real-world study were consistent with those in the HOPE (voxelotor) and SUSTAIN (crizanlizumab) trials, but the rates of AEs were lower. Our study demonstrates that the most common AEs and symptoms of an increased risk associated with the individual drugs varied by treatment. Disproportionate reporting signals of drug-related AEs may also capture information that is independent of subjective measures of patient-reported symptoms. Our study highlights the important need for facilitating patient-physician communication in routine clinical care to understand patient-reported symptoms.

PMID:37950855 | DOI:10.1002/ajh.27153

Categories: Literature Watch

Adverse events of epidiolex: A real-world drug safety surveillance study based on the FDA adverse event reporting system (FAERS) database

Fri, 2023-11-10 06:00

Asian J Psychiatr. 2023 Dec;90:103828. doi: 10.1016/j.ajp.2023.103828. Epub 2023 Nov 4.

ABSTRACT

Epidiolex, the first FDA-approved drug with cannabis extract, treats Dravet and Lennox-Gastaut syndromes. Using data from the FAERS database between 2018 and 2023, this study analyzed 13,275 Epidiolex-related adverse events. Through computational methods (ROR, PRR, BCPNN, EBGM), we found that real-world adverse reactions largely align with those in Epidiolex's drug leaflet. However, Seizure cluster, Blood ketone body decrease, Cortical visual impairment, Hyperactive pharyngeal reflex, and Poverty of speech emerged as potential new side effects not previously listed, warranting further attention for drug safety.

PMID:37949044 | DOI:10.1016/j.ajp.2023.103828

Categories: Literature Watch

Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment: A systematic review and meta-analysis of randomized controlled trials

Fri, 2023-11-10 06:00

Int Immunopharmacol. 2023 Dec;125(Pt B):111176. doi: 10.1016/j.intimp.2023.111176. Epub 2023 Nov 8.

ABSTRACT

OBJECTIVE: This study was performed to evaluate the efficacy, safety and immunological function of toripalimab combination therapy, aiming to provide a reference for the clinical combined use of toripalimab and the development of subsequent indications for cancer treatment.

MATERIALS AND METHODS: The meta-analysis was conducted by searching PubMed, Cochrane Library, Web of Science, EMBASE, CNKI database and Wanfang database until September 22, 2023. Only randomized controlled trials (RCTs) that involved cancer participants that received toripalimab combination therapy including a combination and control group were selected. The clinical outcomes of complete response rate (CR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), treatment related adverse effects (AEs) and immune-related adverse effects (irAEs) and immunological function index (CD3+, CD4+, CD8+ and CD4+/CD8+ T cells ratio) were extracted and evaluated. A random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using Stata software (version 12.0). Subgroup analysis was done to estimate whether the effects of PD-L1 expression on PFS. Egger's test were carried out to measure publication bias.

RESULTS: A total of 11 RCTs involving 1856 patients met the inclusion criteria. Both toripalimab plus chemotherapy and toripalimab plus targeted therapy had a trend of better CR [RR = 1.74, 95%CI (1.23, 2.45), P = 0.002], OS [HR = 1.94, 95%CI (1.76, 2.15), P < 0.001] and PFS [HR = 1.70, 95%CI (1.57, 1.83), P < 0.001], and an improvement of ORR [RR = 1.21, 95%CI (1.09, 1.35), P = 0.001] was found with toripalimab plus chemotherapy while not that plus targeted therapy compared to monotherapy. Subgroup analysis showed that toripalimab plus chemotherapy extended PFS whether PD-L1 positive or negative [HR = 1.78, 95%CI (1.60, 1.98), P < 0.001; HR = 1.60, 95%CI (1.37, 1.87), P < 0.001]. Additionally, toripalimab combined regimens significantly increased the proportion of CD3+, CD4+, and CD4+/CD8+ T cells [SMD = 0.79, 95% CI (0.19, 1.40), p = 0.01; SMD = 1.40, 95% CI (0.72, 2.07), p < 0.001; SMD = 1.46, 95% CI (0.64, 2.28), p < 0.001]. The incidence of any grade [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] and grade 3 or worse irAEs [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] were higher with toripalimab combined regimens as compared to single treatment while no difference was found for treatment related AEs. Sensitivity analysis indicated that no individual study had influence on the pooled results.

CONCLUSIONS: Based on the available data, both toripalimab plus chemotherapy and toripalimab plus targeted therapy demonstrated superior clinical outcomes and regulation of cellular immunity at the cost of greater but manageable toxicity. More clinical trials need to be performed to further evaluate the efficacy and safety for other toripalimab combined regimens.

PMID:37948860 | DOI:10.1016/j.intimp.2023.111176

Categories: Literature Watch

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer

Fri, 2023-11-10 06:00

Int Immunopharmacol. 2023 Dec;125(Pt B):111138. doi: 10.1016/j.intimp.2023.111138. Epub 2023 Nov 8.

ABSTRACT

BACKGROUND: Baseline corticosteroids exposure is associated with inferior clinical outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) axis blockade. Dexamethasone is a potent corticosteroid used in the prevention of chemotherapy-associated adverse events (CAAEs).

OBJECTIVE: Since dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC.

METHODS: The study retrospectively analyzed the medical records of 254 advanced non-squamous NSCLC patients who received front-line treatment with a PD-1 pathway inhibitor and platinum-based chemotherapy at three academic institutions. The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dose of dexamethasone: High-d (≥24 mg), Moderate-d (12-24 mg), and Low-d (<12 mg). Spearman's rank correlation was used to assess the correlation between the dosage of dexamethasone and progression-free survival (PFS). Logistic regression was used to assess the correlation between dexamethasone dosage and the occurrence of immune related adverse effects (irAE). Univariate and multivariate Cox proportional hazards regression models were used to analyze the differences in survival among the different dexamethasone dosage groups.

RESULT: The dosage of prophylactic dexamethasone was not significantly correlated with PFS (Spearman's rho = -0.103, P = 0.098). Results from the univariate [hazard ratio (HR)Low-d/High-d, 1.00; P = 0.997; HRModerate-d/High-d, 0.85; P = 0.438] and multivariate (HRLow-d/High-d, 0.71; P = 0.174; HRModerate-d/High-d, 0.87; P = 0.512) analyses showed no significant association between dexamethasone and PFS. Dexamethasone did not have significant effect on the objective response rate, disease control rate or overall survival. The toxicity profiles of irAE were similar across all three groups.

CONCLUSION: The results of this study suggest that the use of prophylactic dexamethasone does not have an adverse effect on the clinical outcomes of non-squamous NSCLC patients treated with PD-1 blockade therapy and chemotherapy. Routine use of dexamethasone for preventing CAAEs should be recommended for patients undergoing combined immunotherapy and chemotherapy.

PMID:37948858 | DOI:10.1016/j.intimp.2023.111138

Categories: Literature Watch

Moving toward a contemporary classification of drug-induced kidney disease

Fri, 2023-11-10 06:00

Crit Care. 2023 Nov 9;27(1):435. doi: 10.1186/s13054-023-04720-2.

ABSTRACT

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including "dysfunction without damage," "damage without dysfunction," "both dysfunction and damage," and "neither dysfunction nor damage" using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient's kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.

PMID:37946280 | DOI:10.1186/s13054-023-04720-2

Categories: Literature Watch

Milestones and turning points in the experience of physical activity throughout cancer care: a qualitative study to inform physical activity promotion

Thu, 2023-11-09 06:00

Support Care Cancer. 2023 Nov 9;31(12):682. doi: 10.1007/s00520-023-08093-8.

ABSTRACT

PURPOSE: Physical activity (PA) is an important supportive care strategy to manage cancer and treatment-related side effects, yet PA participation is low among people diagnosed with cancer. This study examined patients', health professionals', and managers' perspectives on PA throughout cancer care to glean implications for PA promotion.

METHODS: Random selection and purposeful sampling methods allowed for the recruitment of 21 patients (76.2% women) and 20 health professionals and managers (80% women) who participated in individual semi-structured interviews. Interview questions explored facilitators and barriers to PA participation and promotion across the cancer care continuum. Interviews were audio-recorded and transcribed. Then, qualitative thematic analysis was performed.

RESULTS: The analysis produced five main themes describing milestones in PA participation throughout cancer care: (1) Getting Started, (2) Discovering PA Resources, (3) Taking Action, (4) Striving for Change, and (5) Returning to a "New Normal." The sub-themes underscored turning points, i.e., tasks and challenges to PA participation that had to be overcome at each milestone. Achieving milestones and successfully navigating turning points were dependent on clinical, social, and community factors.

CONCLUSION: Cancer patients appear to progress through a series of milestones in adopting and maintaining PA throughout cancer care. Intervention strategies aimed at promoting PA could test whether support in navigating turning points could lead to greater PA participation. These findings require replication and extension, specifically among patients who are men, younger adults, and culturally diverse.

PMID:37943370 | DOI:10.1007/s00520-023-08093-8

Categories: Literature Watch

Narrow-Band Intense Pulsed Light as Treatment for Erythematotelangiectatic Rosacea: A Retrospective Study

Thu, 2023-11-09 06:00

J Drugs Dermatol. 2023 Nov 1;22(11):1095-1098. doi: 10.36849/JDD.4920.

ABSTRACT

BACKGROUND: Erythematotelangiectatic rosacea can be successfully treated using various laser and light-based devices. However, the use of narrow-band intense pulsed light for the treatment of erythematotelangiectatic rosacea has not been investigated in detail. This retrospective study aimed to analyze the clinical efficacy of narrow-band intense pulsed light (500-600 nm) for the treatment of erythematotelangiectatic rosacea among Chinese individuals.&nbsp; Methods: Patients with erythematotelangiectatic rosacea who had completed 3 sessions of treatment with narrow-band intense pulsed light and follow-up from July 2016 to December 2018 were retrospectively evaluated. Clinical improvement was assessed by 2 blinded dermatologists based on photographs obtained at each follow-up visit using the clinician erythema assessment scale and 5-grade scale.

RESULTS: Forty-five patients with erythematotelangiectatic rosacea treated with narrow-band intense pulsed light were included in this study. The effectiveness and excellent rates after 3 treatment sessions were 68.9% and 35.6%, respectively. An average of 2 treatment sessions was required among patients who achieved good or excellent clearance of erythema and telangiectasia. Except for transient erythema and edema, no severe adverse effects were observed.

CONCLUSIONS: Narrow-band intense pulsed light is a safe and effective treatment for erythematotelangiectatic rosacea. Even with a small number of treatment sessions, narrow-band intense pulsed light can deliver a significant therapeutic effect, which may be applicable in clinical practice. J Drugs Dermatol. 2023;22(11):1095-1098&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.4920.

PMID:37943269 | DOI:10.36849/JDD.4920

Categories: Literature Watch

Dapsone to Treat Moderate-to-Severe Hidradenitis Suppurativa: A Retrospective Case-Series

Thu, 2023-11-09 06:00

J Drugs Dermatol. 2023 Nov 1;22(11):e12-e16. doi: 10.36849/JDD.4936.

ABSTRACT

BACKGROUND: Management of hidradenitis suppurativa (HS) is challenging since no single treatment provides consistently effective results, leaving patients with frequent relapses. Dapsone combines anti-microbial and anti-inflammatory properties that address aspects of HS pathogenesis. Few studies have evaluated the efficacy of oral dapsone on HS, especially in severe disease.

OBJECTIVE: This study aims to evaluate the clinical outcomes of patients with moderate-to-severe HS treated with dapsone.

METHODS: This retrospective chart review evaluated HS patients treated with oral dapsone over the past 10 years at one center. Treatment outcomes were classified based on Hurley staging, physician exam, and symptom progression. Adverse effects and concomitant treatment with dapsone were reviewed.

RESULTS: Nineteen (19) patients with moderate-to-severe (Hurley Stage II-III) HS treated with oral dapsone were identified. Within 1-3 months, on dosages of dapsone varying from 25-100 mg/day, 3 patients (15.8%) had a clinically significant improvement in symptoms, 10 patients (52.6%) had a slight improvement, and 6 patients (31.6%) had no change in disease state; no patients deteriorated. The majority who improved were also on other medications, most commonly adalimumab. 4 patients experienced adverse effects, with nausea being most common; otherwise, dapsone was well-tolerated.

CONCLUSIONS: Dapsone may have some efficacy for moderate-to-severe HS and seems well-tolerated. J Drugs Dermatol. 2023;22(11):e12-e16&nbsp; &nbsp; doi:10.36849/JDD.4936e.

PMID:37943259 | DOI:10.36849/JDD.4936

Categories: Literature Watch

Pharmacogenetic Approach for the Prevention of Rivaroxaban's ADRs: A Systematic Review and Meta-Analysis

Thu, 2023-11-09 06:00

Genet Res (Camb). 2023 Oct 31;2023:6105320. doi: 10.1155/2023/6105320. eCollection 2023.

ABSTRACT

INTRODUCTION: Pharmacogenetics is a potential approach that can be applied to decline the burden of rivaroxaban's ADRs. The current systematic review and meta-analysis aim to identify genetic variants correlated with rivaroxaban exposure and evaluate their importance.

METHODS: We systematically searched PubMed, Web of Science, and Scopus databases for all observational and interventional studies. The fixed effect method was used to pool the data when the Q-test's p value was higher than 0.1. We used random models when the p value was less than 0.1.

RESULTS: Data from ten studies (4721 participants) were analyzed in the current review. Qualitative synthesis from included studies found that two variants of ABCB1 (rs1045642 and rs2032582) and one variant of APOB (rs13306198) are potential contributors to rivaroxaban concentrations. Both wild homozygotes (AA) and heterozygotes (AC) of rs1045642 have significantly lower rivaroxaban concentrations compared to mutated homozygotes (CC) (SMD = 0.516, 95% CI: 0.115 to 0.917; SMD = 0.772, 95% CI: 0.088 to 1.455, respectively). Nevertheless, pooling unadjusted odds ratios did not yield a statistically significant correlation between rivaroxaban ADRs and genetic mutations.

CONCLUSION: This study revealed that being an AC or CC for rs1045642 is attributed to a considerably higher rivaroxaban level in participants using rivaroxaban. That is to say, rs1045642 is a remarkable predictor of rivaroxaban metabolism. We concluded that identifying rs1045642 before drug administration might decrease ADRs although further studies adjusted for potential confounders are strongly suggested.

PMID:37942082 | PMC:PMC10630013 | DOI:10.1155/2023/6105320

Categories: Literature Watch

Daptomycin-Induced Acute Liver Failure: A Rare Case Report

Thu, 2023-11-09 06:00

Cureus. 2023 Oct 8;15(10):e46692. doi: 10.7759/cureus.46692. eCollection 2023 Oct.

ABSTRACT

Acute liver failure (ALF) is characterized by severe liver injury, encephalopathy, and impaired coagulation/synthetic function. Drug-induced liver injury (DILI) can rarely, in a dose-dependent manner, lead to ALF. This article presents a rare case of daptomycin-induced acute liver failure in a patient with no prior liver disease. A 73-year-old male with multiple comorbidities including heart failure, diabetes, and chronic kidney disease received daptomycin treatment for diabetic left foot osteomyelitis. Five days after starting therapy, he developed weakness, jaundice, and drowsiness, leading to ICU admission. Physical examination and labs revealed hepatomegaly, elevated liver enzymes and abnormal ultrasound findings. Autoimmune and infectious causes were ruled out. Daptomycin was discontinued, and the patient's labs showed significant improvement within three days. One week after recovery from acute liver failure, he experienced cardiogenic shock due to worsening of his underlying heart failure and was transferred to the Cardiac ICU before ultimately being discharged to inpatient hospice care. To our best knowledge, this is the first reported case of daptomycin-induced acute liver failure, presenting with massive liver enzyme elevations, synthetic dysfunction, and encephalopathy. The Naranjo scale score suggests a probable causal relationship between daptomycin and liver injury. While a few cases of daptomycin-induced liver injury have been reported, there are no previous reports of acute liver failure. The rapid development of liver failure following daptomycin administration and subsequent recovery after discontinuation is noteworthy. However, various confounding factors and the mechanism of daptomycin-induced liver failure remain unclear. Further research is needed to identify predisposing factors and better understand this rare complication. While rare, this care also raises caution to follow liver function closely while prescribing daptomycin.

PMID:37942364 | PMC:PMC10629966 | DOI:10.7759/cureus.46692

Categories: Literature Watch

Improving the impact of pharmacy interventions in hospitals

Wed, 2023-11-08 06:00

BMJ Open Qual. 2023 Nov;12(4):e002276. doi: 10.1136/bmjoq-2023-002276.

ABSTRACT

The clinical and pharmaceutical interventions of pharmacy professionals are considered impactful inputs towards optimised patient care and safety, by rationalising prescriptions, enhancing therapeutic choices and reducing and preventing medication errors and adverse effects. Pharmacy interventions (PIs), related to the identification, prevention and resolution of drug-related problems, should be recorded for optimal clinical governance and potential health outcomes.Between October 2020 and October 2021, the community hospitals at Powys Teaching Health Board recorded 158 PIs, corresponding to 0.4 interventions per staff per week. Only two members of the team were recording these PIs. Poor indicative PIs can result in lost opportunities for medication optimisation and prescribing rationalisation, increased costs and unidentified training potential.The aims of this project were (1) to record 180 interventions between 22 November 2021 and 8 April 2022 (20 weeks), corresponding to an average threefold increase, compared to the interventions recorded between October 2020 and October 2021 (52 weeks); (2) to have all hospital pharmacy staff recording at least one intervention during the same period.The number of interventions recorded and the number of pharmacy staff recording each intervention were two process measures. The project was completed through two Plan-Do-Study-Act cycles and applied theory on managing change in healthcare.The most successful intervention influencing positively the process measures was the implementation of a new Pharmacy Intervention Record Tool (xPIRT) toolkit that included an online recording tool (xPIRT) and an interactive panel with up-to-date results from all interventions recorded (xPIRT Dashboard). Motivating change was proven to be one of the best determinants of user satisfaction and engagement that contributed to meet the project's targets. xPIRT Dashboard provided staff the capacity to act on possible personal motivators and the possibility to improving care with medicines on their wards. The implementation of xPIRT toolkit was able to increase the representativity and significance of PIs recorded by the hospital pharmacy team, and it is expected to be used for personal professional development, demonstrating team activity and impact, service planning, prescribing practice optimisation and to identify education/training needs. This toolkit can be easily applied and adapted to other health organisations, settings and services.

PMID:37940333 | PMC:PMC10632884 | DOI:10.1136/bmjoq-2023-002276

Categories: Literature Watch

Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance

Wed, 2023-11-08 06:00

PLoS One. 2023 Nov 8;18(11):e0293605. doi: 10.1371/journal.pone.0293605. eCollection 2023.

ABSTRACT

Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.

PMID:37939153 | PMC:PMC10631690 | DOI:10.1371/journal.pone.0293605

Categories: Literature Watch

Adjuvants for balanced anesthesia in ambulatory surgery

Wed, 2023-11-08 06:00

Best Pract Res Clin Anaesthesiol. 2023 Sep;37(3):409-420. doi: 10.1016/j.bpa.2022.12.003. Epub 2023 Jan 4.

ABSTRACT

Balanced anesthesia relies on the simultaneous administration of different drugs to attain an anesthetic state. The classic triad of anesthesia is a combination of a hypnotic, an analgesic, and a neuromuscular blocker. It is predominantly the analgesic pillar of this triad that became more and more supported by adjuvant therapy. The aim of this approach is to evolve into an opioid-sparing technique to cope with undesirable side effects of the opioids and is fueled by the opioid epidemic. The optimal strategy for balanced general anesthesia in ambulatory surgery must aim for a transition to a multimodal analgesic regimen dealing with acute postoperative pain and ideally reduce the most common adverse effects patients are faced with at home; sore throat, delayed awakening, memory disturbances, headache, nausea and vomiting, and negative behavioral changes. Over the years, this continuum of "multimodal general anesthesia" adopted many drugs with different modes of action. This review focuses on the most recent evidence on the different adjuvants that entered clinical practice and gives an overview of the different mechanisms of action, the potential as opioid-sparing or hypnotic-sparing drugs, and the applicability specifically in ambulatory surgery.

PMID:37938086 | DOI:10.1016/j.bpa.2022.12.003

Categories: Literature Watch

Adverse drug reactions in hospitals: population estimates for Portugal and the ICD-9-CM to ICD-10-CM crosswalk

Wed, 2023-11-08 06:00

BMC Health Serv Res. 2023 Nov 8;23(1):1222. doi: 10.1186/s12913-023-10225-z.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADR), both preventable and non-preventable, are frequent and pose a significant burden. This study aimed to produce up-to-date estimates for ADR rates in hospitals, in Portugal, from 2010 to 2018. In addition, it explores possible pitfalls when crosswalking between ICD-9-CM and ICD-10-CM code sets for ADR identification.

METHODS: The Portuguese Hospital Morbidity Database was used to identify hospital episodes (outpatient or inpatient) with at least one ICD code of ADR. Since the study period spanned from 2010 to 2018, both ICD-9-CM and ICD-10-CM codes based on previously published studies were used to define episodes. This was an exploratory study, and descriptive statistics were used to provide ADR rates and summarise episode features for the full period (2010-2018) as well as for the ICD-9-CM (2010-2016) and ICD -10-CM (2017-2018) eras.

RESULTS: Between 2010 and 2018, ADR occurred in 162,985 hospital episodes, corresponding to 1.00% of the total number of episodes during the same period. Higher rates were seen in the oldest age groups. In the same period, the mean annual rate of episodes related to ADR was 174.2/100,000 population. The episode rate (per 100,000 population) was generally higher in males, except in young adults (aged '15-20', '25-30' and '30-35' years), although the overall frequency of ADR in hospital episodes was higher in females.

CONCLUSIONS: Despite the ICD-10-CM transition, administrative health data in Portugal remain a feasible source for producing up-to-date estimates on ADR in hospitals. There is a need for future research to identify target recipients for preventive interventions and improve medication safety practices in Portugal.

PMID:37940971 | DOI:10.1186/s12913-023-10225-z

Categories: Literature Watch

Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias

Wed, 2023-11-08 06:00

BMC Cancer. 2023 Nov 8;23(1):1078. doi: 10.1186/s12885-023-11618-3.

ABSTRACT

BACKGROUND: Several studies have reported an association between severe neutropenia and long-term survival in patients treated with trifluridine-tipiracil (TAS-102). Because some of these studies failed to address immortality time bias, however, their findings should be interpreted with caution. Additionally, the association between severe neutropenia and survival in patients receiving TAS-102 in combination with bevacizumab (Bmab) remains unclear.

PATIENTS AND METHODS: We conducted a single-center retrospective cohort study in patients with colorectal cancer who received Bmab + TAS-102. We compared overall survival (OS) between patients who developed grade ≥ 3 neutropenia during the treatment period and those who did not. To account for immortal time bias, we used two approaches, time-varying Cox regression and landmark analysis.

RESULTS: Median OS was 15.3 months [95% CI: 14.1-NA] in patients with grade ≥ 3 neutropenia and 10.0 months [95% CI: 8.1-NA] in those without. In time-varying Cox regression, onset grade ≥ 3 neutropenia was significantly related to longer survival after adjustment for age and modified Glasgow Prognostic Score. Additionally, 30-, 60-, 90-, and 120-day landmark analysis showed that grade ≥ 3 neutropenia was associated with longer survival after adjustment for age and modified Glasgow Prognostic Score, with respective HRs of 0.30 [0.10-0.90], 0.65 [0.30-1.42], 0.39 [0.17-0.90], and 0.41 [0.18-0.95].

CONCLUSION: We identified an association between long-term survival and the development of severe neutropenia during the early cycle of Bmab + TAS-102 using an approach that addressed immortality time bias.

PMID:37940878 | DOI:10.1186/s12885-023-11618-3

Categories: Literature Watch

A National Survey of Physicians' Views on the Importance and Implementation of Deintensifying Diabetes Medications

Wed, 2023-11-08 06:00

J Gen Intern Med. 2023 Nov 8. doi: 10.1007/s11606-023-08506-8. Online ahead of print.

ABSTRACT

BACKGROUND: Guidelines recommend deintensifying hypoglycemia-causing medications for older adults with diabetes whose hemoglobin A1c is below their individualized target, but this rarely occurs in practice.

OBJECTIVE: To understand physicians' decision-making around deintensifying diabetes treatment.

DESIGN: National physician survey.

PARTICIPANTS: US physicians in general medicine, geriatrics, or endocrinology providing outpatient diabetes care.

MAIN MEASURES: Physicians rated the importance of deintensifying diabetes medications for older adults with type 2 diabetes, and of switching medication classes, on 5-point Likert scales. They reported the frequency of these actions for their patients, and listed important barriers and facilitators. We evaluated the independent association between physicians' professional and practice characteristics and the importance of deintensifying and switching diabetes medications using multivariable ordered logistic regression models.

KEY RESULTS: There were 445 eligible respondents (response rate 37.5%). The majority of physicians viewed deintensifying (80%) and switching (92%) diabetes medications as important or very important to the care of older adults. Despite this, one-third of physicians reported deintensifying diabetes medications rarely or never. While most physicians recognized multiple reasons to deintensify, two-thirds of physicians reported barriers of short-term hyperglycemia and patient reluctance to change medications or allow higher glucose levels. In multivariable models, geriatricians rated deintensification as more important compared to other specialties (p=0.027), and endocrinologists rated switching as more important compared to other specialties (p<0.006). Physicians with fewer years in practice rated higher importance of deintensification (p<0.001) and switching (p=0.003).

CONCLUSIONS: While most US physicians viewed deintensifying and switching diabetes medications as important for the care of older adults, they deintensified infrequently. Physicians had ambivalence about the relative benefits and harms of deintensification and viewed it as a potential source of conflict with their patients. These factors likely contribute to clinical inertia, and studies focused on improving shared decision-making around deintensifying diabetes medications are needed.

PMID:37940754 | DOI:10.1007/s11606-023-08506-8

Categories: Literature Watch

Head-to-head trial of pegunigalsidase alfa versus agalsidase beta in patients with Fabry disease and deteriorating renal function: results from the 2-year randomised phase III BALANCE study

Wed, 2023-11-08 06:00

J Med Genet. 2023 Nov 8:jmg-2023-109445. doi: 10.1136/jmg-2023-109445. Online ahead of print.

ABSTRACT

BACKGROUND: Pegunigalsidase alfa is a PEGylated α-galactosidase A enzyme replacement therapy. BALANCE (NCT02795676) assessed non-inferiority of pegunigalsidase alfa versus agalsidase beta in adults with Fabry disease with an annualised estimated glomerular filtration rate (eGFR) slope more negative than -2 mL/min/1.73 m2/year who had received agalsidase beta for ≥1 year.

METHODS: Patients were randomly assigned 2:1 to receive 1 mg/kg pegunigalsidase alfa or agalsidase beta every 2 weeks for 2 years. The primary efficacy analysis assessed non-inferiority based on median annualised eGFR slope differences between treatment arms.

RESULTS: Seventy-seven patients received either pegunigalsidase alfa (n=52) or agalsidase beta (n=25). At baseline, mean (range) age was 44 (18-60) years, 47 (61%) patients were male, median eGFR was 74.5 mL/min/1.73 m2 and median (range) eGFR slope was -7.3 (-30.5, 6.3) mL/min/1.73 m2/year. At 2 years, the difference between median eGFR slopes was -0.36 mL/min/1.73 m2/year, meeting the prespecified non-inferiority margin. Minimal changes were observed in lyso-Gb3 concentrations in both treatment arms at 2 years. Proportions of patients experiencing treatment-related adverse events and mild or moderate infusion-related reactions were similar in both groups, yet exposure-adjusted rates were 3.6-fold and 7.8-fold higher, respectively, with agalsidase beta than pegunigalsidase alfa. At the end of the study, neutralising antibodies were detected in 7 out of 47 (15%) pegunigalsidase alfa-treated patients and 6 out of 23 (26%) agalsidase beta-treated patients. There were no deaths.

CONCLUSIONS: Based on rate of eGFR decline over 2 years, pegunigalsidase alfa was non-inferior to agalsidase beta. Pegunigalsidase alfa had lower rates of treatment-emergent adverse events and mild or moderate infusion-related reactions.

TRIAL REGISTRATION NUMBER: NCT02795676.

PMID:37940383 | DOI:10.1136/jmg-2023-109445

Categories: Literature Watch

Impact of sex and age on vaccine-related side effects and their progression after booster mRNA COVID-19 vaccine

Tue, 2023-11-07 06:00

Sci Rep. 2023 Nov 7;13(1):19328. doi: 10.1038/s41598-023-46823-4.

ABSTRACT

In mRNA COVID-19 vaccination, side effects after the first and second dose have been well reported. However, studies about side effects after booster vaccine are sparse. 272 healthcare workers who received the third mRNA COVID-19 vaccine were recruited, and impact of sex, age, and symptoms on the side effect progression was statistically analyzed. Females and younger adults had a higher frequencies of general fatigue, headache, joint pain, chills and axillary pain compared to males and elderly adults, respectively. In longitudinal analysis, prolonged time to recovery from side effects was found among females and younger adults. Finally, between the third and second dose vaccinations, 52% of subjects had a longer duration of side effects following the third vaccine compared to the second, and joint pain was the culprit symptom related to the prolonged duration of side effects. Following the second vaccine dose, 25% of subjects had a longer duration of side effects and asthma and ear fullness, which exacerbated the underlying allergic condition, and COVID arm symptom were the culprit symptoms. These highlight the impact of sex, age, and culprit symptoms on the progress of side effects following the booster mRNA COVID-19 vaccine.

PMID:37935801 | PMC:PMC10630308 | DOI:10.1038/s41598-023-46823-4

Categories: Literature Watch

Risk Management and Mitigating Risk Opportunities for Opioid Prescribing

Tue, 2023-11-07 06:00

J Am Podiatr Med Assoc. 2023 Sep-Oct;113(5):21-166. doi: 10.7547/21-166.

ABSTRACT

All clinicians are ethically obliged to prescribe responsibly and cautiously to diminish the potential for opioid diversion and to help minimize the growth of the current opioid abuse epidemic. Podiatric physicians should establish procedures to better control and limit opioid prescription and develop analgesic regimens to treat pain. The main purpose and goal of this review is to present data congruent with clinical, medical, and legal reports for allowing an appreciation of the possibility of the risk assumed when ordering and prescribing opioids within the podiatric medical profession. First, the concept and process of risk management, illustrated using a root cause analysis approach, is introduced, and application of these principles specifically to opioid prescribing is presented. Then, several examples found in both the medical and legal literature documenting the reasons for opioid prescription risk are presented. Finally, mitigating strategies for safe opioid prescribing are offered so that mitigation of opioid harm can be possible and realized by the lower-extremity specialist. Risk management strategies and tools to mitigate opioid harm, lessen opioid adverse effects, and reduce opioid deaths are presented narratively and graphically.

PMID:37934585 | DOI:10.7547/21-166

Categories: Literature Watch

"Take the tablet or don't take the tablet?"-A qualitative study of patients' experiences of self-administering anti-cancer medications related to adherence and managing side effects

Tue, 2023-11-07 06:00

Support Care Cancer. 2023 Nov 7;31(12):680. doi: 10.1007/s00520-023-08122-6.

ABSTRACT

PURPOSE: Medication non-adherence is a well-recognised problem in cancer care, negatively impacting health outcomes and healthcare resources. Patient-related factors influencing medication adherence (MA) are complicated and interrelated. There is a need for qualitative research to better understand their underlying interaction processes and patients' needs to facilitate the development of effective patient-tailored complex interventions. This study aimed to explore experiences, perceptions, and needs relating to MA and side effect management of patients who are self-administering anti-cancer treatment.

METHODS: Semi-structured audio-recorded interviews with patients who have haematological cancer were conducted. A comparative, iterative, and predominantly inductive thematic analysis approach was employed.

RESULTS: Twenty-five patients from a specialist cancer hospital were interviewed. While self-administering cancer medications at home, patients' motivation to adhere was affected by cancer-related physical reactions, fears, cancer literacy and beliefs, and healthcare professional (HCP) and informal support. Patients desired need for regular follow-ups from respectful, encouraging, informative, responsive, and consistent HCPs as part of routine care. Motivated patients can develop high adherence and side effect self-management over time, especially when being supported by HCPs and informal networks.

CONCLUSION: Patients with cancer need varied support to medically adhere to and manage side effects at home. HCPs should adapt their practices to meet the patients' expectations to further support them during treatment. We propose a multi-dimensional and technology- and theory-based intervention, which incorporates regular HCP consultations providing tailored education and support to facilitate and maintain patient MA and side effect self-management.

PMID:37934298 | DOI:10.1007/s00520-023-08122-6

Categories: Literature Watch

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