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Medeniyet Medical Journal Jun 2024Dipeptidyl-peptidase 4 inhibitors (DPP4i) are commonly used as antidiabetic medications. Although these drugs are generally recognized for their favorable clinical...
Dipeptidyl-peptidase 4 inhibitors (DPP4i) are commonly used as antidiabetic medications. Although these drugs are generally recognized for their favorable clinical safety profile, emerging evidence points to the potential for adverse events associated with DPP4i. Notably, cases of bullous pemphigoid (BP) linked to DPP4i therapy have recently been documented in the medical literature. This report presents four cases of BP in elderly patients resulting from DPP4i treatment, involving two cases with ligandliptin and two with vildagliptin use. Successful remission was achieved in all cases through discontinuation of the implicated medication and implementation of topical corticosteroid therapy. It is imperative for clinicians to be vigilant about the potential risk of BP development when employing DPP4i drugs, particularly in the context of elderly patients with diabetes.
PubMed: 38940531
DOI: 10.4274/MMJ.galenos.2024.76508 -
The Oncologist Jun 2024There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due...
BACKGROUNDS
There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer.
METHODS
Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest.
RESULTS
Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05).
CONCLUSION
ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.
PubMed: 38940446
DOI: 10.1093/oncolo/oyae134 -
Acta Medica Philippina 2024Indigenous peoples (IPs) remain vulnerable to soil-transmitted helminthiasis (STH) due to limited access to sanitary toilets, clean water, quality health education, and...
BACKGROUND
Indigenous peoples (IPs) remain vulnerable to soil-transmitted helminthiasis (STH) due to limited access to sanitary toilets, clean water, quality health education, and services. The World Health Organization recommends periodic mass drug administration (MDA) of anthelminthics, health education, and improvements in water, sanitation, and hygiene (WASH) as control strategies to reduce morbidities caused by STH in target populations such as school-age children (SAC).This paper complements the published results of the parasitological survey (prevalence and intensity of STH) conducted in selected Aeta and Ata-Manobo communities.
OBJECTIVES
This study aimed to describe the accessibility of STH control strategies to respond to the needs of SAC in IP communities in Pampanga and Davao del Norte, the Philippines. It likewise intended to describe access of these IP communities to STH control strategies.
METHODS
Data on accessibility of and access to STH control strategies were collected using key informant interviews (KIIs) and focus group discussions (FGDs). Eleven officials and workers from the departments of health and education, local government units, and two IP leaders were interviewed on the existing STH burden in SAC, implementation of STH control strategies, particularly of MDA, health education campaigns, and improvements in WASH including good practices and challenges in program implementation.Three FGDs with parents, elementary school teachers of IP schools, and rural health midwives were conducted separately. Guide questions focused on accessibility of and access to STH prevention and control strategies for SAC in IP communities. Informed consent to conduct and record KIIs and FGDs were obtained from participants prior to participation.Analysis of a multi-disciplinary team was based on the accessibility framework for IPs accessing indigenous primary health care services by Davy et al. (2016).
RESULTS
The characteristics of the STH control strategies and the target populations are interrelated factors that influence accessibility. Challenges in the availability of the MDA program, particularly, inadequate staffing, drug shortages, and delays in delivery affect accessibility of and access to the free STH control strategies. Perceived harm, adverse events, stigma, beliefs, and practices likewise affect access. Lack of information on the similarity of treatment through community- and school-based MDA programs also affected engagement of SAC.IP communities are special settings where geographic isolation, peace and order situation as well as water supply need to be considered to help ensure access to STH control strategies, high MDA coverage, and improvements in WASH leading to desired outcomes.
CONCLUSIONS
Considering the context of IP communities and addressing the challenges in the accessibility of and access to STH control strategies are necessary to ensure successful implementation of an integrated approach in STH prevention and control strategies. Challenges in the accessibility of STH control strategies are inadequate staffing, poor inventory, and delays in the delivery of drugs, as well as poor sanitation and hygiene. Access of SAC is likewise affected by misconceptions on safety and efficacy of anthelminthics, including stigma and cultural practices. The similarity of the MDA programs based in school or community need to be disseminated.
PubMed: 38939852
DOI: 10.47895/amp.vi0.6439 -
Acta Medica Philippina 2024Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by , a normal commensal in the skin. Keratolytic agents are popular, cheap, and...
BACKGROUND
Pityriasis versicolor is a common fungal infection of the superficial skin layer caused by , a normal commensal in the skin. Keratolytic agents are popular, cheap, and readily available over-the-counter treatments for pityriasis versicolor. Conventional antifungal agents are more expensive, requiring prescription, and may induce resistant strains. However, evidence of their comparative safety and efficacy is still lacking.
OBJECTIVES
To assess the efficacy and safety of synthetic antifungals compared to keratolytic agents in the topical treatment of pityriasis versicolor through a systematic review.
METHODS
We searched the following databases: MEDLINE (from 1966) through PubMed, CENTRAL (Issue 9 of 12, September 2021), EMBASE (from 1974), LILACS (from 1987); Herdin (from 1970), www.clinicaltrials.gov, www.isrctn.com, www.trialregister.nl. We contacted researchers in the field, hand searched relevant conference abstracts, and the Journal of the Philippine Dermatological Society 1992-2019. We included all randomized controlled trials involving patients with diagnosed active pityriasis versicolor where topical antifungal was compared with a topical keratolytic for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias using the Cochrane collaboration tool, and extracted data from included studies. We used RevMan 5.3 to pool dichotomous outcomes using risk ratios (RR) and continuous outcomes using the mean difference (MD), using random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi² test and the I² test. We presented results using forest plots with 95% confidence intervals. We planned to create a funnel plot to determine publication bias but were unable to due to few studies. A Summary of Findings table was created using GRADE profile software for the primary outcomes.
RESULTS
We included 8 RCTs with a total of 617 participants that compared azole preparations (ketoconazole, bifonazole and econazole) versus keratolytic agents (selenium sulfide, adapalene, salicylic-benzoic acid). Pooled data showed that azoles did not significantly differ from keratolytic agents for clinical cure (RR 0.99, 0.88, 1.12; 4 RCTs, N=274, I=55%; very low-quality evidence), and adverse events (0.59 [0.17, 2.06]; very low-quality evidence) based on 6 RCTs (N=536). There were two patients given a keratolytic agent (selenium sulfide shampoo) who had acute dermatitis and discontinued treatment.
CONCLUSION
It is uncertain whether topical azoles are as effective as keratolytic agents in clinical clearance and occurrence of adverse events in patients with pityriasis versicolor. A wider search of grey literature and local studies are warranted. Larger RCTs with low risk of bias are recommended.
PubMed: 38939846
DOI: 10.47895/amp.vi0.5605 -
Frontiers in Pharmacology 2024Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell...
BACKGROUND
Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell carcinoma. However, comprehensive evaluation of its long-term safety profile in a large sample population remains elusive. The current study assessed Tivozanib-related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System.
METHODS
Disproportionality analyses, utilizing reporting odds ratio proportional reporting ratio Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker (MGPS) algorithms, were conducted to quantify signals of Tivozanib-related AEs. Weibull distribution was used to predict the varying risk incidence of AEs over time.
RESULTS
Out of 5,361,420 reports collected from the FAERS database, 1,366 reports of Tivozanib-associated AEs were identified. A total of 94 significant disproportionality preferred terms (PTs) conforming to the four algorithms simultaneously were retained. The most common AEs included fatigue, diarrhea, nausea, blood pressure increased, decreased appetite, and dysphonia, consistent with prior specifications and clinical trials. Unexpected significant AEs such as dyspnea, constipation, pain in extremity, stomatitis, and palmar-plantar erythrodysaesthesia syndrome was observed. The median onset time of Tivozanib-related AEs was 37 days (interquartile range [IQR] 11.75-91 days), with a majority (n = 127, 46.35%) occurring within the initial month following Tivozanib initiation.
CONCLUSION
Our observations align with clinical assertions regarding Tivozanib's safety profile. Additionally, we unveil potential novel and unexpected AE signatures associated with Tivozanib administration, highlighting the imperative for prospective clinical studies to validate these findings and elucidate their causal relationships. These results furnish valuable evidence to steer future clinical inquiries aimed at elucidating the safety profile of Tivozanib.
PubMed: 38939844
DOI: 10.3389/fphar.2024.1408135 -
JACC. Advances Jan 2024It is unknown how well cardiologists predict which Fontan patients are at risk for major adverse events (MAEs).
BACKGROUND
It is unknown how well cardiologists predict which Fontan patients are at risk for major adverse events (MAEs).
OBJECTIVES
The purpose of this study was to examine the accuracy of cardiologists' ability to identify the "good Fontan" patient, free from MAE within the following year, and compare that predicted risk cohort to patients who experienced MAE.
METHODS
This prospective, multicenter study included patients ≥10 years with lateral tunnel or extracardiac Fontan. The cardiologist was asked the yes/no "surprise" question: would you be surprised if your patient has a MAE in the next year? After 12 months, the cardiologist was surveyed to assess MAE. Agreement between cardiologist predictions of MAE and observed MAE was determined using the simple kappa coefficient. Multivariable generalized linear mixed effects models were performed to identify factors associated with MAE.
RESULTS
Overall, 146 patients were enrolled, and 99/146 (68%) patients w`ere predicted to be a "good Fontan." After 12 months, 17 (12%) experienced a MAE. The simple kappa coefficient of cardiologists' prediction was 0.17 (95% CI: 0.02-0.32), suggesting prediction of MAE was 17% better than random chance. In the multivariable cardiologist-predicted MAE (N = 47) model, diuretic/beta-blocker use ( ≤ 0.001) and systolic dysfunction ( = 0.005) were associated with MAE. In the observed multivariable MAE (N = 17) model, prior unplanned cardiac admission ( = 0.006), diuretic/beta-blocker use ( = 0.028), and ≥moderate atrioventricular valve regurgitation ( = 0.049) were associated with MAE.
CONCLUSIONS
Cardiologists are marginally able to predict which Fontan patients are at risk for MAE over a year. There was overlap between factors associated with a cardiologist's prediction of risk and observed MAE, namely the use of diuretic/beta-blocker.
PubMed: 38939804
DOI: 10.1016/j.jacadv.2023.100736 -
Journal of Arrhythmia Jun 2024The Mt FUJI study was a multicenter, prospective, randomized, single-blind, controlled trial comparing delivery catheter-based and stylet-based right ventricular (RV)...
BACKGROUND
The Mt FUJI study was a multicenter, prospective, randomized, single-blind, controlled trial comparing delivery catheter-based and stylet-based right ventricular (RV) lead placement at the RV septum. This study extended the follow-up duration to 1 year after implantation.
METHODS
Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid-term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events.
RESULTS
At the 1-year follow-up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, = .332), BNP levels (+8.0 [-11.1, 26.5] pg/mL vs. -8.7 [-15.3, 13.2] pg/mL, = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, < .001). All-cause death, hospitalization for heart failure, new development of atrial fibrillation, and pacing-induced cardiomyopathy occurred in seven patients in the delivery catheter group and five in the stylet group.
CONCLUSION
The delivery catheter system was similarly useful and safe compared to the stylet system in the mid-term follow-up from the Mt FUJI trial. Further long-term evaluations are warranted.
PubMed: 38939791
DOI: 10.1002/joa3.13034 -
Journal of Arrhythmia Jun 2024Warfarin is considered the primary oral anticoagulant for patients with atrial fibrillation and end-stage renal disease (ESRD) requiring dialysis. Although warfarin can...
BACKGROUND
Warfarin is considered the primary oral anticoagulant for patients with atrial fibrillation and end-stage renal disease (ESRD) requiring dialysis. Although warfarin can offer significant stroke prevention in this population, the accompanying major bleeding risks make warfarin nearly prohibitive. Apixaban was shown to be superior to warfarin in preventing stroke or systemic embolism, with a lower risk of bleeding and mortality in a large, randomized trial of individuals with mostly normal renal function but none with ESRD.
METHODS
We systematically reviewed evidence comparing apixaban versus warfarin for atrial fibrillation in this population, and evaluated outcomes of stroke or systemic embolism, and major bleeding using random-effects models. The main safety outcome was major bleeding, and the main effectiveness outcome was stroke or systemic embolism.
RESULTS
We found five observational studies of 10 036 patients (2638 receiving apixaban, and 7398 receiving warfarin) meeting inclusion criteria. Pooled analysis demonstrated a significant reduction in major bleeding with apixaban as compared to warfarin (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.42-0.61; < .0001). Apixaban was also associated with a reduction in intracranial bleeding (OR 0.58, 95% CI 0.37-0.92; = .02) and in gastrointestinal bleeding (OR 0.61, 95% CI 0.51-0.73; < .0001). Furthermore, apixaban was associated with a reduction in stroke/systemic embolism (OR 0.64, 95% CI 0.50-0.82; < .0001).
CONCLUSION
Apixaban was associated with superior outcomes and reduced adverse events compared to warfarin in observational studies of patients with atrial fibrillation on dialysis. Randomized controlled studies are needed to confirm these findings.
PubMed: 38939758
DOI: 10.1002/joa3.13051 -
JACC. Advances Apr 2024Statins are highly effective for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and mortality. Data on the benefit of statins in adults with heart...
BACKGROUND
Statins are highly effective for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and mortality. Data on the benefit of statins in adults with heart failure with preserved ejection fraction (HFpEF) and without ASCVD are limited.
OBJECTIVES
The purpose of this study was to determine whether statins are associated with a lower risk of mortality and major adverse cardiovascular events (MACE) in HFpEF.
METHODS
Veterans Health Administration data from 2002 to 2016, linked to Medicare and Medicaid claims and pharmaceutical data, were collected. Patients had a new HFpEF diagnosis and no known ASCVD or prior statin use at baseline. Cox proportional hazards models were fit to evaluate the association of new statin use with outcomes (all-cause mortality and MACE). Propensity score overlap weighting (PSW) was used to balance baseline characteristics.
RESULTS
Among 7,970 Veterans, 47% initiated a statin over a mean 6.0-year follow-up. At HFpEF diagnosis, mean age was 69 ± 12 years, 96% were male, 67% were White, 14% were Black, and mean EF was 60% ± 6%. Before PSW, statin users were younger with more prevalent metabolic syndrome, arthritis, and other chronic conditions. All characteristics were balanced after PSW. There were 5,314 deaths and 4,859 MACE events. After PSW, the hazard for all-cause mortality for statin users vs nonusers was 22% lower (HR: 0.78; 95% CI: 0.73-0.83). The HR for MACE was 0.79 (95% CI: 0.74-0.84), 0.69 (95% CI: 0.60-0.80) for all-cause hospitalization, and 0.72 (95% CI: 0.59-0.88) for HF hospitalization.
CONCLUSIONS
New statin use was associated with reduced all-cause mortality, MACE, and hospitalization in Veterans with HFpEF without prevalent ASCVD.
PubMed: 38939680
DOI: 10.1016/j.jacadv.2024.100869 -
JACC. Advances Apr 2024There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
BACKGROUND
There is a paucity of data on long-term outcomes after Fontan palliation in patients with a dominant morphological univentricular right (uRV) vs left (uLV) ventricle.
OBJECTIVES
The purpose of this study was to compare the incidence of atrial arrhythmias, thromboembolic events, cardiac transplantation, and death following Fontan palliation in patients with uRV vs uLV.
METHODS
The Alliance for Adult Research in Congenital Cardiology conducted a multicenter retrospective cohort study on patients with total cavopulmonary connection Fontan palliation across 12 centers in North America. All components of the composite outcome, that is, atrial arrhythmias, thromboembolic events, cardiac transplantation, and death, were reviewed and classified by a blinded adjudicating committee. Time-to-event analyses were performed that accounted for competing risks.
RESULTS
A total of 384 patients were followed for 10.5 ± 5.9 years. The composite outcome occurred in 3.7 vs 1.7 cases per 100 person-years for uRV (N = 171) vs uLV (N = 213), respectively ( < 0.001). In multivariable analyses, uRV conferred a >2-fold higher risk of the composite outcome (HR: 2.17, 95% CI: 1.45-3.45, < 0.001). In secondary analyses of components of the primary outcome, uRV was significantly associated with a greater risk of cardiac transplantation or death (HR: 9.09, 95% CI: 2.17-38.46, < 0.001) and atrial arrhythmias (HR: 2.17, 95% CI: 1.20-4.00, = 0.010) but not thromboembolic events (HR: 1.64, 95% CI: 0.86-3.16, = 0.131).
CONCLUSIONS
Fontan patients with uRV vs uLV morphology have a higher incidence of adverse cardiovascular events, including atrial arrhythmia, cardiac transplantation, and all-cause mortality.
PubMed: 38939676
DOI: 10.1016/j.jacadv.2024.100871