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Lung Cancer (Amsterdam, Netherlands) Jun 2024Mirtazapine blocks 5-hydroxytryptamine type (5-HT), 5-HT, 5-HT and histamine H receptors, similarly to olanzapine. This study aimed to investigate the efficacy and...
BACKGROUND
Mirtazapine blocks 5-hydroxytryptamine type (5-HT), 5-HT, 5-HT and histamine H receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers.
METHODS
We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h).
RESULTS
Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0.
CONCLUSIONS
Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.
Topics: Humans; Granisetron; Male; Mirtazapine; Female; Dexamethasone; Middle Aged; Aged; Nausea; Vomiting; Prospective Studies; Carboplatin; Antiemetics; Thoracic Neoplasms; Adult; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Japan; Drug Therapy, Combination
PubMed: 38678830
DOI: 10.1016/j.lungcan.2024.107801 -
Korean Journal of Ophthalmology : KJO Jun 2024To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in...
PURPOSE
To assess efficacy, safety, and tolerability of the preservative-free (PF) fixed-dose combination (FC) of tafluprost 0.0015%/timolol 0.5% (PF tafluprost/timolol FC) in treatments-naive patients with primary open-angle glaucoma (POAG).
METHODS
This was a retrospective, real-world clinical practice setting study that included 107 eyes of 107 subjects with POAG who had never been treated for glaucoma. All subjects were received PF tafluprost/timolol FC once daily. Intraocular pressure (IOP) levels were documented for each eye at the untreated baseline and up to 6 months after the initiation of medical treatment. All adverse events, including ocular and systemic adverse reactions, were recorded. Additionally, the reasons for medication discontinuations were thoroughly documented.
RESULTS
A total of 32 POAG patients with high-baseline IOP (>21 mmHg) and 75 with normal-baseline IOP were included in the study. The subjects' baseline mean age was 62.4 ± 8.7 years (range, 26.0-85.0 years); among them, 42 were female (39.3%). Mean IOP at baseline for all patients was 18.6 ± 4.3 mmHg. The mean IOP at 6 months was 12.6 ± 4.7 mmHg, representing a significant decrease compared to the baseline (-32%, p < 0.001). In POAG patients with high-baseline IOP, mean IOP was significantly lowered from 28.0 ± 5.7 mmHg at baseline to 18.0 ± 5.5 mmHg (-35%, p < 0.001); in patients with normal-baseline IOP, from 14.6 ± 3.4 mmHg at baseline to 10.3 ± 4.1 mmHg (-29%, p < 0.001). PF tafluprost/timolol FC was well-tolerated and safe. After 6 months, 97.2% of all patients remained on therapy.
CONCLUSIONS
In this real-world observational study, once-daily treatment with PF tafluprost/timolol FC demonstrated clinically relevant and statistically significant efficacy, as well as safety and good tolerability, in treatment-naive patients diagnosed with POAG.
Topics: Humans; Glaucoma, Open-Angle; Female; Male; Retrospective Studies; Intraocular Pressure; Middle Aged; Prostaglandins F; Timolol; Adult; Aged; Treatment Outcome; Ophthalmic Solutions; Preservatives, Pharmaceutical; Drug Combinations; Antihypertensive Agents; Follow-Up Studies; Tonometry, Ocular; Aged, 80 and over; Dose-Response Relationship, Drug
PubMed: 38665112
DOI: 10.3341/kjo.2024.0021 -
Clinical Cardiology May 2024Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents... (Comparative Study)
Comparative Study
BACKGROUND
Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients.
HYPOTHESIS
The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR).
METHODS
The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker.
RESULTS
On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026).
CONCLUSION
In patients with GFR ≥ 30 mL/min/1.73 m, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m would require further investigation.
Topics: Humans; Atrial Fibrillation; Female; Male; Calcium Channel Blockers; Adrenergic beta-Antagonists; Glomerular Filtration Rate; Aged; Heart Rate; Renal Insufficiency, Chronic; Retrospective Studies; Treatment Outcome; Middle Aged; Hospitalization; Kidney; Risk Factors; Follow-Up Studies
PubMed: 38664980
DOI: 10.1002/clc.24257 -
Critical Care (London, England) Apr 2024
Topics: Extracorporeal Membrane Oxygenation; Humans; Adrenergic beta-Antagonists; Male
PubMed: 38664835
DOI: 10.1186/s13054-024-04923-1 -
Pulmonary Pharmacology & Therapeutics Jun 2024Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Evaluating the pharmacokinetics of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide delivered via pressurised metered-dose inhaler using a low global warming potential propellant.
INTRODUCTION
Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.
METHODS
The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90 % confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (C) and area under the plasma concentration-time curve between time zero and the last quantifiable timepoint (AUC) for the analytes were between 80 and 125 %.
RESULTS
In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB C in Study 2 (upper 90 % CI 125.11 %). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96 % for C and 127.34 % for AUC). In Study 1, GB AUC lower CI was 74.54 %; in Study 2 upper limits were 135.64 % for C and 129.12 % for AUC. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC, although not for C. Both formulations were similarly well tolerated in all three studies.
CONCLUSIONS
Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.
Topics: Beclomethasone; Humans; Formoterol Fumarate; Metered Dose Inhalers; Cross-Over Studies; Male; Glycopyrrolate; Drug Combinations; Administration, Inhalation; Adult; Double-Blind Method; Female; Aerosol Propellants; Middle Aged; Young Adult; Area Under Curve; Therapeutic Equivalency; Bronchodilator Agents; Anti-Asthmatic Agents; Fluorocarbons
PubMed: 38663512
DOI: 10.1016/j.pupt.2024.102299 -
Saudi Medical Journal Apr 2024To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting...
OBJECTIVES
To investigate differences in the incidence of enteropathy or intestinal malabsorption in patients taking angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB), and beta blockers (BBs) at a single center in Korea.
METHODS
In this retrospective study, we utilized data from the Yangsan electronic medical records to identify 129,169 patients. These individuals were prescribed olmesartan, other ARBs, ACEI, CCB, and BBs between November 2008 and February 2021.
RESULTS
Of the 44,775 patients, 51 (0.11%) were observed to have enteropathy or intestinal malabsorption. Compared with the ACEI group, the adjusted odds ratios (ORs) for enteropathy and intestinal malabsorption were OR=1.313 (95% confidence interval [CI]: [0.188-6.798], =0.893) for olmesartan, OR=0.915 (95% CI: [0.525-1.595], =0.754) for the other ARBs, OR=0.928 (95% CI: [0.200-4.307]; =0.924) for the CCB, and OR=0.663 (95% CI: [0.151-2.906]; =0.586) for the BBs group. These findings were adjusted for factors such as age, gender, duration of antihypertensive medication, and comorbidities.
CONCLUSION
In a retrospective cohort study of patients on antihypertensive medications, no significant difference was found in the incidence of enteropathy or intestinal malabsorption when ACEI was compared to olmesartan, other ARBs, CCB, and BBs.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Malabsorption Syndromes; Antihypertensive Agents; Aged; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Calcium Channel Blockers; Intestinal Diseases; Adrenergic beta-Antagonists; Imidazoles; Tetrazoles; Incidence; Adult; Republic of Korea; Cohort Studies; Hypertension
PubMed: 38657980
DOI: 10.15537/smj.2024.45.4.20230739 -
International Journal of Chronic... 2024To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany.
PURPOSE
To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany.
PATIENTS AND METHODS
Retrospective cohort study of patients with COPD and ≥1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015-31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting β-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-month pre-index period.
RESULTS
In total, 18,630 patients were identified as prevalent triple therapy users (MITT: 17,945; FF/UMEC/VI: 700; BDP/GLY/FOR: 908; non-mutually exclusive) and 2932 patients were identified as incident triple therapy initiators (MITT: 2246; FF/UMEC/VI: 311; BDP/GLY/FOR: 395; non-mutually exclusive). For both the prevalent and incident cohorts, more than two-thirds of patients experienced ≥1 moderate/severe exacerbation in the preceding 24 months; in both cohorts more BDP/GLY/FOR users experienced ≥1 moderate/severe exacerbation, compared with FF/UMEC/VI and MITT users. Overall, 97.9% of prevalent triple therapy users and 86.4% of incident triple therapy initiators received maintenance treatment in the 24-month pre-index period.
CONCLUSION
In a real-world setting in Germany, triple therapy was most frequently used after maintenance therapy in patients with recent exacerbations, in line with current treatment recommendations.
Topics: Humans; Male; Pulmonary Disease, Chronic Obstructive; Female; Retrospective Studies; Germany; Aged; Administration, Inhalation; Middle Aged; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Nebulizers and Vaporizers; Glycopyrrolate; Drug Combinations; Chlorobenzenes; Quinuclidines; Treatment Outcome; Benzyl Alcohols; Beclomethasone; Formoterol Fumarate; Drug Therapy, Combination; Time Factors; Aged, 80 and over
PubMed: 38646606
DOI: 10.2147/COPD.S431291 -
Scientific Reports Apr 2024Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective...
Currently, the utilization patterns of medications for heart failure (HF) after worsening HF events remain unelucidated in Japan. Here, we conducted a retrospective cohort study evaluating the changes in HF drug utilization patterns in 6 months before and after hospitalizations for HF. The adherence to newly initiated HF medications was evaluated based on the proportion of days covered (PDC) and persistence as continuous treatment episodes among new users. The study included 9091 patients hospitalized for HF between January 2016 and September 2019, including 2735 (30.1%) patients who were newly prescribed at least one HF medication after hospitalization. Despite increases in the use of foundational HF therapy (beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers, or mineralocorticoid receptor antagonists), 35.6% and 7.6% of patients were treated with the HF foundational monotherapy or diuretics alone after hospitalization, respectively. The mean PDC of newly initiated HF medications ranged from 0.57 for thiazide diuretics to 0.77 for sodium-glucose cotransporter-2 inhibitors. Continuous use of HF medications during the first year after initiation was observed in 30-60% of patients. The mean PDC and one-year continuous HF medication use were consistently lower in patients aged ≥ 75 years and in patients with a history of HF hospitalization for all HF medication classes except for tolvaptan and digoxin. Despite the guideline recommendations of HF pharmacotherapy, both treatment and adherence were suboptimal after HF hospitalization, especially in vulnerable populations such as older patients and those with prior HF hospitalizations.
Topics: Humans; Retrospective Studies; Japan; Sodium-Glucose Transporter 2 Inhibitors; Heart Failure; Angiotensin-Converting Enzyme Inhibitors; Hospitalization; Adrenergic beta-Antagonists; Diuretics; Angiotensin Receptor Antagonists; Mineralocorticoid Receptor Antagonists
PubMed: 38643208
DOI: 10.1038/s41598-024-60011-y -
Current Opinion in Pharmacology Jun 2024β-blockers are a solid pillar in the treatment of cardiovascular diseases. However, they are highly discussed regarding effectiveness for certain indications and... (Review)
Review
β-blockers are a solid pillar in the treatment of cardiovascular diseases. However, they are highly discussed regarding effectiveness for certain indications and side-effects. Even though there are up to 20 licensed compounds, only four are used for heart failure (HF) therapy. On the receptor level several key characteristics seem to influence the clinical outcome: subtype selectivity, antagonistic vs (inverse/biased) agonistic properties and -in particular- ancillary capacities. On a molecular level, divergent and novel signaling patterns are being identified and extra-cardiac effects on e.g. inflammation, metabolism and oxidative stress are highlighted. This review discusses different well-known and newly discovered characteristics that need to be considered for HF therapy and in the context of co-morbidities.
Topics: Humans; Signal Transduction; Animals; Heart Failure; Receptors, Adrenergic, beta; Adrenergic beta-Antagonists
PubMed: 38636195
DOI: 10.1016/j.coph.2024.102458 -
Journal of Hypertension Jun 2024Originally, the beta-blockers were equally ranked alongside the other antihypertensive drug classes. Things changed when two major long-term randomized controlled...
Originally, the beta-blockers were equally ranked alongside the other antihypertensive drug classes. Things changed when two major long-term randomized controlled trials, ASCOT-BPLA and LIFE showed that the patients receiving the beta-blockers based regimes suffered 25-30% more strokes than those receiving a calcium channel blocker based regime or an angiotensin receptor blocker based regime. The inferiority of the beta-blockers at stroke prevention was not due to differences in blood pressure control during the follow-up period in both trials. The 2023 European Society of Hypertension (ESH) guidelines still argue in favour of beta-blockers that their clinical inferiority was simply to lesser blood pressure reduction rather than class effect. The analysis argues that the return of beta-blockers as a first-line option for the management of uncomplicated hypertension by the ESH is a cause for concern and should be reconsidered.
Topics: Humans; Hypertension; Antihypertensive Agents; Practice Guidelines as Topic; Europe; Societies, Medical; Adrenergic beta-Antagonists; Blood Pressure; Calcium Channel Blockers
PubMed: 38634468
DOI: 10.1097/HJH.0000000000003733