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British Journal of Hospital Medicine... Apr 2024There is a significant burden of cardiovascular disease morbidity and mortality in the end-stage kidney disease population, driven by traditional and non-traditional... (Review)
Review
There is a significant burden of cardiovascular disease morbidity and mortality in the end-stage kidney disease population, driven by traditional and non-traditional risk factors. Despite its prevalence, heart failure is difficult to diagnose in the dialysis population due to overlapping clinical presentations, limitations of investigations, and the impact on the cardiorenal axis. 'Foundation therapies' are the key medications which improve patient outcomes in heart failure with reduced ejection fraction and include beta-blockers, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. They are underutilised in the dialysis population due to the exclusion of chronic kidney disease patients from major trials and legitimate clinical concerns e.g. hyperkalaemia, intradialytic hypotension and residual kidney function preservation. A coordinated cardiorenal multidisciplinary approach can guide appropriate diagnostic considerations (biomarkers interpretation, imaging, addressing unique complications of kidney disease), optimise dialysis management (prescription length, frequency and ultrafiltration targets) and when at euvolaemia facilitate the stepwise introduction of appropriate foundation therapies.
Topics: Humans; Heart Failure; Renal Dialysis; Kidney Failure, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System
PubMed: 38708982
DOI: 10.12968/hmed.2023.0452 -
PloS One 2024We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparison of the efficacy and complications of tolterodine and α-adrenergic receptor blockers in improving ureteral stent-related symptoms: A systematic review and meta-analysis.
OBJECTIVE
We conducted a systematic evaluation of the therapeutic efficacy and complications of tolterodine and α-adrenergic receptor blockers in alleviating ureteral stent-related symptoms.
METHODS
Until August 2023, we conducted a comprehensive literature search on PubMed, Embase, Web of Science, and Cochrane Library to identify randomized controlled trials evaluating the efficacy and complications of tolterodine and α-adrenergic receptor blockers in treating ureteral stent-related symptoms. Two reviewers independently screened studies and extracted data. The scores from various domains of the Ureteral Stent Symptom Questionnaire (USSQ) were summarized and compared, and statistical analysis was performed using RevMan 5.4.0 software.
RESULTS
A total of 8 studies met the inclusion criteria for our analysis. These studies were conducted at different centers. All studies were randomized controlled trials, involving a total of 487 patients, with 244 patients receiving α-adrenergic receptor blockers and 243 patients receiving tolterodine. The results showed that tolterodine demonstrated significantly better improvement in body pain (MD, 1.56; 95% CI [0.46, 2.66]; p = 0.005) (MD, 0.46; 95% CI [0.12, 0.80]; p = 0.008) (MD, 3.21; 95% CI [1.89, 4.52]; p = 0.00001) among patients after ureteral stent placement compared to α-adrenergic receptor blockers at different time points. Additionally, at 4 weeks, tolterodine showed superior improvement in general health (MD, 0.15; 95% CI [0.03, 0.27]; p = 0.01) and urinary symptoms (MD, 1.62; 95% CI [0.59, 2.66]; p = 0.002) compared to α-adrenergic receptor blockers, while at 6 weeks, tolterodine showed better improvement in work performance (MD, -1.60; 95% CI [-2.73, -0.48]; p = 0.005) compared to α-adrenergic receptor blockers. Additionally, the incidence of dry mouth (RR, 4.21; 95% CI [1.38, 12.87]; p = 0.01) is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, there were no significant statistical differences between the two drugs in other outcomes.
CONCLUSION
This meta-analysis suggests that tolterodine is superior to α-adrenergic receptor blockers in improving physical pain symptoms after ureteral stent placement, while α-adrenergic receptor blockers are more effective than tolterodine in enhancing work performance. Additionally, the incidence of dry mouth is higher with the use of tolterodine compared to α-adrenergic receptor blockers. However, higher-quality randomized controlled trials are needed to further investigate this issue.
Topics: Tolterodine Tartrate; Humans; Stents; Adrenergic alpha-Antagonists; Ureter; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38701097
DOI: 10.1371/journal.pone.0302716 -
World Journal of Urology May 2024Men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH), will have deterioration in the quality of life. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Men with overactive bladder (OAB) and benign prostatic hyperplasia (BPH), will have deterioration in the quality of life.
OBJECTIVE
The aim of this study was to evaluate the effect of combining pelvic floor muscle training with the urgency suppression technique (PFMT-st) and silodosin in comparison with silodosin in men with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) after 12 weeks of treatment.
PATIENTS AND METHODS
A total of 158 patients were randomized into two groups. The control group received oral silodosin at a daily dose of 8 mg. The experimental group was administered PFMT-st and silodosin. The evaluation methods included the number of voids and intensity of urgencies over 24 h using a micturition diary, the International Prostate Symptom Score (IPSS), the Overactive Bladder Questionnaire (OAB-q), and the patient global impression of improvement (PGI-I).
RESULTS
142 of 172 (86.6%) men were assessed (70 in the control group, 72 in the experimental group). The significant changes were in favor of the experimental group (p < 0.001) in the number of voids per 24 h (- 1.95 ± 1.94 vs. - 0.90 ± 1.44), the OAB-q symptom score (- 14.25 ± 10.05 vs. - 9.28 ± 10.60), the intensity of urgencies (- 0.97 ± 0.53 vs. 0.24 ± 0.57), the IPSS (- 4.59 ± 3.00 vs. - 2.30 ± 3.63), and in the PGI-I (2.24 ± 0.79 vs. 3.60 ± 0.92).
CONCLUSIONS
The addition of PFMT-st to silodosin treatment significantly improved OAB in men with BPH. This is the first study to confirm that PFMT-st should be the first-choice treatment for OAB in BPH.
Topics: Humans; Male; Prostatic Hyperplasia; Urinary Bladder, Overactive; Pelvic Floor; Aged; Middle Aged; Exercise Therapy; Combined Modality Therapy; Treatment Outcome; Indoles
PubMed: 38698269
DOI: 10.1007/s00345-024-04974-7 -
Missouri Medicine 2024
Topics: Humans; Migraine Disorders; Nasal Sprays; Adrenergic beta-Antagonists; Administration, Intranasal
PubMed: 38694613
DOI: No ID Found -
International Journal of Pharmaceutics May 2024Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong... (Comparative Study)
Comparative Study
Utilizing the allyl-terminated copolymer methoxy(poly(ethylene glycol))-block-poly(jasmine lactone) in the development of amorphous solid dispersions: A comparative study of functionalized and non-functionalized polymer.
Molecular interactions are crucial to stabilize amorphous drugs in amorphous solid dispersions (ASDs). Most polymers, however, have only a limited ability to form strong molecular interactions with drugs. Polymers tailored to fit the physicochemical properties of the drug molecule to be incorporated, for instance by allowing the incorporation of specific functional groups, would be highly sought-for in this regard. For this purpose, the novel allyl-terminated polymer methoxy(polyethylene glycol)-block-poly(jasmine lactone) (mPEG-b-PJL) has been synthesized and functionalized to potentially enhance specific drug-polymer interactions. This study investigated the use of mPEG-b-PJL in ASDs, using carvedilol (CAR), a weakly basic model drug. The findings revealed that the acidic functionalized form of the polymer (mPEG-b-PJL-COOH) indeed established stronger molecular interactions with CAR compared to its non-functionalized counterpart mPEG-b-PJL. Evaluations on polymer effectiveness in forming ASDs demonstrated that mPEG-b-PJL-COOH outperformed its non-functionalized counterpart in miscibility, drug loading ability, and stability, inferred from reduced molecular mobility. However, dissolution tests indicated that ASDs with mPEG-b-PJL-COOH did not significantly improve the dissolution behaviour compared to amorphous CAR alone, despite potential solubility enhancement through micelle formation. Overall, this study confirms the potential of functionalized polymers in ASD formulations, while the challenge of improving dissolution performance in these ASDs remains an area of further development.
Topics: Polyethylene Glycols; Solubility; Carvedilol; Drug Stability; Polymers; Lactones; Chemistry, Pharmaceutical; Drug Compounding
PubMed: 38685442
DOI: 10.1016/j.ijpharm.2024.124175 -
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