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The Nurse Practitioner Jun 2024Atopic dermatitis (AD), a chronic inflammatory, pruritic skin disorder, is seen primarily in the pediatric population but can be found among all age groups. The symptoms...
Atopic dermatitis (AD), a chronic inflammatory, pruritic skin disorder, is seen primarily in the pediatric population but can be found among all age groups. The symptoms of AD can cause embarrassment in patients and can interrupt daily activities and productivity, potentially resulting in avoidance of social situations. In addition to nonpharmacologic management, mainstay pharmacologic treatments for AD are topical medications including corticosteroids, calcineurin inhibitors, phosphodiesterase-4 inhibitors, and topical Janus kinase (JAK) inhibitors. Promising new drugs-oral JAK inhibitors and monoclonal antibodies-have emerged as new treatment options for moderate-to-severe AD.
Topics: Dermatitis, Atopic; Humans; Janus Kinase Inhibitors; Phosphodiesterase 4 Inhibitors; Adrenal Cortex Hormones; Calcineurin Inhibitors; Dermatologic Agents; Nurse Practitioners
PubMed: 38941080
DOI: 10.1097/01.NPR.0000000000000183 -
Circulation Jun 2024We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined...
Tadalafil for Treatment of Combined Postcapillary and Precapillary Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction: A Randomized Controlled Phase 3 Study.
BACKGROUND
We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension.
METHODS
In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline.
RESULTS
Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; =0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; =0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group.
CONCLUSIONS
The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points.
REGISTRATION
URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.
PubMed: 38939948
DOI: 10.1161/CIRCULATIONAHA.124.069340 -
Andrology Jun 2024Erectile dysfunction (ED) is prevalent not only among older males but also in younger. The physical activity has been considered a potential protective factor against... (Review)
Review
BACKGROUND
Erectile dysfunction (ED) is prevalent not only among older males but also in younger. The physical activity has been considered a potential protective factor against ED. However, there is a lack of comprehensive research on the impact of exercise interventions specifically on ED patients.
OBJECTIVES
This study aimed to assess the effectiveness of the physical activity in addressing ED symptoms among adult males, without the use of the phosphodiesterase-5 inhibitors (PDE5i) therapy. Additionally, subgroup analysis was performed to evaluate the effects of different exercise modes.
METHODS
Employing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic literature search. A registered protocol is available at PROSPERO (CRD42023441717). Our search spanned PubMed, Web of Science, Embase, and Cochrane Library, with data collection ending on 11 April 2024. The Cochrane Risk of Bias tool was applied by two independent authors to assess randomized controlled trial (RCT) quality. The primary endpoint was determined as the International Index of Erectile Function (IIEF) scores.
RESULTS
A total of seven RCTs were included. Utilizing a random-effects model, the estimated standardized mean difference (SMD) was 0.69 (95% confidence interval [CI] 0.37 to 1.02, p < 0.0001) for the overall impact of the physical activity. Subgroup analysis revealed SMDs of 0.81 (95% CI 0.56 to 1.06; p < 0.00001) for aerobic training alone. However, no significant improvement was observed with pelvic floor muscle training (PFMT) (SMD 0.03; 95% CI -0.68 to 0.75; p = 0.93) and a combination of aerobic and resistance training (SMD 0.84; 95% CI -0.41 to 2.09; p = 0.19) CONCLUSION: The findings of this study highlight a significant improvement in the erectile function following exercise interventions for adult men with ED, who are not receiving the PDE5i therapy, especially in conducting aerobic training alone. However, PFMT and a combination of aerobic and resistance training did not show significant improvements in erectile function from this study.
PubMed: 38937909
DOI: 10.1111/andr.13682 -
Scientific Reports Jun 2024Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both...
Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH) is a singular pathological entity necessitating early diagnostic approaches and both prophylactic and curative interventions. This retrospective before-after study investigates the effects of a management strategy integrating perfusion computed tomography (CTP), vigilant clinical monitoring and standardized systemic administration of milrinone on the occurrence of delayed cerebral infarction (DCIn). The period included 277 patients, and the one 453. There was a higher prevalence of Modified Fisher score III/IV and more frequent diagnosis of vasospasm in the period. Conversely, the occurrence of DCIn was reduced with the management strategy (adjusted OR 0.48, 95% CI [0.26; 0.84]). Notably, delayed ischemic neurologic deficits were less prevalent at the time of vasospasm diagnosis (24 vs 11%, ), suggesting that CTP facilitated early detection. In patients diagnosed with vasospasm, intravenous milrinone was more frequently administered (80 vs 54%, ) and associated with superior hemodynamics. The present study from a large cohort of aSAH patients suggests, for one part, the interest of CTP in early diagnosis of vasospasm and DCI, and for the other the efficacy of CT perfusion-guided systemic administration of milrinone in both preventing and treating DCIn.
Topics: Humans; Subarachnoid Hemorrhage; Milrinone; Male; Female; Middle Aged; Cerebral Infarction; Retrospective Studies; Tomography, X-Ray Computed; Aged; Vasospasm, Intracranial; Adult; Administration, Intravenous
PubMed: 38937568
DOI: 10.1038/s41598-024-65706-w -
Sexual Medicine Reviews Jun 2024Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new...
INTRODUCTION
Prior consensus meetings have addressed the relationship between phosphodiesterase type 5 (PDE5) inhibition and cardiac health. Given significant accumulation of new data in the past decade, a fourth consensus conference on this topic was convened in Pasadena, California, on March 10 and 11, 2023.
OBJECTIVES
Our meeting aimed to update existing knowledge, assess current guidelines, and make recommendations for future research and practice in this area.
METHODS
An expert panel reviewed existing research and clinical practice guidelines.
RESULTS
Key findings and clinical recommendations are the following: First, erectile dysfunction (ED) is a risk marker and enhancer for cardiovascular (CV) disease. For men with ED and intermediate levels of CV risk, coronary artery calcium (CAC) computed tomography should be considered in addition to previous management algorithms. Second, sexual activity is generally safe for men with ED, although stress testing should still be considered for men with reduced exercise tolerance or ischemia. Third, the safety of PDE5 inhibitor use with concomitant medications was reviewed in depth, particularly concomitant use with nitrates or alpha-blockers. With rare exceptions, PDE5 inhibitors can be safely used in men being treated for hypertension, lower urinary tract symptoms and other common male disorders. Fourth, for men unresponsive to oral therapy or with absolute contraindications for PDE5 inhibitor administration, multiple treatment options can be selected. These were reviewed in depth with clinical recommendations. Fifth, evidence from retrospective studies points strongly toward cardioprotective effects of chronic PDE5-inhibitor use in men. Decreased rates of adverse cardiac outcomes in men taking PDE-5 inhibitors has been consistently reported from multiple studies. Sixth, recommendations were made regarding over-the-counter access and potential risks of dietary supplement adulteration. Seventh, although limited data exist in women, PDE5 inhibitors are generally safe and are being tested for use in multiple new indications.
CONCLUSION
Studies support the overall cardiovascular safety of the PDE5 inhibitors. New indications and applications were reviewed in depth.
PubMed: 38936840
DOI: 10.1093/sxmrev/qeae043 -
Archivio Italiano Di Urologia,... Jun 2024Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia...
Pentoxifylline treatment as a safe method for selecting viable testicular spermatozoa before cryopreservation of a small numbers of spermatozoa in azoospermia individuals.
BACKGROUND
Single sperm cryopreservation (SSC) is a specific technique especially used in individuals with small numbers of sperm who suffered from non-obstructive azoospermia (NOA). Testicular specimens possess poor motility and low population of viable spermatozoa. Therefore, sperm selection methods such as applying pentoxifylline (PTX) may improve motility in these cases. The main aim of this study was to evaluate the protective effects of PTX on testicular spermatozoa before and after performing SSC.
METHODS
Thirty testicular samples were obtained from men with azoospermia. This study was conducted in two phases. Phase 1 evaluated the effect of PTX for sperm selection before SSC. Twenty testicular samples were divided to two experimental groups: SSC without (I) and with PTX treatment (II). For PTX treatment spermatozoa were incubated with PTX at 37°C for 30 min and only motile spermatozoa were selected for SSC. In phase 2, ten testicular samples were cryopreserved with SSC and warming procedure was carried out in droplet with and without PTX. Motility and viability rates, morphology by motile sperm organelle morphology examination (MSOME), DNA fragmentation by sperm chromatin dispersion test (SCD) and mitochondrial membrane potential (MMP) were evaluated.
RESULTS
In phase 1, post warm motility rate was higher in PTX exposed group compared to the unexposed group (25.6 ± 8.13 vs. 0.85 ± 2.1) (p > 0.00). Recovery rate, viability and morphology were not significantly different between groups. DNA integrity and MMP were also similar between both groups. In phase 2 although motility increased in PTX group compared to without PTX group (29.30 ± 12.73 vs. 1.90 ± 2.64) (p > 0.00), the viability rate was not different (70.40 ± 12.12 vs. 65.30 ± 11.87). All above mentioned parameters were similar between the two SSC groups.
CONCLUSIONS
Supplementation of testicular spermatozoa with PTX before cryopreservation increases motility and did not have adverse effects on viability, morphology, DNA integrity and MMP. PTX could be used as sperm selection method before single sperm cryopreservation, but PTX could not maintain motile the most of viable testicular sperms.
Topics: Male; Humans; Pentoxifylline; Cryopreservation; Azoospermia; Spermatozoa; Sperm Motility; Semen Preservation; DNA Fragmentation; Testis; Adult; Cell Survival; Membrane Potential, Mitochondrial
PubMed: 38934523
DOI: 10.4081/aiua.2024.12525 -
International Journal of Urology :... Jun 2024Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder... (Review)
Review
Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.
PubMed: 38934050
DOI: 10.1111/iju.15518 -
Sensors (Basel, Switzerland) Jun 2024Movement-related cortical potential (MRCP) is observed in EEG recordings prior to a voluntary movement. It has been used for e.g., quantifying motor learning and for...
Movement-related cortical potential (MRCP) is observed in EEG recordings prior to a voluntary movement. It has been used for e.g., quantifying motor learning and for brain-computer interfacing (BCIs). The MRCP amplitude is affected by various factors, but the effect of caffeine is underexplored. The aim of this study was to investigate if a cup of coffee with 85 mg caffeine modulated the MRCP amplitude and the classification of MRCPs versus idle activity, which estimates BCI performance. Twenty-six healthy participants performed 2 × 100 ankle dorsiflexion separated by a 10-min break before a cup of coffee was consumed, followed by another 100 movements. EEG was recorded during the movements and divided into epochs, which were averaged to extract three average MRCPs that were compared. Also, idle activity epochs were extracted. Features were extracted from the epochs and classified using random forest analysis. The MRCP amplitude did not change after consuming caffeine. There was a slight increase of two percentage points in the classification accuracy after consuming caffeine. In conclusion, a cup of coffee with 85 mg caffeine does not affect the MRCP amplitude, and improves MRCP-based BCI performance slightly. The findings suggest that drinking coffee is only a minor confounder in MRCP-related studies.
Topics: Humans; Caffeine; Male; Electroencephalography; Female; Movement; Adult; Brain-Computer Interfaces; Young Adult; Coffee
PubMed: 38931814
DOI: 10.3390/s24124030 -
Pharmaceuticals (Basel, Switzerland) Jun 2024(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At...
(1) Background: Globally, about 600 million people are afflicted with diabetes, and one of its most prevalent complications is neuropathy, a debilitating condition. At the present time, the exploration of novel therapies for alleviating diabetic-neuropathy-associated pain is genuinely captivating, considering that current therapeutic options are characterized by poor efficacy and significant risk of side effects. In the current research, we evaluated the antihyperalgesic effect the sildenafil (phosphodiesterase-5 inhibitor)-metformin (antihyperglycemic agent) combination and its impact on biochemical markers in alloxan-induced diabetic neuropathy in rats. (2) Methods: This study involved a cohort of 70 diabetic rats and 10 non-diabetic rats. Diabetic neuropathy was induced by a single dose of 130 mg/kg alloxan. The rats were submitted to thermal stimulus test using a hot-cold plate and to tactile stimulus test using von Frey filaments. Moreover, at the end of the experiment, the animals were sacrificed and their brains and livers were collected to investigate the impact of this combination on TNF-α, IL-6, nitrites and thiols levels. (3) Results: The results demonstrated that all sildenafil-metformin combinations decreased the pain sensitivity in the von Frey test, hot plate test and cold plate test. Furthermore, alterations in nitrites and thiols concentrations and pro-inflammatory cytokines (specifically TNF-α and IL-6) were noted following a 15-day regimen of various sildenafil-metformin combinations. (4) Conclusions: The combination of sildenafil and metformin has a synergistic effect on alleviating pain in alloxan-induced diabetic neuropathy rats. Additionally, the combination effectively decreased inflammation, inhibited the rise in NOS activity, and provided protection against glutathione depletion.
PubMed: 38931450
DOI: 10.3390/ph17060783 -
Nutrients Jun 2024Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared... (Randomized Controlled Trial)
Randomized Controlled Trial
Guarana (GUA), a Brazilian seed extract, contains caffeine and other bioactive compounds that may have psychoactive effects. To assess the acute effects of GUA compared to a low dose of caffeine (CAF) on cognitive and mood parameters, twenty participants completed a double-blind, crossover experiment where they ingested capsules containing the following: (1) 100 mg CAF, (2) 500 mg GUA containing 130 mg caffeine, or (3) placebo (PLA). Cognitive tests (Simon and 2N-Back Task) were performed at the baseline (pre-ingestion) and 60 min after ingestion. The response time for the cognitive tests and heart rate variability were unaffected ( > 0.05) by treatment, although 2N-Back was overall faster ( = 0.001) across time. The accuracy in the 2N-Back Task showed a significant interaction effect ( = 0.029) due to higher post-ingestion versus pre-ingestion levels ( = 0.033), but only with the PLA. The supplements also had no effect on cognitive measures following physical fatigue ( = 11). There was an interaction effect on perceived mental energy, where the pre-ingestion of GUA had lower mental pep ratings compared to post-ingestion ( = 0.006) and post-exercise ( = 0.018) levels. Neither the acute ingestion of GUA nor low dose of CAF influenced cognitive performance or provided consistent benefit on mood or mental workload through vagal modulation. Additional investigations are beneficial to determining the lowest effective dose for CAF or GUA to influence mood and/or cognitive performance.
Topics: Humans; Caffeine; Paullinia; Male; Cross-Over Studies; Double-Blind Method; Cognition; Adult; Young Adult; Female; Heart Rate; Affect; Vagus Nerve; Plant Extracts; Dietary Supplements
PubMed: 38931247
DOI: 10.3390/nu16121892