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Frontiers in Medicine 2023Systematic review.
STUDY DESIGN
Systematic review.
OBJECTIVE
The objective of this study was to evaluate the impact of phosphodiesterase (PDE) inhibitors on neurobehavioral outcomes in preclinical models of traumatic and non-traumatic spinal cord injury (SCI).
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered with PROSPERO (CRD42019150639). Searches were performed in MEDLINE and Embase. Studies were included if they evaluated the impact of PDE inhibitors on neurobehavioral outcomes in preclinical models of traumatic or non-traumatic SCI. Data were extracted from relevant studies, including sample characteristics, injury model, and neurobehavioral assessment and outcomes. Risk of bias was assessed using the SYRCLE checklist.
RESULTS
The search yielded a total of 1,679 studies, of which 22 met inclusion criteria. Sample sizes ranged from 11 to 144 animals. PDE inhibitors used include rolipram ( = 16), cilostazol ( = 4), roflumilast ( = 1), and PDE4-I ( = 1). The injury models used were traumatic SCI ( = 18), spinal cord ischemia ( = 3), and degenerative cervical myelopathy ( = 1). The most commonly assessed outcome measures were Basso, Beattie, Bresnahan (BBB) locomotor score ( = 13), and grid walking ( = 7). Of the 22 papers that met the final inclusion criteria, 12 showed a significant improvement in neurobehavioral outcomes following the use of PDE inhibitors, four papers had mixed findings and six found PDE inhibitors to be ineffective in improving neurobehavioral recovery following an SCI. Notably, these findings were broadly consistent across different PDE inhibitors and spinal cord injury models.
CONCLUSION
In preclinical models of traumatic and non-traumatic SCI, the administration of PDE inhibitors appeared to be associated with statistically significant improvements in neurobehavioral outcomes in a majority of included studies. However, the evidence was inconsistent with a high risk of bias. This review provides a foundation to aid the interpretation of subsequent clinical trials of PDE inhibitors in spinal cord injury.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=150639, identifier: CRD42019150639.
PubMed: 37675134
DOI: 10.3389/fmed.2023.1237219 -
Journal of Sport and Health Science Jul 2024The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The genetic variation of a specific gene, human cytochrome P450 enzyme 1A2 (CYP1A2) (rs762551), may be one reason for this difference. This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes' exercise performance after caffeine intake.
METHODS
A literature search through 4 databases (Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure) was conducted until March 2023. The effect size was expressed as the weighted mean difference (WMD) by calculating fixed effects meta-analysis if heterogeneity was not significant (I ≤ 50% and p ≥ 0.1). Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2.
RESULTS
The final number of studies meeting the inclusion criteria was 12 (n = 666 participants). The overall analysis showed that the cycling time trial significantly improved after caffeine intake (WMD = -0.48, 95% confidence interval (95%CI): -0.83 to -0.13, p = 0.007). In subgroup analyses, acute caffeine intake improved cycling time trial only in individuals with the A allele (WMD = -0.90, 95%CI: -1.48 to -0.33, p = 0.002), but not the C allele (WMD = -0.08, 95%CI: -0.32 to 0.17, p = 0.53). Caffeine supplementation did not influence the Wingate (WMD = 8.07, 95%CI: -22.04 to 38.18, p = 0.60) or countermovement jump test (CMJ) performance (WMD = 1.17, 95%CI: -0.02 to 2.36, p = 0.05), and these outcomes were not influenced by CYP1A2 genotype.
CONCLUSION
Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation. However, compared to placebo, acute caffeine supplementation failed to increase the Wingate or CMJ performance, regardless of CYP1A2 genotype.
Topics: Cytochrome P-450 CYP1A2; Humans; Caffeine; Athletic Performance; Performance-Enhancing Substances; Genotype; Dietary Supplements; Bicycling
PubMed: 38158179
DOI: 10.1016/j.jshs.2023.12.005 -
Medicina (Kaunas, Lithuania) Jul 2023: This study aimed to assess the comparative effectiveness of continuous positive airway pressure (CPAP) therapy and sildenafil pharmacological therapy in improving... (Meta-Analysis)
Meta-Analysis Review
: This study aimed to assess the comparative effectiveness of continuous positive airway pressure (CPAP) therapy and sildenafil pharmacological therapy in improving sexual function among patients with obstructive sleep apnea (OSA) and erectile dysfunction (ED). : Population: Patients affected by OSA and ED; Intervention: CPAP therapy vs. Comparison: Sildenafil pharmacological therapy; Outcomes: Improvement in erectile function, as measured by the International Index of Erectile Function 5 (IIEF-5) scoring system; Time: A systematic review of the literature from the past 20 years; Study Design: Observational studies comparing erectile function improvements after OSA treatment. : A total of eight papers were included in the qualitative summary, involving four hundred fifty-seven patients with ED and OSA. Erectile function improvements were observed in both treatment groups. After sildenafil and CPAP treatment, the mean IIEF-5 domain scores were 37.7 and 27.3, respectively ( < 0.001). Sildenafil 100 mg demonstrated a higher therapeutic impact compared to CPAP treatment. : CPAP therapy significantly improved sexual parameters in most studies for OSA patients with ED. The findings suggest that CPAP therapy effectively alleviates erectile dysfunction symptoms, resulting in improved sexual performance in OSA patients. The comparison of the two treatments indicates that sildenafil has a more substantial therapeutic impact on erectile function than CPAP therapy; however, a combined treatment will provide a cumulative effect.
Topics: Male; Humans; Sildenafil Citrate; Erectile Dysfunction; Continuous Positive Airway Pressure; Sleep Apnea, Obstructive; Sexual Dysfunction, Physiological
PubMed: 37512129
DOI: 10.3390/medicina59071318 -
Cureus Mar 2024Psoriasis is a chronic autoimmune inflammatory skin disease that is associated with other conditions, one of them being psoriatic arthritis (PsA). Apremilast, a... (Review)
Review
Psoriasis is a chronic autoimmune inflammatory skin disease that is associated with other conditions, one of them being psoriatic arthritis (PsA). Apremilast, a phosphodiesterase-4 inhibitor, displayed promising results in multiple trials for patients with PsA. This systematic review and meta-analysis aims to showcase its efficacy and safety when compared to placebo. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was adopted after registration on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023476245). Four databases were systematically searched from their inception until October 25, 2023. As a result, five randomized controlled trials were included with 1,849 participants, after thorough screening. The primary efficacy endpoint evaluated in this meta-analysis was the American College of Rheumatology Response Criteria 20 (ACR20). The results significantly favored apremilast (risk ratio [RR] = 1.92, 95% confidence interval [CI] 1.66-2.21; < 0.00001; = 0%) as opposed to placebo. Similarly, secondary efficacy endpoints, ACR50 (RR = 2.34, 95% CI 1.79-3.06; < 0.00001; = 0%), ACR70 (RR = 2.89, 95% CI 1.62-5.18; = 0.0003; = 0%), and the Health Assessment Questionnaire and Disability Index (HAQ-DI; standardized mean difference [SMD] = -0.26, 95% CI -0.34 to -0.17; < 0.00001; = 0%) were also in significant favor of apremilast. However, apremilast had a higher occurrence of gastrointestinal adverse events than placebo (RR = 1.21, 95% CI 1.12-1.30; < 0.00001; = 19%). To conclude, apremilast shows promising efficaciousness with some nonserious side effects when compared to placebo, but further trials are needed for comparison with other management lines.
PubMed: 38590459
DOI: 10.7759/cureus.55773 -
Nutrients Jun 2024This systematic review aimed to evaluate the effectiveness of the independent or combined use of nutritional ergogenic aids belonging to Group A of the ABCD... (Review)
Review
This systematic review aimed to evaluate the effectiveness of the independent or combined use of nutritional ergogenic aids belonging to Group A of the ABCD classification by the Australian Institute of Sport (AIS) in the context of cycling (caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates, and glycerol). A comprehensive search was carried out using three databases: PubMed, Scopus, and Web of Science. All the databases were searched for Randomized Controlled Trials or crossover design studies assessing the effects of supplementation on cycling performance in comparison with placebos in healthy adults. The methodological quality of each study was evaluated using the Physiotherapy Evidence Database scale. Thirty-six articles involving 701 participants were included in this review, examining supplementation with caffeine (n = 5), creatine (n = 2), sodium bicarbonate (n = 6), beta-alanine (n = 3), and nitrates (n = 8). Additionally, supplemental combinations of caffeine and creatine (n = 3), caffeine and sodium bicarbonate (n = 3), caffeine and nitrates (n = 1), creatine and sodium bicarbonate (n = 1), and sodium bicarbonate and beta-alanine (n = 4) were analyzed. A benefit for cyclists' athletic performnce was found when consuming a caffeine supplement, and a potential positive effect was noted after the consumption of sodium bicarbonate, as well as after the combination of caffeine and creatine. However, no statistically significant effects were identified for the remaining supplements, whether administered individually or in combination.
Topics: Humans; Dietary Supplements; Bicycling; Athletic Performance; Nitrates; Performance-Enhancing Substances; Caffeine; Creatine; Sodium Bicarbonate; beta-Alanine; Adult; Male; Female; Randomized Controlled Trials as Topic
PubMed: 38892701
DOI: 10.3390/nu16111768 -
Journal of Cardiovascular Development... Dec 2023Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is... (Review)
Review
Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) -3.68, 95% CI [-2.03, -5.32], < 0.0001) and PVR (MD -1.40 Wood units, 95% CI [-1.97, -0.82], < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m, 95% CI [0.14, 0.39], < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [-8.55, 33.79], = 0.24), PaO (MD -2.20 mm Hg, 95% CI [-4.62, 0.22], = 0.08), or BNP or NT-proBNP therapy (MD -0.15, 95% CI [-0.46, 0.17], = 0.36). The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD.
PubMed: 38132665
DOI: 10.3390/jcdd10120498 -
The European Respiratory Journal Dec 2023There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is uncertainty about the best treatment option for children/adolescents with uncontrolled asthma despite inhaled corticosteroids (ICS) and international guidelines make different recommendations. We evaluated the pharmacological treatments to reduce asthma exacerbations and symptoms in uncontrolled patients age <18 years on ICS.
METHODS
We searched MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Embase, Web of Science, National Institute for Health and Care Excellence Technology Appraisals, National Institute for Health and Care Research Health Technology Assessment series, World Health Organization International Clinical Trials Registry, conference abstracts and internal clinical trial registers (1 July 2014 to 5 May 2023) for randomised controlled trials of participants age <18 years with uncontrolled asthma on any ICS dose alone at screening. Studies before July 2014 were retrieved from previous systematic reviews/contact with authors. Patients had to be randomised to any dose of ICS alone or combined with long-acting β-agonists (LABA) or combined with leukotriene receptor antagonists (LTRA), LTRA alone, theophylline or placebo. Primary outcomes were exacerbation and asthma control. The interventions evaluated were ICS (low/medium/high dose), ICS+LABA, ICS+LTRA, LTRA alone, theophylline and placebo.
RESULTS
Of the 4708 publications identified, 144 trials were eligible. Individual participant data were obtained from 29 trials and aggregate data were obtained from 19 trials. Compared with ICS Low, ICS Medium+LABA was associated with the lowest odds of exacerbation (OR 0.44, 95% credibility interval (95% CrI) 0.19-0.90) and with an increased forced expiratory volume in 1 s (mean difference 0.71, 95% CrI 0.35-1.06). Treatment with LTRA was the least preferred. No apparent differences were found for asthma control.
CONCLUSIONS
Uncontrolled children/adolescents on low-dose ICS should be recommended a change to medium-dose ICS+LABA to reduce the risk for exacerbation and improve lung function.
Topics: Adolescent; Child; Humans; Administration, Inhalation; Adrenal Cortex Hormones; Anti-Asthmatic Agents; Asthma; Drug Therapy, Combination; Leukotriene Antagonists; Network Meta-Analysis; Systematic Reviews as Topic; Theophylline
PubMed: 37945034
DOI: 10.1183/13993003.01011-2023 -
Nutrients Apr 2024This study aimed to explore the effects of acute ingestion of caffeine capsules on muscle strength and muscle endurance. We searched the PubMed, Web of Science,... (Meta-Analysis)
Meta-Analysis
This study aimed to explore the effects of acute ingestion of caffeine capsules on muscle strength and muscle endurance. We searched the PubMed, Web of Science, Cochrane, Scopus, and EBSCO databases. Data were pooled using the weighted mean difference (WMD) and 95% confidence interval. Fourteen studies fulfilled the inclusion criteria. The acute ingestion of caffeine capsules significantly improved muscle strength (WMD, 7.09, < 0.00001) and muscle endurance (WMD, 1.37; < 0.00001), especially in males (muscle strength, WMD, 7.59, < 0.00001; muscle endurance, WMD, 1.40, < 0.00001). Subgroup analyses showed that ≥ 6 mg/kg body weight of caffeine (WMD, 6.35, < 0.00001) and ingesting caffeine 45 min pre-exercise (WMD, 8.61, < 0.00001) were more effective in improving muscle strength, with the acute ingestion of caffeine capsules having a greater effect on lower body muscle strength (WMD, 10.19, < 0.00001). In addition, the acute ingestion of caffeine capsules had a greater effect in moderate-intensity muscle endurance tests (WMD, 1.76, < 0.00001). An acute ingestion of caffeine capsules significantly improved muscle strength and muscle endurance in the upper body and lower body of males.
Topics: Adult; Female; Humans; Male; Young Adult; Caffeine; Capsules; Muscle Strength; Muscle, Skeletal; Physical Endurance
PubMed: 38674836
DOI: 10.3390/nu16081146 -
Journal of Perinatology : Official... Jun 2024This systematic review and meta-analysis evaluated the evidence for dose and effectiveness of caffeine in preterm infants. MEDLINE, EMBASE, CINHAL Plus, CENTRAL, and... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the evidence for dose and effectiveness of caffeine in preterm infants. MEDLINE, EMBASE, CINHAL Plus, CENTRAL, and trial databases were searched to July 2022 for trials randomizing preterm infants to caffeine vs. placebo/no treatment, or low (≤10 mg·kg) vs. high dose (>10 mg·kg caffeine citrate equivalent). Two researchers extracted data and assessed risk of bias using RoB; GRADE evaluation was completed by all authors. Meta-analysis of 15 studies (3530 infants) was performed in REVMAN across four epochs: neonatal/infant (birth-1 year), early childhood (1-5 years), middle childhood (6-11 years) and adolescence (12-19 years). Caffeine reduced apnea (RR 0.59; 95%CI 0.46,0.75; very low certainty) and bronchopulmonary dysplasia (0.77; 0.69,0.86; moderate certainty), with higher doses more effective. Caffeine had no effect on neurocognitive impairment in early childhood but possible benefit on motor function in middle childhood (0.72; 0.57,0.91; moderate certainty). The optimal dose remains unknown; further long-term studies, are needed.
Topics: Humans; Caffeine; Infant, Newborn; Infant, Premature; Apnea; Neurodevelopmental Disorders; Infant; Child; Child, Preschool; Adolescent; Central Nervous System Stimulants; Bronchopulmonary Dysplasia; Infant, Premature, Diseases
PubMed: 38553606
DOI: 10.1038/s41372-024-01939-x -
The International Journal of Lower... Jun 2024The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant... (Meta-Analysis)
Meta-Analysis
The venous leg ulcers are debilitating, painful, and often unresponsive to advanced dressing treatments, so drugs used locally and systematically are essential adjuvant therapy-pentoxifylline (PTX) whose anti-inflammatory effects may offer a promising avenue to treat venous leg ulcers. However, the current results are controversial. To further evaluate the efficacy and safety of PTX, we performed an updated meta-analysis of randomized placebo-controlled trials of PTX in the treatment of venous leg ulcers. We systematically searched multiple electronic databases PubMed, Web of Science, Embase, the Cochrane Library, the Cochrane Central Register of Controlled Trials, China Science and Technology Journal Database, WanFang Data, China National Knowledge Infrastructure, and the Chinese Biomedical Literature Database to identify eligible studies. Randomized clinical trials of pentoxifylline versus placebo treatment in patients with venous leg ulcers were considered for inclusion. The primary outcomes included ulcer healing rate and the incidence of adverse events after treatment. The secondary outcomes were the ulcer significant improvement (the ulcer size shrank by more than 60% after treatment) rate, mean duration of complete wound healing and changes in mean ulcer size. A meta-analysis and qualitative analysis were conducted to estimate endpoints. A total of 13 randomized clinical trials, including 921 individuals, were finally included. Compared with placebo, pentoxifylline significantly improved the ulcer healing rate (RR = 1.59, 95%CI 1.22 to 2.07, < .001) and significant improvement rate (RR = 2.36, 95%CI 1.31 to 4.24, = .004) while increased the incidence of gastrointestinal disturbances (RR = 2.29, 95%CI 1.04 to 5.03, = .04) at the same time. Moreover, pentoxifylline also shortened mean duration of complete wound healing ( = .007) and shrank ulcer size ( = .02). Currently available evidence suggests that pentoxifylline could help venous leg ulcers heal more quickly and effectively. However, the evidence is insufficient to prove the results due to moderate-certainty evidence. Large-scale, well-designed randomized clinical trials are warranted.
Topics: Humans; Pentoxifylline; Randomized Controlled Trials as Topic; Treatment Outcome; Varicose Ulcer; Wound Healing
PubMed: 34779680
DOI: 10.1177/15347346211050769