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Cardiovascular Diabetology Jul 2022The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy.
METHODS
We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs.
RESULTS
Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36-1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56-2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35-2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39-0.79).
CONCLUSION
Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.
Topics: Adenosine Triphosphate; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Defibrillators, Implantable; Diabetes Mellitus; Humans; Proportional Hazards Models; Risk Factors
PubMed: 35906611
DOI: 10.1186/s12933-022-01580-y -
Presse Medicale (Paris, France : 1983) Mar 2017To provide a systematic review of epidemiological data regarding the association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men. (Review)
Review
AIM
To provide a systematic review of epidemiological data regarding the association between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) in men.
SEARCH STRATEGY
A research has been conducted on the Medline database using the keywords: ("erectile dysfunction" or "sexual dysfunction") and ("benign prostatic hyperplasia" or "lower urinary tract symptoms"). The eligibility of studies was defined using the PICOS method in accordance with the PRISMA statement. Cross-sectional studies and prospective cohorts assessing the association between LUTS and ED in the primary care setting or in general practice (i.e. exclusion of patients seen in outpatient urology or andrology) were included.
RESULTS
Among 898 reports assessed, seven studies were included in this systematic review (whole cohort: 1,196,393 men). There were five cross-sectional studies and two prospective cohorts. The whole seven studies reported an association between LUTS and ED (range of odds-ratio: 1.52-4.03). Four common pathogenic mechanisms were found in the literature, all of them being somewhat related with metabolic syndrome and cardiovascular risk factors: reduced nitric oxide (NO) pathway signalling, increased RhoA-Rho kinase signalling, autonomic nervous system hyperactivity and pelvic atherosclerosis.
LIMITATIONS
The main limitations of this review were: a possible publication bias, the relatively low number of included studies and the lack of assessment of potential confounders such as factors related to sexual partner.
CONCLUSION
The close epidemiological and pathogenic links between LUTS and ED have given rise to a new nosological entity: the erectile urogenital dysfunction, which should be assessed globally with special considerations to frequently associated comorbidities such as metabolic syndrome and cardiovascular risk factors.
Topics: Atherosclerosis; Autonomic Nervous System; Cardiovascular Diseases; Comorbidity; Cross-Sectional Studies; Cyclic GMP; Endothelium, Vascular; Erectile Dysfunction; Humans; Impotence, Vasculogenic; Lower Urinary Tract Symptoms; Male; Metabolic Syndrome; Muscle, Smooth; Nitric Acid; Prospective Studies; Prostatic Hyperplasia; Risk Factors; Signal Transduction; rho-Associated Kinases; rhoA GTP-Binding Protein
PubMed: 27745762
DOI: 10.1016/j.lpm.2016.09.002 -
Journal of Cell Science Nov 2018Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a... (Meta-Analysis)
Meta-Analysis
Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a meta-analysis of 278 systematically identified studies that investigated mechanically stimulated ATP release (MSAR) to quantify the amounts, kinetics and mechanisms of ATP release under normal and pathological conditions. Mechanically stimulated mammalian cells were shown to release 38.6 [95% confidence interval (CI): 18.2-81.8] amol ATP/cell on average with a characteristic time constant of 32 s (95% CI: 16-66). Analysis of ATP release mechanisms revealed the existence of conserved and tissue-specific release routes. We assessed ATP release in pathophysiological states, and found that ATP release was elevated in inflammation and injury, and attenuated in hereditary (such as cystic fibrosis) and metabolic (such as type II diabetes) conditions. Our study links cell-specific ATP release mechanisms to pathophysiological changes in ATP release and allows ATP release-targeting interventions to be mapped to site-specific effects. This work demonstrates that quantitative synthesis of basic research can generate non-trivial hypotheses and inform evidence-driven translational studies.
Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Humans
PubMed: 30333142
DOI: 10.1242/jcs.223354 -
The Korean Journal of Internal Medicine Jan 2024The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
The effectiveness of remdesivir treatment in reducing mortality and the requirement for mechanical ventilation (MV) remains uncertain, as randomized controlled trials (RCTs) have produced conflicting results.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other data resources to find RCTs published prior to April 10, 2023. The selection of studies, assessment of risk of bias, and meta-analysis were conducted according to PRISMA guidelines. The primary outcomes were all-cause mortality and the need to initiate MV.
RESULTS
A total of 5,068 articles were screened, from eight RCTs comprising 11,945 patients. The meta-analysis found that, compared to standard care or placebo, remdesivir treatment provided no significant all-cause mortality benefit (pooled risk ratio [RR], 0.93; 95% confidence interval [CI], 0.85-1.02; 8 studies; high certainty evidence), while subgroup analyses revealed a trend towards reduced mortality among patients requiring oxygen but not MV (pooled RR, 0.88; 95% CI, 0.77-1.00; 6 studies; I2 = 4%). The need to initiate MV (pooled RR, 0.74; 95% CI, 0.59-0.94; 7 studies; moderate certainty evidence) in remdesivir-treated patients was also reduced compared to controls. Remdesivir significantly increased clinical improvement and discharge and significantly reduced serious adverse events.
CONCLUSION
In this systematic review and meta-analysis of RCTs, it was found that remdesivir treatment did not show a substantial decrease in the risk of mortality. However, it was linked to a reduction in the necessity for additional ventilatory support, suggesting remdesivir could be beneficial for COVID-19 patients, particularly those who are not on MV.
Topics: Humans; COVID-19; Respiration, Artificial; COVID-19 Drug Treatment; Patient Acuity; Adenosine Monophosphate; Alanine
PubMed: 38151918
DOI: 10.3904/kjim.2023.357 -
Theranostics 2021Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We...
Treatment of severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19): a systematic review of , , and clinical trials.
Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of , , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; COVID-19; Carbamates; Coronavirus Infections; Disease Models, Animal; Drug Combinations; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Imidazoles; Immunization, Passive; Pyrrolidines; Randomized Controlled Trials as Topic; Severe Acute Respiratory Syndrome; Sofosbuvir; Treatment Outcome; Valine; COVID-19 Serotherapy
PubMed: 33391531
DOI: 10.7150/thno.48342 -
Archives of Gynecology and Obstetrics Aug 2021To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy... (Meta-Analysis)
Meta-Analysis Review
Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.
PURPOSE
To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer.
RESULTS
We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events).
CONCLUSIONS
PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.
Topics: Adenosine Diphosphate; Antineoplastic Agents; Carcinoma, Ovarian Epithelial; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Ribose; Treatment Outcome
PubMed: 34021367
DOI: 10.1007/s00404-021-06070-2 -
Frontiers in Public Health 2023Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Aging is associated with decreased nicotinamide adenine dinucleotide (NAD) levels, which in turn cause dysfunctional mitochondria and indirectly affect a myriad of diseases. Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) serves as a central rate-limiting enzyme in NAD synthesis, making it an indispensable health mediator. This meta-analysis examined the effect of exercise training on the expression of iNAMPT in humans.
METHODS
We searched PubMed, Scopus, ClinicalTrials.gov, and the International Clinical Trials Registry Platform for studies published between the inception of the database and July 5, 2023. Using the common-effect model, evidence for the change in iNAMPT following exercise training was synthesized as Cohen's .
RESULTS
The search yielded five eligible studies. The overall effect size is 0.81, with a 95% confidence interval of 0.55 to 1.07. Therefore, a random adult will have a 71.7% probability that iNAMPT will be up-regulated following exercise training. In general, exercise training resulted in a 1.46-fold increase in iNAMPT. Our probability statistics indicate that subgroups of interest may differ practically. Specifically, there is a 79.3% probability of increased iNAMPT in men, compared to a 69.0% probability in the overall population; young adults have a 75.6% probability of having an increased iNAMPT, whereas aged adults have a 68.7% probability; and, iNAMPT has a 75.1% probability increase after aerobic exercise and a 66.4% probability increase after resistance exercise.
CONCLUSION
Exercise training is effective for increasing iNAMPT levels in skeletal muscles. This essential enzyme regulates not only cellular energetics but also healthspan. Therefore, exercise should be promoted as a natural slow-aging lifestyle.
Topics: Humans; Aging; Exercise; Muscle, Skeletal; NAD; Nicotinamide Phosphoribosyltransferase
PubMed: 37954044
DOI: 10.3389/fpubh.2023.1287421 -
Expert Review of Anti-infective Therapy Oct 2021: Currently, there is no approved therapeutic entity for coronavirus disease 2019 (COVID-19) and clinicians are primarily relying on drug repurposing. However, findings...
: Currently, there is no approved therapeutic entity for coronavirus disease 2019 (COVID-19) and clinicians are primarily relying on drug repurposing. However, findings across studies are widely disparate, making it difficult to draw firm conclusions. Since clinicians need accurate evidence to treat COVID-19, this manuscript systematically analyzed the published and ongoing studies evaluating the pharmacological interventions for COVID-19.: A systematic search of observational studies and Clinical Trials on the treatment and prevention of COVID-19 was performed by using various databases from inception to 2 December 2020.: A total of 460 studies met the inclusion criteria. Of these, 37 were research studies, 386 were ongoing trials, and 37 were completed trials. Anti-virals, steroids, anti-malarial, plasma exchange, and monoclonal antibodies were the most common treatment modalities used alone or in combination in these studies. However, tocilizumab, plasma exchange, and steroids have shown significant improvements in patient's clinical and radiological status. Tocilizumab reported minimum hospital stay of 2 days along with maximum recovery and patient's stability rate. Existing literature demonstrate promising results of tocilizumab, plasma exchange, and steroids among COVID-19 patients. Nevertheless, these studies are accompanied by several methodological disparities which should be considered while interpreting the results.
Topics: Adenosine Monophosphate; Alanine; Amides; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antimalarials; Antiviral Agents; COVID-19; Chloroquine; Clinical Trials as Topic; Humans; Hydroxychloroquine; Immunization, Passive; Indoles; Intensive Care Units; Length of Stay; Lopinavir; Methylprednisolone; Observational Studies as Topic; Patient Admission; Pyrazines; Ritonavir; SARS-CoV-2; Survival Rate; COVID-19 Drug Treatment; COVID-19 Serotherapy
PubMed: 33719819
DOI: 10.1080/14787210.2021.1902805 -
American Journal of TherapeuticsRemdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time...
BACKGROUND
Remdesivir (RDV) is the main antiviral for the treatment of moderate to severe forms of Coronavirus disease 2019 (COVID-19). Several studies revealed a shortening time to clinical improvement of COVID-19 and mortality benefits in patients receiving RDV. The patients with renal disease were excluded from large clinical trials of RDV, and the probable nephrotoxicity of the drug, its metabolites, and the vehicle (sulfobutylether-β-cyclodextrin) have led to the recommendation against using RDV in patients with an estimated glomerular filtration rate of <30 mL/min.
AREAS OF UNCERTAINTY
This systematic review aimed to collect data about the necessity and safety administration of RDV in the setting of renal impairment.
DATA SOURCES
Search through databases including MEDLINE, ScienceDirect, Cochrane Library, and PubMed was performed. The studies were carried out in adults and enrolled patients with different types of renal impairment (ie, acute kidney injury, chronic kidney disease, kidney transplant, and renal replacement therapy) were included. Eligible studies were assessed, and required data were extracted.
RESULTS
Twenty-two cross-sectional studies, cohorts, case reports, and case series were included in this review. The mortality rate was between 7.3% and 50%, and various severity of COVID-19 was included in the studies. None of them reported an increase in adverse effects attributed to RDV administration. A decrease in inflammatory mediators and other benefits were obvious.
CONCLUSIONS
Although the manufacturer's labeling does not recommend RDV administration in patients with severe renal impairment, it seems that nephrotoxicity is less concerning in the population of these patients. Moreover, RDV may be helpful in acute kidney injury induced by the viral invasion of COVID-19. To the best of our knowledge, this is the first systematic review of the use of RDV in kidney failure. Larger, well-designed, and pharmacokinetic studies are required to have a safe and logical recommendation about the use of RDV in patients with renal disorders.
Topics: Acute Kidney Injury; Adenosine Monophosphate; Adult; Alanine; Antiviral Agents; Cross-Sectional Studies; Humans; Renal Insufficiency, Chronic; COVID-19 Drug Treatment
PubMed: 35984955
DOI: 10.1097/MJT.0000000000001543 -
Revista Espanola de Quimioterapia :... Jun 2022A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and...
OBJECTIVE
A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19.
METHODS
A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability.
RESULTS
A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution.
CONCLUSIONS
We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; COVID-19 Drug Treatment
PubMed: 35294145
DOI: 10.37201/req/154.2021