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Neuroscience and Biobehavioral Reviews Dec 2023Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing... (Meta-Analysis)
Meta-Analysis Review
Non-Alzheimer's dementia (NAD) accounts for 30% of all neurodegenerative conditions and is characterized by cognitive decline beyond mere memory dysfunction. Diagnosing NAD remains challenging due to the lack of established biomarkers. Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with NAD and healthy controls. Our meta-analyses indicated that TMS neurophysiological examinations revealed decreased glutamatergic function in patients with frontotemporal dementia (FTD) and decreased GABAergic function in patients with FTD, progressive supranuclear palsy, Huntington's disease, cortico-basal syndrome, and multiple system atrophy-parkinsonian type. In addition, decreased cholinergic function was found in dementia with Lewy body and vascular dementia. These results suggest the potential of TMS as an additional diagnostic tool to differentiate NAD.
Topics: Humans; Transcranial Magnetic Stimulation; Frontotemporal Dementia; Neurodegenerative Diseases; NAD; Alzheimer Disease; Cholinergic Agents; Neural Inhibition; Evoked Potentials, Motor
PubMed: 37926239
DOI: 10.1016/j.neubiorev.2023.105451 -
Advances in Therapy Dec 2023Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL)... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Clofarabine monotherapy at a dose of 52 mg/m per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1-21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted.
METHODS
A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m. The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety.
RESULTS
A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3-4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia.
CONCLUSION
In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.
Topics: Child; Humans; Acute Disease; Antineoplastic Combined Chemotherapy Protocols; Clofarabine; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Clinical Trials as Topic
PubMed: 37819554
DOI: 10.1007/s12325-023-02696-7 -
American Journal of Cardiovascular... Jan 2024Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor as compared with the oral P2Y12 inhibition, clopidogrel, or placebo in acute coronary syndromes.
METHODS
This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, major bleeding, minor bleeding, and the need for blood transfusion.
RESULTS
The analysis was comprised of 6 studies including 26,444 patients treated with cangrelor, clopidogrel, or placebo. There were no statistically significant differences in the incidence of all-cause mortality, myocardial infarction, stent thrombosis, target vessel revascularization, or major bleeding. Cangrelor was associated with a higher risk of minor bleeding than clopidogrel or placebo, with no difference in requiring blood transfusion.
CONCLUSION
Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.
Topics: Humans; Clopidogrel; Acute Coronary Syndrome; Platelet Aggregation Inhibitors; Network Meta-Analysis; Purinergic P2Y Receptor Antagonists; Adenosine Monophosphate; Myocardial Infarction; Hemorrhage; Percutaneous Coronary Intervention; Treatment Outcome; Thrombosis
PubMed: 37995040
DOI: 10.1007/s40256-023-00616-2 -
BJU International Dec 2023To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic... (Meta-Analysis)
Meta-Analysis Review
Poly(adenosine diphosphate-ribose) polymerase inhibitor combinations in first-line metastatic castrate-resistant prostate cancer setting: a systematic review and meta-analysis.
OBJECTIVES
To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among patients with metastatic castrate-resistant prostate cancer (mCRPC) receiving a combination of first-line poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARAT) vs placebo/ARAT.
MATERIALS AND METHODS
We conducted a systematic review/meta-analysis of all published Phase III randomised controlled trials using EMBASE, MEDLINE, and Cochrane (inception until 6 June 2023). Published full-text manuscripts and conference abstracts were inclusion eligible. Study selection/data extraction were independently performed by two authors. The Cochrane Risk-of-Bias 2 Tool was used, and certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Pooled hazard ratios (HRs) and relative risks, with corresponding confidence intervals (CIs), were generated using random-effects models.
RESULTS
Three trials were identified: PROpel, MAGNITUDE, and TALAPRO-2. Compared to placebo/ARAT, the PARPi/ARAT combination was associated with a 35% rPFS improvement in the overall cohort (HR 0.65, 95% CI 0.56-0.76), with 68%, 45%, and 26% improvements in the BReast CAncer gene 1/gene 2 (BRCA1/2)-mutated (BRCA1/2m; P < 0.001), homologous recombination repair-mutated (HRRm; P < 0.001), and non-HRRm cohorts (P = 0.003), respectively. OS data maturity ranged from 31% to 48%, with overall cohort OS data unavailable from MAGNITUDE. The PROpel/TALAPRO-2 pooled analysis demonstrated a 16% OS improvement in the overall cohort (HR 0.84, 95 CI 0.72-0.98; P = 0.02). OS in the HRRm (HR 0.76, 95% CI 0.61-0.95) and the BRCA1/2m cohorts (HR 0.53, 95% CI 0.18-1.56) were improved, with a higher effect magnitude compared to the overall cohort. This combination was associated with a 45% relative risk increase in Grade ≥3 TEAEs, including 6.22-fold for Grade ≥3 anaemia (31.9% vs 4.9%).
CONCLUSIONS
The addition of PARPi to ARAT in the first-line mCRPC setting is associated with rPFS benefits across subgroups, with the greatest magnitude of benefit in BRCA1/2m patients. OS benefits remain inconsistent irrespective of HRRm status, with significant increases in Grade ≥3 TEAEs, particularly anaemia. Currently, we suggest this combined approach be selectively offered to HRRm patients, preferentially BRCA1/2m.
Topics: Male; Humans; BRCA1 Protein; Ribose; Prostatic Neoplasms, Castration-Resistant; BRCA2 Protein; Anemia; Adenosine Diphosphate
PubMed: 37461140
DOI: 10.1111/bju.16130 -
Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review.American Journal of Physiology.... Apr 2024Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including... (Review)
Review
Nicotinamide adenine dinucleotide (NAD) is an essential pyridine nucleotide cofactor that is present in cells and in several important biological processes, including oxidative phosphorylation and production of adenosine triphosphate, DNA repair, calcium-dependent secondary messenger and gene expression. The purpose of this systematic review is to examine whether the coenzyme formulae NAD and NADH are safe and effective when acting as a supplement to humans. This systematic review of randomized clinical trials performed a search in six electronic databases: PubMed, MEDLINE (), Embase, Cochrane CENTRAL (clinical trials), Web of Science, and Scopus. Secondary search included the databases (e.g., Clinical trials.gov, Rebec, Google Scholar - advance). Two reviewers assessed and extracted the studies independently. The risk of bias in studies was performed using version 2 of the Cochrane risk of bias tool for randomized trials. This review includes 10 studies, with a total of 489 participants. The studies included different clinical conditions, such as chronic fatigue syndrome (CFS), older adults, Parkinson's disease, overweight, postmenopausal prediabetes, and Alzheimer's disease. Based on studies, the supplementation with NADH and precursors was well tolerated and observed clinical results such as, a decrease in anxiety conditions and maximum heart rate was observed after a stress test, increased muscle insulin sensitivity, insulin signaling. Quality of life, fatigue intensity, and sleep quality among others were evaluated on patients with CFS. All studies showed some side effects, thus, the most common associated with NADs use are muscle pain, nervous disorders, fatigue, sleep disturbance, and headaches. All adverse events cataloged by the studies did not present a serious risk to the health of the participants. Overall, these findings support that the oral administration of NADH can be associated to an increase in general quality of life and improvement on health parameters (e.g., a decrease in anxiety, maximum heart rate, inflammatory cytokines in serum, and cerebrospinal fluid). NADH supplementation is safe and has a low incidence of side effects. Future investigations are needed to evidence the clinical benefits regarding specific diseases and doses administered.
Topics: Humans; Aged; Quality of Life; Fatigue Syndrome, Chronic; NAD; Dietary Supplements
PubMed: 37971292
DOI: 10.1152/ajpendo.00242.2023 -
Journal of Obesity 2024Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Type 2 diabetes mellitus and metabolic syndrome represent two closely intertwined public health challenges that have reached alarming epidemic proportions in low- and middle-income countries, particularly in sub-Saharan Africa. Therefore, the current study aimed to determine the weighted pooled prevalence of metabolic syndrome and its components among individuals with type 2 diabetes mellitus in sub-Saharan Africa as defined by the 2004 National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATP III 2004) and/or the International Diabetes Federation (IDF) criteria.
METHODS
A systematic search was conducted to retrieve studies published in the English language on the prevalence of metabolic syndrome among type 2 diabetic individuals in sub-Saharan Africa. Searches were carried out in PubMed, Embase, Scopus, Google Scholar, African Index Medicus, and African Journal Online from their inception until July 31, 2023. A random-effects model was employed to estimate the weighted pooled prevalence of metabolic syndrome in sub-Saharan Africa. Evidence of between-study variance attributed to heterogeneity was assessed using Cochran's Q statistic and the I2 statistic. The Joanna Briggs Institute quality appraisal criteria were used to evaluate the methodological quality of the included studies. The summary estimates were presented with forest plots and tables. Publication bias was checked with the funnel plot and Egger's regression test.
RESULTS
Overall, 1421 articles were identified and evaluated using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, and 30 studies that met the inclusion criteria were included in the final analysis. The weighted pooled prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa was 63.1% (95% CI: 57.9-68.1) when using the NCEP-ATP III 2004 criteria and 60.8% (95% CI: 50.7-70.0) when using the IDF criteria. Subgroup analysis, using NCEP-ATP III 2004 and IDF criteria, revealed higher weighted pooled prevalence among females: 73.5% (95% CI: 67.4-79.5), 71.6% (95% CI: 60.2-82.9), compared to males: 50.5% (95% CI: 43.8-57.2), 44.5% (95% CI: 34.2-54.8), respectively. Central obesity was the most prevalent component of metabolic syndrome, with a pooled prevalence of 55.9% and 61.6% using NCEP-ATP III 2004 and IDF criteria, respectively. There was no statistical evidence of publication bias in both the NCEP-ATP III 2004 and IDF pooled estimates.
CONCLUSIONS
The findings underscore the alarming prevalence of metabolic syndrome among individuals with type 2 diabetes mellitus in sub-Saharan Africa. Therefore, it is essential to promote lifestyle modifications, such as regular exercise and balanced diets, prioritize routine obesity screenings, and implement early interventions and robust public health measures to mitigate the risks associated with central obesity.
Topics: Male; Adult; Female; Humans; Metabolic Syndrome; Diabetes Mellitus, Type 2; Risk Factors; Obesity, Abdominal; Prevalence; Obesity; Africa South of the Sahara; Adenosine Triphosphate
PubMed: 38410415
DOI: 10.1155/2024/1240457 -
Expert Review of Anticancer Therapy 2024Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparison of poly (ADP-ribose) polymerase inhibitors (PARPis) as maintenance therapy for newly-diagnosed and platinum-sensitive recurrent ovarian cancer with mutational status: a systematic review and network meta-analysis.
BACKGROUND
Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) treatment for ovarian cancer (OC) are ever-changing. This study aimed to compare the efficacy and overall safety of available PARPi as maintenance therapy for BRCA mutation status in patients with newly diagnosed and platinum-sensitive recurrent (PSR) OC patients.
RESEARCH DESIGN AND METHODS
Relevant RCTs were systematically retrieved from PubMed and Embase until 31 May 2022. Progression-free survival (PFS) and overall survival (OS) based on mutation status and adverse events (AEs) regardless of mutation were efficacy and safety endpoints.
RESULTS
In newly diagnosed BRCAm-OC patients, olaparib (HR: 0.33; 95% confidence interval [CI]: 0.25, 0.43) and other PARPis [niraparib (HR: 0.40; 95% CI: 0.29, 0.55), rucaparib (HR: 0.40; 95% CI: 0.21, 0.76) and veliparib (HR: 0.44; 95% CI: 0.28, 0.69)] had a statistically significant effect on PFS versus placebo. In BRCAm-PSROC patients, Olaparib exhibited significant benefit (HR: 0.69; 95% CI: 0.54, 0.88) for OS compared to other PARPis. In BRCAwt-PSR OC patients, Olaparib showed a favorable OS benefit than other PARPis (HR: 0.84; 95% CI: 0.57,1.22). Overall, safety profile of all PARPis was acceptable.
CONCLUSION
All PARPis showed significant benefit, with olaparib showing greater benefit in newly diagnosed and PSR OC women.
REGISTRATION
CRD42021288932.
Topics: Female; Humans; Adenosine Diphosphate; Carcinoma, Ovarian Epithelial; Neoplasm Recurrence, Local; Network Meta-Analysis; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Ribose
PubMed: 38174379
DOI: 10.1080/14737140.2023.2298832 -
Cytotherapy Sep 2023The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults...
A systematic review on the cost-effectiveness assessment of tisagenlecleucel for refractory or relapsing B-cell acute lymphoblastic leukemia (R/R B-ALL) treatment in children and young adults.
BACKGROUND AIMS
The advanced therapy product tisagenlecleucel is a CD19-directed genetically modified autologous T-cell immunotherapy that has brought hope for children and young adults with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). We sought to evaluate the cost-effectiveness of tisagenlecleucel compared with conventional salvage therapies in pediatric and young adult patients with R/R B-ALL.
METHODS
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses parameters as registered in International Prospective Register of Systematic Reviews (CRD42021266998). Literature was searched using the MEDLINE databases via PubMed, EMBASE, Lilacs, the Cochrane Central Register of Controlled Trials and Web of Science in January 2022. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts were reviewed.
RESULTS
In total, 5627 publications were identified, from which six eligible studies were selected. The conventional therapies identified were blinatumomab (Blina), clofarabine monotherapy (Clo-M), clofarabine combined with cyclophosphamide and etoposide (Clo-C) and the combination of fludarabine, cytarabine and idarubicin (FLA-IDA). The discounted incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained for tisagenlecleucel compared with Clo-C and Blina averages was $38 837 and $25 569, respectively. In relation to the cost of the drug, the average of tisagenlecleucel was approximately 4.3 times, 10.8 times or 4.7 times greater than the Clo-M, Clo-C and Blina, respectively.
CONCLUSIONS
This systematic review highlighted that tisagenlecleucel is a much more expensive therapy than conventional alternatives. However, tisagenlecleucel performed well on the ICER, not exceeding $100 000/QALY. It was also found that the advanced therapy product was more effective than the conventional small molecule and biological drugs, in terms of life years and QALY gained.
Topics: Humans; Young Adult; Child; Clofarabine; Cost-Benefit Analysis; Receptors, Antigen, T-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence
PubMed: 37341664
DOI: 10.1016/j.jcyt.2023.05.011 -
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 -
PloS One 2023The metabolic syndrome (MS) is a leading cause of death worldwide. Several studies have found MS to be prevalent in various African regions. However, no specific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The metabolic syndrome (MS) is a leading cause of death worldwide. Several studies have found MS to be prevalent in various African regions. However, no specific estimates of MS prevalence in African populations exist. The aim of this study was to estimate the overall prevalence of MS in the African populations.
METHODS
A systematic review was conducted in PubMed, Web of Science, Africa Index Medicus, and African Journal Online Scopus to find studies published up to the 15th of August 2022. Pooled prevalence was calculated based on six diagnostic methods. The pooled prevalence of MS was estimated using a random-effects model. Our risk of bias analysis was based on the Hoy et al. tool. A Heterogeneity (I2) assessment was performed, as well as an Egger test for publication bias. PROSPERO number CRD42021275176 was assigned to this study.
RESULTS
In total, 297 studies corresponding to 345 prevalence data from 29 African countries and involving 156 464 participants were included. The overall prevalence of MS in Africa was 32.4% (95% CI: 30.2-34.7) with significant heterogeneity (I2 = 98.9%; P<0.001). We obtained prevalence rates of 44.8% (95% CI: 24.8-65.7), 39.7% (95% CI: 31.7-48.1), 33.1% (95% CI: 28.5-37.8), 31.6% (95% CI: 27.8-35.6) and 29.3% (95% CI: 25.7-33) using the WHO, revised NCEP-ATP III, JIS, NCEP/ATP III and IDF definition criteria, respectively. The prevalence of MS was significantly higher in adults >18 years with 33.1% (95%CI: 30.8-35.5) compared to children <18 years with 13.3% (95%CI: 7.3-20.6) (P<0.001). MS prevalence was significantly higher in females with 36.9% (95%CI: 33.2-40.7) compared to males with 26.7% (95%CI: 23.1-30.5) (P<0.001). The prevalence of MS was highest among Type 2 diabetes patients with 66.9% (95%CI: 60.3-73.1), followed by patients with coronary artery disease with 55.2% (95%CI: 50.8-59.6) and cardiovascular diseases with 48.3% (95%CI: 33.5-63.3) (P<0.001). With 33.6% (95% CI: 28.3-39.1), the southern African region was the most affected, followed by upper-middle income economies with 35% (95% CI: 29.5-40.6).
CONCLUSION
This study, regardless of the definition used, reveals a high prevalence of MS in Africa, confirming the ongoing epidemiological transition in African countries. Early prevention and treatment strategies are urgently needed to reverse this trend.
Topics: Male; Adult; Child; Female; Humans; Metabolic Syndrome; Prevalence; Diabetes Mellitus, Type 2; Africa; Adenosine Triphosphate
PubMed: 37498832
DOI: 10.1371/journal.pone.0289155