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BMC Cancer Nov 2023Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children with acute lymphoblastic leukaemia (ALL) experience multiple symptoms that occur in complicated patterns and negatively affect patient outcomes. To date, no systematic review has been performed on the prevalence of symptoms in children with ALL.
OBJECTIVE
The study aimed to report and analyse the prevalence of symptoms in children with ALL during treatment.
METHODS
A systematic search was conducted in eight databases (PubMed, Ovid Embase, Web of Science, CINAHL, PsycINFO, China WanFang Database, China Science and Technology Journal Database, and China National Knowledge Infrastructure) for studies published between January 1, 2000, and August 12, 2023. The methodological quality of the included studies was evaluated and a meta-analysis was performed to pool the prevalence of symptoms.
RESULTS
In total, 17 studies were included, from which 34 symptoms were identified. The symptom prevalence ranged between 1.5 and 91.0% and the most frequent symptoms observed were fatigue, lack of energy, dry mouth, lack of appetite, sweating, and feeling irritable, which occurred in at least 60% of the patients.
CONCLUSIONS
Symptoms remain highly prevalent in paediatric patients with ALL, which provides support for the need for symptom assessment in the clinical setting. Specific intervention is urgently needed to mitigate the symptoms in children with ALL and help them cope with the symptom burden.
Topics: Humans; Child; Prevalence; Emotions; China; Fatigue; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37968600
DOI: 10.1186/s12885-023-11581-z -
Frontiers in Bioscience (Landmark... Oct 2023In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most...
BACKGROUND
In the past 10 years, significant progress has been made in understanding the pathogenic chain of events that causes Alzheimer's disease (AD). According to the most widely accepted concept, the production and aggregation of β-amyloid (Aβ) peptides play a critical role in AD. As a result, therapeutic intervention with these processes is the focus of intense research. The Aβ peptide is cleaved by the α-secretase, β-secretase, and γ-secretase enzymes in a region near the pathogenic amyloid precursor protein (APP) and mutations occurring site.
METHODS
In the current review, a complete picture of the risk factors behind AD has been investigated. Mutations involved in AD progression have also been screened in various studies.
RESULTS
Most of the mutations in the amyloid precursor protein (APP) can lead to the accumulation of APP oligomers in the brain, leading to AD. Several point mutations in APP can cause familial AD (FAD), including the Swedish mutation (K>M670/671N>L) and the A673>V mutation. The pathogenic A673>V mutation and Swedish mutation (M670>K/N671>L) are present in the same region of amyloid precursor protein (). However, the A673>T mutation has been shown to confer protection against AD.
CONCLUSION
More investigations are needed from geographically distinct regions on mutations associated with AD development and applications of nanomedicines for better management of the disease burden in the future. Nanotechnology-produced metal nanoparticles (NPs) have gotten much attention because of their wide range of uses in the medicinal and agricultural industries. Nanomedicine containing potential phytochemicals, including GX-50 and curcumin conjugated with NPs, maybe a potential candidate for treating AD.
Topics: Humans; Alzheimer Disease; Amyloid beta-Protein Precursor; Amyloid beta-Peptides; Mutation; Amyloid Precursor Protein Secretases
PubMed: 37919079
DOI: 10.31083/j.fbl2810258 -
Brain Sciences Oct 2023β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in... (Review)
Review
β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This systematic review, conducted according to the PRISMA guideline and assisted by the MySLR platform, addressed this issue. A total of 16 eligible original research articles were identified. Dietary intake or β-carotene serum levels were associated with improved measures of cognitive function in 7 out of 10 epidemiological studies included. In intervention studies, β-carotene consumption alone did not promote better cognitive function in the short term, but only in a long-term intervention with a mean duration of 18 years. However, all but one intervention study suggested the beneficial effects of β-carotene supplementation at doses ranging from 6 mg to 50 mg per day in combination with a multicomplex such as vitamin E, vitamin C, zinc, or selenium for a period of 16 weeks to 20 years. Despite the current limitations, the available evidence suggests a potential association between β-carotene dietary/supplementary intake and the maintenance of cognitive function. The β-carotene most probably does not act alone but in synergy with other micronutrients.
PubMed: 37891835
DOI: 10.3390/brainsci13101468 -
Leukemia Dec 2023In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory...
In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (r/r ALL), the objective was to compare the efficacy of tisagenlecleucel with historical controls from multiple disease registries using patient-level adjustment of the historical controls. The analysis is based on patient-level data of three tisagenlecleucel studies (ELIANA, ENSIGN and CCTL019B2001X) vs. three registries in Germany/Austria. Statistical analyses were fully pre-specified and propensity score weighting of the historical controls by fine stratification weights was used to adjust for relevant confounders identified by systematic literature review. Results showed high comparability of cohorts after adjustment with absolute SMD ≤ 0.1 for all pre-specified confounders and favorable outcomes for tisagenlecleucel compared to SOC for all examined endpoints. Hazard ratios for OS, EFS and RFS were 0.54 (95% CI: 0.41-0.71, p < 0.001), 0.67 (0.52-0.86, p = 0.001) and 0.77 (0.51-1.18, p = 0.233). The OS, EFS and RFS survival probability at 2 years was 59.49% for tisagenlecleucel vs. 36.16% for SOC population, 42.31% vs. 30.23% and 59.60% vs. 54.57%, respectively. Odds ratio for ORR was 1.99 (1.33-2.97, p < 0.001). Results for OS and ORR were statistically significant after adjustment for confounders and provide evidence supporting a superiority of tisagenlecleucel in r/r ALL given the good comparability of cohorts after adjustment for confounders.
Topics: Humans; Child; Young Adult; Standard of Care; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Receptors, Antigen, T-Cell; Austria; Immunotherapy, Adoptive
PubMed: 37880478
DOI: 10.1038/s41375-023-02042-4 -
Neuropsychiatric Disease and Treatment 2023Subthreshold depression (StD) is considered to be the "precursor" stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and... (Review)
Review
BACKGROUND
Subthreshold depression (StD) is considered to be the "precursor" stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and functional impairment. There have been various non-pharmacological interventions for StD. However, the comparison of their effectiveness still lacks sufficient evidence. We performed a systematic review and network meta-analysis to evaluate and rank the efficacy of multiple non-pharmacological interventions targeting StD.
METHODS
We conducted a thorough search across various databases including PubMed, Medline, Embase, Web of Science and PsycINFO from inception to December 2022. All included studies were randomized controlled trials (RCTs) of non-pharmacological interventions for patients with StD compared with control group (CG). Several universal scales for measuring depression severity were used as efficacy outcomes. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each intervention using the "Stata 17.0" software.
RESULTS
A total of thirty-six trials were included, involving twenty-eight interventions and 7417 participants. The research found that most non-pharmacological interventions were superior to controls for StD. In each outcome evaluation by different scales for measuring depression, psychotherapy always ranked first in terms of treatment effectiveness, especially Problem-solving Therapy (PST), Behavioral Activation Therapy (BAT), Cognitive Behavioral Therapy (CBT)/Internet-based CBT (I-CBT)/Telephone-based CBT (T-CBT). Since different groups could not be directly compared, the total optimal intervention could not be determined.
CONCLUSION
Here, we show that psychotherapy may be the better choice for the treatment of StD. This study provides some evidence on StD management selection for clinical workers. However, to establish its intervention effect more conclusively, the content, format and operators of psychotherapy still require extensive exploration to conduct more effective, convenient and cost-effective implementation in primary healthcare. Notably, further research is also urgently needed to find the biological and neural mechanisms of StD by examining whether psychotherapy alters neuroplasticity in patients with StD.
PubMed: 37867932
DOI: 10.2147/NDT.S425509 -
Frontiers in Nutrition 2023Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several...
The effects of NAD+ precursor (nicotinic acid and nicotinamide) supplementation on weight loss and related hormones: a systematic review and meta-regression analysis of randomized controlled trials.
BACKGROUND
Despite the fact that obesity and overweight are serious major health problems worldwide, fighting against them is also considered a challenging issue. Several interventional studies have evaluated the potential weight-reduction effect of nicotinamide adenine dinucleotide (NAD+) precursor. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of NAD+ precursor supplementation on weight loss, adiponectin, and leptin.
METHODS
Scopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the weight loss and related hormones effects of NAD+ precursor. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.
RESULTS
Twenty two treatment arms with 5,144 participants' were included in this systematic review and meta-regression analysis. The pooled findings showed that NAD+ precursor supplementation has an effect on lowering BMI (weighted mean difference (WMD): -0.19 kg/m2, 95% confidence interval (CI): -0.29 to -0.09, < 0.001) and increasing adiponectin (WMD: 1.59 μg/mL, 95% CI: 0.49 to 2.68, = 0.004) in humans compared with control groups. However, no significant effect was observed on body weight and leptin. There was a significant relationship between doses of intervention with changes in BMI. In addition, subgroup analysis showed that BMI reduction was greater when receiving nicotinic acid (NA) supplementation than nicotinamide (NE) supplementation.
CONCLUSION
NAD+ precursor had significant effects on weight management with the reduction of BMI and increasing adiponectin.
PubMed: 37854354
DOI: 10.3389/fnut.2023.1208734 -
Journal of Speech, Language, and... Nov 2023The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for... (Review)
Review
PURPOSE
The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for neurological speech motor involvement and (b) report the state of the high-quality evidence on vocal characteristic trends of infants diagnosed or at high risk for cerebral palsy (CP).
METHOD
The PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) extension for scoping reviews was followed for reporting our review. Studies measured prelinguistic vocal characteristics of infants under 24 months with birth risk or genetic conditions known to commonly present with speech motor involvement. Fifty-five studies met criteria for Part 1. Eleven studies met criteria for synthesis in Part 2.
RESULTS
A smaller percentage of studies examined infants with or at risk for CP compared to studies examining genetic conditions such as Down syndrome. The median year of publication was 1999, with a median sample size of nine participants. Most studies were conducted in laboratory settings and used human coding of vocalizations produced during caregiver-child interactions. Substantial methodological differences were noted across all studies. A small number of high-quality studies of infants with or at risk for CP revealed high rates of marginal babbling, low rates of canonical babbling, and limited consonant diversity under 24 months. Mixed findings were noted across studies of general birth risk factors.
CONCLUSIONS
There is limited evidence available to support the early detection of speech motor involvement. Large methodological differences currently impact the ability to synthesize findings across studies. There is a critical need to conduct longitudinal research with larger sample sizes and advanced, modern technologies to detect vocal precursors of speech impairment to support the accurate diagnosis and prognosis of speech development in infants with CP and other clinical populations.
Topics: Humans; Infant; Speech; Speech Disorders; Cerebral Palsy
PubMed: 37850852
DOI: 10.1044/2023_JSLHR-23-00336 -
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 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761 -
International Journal of Environmental... Sep 2023Conduct a systematic review concerning the literature that reflects whether the callous and unemotional traits present in childhood and/or adolescence are precursors in... (Review)
Review
OBJECTIVE
Conduct a systematic review concerning the literature that reflects whether the callous and unemotional traits present in childhood and/or adolescence are precursors in the development of female psychopathy in adulthood.
MATERIALS AND METHODS
A systematic review involved consulting three databases-EBSCO, the Web of Science, and PubMed-for peer-reviewed and quantitative studies within the period 2000-2023. Nine articles with quality of three and above were included.
RESULTS
The presence of callous and unemotional traits designates a group of youth that show characteristics associated with psychopathy, specifically when predicting a more severe and chronic pattern of antisocial behaviour. Children with high rates of callous and unemotional traits, who show symptoms of attention deficit hyperactivity disorder in combination with severe conduct problems, are most likely to show features associated with psychopathy. The multidimensional psychopathy construct is considered a better predictor of future and stable antisocial behaviour than the callous and unemotional traits alone model.
CONCLUSIONS
According to the studies selected, the callous and unemotional traits in childhood seem to be precursors of female psychopathy in adulthood, but only because of the way they seem to enhance conduct problems, disruptive behaviour disorders, and, as a possible outcome, delinquency and antisocial traits, which may be precursors of future psychopathy.
Topics: Adolescent; Child; Female; Humans; Antisocial Personality Disorder; Databases, Factual; Phenotype; Problem Behavior; PubMed
PubMed: 37754645
DOI: 10.3390/ijerph20186786