Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.
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ABSTRACT:
SUBMITTER: Bilder DA
PROVIDER: S-EPMC5152552 | biostudies-literature | 2016 May-Jun
REPOSITORIES: biostudies-literature
Publications
Systematic Review and Meta-Analysis of Neuropsychiatric Symptoms and Executive Functioning in Adults With Phenylketonuria.
Bilder Deborah A DA Noel J Kay JK Baker Erin R ER Irish William W Chen Yinpu Y Merilainen Markus J MJ Prasad Suyash S Winslow Barbara J BJ
Developmental neuropsychology 20160501 4
This systematic review and meta-analysis (MA) investigates the impact of elevated blood phenylalanine (Phe) on neuropsychiatric symptoms in adults with phenylketonuria (PKU). The meta-analysis of PKU is challenging because high-quality evidence is lacking due to the limited number of affected individuals and few placebo-controlled, double-blind studies of adults with high and low blood Phe. Neuropsychiatric symptoms associated with PKU exceed general population estimates for inattention, hyperac ...[more]
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Project description:BackgroundEven though early dietary management of phenylketonuria (PKU) successfully prevents severe neurological impairments, deficits in cognitive functioning are still observed. These deficits are believed to be the result of elevated levels of phenylalanine throughout life. Research on cognitive functioning in adults with PKU (AwPKU) often focuses on domains shown to be compromised in children with PKU, such as attention and executive functions, whereas other cognitive domains have received less attention. This systematic review aimed to provide an overview of cognitive functioning across domains examined in early treated (ET) AwPKU.MethodsA systematic search was performed in Ovid MEDLINE(R), PsycINFO, Web of Science, Cochrane, Scopus, Embase, ScienceDirect, and PubMed for observational studies on cognitive performance in ET AwPKU.ResultsTwenty-two peer-reviewed publications, reporting on outcomes from 16 studies were reviewed. Collectively, the results most consistently showed deficits in vigilance, working memory and motor skills. Deficits in other cognitive domains were less consistently observed or were understudied. Furthermore, despite reports of several associations between cognitive performance and phenylalanine (Phe) levels throughout life the relationship remains unclear. Inconsistencies in findings across studies could be explained by the highly heterogeneous nature of study samples, resulting in large inter- and intra-variability in Phe levels, as well as the use of a variety of tests across cognitive domains, which differ in sensitivity. The long-term cognitive outcomes of early and continuous management of PKU remain unclear.ConclusionsTo better understand the development of cognitive deficits in ET AwPKU, future research would benefit from 1) (inter)national multicentre-studies; 2) more homogeneous study samples; 3) the inclusion of other nutritional measures that might influence cognitive functioning (e.g. Phe fluctuations, Phe:Tyrosine ratio and micronutrients such as vitamin B12); and 4) careful selection of appropriate cognitive tests.
| S-EPMC6117942 | biostudies-literature
Project description:The nature and extent of persistent neuropsychiatric symptoms after COVID-19 are not established. To help inform mental health service planning in the pandemic recovery phase, we systematically determined the prevalence of neuropsychiatric symptoms in survivors of COVID-19. For this pre-registered systematic review and meta-analysis (PROSPERO ID CRD42021239750), we searched MEDLINE, EMBASE, CINAHL and PsycINFO to 20 February 2021, plus our own curated database. We included peer-reviewed studies reporting neuropsychiatric symptoms at post-acute or later time-points after COVID-19 infection and in control groups where available. For each study, a minimum of two authors extracted summary data. For each symptom, we calculated a pooled prevalence using generalized linear mixed models. Heterogeneity was measured with I 2. Subgroup analyses were conducted for COVID-19 hospitalization, severity and duration of follow-up. From 2844 unique titles, we included 51 studies (n = 18 917 patients). The mean duration of follow-up after COVID-19 was 77 days (range 14-182 days). Study quality was most commonly moderate. The most prevalent neuropsychiatric symptom was sleep disturbance [pooled prevalence = 27.4% (95% confidence interval 21.4-34.4%)], followed by fatigue [24.4% (17.5-32.9%)], objective cognitive impairment [20.2% (10.3-35.7%)], anxiety [19.1% (13.3-26.8%)] and post-traumatic stress [15.7% (9.9-24.1%)]. Only two studies reported symptoms in control groups, both reporting higher frequencies in COVID-19 survivors versus controls. Between-study heterogeneity was high (I 2 = 79.6-98.6%). There was little or no evidence of differential symptom prevalence based on hospitalization status, severity or follow-up duration. Neuropsychiatric symptoms are common and persistent after recovery from COVID-19. The literature on longer-term consequences is still maturing but indicates a particularly high prevalence of insomnia, fatigue, cognitive impairment and anxiety disorders in the first 6 months after infection.
| S-EPMC8833580 | biostudies-literature
Project description:BACKGROUND:In 2016, the global number of individuals living with dementia was 43.8 million, representing a 117% increase from 1990-mainly due to increases in aging and population growth. Up to 90% of individuals with dementia experience neuropsychiatric symptoms (NPS). However, the limitations of current treatments for NPS have drivent he search for safer pharmacotherapies-including cannabinoids. AIM:To assess the efficacy and acceptability of cannabinoids for the treatment of NPS in individuals with dementia. DESIGN:Systematic review and meta-analysis of clinical trials. SETTING AND PARTICIPANTS:Of 6,902 papers, 9 were eligible (n = 205, 44% female, 78 ± 7 years, 85% Alzheimer disease). Trials were in North America and Europe and explored tetrahydrocannabinol (n = 3), dronabinol (n = 5), or nabilone (n = 1). MEASUREMENT:Titles/abstracts were independently screened by one reviewer and reviewed by a second. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on the standardized mean difference (SMD) for several NPS instruments, trial completion, and adverse events. Data were pooled using random-effects models. FINDINGS:Cannabinoids led to significant improvements across NPS instruments, including the Cohen Mansfield Agitation Inventory (SMD = -0.80; 95% confidence interval [CI], -1.45 to -0.16), the Neuropsychiatric Inventory (SMD = -0.61; CI, -1.07 to -0.15), and nocturnal actigraphy (SMD = -1.05; CI, -1.56 to -0.54h). Cannabinoids were well-tolerated, with an overall trial completion rate of 93% (193/205) and no serious treatment-related adverse events. Treatment efficacy was associated with baseline dementia severity and dose, but not dementia subtype, age, or sex. The overall study quality was rated as low. CONCLUSIONS:There is preliminary evidence for the efficacy and tolerability of cannabinoids as treatments for NPS. Population-based studies are needed to characterize their real-world effectiveness and acceptability.
| S-EPMC7265608 | biostudies-literature
Project description:BackgroundThere are currently no systematic reviews or meta-analyses of Chinese calligraphy therapy (CCT) to reduce neuropsychiatric symptoms. The aim of this systematic review and meta-analysis was to explore the efficacy of CCT for people with neuropsychiatric symptoms.MethodsWe searched Chinese and English databases, including the Cochrane Central Register of Controlled Trials and Wanfang Data for relevant articles published between the earliest year available and December 2016. The search was limited to randomized controlled trials and controlled clinical studies and the associated keywords were "handwriting," "Chinese calligraphy," "Chinese calligraphy therapy," "Calligraphy exercise," and "Calligraphy training." The 21 articles that met these criteria were used in the analysis. The Joanna Briggs Institute critical appraisal checklist was used to assess methodological quality.ResultsCCT significantly reduced psychosis (10 studies, 965 subjects, standardized mean difference [SMD]?=?-?0.17, 95% confidence intervals [CI] [-?0.30, -?0.40], Z?=?2.60, p?<?0.01), anxiety symptoms (9 studies, 579 subjects, SMD?=?-?0.78, 95% CI [-?0.95, -?0.61], Z?=?8.98, p?<?0.001), and depressive symptoms (7 studies, 456 subjects, SMD?=?-?0.69, 95% CI [-?0.88, -?0.50], Z?=?7.11, p?<?0.001). CCT also significantly improved cognitive function (2 studies, 55 subjects, MD?=?2.17, 95% CI [-?0.03, 4.38], Z?=?1.93, p?=?0.05) and neurofeedback (3 studies, 148 subjects, SMD?=?-?1.09, 95% CI [-?1.44, -?0.73], Z?=?6.01, p?<?0.001). The therapy also significantly reduced the positive psychopathological expression of schizophrenia symptoms (4 studies, 287 subjects, SMD?=?-?0.35, 95% CI [-?0.59, -?0.12], Z?=?2.96, p?=?0.003) and reduced the negative symptoms of schizophrenia (4 studies, 276 subjects, SMD?=?-?1.39, 95% CI [-?1.65, -?1.12], Z?=?10.23, p?<?0.001).ConclusionsCCT exerts a curative effect on neuropsychiatric symptoms, but the evidence remains insufficient. A large number of RCTs are needed to facilitate additional systematic reviews of evidence for CCT.
| S-EPMC5842540 | biostudies-literature
Project description:The aim of the present study was to assess the effects of nutritional supplementation on neuropsychiatric symptoms among people with dementia.Methods/designRandomized controlled trials (RCTs) were searched in the Databases PubMed, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception until January 31, 2020. Studies of RCTs carried out on people with any type of dementia who were taking nutritional supplements and had neuropsychiatric symptoms were included in this systematic review and meta-analysis. Neuropsychiatric symptoms were assessed with the validated Neuropsychiatric Inventory (NPI). Effect sizes were calculated with standardized mean differences (SMD) and 95% confidence intervals (95%CI), applying a random effect model.ResultsThe search yielded 1034 studies with four studies being included in the meta-analysis with a total of 377 people with dementia (mean age 69.3 [SD: 7.7] years). The diagnoses comprised mild to late Alzheimer's disease and frontotemporal dementia. Two studies included a multicomponent supplementation, one an omega-3, and one a special supplement tailored for cognitive impairment. The median follow-up was 18 weeks, with a range from 12 to 24 weeks. Pooled data showed that nutritional supplementation did not improve NPI (SMD = -0.33; [95%CI: -0.74 to 0.08]; P = 0.11; I2 = 45%).ConclusionsThe findings of this meta-analysis demonstrated no significant impact on NPI through nutritional supplementation. However, the generalization of the results is limited, as different supplements were used in different stages of dementia with a short follow-up time.
| S-EPMC7692950 | biostudies-literature
Project description:BackgroundPrescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia.MethodsWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies.ResultsOur systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47).ConclusionAlthough antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms.Prospero registrationCRD42017050130.
| S-EPMC7298771 | biostudies-literature
Project description:Patients with Phenylketonuria (PKU) reportedly have decreased bone mineral density (BMD). The primary aim of this study was to perform a systematic review and meta-analysis to determine the extent and significance of low BMD in early treated patients with PKU. Secondary aims were to assess other bone status indicators including bone turnover markers (BTM) and to define areas for future research. Two research teams (Amsterdam, Netherlands and Atlanta, USA) performed literature searches for articles reporting data on BMD, osteopenia and osteoporosis, BTM or other bone indicators in patients with PKU. Included articles were compared between research teams and assessed for quality and risk of bias. A total of 13 unique articles were included; 11/13 articles reported BMD including a total of 360 patients. Ten out of 11 articles found BMD was significantly lower in patients with PKU. Meta-analyses for total BMD (TBMD; 3 studies; n = 133), lumbar spine BMD (LBMD; 7 studies; n = 247), and femoral neck BMD (FBMD; 2 studies; n = 78) Z-scores were performed. Overall effect sizes were: TBMD -0.45 (95% CI -0.61, -0.28); LBMD -0.70 (95% CI -0.82, -0.57); FBMD -0.96 (95% CI -1.42, -0.49). Definitions of osteopenia and osteoporosis were highly heterogeneous between studies and did not align with World Health Organization standards and the International Society for Clinical Densitometry positions on BMD measurement. Despite individual study findings of low BMD indicating higher risk of osteoporosis, pooled available data suggest reduction in BMD is not clinically important when using standard definitions of low BMD. Results from studies evaluating BTM are inconclusive. Phenylalanine concentration, vitamin D, PTH, and nutrient intake do not correlate with BMD or BTM. We recommend forthcoming studies use standard definitions of low BMD to determine clinical implications of BMD Z-scores below 0, explore cause of low BMD in the subset of patients with low BMD for chronological age (Z-score < -2) and assess fracture risk in patients with PKU.
| S-EPMC4340652 | biostudies-literature
Project description:In phenylketonuria (PKU), synthetic protein derived from L-amino acids (AAs) is essential in a low-phenylalanine (Phe) diet. Glycomacropeptide (GMP), an intact protein, is very low in Phe in its native form. It has been modified and adapted for PKU to provide an alternative protein source through supplementation with rate-limiting amino acids (GMP-AAs), although it still contains residual Phe. This review aims to systematically evaluate published intervention studies on the use of GMP-AAs in PKU by considering its impact on blood Phe control (primary aim) and changes in tyrosine control, nutritional biomarkers, and patient acceptability or palatability (secondary aims). Four electronic databases were searched for articles published from 2007 to June 2018. Of the 274 studies identified, only eight were included. Bias risk was assessed and a quality appraisal of the body of evidence was completed. A meta-analysis was performed with two studies with adequate comparable methodology which showed no differences between GMP-AAs and AAs for any of the interventions analysed. This work underlines the scarcity and nature of studies with GMP-AAs interventions. All were short-term with small sample sizes. There is a need for better-designed studies to provide the best evidence-based recommendations.
| S-EPMC6266274 | biostudies-other
Project description:BACKGROUND:Phenylketonuria (PKU), which is characterized by a deficiency of phenylalanine hydroxylase activity, is an autosomal recessive disorder of phenylalanine (Phe) metabolism. Newborn screening is the main population-based public health screening program that allows successful identification and treatment of PKU with low-Phe diet. The aim of this study was to evaluate the epidemiology of PKU screening in Iranian newborns. METHODS:The present study was designed based on MOOSE protocol and reporting was done in accordance with the PRISMA guidelines. The protocol of this systematic review was published in PROSPERO before it was performed (CRD42020162626). A comprehensive search was done in 10/10/2019 to find related literature on international online databases Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, EBSCO, CINAHL, Cochrane Library, national online databases and the Google Scholar search engine. Heterogeneity among studies was assessed by I2 index and Q test. All meta-analyses were performed using Comprehensive Meta-Analysis Software ver. 2. P?<?0.05 was considered significant. RESULT:Finally, 18 studies with 3,339,327 Iranian neonates were included. The prevalence of suspected hyperphenylalaninemia (HPA) was estimated to be 45.6/100,000 (95% CI: 23.9-87.1). The prevalence of suspected HPA in girls and boys infants in Iran was estimated to be 38.0/100,000 (95% CI: 15.1-95.5) and 43.3/100,000 (95% CI: 16.2-116.2), respectively. The prevalence of PKU was estimated to be 16.5/100,000 (95% CI: 12.9-21.2). The prevalence of PKU in girls and boys infants was estimated to be 13.3/100,000 (95% CI: 7.5-15.8) and 10.9/100,000 (95% CI: 7.5-15.8), respectively. The prevalence of mild to moderate HPA was estimated 9.7/100,000 (95% CI: 5.1-18.4) and the prevalence of classical PKU was estimated 4.4/100,000 (95% CI: 2.5-7.8). Sensitivity analysis for all meta-analysis with the omission of one study showed that overall estimation is still robust. CONCLUSION:The results of this meta-analysis showed that PKU is prevalent in Iranian neonates. It should be considered that for PKU there is a highly effective dietary treatment which can prevent the clinical symptoms of PKU if initiated early after detection by newborn screening.
| S-EPMC7379797 | biostudies-literature
Project description:There is an ongoing debate regarding the impact of phenylketonuria (PKU) and its treatment on growth. To date, evidence from studies is inconsistent, and data on the whole developmental period is limited. The primary aim of this systematic review was to investigate the effects of a phenylalanine (Phe)-restricted diet on long-term growth in patients with PKU. Four electronic databases were searched for articles published until September 2018. A total of 887 results were found, but only 13 articles met eligibility criteria. Only three studies had an adequate methodology for meta-analysis. Although the results indicate normal growth at birth and during infancy, children with PKU were significantly shorter and had lower weight for age than reference populations during the first four years of life. Impaired linear growth was observed until the end of adolescence in PKU. In contrast, growth impairment was not reported in patients with mild hyperphenylalaninemia, not requiring dietary restriction. Current evidence indicates that even with advances in dietary treatments, "optimal" growth outcomes are not attained in PKU. The majority of studies include children born before 1990s, so further research is needed to show the effects of recent dietary practices on growth in PKU.
| S-EPMC6769966 | biostudies-literature