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Clinical Nutrition (Edinburgh, Scotland) Sep 2022Lifestyle interventions that focus on reduced energy intake and improved dietary pattern are the mainstay of non-alcoholic fatty liver disease (NAFLD) management.... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Lifestyle interventions that focus on reduced energy intake and improved dietary pattern are the mainstay of non-alcoholic fatty liver disease (NAFLD) management. However, it remains unclear which dietary approaches are most beneficial and promote greatest adherence. We aimed to synthesise data from randomised and clinical controlled trials, describing the effects of Mediterranean Diet and Calorie Restriction interventions on NAFLD surrogate markers, in adults.
METHODS
We searched MEDLINE, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (October 2021). Study quality was assessed using the Cochrane Collaboration's tools: risk of bias for randomised controlled trials, and risk of bias in non-randomised studies of interventions. Meta-analyses were performed using a random effects model, and the I statistic was used to assess heterogeneity.
RESULTS
Of 4041 records identified, 26 articles with 3037 participants met the inclusion criteria, including studies on calorie-restricted interventions (CRI) (n 9), Mediterranean diet (MD) interventions (n 13) and MD component interventions (n 4). Studies were heterogeneous regarding intervention components, assessment of liver status and diet outcomes. 3 studies reported zero attrition and mean attrition rate for the remaining 23 studies was 14%. Post-intervention meta-analyses revealed that dietary interventions reduced alanine aminotransferase (ALT) (P < 0.001), aspartate aminotransferase (AST) (P = 0.004), Fatty Liver Index (FLI) (P < 0.001), hepatic steatosis (HS) (P = 0.02), and liver stiffness (P = 0.01). CRI had favourable effects on ALT (P < 0.001), HS (P < 0.001) and liver stiffness (P = 0.009). MD reduced ALT (P = 0.02), FLI (P < 0.001) and liver stiffness (P = 0.05). There was a dose-response relationship between degree of calorie restriction and beneficial effects on liver function and weight loss, suggesting that this approach should remain the cornerstone of NAFLD management. In addition, diet composition changes have potential for improving NAFLD and the limited data suggest that MD may be an effective diet therapy.
CONCLUSION
These results support the current guidelines in NAFLD. However, further studies, which robustly evaluate the effects of interventions on dietary intake, acceptability and sustainability of the interventions, and quality of life and other patient-related outcomes are needed to support effective care delivery.
Topics: Adult; Humans; Caloric Restriction; Diet, Mediterranean; Life Style; Non-alcoholic Fatty Liver Disease; Quality of Life; Controlled Clinical Trials as Topic
PubMed: 35947894
DOI: 10.1016/j.clnu.2022.06.037 -
The European Respiratory Journal Dec 2022Physical inactivity is common in asthma and is recognised as an important modifiable risk for poor clinical outcomes such as impaired asthma control and health-related... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Physical inactivity is common in asthma and is recognised as an important modifiable risk for poor clinical outcomes such as impaired asthma control and health-related quality of life (HRQoL). Despite evidence supporting the role of physical activity in reducing the risk of these outcomes, little is known about optimal interventions for increasing physical activity in those with severe disease. This systematic review and meta-analysis evaluates the effectiveness of interventions in increasing physical activity in severe asthma.
METHODS
MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, Informit, SPORTDiscus and Cochrane databases were searched up to September 2021 for physical activity-based intervention studies that assessed physical activity outcomes ( steps per day, time spent undertaking physical activity) in adults with severe asthma. Data on asthma-related ( asthma control) and health-related outcomes ( HRQoL) were assessed as secondary outcomes. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Random-effects meta-analyses synthesised data where possible.
RESULTS
Four randomised controlled trials (all 12 weeks in duration) including 176 adults with moderate-to-severe asthma were included. An increase in physical activity was reported with a moderate-vigorous intensity aerobic and resistance training intervention (steps per day and time spent undertaking physical activity), and an unsupervised pedometer-based intervention (steps per day). Meta-analyses showed that physical activity interventions had an overall positive effect on steps per day (mean difference (MD) 1588, 95% CI 399-2778; p0.009, I=23), asthma control (MD -0.65, 95% CI -0.95--0.35; p<0.0001, I=0%) and HRQoL (MD 0.56, 95% CI 0.10-1.01; p0.02, I=16%) compared to control.
CONCLUSION
While there is some evidence supporting the effectiveness of interventions in improving physical activity in adults with severe asthma, higher-quality, large-scale studies of longer duration are needed to determine the optimal intervention.
Topics: Adult; Humans; Quality of Life; Exercise; Sedentary Behavior; Asthma; Actigraphy
PubMed: 35896208
DOI: 10.1183/13993003.00546-2022 -
Journal of the American Medical... Feb 2020Polypharmacy is widespread among older people, but the adverse outcomes associated with it are unclear. We aim to synthesize current evidence on the adverse health,...
OBJECTIVE
Polypharmacy is widespread among older people, but the adverse outcomes associated with it are unclear. We aim to synthesize current evidence on the adverse health, social, medicines management, and health care utilization outcomes of polypharmacy in older people.
DESIGN
A systematic review, of systematic reviews and meta-analyses of observational studies, was conducted. Eleven bibliographic databases were searched from 1990 to February 2018. Quality was assessed using AMSTAR (A Measurement Tool to Assess Systematic Reviews).
SETTING AND PARTICIPANTS
Older people in any health care setting, residential setting, or country.
RESULTS
Twenty-six reviews reporting on 230 unique studies were included. Almost all reviews operationalized polypharmacy as medication count, and few examined medication classes or disease states within this. Evidence for an association between polypharmacy and many adverse outcomes, including adverse drug events and disability, was conflicting. The most consistent evidence was found for hospitalization and inappropriate prescribing. No research had explored polypharmacy in the very old (aged ≥85 years), or examined the potential social consequences associated with medication use, such as loneliness and isolation.
CONCLUSIONS AND IMPLICATIONS
The literature examining the adverse outcomes of polypharmacy in older people is complex, extensive, and conflicting. Until polypharmacy is operationalized in a more clinically relevant manner, the adverse outcomes associated with it will not be fully understood. Future studies should work toward this approach in the face of rising multimorbidity and population aging.
Topics: Aged; Aged, 80 and over; Drug-Related Side Effects and Adverse Reactions; Humans; Inappropriate Prescribing; Medication Therapy Management; Patient Acceptance of Health Care; Polypharmacy
PubMed: 31926797
DOI: 10.1016/j.jamda.2019.10.022 -
Gastroenterology May 2020Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Biopsy-confirmed liver fibrosis is a prognostic factor for patients with nonalcoholic fatty liver disease (NAFLD). We performed a systematic review to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with nonalcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate endpoint.
METHODS
We searched the MEDLINE, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. We collected data on mortality (all cause and liver related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, we calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. We performed fixed-effect and random-effect model meta-analyses. Metaregression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years).
RESULTS
Our meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs 4): all-cause mortality RR, 3.42 (95% CI, 2.63-4.46); liver-related mortality RR, 11.13 (95% CI, 4.15-29.84); liver transplant RR, 5.42 (95% CI, 1.05-27.89); and liver-related events RR, 12.78 (95% CI, 6.85-23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings.
CONCLUSIONS
In a systematic review and meta-analysis, we found biopsy-confirmed fibrosis to be associated with risk of mortality and liver-related morbidity in patients with NAFLD, with and without adjustment for confounding factors and in patients with reported NASH. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid endpoint for use in clinical trials.
Topics: Biopsy; Confounding Factors, Epidemiologic; Humans; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prognosis; Quality of Life; Risk Assessment; Severity of Illness Index
PubMed: 32027911
DOI: 10.1053/j.gastro.2020.01.043 -
PLoS Medicine Apr 2020Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the... (Meta-Analysis)
Meta-Analysis
Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD.
METHODS AND FINDINGS
We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome.
CONCLUSIONS
In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease.
TRIAL REGISTRATION
PROSPERO CRD42018115459.
Topics: Humans; Incidence; Liver Diseases; Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Observational Studies as Topic; Population Surveillance; Risk Factors
PubMed: 32353039
DOI: 10.1371/journal.pmed.1003100 -
Liver International : Official Journal... Feb 2021Fibrosis is the strongest predictor for long-term clinical outcomes among patients with non-alcoholic fatty liver disease (NAFLD). There is growing interest in employing...
BACKGROUND & AIMS
Fibrosis is the strongest predictor for long-term clinical outcomes among patients with non-alcoholic fatty liver disease (NAFLD). There is growing interest in employing non-invasive methods for risk stratification based on prognosis. FIB-4, NFS and APRI are models commonly used for detecting fibrosis among NAFLD patients. We aimed to synthesize existing literature on the ability of these models in prognosticating NAFLD-related events.
METHODS
A sensitive search was conducted in two medical databases to retrieve studies evaluating the prognostic accuracy of FIB-4, NFS and APRI among NAFLD patients. Target events were change in fibrosis, liver-related event and mortality. Two reviewers independently performed reference screening, data extraction and quality assessment (QUAPAS tool).
RESULTS
A total of 13 studies (FIB-4:12, NFS: 11, APRI: 10), published between 2013 and 2019, were retrieved. All studies were conducted in a secondary or tertiary care setting, with follow-up ranging from 1 to 20 years. All three markers showed consistently good prognostication of liver-related events (AUC from 0.69 to 0.92). For mortality, FIB-4 (AUC of 0.67-0.82) and NFS (AUC of 0.70-0.83) outperformed APRI (AUC of 0.52-0.73) in all studies. All markers had inconsistent performance for predicting change in fibrosis stage.
CONCLUSIONS
FIB-4, NFS, and APRI have demonstrated ability to risk stratify patients for liver-related morbidity and mortality, with comparable performance to a liver biopsy, although more head-to-head studies are needed to validate this. More refined models to prognosticate NAFLD-events may further enhance performance and clinical utility of non-invasive markers.
Topics: Biopsy; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Prognosis; Retrospective Studies; Severity of Illness Index
PubMed: 32946642
DOI: 10.1111/liv.14669 -
Physiotherapy Theory and Practice Jul 2023Balance impairments are common in cerebellar ataxia. Exercises are beneficial in this population. (Meta-Analysis)
Meta-Analysis
Effects of therapeutic exercise on disease severity, balance, and functional Independence among individuals with cerebellar ataxia: A systematic review with meta-analysis.
BACKGROUND
Balance impairments are common in cerebellar ataxia. Exercises are beneficial in this population.
OBJECTIVE
Explore the benefits of therapeutic exercises on disease severity, balance and functional independence in cerebellar ataxia.
METHODS
Databases were searched from inception until July 2021. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale and the Newcastle-Ottawa Scale (NOS); and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool.
RESULTS
Twenty-six studies were included and eight studies of low to high PEDro methodological quality were meta-analyzed. 'Low' to 'moderate' GRADE quality evidence supports the use of therapeutic exercises to reduce disease severity, assessed using the Scale for the Assessment and Rating of Ataxia [weighted mean difference (WMD): -3.3; 95% confidence interval (95%CI): -3.7, -2.8; p < .01]; and improve balance, assessed using the Berg Balance Scale (WMD: 2.6; 95%CI: 1.1, 4.2; p < .01). The effect of therapeutic exercises on functional independence was insignificant (WMD: 1.6; 95%CI: -1.5, 4.6; p = .31).
CONCLUSION
Low to moderate evidence from studies of low to high methodological quality provides some support for therapeutic exercises for reducing disease severity among non-hereditary degenerative cerebellar ataxia and improving balance among acquired cerebellar ataxia. Exercises did not benefit functional independence. Additional studies of large sample size and high methodological quality are necessary to substantiate these findings.
Topics: Humans; Cerebellar Ataxia; Functional Status; Exercise Therapy; Exercise; Ataxia; Patient Acuity
PubMed: 35212247
DOI: 10.1080/09593985.2022.2037115 -
Respirology (Carlton, Vic.) Nov 2023Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health... (Review)
Review
Long COVID, or post-acute COVID-19 sequelae, is experienced by an estimated one in eight adults following acute COVID-19. Long COVID is a new and complex chronic health condition that typically includes multiple symptoms that cross organ systems and fluctuate over time; a one-size-fits-all approach is, therefore, not likely to be appropriate nor relevant for long COVID treatment. 'Treatable Traits' is a personalized medicine approach, purpose-built to address the complexity and heterogeneity of complex chronic conditions. This comprehensive review aimed to understand how a treatable traits approach could be applied to long COVID, by first identifying the most prevalent long COVID treatable traits and then the available evidence for strategies to target these traits. An umbrella review of 22 systematic reviews identified 34 symptoms and complications common with long COVID, grouped into eight long COVID treatable trait clusters: neurological, chest, psychological, pain, fatigue, sleep impairment, functional impairment and other. A systematic review of randomized control trials identified 18 studies that explored different intervention approaches for long COVID prevention (k = 4) or management (k = 14). While a single study reported metformin as effective for long COVID prevention, the findings need to be replicated and consensus is required around how to define long COVID as a clinical trial endpoint. For long COVID management, current evidence supports exercise training or respiratory muscle training for long COVID treatable traits in the chest and functional limitation clusters. While there are studies exploring interventions targeting other long COVID treatable traits, further high-quality RCTs are needed, particularly targeting treatable traits in the clusters of fatigue, psychological, pain and sleep impairment.
Topics: Adult; Humans; Post-Acute COVID-19 Syndrome; COVID-19; Chronic Disease; Fatigue; Pain
PubMed: 37715729
DOI: 10.1111/resp.14596 -
Human Reproduction Update Sep 2019A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the...
BACKGROUND
A defining feature of sexual reproduction is the transmission of genomic information from both parents to the offspring. There is now compelling evidence that the inheritance of such genetic information is accompanied by additional epigenetic marks, or stable heritable information that is not accounted for by variations in DNA sequence. The reversible nature of epigenetic marks coupled with multiple rounds of epigenetic reprogramming that erase the majority of existing patterns have made the investigation of this phenomenon challenging. However, continual advances in molecular methods are allowing closer examination of the dynamic alterations to histone composition and DNA methylation patterns that accompany development and, in particular, how these modifications can occur in an individual's germline and be transmitted to the following generation. While the underlying mechanisms that permit this form of transgenerational inheritance remain unclear, it is increasingly apparent that a combination of genetic and epigenetic modifications plays major roles in determining the phenotypes of individuals and their offspring.
OBJECTIVE AND RATIONALE
Information pertaining to transgenerational inheritance was systematically reviewed focusing primarily on mammalian cells to the exclusion of inheritance in plants, due to inherent differences in the means by which information is transmitted between generations. The effects of environmental factors and biological processes on both epigenetic and genetic information were reviewed to determine their contribution to modulating inheritable phenotypes.
SEARCH METHODS
Articles indexed in PubMed were searched using keywords related to transgenerational inheritance, epigenetic modifications, paternal and maternal inheritable traits and environmental and biological factors influencing transgenerational modifications. We sought to clarify the role of epigenetic reprogramming events during the life cycle of mammals and provide a comprehensive review of how the genomic and epigenomic make-up of progenitors may determine the phenotype of its descendants.
OUTCOMES
We found strong evidence supporting the role of DNA methylation patterns, histone modifications and even non-protein-coding RNA in altering the epigenetic composition of individuals and producing stable epigenetic effects that were transmitted from parents to offspring, in both humans and rodent species. Multiple genomic domains and several histone modification sites were found to resist demethylation and endure genome-wide reprogramming events. Epigenetic modifications integrated into the genome of individuals were shown to modulate gene expression and activity at enhancer and promoter domains, while genetic mutations were shown to alter sequence availability for methylation and histone binding. Fundamentally, alterations to the nuclear composition of the germline in response to environmental factors, ageing, diet and toxicant exposure have the potential to become hereditably transmitted.
WIDER IMPLICATIONS
The environment influences the health and well-being of progeny by working through the germline to introduce spontaneous genetic mutations as well as a variety of epigenetic changes, including alterations in DNA methylation status and the post-translational modification of histones. In evolutionary terms, these changes create the phenotypic diversity that fuels the fires of natural selection. However, rather than being adaptive, such variation may also generate a plethora of pathological disease states ranging from dominant genetic disorders to neurological conditions, including spontaneous schizophrenia and autism.
Topics: Animals; Biological Evolution; DNA Methylation; Epigenesis, Genetic; Genome; Germ Cells; Heredity; Histone Code; Histones; Humans; Mammals; Mutation; Parents; Phenotype
PubMed: 31374565
DOI: 10.1093/humupd/dmz017 -
Tropical Animal Health and Production Jun 2022The present study intended to determine the prevalence of Newcastle disease in unvaccinated backyard poultry in Africa. Using the PRISMA approach, a systematic review... (Meta-Analysis)
Meta-Analysis Review
The present study intended to determine the prevalence of Newcastle disease in unvaccinated backyard poultry in Africa. Using the PRISMA approach, a systematic review and meta-analysis of 107 epidemiological studies was conducted. The meta-analysis identified significant variation of both seroprevalence (I = 99.38, P = 0.00) and Newcastle disease virus prevalence (I = 99.52, P = 0.00) reported in various studies included in this review. Publication bias was not detected in either case. Seroprevalence of Newcastle disease was 40.2 (95%CI 32.9-47.8). Seroprevalence was significantly influenced by sampling frame and the African region where the studies were conducted. The prevalence of Newcastle disease virus (NDV) was 12% (95%CI 7.3-17.8), and the variation was influenced by sampling frame, diagnostic test, and regions where the studies were conducted. Also, Newcastle disease (ND) accounted for 33.1% (95%CI 11.9-58.1) of sick chickens. Results also indicated that genotypes VI and VII are widely distributed in all countries included in the study. However, genotype V is restricted in East Africa, and genotypes XIV, XVII, and XVIII are restricted in West and Central Africa. On the other hand, genotype XI occurs in Madagascar only. In addition, virulent genotypes were isolated from apparently healthy and sick birds. It is concluded that several genotypes of NDV are circulating and maintained within the poultry population. African countries should therefore strengthen surveillance systems, be able to study the viruses circulating in their territories, and establish control programs.
Topics: Africa; Animals; Chickens; Genotype; Newcastle Disease; Newcastle disease virus; Phylogeny; Poultry; Poultry Diseases; Seroepidemiologic Studies
PubMed: 35705876
DOI: 10.1007/s11250-022-03198-4