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Frontiers in Neurology 2023The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD...
BACKGROUND/OBJECTIVES
The timely diagnosis of inherited metabolic disorders (IMD) is essential for initiating treatment, prognostication and genetic testing of relatives. Recognition of IMD in adults is difficult, because phenotypes are different from those in children and influenced by symptoms from acquired conditions. This systematic literature review aims to answer the following questions: (1) What is the diagnostic yield of exome/genome sequencing (ES/GS) for IMD in adults with unsolved phenotypes? (2) What characteristics do adult patients diagnosed with IMD through ES/GS have?
METHODS
A systematic search was conducted using the following search terms (simplified): "Whole exome sequencing (WES)," "Whole genome sequencing (WGS)," "IMD," "diagnostics" and the 1,450 known metabolic genes derived from ICIMD. Data from 695 articles, including 27,702 patients, were analyzed using two different methods. First, the diagnostic yield for IMD in patients presenting with a similar phenotype was calculated. Secondly, the characteristics of patients diagnosed with IMD through ES/GS in adulthood were established.
RESULTS
The diagnostic yield of ES and/or GS for adult patients presenting with unexplained neurological symptoms is 11% and for those presenting with dyslipidemia, diabetes, auditory and cardiovascular symptoms 10, 9, 8 and 7%, respectively. IMD patients diagnosed in adulthood (n = 1,426), most frequently portray neurological symptoms (65%), specifically extrapyramidal/cerebellar symptoms (57%), intellectual disability/dementia/psychiatric symptoms (41%), pyramidal tract symptoms/myelopathy (37%), peripheral neuropathy (18%), and epileptic seizures (16%). The second most frequently observed symptoms were ophthalmological (21%). In 47% of the IMD diagnosed patients, symptoms from multiple organ systems were reported. On average, adult patients are diagnosed 15 years after first presenting symptoms. Disease-related abnormalities in metabolites in plasma, urine or cerebral spinal fluid were identified in 40% of all patients whom underwent metabolic screening. In 52% the diagnosis led to identification of affected family members with the same IMD.
CONCLUSION
ES and/or GS is likely to yield an IMD diagnosis in adult patients presenting with an unexplained neurological phenotype, as well as in patients with a phenotype involving multiple organ systems. If a gene panel does not yield a conclusive diagnosis, it is worthwhile to analyze all known disease genes. Further prospective research is needed to establish the best diagnostic approach (type and sequence of metabolic and genetic test) in adult patients presenting with a wide range of symptoms, suspected of having an IMD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42021295156.
PubMed: 37560457
DOI: 10.3389/fneur.2023.1206106 -
The Malaysian Journal of Medical... Dec 2023Neurological rehabilitation is a physician-supervised programme for individuals with nervous system diseases, injuries or disorders. Neurological rehabilitation, also... (Review)
Review
Neurological rehabilitation is a physician-supervised programme for individuals with nervous system diseases, injuries or disorders. Neurological rehabilitation, also known as neurorehabilitation, is part of the rehabilitation process that improves function, reduces severity and enhances a patient's well-being. Because neurological injuries occur in the brain, spine and nerves, affecting multiple body parts including organs, blood vessels, muscles and bones, rehabilitation requires a multidisciplinary approach. This study conducted a systematic literature review (SLR) on the use of mobile game in neurorehabilitation. The steps undertaken in the literature review included the collection, identification, categorisation, summarisation and synthesis of relevant studies in the research domain. A total of 50 related articles were reviewed. The study identified that the effects on cognitive skills, handgrip strength, memory, attention, visuospatial abilities, executive function tasks, motor functionality, and improvements in balance, visual perception, and functional mobility are impacts of the use of mobile games in neurological rehabilitation. Furthermore, several research challenges and recommendations for future research were identified.
PubMed: 38239257
DOI: 10.21315/mjms2023.30.6.4 -
Bulletin of the World Health... May 2024To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and... (Review)
Review
OBJECTIVE
To obtain insights into reducing the shortfall in financing for pandemic preparedness and response measures, and reducing the risk of another pandemic with social and economic costs comparable to those of the coronavirus disease.
METHODS
We conducted a systematic scoping review using the databases ScienceDirect, Scopus, JSTOR, PubMed® and EconLit. We included articles published in any language until 1 August 2023, and excluded grey literature and publications on epidemics. We categorized eligible studies according to the elements of a framework proposed by the World Health Organization Council on the Economy of Health for All: (i) root/structural causes; (ii) social position/foundations; (iii) infrastructure and systems; and (iv) communities, households and individuals.
FINDINGS
Of the 188 initially identified articles, we included 60 in our review. Most (53/60) were published after 2020, when academic interest had shifted towards global financing mechanisms. Most (37/60) addressed two or more of the council framework elements. The most frequently addressed element was infrastructure and systems (54/60), discussing topics such as health systems, financial markets and innovation ecosystems. The roots/structural causes were discussed in 25 articles; communities, households and individuals in 22 articles; and social positions/foundations in 11.
CONCLUSION
Our review identified three important gaps: a formal definition of pandemic preparedness and response, impeding the accurate quantification of the financing shortfall; research on the extent to which financing for pandemic preparedness and response has been targeted at the most vulnerable households; and an analysis of specific financial instruments and an evaluation of the feasibility of their implementation.
Topics: Humans; COVID-19; Pandemics; Global Health; SARS-CoV-2; Healthcare Financing; Pandemic Preparedness
PubMed: 38680465
DOI: 10.2471/BLT.23.290207 -
Nutrition Reviews Dec 2023Sepsis refers to a usually lethal medical condition that results from an extreme, uncontrolled, and multifaceted immune system response to infection. Ginger (Zingiber...
Therapeutic effects and mechanisms of action of ginger and its bioactive components on inflammatory response, oxidative stress, the immune system, and organ failure in sepsis: a comprehensive systematic review.
CONTEXT
Sepsis refers to a usually lethal medical condition that results from an extreme, uncontrolled, and multifaceted immune system response to infection. Ginger (Zingiber officinale Roscoe; Zingiberaceae) is 1 of the most popular spice. It is widely used as a traditional herb and as medicine in the treatment of some inflammatory conditions, such as vomiting, pain, cancer, diabetes, and cardiovascular diseases, because of its varied medical characteristics, including anti-inflammatory, antioxidant, antimicrobial, and antitumor effects.
OBJECTIVE
The aim of this study was to demonstrate the potential roles of ginger and its elements in sepsis.
DATA SOURCES
This systematic review article was conducted and reported by following the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). Electronic databases, including Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest, were searched using related key words up to January 2023.
DATA EXTRACTION
Among 141 found articles, 48 eligible articles were included and reviewed for their details. Data were extracted, including the first author's name, year of publication, name of origin country, study design, number and type of subject, dosage and type of intervention, study duration, assay, and main results.
DATA ANALYSIS
The data from the included articles showed that ginger and its bioactive elements, such as gingerol (1-300 µg/mL or 1-100 mg/kg for 24 hours to 14 days), shogaol (0.2-100 µg/mL or 10-40 mg/kg body weight for 24 hours to 8 days), gingerdione (1-100 µg/mL for 20-48 hours), and zingerone (2-20 µM for 4 hours to 8 days), can be effective in sepsis via suppressing the gene expression and production of pro-inflammatory cytokines and oxidant agents, downregulating immune response, and protecting against sepsis-induced organ failures in experimental and animal models.
CONCLUSION
Ginger has potential therapeutic effects in sepsis. Human clinical trials are recommended.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42023373613.
PubMed: 38102801
DOI: 10.1093/nutrit/nuad156 -
Critical Reviews in Toxicology Sep 2023Malathion and diazinon are pesticides commonly used in agriculture to avoid insects that damage crops; however, they may cause impairment to the male genital system of... (Review)
Review
Malathion and diazinon are pesticides commonly used in agriculture to avoid insects that damage crops; however, they may cause impairment to the male genital system of exposed humans. The present work carried out a systematic review of the literature concerning the primary studies that assessed the reproductive effects resulting from male rats and mice exposed to malathion or diazinon. The search for articles was performed on the databases PubMed, LILACS, Scopus, and SciELO, using different combinations of the search terms "malathion," "diazinon," "mice," "rats," "male reproduction," "fertility," and "sperm," followed by the Boolean operators AND or OR. The results obtained indicate that both pesticides act as reproductive toxicants by reducing sperm quality, diminishing hormonal concentrations, inducing increased oxidative stress, and provoking histopathological damage in reproductive organs. Then, the exposure to malathion and diazinon may provoke diminished levels of testosterone by increasing acetylcholine stimulation in the testis through muscarinic receptors, thus, providing a reduction in steroidogenic activity in Leydig cells, whose effect is related to lower levels of testosterone in rodents, and consequently, it is associated with decreased fertility. Considering the toxic effects on the male genital system of rodents and the possible male reproductive toxicity in humans, it is recommended the decreased use of these pesticides and their replacement for others that show no or few toxic effects for non-target animals.
Topics: Humans; Male; Rats; Animals; Mice; Malathion; Diazinon; Insecticides; Rodentia; Semen; Pesticides; Reproduction; Testosterone
PubMed: 37922518
DOI: 10.1080/10408444.2023.2270494 -
Medical Decision Making : An... 2023Medically assisted reproduction (MAR) is a challenging application area for health economic evaluations, entailing a broad range of costs and outcomes, stretching out... (Review)
Review
BACKGROUND
Medically assisted reproduction (MAR) is a challenging application area for health economic evaluations, entailing a broad range of costs and outcomes, stretching out long-term and accruing to several parties.
PURPOSE
To systematically review which costs and outcomes are included in published economic evaluations of MAR and to compare these with health technology assessment (HTA) prescriptions about which cost and outcomes should be considered for different evaluation objectives.
DATA SOURCES
HTA guidelines and systematic searches of PubMed Central, Embase, WOS CC, CINAHL, Cochrane (CENTRAL), HTA, and NHS EED.
STUDY SELECTION
All economic evaluations of MAR published from 2010 to 2022.
DATA EXTRACTION
A predetermined data collection form summarized study characteristics. Essential costs and outcomes of MAR were listed based on HTA and treatment guidelines for different evaluation objectives. For each study, included costs and outcomes were reviewed.
DATA SYNTHESIS
The review identified 93 cost-effectiveness estimates, of which 57% were expressed as cost-per-(healthy)-live-birth, 19% as cost-per-pregnancy, and 47% adopted a clinic perspective. Few adopted societal perspectives and only 2% used quality-adjusted life-years (QALYs). Broader evaluations omitted various relevant costs and outcomes related to MAR. There are several cost and outcome categories for which available HTA guidelines do not provide conclusive directions regarding inclusion or exclusion.
LIMITATIONS
Studies published before 2010 and of interventions not clearly labeled as MAR were excluded. We focus on methods rather than which MAR treatments are cost-effective.
CONCLUSIONS
Economic evaluations of MAR typically calculate a short-term cost-per-live-birth from a clinic perspective. Broader analyses, using cost-per-QALY or BCRs from societal perspectives, considering the full scope of reproduction-related costs and outcomes, are scarce and often incomplete. We provide a summary of costs and outcomes for future research guidance and identify areas requiring HTA methodological development.
HIGHLIGHTS
The cost-effectiveness of MAR procedures can be exceptionally complex to estimate as there is a broad range of costs and outcomes involved, in principle stretching out over multiple generations and over many stakeholders.We list 21 key areas of costs and outcomes of MAR. Which of these needs to be accounted for alters for different evaluation objectives (determined by the type of economic evaluation, time horizon considered, and perspective).Published studies mostly investigate cost-effectiveness in the very short-term, from a clinic perspective, expressed as cost-per-live-birth. There is a lack of comprehensive economic evaluations that adopt a broader perspective with a longer time horizon. The broader the evaluation objective, the more relevant costs and outcomes were excluded.For several costs and outcomes, particularly those relevant for broader, societal evaluations of MAR, the inclusion or exclusion is theoretically ambiguous, and HTA guidelines do not offer sufficient guidance.
Topics: Female; Humans; Pregnancy; Cost-Benefit Analysis; Pregnancy, Multiple
PubMed: 37621143
DOI: 10.1177/0272989X231188129 -
The Lancet. Oncology Jul 2024Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systematic evaluations of cancer risk in people living with HIV or AIDS (PLHIV) and solid organ transplant recipients provide unique insights into the role of the immune system in cancer development. In this systematic review and meta-analysis, we expand previous analyses of cancer risk for these two immunocompromised populations.
METHODS
We considered studies published in English and listed on PubMed or Embase up to July 1, 2022. Studies were eligible for inclusion if they used population-based registries and compared cancer incidence in PLHIV or solid organ transplant recipients with the general population in the same geographical area. We extracted the number of observed site-specific cancers and expected cases and calculated meta-standardised incidence ratios for cancer within PLHIV and solid organ transplant recipients. In solid organ transplant recipients meta-standardised incidence ratios were compared by organ type. This project is registered on PROSPERO, CRD42022366679.
FINDINGS
46 studies in PLHIV and 67 in solid organ transplant recipients were included in the analysis. Meta-standardised incidence ratios for cancers associated with human papillomavirus were increased in both populations; the highest meta-standardised incidence ratio in PLHIV was anal cancer (37·28 [95% CI 23·65-58·75], I=97·4%), and in solid organ transplant recipients was cutaneous squamous cell carcinoma (45·87 [31·70-66·38], I=99·0%). Meta-standardised incidence ratios were significantly increased for most non-HPV viral-infection-related cancers in both populations; the highest standard incidence ratios were for Kaposi sarcoma (PLHIV: 801·52 [95% CI 200·25-3208·13], I=100·0%; solid organ transplant recipients: 47·31 [23·09-96·95], I=87·7%) and non-Hodgkin lymphoma (32·53 [19·64-53·87], I=99·8%; 10·24 [8·48-12·35], I=94·9%). Eight types of cancer with no known viral cause showed an increased risk in solid organ transplant recipients only; no cancer type showed increased risk in PLHIV only.
INTERPRETATION
Cancer risk was increased for a range of infection-related cancers in both PLHIV and solid organ transplant recipients, but divergent results in these and other cancers have emerged. The cancer risk patterns probably reflect variances in the degree of impaired immunity, exposure to carcinogenic viruses, and perhaps exposure to carcinogenic immunosuppressive agents.
FUNDING
US National Cancer Institute, National Institutes of Health.
Topics: Humans; Organ Transplantation; HIV Infections; Neoplasms; Incidence; Transplant Recipients; Immunocompromised Host; Risk Factors; Risk Assessment; Female; Male
PubMed: 38936380
DOI: 10.1016/S1470-2045(24)00189-X -
Tissue Engineering and Regenerative... Jul 2024Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human... (Review)
Review
Organoids are essentially an in vitro (lab-grown) three-dimensional tissue culture system model that meticulously replicates the structure and physiology of human organs. A few of the present applications of organoids are in the basic biological research area, molecular medicine and pharmaceutical drug testing. Organoids are crucial in connecting the gap between animal models and human clinical trials during the drug discovery process, which significantly lowers the time duration and cost associated with each stage of testing. Likewise, they can be used to understand cell-to-cell interactions, a crucial aspect of tissue biology and regeneration, and to model disease pathogenesis at various stages of the disease. Lung organoids can be utilized to explore numerous pathophysiological activities of a lung since they share similarities with its function. Researchers have been trying to recreate the complex nature of the lung by developing various "Lung organoids" models.This article is a systematic review of various developments of lung organoids and their potential progenitors. It also covers the in-depth applications of lung organoids for the advancement of translational research. The review discusses the methodologies to establish different types of lung organoids for studying the regenerative capability of the respiratory system and comprehending various respiratory diseases.Respiratory diseases are among the most common worldwide, and the growing burden must be addressed instantaneously. Lung organoids along with diverse bio-engineering tools and technologies will serve as a novel model for studying the pathophysiology of various respiratory diseases and for drug screening purposes.
Topics: Organoids; Humans; Lung; Animals; Tissue Engineering; Regeneration; Regenerative Medicine
PubMed: 38466362
DOI: 10.1007/s13770-024-00628-2 -
Journal of Clinical Nursing Jun 2024The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as... (Meta-Analysis)
Meta-Analysis Review
AIM
The early warning scores (EWS), quick Sequential Organ Failure Assessment (qSOFA) and systemic inflammatory response syndrome (SIRS) criteria have been proposed as sepsis screening tools. This review aims to summarise and compare the performance of EWS with the qSOFA and SIRS criteria for predicting sepsis diagnosis and in-hospital mortality in patients with sepsis.
DESIGN
A systematic review with meta-analysis.
REVIEW METHODS
Seven databases were searched from January 1, 2016 until March 10, 2022. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, likelihood ratios and diagnostic odd ratios were pooled by using the bivariate random effects model. Overall performance was summarised by using the hierarchical summary receiver-operating characteristics curve. This paper adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines.
RESULTS
Ten studies involving 52,474 subjects were included in the review. For predicting sepsis diagnosis, the pooled sensitivity of EWS (65%, 95% CI: 55, 75) was similar to SIRS ≥2 (70%, 95% CI: 49, 85) and higher than qSOFA ≥2 (37%, 95% CI: 20, 59). The pooled specificity of EWS (77%, 95% CI: 64, 86) was higher than SIRS ≥2 (62%, 95% CI: 41, 80) but lower than qSOFA ≥2 (94%, 95% CI: 86, 98). Results were similar for the secondary outcome of in-hospital mortality.
CONCLUSIONS
Although no one scoring system had both high sensitivity and specificity, the EWS had at least equivalent values in most measures of diagnostic accuracy compared with SIRS or qSOFA.
IMPLICATIONS FOR THE PROFESSION
Healthcare systems in which EWS is already in place should consider whether there is any clinical benefit in adopting qSOFA or SIRS.
NO PATIENT OR PUBLIC CONTRIBUTION
This systematic review did not directly involve patient or public contribution to the manuscript.
Topics: Humans; Sepsis; Hospital Mortality; Early Warning Score; Organ Dysfunction Scores; Adult; Systemic Inflammatory Response Syndrome; Sensitivity and Specificity
PubMed: 38379353
DOI: 10.1111/jocn.17061 -
Frontiers in Neurology 2023Hearing can be impaired in many neurological conditions and can even represent a forme of specific disorders. Auditory function can be measured by either subjective or... (Review)
Review
Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative 'window of discovery'.
BACKGROUND
Hearing can be impaired in many neurological conditions and can even represent a forme of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear's perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function.
METHODS
A systematic review of the literature was performed, searching for papers with case-control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated.
RESULTS
Patients with neurological disorders (headache, Parkinson's disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals.
CONCLUSION
Existing data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.
PubMed: 37662038
DOI: 10.3389/fneur.2023.1204132