Empirical evidence for biometal dysregulation in Parkinson's disease from a systematic review and Bradford Hill analysis.
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ABSTRACT:
SUBMITTER: Abdeen AH
PROVIDER: S-EPMC9237090 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo assess the evidence for price-based alcohol policy interventions to determine whether minimum unit pricing (MUP) is likely to be effective.DesignSystematic review and assessment of studies according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, against the Bradford Hill criteria for causality. Three electronic databases were searched from inception to February 2017. Additional articles were found through hand searching and grey literature searches.Criteria for selecting studiesWe included any study design that reported on the effect of price-based interventions on alcohol consumption or alcohol-related morbidity, mortality and wider harms. Studies reporting on the effects of taxation or affordability and studies that only investigated price elasticity of demand were beyond the scope of this review. Studies with any conflict of interest were excluded. All studies were appraised for methodological quality.ResultsOf 517 studies assessed, 33 studies were included: 26 peer-reviewed research studies and seven from the grey literature. All nine of the Bradford Hill criteria were met, although different types of study satisfied different criteria. For example, modelling studies complied with the consistency and specificity criteria, time series analyses demonstrated the temporality and experiment criteria, and the analogy criterion was fulfilled by comparing the findings with the wider literature on taxation and affordability.ConclusionsOverall, the Bradford Hill criteria for causality were satisfied. There was very little evidence that minimum alcohol prices are not associated with consumption or subsequent harms. However the overall quality of the evidence was variable, a large proportion of the evidence base has been produced by a small number of research teams, and the quantitative uncertainty in many estimates or forecasts is often poorly communicated outside the academic literature. Nonetheless, price-based alcohol policy interventions such as MUP are likely to reduce alcohol consumption, alcohol-related morbidity and mortality.
| S-EPMC5777460 | biostudies-literature
Project description:Background and aimsFatal outcome of opioid overdose, once detected, is preventable through timely administration of the antidote naloxone. Take-home naloxone provision directly to opioid users for emergency use has been implemented recently in more than 15 countries worldwide, albeit mainly as pilot schemes and without formal evaluation. This systematic review assesses the effectiveness of take-home naloxone, with two specific aims: (1) to study the impact of take-home naloxone distribution on overdose-related mortality; and (2) to assess the safety of take-home naloxone in terms of adverse events.MethodsPubMed, MEDLINE and PsychINFO were searched for English-language peer-reviewed publications (randomized or observational trials) using the Boolean search query: (opioid OR opiate) AND overdose AND prevention. Evidence was evaluated using the nine Bradford Hill criteria for causation, devised to assess a potential causal relationship between public health interventions and clinical outcomes when only observational data are available.ResultsA total of 1397 records (1164 after removal of duplicates) were retrieved, with 22 observational studies meeting eligibility criteria. Due to variability in size and quality of the included studies, meta-analysis was dismissed in favour of narrative synthesis. From eligible studies, we found take-home naloxone met all nine Bradford Hill criteria. The additional five World Health Organization criteria were all either met partially (two) or fully (three). Even with take-home naloxone administration, fatal outcome was reported in one in 123 overdose cases (0.8%; 95% confidence interval = 0.4, 1.2).ConclusionsTake-home naloxone programmes are found to reduce overdose mortality among programme participants and in the community and have a low rate of adverse events.
| S-EPMC5071734 | biostudies-literature
Project description:BackgroundThe possibility that onchocerciasis may cause epilepsy has been suggested for a long time, but thus far, an etiological link has not been universally accepted. The objective of this review is to critically appraise the relationship between Onchocerca volvulus and epilepsy and subsequently apply the Bradford Hill criteria to further evaluate the likelihood of a causal association.MethodsPubMed and gray literature published until September 15, 2020, were searched and findings from original research were synthesized. Adherence to the 9 Bradford Hill criteria in the context of onchocerciasis and epilepsy was determined to assess whether the criteria are met to strengthen the evidence base for a causal link between infection with O. volvulus and epilepsy, including the nodding syndrome.ResultsOnchocerciasis as a risk factor for epilepsy meets the following Bradford Hill criteria for causality: strength of the association, consistency, temporality, and biological gradient. There is weaker evidence supporting causality based on the specificity, plausibility, coherence, and analogy criteria. There is little experimental evidence. Considering the Bradford Hill criteria, available data suggest that under certain conditions (high microfilarial load, timing of infection, and perhaps genetic predisposition), onchocerciasis is likely to cause epilepsy including nodding and Nakalanga syndromes.ConclusionApplying the Bradford Hill criteria suggests consistent epidemiological evidence that O. volvulus infection is a trigger of epilepsy. However, the pathophysiological mechanisms responsible for seizure induction still need to be elucidated.
| S-EPMC7790236 | biostudies-literature
Project description:BackgroundStudies report an elevated risk of maltreatment in children with attention deficit/hyperactivity disorder (ADHD), and elevated levels of ADHD in people who suffered childhood maltreatment (CM). However, the direction(s) of causality between CM and ADHD remain unclear-does ADHD create a context for CM, does CM cause ADHD, or both?ObjectiveThis study systematically reviews and qualitatively synthesizes the research evidence relating to this question using Bradford-Hill criteria for establishing causality-strength, temporality, dose-response and plausibility.MethodsWe conducted a systematic review, following PRISMA guidelines, of prospective longitudinal studies examining both CM and ADHD. We then used Bradford-Hill criteria to assess the quality of evidence for a causal link between CM and ADHD.ResultsAll 11 included studies demonstrated an association between CM and ADHD. Seven included evidence for temporality: five suggesting that CM precedes ADHD in the lifespan; two suggesting ADHD precedes CM. Four studies demonstrated a dose response relationship in which greater CM exposure was associated with elevated risk of ADHD. Studies presented a range of plausible mechanisms, including CM causing ADHD through biological programming, versus ADHD causing CM through parental stress.ConclusionsThe high quality prospective longitudinal studies reviewed confirm the association between ADHD and CM, but present conflicting evidence about the direction of causality and mechanisms underpinning this association. To better understand the complex interplay between CM and ADHD, more studies using new research designs will be required that can partition effects by type of CM and account for bidirectional effects and other complexities.
| S-EPMC10694545 | biostudies-literature
Project description:In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision-making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta-analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta-analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device-aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow-up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision-making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8252410 | biostudies-literature
Project description:An abundance of evidence suggests that the size and quality of our social relationships improves humans' physical and mental health while increasing lifespan. However most of this evidence comes from observational rather than experimental (randomised trial) evidence, leaving open the possibility that the connection between social relationships and health could be associational rather than causal. However there are examples, including the link between smoking and lung cancer, where a cause was established without experimental evidence. This was sometimes achieved by looking at the totality of evidence, using the 'Bradford Hill Guidelines', which considers factors including the strength of association, reversibility, and evidence of a plausible mechanism. In this paper we apply the Bradford Hill Guidelines to the link between social relationships and health. We conclude that having strong and supportive social relationships causes better health and longer life. Beyond establishing that social relationships are a causal factor for health, the method we used here can be applied to other areas where randomised trials are unethical or not feasible.
| S-EPMC6527915 | biostudies-literature
Project description:Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.
| S-EPMC6353825 | biostudies-literature
Project description:BackgroundInnovation ecosystems are an important driver of regional economic growth and development. STEM assets connected to universities may play an important role in such ecosystems.ObjectiveTo systematically review the literature relating to the effect of university STEM assets on regional economies and innovation ecosystems, providing a better understanding of how the impact is generated and constrained, as well as identifying any gaps in knowledge.MethodsKeyword and text word searches using the Web of Science Core Collection (Clarivate), Econlit (EBSCO) and ERIC (EBSCO) were performed in July 2021 and February 2023. Papers were double screened on abstract and title, and were included if there was consensus that they fulfilled the inclusion criteria of: (i) relating to an OECD country; (ii) having been published between 1 January 2010 and 28 February 2023; and (iii) concerning the impact of STEM assets. Data extraction was undertaken for each article by a single reviewer and checked by a second reviewer. Due to the heterogeneity of the study designs and outcome measures used, it was not possible to perform a quantitative synthesis of results. A narrative synthesis was subsequently undertaken.ResultsOf the 162 articles identified for detailed review, 34 were accepted as being sufficiently relevant to the study to be included for final analysis. Three important features identified were that the literature: i) is predominately concerned with supporting new businesses; ii) describes a high level of involvement with a university in providing that support; and iii studies economic impacts at local, regional and national levels.DiscussionThe evidence points to a gap in the literature relating to looking at the broader impact of STEM assets and any corresponding transformational, system-level effects that go beyond narrowly defined, short to medium-term outcomes. The main limitation of this review is that information on STEM assets in the non-academic literature is not captured.
| S-EPMC10306183 | biostudies-literature
Project description:Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients. Furthermore, knockout or genetic inactivation of NADPH oxidases exert a neuroprotective effect and reduce detrimental aspects of pathology in experimental models of the disease. However, the connections between NADPH oxidases and the biological processes believed to contribute to neuronal death are not well known. This review provides a comprehensive summary of our current understanding about expression and physiological function of NADPH oxidases in neurons, microglia and astrocytes and their pathophysiological roles in PD. It summarizes the findings supporting the role of both microglial and neuronal NADPH oxidases in cellular disturbances associated with PD such as neuroinflammation, alpha-synuclein accumulation, mitochondrial and synaptic dysfunction or disruption of the autophagy-lysosome system. Furthermore, this review highlights different steps that are essential for NADPH oxidases enzymatic activity and pinpoints major obstacles to overcome for the development of effective NADPH oxidases inhibitors for PD.
| S-EPMC5683583 | biostudies-literature
Project description:BackgroundParkinson's disease (PD) is a neurodegenerative disorder associated with inferior clinical outcomes after surgical management of many orthopedic conditions. The purpose of this systematic review was to define the clinical, functional, and patient-reported outcomes of shoulder arthroplasty (SA) in patients with PD.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was completed using the Ovid platform for searches in MEDLINE, EMBASE, Cochrane Central, and Cochrane Systematic Reviews, with additional searches in Web of Science and Scopus. Included studies were full-length, English-language, clinical investigations reporting on SA in patients with PD with at least one clinical outcome.ResultsSeven studies including 7126 patients (7134 SA) met inclusion criteria with a mean age of 72.6 (range, 69.5-75.8 years), 58.9% female, and the average follow-up duration was 65 months (range, 17-119 months). Anatomic total shoulder arthroplasty (aTSA) was the most reported implant surgery (n = 3455, 48.4%) followed by hemiarthroplasty (HA) (n = 2840, 39.8%), and reverse shoulder arthroplasty (RSA) (n = 839,1.8%). SA consistently improved pain. Forward elevation, abduction, and external rotation had a pooled mean increase of 36°, 20°, and 6°, respectively. Complications occurred at a pooled rate of 22.5%, with stiffness (7.1%), need for revision (5.3%), and instability (4.7%) as the most common complications reported. Reoperations inclusive of revisions occurred at a lower pooled rate of 5.6%, with aTSA (n = 201; 9.0%) having the highest rate, followed by HA (n = 158; 7.1%), and then RSA (n = 42; 1.9%).ConclusionsThe results of the present systematic review demonstrate that SA in patients with PD results in consistent pain relief. However, inferior improvements in clinical outcomes may be expected when compared with patients without PD, likely due to the neurodegenerative manifestations of this disorder. In addition, RSA had a lower reoperation rate than HA and aTSA in patients with PD.
| S-EPMC8888176 | biostudies-literature