The burden of psychiatric symptoms in Parkinson's disease includes depression, anxiety, apathy, psychosis, and impulse control disorders. However, the relationship between psychiatric comorbidities and subsequent prognosis and neurological outcomes is not yet well understood. In this systematic review and meta-analysis, in individuals with Parkinson's disease, we aimed to characterise the association between specific psychiatric comorbidities and subsequent prognosis and neurological outcomes: cognitive impairment, death, disability, disease progression, falls or fractures and care home admission. We searched MEDLINE, Embase, PsycINFO and AMED up to 13th November 2023 for longitudinal observational studies which measured disease outcomes in people with Parkinson's disease, with and without specific psychiatric comorbidities, and a minimum of two authors extracted summary data. Studies of individuals with other parkinsonian conditions and those with outcome measures that had high overlap with psychiatric symptoms were excluded to ensure face validity. For each exposure-outcome pair, a random-effects meta-analysis was conducted based on standardised mean difference, using adjusted effect sizes–where available–in preference to unadjusted effect sizes. Study quality was assessed using the Newcastle–Ottawa Scale. Between-study heterogeneity was assessed using the I² statistic and publication bias was assessed using funnel plots. PROSPERO Study registration number: CRD42022373072. There were 55 eligible studies for inclusion in meta-analysis (n = 165,828). Data on participants’ sex was available for 164,514, of whom 99,182 (60.3%) were male and 65,460 (39.7%) female. Study quality was mostly high (84%). Significant positive associations were found between psychosis and cognitive impairment (standardised mean difference [SMD] 0.44, [95% confidence interval [CI] 0.23–0.66], I² 30.9), psychosis and disease progression (SMD 0.46, [95% CI 0.12–0.80], I² 70.3%), depression and cognitive impairment (SMD 0.37 [95% CI 0.10–0.65], I² 27.1%), depression and disease progression (SMD 0.46 [95% CI 0.18–0.74], I² 52.2), depression and disability (SMD 0.42 [95% CI 0.25–0.60], I² 7.9%), and apathy and cognitive impairment (SMD 0.60 [95% CI 0.02–1.19], I² 27.9%). Between-study heterogeneity was moderately high. Psychosis, depression, and apathy in Parkinson's disease are all associated with at least one adverse outcome, including cognitive impairment, disease progression and disability. Whether this relationship is causal is not clear, but the mechanisms underlying these associations require exploration. Clinicians should consider these psychiatric comorbidities to be markers of a poorer prognosis in people with Parkinson's disease. Future studies should investigate the underlying mechanisms and which treatments for these comorbidities may affect Parkinson's disease outcomes. 10.13039/100010269 Wellcome Trust , UK 10.13039/501100000272 National Institute for Health Research (NIHR), 10.13039/501100000272 National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at 10.13039/100009362 South London and Maudsley NHS Foundation Trust and King's College London, 10.13039/501100000272 National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at 10.13039/501100008721 University College London Hospitals NHS Foundation Trust , National Brain Appeal.

Alzheimer’s disease (AD) presents a significant challenge to global health. It is characterized by progressive cognitive deterioration and increased rates of morbidity and mortality among older adults. Among the various pathophysiologies of AD, mitochondrial dysfunction, encompassing conditions such as increased reactive oxygen production, dysregulated calcium homeostasis, and impaired mitochondrial dynamics, plays a pivotal role. This review comprehensively investigates the mechanisms of mitochondrial dysfunction in AD, focusing on aspects such as glucose metabolism impairment, mitochondrial bioenergetics, calcium signaling, protein tau and amyloid-beta-associated synapse dysfunction, mitophagy, aging, inflammation, mitochondrial DNA, mitochondria-localized microRNAs, genetics, hormones, and the electron transport chain and Krebs cycle. While lecanemab is the only FDA-approved medication to treat AD, we explore various therapeutic modalities for mitigating mitochondrial dysfunction in AD, including antioxidant drugs, antidiabetic agents, acetylcholinesterase inhibitors (FDA-approved to manage symptoms), nutritional supplements, natural products, phenylpropanoids, vaccines, exercise, and other potential treatments.

Large language models (LLMs) like ChatGPT have potential applications in medical education such as helping students study for their licensing exams by discussing unclear questions with them. However, they require evaluation on these complex tasks. The purpose of this study was to evaluate how well publicly accessible LLMs performed on simulated UK medical board exam questions. 423 board-style questions from 9 UK exams (MRCS, MRCP, etc.) were answered by seven LLMs (ChatGPT-3.5, ChatGPT-4, Bard, Perplexity, Claude, Bing, Claude Instant). There were 406 multiple-choice, 13 true/false, and 4 "choose N" questions covering topics in surgery, pediatrics, and other disciplines. The accuracy of the output was graded. Statistics were used to analyze differences among LLMs. Leaked questions were excluded from the primary analysis. ChatGPT 4.0 scored (78.2%), Bing (67.2%), Claude (64.4%), and Claude Instant (62.9%). Perplexity scored the lowest (56.1%). Scores differed significantly between LLMs overall (p < 0.001) and in pairwise comparisons. All LLMs scored higher on multiple-choice vs true/false or “choose N” questions. LLMs demonstrated limitations in answering certain questions, indicating refinements needed before primary reliance in medical education. However, their expanding capabilities suggest a potential to improve training if thoughtfully implemented. Further research should explore specialty specific LLMs and optimal integration into medical curricula.

Research on mortality outcomes and non-cancer-related causes of death in patients with cutaneous melanoma (CM) remains limited. This study aimed to identify the prevalence of non-cancer-related deaths following CM diagnosis. The data of 224,624 patients diagnosed with malignant CM in the United States between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We stratified our cohort based on their melanoma stage at diagnosis and further calculated standardized mortality ratios (SMRs) for each cause of death, comparing their relative risk to that of the general US population. The total number of fatalities among melanoma patients was 60,110, representing 26.8% of the total cases. The percentage of deaths is directly proportional to the disease stage, reaching 80% in distant melanoma. The highest fatalities among the localized melanoma group (25,332; 60.5%) occurred from non-cancer causes, followed by melanoma-attributable deaths (10,817; 25.8%). Conversely, melanoma is the leading cause of death in regional and distant melanoma cohorts. Cardiovascular and cerebrovascular diseases were the most prevalent non-cancer causes of death among the three disease-stage cohorts. Compared to the general population, we did not observe an increased risk of death due to non-cancer causes in the localized CM cohort, while patients diagnosed with regional and distant CMs had a statistically significant higher risk of death from all the reported major causes of death.

Background: Celiac disease (CD) is an autoimmune disorder in which genetically susceptible individuals cannot digest gluten (wheat) and its homologs such as Scalin (rye) and Hordein (barley).Aim: This systematic review and meta‐analysis aimed to investigate the measures of associations between CD and psychiatric disorders, specifically anxiety and depression, and explore the relationship between adherence to a Gluten‐Free Diet (GFD) and the psychiatric aspects of the disease.Methods: We searched PubMed, Scopus and Web of Science for articles investigating anxiety and depression in CD patients. The following inclusion criteria were implemented: Primary research articles (either observational or experimental) that include participants with a CD diagnosis ‐confirmed either serologically, with anti‐endomysial antibodies, anti‐tissue transglutaminase antibodies, or with duodenum biopsy, whether on a GFD or not,—who have depression or anxiety symptoms identified through self‐report or clinician‐administered scales.Results: CD patients are at a higher odds of developing anxiety, as the odds ratio was (OR: 2.26, 95% CI: [1.10, 4.67]) and depression symptoms (OR: 3.36, 95% CI: [1.36, 8.32]). Results of both State‐Trait Anxiety Inventory Y‐1 and Y‐2 improved after 1 year of GFD with mean difference of 3.48, 95% CI: (0.26, 6.71), and MD: 3.45, 95% CI: (1.39, 5.52), respectively.Conclusion: Anxiety and depression are prevalent among adults and children CD patients as they are observed to have high odds of anxiety and depression as expressed by various scales. It is reported that GFD is associated with decreased levels of anxiety and depression, however, further studies are required to confirm these findings and to investigate the main mechanism of psychiatric disorders among CD patients.

Background: Several reports examined the survival of laryngeal cancer (LC) patients, most of these studies only focused on the prognosis of the disease, and just a small number of studies examined non-cancer-related causes of death. The objective of the current study is to investigate and quantify the most common causes of deaths following LC diagnosis. Methods: The data of 44,028 patient with LC in the United States diagnosed between 2000 and 2018 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) program and analyzed. We stratified LC patients according to various demographic and clinical parameters and calculated standardized mortality ratios (SMRs) for all causes of death. Results: Over the follow-up period, 25,407 (57.7%) deaths were reported. The highest fatalities (11,121; 43.8%) occurred within 1–5 years following LC diagnosis. Non-cancer causes of death is the leading cause of death (8945; 35.2%), followed by deaths due to laryngeal cancer (8,705; 34.3%), then other cancers deaths (7757; 30.5%). The most common non-cancer causes of death were heart diseases (N = 2953; SMR 4.42), followed by other non-cancer causes of death (N = 1512; SMR 3.93), chronic obstructive pulmonary diseases (N = 1420; SMR 4.90), then cerebrovascular diseases (N = 547; SMR 4.28). Compared to the general population, LC patients had a statistically significant higher risk of death from all reported causes. Conclusions: Non-cancer causes of death is the leading cause of death in LC patients, exceeding deaths attributed to LC itself. These findings provide important insight into how LC survivors should be counselled regarding future health risks.