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Background: The quality of Patient and Public Involvement (PPI) in healthcare research varies considerably and is frequently tokenistic. We aimed to co-produce the Insight | Public Involvement Quality Recognition and Awards programme, based on the UK Standards for Public Involvement (UKSPI) alongside an incremental scale designed by Expert Citizens (a lived experience-led community group), to incentivise and celebrate continuous improvement in PPI. Methods: We used Task and Finish Groups (19/44 [43%] public contributor membership) to co-produce the programme which we piloted in three organisations with different healthcare research models. We used surveys and review sessions to capture learning and reflections. Results: We co-created: A Quality descriptor matrix comprising four incremental quality levels (Welcoming, Listening, Learning, Leading) for each UKSPI standard. An assessment framework including guidance materials, self-assessment form and final report template. An assessor training package. The quality awards event format and nomination form. These materials were modified based on pilot-site feedback. Of survey respondents: 94.4% felt they had made at least 'Some' personal contribution (half said 'Quite a lot'/'A great deal'), 88.9% said they were 'Always'/'Often' able to express their views freely and, 100% stated the programme would have 'A lot of impact'/'Quite a bit of impact'. During the project, we identified the importance of taking time to explain project aims and contributor roles, adapting to the needs of individual contributors and, using smaller bespoke sessions outside the main Task and Finish Groups. Conclusions: We co-produced and piloted a quality recognition programme to incentivise and celebrate continuous quality improvement in PPI. One public contributor stated, "I feel strongly that the Insight framework and awards will raise awareness of the [public involvement] work going on in many community settings. [It] is likely to result in better sharing of positive practice, incentivising research groups of any size to start work or to improve the quality of [PPI] could be one of the main benefits. I'm excited that if this initiative takes off, regionally and then in the longer term nationally, it could be a significant step in advancing the [public] voice." Plain English summary: How researchers involve members of the public in health research varies widely. We developed a scheme that encourages researchers from any health research organisation to improve the quality of public involvement. We used joint workshops with researchers, health workers and members of the public to design the scheme. We then tested it in three research organisations. We recorded the experience of people taking part in the project to learn what went well and what could be improved. We looked at the six areas covered in the UK Standards for Public Involvement. For each area, we worked together to define four levels (Welcoming, Listening, Learning, Leading) of increasing quality. We designed the materials needed for organisations to take part in the scheme. We also created a training pack for assessors and the format of a celebration event. We modified the materials after testing them. We asked those who took part in the project, half of whom were lay members, what they thought. 94% felt they had made at least some personal contribution. 89% said they were often or always able to express their views freely. Everyone thought the project would have some degree of impact. Overall, those members of the public who took part said they enjoyed the process and felt that their views were listened to. Along the way, we learned that it was important to carefully explain the project's aims, be clear about roles and have 1to1 discussions outside the main workshops. [ABSTRACT FROM AUTHOR]

Background: Mutations of mitochondrial DNA (mtDNA) cause a broad spectrum of clinical phenotypes. Anecdotal evidence suggests that voice and swallow problems are a common feature of these diseases. Aims: To characterize accurately the prevalence and severity of voice and swallow problems in a large cohort of patients with mitochondrial disease. Methods & Procedures: Patients with proven mitochondrial disease were sent validated questionnaires to assess both voice and swallow function. The presence of voice and swallow symptoms was correlated with other clinical features of mitochondrial disease in affected patients. Outcomes & Results: From the original 177 patients contacted, 98 swallowing status questionnaires and 96 Voice Handicap Index questionnaires were returned, response rates of 55% and 54%, respectively. Swallow: 48% of patients reported more difficulties with swallowing than control participants. Patients with single mtDNA deletions were most likely to report problems (65.2%), with patients with an m.8344A greater than G point mutation least likely (33.3%). All genotypes had a mean severity score in excess of the normal range, the highest mean score being found in the single large-scale mtDNA deletion group (10.12), the lowest in the m.3243A greater than G group (5.56) Voice; 48% of patients reported some difficulty with voice. Patients with single large-scale deletions showed the highest prevalence (65.2%), patients with the m.3243A greater than G mutation the lowest (33%). The most severe voice difficulties were reported by patients with an m.8344A greater than G point mutation. Patients with an m.3243A greater than G point mutation had the mildest and lowest incidence of voice problems. All genotypes scored outside of the normal range expected on the VHI overall ([greater than or equal]11.5 in control trials). Patients with an m.8344A greater than G point mutation reported a significantly higher degree of physical voice handicap than m.3243A greater than G patients (13.13 versus 4.40, p = 0.02). In patients with either single or multiple mtDNA deletions the likely pathophysiological mechanism is of proximal muscle weakness, whereas in patients with the m.8344A greater than G mutation cerebellar ataxia is the likely cause. Conclusions & Implications: Dysphagia and dysarthria have been identified as symptoms in previous research, however the prevalence and pathophysiology of these symptoms have not been explored. This paper indicates that voice and swallow problems are a common, though predominantly mild feature of mitochondrial disease and that there is a core group of pathophysiological symptoms linked to the presence of voice and swallowing problems. This paper recommends early referral to speech and language therapists to identify emerging dysphonia and dysphagia and to provide appropriate intervention. (Contains 3 tables.)

Background: Mitochondrial disease is a heterogenous group of rare, complex neurometabolic disorders. Despite their individual rarity, collectively mitochondrial diseases represent the most common cause of inherited metabolic disorders in the UK; they affect 1 in every 4300 individuals, up to 15,000 adults (and a similar number of children) in the UK. Mitochondrial disease manifests multisystem and isolated organ involvement, commonly affecting those tissues with high energy demands, such as skeletal muscle. Myopathy manifesting as fatigue, muscle weakness and exercise intolerance is common and debilitating in patients with mitochondrial disease. Currently, there are no effective licensed treatments and consequently, there is an urgent clinical need to find an effective drug therapy.Aim: To investigate the efficacy of 12-week treatment with acipimox on the adenosine triphosphate (ATP) content of skeletal muscle in patients with mitochondrial disease and myopathy.Methods: AIMM is a single-centre, double blind, placebo-controlled, adaptive designed trial, evaluating the efficacy of 12 weeks' administration of acipimox on skeletal muscle ATP content in patients with mitochondrial myopathy. Eligible patients will receive the trial investigational medicinal product (IMP), either acipimox or matched placebo. Participants will also be prescribed low dose aspirin as a non-investigational medical product (nIMP) in order to protect the blinding of the treatment assignment. Eighty to 120 participants will be recruited as required, with an interim analysis for sample size re-estimation and futility assessment being undertaken once the primary outcome for 50 participants has been obtained. Randomisation will be on a 1:1 basis, stratified by Fatigue Impact Scale (FIS) (dichotomised as < 40, ≥ 40). Participants will take part in the trial for up to 20 weeks, from screening visits through to follow-up at 16 weeks post randomisation. The primary outcome of change in ATP content in skeletal muscle and secondary outcomes relating to quality of life, perceived fatigue, disease burden, limb function, balance and walking, skeletal muscle analysis and symptom-limited cardiopulmonary fitness (optional) will be assessed between baseline and 12 weeks.Discussion: The AIMM trial will investigate the effect of acipimox on modulating muscle ATP content and whether it can be repurposed as a new treatment for mitochondrial disease with myopathy.Trial Registration: EudraCT2018-002721-29 . Registered on 24 December 2018, ISRCTN 12895613. Registered on 03 January 2019, https://www.isrctn.com/search?q=aimm. [ABSTRACT FROM AUTHOR]

Concern about the appropriate role of nonsteroidal anti-inflammatory drugs (NSAIDs) in COVID-19 speculate that NSAIDs, in particular ibuprofen, may upregulate the entry point for the virus, the angiotensin-converting enzyme (ACE) 2 receptors and increase susceptibility to the virus or worsen symptoms in existing disease. Adverse outcomes with COVID-19 have been linked to cytokine storm but the most effective way to address exaggerated inflammatory response is complex and unclear. The Expert Working Group on the Commission of Human Medicines in the UK and other organizations have stated that there is insufficient evidence to establish a link between ibuprofen and susceptibility to or exacerbation of COVID-19. NSAID use must also be categorized by whether the drugs are relatively low-dose over-the-counter oral products taken occasionally versus higher-dose or parenteral NSAIDs. Even if evidence emerged arguing for or against NSAIDs in this setting, it is unclear if this evidence would apply to all NSAIDs at all doses in all dosing regimens. Paracetamol (acetaminophen) has been proposed as an alternative to NSAIDs but there are issues with liver toxicity at high doses. There are clearly COVID-19 cases where NSAIDs should not be used, but there is no strong evidence that NSAIDs must be avoided in all patients with COVID-19; clinicians must weigh these choices on an individual basis. [ABSTRACT FROM AUTHOR]

Background: Influenza is rarely confirmed with laboratory testing and accurate assessment of the overall burden of influenza is difficult. We used statistical modelling methods to generate updated, granular estimates of the number/rate of influenza-attributable hospitalisations and deaths in the United Kingdom. Such data are needed on a continuing basis to inform on cost-benefit analyses of treatment interventions, including vaccination.Methods: Weekly age specific data on hospital admissions (1997-2009) and on deaths (1997-2009) were obtained from national databases. Virology reports (1996-2009) of influenza and respiratory syncytial virus detections were provided by Public Health England. We used an expanded set of ICD-codes to estimate the burden of illness attributable to influenza which we refer to as 'respiratory disease broadly defined'. These codes were chosen to optimise the balance between sensitivity and specificity. A multiple linear regression model controlled for respiratory syncytial virus circulation, with stratification by age and the presence of comorbid risk status (conditions associated with severe influenza outcomes).Results: In the United Kingdom there were 28,516 hospitalisations and 7163 deaths estimated to be attributable to influenza respiratory disease in a mean season, with marked variability between seasons. The highest incidence rates of influenza-attributable hospitalisations and deaths were observed in adults aged 75+ years (252/100,000 and 131/100,000 population, respectively). Influenza B hospitalisations were highest among 5-17 year olds (12/100,000 population). Of all estimated influenza respiratory deaths in 75+ year olds, 50 % occurred out of hospital, and 25 % in 50-64 year olds. Rates of hospitalisations and death due to influenza-attributable respiratory disease were increased in adults identified as at-risk.Conclusions: Our study points to a substantial but highly variable seasonal influenza burden in all age groups, particularly affecting 75+ year olds. Effective influenza prevention or early intervention with anti-viral treatment in this age group may substantially impact the disease burden and associated healthcare costs. The high burden of influenza B hospitalisation among 5-17 year olds supports current United Kingdom vaccine policy to extend quadrivalent seasonal influenza vaccination to this age group.Trial Registration: ClinicalTrial.gov, NCT01520935. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests respiratory syncytial virus (RSV) is an important cause of respiratory disease in adults. However, the adult burden remains largely uncharacterized as most RSV studies focus on children, and population-based studies with laboratory-confirmation of infection are difficult to implement. Indirect modelling methods, long used for influenza, can further our understanding of RSV burden by circumventing some limitations of traditional surveillance studies that rely on direct linkage of individual-level exposure and outcome data.Methods: Multiple linear time-series regression was used to estimate RSV burden in the United Kingdom (UK) between 1995 and 2009 among the total population and adults in terms of general practice (GP) episodes (counted as first consultation ≥28 days following any previous consultation for same diagnosis/diagnostic group), hospitalisations, and deaths for respiratory disease, using data from Public Health England weekly influenza/RSV surveillance, Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics. The main outcome considered all ICD-listed respiratory diseases and, for GP episodes, related symptoms. Estimates were adjusted for non-specific seasonal drivers of disease using secular cyclical terms and stratified by age and risk group (according to chronic conditions indicating severe influenza risk as per UK recommendations for influenza vaccination). Trial registration NCT01706302 . Registered 11 October 2012.Results: Among adults aged 18+ years an estimated 487,247 GP episodes, 17,799 hospitalisations, and 8,482 deaths were attributable to RSV per average season. Of these, 175,070 GP episodes (36 %), 14,039 hospitalisations (79 %) and 7,915 deaths (93 %) were in persons aged 65+ years. High- versus low-risk elderly were two-fold more likely to have a RSV-related GP episode or death and four-fold more likely be hospitalised for RSV. In most seasons since 2001, more GP episodes, hospitalisations and deaths were attributable to RSV in adults than to influenza.Conclusion: RSV is associated with a substantial disease burden in adults comparable to influenza, with most of the hospitalisation and mortality burden in the elderly. Treatment options and measures to prevent RSV could have a major impact on the burden of RSV respiratory disease in adults, especially the elderly. [ABSTRACT FROM AUTHOR]

Purpose: To determine the type, incidence, and clinical outcomes of severe complications from strabismus surgery in the United Kingdom. Methods: Cases were identified prospectively through a national surveillance unit between September 1, 2008, and August 31, 2010. Questionnaire data were requested at the time of the complication recognition and at 6 months'' follow-up. Outcome was graded I to V, with a poor or very poor outcome meaning either loss of corrected visual acuity or primary position double vision. Results: A total of 60 completed reports of adverse events and complications were received during the study period. During the same time approximately 24,000 strabismus surgeries were performed in the United Kingdom, yielding an overall incidence of 1 in 400 operations (95% binomial confidence, 1 per 333-500 operations). The most common reported complication was perforation of the globe (19 [0.08%]), followed by a suspected slipped muscle (16 [0.067%]), severe infection (14 [0.06%]), scleritis (6 [0.02%]), and lost muscle (5 [0.02%]). Overall, complications were reported in adults and children in equal numbers; however, scleritis was significantly more common in adults. A poor or very poor clinical outcome was recorded as 1 operation per 2,400. Conclusions: This study provides an assessment of the overall risks associated with strabismus surgery in the United Kingdom. Complications with the potential for a poor outcome are relatively common, but the final clinical outcome is good in the majority of cases.▪ [Copyright &y& Elsevier]

Objective Superoxide dismutase 2 (SOD2) is down- regulated in osteoarthritis (OA). This study was undertaken to investigate the functional effects of this down-regulation in the context of oxidative damage and mitochondrial dysfunction. Methods Lipid peroxidation in articular cartilage from OA patients and from lesion-free control subjects with femoral neck fracture was assessed by measuring malondialdehyde levels using the thiobarbituric acid reactive substances assay. Long-range polymerase chain reaction amplification and a mitochondrial DNA (mtDNA) strand break assay were used to investigate the presence of somatic large-scale mtDNA rearrangements in cartilage. Microscale oxygraphy was used to explore possible changes in mitochondrial respiratory activity between OA and control chondrocytes. RNA interference was used to determine the effects of SOD2 depletion on lipid peroxidation, mtDNA damage, and mitochondrial respiration. Results OA cartilage had higher levels of lipid peroxidation compared to control cartilage, and lipid peroxidation was similarly elevated in SOD2-depleted chondrocytes. SOD2 depletion led to a significant increase in mtDNA strand breaks in chondrocytes, but there was no notable difference in the level of strand breaks between OA and control chondrocytes. Furthermore, only very low levels of somatic, large-scale mtDNA rearrangements were identified in OA cartilage. OA chondrocytes showed less spare respiratory capacity (SRC) and higher proton leak compared to control chondrocytes. SOD2-depleted chondrocytes also showed less SRC and higher proton leak. Conclusion This is the first study to analyze the effects of SOD2 depletion in human articular chondrocytes in terms of changes to oxidation and mitochondrial function. The findings indicate that SOD2 depletion in chondrocytes leads to oxidative damage and mitochondrial dysfunction, suggesting that SOD2 down-regulation is a potential contributor to the pathogenesis of OA. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK. Methods: This was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data. Results: At follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected. Conclusions: Many children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high. [ABSTRACT FROM AUTHOR]

Although there is no more iconic, stalwart, and eloquent defender of liberty and representative democracy than J. S. Mill, he sometimes endorses nondemocratic forms of governance. This article explains the reasons behind this seeming aberration and shows that Mill actually has complex and nuanced views of the transition from nondemocratic to democratic government, including the comprehensive and parallel material, cultural, institutional, and character reforms that must occur, and the mechanism by which they will be enacted. Namely, an enlightened despot must cultivate democratic virtues such as obedience, industriousness, spirit of nationality, and resistance to tyranny in the population and simultaneously prepare the way for his own demise and secure his own legitimacy by transitioning to the rule of law. This challenges recent scholarship that paints Mill’s nondemocratic views as crudely and uncritically imperialist, because it fails to recognize and engage seriously with his sophisticated (if ultimately problematic) theory of individual and institutional development under enlightened colonialism. [ABSTRACT FROM PUBLISHER]

Looks at the White Paper on Fairness at Work report, a package of legislative proposals aimed at extending employee and trade union rights in Great Britain. Objective of the White Paper; Proposal of the White Paper on individual worker rights; Reference to chapter four of the White Paper on trade unions; Assessment of the impact of the White Paper on employment security.

The trade union connection has shaped the ethos and the organisation of the British Labour Party ever since the latter's birth at the turn of the century. Unlike almost every other democratic Socialist party, labour forged links between its industrial and political wings that have survived virtually without question for over 70 years. On the Continent it is at least theoretically possible that the trade unions could be crushed without inflicting vital injury to the political movement, but in Great Britain the relationship is one so close that neither can receive the slightest blow without its effect being felt by both.

The article focuses on the relationship between the trade unions and the Labour Party in Great Britain in the 20th century. The trade unions have made several efforts to cooperate with the ruling Labour Party during the 1940s and 1950s regarding the economic policy of the government. In the wake of current economic crisis, efforts are being made on both sides to maintain a sound relationship.

Focuses on the democracy of labor unions in Great Britain. Demand for government legislation to make postal ballots compulsory for union elections; Difficulty of unions with wide occupational recruitment areas to combine unity with devoluted powers; Reliance of the ultimate state for a union's success or failure in its ability to improve and safeguard the living standards of its members.

Examines industrial relations in Great Britain during 1997, which were said to be dominated by the consequences of the general election victory of the Labor Party. Changes in the government's approach to labor market reform; Aims of the Labor government; Views on the relationship of trade unions with the Labor government.

Symmetrical polyneuropathy is a common feature of mitochondrial disease. Both axonal and demyelinating types are described, with Schwann cell abnormalities demonstrated on nerve biopsy. Some authors have also suggested an increased incidence of entrapment neuropathy. We identified 738 adult patients with proven mitochondrial disease seen in our centre in the past 25 years. One-hundred sixty seven of these patients had undergone nerve conduction studies as part of their routine clinical care, and the results of these studies were reviewed. We found an incidence rate of carpal tunnel syndrome ( CTS) of 50.7 per 100,000 person-years; 32.5 per 100,000 person-years for men and 65.3 per 100,000 person-years for women. One other patient had evidence of ulnar neuropathy at the elbow. The incidence of CTS in mitochondrial disease is similar to published rates for the UK general population. We found no evidence that mitochondrial disease per se increases the risk of entrapment neuropathy. We suggest that the pathophysiological mechanisms for the development of polyneuropathy in mitochondrial disease are quite distinct from the pathophysiology of CTS. Furthermore, it is essential that patients with mitochondrial disease who present with upper limb paraesthesia be referred for neurophysiological testing, so that treatable CTS is not missed. [ABSTRACT FROM AUTHOR]

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk. [ABSTRACT FROM AUTHOR]

Focuses on history, driving, prayer and tools or medical instruments in Great Britain. Details on the history of ports in east of England; Information on motoring experience in driving a vintage car; Description of medical instruments; Presentation of a prayer of the blind.

Purpose and Scope: The aim of this position statement is to provide recommendations regarding the delivery of genomic testing to patients with rare disease in the UK and Ireland. The statement has been developed to facilitate timely and equitable access to genomic testing with reporting of results within commissioned turnaround times., Methods of Statement Development: A 1-day workshop was convened by the UK Association for Clinical Genomic Science and attended by key stakeholders within the NHS Genomic Medicine Service, including clinical scientists, clinical geneticists and patient support group representatives. The aim was to identify best practice and innovations for streamlined, geographically consistent services delivering timely results. Attendees and senior responsible officers for genomic testing services in the UK nations and Ireland were invited to contribute., Results and Conclusions: We identified eight fundamental requirements and describe these together with key enablers in the form of specific recommendations. These relate to laboratory practice (proportionate variant analysis, bioinformatics pipelines, multidisciplinary team working model and test request monitoring), compliance with national guidance (variant classification, incidental findings, reporting and reanalysis), service development and improvement (multimodal testing and innovation through research, informed by patient experience), service demand, capacity management, workforce (recruitment, retention and development), and education and training for service users. This position statement was developed to provide best practice guidance for the specialist genomics workforce within the UK and Ireland but is relevant to any publicly funded healthcare system seeking to deliver timely rare disease genomic testing in the context of high demand and limited resources., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Distinct clinical syndromes have been associated with pathogenic MT-ATP6 variants. In this cohort study, we identified 125 individuals (60 families) including 88 clinically affected individuals and 37 asymptomatic carriers. Thirty-one individuals presented with Leigh syndrome and 7 with neuropathy ataxia retinitis pigmentosa. The remaining 50 patients presented with variable nonsyndromic features including ataxia, neuropathy, and learning disability. We confirmed maternal inheritance in 39 families and demonstrated that tissue segregation patterns and phenotypic threshold are variant dependent. Our findings suggest that MT-ATP6-related mitochondrial DNA disease is best conceptualized as a mitochondrial disease spectrum disorder and should be routinely included in genetic ataxia and neuropathy gene panels. ANN NEUROL 2019;86:310-315., (© 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Context: Abnormal growth and short stature are observed in patients with mitochondrial disease, but it is unclear whether there is a relationship between final adult height and disease severity., Objective: To determine whether patients with genetically confirmed mitochondrial disease are shorter than their peers and whether stature is related to disease severity., Design: Analysis of final adult height in relation to disease severity as determined by the Newcastle Mitochondrial Disease Adult Scale (NMDAS)., Setting: UK Mitochondrial Disease Patient Cohort (Mito Cohort)., Patients: 575 patients were identified with recorded height, weight, and molecular genetic diagnosis of mitochondrial disease within the Mito Cohort., Main Outcome Measures: Adult height, body mass index (BMI), and their association with genetic subgroup and disease severity., Results: Adults with mitochondrial disease were short, with a mean height of -0.49 SD (95% CI, -0.58 to -0.39; n = 575) compared with UK reference data. Patients were overweight, with a BMI SD of 0.52 (95% CI, 0.37 to 0.67; n = 472). The most common genetic subgroup (m.3243A>G mutation) had a height SD of -0.70 (95% CI, -0.85 to -0.54; n = 234) and a BMI SD of 0.12 (95% CI, -0.10 to 0.34; n = 212). NMDAS scores were negatively correlated with height SD (r = -0.25; 95% CI, -0.33 to -0.17; P < 0.001, n = 533). Rate of disease progression also correlated negatively with adult height (P < 0.001)., Conclusion: Final height in mitochondrial disease reflects disease severity and rate of disease progression. Mitochondrial dysfunction and associated subclinical comorbidities affect growth plate physiology., (Copyright © 2019 Endocrine Society.)