Genotype-phenotype correlations in alpha-sarcoglycanopathy: a systematic review.

BACKGROUND: Mutations in the alpha-sarcoglycan gene cause limb-girdle muscular dystrophy 2D, an autosomal recessive muscle wasting disorder primarily affecting the muscles of the shoulder and pelvic girdles. To date, no previous study has collated all known mutations in alpha-sarcoglycan and mapped these to the associated phenotypes. AIMS: To examine for correlations between mutation locations, or mutation type, and the phenotype caused in all reported mutations in alpha-sarcoglycan. METHODS: We present a systematic literature review examining correlations between mutation locations, or mutation type, and the phenotype caused in all reported cases of limb-girdle muscular dystrophy 2D. RESULTS: From 134 unique genotypes collated, a strong prevalence of missense mutations (64% of all unique mutations) was found in this gene. Mutation hotspots were noted in exon three and the extracellular domain, with mutation densities varying significantly between both exons and protein domains (p ≤ 0.01). All compound heterozygous limb-girdle muscular dystrophy 2D patients with cardiac involvement contained at least one mutation in exon three, a novel finding. All non-sense mutations in alpha-sarcoglycan give a severe phenotype, as do genotypes involving a combination of exons four and five. This study confirms on a large, diverse cohort the extremely high prevalence of the c.229C > T mutation. CONCLUSIONS: This study demonstrates the vast variation in disease severity seen between patients possessing the same mutation, highlighting the difficulty identifying genotype-phenotype correlations in this condition. Novel findings including the involvement of exon three in all compound heterozygous patients who suffered from cardiomyopathy, and the severity of mutations involving exons four and five may help to guide investigations and therapeutic decisions in an era of personalised medicine.

Omalizumab-associated eosinophilic granulomatosis with polyangiitis: cause or coincidence?

Omalizumab is an anti-IgE monoclonal antibody used in severe allergic asthma. Herein, we describe a case of eosinophilic granulomatosis with polyangiitis, which manifested 3 months after initiation of omalizumab therapy, while maintenance corticosteroid therapy dose was unchanged.

The unmet needs of patients with advanced incurable head and neck cancer and their carers: A systematic review and meta-ethnography of qualitative data.

INTRODUCTION: Patients with advanced-stage head and neck cancers (HNC) endure a significant symptom burden and suffer greatly towards the end of their lives. Qualitative evidence can provide insight into how existing services meet their needs. We aimed to synthesise qualitative data from patients with advanced HNC and their carers to inform improvements to services and care. METHODS: A systematic search was conducted in MEDLINE and EMBASE for studies containing qualitative data from patients with advanced HNC and their carers. An interpretive account was generated using the meta-ethnography methodology. RESULTS: We identified 8 studies including 38 patients and 25 carers. Twenty-six themes were synthesised into five concepts: psychological impact and adjustment, physical limitations and deliverance of symptomatic care, communication and information needs from healthcare professionals, social support and dependence, and needs of the primary caregiver. We identified that patients had complex psychological needs, centred on uncertainty and fear of suffering. Patients desired full information and found poor communication highly distressing. There was a dearth of literature on the subjective impact of physical limitations. Patients became reliant on social networks, and those with lower quality relationships coped poorly. However, caregivers struggled to meet patients' complex needs, resulting in distress and isolation. CONCLUSIONS: Patients with advanced HNCs have complex needs that are not met in current systems. Further qualitative work focusing on the physical and psychological impact of advanced HNC would be of value.

The Effect of the 2019 Novel Coronavirus Pandemic on Stroke and TIA Patient Admissions: Perspectives and Risk Factors.

BACKGROUND: The 2019 novel coronavirus pandemic has generated concern from stroke specialist centres across the globe. Reductions in stroke admissions have been reported, despite many expecting an increase due to the pro-thrombotic nature of 2019 novel coronavirus. AIMS: To assess the impact of the pandemic and subsequent lockdown on stroke admissions and transient ischaemic attack referrals at the Royal Victoria Infirmary, Newcastle-Upon-Tyne, and additionally on patient behaviours affecting modifiable risk factors or perspectives related to accessing healthcare. METHODS: A single-centre retrospective data analysis was carried out on a "lockdown" cohort of suspected stroke patients admitted between 11 March to 26 May 2020 and a "pre-lockdown" cohort admitted in 2019. Differences in weekly admissions, weekly referrals, onset-to-presentation time and weekly thrombolysis cases were examined. Further analysis interrogated these cohorts separated by Bamford classification and stroke mimics (such as seizure/hemiplegic migraine/functional neurology). A binary-format questionnaire was separately administered to admitted patients from 15 April to 5 June 2020. RESULTS: Significant reductions in weekly posterior circulation infarct (-43%, p = 0.017) and stroke-mimic (-47%, p < 0.001) admissions and weekly referrals diagnosed as non-transient ischaemic attack (-55%, p = 0.002) were observed in the lockdown cohort, with no differences in onset-to-presentation time. Over 25% of questionnaire respondents reported less physical activity, increased isolation and delaying their presentation due to the pandemic. CONCLUSIONS: This study provides evidence of reduced stroke-mimic and posterior circulation infarct admissions. Questionnaire findings suggest that patients need to be informed to ensure they appropriately seek medical advice. Significant communication at the stroke-primary care interface is needed to support referral pathways and management of modifiable risk factors.