Preparing tomorrow's doctors for the genomics era: A nationwide survey of UK medical students.

Introduction: Low confidence in genomics knowledge among clinicians is a major barrier to the integration of genomics into mainstream medicine. Here, we assessed the genomics confidence of UK medical students approaching graduation. Methods: We conducted a web-based nationwide survey of UK medical students in the final 2 years of study where participants rated their confidence in genomics concepts. Results: In total, 145 medical students across 19 medical schools participated. The amount of genomics teaching students reported receiving was positively associated with genomics confidence, with the amount of basic science teaching having the strongest influence. While confidence was high in core genomics principles, such as the difference between DNA, genes and chromosomes (95%), confidence dropped in clinical applications of genomics - only 50% reported a good understanding of the genetic contribution to disease and 28% reported good knowledge of clinically used genomic tests. Overall, 59% reported a poor understanding of variant interpretation; however, over half who reported receiving 'lots' of genomic medicine teaching reported a good understanding of this topic. Conclusion: Gaps in genomics knowledge and drivers in confidence have been identified herein, highlighting the need for improvements in undergraduate genomics education to prepare future doctors to confidently practise in the genomics era.

The effectiveness of pharmacological and lifestyle interventions to reduce the risk of diabetes and hyperglycaemia following gestational diabetes: A systematic review and meta-analysis.

AIMS: To synthesize the available evidence to better understand the effectiveness of interventions to prevent or delay hyperglycaemia and Type 2 diabetes mellitus (T2DM) postnatally in women with current or previous gestational diabetes mellitus (GDM). METHODS: We searched five databases up to December 2020 for primary peer-reviewed articles reporting postpartum glycaemic outcomes in women with (previous) GDM following pharmacological or lifestyle intervention. Outcomes were relative risk of T2DM or continuous measures of glycaemia, change or at follow-up. A minimum of two studies evaluating the same intervention-outcome combination were needed to conduct meta-analyses, otherwise studies were described narratively. Meta-regression was used to evaluate whether associations varied by additional variables. We assessed risk of bias using the Critical Appraisal Skills Programme checklist. PROSPERO record CRD42018102380. RESULTS: We included 31 studies in the review with a total sample size of 8624 participants, and 26 studies in meta-analyses. Two-thirds of studies followed up participants at 1 year or less. Pharmacological interventions were associated with reduced risk of T2DM (0.80 [95% CI 0.64-1.00], n = 6 studies), as were lifestyle interventions albeit with a smaller effect size (0.88 [95% CI 0.76-1.01], n = 12 studies). Dietary and physical activity interventions were associated with a small reduction in fasting plasma glucose, particularly in longer interventions, but inconsistent effects were seen for other continuous outcomes. CONCLUSIONS: Although possibly due to chance, interventions to reduce hyperglycaemia after GDM may be effective. Future research should improve understanding of how interventions affect glucose control and how to optimise interventions for this population.

Early diagnosis of Malan syndrome in an infant presenting with macrocephaly.

We present an infant with persistent macrocephaly and developmental delay. There is a wide range of differential diagnoses for this presentation, including many rare genetic conditions. Here, a diagnosis of Malan syndrome was made-a rare overgrowth syndrome caused by haploinsufficiency of NFIX and features affecting the neurological and musculoskeletal systems. Improvements in genomic medicine technologies and clinical services have revolutionised the way clinicians diagnose rare diseases. We highlight the importance of early genetic testing, particularly if there are red flag features such as developmental delay, and the need for a coordinated strategy to improve the management of rare diseases like Malan syndrome.

Molecular and neurological features of MELAS syndrome in paediatric patients: A case series and review of the literature.

BACKGROUND: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is one of the most well-known mitochondrial diseases, with most cases attributed to m.3243A>G. MELAS syndrome patients typically present in the first two decades of life with a broad, multi-systemic phenotype that predominantly features neurological manifestations--stroke-like episodes. However, marked phenotypic variability has been observed among paediatric patients, creating a clinical challenge and delaying diagnoses. METHODS: A literature review of paediatric MELAS syndrome patients and a retrospective analysis in a UK tertiary paediatric neurology centre were performed. RESULTS: Three children were included in this case series. All patients presented with seizures and had MRI changes not confined to a single vascular territory. Blood heteroplasmy varied considerably, and one patient required a muscle biopsy. Based on a literature review of 114 patients, the mean age of presentation is 8.1 years and seizures are the most prevalent manifestation of stroke-like episodes. Heteroplasmy is higher in a tissue other than blood in most cases. CONCLUSION: The threshold for investigating MELAS syndrome in children with suspicious neurological symptoms should be low. If blood m.3243A>G analysis is negative, yet clinical suspicion remains high, invasive testing or further interrogation of the mitochondrial genome should be considered.

A Systematic Review of Utilisation of Diurnal Timing Information in Clinical Trial Design for Long QT Syndrome.

Diurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 h, and drug delivery. Despite guidelines having been issued around the analysis of 24-h ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.

Hospital intranet system is major barrier to paediatric clinical guideline use a cross-sectional single-centre survey of NHS doctors and nurses.

Across clinical specialties, the use of clinical guidelines is integral to maintaining patient safety, reducing variation in clinical practice and optimising patient care. Identifying specific barriers to the effective use of guidelines within individual healthcare settings allows for the implementation of effective strategies to overcome them, and ultimately improvements in patient care. Here, we report a single-centre survey of paediatric doctors and nurses, which formed part of a quality improvement project within the Acute Paediatrics Department of an NHS district general hospital. The primary aim of the study was to explore the perspective and resource barriers paediatrics healthcare staff experience when using local and national clinical guidelines. The secondary aim of the study was to examine the impact of the Covid-19 pandemic on local and national clinical guideline use. We found that local and national guidelines are frequently used by paediatric doctors and nurses, and that they have positive perceptions of guidelines, overall. However, the NHS Trust's Intranet system was identified as a direct barrier to the use of local paediatric clinical guidelines. Staff throughout the UK in the NHS rely on their Intranet system in order to access local guidelines. Our results provide an impetus for interventions within this NHS Trust, and in the many other NHS Trusts with similar Intranet systems, to increase clinical guideline use and, ultimately, improve patient care.

Horizon Scanning in Cancer Genomics: How Advances in Genomic Medicine Will Change Cancer Care Over the Next Decade.

PURPOSE OF REVIEW: Advances in genomic medicine have the potential to revolutionise cancer patient care by driving forwards the clinical practice of precision oncology. This review aims to outline how genomic medicine advances may alter the care of cancer patients and their families over the next 10 years. RECENT FINDINGS: The translation of oncogenomic advances into the clinical environment will likely be facilitated by the increasing availability of next-generation sequencing technologies and the increasing genomic literacy of healthcare professionals. The implementation of the centralised, nationwide NHS Genomic Medicine Service promises to improve equity of cancer care and to facilitate personalisation of almost every stage of the care pathway, from informing population screening and how we diagnose cancer to delivering prognoses and surveillance. Advances in cancer pharmacogenomics, and other "omics" technologies, have a tremendous potential to optimise patient care. Genomic medicine advances will also enhance the care offered to cancer patients' families. SUMMARY: Genomic medicine advances are likely to transform almost every aspect of a cancer patient's care pathway. Cancer care will profoundly improve over the next decade, increasing UK cancer survival rates and improving patient outcomes.