Aintree University Hospitals NHS Foundation Trust

About: Aintree University Hospitals NHS Foundation Trust is a healthcare organization based out in Liverpool, United Kingdom. It is known for research contribution in the topics: Population & Cancer. The organization has 688 authors who have published 603 publications receiving 36207 citations. The organization is also known as: Aintree Hospitals NHS Trust & Aintree Hospitals National Health Service Trust.

The epigenetic landscape of oral squamous cell carcinoma

Abstract: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between ‘CIMP-high’ and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. Although OSCC seems as much an ‘epigenetic’ as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.

Diabetic Neuropathy and Gait: A Review

Abstract: Diabetic peripheral neuropathy (DPN) is a major sequela of diabetes mellitus and may have a detrimental effect on the gait of people with this complication. DPN causes a disruption in the body’s sensorimotor system and is believed to affect up to 50% of patients with diabetes mellitus, dependent on the duration of diabetes. It has a major effect on morbidity and mortality. The peripheral nervous system controls the complex series of events in gait through somatic and autonomic functions, careful balancing of eccentric and concentric muscle contractions and a reliance on the sensory information received from the plantar surface. In this literature review focussing on kinetics, kinematics and posture during gait in DPN patients, we have identified an intimate link between DPN and abnormalities in gait and demonstrated an increased risk in falls for older patients with diabetes. As such, we have identified a need for further research on the role of gait abnormalities in the development of diabetic foot ulceration and subsequent amputations.

A meta-analysis of survival factors in rhino-orbital-cerebral mucormycosis-has anything changed in the past 20 years?

Abstract: Background Rhino-orbital-cerebral mucormycosis (ROCM) is an uncommon yet potentially lethal fungal infection. Although most cases originate from developing countries, an ageing population and increased prevalence of chronic illness may mean some clinicians practicing in developed countries will encounter ROCM cases in their careers. Yohai et al published a systematic review of 145 case reports from 1970 to 1993 assessing prognostic factors for patients presenting with ROCM. We present an updated review of the literature and assess whether survival outcomes have changed in the two decades since that seminal paper. Search strategy An extensive Medline literature search was performed for case reports published between 1994 and 2015. Results In total, 210 published cases were identified from the literature review, of which 175 patients from 140 papers were included in this review. Fifty-five were female, with an overall mean age of 43 years. Overall survival rate was 59.5%, which was not significantly better than the previous series reported (60%) reported by Yohai et al. Survival rates in patients with chronic renal disease had improved, from 19% to 52%, and in patients with leukaemia (from 13% to 50%). Facial necrosis and hemiplegia remained poor prognostic indicators (33% and 39% survival rates, respectively). Early commencement of medical treatment related to better survival outcomes (61% if commenced within first 12 days of presentation, compared to 33% if after 13 days). Timing of surgery had less of an effect on overall survival. However, in 28 cases that did not receive any surgical treatment, survival was only 21%. Conclusions Although overall survival rates have not improved, survival in patients with renal disease were better, potentially due to the introduction of liposomal amphotericin B which is less nephrotoxic. Prompt recognition of ROCM, reversal of predisposing co-morbidities and aggressive medical treatment remain the cornerstone of managing this highly aggressive disease.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Abstract: Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Human factors in preventing complications in anaesthesia: a systematic review

Abstract: Human factors in anaesthesia were first highlighted by the publication of the Anaesthetists Non-Technical Skills Framework, and since then an awareness of their importance has gradually resulted in changes in routine clinical practice. This review examines recent literature around human factors in anaesthesia, and highlights recent national reports and guidelines with a focus on team working, communication, situation awareness and human error. We highlight the importance of human factors in modern anaesthetic practice, using the example of complex trauma.