Brighton General Hospital

Generalized Linear Models, 2nd edn. By P. McCullagh and J. A. Nelder. ISBN 0 412 31760 5. Chapman and Hall, London, 1989. xx + 512 pp. £30.

Recent reports have suggested that brain stem and cortical Lewy body formation may identify a neurodegenerative disorder in elderly demented individuals which accounts for up to 20% of cases of senile dementia coming to autopsy. Retrospective analysis of case notes of 21 autopsy patients with neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases with neuropathologically proven Alzheimer's disease (AD) identified a characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment; psychotic features including visual and auditory hallucinations, and paranoid delusions; depressive symptoms; falling and unexplained losses of consciousness were all seen significantly more often than in AD. Over half of the SDLT patients in this series who were given neuroleptics in standard dose showed acute and often irreversible adverse reactions indicative of a neuroleptic sensitivity syndrome. The survival time of drug treated patients was reduced by 50%. Operational criteria to aid in the clinical distinction between SDLT and AD patients are proposed and hypotheses regarding possible aetiology and treatment discussed.

BACKGROUND: Population ageing represents a global challenge for future end-of-life care. Given new trends in place of death, it is vital to examine where the rising number of deaths will occur in future years and implications for health and social care. AIM: To project where people will die from 2015 to 2040 across all care settings in England and Wales. DESIGN: Population-based trend analysis and projections using simple linear modelling. Age- and gender-specific proportions of deaths in hospital, care home, home, hospice and 'other' were applied to numbers of expected future deaths. Setting/population: All deaths (2004-2014) from death registration data and predicted deaths (2015-2040) from official population forecasts in England and Wales. RESULTS: Annual deaths are projected to increase from 501,424 in 2014 (38.8% aged 85 years and over) to 635,814 in 2040 (53.6% aged 85 years and over). Between 2004 and 2014, proportions of home and care home deaths increased (18.3%-22.9% and 16.7%- 21.2%) while hospital deaths declined (57.9%-48.1%). If current trends continue, numbers of deaths in care homes and homes will increase by 108.1% and 88.6%, with care home the most common place of death by 2040. If care home capacity does not expand and additional deaths occur in hospital, hospital deaths will start rising by 2023. CONCLUSION: To sustain current trends, end-of-life care provision in care homes and the community needs to double by 2040. An infrastructure across care settings that supports rising annual deaths is urgently needed; otherwise, hospital deaths will increase.

Journal Article The metabolic chiral inversion of 2-arylpropionic acids—a novel route with pharmacological consequences Get access Andrew J Hutt, Andrew J Hutt Department of Pharmacy, Brighton Polytechnic, Moulescombe, Brighton, Sussex Search for other works by this author on: Oxford Academic Google Scholar John Caldwell John Caldwell Department of Pharmacology, St Mary's Hospital Medical School, London W2 P̀, U.K. Correspondence. Department of Pharmacy, Brighton Polytechnic, Moulescombe, Brighton, SussexDepartment of Pharmacology, St Mary's Hospital Medical School, London, W2 1PG. Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 35, Issue 11, November 1983, Pages 693–704, https://doi.org/10.1111/j.2042-7158.1983.tb02874.x Published: 12 April 2011 Article history Received: 21 April 1983 Published: 12 April 2011

The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.

Human scabies, a common infestation, has a worldwide distribution with a variable impact and presentation depending on the clinical situation. In developed, high-income settings, health institution and residential home outbreaks challenge health and social care services. In resource-poor settings, it is the downstream sequelae of staphylococcal and streptococcal bacteraemia, induced by scratching, which have a significant impact on the long-term health of communities. Over the past decade scabies has been recognised as a "neglected tropical disease" (NTD) by the World Health Organisation, has an accepted practical system of global diagnostic criteria and is being adopted into integrated programmes of mass drug administration for NTDs in field settings. This review seeks to summarise the recent advances in the understanding of scabies and highlight the advocacy and research headlines with their implication for diagnosis and management of outbreaks and individuals. In addition, it will indicate the priorities and questions that remain.

BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.

The interaction of five anti-pseudomonas antibiotics with both commercial and pseudomonas alginates was studied by investigation of their binding and diffusion characteristics. The two sources of alginate were qualitatively but not quantitatively similar in these respects. Unlike the beta-lactams, gentamicin and tobramycin bound avidly to both sources of alginate and, when the alginate gel to antibiotic ratio was high, the aminoglycosides exhibited diffusion coefficients which were approximately 20% of the beta-lactam values. At much lower ratios of alginate to antibiotic the aminoglycosides caused precipitation in the alginate with apparent disruption of the gel structure, and ultimately penetrated the gel at a faster rate than the beta-lactams. The strong aminoglycoside binding to alginate was reduced, but not eliminated by the presence of physiological concentrations of salts.

Understanding the three-dimensional (3D) nature of the human form is imperative for effective medical practice and the emergence of 3D printing creates numerous opportunities to enhance aspects of medical and healthcare training. A recently deceased, un-embalmed donor was scanned through high-resolution computed tomography. The scan data underwent segmentation and post-processing and a range of 3D-printed anatomical models were produced. A four-stage mixed-methods study was conducted to evaluate the educational value of the models in a medical program. (1) A quantitative pre/post-test to assess change in learner knowledge following 3D-printed model usage in a small group tutorial; (2) student focus group (3) a qualitative student questionnaire regarding personal student model usage (4) teaching faculty evaluation. The use of 3D-printed models in small-group anatomy teaching session resulted in a significant increase in knowledge (P = 0.0001) when compared to didactic 2D-image based teaching methods. Student focus groups yielded six key themes regarding the use of 3D-printed anatomical models: model properties, teaching integration, resource integration, assessment, clinical imaging, and pathology and anatomical variation. Questionnaires detailed how students used the models in the home environment and integrated them with anatomical learning resources such as textbooks and anatomy lectures. In conclusion, 3D-printed anatomical models can be successfully produced from the CT data set of a recently deceased donor. These models can be used in anatomy education as a teaching tool in their own right, as well as a method for augmenting the curriculum and complementing established learning modalities, such as dissection-based teaching. Anat Sci Educ 11: 44-53. © 2017 American Association of Anatomists.

OBJECTIVES: To describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART). METHODS: The patients from the EuroSIDA study who started HAART with a baseline CD4 count of <350 cells/microL and where all viral load (pVL) measures remained below 500 HIV-1 RNA copies/mL between 6 and 12 months after the start of HAART were included. The risk factors for poor CD4 count rise were analyzed by multiple regression. RESULTS: Seven hundred and eighty patients were included. A low CD4 count response was observed in 225 patients (29%). The risk factors for this condition were older age, lower CD4 count at baseline, higher increase from the nadir to baseline CD4 count and lower pVL at baseline. Patients taking > or =one drug from each of the three antiviral classes were more likely to have a good CD4 response but a minority of the study participants was taking this treatment regimen (3.1%) and the confidence interval was large. CONCLUSIONS: A poor immune reconstitution despite a good virological control is frequent after initiation of HAART among patients with a baseline CD4 count of <350 cells/microL. The underlying mechanisms leading to this condition seems mainly driven by the age and the baseline immunological and virological status of the patients.

This cross-sectional study assessed beliefs about highly active antiretroviral therapy (HAART) and their association with reported adherence to HAART among 109 HIV-positive patients receiving HAART while attending an ambulatory care clinic in Brighton, UK. Patients' beliefs about the necessity for and concerns about HAART and their adherence to it were assessed using validated questionnaires. There was considerable variation in beliefs and reported adherence. A quarter of participants reported low adherence to HAART and this was related to concerns about adverse effects as well as to the way in which each individual balanced concerns against perceptions of necessity. Patients were significantly more likely to report low adherence rates if their concerns were high relative to their perceptions of personal need for HAART. Patients with higher CD4 counts were significantly more likely to hold a view of HAART in which perceptions of necessity were higher relative to their concerns about adverse effects. CD4 was not related to reported adherence. A comparison of most recent viral load results between high and low adherence group identified differences in the predicted direction but these were not statistically significant. These preliminary findings suggest that patients' perceptions of HAART are important determinants of adherence with implications for future research and clinical practice.

This guidance for the management of patients with hymenoptera venom allergy has been prepared by the Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is for use by both adult physicians and pediatricians practising allergy. During the development of these guidelines, all BSACI members were included in the consultation process using a web-based system. Their comments and suggestions were carefully considered by the SOCC. Where evidence was lacking, consensus was reached by the experts on the committee. Included in this guideline are epidemiology, risk factors, clinical features, diagnostic tests, natural history of hymenoptera venom allergy and guidance on undertaking venom immunotherapy (VIT). There are also separate sections on children, elevated baseline tryptase and mastocytosis and mechanisms underlying VIT. Finally, we have made recommendations for potential areas of future research.

BACKGROUND: An age-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. METHOD: To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. RESULTS: Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI. CONCLUSION: An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.

Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.

BACKGROUND: Haemorrhoids are variceal dilatations of the anal and perianal venous plexus and often develop secondary to the persistently elevated venous pressure within the haemorrhoidal plexus (Kumar 2005). Phlebotonics are a heterogenous class of drugs consisting of plant extracts (i.e. flavonoids) and synthetic compounds (i.e. calcium dobesilate). Although their precise mechanism of action has not been fully established, they are known to improve venous tone, stabilize capillary permeability and increase lymphatic drainage. They have been used to treat a variety of conditions including chronic venous insufficiency, lymphoedema and haemorrhoids.Numerous trials assessing the effect of phlebotonics in treating the symptoms and signs of haemorrhoidal disease suggest that there is a potential benefit. OBJECTIVES: The aim of this review was to investigate the efficacy of phlebotonics in alleviating the signs, symptoms and severity of haemorrhoidal disease and verify their effect post-haemorrhoidectomy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2011 issue 9 , MEDLINE (1950 to September 2011) and EMBASE (1974 to September 2011). SELECTION CRITERIA: Only randomised controlled trials evaluating the use of phlebotonics in treating haemorrhoidal disease were used. No cross-over or cluster-randomized trials were included for analysis and any trial which had a quasi-random method of allocation was excluded. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and analysed the eligibility of the data for inclusion. Disagreements were resolved by meaningful discussion. MAIN RESULTS: We considered twenty-four studies for inclusion in the final analysis. Twenty of these studies (enrolling a total of 2344 participants) evaluated the use of phlebotonics versus a control intervention. One of these twenty studies evaluated the use of phlebotonics with a medical intervention and another study with rubber band ligation.The remaining four studies included two which compared different forms of phlebotonics with each other, one study which evaluated phlebotonics with a medical intervention and one study which compared the use of phlebotonics with infrared photocoagulation. Eight studies were excluded for various reasons including poor methodological quality.Phlebotonics demonstrated a statistically significant beneficial effect for the outcomes of pruritus (OR 0.23; 95% CI 0.07 to 0.79) (P=0.02), bleeding (OR 0.12; 95% CI 0.04 to 0.37) (P=0.0002), bleeding post-haemorrhoidectomy (OR 0.18; 95% 0.06 to 0.58)(P=0.004), discharge and leakage (OR 0.12; 95% CI 0.04 to 0.42) (P=0.0008) and overall symptom improvement (OR 15.99 95% CI 5.97 to 42.84) (P< 0.00001), in comparison with a control intervention. Although beneficial they did not show a statistically significant effect compared with a control intervention for pain (OR 0.11; 95% CI 0.01 to 1.11) (P=0.06), pain scores post-haemorrhoidectomy (SMD -1.04; 95% CI -3.21 to 1.12 ) (P= 0.35) or post-operative analgesic consumption (OR 0.54; 95% CI 0.30 to 0.99)(P=0.05). AUTHORS' CONCLUSIONS: The evidence suggests that there is a potential benefit in using phlebotonics in treating haemorrhoidal disease as well as a benefit in alleviating post-haemorrhoidectomy symptoms. Outcomes such as bleeding and overall symptom improvement show a statistically significant beneficial effect and there were few concerns regarding their overall safety from the evidence presented in the clinical trials.However methodological limitations were encountered. In order to enhance our conclusion further, more robust clinical trials which take into account these limitations will need to be performed in the future.

A study of hyponatraemia in the in-patients of a Geriatric Department during a 10-month period showed that 77 patients (11.3%) had plasma sodium concentrations below 130 mmol/l. Thirty-one patients (4.5%) had severe hyponatraemia of less than 125 mmol/l. Seventy-three per cent of hyponatraemias were iatrogenic caused by diuretic or intravenous fluid therapy. Hydrochlorothiazide/amiloride combination has the greatest tendency to produce hyponatraemia compared to all other diuretics (P less than 0.01). Clinical features attributable to hyponatraemia were present in 61%. Nine patients needed hospital admission solely due to hyponatraemia. The mortality rate for hyponatraemia was twice the overall rate for the unit.

Background: Mitral valve-in-valve (ViV) and valve-in-ring (ViR) are alternatives to surgical reoperation in patients with recurrent mitral valve failure after previous surgical valve repair or replacement. Our aim was to perform a large-scale analysis examining midterm outcomes after mitral ViV and ViR. Methods: Patients undergoing mitral ViV and ViR were enrolled in the Valve-in-Valve International Data Registry. Cases were performed between March 2006 and March 2020. Clinical endpoints are reported according to the Mitral Valve Academic Research Consortium (MVARC) definitions. Significant residual mitral stenosis (MS) was defined as mean gradient ≥10 mm Hg and significant residual mitral regurgitation (MR) as ≥ moderate. Results: A total of 1079 patients (857 ViV, 222 ViR; mean age 73.5±12.5 years; 40.8% male) from 90 centers were included. Median STS-PROM score 8.6%; median clinical follow-up 492 days (interquartile range, 76–996); median echocardiographic follow-up for patients that survived 1 year was 772.5 days (interquartile range, 510–1211.75). Four-year Kaplan-Meier survival rate was 62.5% in ViV versus 49.5% for ViR ( P &lt;0.001). Mean gradient across the mitral valve postprocedure was 5.7±2.8 mm Hg (≥5 mm Hg; 61.4% of patients). Significant residual MS occurred in 8.2% of the ViV and 12.0% of the ViR patients ( P =0.09). Significant residual MR was more common in ViR patients (16.6% versus 3.1%; P &lt;0.001) and was associated with lower survival at 4 years (35.1% versus 61.6%; P =0.02). The rates of Mitral Valve Academic Research Consortium–defined device success were low for both procedures (39.4% total; 32.0% ViR versus 41.3% ViV; P =0.01), mostly related to having postprocedural mean gradient ≥5 mm Hg. Correlates for residual MS were smaller true internal diameter, younger age, and larger body mass index. The only correlate for residual MR was ViR. Significant residual MS (subhazard ratio, 4.67; 95% CI, 1.74–12.56; P =0.002) and significant residual MR (subhazard ratio, 7.88; 95% CI, 2.88–21.53; P &lt;0.001) were both independently associated with repeat mitral valve replacement. Conclusions: Significant residual MS and/or MR were not infrequent after mitral ViV and ViR procedures and were both associated with a need for repeat valve replacement. Strategies to improve postprocedural hemodynamics in mitral ViV and ViR should be further explored.

BACKGROUND: Although short-term outcome in severe alcoholic hepatitis (SAH) is well described, its long-term course remains uncharacterised. AIM: To assess determinants of long-term outcome in SAH. METHODS: Data were recorded from a cohort with SAH (admission Discriminant Function (DF) ≥32). Kaplan-Meier (KM) and Cox proportional hazards survival analyses were performed to determine predictors of outcome. RESULTS: One hundred and nine patients were included; 63.3% male, aged 49.6 ± 9.4 years with median follow-up of 40.7 months (95% CI 37.2-44.3). Median DF was 58, 86.2% had cirrhosis and 65.1% received corticosteroids and/or pentoxifylline. Overall mortality was 57.8%, 96.8% of deaths being liver-related and 65.1% occurring after the index hospitalisation. Estimated 5-year survival was 31.8%. Hepatorenal syndrome was the only baseline factor independently associated with mortality (HR 3.78, 95% CI 1.98-7.19, P < 0.0001), although it predicted short-term, rather than long-term outcome (median survival 0.52 months, 95% CI 0.43-0.61). Of the 87 patients (79.8%) who survived index hospitalisation, 65.1% experienced recidivism. Abstinence at last follow-up remained the only independent predictor of survival in multivariate analysis (HR 0.370, 95% CI 0.168-0.818, P = 0.014). Five-year survival was higher in abstainers (75.3%) compared with relapsed and continued drinkers (26.8% and 21.0%, respectively, P = 0.005). However, the survival benefit from abstinence only became statistically significant at 18 months postdischarge (HR 2.714, 95% CI 0.995-7.404, P = 0.051). CONCLUSIONS: Estimated 5-year survival after index hospitalisation with SAH is 31.8% with alcohol relapse occurring in two-thirds of patients. Abstinence remains the only independent predictor of long-term survival. Novel strategies to improve abstinence after admission with SAH are urgently needed.

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.

Sixty male distance athletes were divided into three equal groups according to their personal best time for the 10km run. The runners were measured anthropometrically and each runner completed a detailed questionnaire on his athletic status, training programme and performance. The runners in this study had similar anthropometric and training profiles to other distance runners of a similar standard. The most able runners were shorter and lighter than those in the other two groups and significantly smaller skinfold values (P less than 0.05). There were no significant differences between the groups for either bone widths or circumferences but the elite and good runners had significantly higher ponderal indices (P less than 0.05) than the average runners, indicating that they are more linear. Elite and good runners were also less endomorphic but more ectomorphic than the average runners. The elite runners trained more often, ran more miles per week and had been running longer (P less than 0.05) than good or average runners. A multiple regression and discriminant function analysis indicated that linearity, total skinfold, the type and frequency of training and the number of years running were the best predictors of running performance and success at the 10km distance.