Enhancing diabetes care for the most vulnerable in the 21st century: Interim findings of the National Advisory Panel on Care Home Diabetes (NAPCHD).

Older adults with diabetes may carry a substantial health burden in Western ageing societies, occupy more than one in four beds in care homes, and are a highly vulnerable group who often require complex nursing and medical care. The global pandemic (COVID-19) had its epicentre in care homes and revealed many shortfalls in diabetes care resulting in hospital admissions and considerable mortality and comorbid illness. The purpose of this work was to develop a national Strategic Document of Diabetes Care for Care Homes which would bring about worthwhile, sustainable and effective quality diabetes care improvements, and address the shortfalls in care provided. A large diverse and multidisciplinary group of stakeholders (NAPCHD) defined 11 areas of interest where recommendations were needed and using a subgroup allocation approach were set tasks to produce a set of primary recommendations. Each subgroup was given 5 starter questions to begin their work and a format to provide responses. During the initial phase, 16 key findings were identified. Overall, after a period of 18 months, 49 primary recommendations were made, and 7 major conclusions were drawn from these. A model of community and integrated diabetes care for care home residents with diabetes was proposed, and a series of 5 'quick-wins' were created to begin implementation of some of the recommendations that would not require significant funding. The work of the NAPCHD is ongoing but we hope that this current resource will help leaders to make these required changes happen.

Impact of bariatric surgery on cardiovascular outcomes and mortality: a population-based cohort study.

BACKGROUND: Cohort studies have shown that bariatric surgery may reduce the incidence of and mortality from cardiovascular disease (CVD), but studies using real-world data are limited. This study examined the impact of bariatric surgery on incident CVD, hypertension and atrial fibrillation, and all-cause mortality. METHODS: A retrospective, matched, controlled cohort study of The Health Improvement Network primary care database (from 1 January 1990 to 31 January 2018) was performed (approximately 6 per cent of the UK population). Adults with a BMI of 30 kg/m2 or above who did not have gastric cancer were included as the exposed group. Each exposed patient, who had undergone bariatric surgery, was matched for age, sex, BMI and presence of type 2 diabetes mellitus (T2DM) with two controls who had not had bariatric surgery. RESULTS: A total of 5170 exposed and 9995 control participants were included; their mean(s.d.) age was 45·3(10·5) years and 21·5 per cent (3265 of 15 165 participants) had T2DM. Median follow-up was 3·9 (i.q.r. 1·8- 6·4) years. Mean(s.d.) percentage weight loss was 20·0(13·2) and 0·8(9·5) per cent in exposed and control groups respectively. Overall, bariatric surgery was not associated with a significantly lower CVD risk (adjusted hazard ratio (HR) 0·80; 95 per cent c.i. 0·62 to 1·02; P = 0·074). Only in the gastric bypass group was a significant impact on CVD observed (HR 0·53, 0·34 to 0·81; P = 0·003). Bariatric surgery was associated with significant reduction in all-cause mortality (adjusted HR 0·70, 0·55 to 0·89; P = 0·004), hypertension (adjusted HR 0·41, 0·34 to 0·50; P < 0·001) and heart failure (adjusted HR 0·57, 0·34 to 0·96; P = 0·033). Outcomes were similar in patients with and those without T2DM (exposed versus controls), except for incident atrial fibrillation, which was reduced in the T2DM group. CONCLUSION: Bariatric surgery is associated with a reduced risk of hypertension, heart failure and mortality, compared with routine care. Gastric bypass was associated with reduced risk of CVD compared to routine care.

ANTECEDENTES: Estudios de cohortes han mostrado que la cirugía bariátrica puede reducir la incidencia de enfermedad cardiovascular (cardiovascular disease, CVD) y la mortalidad, pero los estudios basados en datos del mundo real son limitados. Este estudio examinaba el impacto de la cirugía bariátrica (bariatric surgery, BS) en la incidencia de CVD, hipertensión, fibrilación auricular (FA) y mortalidad por cualquier causa. MÉTODOS: Se realizó un estudio retrospectivo de cohortes, controlado por emparejamiento, a partir de la base de datos de atención primaria del The Health Improvement Network (THIN) (1/1/1990 y 31/1/2018) (aproximadamente el 6% de la población del Reino Unido UK). En el grupo de exposición, se incluyeron adultos con un índice de masa corporal (IMC) ≥ 30 kg/m2 que no tenían cáncer gástrico. Cada paciente expuesto (había sido operado de BS) fue emparejado por edad, sexo, IMC y presencia de diabetes tipo 2 (T2D) con 2 controles (sin BS). RESULTADOS: Se incluyeron un total de 5.170 sujetos expuestos y 9.995 participantes controles. La edad media (DE) fue 45,3 (10,5) años, 21,5% (n = 3.265) tenían T2D. La mediana de seguimiento era de 3,9 años (rango intercuartílico 1,8- 6,4). La media ± desviación estándar del % de pérdida de peso fue del 20,0 ± 13,2% en el grupo BS versus 0,8 ± 9,5% en los grupos control. Globalmente, la BS no se asoció con una CVD significativamente más baja (cociente de riesgos instantáneos ajustados, adjusted hazard ratio, HR 0,80; i.c. del 0,62- 1,02, P = 0,074). Solo en el grupo del bypass gástrico se observó un impacto significativo en CVD (0,53, 0,34- 0,81, P = 0,003). BS se asoció con una reducción significativa en la mortalidad de cualquier causa (0,70; i.c. Del 95% 0,55- 0,89, P = 0,004), hipertensión (0,41; 0,34- 0,50, P < 0,001), e insuficiencia cardiaca (0,57, 0,34- 0,96; P = 0.033). Los resultados fueron similares en aquellos pacientes con y sin T2D (expuesto versus control) excepto en la FA incidental que se redujo en el grupo T2D. CONCLUSIONES: La práctica de BS se asoció con una reducción del riesgo de insuficiencia cardiaca y mortalidad.

Temporal and external validation of a prediction model for adverse outcomes among inpatients with diabetes.

AIM: To temporally and externally validate our previously developed prediction model, which used data from University Hospitals Birmingham to identify inpatients with diabetes at high risk of adverse outcome (mortality or excessive length of stay), in order to demonstrate its applicability to other hospital populations within the UK. METHODS: Temporal validation was performed using data from University Hospitals Birmingham and external validation was performed using data from both the Heart of England NHS Foundation Trust and Ipswich Hospital. All adult inpatients with diabetes were included. Variables included in the model were age, gender, ethnicity, admission type, intensive therapy unit admission, insulin therapy, albumin, sodium, potassium, haemoglobin, C-reactive protein, estimated GFR and neutrophil count. Adverse outcome was defined as excessive length of stay or death. RESULTS: Model discrimination in the temporal and external validation datasets was good. In temporal validation using data from University Hospitals Birmingham, the area under the curve was 0.797 (95% CI 0.785-0.810), sensitivity was 70% (95% CI 67-72) and specificity was 75% (95% CI 74-76). In external validation using data from Heart of England NHS Foundation Trust, the area under the curve was 0.758 (95% CI 0.747-0.768), sensitivity was 73% (95% CI 71-74) and specificity was 66% (95% CI 65-67). In external validation using data from Ipswich, the area under the curve was 0.736 (95% CI 0.711-0.761), sensitivity was 63% (95% CI 59-68) and specificity was 69% (95% CI 67-72). These results were similar to those for the internally validated model derived from University Hospitals Birmingham. CONCLUSIONS: The prediction model to identify patients with diabetes at high risk of developing an adverse event while in hospital performed well in temporal and external validation. The externally validated prediction model is a novel tool that can be used to improve care pathways for inpatients with diabetes. Further research to assess clinical utility is needed.

Representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering therapies in Type 2 diabetes.

AIMS: Our aim was to investigate the proportional representation of people of South Asian origin in cardiovascular outcome trials of glucose-lowering drugs or strategies in Type 2 diabetes, noting that these are among the most significant pieces of evidence used to formulate the guidelines on which clinical practice is largely based. METHODS: We searched for cardiovascular outcome trials in Type 2 diabetes published before January 2015, and extracted data on the ethnicity of participants. These were compared against expected values for proportional representation of South Asian individuals, based on population data from the USA, from the UK, and globally. RESULTS: Twelve studies met our inclusion criteria and, of these, eight presented a sufficiently detailed breakdown of participant ethnicity to permit numerical analysis. In general, people of South Asian origin were found to be under-represented in trials compared with UK and global expectations and over-represented compared with US expectations. Among the eight trials for which South Asian representation could be reliably estimated, seven under-represented this group relative to the 11.2% of the UK diabetes population estimated to be South Asian, with the representation in these trials ranging from 0.0% to 10.0%. CONCLUSIONS: Clinicians should exercise caution when generalizing the results of trials to their own practice, with regard to the ethnicity of individuals. Efforts should be made to improve reporting of ethnicity and improve diversity in trial recruitment, although we acknowledge that there are challenges that must be overcome to make this a reality.

What factors influence concordance with medications? Findings from the U.K. Asian Diabetes study.

AIMS: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. METHODS: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. RESULTS: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline; 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. CONCLUSIONS: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.

An FTO variant is associated with Type 2 diabetes in South Asian populations after accounting for body mass index and waist circumference.

AIMS: A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians. METHODS: We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies. RESULTS: In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 × 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 × 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 × 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 × 10(-5) ]. CONCLUSIONS: The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.

Enhanced diabetes care to patients of south Asian ethnic origin (the United Kingdom Asian Diabetes Study): a cluster randomised controlled trial.

BACKGROUND: Delivery of high-quality, evidence-based health care to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive, enhanced care package in UK general practices for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes. METHODS: In this cluster randomised controlled trial, 21 inner-city practices in the UK were assigned by simple randomisation to intervention (enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [nine practices; n=868]) or control (standard care [12 practices; n=618]) groups. All adult patients of south Asian origin with type 2 diabetes were eligible. Prescribing algorithms with clearly defined targets were provided for all practices. Primary outcomes were changes in blood pressure, total cholesterol, and glycaemic control (haemoglobin A1c) after 2 years. Analysis was by intention to treat. This trial is registered, number ISRCTN 38297969. FINDINGS: We recorded significant differences between treatment groups in diastolic blood pressure (1.91 [95% CI -2.88 to -0.94] mm Hg, p=0.0001) and mean arterial pressure (1.36 [-2.49 to -0.23] mm Hg, p=0.0180), after adjustment for confounders and clustering. We noted no significant differences between groups for total cholesterol (0.03 [-0.04 to 0.11] mmol/L), systolic blood pressure (-0.33 [-2.41 to 1.75] mm Hg), or HbA1c (-0.15% [-0.33 to 0.03]). Economic analysis suggests that the nurse-led intervention was not cost effective (incremental cost-effectiveness ratio pound28 933 per QALY gained). Across the whole study population over the 2 years of the trial, systolic blood pressure, diastolic blood pressure, and cholesterol decreased significantly by 4.9 (95% CI 4.0-5.9) mm Hg, 3.8 (3.2-4.4) mm Hg, and 0.45 (0.40-0.51) mmol/L, respectively, and we recorded a small and non-significant increase for haemoglobin A1c (0.04% [-0.04 to 0.13]), p=0.290). INTERPRETATION: We recorded additional, although small, benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes.

Effect of endotoxin on lipid order and motion in erythrocyte membranes.

Electron paramagnetic resonance employing a lipid-specific spin label has been used to investigate the molecular effects of endotoxin on the physical state of bilayer lipids in rat erythrocyte membranes. When added at a concentration as low as 40 micrograms/ml to whole blood (plasma plus leukocytes present), decreased membrane lipid motion was found in subsequently washed and spin-labeled intact erythrocytes (P < 0.02). However, if endotoxin were added to washed, plasma plus leukocyte-free intact erythrocytes, no change in the motion of the spin label was found, suggesting that plasma-soluble substances and/or leukocytes are required to produce the change in the physical state of lipids. The decreased lipid motion found in these studies is discussed with reference to the known decreased deformability of endotoxin-treated red cells and to the pathogenesis of sepsis.

Effect of lipopolysaccharide, leukocytes, and monoclonal anti-lipid A antibodies on erythrocyte membrane elastance.

The micropipette aspiration technique was used to quantify membrane deformability of individual red blood cells (RBCs) before and after exposing whole blood and blood free of leukocytes to lipopolysaccharide (LPS). The ability of an anti-lipid A monoclonal antibody (E5) to inhibit the effects of LPS was also investigated. In the LPS/whole blood studies, a significant increase in elasticity modulus was observed following incubation with LPS. An increase in elasticity modulus indicates a decrease in RBC membrane deformability. The effect depended on the incubation time but was not concentration-dependent in the range studied (25, 40, or 170 micrograms/mL). When incubating blood free of leukocytes with LPS, the elasticity moduli of erythrocytes did not change. Results also showed that preincubation of the LPS with E5 prior to incubation with whole blood partially inhibited the effect of LPS, suggesting a possible mechanism of the beneficial actions of monoclonal antibodies in septic shock.

Effect of lipopolysaccharide on the physical conformation of the erythrocyte cytoskeletal proteins.

Red blood cell deformability is important for effective circulation in the capillaries. It is known that red cell deformability is significantly reduced during septic shock. Surface to volume ratio, physical effects of the cytoskeletal proteins and the fluidity of lipid bilayer are some of the important intrinsic factors that regulate this mechanical function. Alterations in the physical conformation of cytoskeletal proteins in septic conditions could significantly alter their function. In this study, erythrocytes in whole blood were treated with lipopolysaccharide, the outer covering of Gram-negative bacteria released during Gram-negative sepsis. Electron paramagnetic resonance spectroscopy in conjunction with a protein-specific maleimide nitroxide spin label covalently bound to cytoskeletal proteins was used to investigate the resulting changes occurring in the physical state of cytoskeletal proteins in isolated membranes. Treatment of red blood cells with a lipopolysaccharide concentration as low as 40 micrograms/mL of blood solution for 90 minutes showed a significant decrease in the relevant EPR parameter (p < 0.01) of the spin label bound to subsequently isolated membranes, suggestive of a decreased segmental motion of the spin label and an increase in cytoskeletal protein-protein interactions. These results suggest a marked conformational alteration in the cytoskeletal proteins induced by the lipopolysaccharide and may explain, in part, the marked reduction in red blood cell deformability during septic shock. Bacterial lipopolysaccharide does not exert most of its effects on the host directly, but rather elicits the production of host factors that leads to complex septic shock. Leukocytes, endothelial tissue and many other cells release these mediators. Leukocytes are thought to be a particularly important source of such mediators, including cytokines (tumor necrosis factor, interleukins, etc.), oxygen free radicals, proteases, and hydrolyses. In order to characterize the possible mechanism by which the lipopolysaccharide acts on the physical state of the erythrocyte cytoskeleton, erythrocytes void of leukocytes and plasma were treated with lipopolysaccharide. The relevant EPR parameter showed no significant change over the control value. These results indicate that the leukocytes and their factors are responsible for the rearrangements seen in the cytoskeletal proteins of the erythrocyte membrane.

Wilson's disease: a diagnosis made in two individuals greater than 40 years of age.

Wilson's disease is an autosomal recessive disease of copper metabolism which is widely recognized as a disease occurring clinically in children, adolescents, and young adults. Unrecognized and therefore untreated Wilson's disease in patients over age 40 is thought to occur either rarely or not at all. Two cases of Wilson's disease presenting at an age greater than 40 years are presented. The first is a 42-year-old Israeli women who presented with fulminant hepatic failure. The serologic and biochemical investigations obtained at the time of her fulminant hepatic failure included copper studies which suggested the diagnosis of Wilson's disease, which was confirmed by an examination of the native liver following successful orthotopic liver transplantation. The second case is that of a 56-year-old white male who presented to the hospital with a three-year history of neurological dysfunction, pancytopenia, and mild splenomegaly. A battery of serologic and biochemical investigations suggested a diagnosis of Wilson's disease. The diagnosis was confirmed by quantitative hepatic copper estimation and the demonstration of Wilson's disease in three of his siblings, all of whom were diagnosed after the proband case had been identified. This man and his siblings have been treated with d-penicillamine, with remarkable improvement in their neurologic and hepatic function. The proband is currently well 11 years after his diagnosis was established. These two cases demonstrate that a diagnosis of Wilson's disease should be considered as part of the differential diagnosis of individuals in the fourth and fifth decades of life who present with unexplained liver disease.

The relationship between high-sensitivity CRP and polyclonal free light chains as markers of inflammation in chronic disease.

INTRODUCTION: Serum concentrations of polyclonal free light chains (FLC) represent the activity of the adaptive immune system. This study assessed the relationship between polyclonal FLC and the established marker of innate immunity, C-reactive protein (CRP), in chronic and acute disease. METHODS: We utilized four cross-sectional chronic disease patient cohorts: chronic kidney disease (CKD), diabetes, vasculitis and kidney transplantation; and a longitudinal intensive care case series to assess the kinetics of production in acute disease. RESULTS: There was a weak association between polyclonal FLC and high-sensitivity CRP (hs-CRP) in the study cohorts. A longitudinal assessment in acute disease showed a gradual increase in FLC concentrations over time, often when CRP levels were falling, demonstrating clear differences in the response kinetics of CRP and FLC in this setting. CONCLUSION: Polyclonal FLC and hs-CRP provide independent information as to inflammatory status. Prospective studies are now required to assess the utility of hs-CRP and polyclonal FLC in combination for risk stratification in disease populations.

Abnormal retinal vascular function and lipid levels in a sample of healthy UK South Asians.

BACKGROUND/AIMS: To investigate ethnic differences in retinal vascular function and their relationship to traditional risk indicators for cardiovascular disease (CVD). METHODS: A total of 90 normoglycaemic subjects (45 South Asian (SA) and 45 age- and gender-matched white Europeans (WEs)) were recruited for the present study. Retinal vessel reactivity to flickering light was assessed by means of the dynamic retinal vessel analyser according to a modified protocol. Fasting plasma glucose, triglycerides (TG), total, LDL and HDL cholesterol were also measured in all individuals. RESULTS: SA individuals showed higher fasting triglyceride (p=0.001) and lower HDL levels (p=0.007), leading to a higher TG:HDL-C ratio (p=0.001) than age-matched WE subjects. Additionally, in SAs, the retinal arterial reaction time in response to flicker stimulation was significantly longer in the last flicker cycle than in the WEs (p=0.039), and this change correlated positively with measured plasma TG levels (r=0.60; p=0.01). No such relationship was observed in the WEs (p>0.05). CONCLUSION: Even in the absence of overt vascular disease, in otherwise healthy SAs there are potential signs of retinal vascular function impairment that correlates with established plasma markers for CVD risk.

Inhaled insulin: new technology, new possibilities.

The prevalence of diabetes is reaching epidemic proportions with an increasing need for new therapies. Several new therapies are in development and amongst these is inhaled insulin. Inhaled insulin is a novel way of delivering insulin and has been shown to have an efficacy comparable to subcutaneous insulin in patients with both type 1 and type 2 diabetes. Several inhaled insulin delivery systems are currently in development and the first of these, Exubera has recently been granted license in Europe and in the USA. In this article we review the efficacy and safety profile of Exubera and discuss its potential place in the management of diabetes.

Type 2 diabetes and cardiovascular risk in the UK south Asian community.

A popular hypothesis for the greater prevalence of type 2 diabetes and cardiovascular disease in UK south Asians is that they have an increased susceptibility of developing insulin resistance in response to certain environmental factors, including obesity and adoption of a sedentary lifestyle. Insulin resistance is postulated as a central feature of the metabolic syndrome, culminating in type 2 diabetes, atherosclerotic vascular disease and CHD; a pathway potentially accelerated by migration/urbanisation. We describe and compare the prevalence of type 2 diabetes, cardiovascular disease and their associated risk factors in UK south Asian and white Caucasian populations to determine possible reasons for the increased preponderance of these diseases in south Asians, and highlight key evidence for optimal risk factor management. Finally, we describe a UK community-based programme that attempts to reduce the morbidity and mortality from type 2 diabetes and cardiovascular disease in south Asians through a new approach to management.

Barrett's esophagus and achalasia. A case report.

A 70-year-old woman with no previous gastroesophageal surgery gave a 6-month history of dysphagia. Barium studies suggested a diagnosis of achalasia. Esophageal manometry showed absence of peristalsis and a high lower esophageal sphincter pressure. Endoscopy showed a dilated esophagus with food residue, and Barrett's esophagus was present. The association of Barrett's esophagus and achalasia must be rare.

Upper gastrointestinal lesions in elderly patients presenting for endoscopy: relevance of NSAID usage.

The occurrence of upper gastrointestinal disease and the relevance of nonsteroidal antiinflammatory drug (NSAID) usage were documented in 511 consecutive patients (321 women, 190 men) over 70 yr old, referred for upper gastrointestinal endoscopy in a district general hospital. The findings were benign esophageal disease (43%), normal (15%), gastric ulcer (11.5%), and duodenal ulcer (11%). Gastric ulcers were more common in women taking NSAIDs (25%) than in NSAID abstainers (7%) p less than 0.001 and male NSAID users (8%) p less than 0.001. Esophagitis and esophageal stricture were not influenced by NSAID usage, but gastric erosions were more common (10% vs. 3%) p less than 0.01. Of 142 patients receiving NSAIDs, 41% presented with hemorrhage, compared with 20.5% of NSAID abstainers (p less than 0.001). Hemorrhage was as common in aspirin takers (15 of 33, 45%) as in standard-dose NANSAID takers (43 of 109, 39%), even though 86% were taking 300 mg of aspirin per day or less. In elderly patients, esophageal disease is common. NSAID use, even low-dose aspirin, is associated with an increased risk of hemorrhage. In females, NSAID usage is associated with gastric ulcer.

Liver transplantation for Wilson's disease.

BACKGROUND/AIMS: As has been the case with other metabolic diseases of the liver in the last decade, orthotopic liver transplantation has been applied to the treatment of Wilson's disease with increasing frequency. The experience at the University of Pittsburg with orthotopic liver transplantation for Wilson's disease is reported. METHODS: Between February 1981 and December 1991, 51 orthotopic liver transplants were performed on 39 patients (16 pediatric, 23 adults) with Wilson's disease. Twenty-two patients were transplanted because of a presentation co-existent with fulminant hepatic failure. Seventeen presented with chronic advanced liver disease with (n=9) or without (n=8) associated neurologic dysfunction. RESULTS: The rate of primary graft survival (n-39) was 73% and patient survival was 79.4%. No patient mortality occurred beyond 3 weeks post-orthotopic liver transplantation. Survival was butter for those with a chronic advanced liver disease presentation (90%) than it was for those with a fulminant hepatic failure (73%) presentation, but the difference was not statistically significant. CONCLUSIONS: 1) Currently, orthotopic liver transplantation is the treatment of choice for Wilson's disease presenting as fulminant hepatic hepatic failure; 2) orthotopic liver transplantation should be considered for patients with Wilson's disease with advanced, chronic liver disease for whom no other therapy is possible; 3)orthotopic liver transplantation only partially corrects the underlying metabolic defect of patients with Wilson's disease and converts the copper kinetics from that characteristic of an individual affected with a homozygous disease to that of an individual who is an obligate heterozygote, thereby effecting a phenotypic cure.

Increased occurrence of psoriasis in patients with Crohn's disease and their relatives.

One hundred thirty-six unselected patients with Crohn's disease (43 men, 93 women) were studied for the possibility of psoriasis and questioned regarding their family history, as were 136 controls, matched for age and sex. Psoriasis was present in 13 of the 136 patients with Crohn's disease (9.6%), compared with three of 136 controls (2.2%) (p less than 0.02). Age at onset and anatomical site of Crohn's disease did not influence the result, and there was no difference between the sexes. Fourteen (three with psoriasis) of the 136 Crohn's patients (10%) had a family history of psoriasis in first-degree relatives compared with four of 136 controls (2.9%) (p less than 0.02). Psoriasis is more common in patients with Crohn's disease and their first-degree relatives than in controls, suggesting the possibility of a genetic link. Psoriasis should be included among the extraintestinal manifestations of the condition.