Newham University Hospital

We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.

STUDY OBJECTIVE: The aim was to determine whether abdominal fatness in adult men is associated with retarded growth in fetal life and infancy. DESIGN: This was a follow up study of (1) men born during 1920-30 whose birthweights and weights at one year were recorded at the time by health visitors; and (2) men born during 1935-43 whose size at birth was measured in detail. The main outcome measure was the ratio of waist circumference to hip girth. SETTING: Hertfordshire and Preston, England. SUBJECTS: Subjects were 845 men born in east Hertfordshire who still live there; and 239 men born in Preston who still live in or close to the city. MAIN RESULTS: After allowing for body mass index, mean waist to hip ratio fell with increasing birthweight and rose as the ratio of placental weight to birthweight increased. These trends were independent of duration of gestation and therefore reflected retarded fetal growth. Waist to hip ratio also fell with increasing weight at one year. All these trends were independent of adult height, alcohol consumption, smoking, social class, and age. CONCLUSIONS: The tendency to store fat abdominally, which is known to increase the risk of cardiovascular disease and diabetes independently of obesity, may be a persisting response to adverse conditions and growth failure in fetal life and infancy.

Neutrophils contain antimicrobial peptides with antituberculous activity, but their contribution to immune resistance to tuberculosis (TB) infection has not been previously investigated to our knowledge. We determined differential white cell counts in peripheral blood of 189 adults who had come into contact with patients diagnosed with active TB in London, United Kingdom, and evaluated them for evidence of TB infection and capacity to restrict mycobacterial growth in whole-blood assays. Risk of TB infection was inversely and independently associated with peripheral blood neutrophil count in contacts of patients diagnosed with pulmonary TB. The ability of whole blood to restrict growth of Mycobacterium bovis bacille Calmette Guérin and Mycobacterium tuberculosis was impaired 7.3- and 3.1-fold, respectively, by neutrophil depletion. In microbiological media, human neutrophil peptides (HNPs) 1-3 killed M. tuberculosis. The neutrophil peptides cathelicidin LL-37 and lipocalin 2 restricted growth of the organism, the latter in an iron-dependent manner. Black African participants had lower neutrophil counts and lower circulating concentrations of HNP1-3 and lipocalin 2 than south Asian and white participants. Neutrophils contribute substantially to innate resistance to TB infection, an activity associated with their antimicrobial peptides. Elucidation of the regulation of neutrophil antimicrobial peptides could facilitate prevention and treatment of TB.

BACKGROUND: The aims of this study were to measure objectively the extent and severity of motor impairment in children with Asperger's syndrome and to determine whether the motor difficulties experienced by such children differed in any way from those classified as having a Specific Developmental Disorder of Motor Function (SDD-MF). Criteria derived from ICD 10-R were used to identify 11 children with Asperger's syndrome and a matched group of 9 children with a Specific Developmental Disorder of Motor Function. Children in both groups were required to have a verbal IQ of 80 or greater on the WISC IIIR. METHOD: The Autism Diagnostic Interview (Revised; Lord, Rutter, & LeCouteur, 1994) was used to identify features of AS in the first group and to exclude them in the latter. The Movement Assessment Battery for Children (Henderson & Sugden, 1992) provided a standardised test of motor impairment. A Gesture Test based on that by Cermak, Coster, and Drake (1980) was used to assess the child's ability to mime the use of familiar tools and to imitate meaningless sequences of movements. RESULTS: All the children with Asperger's syndrome turned out to meet our criterion for a diagnosis of motor impairment, five of the six most severely motor impaired children in the whole study being from this group. Performance of the Asperger group was also slightly poorer on the Gesture Test. The profile of performance on each test was examined in detail but no evidence of group differences in the pattern of impairment was found. CONCLUSIONS: This study is consistent with others suggesting a high prevalence of clumsiness in Asperger's syndrome. Our findings also attest to the widespread prevalence of motor impairment in developmental disorders and the problems such co-morbidity poses for attempts to posit discrete and functionally coherent impairments underlying distinct syndromes.

AIM: This paper reports a literature review examining factors that enhance retention of knowledge and skills during and after resuscitation training, in order to identify educational strategies that will optimize survival for victims of cardiopulmonary arrest. BACKGROUND: Poor knowledge and skill retention following cardiopulmonary resuscitation training for nursing and medical staff has been documented over the past 20 years. Cardiopulmonary resuscitation training is mandatory for nursing staff and is important as nurses often discover the victims of in-hospital cardiac arrest. Many different methods of improving this retention have been devised and evaluated. However, the content and style of this training lack standardization. METHOD: A literature review was undertaken using the Cumulative Index to Nursing and Allied Health Literature, MEDLINE and British Nursing Index databases and the keywords 'cardiopulmonary resuscitation', 'basic life support', 'advanced life support' and 'training'. Papers published between 1992 and 2002 were obtained and their reference lists scrutinized to identify secondary references, of these the ones published within the same 10-year period were also included. Those published in the English language that identified strategies to enhance the acquisition or retention of Cardiopulmonary resuscitation skills and knowledge were included in the review. RESULTS: One hundred and five primary and 157 secondary references were identified. Of these, 24 met the criteria and were included in the final literature sample. Four studies were found pertaining to cardiac arrest simulation, three to peer tuition, four to video self-instruction, three to the use of different resuscitation guidelines, three to computer-based learning programmes, two to voice-activated manikins, two to automated external defibrillators, one to self-instruction, one to gaming and the one to the use of action cards. CONCLUSIONS: Resuscitation training should be based on in-hospital scenarios and current evidence-based guidelines, including recognition of sick patients, and should be taught using simulations of a variety of cardiac arrest scenarios. This will ensure that the training reflects the potential situations that nurses may face in practice. Nurses in clinical areas, who rarely see cardiac arrests, should receive automated external defibrillation training and have access to defibrillators to prevent delays in resuscitation. Staff should be formally assessed using a manikin with a feedback mechanism or an expert instructor to ensure that chest compressions and ventilations are adequate at the time of training. Remedial training must be provided as often as required. Resuscitation training equipment should be made available at ward/unit level to allow self-study and practice to prevent deterioration between updates. Video self-instruction has been shown to improve competence in resuscitation. An in-hospital scenario-based video should be devised and tested to assess the efficacy of this medium in resuscitation training for nurses.

OBJECTIVES: To assess diagnostic accuracy of screening tests for pre-diabetes and efficacy of interventions (lifestyle or metformin) in preventing onset of type 2 diabetes in people with pre-diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHOD: Medline, PreMedline, and Embase. Study protocols and seminal papers were citation-tracked in Google Scholar to identify definitive trials and additional publications. Data on study design, methods, and findings were extracted onto Excel spreadsheets; a 20% sample was checked by a second researcher. Data extracted for screening tests included diagnostic accuracy and population prevalence. Two meta-analyses were performed, one summarising accuracy of screening tests (with the oral glucose tolerance test as the standard) for identification of pre-diabetes, and the other assessing relative risk of progression to type 2 diabetes after either lifestyle intervention or treatment with metformin. ELIGIBILITY CRITERIA: Empirical studies evaluating accuracy of tests for identification of pre-diabetes. Interventions (randomised trials and interventional studies) with a control group in people identified through screening. No language restrictions. RESULTS: had no other glycaemic abnormality). Lifestyle interventions were associated with a 36% (28% to 43%) reduction in relative risk of type 2 diabetes over six months to six years, attenuating to 20% (8% to 31%) at follow-up in the period after the trails. CONCLUSIONS: is neither sensitive nor specific for detecting pre-diabetes; fasting glucose is specific but not sensitive. Interventions in people classified through screening as having pre-diabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial populations. As screening is inaccurate, many people will receives an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention. These findings suggest that "screen and treat" policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes. REGISTRATION: PROSPERO (No CRD42016042920).

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

CONTEXT: Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality. OBJECTIVE: The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development. DESIGN: Granulosa cells were prepared from follicular fluid aspirated from 4- to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles. SETTING: The study was conducted at a university hospital. PATIENTS: Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study. MAIN OUTCOME MEASURES: Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured. RESULTS: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with women with regular ovulatory cycles (P=0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase-3 (P=0.001) and increased levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P=0.032). Gene expression profiling confirmed the immunocytochemical findings. CONCLUSIONS: Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS.

The Achilles tendon is the strongest and thickest tendon in the human body. It is also the commonest tendon to rupture. It begins near the middle of the calf and is the conjoint tendon of the gastrocnemius and soleus muscles. The relative contribution of the two muscles to the tendon varies. Spiralisation of the fibres of the tendon produces an area of concentrated stress and confers a mechanical advantage. The calcaneal insertion is specialised and designed to aid the dissipation of stress from the tendon to the calcaneum. The insertion is crescent shaped and has significant medial and lateral projections. The blood supply of the tendon is from the musculotendinous junction, vessels in surrounding connective tissue and the osteotendinous junction. The vascular territories can be classified simply in three, with the midsection supplied by the peroneal artery, and the proximal and distal sections supplied by the posterior tibial artery. This leaves a relatively hypovascular area in the mid-portion of the tendon where most problems occur. The Achilles tendon derives its innervation from the sural nerve with a smaller supply from the tibial nerve. Tenocytes produce type I collagen and form 90% of the cellular component of the normal tendon. Evidence suggests ruptured or pathological tendon produce more type III collagen, which may affect the tensile strength of the tendon. Direct measurements of forces reveal loading in the Achilles tendon as high as 9 KN during running, which is up to 12.5 times body weight.

An estimated 1049 million persons harbour T. trichiura, including 114 million preschool-age children and 233 million school-age children. The prevalence of T. trichiura is high and may reach 95% in children in many parts of the world where protein energy malnutrition and anaemias are also prevalent and access to medical care and educational opportunities is often limited. The Trichuris dysentery syndrome (TDS) associated with heavy T. trichiura, which includes chronic dysentery, rectal prolapse, anaemia, poor growth, and clubbing of the fingers constitutes an important public health problem, as do lighter but still heavy infections, even if not strictly TDS, especially in children. The profound growth stunting in TDS can be reversed by repeated treatment for the infection and, initially, oral iron. However findings from Jamaica strongly suggest that the significant developmental and cognitive deficits seen are unlikely to disappear without increasing the positive psychological stimulation in the child's environment. The severe stunting in TDS now appears likely to be a reaction at least in part to a chronic inflammatory response and concomitant decreases in plasma insulin-like growth factor-1 (IGF-1), increases in tumor necrosis factor-alpha (TNF-alpha) in the lamina propria of the colonic mucosa and peripheral blood (which likely decrease appetite and intake of all nutrients) and a decrease in collagen synthesis. Improvements in cognitive performance have been found after treatment for relatively heavy infections (without chronic dysentery) in school-going children; it is unclear precisely how much T. trichiura interferes with children's ability to access educational opportunities, but treatment of infections whenever possible is obviously sensible. The blood loss that can occur in T. trichiura infection is likely to contribute to anaemia, particularly if the child also harbours hookworm, malaria and/or has a low intake of dietary iron. Community control is important, particularly for the individuals within a population who harbour heavy worm burdens; this means children, with special attention to girls who will experience increased iron requirements and blood loss due to menstruation, pregnancies, and lactation. Mebendazole and albendazole, both of which are on the WHO Essential Drugs List, are very effective against T. trichiura; multiple doses are needed to attain complete parasitological cure in all cases. However the goal of control programmes in endemic areas is morbidity reduction, which follows when intensity of infection is significantly reduced.

BACKGROUND: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. METHODS: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy. RESULTS: Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir. CONCLUSIONS: Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

AIMS: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. METHODS: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King's College Hospitals between 1996 and 2001 with either hypocalcaemia or rickets caused by vitamin D deficiency. Children with plasma 25-hydroxyvitamin D levels <25 nmol/l (10 ng/ml) were considered to have vitamin D deficiency. RESULTS: Sixty five children, mostly from Black or Asian ethnic minority groups, were identified, 29 of whom had hypocalcaemic symptoms. Seventeen of these had no radiological evidence of rickets. The remainder (48 children) had radiological evidence of rickets with or without clinical signs. Symptoms and signs reverted to normal in all cases with vitamin D supplementation. All children who presented with symptomatic hypocalcaemia were aged either <3 or >10 years. There was a strong correlation between age at presentation and population growth velocity reference data. CONCLUSIONS: Rickets remains a problem in the UK especially in "at risk" ethnic minority groups. Symptomatic hypocalcaemia is an important, but under-recognised presenting feature. Growth rate is likely to be an important factor in determining the mode of presentation. Unexplained hypocalcaemia should be attributed to vitamin D deficiency in "at risk" ethnic minority groups until proved otherwise.

BACKGROUND: African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade. RESULTS: Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks. CONCLUSION: The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.

SUMMARY Neurological complications and other causes of morbidity were studied in 122 of 131 individuals (64 males. 67 females) with tuberous sclerosis, in a population in which its prevalence was 1/26,500. Seizures occurred in 78 per cent, beginning at less than one year of age in 69 per cent (in more males than females in both cases) and after age 16 in 4 per cent. More males than females also had infantile spasms and persistent seizures. Learning disorder occurred in 53 per cent (also in more males), all with a history of seizures, and was strongly correlated with age at onset of seizures, type of seizure and outcome for seizure control. Of subjects with learning disorder. 85 per cent required supervision for daily living and 65 per cent had little or no language: 97 per cent were fully mobile. Hcmiparesis had occurred in eight of the 131, giant cell astrocytomas in nine, bilateral polycystic kidney disease in two. and haemorrhagic complication relating to renal angiomyolipomas in six. RÉSUMÉ De la morbidité associée à la sclérose tübereuse: une étude de population. Les complications neurologiques et les autres causes de morbidité ont étéétudiées chez 122 parrni 131 patients (64 garçons, 67 filles) avec sclérose tubéreuse. dans une population où la prévalence était de 1/26 500. II y avait des crises comitiales dans 78 pour cent des cas, débutant à un âge inférieur à un an dans 69 pour cent (avec plus de garcons que de filles clans les deux cas) et après l'âge de 16 ans dans quatre pour cent. Egalement plus de garçons que de filles avaient présenté des spasmes en flexion et des crises persistantes. Des troubles des apprentissages existaient dans 53 pour cent des cas (également plus fréquents chez les garçons). tous avec un historique de crises et une forte corrélation avec l'âge au début des crises, le type des crises, et le devenir du contrôle de la comitialité. Parmi les sujets avec troubles d'apprentissage. 85 pour cent, exigeaient une surveillance constante pour la vie joumalière et 65 pour cent avaient un langage peu développé ou nul; 97 pour cent se déplaçaient pleinemeni. Une hemiparésie était présente dans huit des 131 cas, il y cu un astrocytome à cellules géantes dans neuf cas. des reins polykystiques bilatéraux dans deux cas et des complications hémorragiques liées à une angiomyolipomatose rénale dans six cas. ZUSAMMENFASSUNG Morbidität bei tubetöser Hirnsklerose: cine Populalionssludie Bei 122 von 131 Patientcn (64 mannliche und 67 weibliche) mil tuberöser Hirnsklerose aus einer Population mil einer Häufigkeit von 1/26 500 wurden neurologische Komplikationen und andere Erkrankungsursachcn untersucht. Anfälle traten bei 78 Prozent auf, die bei 69 Prozent bereits im ersten Lebensjahr begannen (in beiden Fällen bei mehr Jungen als Mädchen) und bei 4 Prozent nach dem 16. Lebensjahr. Auch bei den BNS Krämpfen und den persistierenden Anfallsleiden war die Zahl der Jungen höher als die der Mädchen. Bei 53 Prozent fanden sich Lernstörungen (auch vorwiegend bei Jungen), allc hatten Anfälle in der Anamnese und es bestand eine enge Korrelation zum Alter bei Beginn der Anfälle, zur Art der Anfälle und zur Anfallskontrolle. Von den Patienten mit Lernproblemen brauchten 85 Prozent eine Betreuung im täglichen Leben und 65 Prozent konnten kaum oder gar nicht sprechen. 97 Prozent konnten sich uneingeschränkt bewegen. Acht der 131 Patienten hattcn einc Hcmiparese, neun eine bilateralc polyzystische Nierenerkrankung und sechs hämorrhagische Komplikationen in Verbindung mit renalen Angiomyelolipomen. RESUMEN Morbilidad asociada a esclerosis tiiberosa: estudio de población. Se estudiaron las complicaciones neurológicas y otras causas de morbilidad en 122 de 131 individuos (64 varones y 67 hembras) con esclerosis tuberosa, en una población en la que la prevalencia era de 1/26 500. Aparecieron convulsiones en el 78 por ciento iniciándose a menos de un año de edad en el 69 por ciento (más en varones que en hembras en ambos casos) y después de los 16 en el 4 por ciento. Igualmcntc los espasmos infantiles y las convulsiones existentes se vieron más en varones que en hembras. Alteraciones en el aprendizaje ocurrieron en el 53 por ciento (también más en varones), todos con una historia de convulsiones y estaban fuertemente correlacionadas con la edad de inicio de las convulsiones, el tipo de convulsión y el curso del control de las mismas. De los individuos con alteraciones del aprendizaje, el 85 por ciento requirieron una supervisión para su vida diaria y el 65 por ciento no tenían lenguaje o muy poco; el 97 por ciento tenian una movilidad completa. La hemiparesia estaba presente en ocho dc los 131 casos, astrocitomas de células gigantes en nueve, enfermedad poliquística renal en dos y complicaciones hemorragicas en relatión con angiomiolipomas de riñón en seis.

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Les anti-inflammatoires non steroidiens peuvent aussi exerce des effets nefastes sur l'intestin au-dela du duodenum. Leur utilisation doit etre recherchee chez tout malade presentant des symptomes intestinaux bas comme une diarrhee ou une hemorragie rectale. Devant une douleur abdominale, une anemie sous anti-inflammatoire non steroidien il faut savoir que la lesion peut se situer dans l'estomac et le duodenum mais aussi plus bas

In this retrospective pilot study we examine the feasibility of establishing a confidential enquiry into why some patients die after emergency admission to hospital. After excluding those who died in the first hour or who were admitted for palliative care, pairs of physicians were able to collect quantitative and qualitative data on 200 consecutive deaths. Both physicians reported shortfalls of care in 14 patients and one of the pair in 25 patients whose deaths would not have been the expected outcome. In 25, the shortfalls of care may have contributed to their deaths. Major problems were delays in seeing doctors, inaccurate diagnoses, delays in investigations and initiation of treatment. They occurred mostly in those admitted at night. It is possible that establishing the correct diagnosis and starting appropriate treatment may have been delayed in 64% of the 200 patients. The headline figures appear worse than some previous external assessment studies but this study did concentrate on those in whom problems were more likely. Nevertheless, the frequency is too high to be overlooked. In this feasibility study we have demonstrated that it is practicable for local staff to collect and assess data in hospitals and that the types of problems identified are relevant to anyone planning how to organise emergency care. A larger definitive study should be performed.

OBJECTIVES: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes. METHODS: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed. RESULTS: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09). CONCLUSION: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina.

The hypoxia-inducible factor (HIF) family of transcription factors directs a coordinated cellular response to hypoxia that includes the transcriptional regulation of a number of metabolic enzymes. Chuvash polycythemia (CP) is an autosomal recessive human disorder in which the regulatory degradation of HIF is impaired, resulting in elevated levels of HIF at normal oxygen tensions. Apart from the polycythemia, CP patients have marked abnormalities of cardiopulmonary function. No studies of integrated metabolic function have been reported. Here we describe the response of these patients to a series of metabolic stresses: exercise of a large muscle mass on a cycle ergometer, exercise of a small muscle mass (calf muscle) which allowed noninvasive in vivo assessments of muscle metabolism using (31)P magnetic resonance spectroscopy, and a standard meal tolerance test. During exercise, CP patients had early and marked phosphocreatine depletion and acidosis in skeletal muscle, greater accumulation of lactate in blood, and reduced maximum exercise capacities. Muscle biopsy specimens from CP patients showed elevated levels of transcript for pyruvate dehydrogenase kinase, phosphofructokinase, and muscle pyruvate kinase. In cell culture, a range of experimental manipulations have been used to study the effects of HIF on cellular metabolism. However, these approaches provide no potential to investigate integrated responses at the level of the whole organism. Although CP is relatively subtle disorder, our study now reveals a striking regulatory role for HIF on metabolism during exercise in humans. These findings have significant implications for the development of therapeutic approaches targeting the HIF pathway.

AIMS: Remote patient management (telemonitoring) may help to detect early signs of cardiac decompensation, allowing optimization of and adherence to treatments in chronic heart failure (CHF). Two meta-analyses have suggested that telemedicine in CHF can reduce mortality by 30-35%. The aim of the TIM-HF study was to investigate the impact of telemedical management on mortality in ambulatory CHF patients. Methods CHF patients [New York Heart Association (NYHA) II/III, left ventricular ejection fraction (LVEF)≤35%] with a history of cardiac decompensation with hospitalization in the past or therapy with intravenous diuretics in the prior 24 months (no decompensation required if LVEF≤25%) were randomized 1:1 to an intervention group of daily remote device monitoring (electrocardiogram, blood pressure, body weight) coupled with medical telephone support or to usual care led by the patients' local physician. In the intervention group, 24/7 physician-led medical support was provided by two central telemedical centres. A clinical event committee blinded to treatment allocation assessed cause of death and reason for hospitalization. The primary endpoint was total mortality. The first secondary endpoint was a composite of cardiovascular mortality or hospitalization due to heart failure. Other secondary endpoints included cardiovascular mortality, all-cause and cause-specific hospitalizations (all time to first event) as well as days lost due to heart failure hospitalization or cardiovascular death (in % of follow-up time), and changes in quality of life and NYHA class. Overall, 710 CHF patients were recruited. The mean follow-up was 21.5±7.2 months, with a minimum of 12 months. Perspective The study will provide important prospective outcome data on the impact of telemedical management in patients with CHF.