Management of incidental durotomies in an integrated Orthopaedic and Neurosurgical Spinal Unit.

Introduction: Incidental durotomy (ID) is an intraoperative event associated to prolonged bed rest and hospital stay, antibiotic use, higher patient dissatisfaction, and leg pain among other complications of its postoperative course. Several repair techniques and postsurgical care have been proposed for its management. This study was designed to develop an agreed protocol in cases of ID among Orthopaedic Surgeons (OS) and Neurosurgeons (NS) integrated into a Spinal Surgery Unit. Research question: Incidental durotomies management protocol. Materials and methods: From 997 eligible cases operated in Hospital del Mar (Barcelona, Spain) from April 2018 to March 2022, demographic, clinical, surgical and postoperative data was collected for statistical analysis from the morbidity and mortality database, with 79 identified IDs. Redo procedures were significantly associated to OS, and cervical and anterior/lateral approaches to NS, both groups were not comparable. Results: ID occurred in 7.9% of cases, more frequently after the lockdown (p=0.03), in females (p=0.04), during posterior approaches (p=0.003), and less frequently in the cervical spine (p=0.009). IDs were linked to postoperative infections (p< 0.001) and nerve root damage (p< 0.001). Patients without ID evolved more satisfactorily during the postoperative period (p=0.002), and those with CSF leak (20/79) spent on bed rest more than twice the time as those without (p<0.001). Multivariable logistic regression showed strong association between posterior approaches and ID, between complicated postoperative courses and ID. Discussion and conclusions: ID is linked to an adverse postoperative recovery, and it should be primarily repaired under microscope, with early mobilization of patients after surgery.

Changes in the prognostic values of modern cardiovascular biomarkers in relation to duration of diabetes mellitus.

BACKGROUND: Based on the complex pathophysiology of type 2 diabetes and atherosclerosis we hypothesized a dynamic change in prognostic value of cardiovascular biomarkers over time. METHODS: In this prospective study 746 patients with type 2 diabetes mellitus, being followed up for 60 months were analysed. The primary endpoint was defined as unplanned hospitalization for cardiovascular disease or death. Beside others, especially the prognostic performance of the biomarkers of interest (GDF-15, NT-proBNP, hs-TnT) was evaluated in relation to quartiles of diabetes duration. RESULTS: In patients having a diabetes duration below 7 years lnGDF-15 (HR 2.84; p < 0.01) and lnhs-TnT (HR 2.96; p < 0.01) were significant predictors of the primary endpoint. LnAge (HR 40.01; p < 0.01) and lnNT-proBNP (HR 1.56; p = 0.03) were significant predictors in patients with a diabetes duration between 7 and 12 years. In the third quartile (diabetes duration 12-22 years) lnurinary albumin to creatinine ratio (HR 1.25; p = 0.005) and lnNT-proBNP (HR 2.13, p < 0.001) predicted the endpoint. In patients with a diabetes duration above 22 years, lnAge (HR 75.35; p = 0.001) and lnNT-proBNP (HR 2.0; p < 0.01) were the only significant predictors of the endpoint. CONCLUSION: Prognostic power of cardiovascular biomarkers changes dynamically in relation to duration of type 2 diabetes mellitus. In patients with shorter duration of the disease markers of subclinical cardiovascular dysfunction and inflammation perform better than markers of systemic advanced organ dysfunction and cardiovascular disease.

A lesson from history? Worsening mortality and the rise of the Nazi Party in 1930s Germany.

OBJECTIVES: The aim of the study was to test the hypothesis that worsening mortality rates in the early 1930s were associated with increasing votes for the Nazi Party. STUDY DESIGN: The study consist of panel data with fixed effects. METHODS: We used district- and city-level regression models of Nazi vote shares on changes in all-cause mortality rates in 866 districts and 214 cities during federal elections from 1930 to 1933, adjusting for election and district/city-level fixed effects and sociodemographic factors. As a falsification test, we used a subset of deaths less susceptible to sociopolitical factors. RESULTS: Historical downward trends in mortality rates reversed in the early 1930s in Germany. At the district/city level, these increases were positively associated with a rising Nazi vote share. Each increase of 10 deaths per 1000 population was associated with a 6.51-percentage-point increase in Nazi vote share (95% confidence interval = 1.17-11.8). The strongest associations were with deaths due to infectious and communicable diseases, suicides, and alcohol-related deaths. Worsening mortality had no association with votes for the Communist Party or for other contemporary political parties. Greater welfare payments were associated with smaller increases in both mortality and Nazi vote share, and adjusting for welfare generosity mitigated the association by approximately one-third. CONCLUSIONS: Worsening mortality rates were positively associated with the rise of the Nazi Party in 1930s Germany. Social security mitigated the association between mortality and Nazi vote share. Our findings add to the growing evidence that population health declines can be a 'canary in the coal mine' for the health of democracies.

GDF15 reflects beta cell function in obese patients independently of the grade of impairment of glucose metabolism.

BACKGROUND AND AIMS: Growth differentiation factor 15 (GDF15) is a strong predictor of cardiovascular morbidity and mortality found to be both marker and target of impaired glucose metabolism. GDF15 increases following glucose administration and is up-regulated in obesity and diabetes. We investigate here the relationship between GDF15 and beta cell function. METHODS AND RESULTS: In this cross-sectional study we evaluated GDF15 concentrations in 160 obese subjects (BMI 35-63 kg/m2, age 39.4 ± 18.6 years, m/f 38/122) who underwent a 75 g oral glucose tolerance test (OGTT). Based on the OGTT results, the cohort was divided into two groups: 1) normal fasting glucose and normal glucose tolerance (n = 80), 2) impaired fasting glucose, impaired glucose tolerance or type 2 diabetes (n = 80). The relationship of GDF15 to fasting and OGTT-based dynamic insulin sensitivity and insulin secretion parameters was evaluated. GDF15 was higher in the prediabetes and diabetes groups and correlated with HbA1c, glucose, insulin as well as baseline and dynamic indices of insulin sensitivity and estimated beta cell function. Multiple regression analysis revealed that age, waist-to-height ratio, glomerular filtration rate and prehepatic beta cell function, but not the grade of impairment of glucose metabolism, were independent predictors of GDF15. Subgroup analysis showed that of all parameters of glucose metabolism only C-peptide, fasting prehepatic beta cell function and insulinogenic index remained significantly related to GDF15 in both groups. CONCLUSION: We conclude that in patients with severe obesity, GDF15 strongly relates to beta cell function and should be further investigated as a potential therapeutic target and biomarker guiding treatment options.

A Multi-feature Fuzzy Index to Assess Stress Level from Bio-signals.

A mono-feature fuzzy index that evaluates the stress level from one feature extracted from ECG or GSR is presented. It is build using several measures of the feature recorded when the subject is at rest. The mono-feature fuzzy index can be merged in a multi-feature stress index without any tuning. It can be used to select relevant features and to detect stress. The performance of the stress index is analyzed on a data set made of 160 time periods of time when 20 subjects had to perform stressful tasks and corresponding control tasks. The stress was induced by 4 different tasks. The performances reached are 72% of correctly classified time periods in stress and no stress situations. Interesting conclusions could also be made on the tasks ability to induce stress.

Vitamin D and critical illness: what endocrinology can learn from intensive care and vice versa.

The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future.

Targeted multiple biomarker approach in predicting cardiovascular events in patients with diabetes.

OBJECTIVE: We hypothesised that biomarkers representing different pathophysiological pathways of atherosclerosis namely growth differentiation factor 15 (GDF-15), N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TnT) could enhance cardiovascular risk prediction in patients with type 2 diabetes mellitus. METHODS: This is a prospective study in 746 patients with type 2 diabetes mellitus, who were followed up for 60 months. The primary endpoint was defined as unplanned hospitalisation for cardiovascular disease or death. The prognostic performance of the biomarkers of interest (GDF-15 in comparison with NT-proBNP and hs-TnT) was evaluated in univariate as well as in stepwise Cox regression models. HRs are presented per standard unit increase. RESULTS: The primary endpoint was registered in 171 patients (22.9%). In univariate Cox regression models, GDF-15 as well as hs-TnT provided significant prognostic information. Even after adjusting for established cardiovascular risk factors, GDF-15, hs-TnT and NT-proBNP remained strong independent predictors of the endpoint (logGDF-15: HR 1.37, p<0.01, CI 1.12 to 1.68; loghs-TnT: HR 1.43, p<0.01, CI 1.13 to 1.1.82; logNT-proBNP: HR 1.45, p<0.01, CI 1.26 to 1.66). The number of elevated markers showed a strong complementarity to predict future long-term risk. Adding hs-TnT and GDF-15 to a zero model already including NT-proBNP led to a net reclassification improvement (NRI) of 33.6% (CI 16.0% to 50.8%, NRI for patients with event: 11.1% CI -4.7% to 26.6%, for patients without event: 22.5% CI 13.6% to 30.5%). CONCLUSIONS: GDF-15 and hs-TnT are strong independent cardiovascular biomarkers augmenting the predictive value of NT-proBNP in patients with diabetes.

Strong association of serum- and glucocorticoid-regulated kinase 1 with peripheral and adipose tissue inflammation in obesity.

OBJECTIVE: The serum- and glucocorticoid-regulated kinase 1 (SGK1) is an early transcriptional target of glucocorticoids and is activated via insulin. Here we investigate the regulation of SGK1 expression in human obesity, diet-induced murine obesity and human monocytic cell line THP-1 monocytes. SUBJECTS AND METHODS: SGK1 expression was studied in subcutaneous and omental adipose tissue (AT) of 20 morbidly obese and 20 age- and gender-matched non-obese controls in murine diet-induced obesity and the THP-1 cell line. The regulation of SGK1 by inflammatory signals was tested in THP-1 cells. RESULTS: Murine diet-induced obesity is associated with a significant upregulation of Sgk1 in gonadal AT. Sgk1 expression is highest in the macrophage-rich stromal vascular fraction and lower in adipocytes. In humans, AT SGK1 is predominantly expressed in CD14(+) macrophages and significantly upregulated in omental and subcutaneous AT of obese subjects. SGK1 mRNA expression in both omental and subcutaneous AT correlates with body mass index, circulating leptin and C-reactive protein, and the local expression of inflammatory markers including monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. The expression of SGK1 in THP-1 cells is upregulated by inflammatory signals, such as lipopolysaccharide and tumour necrosis factor-α, as well as during the induction of monocyte-to-macrophage maturation. CONCLUSIONS: Our data present the first link between SGK1 and obesity-associated inflammation. SGK1 expression is stimulated in response to inflammatory signals and increased in AT macrophages. The characterisation of SGK1 functions in obesity and immunity may help identify potential therapeutic targets in the treatment of obesity.

Effects of B-type natriuretic peptide on cardiovascular biomarkers in healthy volunteers.

Cardiovascular biomarkers provide independent prognostic information in the assessment of mortality and cardiovascular complications. However, little is known about possible interactions between these biomarkers. In the present study, we evaluated the influence of B-type natriuretic peptide (BNP) on midregional-proadrenomedullin (MR-proADM), C-terminal-proendothelin-1 (CT-proET-1), growth differentiation factor-15 (GDF-15), midregional-proatrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin in healthy volunteers. Ten healthy male subjects (mean age 24 yr) participating in a randomized, placebo-controlled, single-blinded crossover study received placebo or 3.0 pmol·kg(-1)·min(-1) human BNP 32 during a continuous infusion lasting for 4 h. Effects of BNP on other cardiovascular biomarkers were assessed. BNP did not change concentrations of MR-proADM, copeptin, CT-proET1, GDF-15, or procalcitonin. In contrast, MR-proANP was significantly decreased during BNP infusion. BNP as an established cardiovascular biomarker did not affect plasma concentrations of other cardiovascular biomarkers in a model of healthy volunteers.

Association of nutritional risk index with metabolic biomarkers, appetite-regulatory hormones and inflammatory biomarkers and outcome in patients with chronic heart failure.

AIMS: We aimed to evaluate the association of the nutritional status by using the nutritional risk index (NRI) with metabolic and inflammatory biomarkers, and appetite-regulatory hormones in a cohort of stable patients with heart failure (HF), and to analyse its prognostic value. METHODS AND RESULTS: In this prospective observational cohort study, we included 137 stable chronic HF patients (median age, 60 years; median body mass index, 27 kg/m(2) ) with optimised medical treatment. Baseline NRI of < 113 (n = 45) was associated with a significant increase in the levels of ghrelin (p < 0.001), peptide YY (p = 0.007), pentraxin-3 (p = 0.001), tumour necrosis factor-alpha (p = 0.018), adiponectin (p < 0.0001) and the N-terminal prohormone of brain natriuretic peptide (NT-proBNP; p < 0.0001) compared with those in patients with NRI of ≥ 113. The NRI was found to be correlated with the homoeostasis model assessment of insulin resistance index (r = 0.444; p < 0.0001) and inversely correlated with the NT-proBNP level (r = -0.410; p < 0.0001). The overall mortality rate was 20%. A baseline NRI of < 113 was associated with a higher risk of all-cause mortality (log rank = 0.031). CONCLUSION: We propose that the NRI is a useful and easily applicable tool for the early identification of nutritional depletion in patients with chronic HF as it discriminates metabolic changes prior to the clinical manifestation of body wasting. Furthermore, poor nutritional status, represented as a low NRI, is associated with an increased incidence of death in such cases.

Reversal of moderate and intense neuromuscular block induced by rocuronium with low doses of sugammadex for intraoperative facial nerve monitoring.

We report two cases in which moderate and intense rocuronium-induced neuromuscular block was reversed intraoperatively with low sugammadex doses in order to facilitate electromyographic evaluation of facial nerve function during surgery of the parotid gland and the middle ear. Acceleromyography was used to assess reversal of neuromuscular block before starting electromyography monitoring. Rocuronium-induced neuromuscular block was reversed with sugammadex 0.22mgkg(-1) when the TOF ratio was 0.14 in the first patient, and with sugammadex 2mgkg(-1) during intense block (PTC 0) in the second patient. In each case, appropriate neuromuscular function (TOF ratio≥0.9) was established soon after sugammadex administration, and electromyographic evaluation of facial nerve was successfully conducted. The use of rocuronium and sugammadex, coupled with objective neuromuscular monitoring with acceleromyography, assured complete restoration of neuromuscular function and created the optimal conditions for the surgical team.

[Flat, depressed and polypoid colorectal lesions: a comparative study using a index of histological advance]. / Lesiones planas, deprimidas y polipoides colorrectales: estudio comparativo utilizando un índice de avance histológico.

BACKGROUND: It has been described that the histological changes in flat and depressed colon lesions are more advanced than the ones in polypoid lesions. OBJECTIVES: To compare the histological findings in flat or depressed (non polypoid) and elevated (polypoid) colon lesions. To validate the use of a newly developed Histological Advance Index to compare results. MATERIALS & METHODS: Prospective observational study. Population in study consisted of adult patients programmed for an elective colonoscopy at a private endoscopy center in Lima- Perú. Two groups: 417 found to have non polypoid lesions (which included flat, depressed and lateral spreading tumors or LST), and 405 with polypoid lesions. RESULTS: Total of 8,248 patients, with 417(5%) in the non polypoid group; 368(4.5%) in the flat lesion group, 27(0.32%) in the depressed and 22 (0.26%) LSTs. According to our index, flat and polypoid lesions showed no difference in histological findings. LSTs had a more advanced histology and depressed lesions reached the highest index scores. Flat lesions were found more often in right colon compared with polypoid ones (31% vs 22%, p<0.01), with a higher percentage of serrated lesions (9% vs 2%, p<0.01) and high grade dysplasia (5% vs 3%, NS). In contrast, depressed lesions, showed high grade dysplasia in 3.7% (NS) but cancer in 18% (p<0.01) LSTs were found mainly in right colon and rectum, showing villous component in 23%(p< 0.01) and high grade dysplasia in 32%(p <0.01), but no cancer was found. CONCLUSIONS: Flat and polypoid lesions showed similar histological findings, but LSTs were found to have a higher prevalence of villous lesions and high grade dysplasia. Depressed lesions were found to have a higher prevalence of malignancy. Histological Advance Index proved to be a useful tool to compare groups and quantify differences. .

Lesiones planas, deprimidas y polipoides colorrectales: estudio comparativo utilizando un índice de avance histológico / Flat lesions, and polypoid colorectal depressed: a comparative study using a histologic progress index

ANTECEDENTES: Se ha descrito que las lesiones planas y deprimidas colorrectales, llamadas también no polipoides (LNP) tienen una histología más avanzada que las polipoides o protruidas (LP). OBJETIVOS: Comparar el grado de avance histológico de las LNP con el de las LP, a nivel del colon y recto. Validar el uso de un Índice de Avance Histológico (IAH) para objetivar estas diferencias. METODOLOGÍA: Estudio observacional, prospectivo, realizado en adultos programados a colonoscopía en un Centro Endoscópico privado de Lima- Perú. Dos grupos: 417 pacientes con LNP (planas, deprimidas y de crecimiento lateral o LST) y 405 pacientes con solo LP. RESULTADOS: 417/ 8,248 pacientes (5%) tuvieron LNP; 368 (4.5%) planas, 27(0.32%) deprimidas y 22(0.26%) LST. Según nuestro IAH, las lesiones planas y polipoides mostraron similar avance histológico. Las LST tuvieron una histología más avanzada y las deprimidas alcanzaron los valores más altos. Las lesiones planas tuvieron mayor tendencia que las polipoides a situarse en colon derecho (31% vs 22% p< 0.01), a presentar histología aserrada (9% vs 2% p< 0.01) y displasia de alto grado (5% vs 3% NS), pero menor tendencia al cáncer (0.2% vs 1% NS). Comparadas con las polipoides, las deprimidas tuvieron similar displasia de alto grado (3.7% /NS) pero una alta proporción de cáncer (18 % p < 0.01), mientras que las LST se localizaron sobre todo en colon derecho y recto, con componente velloso en 23% (p< 0.01) y displasia de alto grado en 32% (p< 0.01), pero no cáncer. CONCLUSIONES: Las lesiones planas mostraron un grado de avance histológico similar a las polipoides, pero las de crecimiento lateral si tuvieron una histología más avanzada y las deprimidas desarrollaron cáncer en una elevada proporción. El Índice de Avance Histológico fue una herramienta útil para comparar los grupos y resaltar sus diferencias.

BACKGROUND: It has been described that the histological changes in flat and depressed colon lesions are more advanced than the ones in polypoid lesions. Objectives: To compare the histological findings in flat or depressed (non polypoid) and elevated (polypoid) colon lesions. To validate the use of a newly developed Histological Advance Index to compare results. MATERIALS & METHODS: Prospective observational study. Population in study consisted of adult patients programmed for an elective colonoscopy at a private endoscopy center in Lima- Perú. Two groups: 417 found to have non polypoid lesions (which included flat, depressed and lateral spreading tumors or LST), and 405 with polypoid lesions. RESULTS: Total of 8,248 patients, with 417(5%) in the non polypoid group; 368(4.5%) in the flat lesion group, 27(0.32%) in the depressed and 22 (0.26%) LSTs. According to our index, flat and polypoid lesions showed no difference in histological findings. LSTs had a more advanced histology and depressed lesions reached the highest index scores. Flat lesions were found more often in right colon compared with polypoid ones (31% vs 22%, p<0.01), with a higher percentage of serrated lesions (9% vs 2%, p<0.01) and high grade dysplasia (5% vs 3%, NS). In contrast, depressed lesions, showed high grade dysplasia in 3.7% (NS) but cancer in 18% (p<0.01) LSTs were found mainly in right colon and rectum, showing villous component in 23%(p< 0.01) and high grade dysplasia in 32%(p <0.01), but no cancer was found. CONCLUSIONS: Flat and polypoid lesions showed similar histological findings, but LSTs were found to have a higher prevalence of villous lesions and high grade dysplasia. Depressed lesions were found to have a higher prevalence of malignancy. Histological Advance Index proved to be a useful tool to compare groups and quantify differences.

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men.

AIMS/HYPOTHESIS: B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism. METHODS: Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m(2); fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg(-1) min(-1) BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured. RESULTS: Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects. CONCLUSIONS/INTERPRETATION: Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01324739 FUNDING: The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

Ethnic factors in mental health service utilisation among people with intellectual disability in high-income countries: systematic review.

BACKGROUND: An emerging literature suggests that ethnic and cultural factors influence service utilisation among people with intellectual disability (ID), but this has not previously been reviewed. AIMS: To investigate possible ethnic variation in uptake of mental health services in children, adolescents and adults with ID in high-income countries. METHOD: A systematic review using main databases of studies that consider ethnic influences on mental health utilisation of people with ID. Methodological quality of studies was assessed. RESULTS: Nine studies that reached selection criteria were identified. Six studies that compared two or more ethnic groups found a variation in levels of mental health service utilisation. The most consistent finding was that South Asian children, adolescents and adults with ID in the UK had lower use of mental health services than White British comparison groups. CONCLUSION: Ethnic influences on mental health service utilisation were identified. Understanding their significance and potential negative consequences requires further investigation.

Serum uric acid is related to cardiovascular events and correlates with N-terminal pro-B-type natriuretic peptide and albuminuria in patients with diabetes mellitus.

BACKGROUND: Hyperuricemia is a risk factor for cardiovascular events and renal insufficiency. It correlates to intima-media thickness and microalbuminuria. In this study we evaluated uric acid as an independent marker for cardiac events in patients with diabetes. METHODS: In a prospective observational study we recruited 494 patients with diabetes. Patients were then followed for 12.8 months (mean follow-up) and hospitalizations as a result of cardiac events (ischaemic heart disease, arrhythmias, heart failure) were recorded. RESULTS: The median duration of diabetes was 11 ± 10.35 years. Patients were in the mean 60 ± 13 years old and mean HbA(1c) was 62 ± 13 mmol/mol (7.8 ± 3.3%). At baseline, mean uric acid was 321.2 ± 101.1 µmol/l (range 101.1-743.5 µmol/l), median N-terminal pro-B-type natriuretic peptide was 92 ± 412 pg/ml and median urinary albumin to creatinine ratio was 8 ± 361 mg/g; Uric acid significantly correlated to N-terminal pro-B-type natriuretic peptide (r = 0.237, P < 0.001) and urinary albumin:creatinine ratio (r = 0.198, P < 0.001). In a Cox regression model, including age, estimated glomerular filtration rate, gender, systolic blood pressure, smoking and alcohol consumption, uric acid was the best predictor of cardiac events (hazard ratio 1.331, confidence interval 1.095-1.616, P = 0.04). However, uric acid lost its prognostic value when the natural logarithm of N-terminal pro-B-type natriuretic peptide was added to the model. CONCLUSION: Serum uric acid is a predictor of cardiac events and correlates to N-terminal pro-B-type natriuretic peptide and albuminuria, underscoring the importance of uric acid as a cardiovascular risk marker in patients with diabetes.

Ethnic variation in service utilisation among children with intellectual disability.

BACKGROUND: This study examined whether service utilisation among children with intellectual disability (ID) varied by ethnic cultural group. METHOD: Survey carried out in four special schools in London. Information was provided by school teachers using case files, and 242 children aged 7 to 17 years with mild and moderate ID were identified. Ethnic categories were derived from self-reported main categories. Service utilisation categorised as use of: child and adolescent mental health services (CAMHS), social services, physical health and education services. RESULTS: Child and adolescent mental health services uptake was lower for South Asians than for White British (P = 0.0487). There were statistically significant differences among ethnic groups for community-based social services uptake (being the highest for the Black groups and the lowest for South Asians, P = 0.015) and respite care uptake (being the highest for the Black and White European groups and the lowest for South Asians, P = 0.009). In regression analysis family structure predicted CAMHS service utilisation and social service community support. Ethnicity predicted use of respite care. CONCLUSIONS: Significant ethnic differences in service utilisation among children with ID were found for both CAMHS and social service contact. There was particularly low service use for the South Asian group. These differences might arise because of differences in family organisation, as more South Asian children lived in two-parent families, which may have been better able to provide care than single-parent families. Other factors such as variation in parental belief systems and variation in psychopathology may be relevant. Implications are discussed.

Opera and madness: Britten's Peter Grimes--a case study.

In this paper, Britten's opera Peter Grimes (1945) is used as an illustrative case study through which to examine the depiction of psychiatric disorders in opera. It is argued that Peter Grimes is a powerful example of how opera, in the hands of a great composer, can become an invaluable tool for examining subjective human experience. After a brief discussion of opera as a vehicle to express emotions, various operas are drawn upon to provide a historical perspective and to demonstrate the long interconnection existing between opera and madness. An in-depth analysis of Peter Grimes, its background and central character, is then provided, in order to demonstrate how opera can elicit empathy for individuals affected by mental health problems.

Reduced TGF-beta1 expression and its target genes in human insulinomas.

Aiming to identify signalling pathways relevant for ss-cell growth we performed an explorative micro-array analysis comparing the gene expression profiles of three human insulinomas and one normal pancreatic islet preparation. This revealed an insulinoma-associated down-regulation of the transforming growth factor beta 1 (TGF-beta1) and its target genes. Comparative quantitative real-time PCR (qRT-PCR) including an expanded sample number of both insulinomas (n=9) and pancreatic islet preparations (n=4) confirmed the decreased TGF-beta1 expression and its target molecules (TGFBI, NNMT, RPN2) in insulinomas. Similarly, TGF-beta1 immunofluorescence analysis revealed reduced expression in insulinomas when compared to pancreatic islets. In contrast, TGFBR2 (transforming growth factor beta receptor II) was found up-regulated. However, the consistent down-regulation of the TGF-beta1 targets TGFBI (transforming growth factor, beta-induced), NNMT (nicotinamide N-methyltransferase), RPN2 (ribophorin II) indicates that the parallel up-regulation of TGFBR2 does not compensate for the only marginal TGF-beta1 expression levels in insulinomas. TGFBR2 expression was confirmed at the protein level in insulinomas. SMAD2/3 protein expression was found at higher levels in human pancreatic islets when compared with insulinomas by dual colour confocal microscopy. TGF-beta1 signalling is known to be involved in cell replication and is abrogated in ductal pancreatic tumours. The down-regulation of TGF-beta1 expression and its target molecules in insulinomas is a new aspect of this cytokine. Our data underline parallels in endocrine and exocrine pancreatic tumour development, which may implicate common progenitor cells.

[Dimensional approach of social behaviour deficits in children. Preliminary validation study of the French version of the Children's Social Behaviour Questionnaire (CSBQ)]. / Approche dimensionnelle des troubles des comportements sociaux chez l'enfant. Etude préliminaire de validation de la version française du Children's Social Behavior Questionnaire (CSBQ).

UNLABELLED: Social deficit is the core symptom of pervasive developmental disorder. In other child psychiatric disorders, social problems are also described but mainly as a result of the disease symptomatology. However, some recent studies suspect that in several disorders such as attention deficit hyperactive disorder, patients have an endogenous social disturbance. The aim of our research was to study abnormal child social behaviour in several disorders, using a dimensional approach. It is a preliminary validation study of the French version of the Children's Social Behaviour Questionnaire, a dimensional instrument constructed by Luteijn, Minderaa et al. METHODOLOGY: Five clinical groups, according to the DSM IV criteria, formed a population of 103 children aged 6 to 16 years old: autistic disorder, attention deficit hyperactive disorder (ADHD), emotional disorder (anxious, depressed), mental retardation and normal children. Parents completed the Child Behaviour Checklist (CBCL) and the Children's Social Behaviour Questionnaire (CSBQ). The research worker and the child's physician completed a data form. The data form included information about medical history, development and socio-demographic criteria. The CBCL explored children's behaviours and general psychopathology, and included social dimensions (withdrawn, social problems, aggressive/delinquent behaviours, thought problems). The CSBQ, a dimensional questionnaire, explored children's social behaviours and included five dimensions: <>, <>, <>, <>, <>. The English version of the CSBQ, validated with in the Netherlands Dutch population was translated into French and the translation was validated (double back translation). As the CBCL and CSBQ questionnaires are both dimensional instruments, dimensions have been compared. All instrument results were analysed separately; correlations and comparisons were made between groups. RESULTS: Correlations between CSBQ and CBCL dimensions are consistent. Positive correlations exist for: <> dimension with <>, <> and <>; <> with <> and <>; <> with <> and <>; <> with <>, <> and <>; social stereotypes>> with <>. Mean CSBQ results are as follows: 1. autistic group has the highest score for the <> dimension, ADHD group has the highest score for the <> dimension, mental retardation group has the highest score for the <> dimension. 2. comparisons between groups shows: significant difference between the autistic and ADHD groups for <> and <> but not for <> and <>; between the autistic and mental retardation groups, there is a significant difference for <> but not for the other dimensions; between the ADHD and mental retardation groups, there is a significant difference only for <>; there is no significant difference between the ADHD and emotional groups; control group has very low scores. CBCL results are: abnormal scores in all groups except normal control group, for <> and <>; abnormal scores in the autistic and emotional groups for <>, <> and <>; abnormal scores in the ADHD group for <>, <> and <>; the <> score is borderline. DISCUSSION: Social behaviour profiles are different and characteristic for each disorder. However, social symptoms are not specific for one disorder and common social signs do exist between different disorders. Our results are concordant with the Luteijn study and literature data. The results support the hypothesis of a dimensional pathogenesis in social behaviour disturbance. We discuss the benefit of a dimensional approach to complete the categorical one. The Children's Social Behaviour Questionnaire seems to be an interesting instrument to explore social behaviour disturbances in several child disorders.