St. Columcille's Hospital

Global obesity rates have increased exponentially in recent decades. People are becoming obese younger, morbid obesity is increasing and the full health implications are only beginning to be seen. This article discusses the latest epidemiological data on obesity in adults and children, and systemically reviews the complications associated with the condition.

With the emerging obesity pandemic, identifying those who appear to be protected from adverse consequences such as type 2 diabetes and certain malignancies will become important. We propose that the circulating immune system plays a role in the development of these comorbidities. Clinical data and blood samples were collected from 52 patients with severe obesity attending a hospital weight-management clinic and 11 lean healthy controls. Patients were classified into metabolically "healthy obese" (n = 26; mean age 42.6 years, mean BMI 46.8 kg/m(2)) or "unhealthy obese" (n = 26; mean age 45 years, mean BMI 47.5 kg/m(2)) groups, based upon standard cutoff points for blood pressure, lipid profile, and fasting glucose. Circulating lymphoid populations and phenotypes were assessed by flow cytometry. Obese patients had significantly less circulating natural killer (NK) and cytotoxic T lymphocytes (CTL) compared to lean controls. There were significantly higher levels of NK cells and CTLs in the healthy obese group compared to the unhealthy obese group (NK: 11.7% vs. 6.5%, P < 0.0001, CD8 13.4% vs. 9.3%, P = 0.04), independent of age and BMI and these NK cells were also less activated in the healthy compared to the unhealthy group (CD69, 4.1% vs. 11.8%, P = 0.03). This is the first time that quantitative differences in the circulating immune system of obese patients with similar BMI but different metabolic profiles have been described. The significantly higher levels of CTLs and NK cells, which express fewer inhibitory molecules, could protect against malignancy, infection, and metabolic disease seen in obesity.

OBJECTIVE: Several studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity. SUBJECTS: Thirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40-71). RESULTS: There was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9+/-10.9 microm) when compared with metabolically unhealthy patients (100.0+/-7.6 microm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1+/-8.5 microm versus 107.9+/-7.1 microm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis. CONCLUSION: Metabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.

AIMS/HYPOTHESIS: The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells. METHODS: We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. RESULTS: The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. CONCLUSIONS/INTERPRETATION: The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.

BACKGROUND: Some governments have recently shown a willingness to introduce taxes on unhealthy foods and drinks. In 2011, the Irish Minister for Health proposed a 10% tax on sugar sweetened beverages (SSBs) as a measure to combat childhood obesity. Whilst this proposed tax received considerable support, the Irish Department of Finance requested a Health Impact Assessment of this measure. As part of this assessment we set out to model the impact on obesity. METHODS: We used price elasticity estimates to calculate the effect of a 10% SSB tax on SSB consumption. SSBs were assumed to have an own-price elasticity of -0.9 and we assumed a tax pass-on rate to consumers of 90%. Baseline SSB consumption and obesity prevalence, by age, sex and income-group, for Ireland were taken from the 2007 Survey on Lifestyle and Attitude to Nutrition. A comparative risk assessment model was used to estimate the effect on obesity arising from the predicted change in calorie consumption, both for the whole population and for sub-groups (age, sex, income). Sensitivity analyses were conducted on price-elasticity estimates and tax pass-on rates. RESULTS: We estimate that a 10% tax on SSBs will result in a mean reduction in energy intake of 2.1 kcal/person/day. After adjustment for self-reported data, the 10% tax is predicted to reduce the percentage of the obese adult population (body mass index [BMI] ≥ 30 kg/m(2)) by 1.3%, equating to 9,900 adults (95% credible intervals: 7,750 to 12,940), and the overweight or obese population (BMI ≥ 25 kg/m(2)) by 0.7%, or 14,380 adults (9,790 to 17,820). Reductions in obesity are similar for men (1.2%) and women (1.3%), and similar for each income group (between 1.1% and 1.4% across income groups). Reductions in obesity are greater in young adults than older adults (e.g. 2.9% in adults aged 18-24 years vs 0.6% in adults aged 65 years and over). CONCLUSIONS: This study suggests that a tax on SSBs in Ireland would have a small but meaningful effect on obesity. While such a tax would be perceived as affecting the whole population, from a health prospective the tax will predominantly affect younger adults who are the main consumers of SSBs.

OBJECTIVE: Transgender and non-binary individuals frequently engage with healthcare services to obtain gender-affirming care. Little data exist on the experiences of young people accessing gender care. This systematic review and meta-ethnography aimed to identify and synthesise data on youths' experiences accessing gender-affirming healthcare. METHOD: A systematic review and meta-ethnography focusing on qualitative research on the experiences of transgender and non-binary youth accessing gender care was completed between April-December 2020. The following databases were used: PsychINFO, MEDLINE, EMBASE, and CINAHL. The protocol was registered on PROSPERO, international prospective register of Systematic Reviews (CRD42020139908). RESULTS: Ten studies were included in the final review. The sample included participants with diverse gender identities and included the perspective of parents/caregivers. Five dimensions (third-order constructs) were identified and contextualized into the following themes: 1.) Disclosure of gender identity. 2.) The pursuit of care. 3.) The cost of care. 4.) Complex family/caregiver dynamics. 5.) Patient-provider relationships. Each dimension details a complicated set of factors that can impact healthcare navigation and are explained through a new conceptual model titled "The Rainbow Brick Road". CONCLUSION: This synthesis expands understanding into the experience of transgender and non-binary youth accessing gender-affirming healthcare. Ryvicker's behavioural-ecological model of healthcare navigation is discussed in relation to the findings and compared to the authors' conceptual model. This detailed analysis reveals unique insights on healthcare navigation challenges and the traits, resources, and infrastructure needed to overcome these. Importantly, this paper reveals the critical need for more research with non-binary youth and research which includes the population in the design.

BACKGROUND: Obesity is characterized by chronic inflammation, immune dysregulation, and alteration of gene expression, associated with type 2 diabetes mellitus and cardiovascular disease. The degree to which these changes occur in childhood obesity is not fully defined. AIMS AND METHODS: The aim was to investigate the effect of childhood obesity on immune cell frequency, macrophage activation, cytokine production, and specific regulators of metabolic gene expression. Profiling was performed on peripheral blood from 29 obese and 20 nonobese children using real-time PCR, ELISA, and flow cytometry. RESULTS: Fasting glucose was similar in both groups, but there was a higher degree of insulin resistance in obese subjects (homeostasis model of assessment for insulin resistance, 4.8 vs 0.84; P < .001). Soluble CD163, a marker of macrophage polarization to a proinflammatory profile, was elevated in the obese compared to nonobese children (135 vs 105 ng/mL; P = .03). Invariant natural killer T cells were reduced in the obese children (CD3 T cells, 0.31 vs 0.53%; P = .001). Cytokine profiling revealed significantly elevated TNF-α (6.7 vs 5.1 pg/mL; P = .01) and leptin (1186 vs 432 pg/mL; P < .001) and reduced adiponectin (884 vs 1321 pg/mL; P = .001) in obese compared to nonobese children. Stimulation of peripheral blood mononuclear cells from obese children resulted in higher levels of IL-1β (2100 vs 1500 pg/mL; P = .018). There was a 4-fold increase in expression of microRNA33a (P = .001) and a 3-fold increase in microRNA33b (P = .017) in obese children. CONCLUSION: Childhood obesity is associated with changes in immune cell frequency, inflammatory environment, and regulation of metabolic gene expression. These changes have been causally linked to the onset of metabolic disease in adulthood and suggest the future trajectory of obese children to the development of type 2 diabetes mellitus and premature cardiovascular disease.

INTRODUCTION: Gender dysphoria (GD) is a condition in which there is a marked incongruence between an individual's psychological perception of his/her sex and their biological phenotype. Gender identity disorder was officially renamed "gender dysphoria" in the DSM-V in 2013. The prevalence and demographics of GD vary according to geographical location and has not been well-documented in Ireland. METHODS: We retrospectively reviewed medical records of 218 patients with suspected or confirmed GD referred to our endocrine service for consideration of hormonal therapy (HT) between 2005 and early 2014. We documented their demographics, clinical characteristics, and treatment during the study period. RESULTS: The prevalence of GD in the Irish population was 1:10,154 male-to-female (MTF) and 1:27,668 female-to-male (FTM), similar to reported figures in Western Europe. 159 of the patients were MTF and 59 were FTM, accounting for 72.9% and 27.1% of the cohort, respectively. The rate of referral has increased year-on-year, with 55 patients referred in 2013 versus 6 in 2005. Mean ages were 32.6 years (MTF) and 32.2 years (FTM). 22 of the patients were married and 41 had children, with 2 others having pregnant partners. 37.6% were referred by a psychologist, with the remainder evenly divided between GPs and psychiatric services. There were low rates of coexistent medical illness although psychiatric conditions were more prevalent, depression being a factor in 34.4% of patients. 5.9% of patients did not attend a mental health professional. 74.3% are currently on HT, and 9.17% have had gender reassignment surgery (GRS). Regret following hormonal or surgical treatment was in line with other Western European countries (1.83%). CONCLUSION: The incidence of diagnosis and referral of GD in Ireland is increasing. This brings with it multiple social, health, and financial implications. Clear and accessible treatment pathways supported by mental health professionals is essential.

PURPOSE OF REVIEW: The 'obesity epidemic' is a growing concern globally, and obesity trends are projected to continue increasing in both prevalence and overall mean BMI. Cardiovascular and metabolic comorbidities have historically been well described; however, obesity-related respiratory disease is now increasingly prevalent, in particular, sleep disordered breathing. The surge in clinically significant obstructive sleep apnoea and obesity hypoventilation syndrome is associated with increased cardiopulmonary morbidity, quality-of-life impairment, and a potential rise in the frequency of road traffic accidents. RECENT FINDINGS: We discuss recent trends in obesity and obesity-related sleep disordered breathing. We also discuss recently published international guidelines regarding the diagnosis and management of sleep disordered breathing, and in particular, the role of weight management interventions, such as bariatric surgery, in this area. We discuss possible approaches to meet the growing demand for sleep assessment and management in the future. SUMMARY: Obesity-related respiratory disease reflects an increasing proportion of patients in both inpatient and outpatient settings. It is important to recognize the impact of obesity on pulmonary physiology in order to appropriately care for this population, as well as plan for the future.

A 35-year-old man developed progressive memory problems and personality changes over the course of 6 months. This amnesia culminated in overt functional impairment as he began getting lost in familiar places and paid his rent multiple times in one day. He then displayed increased aggression and was admitted to hospital after assaulting a family member.

Nutrition knowledge and skills enable individuals with type 2 diabetes (T2DM) to make food choices that optimise metabolic self-management and quality of life. The present study examined the relationship between nutrition knowledge and skills, and nutrient intake in T2DM. A cross-sectional analysis of diabetes-related nutrition knowledge and nutrient intake was conducted in 124 T2DM individuals managed in usual care (64% male, age 57.4 (sd 5.6) years, BMI 32.5 (sd 5.8) kg/m2), using the Audit of Diabetes Knowledge (ADKnowl) questionnaire and a 4 d food diary. Data on sociodemographic characteristics, food label use and weight management were also collected. The average ADKnowl dietary subscale score was 59.2 (sd 16.4) %. Knowledge deficits relating to the impact of macronutrients/foods on blood glucose and lipids were identified. Lower diabetes-related nutrition knowledge was associated with lower intakes of sugar (10.8 (sd 4.7) v. 13.7 (sd 4.6) % for lower dietary knowledge score v. higher dietary knowledge score, P< 0.001), non-milk sugar (9.1 (sd 4.8) v. 12.1 (sd 4.7) % for lower dietary knowledge score v. higher dietary knowledge score, P< 0.001) and fruit/vegetables (230.8 (sd 175.1) v. 322.8 (sd 179.7) g for lower dietary knowledge score v. higher dietary knowledge score, P< 0.001), and higher dietary glycaemic index (GI) (61.4 (sd 4.5) v. 58.4 (sd 4.6) for lower dietary knowledge score v. higher dietary knowledge score, P< 0.002). The majority of the participants were dissatisfied with their weight. Sugar was the most frequently checked nutrient on food labels (59%), with only 12.1% checking foods for their energy content. Significant knowledge and skill deficits, associated with the impact of macronutrients/foods on metabolic parameters and food label use, were found. Lower diabetes-related nutrition knowledge was associated with lower sugar and fruit/vegetable intake and higher dietary GI. Dietary education, integrated throughout the lifespan of T2DM, may improve nutrition knowledge and skills and promote more balanced approaches to dietary self-management of T2DM.

BACKGROUND: This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. SUMMARY: It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. KEY MESSAGES: People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay.

BACKGROUND: High continuity of care is prized by users of mental health services and lauded in health policy. It is especially important in long-term conditions like schizophrenia. However, it is not routinely measured, and therefore not often evaluated when service reorganisations take place. In addition, the impact of continuity of care on clinical outcomes is unclear.AimsWe set out to examine continuity of care in people with schizophrenia, and to relate this to demographic variables and clinical outcomes. METHOD: Pseudoanonymised community data from 5552 individuals with schizophrenia presenting over 11 years were examined for changes in continuity of care using the numbers of community teams caring for them and the Modified Modified Continuity Index (MMCI). These and demographic variables were related to clinical outcomes measured with the Health of the Nation Outcome Scales (HoNOS). Data were analysed using generalised estimating equations and multivariate marginal models. RESULTS: There was a significant decline in MMCI and significant worsening of HoNOS total scores over 11 years. Higher (worse) HoNOS scores were significantly and independently related to older age, later years and both lower MMCI and more teams caring for the individual in each year. Most HoNOS scales contributed to the higher total scores. CONCLUSIONS: There is evidence of declining continuity of care in this 11-year study of people with schizophrenia, and of an independent effect of this on worse clinical outcomes. We suggest that this is related to reorganisation of services.Declaration of interestNone.

BACKGROUND: Adjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin's place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication. OBJECTIVE: To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology. METHODS: A list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be 'adopted or adapted' from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008-2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. FINDINGS: We confirmed that no published guideline-of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs. CONCLUSION: All 11 recommendations and 7 supporting good practice developed here were formulated de novo. CLINICAL IMPLICATIONS: These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.

CONTEXT: Dysfunctional adipose tissue has been proposed as a key pathological process linking obesity and metabolic disease. Preadipocyte factor-1 (Pref-1) has been shown to inhibit differentiation in adipocyte precursor cells and could thereby play a role in determining adipocyte size, adipose tissue functioning, and metabolic profile in obese individuals. OBJECTIVE: We hypothesized that adipose tissue from metabolically healthy obese (MHO) and matched metabolically unhealthy obese individuals would demonstrate distinct differences in relation to Pref-1 expression, adipocyte size, and inflammatory markers. DESIGN, SETTING, AND PATIENTS: This was a cross-sectional study, investigating obese patients undergoing bariatric surgery at a tertiary referral centre. Patients included 12 MHO and 17 age- and body mass index-matched metabolically unhealthy obese individuals. MAIN OUTCOME MEASURES: Pref-1, monocyte chemotactic protein-1, TNF-α, granulocyte colony-stimulating factor, IL-6, and adiponectin levels, macrophage numbers, and adipocyte size were measured in omental and subcutaneous adipose tissue. RESULTS: The MHO group had a lower level of Pref-1 (per 1000 adipocytes) in both subcutaneous [160 (136-177) versus 194 (153-355); P < 0.05] and omental adipose tissue [102 (32-175) versus 194 (100-350); P < 0.005]. This was associated with lower numbers of macrophages, lower levels of TNF-α, monocyte chemotactic protein-1, and granulocyte colony-stimulating factor, and higher levels of adiponectin. Omental Pref-1 showed strong correlations with adipocyte size (r = 0.67, P < 0.0005) and metabolic and adipokine parameters, including percent fatty liver (r = 0.62, P < 0.005), fasting glucose (r = 0.68, P < 0.0005), triglyceride (r = 0.60, P < 0.005), high-density lipoprotein cholesterol (r = -0.46, P < 0.05), and adiponectin (r = -0.71, P < 0.05). CONCLUSION: Adipose tissue in MHO individuals had lower levels of Pref-1, a known inhibitor of preadipocyte differentiation, and a more favorable inflammatory profile. These factors may be key to protecting this subgroup of obese individuals from the adverse metabolic profile associated with excess adiposity.

We investigated if the magnitude of the type 2 diabetes (T2D)-induced impairments in peak oxygen uptake (V̇o2) and V̇o2 kinetics was affected by age. Thirty-three men with T2D (15 middle-aged, 18 older), and 21 nondiabetic (ND) men (11 middle-aged, 10 older) matched by age were recruited. Participants completed four 6-min bouts of constant-load cycling at 80% ventilatory threshold for the determination of V̇o2 kinetics. Cardiac output (inert-gas rebreathing) was recorded at rest and 30 and 240 s during two additional bouts. Peak V̇o2 (determined from a separate graded test) was significantly (P < 0.05) reduced in middle-aged and older men with T2D compared with their respective ND counterparts (middle-aged, 3.2 ± 0.5 vs. 2.5 ± 0.5 l/min; older, 2.7 ± 0.4 vs. 2.4 ± 0.4 l/min), and the magnitude of these impairments was not affected by age. However, the time constant of phase II of the V̇o2 response was only slowed (P < 0.05) in middle-aged men with T2D compared with healthy counterparts, whereas it was similar among older men with and without T2D (middle-aged, 26.8 ± 9.3 vs. 41.6 ± 12.1 s; older, 40.5 ± 7.8 vs. 41.1 ± 8.5 s). Similarly, the "gains" in systemic vascular conductance (estimated from the slope between cardiac output and mean arterial pressure responses) were lower (P < 0.05) in middle-aged men with T2D than ND controls, but similar between the older groups. The results suggest that the mechanisms by which T2D induces significant reductions in peak exercise performance are linked to a slower dynamic response of V̇o2 and reduced systemic vascular conductance responses in middle-aged men, whereas this is not the case in older men.

In the past few years, there have been advances in the treatment of neuroendocrine tumours (NETs) and improvements in our understanding of NET biology. However, the benefits to patients have been relatively modest and much remains yet to be done. The 'Hallmarks of Cancer', as defined by Hanahan and Weinberg, provide a conceptual framework for understanding the aberrations that underlie tumourigenesis and to help identify potential targets for therapy. In this study, our objective is to review the major molecular characteristics of NETs, based on the recently modified 'Hallmarks of Cancer', and highlight areas that require further research.

The aim of this study was to compare the attitudes of elderly patients and their relatives towards telling the truth about cancer. 120 patients were asked if they would wish to be told about bad news, such as cancer, which might emerge during the admission. Matched relatives were asked if such information should be disclosed to the patient. Of the 120 patients, 99 (83%) wanted to be told the truth; 66 relatives (55%) relatives wanted their next of kin informed. There was agreement in 73 (61%) pairs. The kappa statistic was 0.16 (95% confidence interval -0.03 to 0.35), which indicates poor agreement. We conclude that most elderly people wish to be informed of a diagnosis of cancer. Patient preferences cannot be predicted by talking to relatives.

CONTEXT: Tissue cortisol exposure is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). 11β-HSD1 in vivo, acts as an oxoreductase converting inactive cortisone to active cortisol. We hypothesized that 11β-HSD1 activity is dysregulated in obesity and alters following bariatric surgery induced weight loss in different tissues. METHODS: We recruited 21 patients prior to undergoing bariatric surgery and performed cortisol generation profiles (following oral cortisone administration), urinary corticosteroid metabolite analysis, adipose tissue microdialysis, and tissue gene expression before and after weight loss, following bariatric surgery. Archived tissue samples from 20 previous bariatric surgery patients were also used for tissue gene expression studies. RESULTS: Gene expression showed a positive correlation with 11β-HSD1 and BMI in omental adipose tissue (OM) (r = +0.52, P = .0001) but not sc adipose tissue (r = +0.28, P = .17). 11β-HSD1 expression in liver negatively correlated with body mass index (BMI) (r = -0.37, P = .04). 11β-HSD1 expression in sc adipose tissue was significantly reduced after weight loss (0.41 ± 0.28 vs 0.17 ± 0.1 arbitrary units, P = .02). Following weight loss, serum cortisol generation increased during a cortisol generation profile (area under the curve 26 768 ± 16 880 vs 47 579 ± 16 086 nmol/L/minute, P ≤ .0001.) Urinary corticosteroid metabolites demonstrated a significant reduction in total cortisol metabolites after bariatric surgery (15 224 ± 6595 vs 8814 ± 4824 μg/24 h, P = .01). Microdialysis of sc adipose tissue showed a threefold reduction in cortisol/cortisone ratio after weight loss. CONCLUSIONS: This study highlights the differences in tissue specific regulation of cortisol metabolism in obesity and after weight loss. Following bariatric surgery hepatic 11β-HSD1 activity increases, sc adipose tissue 11β-HSD1 activity is reduced and total urinary cortisol metabolites are reduced indicating a possible reduction in hypothalamic pituitary adrenal axis drive. 11β-HSD1 expression correlates positively with BMI in omental adipose tissue and negatively within hepatic tissue. 11β-HSD1 expression is reduced in sc adipose tissue after weight loss.

BACKGROUND: Neuromuscular weakness, a frequent complication of prolonged bed rest and critical illness, is associated with morbidity and mortality. Mobilisation physiotherapy has widespread application in patients hospitalised with non-critical illness. OBJECTIVES: We reviewed the literature to evaluate the worldwide availability of mobilisation therapy in intensive care units and the role of mobilisation therapy in patients requiring medical or surgical high dependency or intensive care. METHODS: We searched PubMed (1980 to August 2009) using the MeSH terms "physiotherapy" and "intensive care". Additional keyword search terms, "mobilisation", "mobilization", and "fast-track", were used. In addition, we examined reference lists in recent studies and reviews. RESULTS: Routine mobilisation physiotherapy is least likely to be available in ICUs in the United States. Early mobilisation is appropriate for patients with pulmonary thromboembolic disease, community-acquired pneumonia and in elderly hospitalised patients. Although fast-track cardiac and noncardiac surgery with early ambulation is safe and reduces hospital length of stay, it does not alter postoperative mortality. Up to 25% of patients can be safely mobilised within 72 hours of ICU admission. This therapy may reduce hospital and ICU length of stay, shorten duration of mechanical ventilation, and improve muscle strength and functional independence scores. Pooled data show a nonsignificant mortality benefit in favour of early mobilisation (odds ratio, 0.77; 95% CI, 0.49-1.21). CONCLUSIONS: The data in support of mobilisation therapy for perioperative and critically ill patients, while of a low level of evidence, are substantial. This justifies a paradigm shift in attitudes towards physiotherapy and the prevention of critical illness weakness.