Long-term weight loss effects on all cause mortality in overweight/obese populations

This systematic review assesses the long-term effectiveness of weight loss on all cause mortality in overweight/obese people. Medline, Embase and Cinahl were searched (1966–2005). Cohort studies and trials on participants with Body Mass Index ¡Ý25 kg/m2, with weight change and mortality with ¡Ý 2 years follow-up were included finally identifying 11 papers based on 8 studies. There may be gender differences in the benefits for all cause mortality. The impact of weight loss in men on mortality was not clear with some studies indicating weight loss to be detrimental, while a recent cohort study showed benefits, if it were a personal decision. Other studies with no gender separation had similarly mixed results. However, one study indicated that overweight/obese women with obesity related illness, who lost weight intentionally within one year, had significantly reduced mortality rates of 19% -25%. In contrast, studies of overweight/obese diabetics irrespective of gender, showed significant benefit of intentional weight loss on mortality in a metaanalysis, HR=0.75(0.67- 0.83). There is some evidence that intentional weight loss has long-term benefits on all cause mortality for women and more so for diabetics. Long-term effects especially for men are not clear and need further investigation.National Health Service (NHS) R&D Health Technology Assessment Board

Calcium supplements and cancer risk : a meta-analysis of randomised controlled trials

Peer reviewedPublisher PD

Effect of calcium supplements on risk of myocardial infarction and cardiovascular events : meta-analysis

Peer reviewedPublisher PD

Diffuse intestinal T-cell lymphosarcoma in a yellow-naped Amazon parrot (Amazona ochrocephala auropalliata)

A 10-year-old, intact, female yellow-naped Amazon parrot was examined because of anemia, lymphocytic leukocytosis, regurgitation, and weight loss. A positive fecal occult blood and monoclonal globulinopathy were present. A distended proventriculus and diffusely thickened loops of small intestine with irregular luminal surfaces were identified with contrast radiography and contrast computed tomography. A micro positron emission tomography scan was performed with (18)F-fluorodeoxyglucose. Diffuse intestinal T-cell lymphosarcoma was diagnosed based on histopathology and immunohistochemistry of full thickness small intestinal biopsies. The patient was treated with a multidrug chemotherapy protocol with little to no effect. Euthanasia was elected, and intestinal lymphosarcoma was confirmed on histopathology of necropsy intestinal samples; no other organs demonstrated neoplastic infiltration. To the authors\u27 knowledge, no reports are currently available detailing the clinical presentation or diagnosis of diffuse intestinal T-cell lymphosarcoma in any avian species

Factors Influencing the Participation of Older People in Clinical Trials : Data Analysis from the MAVIS Trial

Peer reviewedPostprin

Patterns of weight change after the diagnosis of type 2 diabetes in Scotland and their relationship with glycaemic control, mortality and cardiovascular outcomes:a retrospective cohort study

OBJECTIVES: To determine weight change patterns in Scottish patients 2 years after diagnosis of type 2 diabetes and to examine these in association with medium-term glycaemic, mortality and cardiovascular outcomes. SETTING: Using a retrospective cohort design, ethical approval was obtained to link the Scottish diabetes care database to hospital admission and mortality records. PARTICIPANTS: 29 316 overweight/obese patients with incident diabetes diagnosed between 2002 and 2006 were identified with relevant information for ≥2 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Weight records over time provided intrapatient weight change and variation and glycated haemoglobin (HbA1c) gave measures of glycaemic control. These characteristics and demographic variables at diagnosis were linked with notifications of death (2-5 years after diagnosis) and cardiovascular events (0-5 year after diagnosis). RESULTS: By 2 years, 36% of patients had lost ≥2.5% of their weight. Increasing age, being female and a higher body mass index at diagnosis were associated with larger proportions of weight lost (p<0.001). Multivariable modelling showed that inadequate glycaemic control at 2 years was associated with being younger at baseline, being male, having lower levels of obesity at diagnosis, gaining weight or being weight stable with weight change variability, and starting antidiabetic medication. While weight change itself was not related to mortality or cardiovascular outcomes, major weight variability was independently associated with poorer survival and increased cardiovascular outcome risks, as was deprivation. CONCLUSIONS: Our results suggest that weight loss or being weight stable with little weight variability early after diabetes diagnosis, are associated with better glycaemic control and we identified groups less able to lose weight. With respect to mortality and cardiovascular outcomes, although weight change at 2 years was a weak predictor, major weight variability appeared to be the more relevant factor

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients

Background: Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design: 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. Discussion: To date more than 285 patients have been recruited to the trial from 10 sites in Scotland. Recruitment is due to finish in August 2008 with a further six months follow up. We expect to report the results of the trial in summer 2009. Trial registration: This trial is registered with the International Standard Randomised Controlled Trial Number system. ISRCTN87144826Not peer reviewedPublisher PD

Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. Areas covered: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Expert opinion: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis