The feasibility and acceptability of assessing and managing sarcopenia and frailty among older people with upper limb fracture.

BACKGROUND: sarcopenia and frailty are associated with increased risk of falls and fractures. This study evaluated the feasibility of assessing sarcopenia and frailty among older people attending fracture clinics. METHODS: patients aged 65+ years with an arm fracture attending fracture clinics in one UK city were recruited. Sarcopenia was assessed using gait speed, grip strength, skeletal muscle mass index SMI, SARC-F questionnaire and the European Working Group on Sarcopenia in Older People (EWGSOP) I and II criteria. Frailty was assessed using Fried Frailty Phenotype (FFP), FRAIL scale, PRISMA-7, electronic Frailty Index (e-FI), Clinical Frailty Score (CFS) and Study of Osteoporotic Fracture. The sensitivity and specificity of each tool was calculated against the EWGSOP II criteria (sarcopenia) and FFP (frailty). Patients identified to have either condition were referred for Comprehensive Geriatric Assessment (CGA). Interviews with 13 patients and nine staff explored the acceptability of this process. RESULTS: hundred patients (Mean age 75 years) were recruited. Most sarcopenia and frailty assessments were quick with complete data collection and were acceptable to patients and staff. Sarcopenia was identified among 4-39% participants depending on the tool and frailty among 9-25%. Both conditions were more common among men than women with all tools. The SARC-F and PRISMA-7 had the best sensitivity (100 and 93%, respectively) and specificity (96 and 87%). CGA among 80% of referred participants led to three interventions per participant (e.g. medication changes and investigations). CONCLUSION: SARC-F and PRISMA-7 are recommended for use in fracture clinics to screen for sarcopenia and frailty.

Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care.

BACKGROUND: There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial. METHODS: This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures. RESULTS: All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients. CONCLUSIONS: This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care, and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context. TRIAL REGISTRATION: Current Controlled Trials ISRCTN31685626.

Microbial epidemiology and carriage studies for the evaluation of vaccines.

Respiratory tract infections are responsible for over 2.8 million deaths per year worldwide. Colonization is the first step in the process of microbes occupying the respiratory tract, which may lead to subsequent infection. Carriage, in contrast, is defined as the occupation of microbial species in the respiratory tract. The duration of carriage may be affected by host immunity, the composition and interactions between members of the microbial community, and the characteristics of colonizing bacteria, including physiology associated with being present in a bacterial biofilm. Numerous vaccines have been implemented to control infections caused by bacteria that can colonize and be subsequently carried. Such vaccines are often species-specific and may target a limited number of strains thereby creating a vacant niche in the upper respiratory tract. Epidemiological changes of bacteria found in both carriage and disease have therefore been widely reported, since the vacant niche is filled by other strains or species. In this review, we discuss the use of carriage-prevalence studies in vaccine evaluation and argue that such studies are essential for (1) examining the epidemiology of carriage before and after the introduction of new vaccines, (2) understanding the dynamics of the respiratory tract flora and (3) identifying the disease potential of emerging strains. In an era of increasing antibiotic resistance, bacterial carriage-prevalence studies are essential for monitoring the impact of vaccination programmes.

Issues with using baseline in last observation carried forward analysis.

The topic of this paper was prompted by a study for which one of us was the statistician. It was submitted to Annals of Internal Medicine. The paper had positive reviewer comment; however, the statistical reviewer stated that for the analysis to be acceptable for publication, the missing data had to be accounted for in the analysis through the use of baseline in a last observation carried forward imputation. We discuss the issues associated with this form of imputation and recommend that it should not be undertaken as a primary analysis.

Ecology and diversity in upper respiratory tract microbial population structures from a cross-sectional community swabbing study.

PURPOSE: Respiratory tract infections (RTIs) are responsible for over 2.8 million deaths per year worldwide with pathobiont carriage a required precursor to infection. We sought to determine carriage epidemiology for both bacterial and viral respiratory pathogens as part of a large population-based cross-sectional carriage study. METHODOLOGY: Nose self-swab samples were collected in two separate time-points, May to August 2012 (late spring/summer) and February to April 2013 (winter/early spring). The presence of six bacterial species: S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus, P. aeruginosa and N. meningitidis in addition to respiratory syncytial virus, influenza viruses A and B, rhinovirus/enterovirus, coronavirus, parainfluenza viruses 1-3 and adenovirus was determined using culture and PCR methods.Results/Key findings. Carriage was shown to vary with age, recent RTI and the presence of other species. Spatial structures of microbial communities were more disordered in the 0-4 age group and those with recent RTI. Species frequency distributions were flatter than random expectation in young individuals (X2=20.42, P=0.002), indicating spatial clumping of species consistent with facilitative relationships. Deviations from a neutral model of ecological niches were observed in summer samples and from older individuals but not in the winter or younger individuals (0-4 years), suggesting the presence of seasonal and age-dependent niche processes in respiratory community assembly. CONCLUSION: The application of epidemiological methods and ecological theory to respiratory tract samples has yielded novel insights into the factors that drive microbial community composition.

The nuclear BAG-1 isoform, BAG-1L, enhances oestrogen-dependent transcription.

BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets including heat-shock proteins and some nuclear hormone receptors. BAG-1 exists as three major isoforms, BAG-1L, BAG-1M and BAG-1S. BAG-1L contains a nuclear localization signal, which is not present in the other isoforms, and is predominantly localized in the cell nucleus. Here we have investigated the effects of BAG-1 on function of the oestrogen receptor (ER), a key growth control molecule and target for hormonal therapy in breast cancer. We demonstrate that BAG-1L, but not BAG-1S or BAG-1M, increased oestrogen-dependent transcription in breast cancer cells. BAG-1L interacted with and stimulated the activity of both ER alpha and beta. Although BAG-1L and ERs colocalize to the nucleus, fusing BAG-1S to an heterologous nuclear localization sequence was not sufficient to stimulate transcription. Consistent with an important effect on receptor function, nuclear BAG-1 expression in breast cancers was associated with expression of the progesterone receptor, a transcriptional target of ERalpha, and was associated with improved survival in patients treated with hormonal therapy. These data suggest that BAG-1L is an important determinant of ER function in vitro and in human breast cancer.

Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease.

BACKGROUND: Crohn disease (CD) is associated with osteoporosis and other extraintestinal manifestations that might be mediated by cytokines from circulating (peripheral blood) mononuclear cells (PBMCs). Fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduces disease activity in patients with CD with raised laboratory markers of inflammation and in healthy subjects alters PBMC function. OBJECTIVE: We investigated the effect of fish oil plus antioxidants on cytokine production by PBMCs from patients with CD with raised C-reactive protein concentrations (>/=6.9 mg/L) or erythrocyte sedimentation rates (>/=18 mm/h). DESIGN: A randomized placebo-controlled trial of fish oil (2.7 g EPA and DHA/d; n = 31) or placebo (olive oil; n = 31) for 24 wk was conducted in patients with CD. The fish-oil group additionally received an antioxidant preparation (vitamins A, C, and E and selenium). Exclusion criteria included corticosteroid use. Fatty acid composition was measured by gas chromatography. Production of tumor necrosis factor alpha, interferon gamma (IFN-gamma), and prostaglandin E(2) (PGE(2)) was measured by enzyme-linked immunosorbent assays after stimulation with mitogen and endotoxin (lipopolysaccharide). RESULTS: Fish-oil plus antioxidant dietary supplementation was associated with higher EPA and DHA incorporation into PBMCs (P < 0.001) and lower arachidonic acid (P = 0.006) and lower production of IFN-gamma by mitogen-stimulated PBMCs (P = 0.012) and of PGE(2) by lipopolysaccharide-stimulated PBMCs (P = 0.047). CONCLUSION: Dietary supplementation with fish oil plus antioxidants is associated with modified PBMC composition and lower production of PGE(2) and IFN-gamma by circulating monocytes or macrophages. The response of extraintestinal manifestations of CD should be investigated in a randomized controlled trial.

Suicide in schizophrenia: a retrospective case-control study of 51 suicides.

The aim of this study was to identify factors associated with suicide in patients with schizophrenia who required inpatient admission and to compare these factors with the risk profile of patients with other diagnoses also requiring inpatient care. A retrospective, matched case-control study of 51 patients with schizophrenia requiring psychiatric inpatient care was undertaken. A priori specified risk factors were investigated within the schizophrenia group and compared with those of patients with other psychiatric diagnoses. The results show that previous suicide attempts are associated with an increased risk of suicide across all diagnoses. The presence of depressive symptoms and involvement of police with the index admission become more significant factors in patients with schizophrenia, compared to those with other diagnoses. Supportive mental health accommodation is associated with a reduced risk of suicide. Suicide of individuals is difficult to predict in patients with schizophrenia. Young men appear particularly vulnerable at times of inpatient care. Depressive symptoms and previous suicide attempts are significant risk factors.

Peripheral blood mononuclear cell fatty acid composition and inflammatory mediator production in adult Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with nutritional deficiencies, altered plasma concentrations of polyunsaturated fatty acids (PUFA) and an anti-inflammatory response to fish oil that contains n-3 PUFA. This suggests that, in CD, immune cells may have altered n-3 PUFA composition with functional consequences. The aim of this study is to investigate n-3 and n-6 PUFA composition and synthetic function of peripheral blood mononuclear cells (PBMC) in the basal state. METHODS: A case control study of 52 adult CD patients and healthy, age- and sex-matched controls. Composition of PBMC and plasma phospholipids were measured by gas chromatography and production of tumour necrosis factor-alpha, prostaglandin E2 (PGE2) and interferon-gamma (IFN-gamma) by PBMC were measured by ELISA. RESULTS: CD was associated with higher concentrations of eicosapentaenoic acid and other n-3 PUFA, and lower arachidonic acid (AA) (n-6 PUFA) in PBMC. This was not explained by differences in dietary fat intake. Lower rates of production of PGE2 and IFN-gamma by PBMC were noted in quiescent and active CD, respectively, compared to controls. CONCLUSIONS: CD is associated with a greater availability, and not a deficiency, of n-3 PUFA in PBMC, but lower concentrations of AA, and lower rates of production of PGE2 and IFN-gamma, compared to healthy controls.

Interrater reliability of Engel, International League Against Epilepsy, and McHugh seizure outcome classifications following vagus nerve stimulator implantation.

OBJECT: Interrater reliability as measured by the kappa (κ) statistic is a widely used and valuable tool to measure the robustness of a scoring system. Seizure frequency reduction is a central outcome measure following vagus nerve stimulation (VNS). A specific VNS scoring system has been proposed by McHugh, but its interrater reliability has not been tested. The authors assessed its interrater reliability and compared it with that of the Engel and International League Against Epilepsy (ILAE) systems. METHODS: Using the Engel, ILAE, and McHugh scoring systems, 3 observers independently rated the medical records of children who had undergone vagus nerve stimulator implantation between January 2001 and April 2011 at the Southampton University Hospital. The interrater agreements were then calculated using the κ statistic. RESULTS: Interrater reliability for the McHugh scale (κ0.693) was very good and was superior to those of the Engel (κ0.464) and ILAE (κ0.491) systems for assessing outcome in patients undergoing VNS. CONCLUSIONS: The authors recommend considering the McHugh scoring system when assessing outcomes following VNS.

Very good inter-rater reliability of Engel and ILAE epilepsy surgery outcome classifications in a series of 76 patients.

The inter-rater reliability, expressed as kappa score, k, of the Engel and International League Against Epilepsy (ILAE) classifications of epilepsy surgery seizure outcome has not previously been evaluated. In a consecutive series of 76 patients (40 male; 25 children), 75 undergoing resective and 1 disconnective surgery at a mean age of 27.5 years (13 months-62 years), one observer classified 88% (n=67) and a second observer classified 87% (n=66) of patients as either Engel I or II (free from or rare disabling seizures) after a median follow up of 36 months (range 12-92 months); comparably, both observers classified 84% (n=64) as ILAE 1-3. Correlation for Engel versus ILAE for observer 1 was 0.933 (p<.0005) and for observer 2 was 0.931 (p<.0005). Both ILAE (k 0.81, 95% confidence intervals 0.69, 0.91) and Engel (k 0.77, 95% CI 0.65, 0.87) classifications have very acceptable inter-rater reliability as well as significant correlation.

Simple anatomical information improves the accuracy of locating specific spinous processes during manual examination of the low back.

The objective of the study was to test whether a teaching protocol including simple anatomical information on the surface anatomy of spinous processes, improves physiotherapy students' ability to accurately locate selected thoracic and lumbar spinal segments - T12 and L3. First year physiotherapy students were allocated to Group 1 (n=35) and Group 2 (n=34). Both groups were taught to identify spinous processes by counting up from the sacrum, but Group 2 received supplementary anatomical information on the shapes and vertical length of the tips of L5 to T12 spinous processes. The spinous processes of L3 and T12 were located by two experienced physiotherapists and marked on a model using an invisible skin marker. Volunteer students were asked to locate these spinous processes and accuracy was confirmed using an ultraviolet lamp. Students with supplementary anatomical information (Group 2) were significantly better at locating T12 (difference in proportions 36% (95% confidence interval 14 to 51%)) and both T12 and L3 (difference in proportions 33% (11 to 48%)). Group 2 students were also better than Group 1 students at locating L3 (difference in proportions 28% (4 to 48%)), but the difference was not significant. Including simple anatomical information when teaching manual examination skills improved the accuracy of locating specific low back spinal levels.

Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database.

OBJECTIVE: To explore the reasons behind the recent increase in antidepressant prescribing in the United Kingdom. Design Detailed retrospective analysis of data on general practitioner consultations and antidepressant prescribing. Data source Data were obtained from the general practice research database, which contains linked anonymised records of over 3 million patients registered in the UK. Data were extracted for all new incident cases of depression between 1993 and 2005. Review methods Detailed analysis of general practitioner consultations and antidepressant prescribing was restricted to 170 practices that were contributing data for the full duration of the study. RESULTS: In total, 189 851 people within the general practice research database experienced their first episode of depression between 1993 and 2005, of whom 150,825 (79.4%) received a prescription for antidepressants in the first year of diagnosis. This proportion remained stable across all the years examined. The incidence of new cases of depression rose in young women but fell slightly in other groups such that overall incidence increased then declined slightly (men: 7.83 cases per 1000 patient years in 1993 to 5.97 in 2005, women: 15.83 cases per 1000 patient years in 1993 to 10.06 in 2005). Antidepressant prescribing nearly doubled during the study period-the average number of prescriptions issued per patient increased from 2.8 in 1993 to 5.6 in 2004. The majority of antidepressant prescriptions were given as long term treatment or as intermittent treatment to patients with multiple episodes of depression. CONCLUSIONS: The rise in antidepressant prescribing is mainly explained by small changes in the proportion of patients receiving long term treatment. Previous clinical guidelines have focused on antidepressant initiation and appropriate targeting of antidepressants. To address the costly rise in antidepressant prescribing, future research and guidance needs to concentrate on appropriate long term prescribing for depression and regular review of medication.

Self-rated activity levels and longevity: evidence from a 20 year longitudinal study.

The study reports on factors predicting the longevity of 328 people over the age of 65 drawn from an English city and followed over 20 years. Both the reported activities score and the individual's comparative evaluation of their own level of activity independently reduced the risk of death, even when health and cognitive status were taken into account. The analysis has provided a strong test of the relevance of measures of reported activity and measures of self-perception to longevity. The study confirms the important predictive role of reported activity levels even when detailed health measures are taken into account. But in addition personal perception of one's own relative level of activity, and to a lesser extent subjective assessment of health, also predicted longevity.

High-dose fish oil and antioxidants in Crohn's disease and the response of bone turnover: a randomised controlled trial.

Crohn's disease is associated with altered bone turnover that may be influenced by nutritional status, the systemic inflammatory response, cytokine production by circulating (peripheral blood) mononuclear cells (PBMC) and antioxidant micronutrient intake. High-dose fish oil is associated with reductions in disease relapse and inflammatory markers, and modulates PBMC function. The effect of fish oil plus antioxidants on bone turnover and PBMC function (the production of interferon-gamma and prostaglandin E2) in Crohn's disease was investigated in a randomised-controlled trial. Patients with currently or recently raised biochemical markers of inflammation (C-reactive protein > or = 6.9 mg/l or erythrocyte sedimentation rate > or =18 mm/h) received fish oil (providing 2.7 g/d EPA and DHA) and antioxidants (vitamins A, C and E, and Se) (n 31) or placebo (n 30) for 24 weeks. Bone turnover was assessed by measuring the concentrations of urinary deoxypyridinoline (bone resorption) and serum osteocalcin (bone formation). Fish oil plus antioxidants were associated with increases in EPA, DHA Se in plasma (all P < 0.01), and with a reduction in interferon-gamma production by mitogen-stimulated PBMC, which demonstrated a negative correlation with deoxypyridinoline/creatinine:osteocalcin ratio (r - 0.33, P = 0.009). There were no differences between the groups at 24 weeks in the response of deoxypyridinoline or osteocalcin or their ratio, or in nutritional status. Dietary supplementation in Crohn's disease with high intakes of EPA and DHA, as fish oil, plus antioxidants was associated with a modulated production of interferon-gamma by PBMC but not altered indices of bone turnover.

Patient characteristics and outcomes of cardiac rehabilitation.

PURPOSE: To investigate changes in physical fitness and psychological characteristics of patients after cardiac rehabilitation, and to assess predictors of defaulting from the program. METHODS: A prospective study of 1902 consecutive patients admitted to a community-based, hospital-linked cardiac rehabilitation program was conducted over a period of 6 years and 7 months. The cardiac rehabilitation program centered on a 2-to 6-month circuit training course with education, stress management, relaxation, and risk factor monitoring. Before and after the program, measures of physical fitness and of hospital anxiety and depression were performed. RESULTS: The course was completed by 1443 patients (76%), with 240 patients (13%) defaulting. For those who completed the course, peak oxygen consumption per minute increased by 3.2 mL/min/kg (95% confidence interval [CI], 3.1-3.4) or 19% (95% CI, 17.7%-20.3%). According to the hospital anxiety and depression scores, anxiety fell by 1.1 (95% CI, -1.3 to -0.98) and depression by 1.3 (95% CI, -1.4 to -1.2). The main predictors of defaulting were depression (patients with depression were twice as likely to default as nondepressed patients) and diagnosis (patients who had experienced angina or percutaneous transluminal coronary angioplasty were twice as likely to default as those who had experienced infarct or coronary artery bypass graft). CONCLUSIONS: The identification of depressed coronary patients known to be at increased risk should be a priority for cardiac rehabilitation coordinators. Every effort should be made to keep them in the cardiac rehabilitation program.