In-home dementia caregiving is associated with greater psychological burden and poorer mental health than out-of-home caregiving: a cross-sectional study.

INTRODUCTION: Caregivers who live with a person with dementia who receives care, compared with those who live elsewhere, are often considered to experience greater levels of psychological and affective burden. The evidence for this is, however, only limited to studies employing small sample sizes and that failed to examine caregivers' psychological wellbeing. We address these issues in a large cohort of dementia caregivers. METHODS: We conducted a cross-sectional study comparing caregivers living with a dementia care recipient (n = 240) to caregivers living elsewhere (n = 255) on caregivers' burden, anxiety, and depression. RESULTS: We found that caregivers living with the care recipient relative to those living elsewhere showed significantly greater burden and depression, but we found no group difference in anxiety. CONCLUSIONS: Our study adds to the evidence by showing that cohabiting with a care recipient with dementia is associated with greater burden and poorer psychological wellbeing. Strategies aiming to improve caregivers' burden and psychological wellbeing should take account of caregivers' living arrangements.

Use of antibiotic and prevalence of antibiotic-associated diarrhoea in-patients with spinal cord injuries: a UK national spinal injury centre experience.

BACKGROUND: This was a retrospective audit, with the aims being to (1) record the use of antibiotics; (2) establish the prevalence of antibiotic-associated diarrhoea (AAD) and Clostridium difficile-associated diarrhoea (CDAD); and (3) assess if there was any seasonal variation in antibiotic use and incidence of AAD. METHODS: The study was performed at a single spinal cord injury (SCI) centre in the UK. Data were collected using a standardised questionnaire during October 2014 to June 2015. We define AAD as two or more watery stools of type 5, 6 or 7 (Bristol stool scale) over 24 h. RESULTS: Three-hundred-and-nineteen adults (mean age: 55.9 years, 29.2% female) with SCI (58.2% tetraplegia; 43.7% complete SCI) were included. Of 70 (21.9%) patients on antibiotics, the top three indications for antibiotics were urinary-tract infections, infected pressure ulcers and other skin infections. Seventeen of 78 (21.8%) developed AAD and three of 319 (0.94%) developed CDAD. AAD was more common in the summer season than in spring, autumn and winter (47.1%, 10.0%, 10.0%, 23.8%, P=0.025). AAD was associated with older adults greater than 65 years (70.6% vs 23.8%, P=0.007). Polypharmacy and the summer season were identified as independent predictors for AAD. CONCLUSION: This survey found that AAD is common in SCI patients and may be a risk factor for a poorer outcome and increased hospital costs. A multicentre study is underway to establish the incidence and risk factors for AAD.

Review of dietetic service provision and activity in spinal cord injury centres: a multicentre survey in the UK and Republic of Ireland.

OBJECTIVES: The present study was undertaken to review the service provision in spinal cord injury (SCI) centres (SCICs); to establish and compare how much time dietitians spend in direct and indirect contact with patients; and to document current nutritional screening practices. METHODS: All 12 SCICs in the United Kingdom and the Republic of Ireland were surveyed by a postal questionnaire in April 2014. Data collected included the number of whole-time-equivalent (WTE) staff available, whether a nutrition team was present and the use of nutrition screening tools. A work sampling tool was used to capture dietetic activity for a period of 1 week. RESULTS: Eight (66.7%) SCICs responded (390/531 of total SCI beds) and the average numbers of patients per WTE staff, including consultants, nurses, dietitians, physiotherapists, occupational therapists were recorded. Six out of eight SCICs used a validated nutritional screening tool. Thirty-two work sampling tools were analysed, revealing that spinal dietitians spend 39.1% of the working day in direct patient-related activities. Staffing levels varied and were below clinical recommendations in six out of eight SCICs. CONCLUSION: The resources allocated to nutritional care in SCICs appear to be varied and limited. This suggests malnutrition may continue to be under-recognised and under-treated. To address the complex nutritional needs of this special population group there is a clear need to establish staffing level for dietitians. Information collected from the present study could contribute to the supply analysis of a future workforce planning exercise in SCIC dietetic service.

Knowledge, attitudes and practices of medical staff towards obesity management in patients with spinal cord injuries: an International survey of four western European countries.

OBJECTIVE: To (1) examine the opinions of medical staff working in spinal cord injury (SCI) centres (SCICs); (2) evaluate their knowledge, attitudes and practices towards obesity prevention and management; (3) report the number of beds and dietitians available at each SCIC. METHODS: A 37-item questionnaire was sent to 23 SCICs in the UK, the Netherlands, Belgium and the Republic of Ireland between September 2012 and January 2013. RESULTS: Eighteen SCICs returned the questionnaires for analysis. All respondents stated that they had an interest in obesity treatment but only 2.3% of the respondents received training in obesity management. Sixty-one percent of staff did not consider body mass index (BMI) to be appropriate for use in SCI patients and subsequently less than half of the respondents use BMI routinely. The majority of respondents reported that they are confident in dealing with overweight (74.5%) and obese (66.1%) SCI adults, less than half (44.1%) are confident in treating overweight and obese SCI children. Respondents also indicated the need for nationally adopted guidelines and a lack of physical activity provision. There were 17.5 whole-time equivalent (WTE) dietitians recorded in 22 SCICs, equivalent to 47.8 beds per WTE dietitians (range 10-420). Non-UK SCIC dietitians are significantly better resourced than in UK SCICs (beds per WTE dietitian: 36 vs 124, P=0.035). CONCLUSION: Medical staff expressed the need to participate in obesity prevention and management. Appropriate training should be considered for all medical staff and the development of specific weight management guidelines and dietetic provision should be considered.

Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

Validation of the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) in patients with spinal cord injuries (SCIs).

OBJECTIVES: To validate the Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) in paediatric spinal cord injuries (SCIs) patients admitted to the tertiary SCI centre. METHODS: children's baseline clinical data, anthropometric measurements and STAMP score were assessed on admission. The validity of STAMP was assessed by (i) comparison with a full dietetic assessment (criterion validity); (ii) comparison with generic paediatric screening tools: the Paediatric Yorkhill Malnutrition Score (PYMS; concurrent validity); and (iii) completion of an additional STAMP to assess inter- and intra-rater reliability. The agreement was assessed using Cohen's κ-statistics. RESULTS: Fifty-one children were screened by STAMP. The prevalence of undernutrition risk was 58.8%. STAMP had moderate agreement with dietitian assessment (κ: 0.507) and a fair agreement with PYMS (κ: 0.314). The STAMP had substantial reliability (inter-rater reliability: κ: 0.752; intra-rater reliability: κ: 0.635). When compared with dietetic assessment as a reference standard, STAMP had a sensitivity of 83.3%, specificity of 66.7% and an overall agreement of 76.5%. CONCLUSION: The present study shows that undernutrition is common in children with SCI. The STAMP is an acceptable (valid and reliable) tool to identify paediatric SCI patients at risk of undernutrition.

Meal provision in a UK National Spinal Injury Centre: a qualitative audit of service users and stakeholders.

STUDY DESIGN: A single centre survey. OBJECTIVES: The objective of this study is to (1) assess patients' food intake and (2) measure satisfaction with current food provision, as judged by patients and by stakeholders (medical and nursing staff, managers and catering staff). METHODS: Standardised questionnaires were used to record food intake over a 24-h period, and to evaluate the quality, ordering, delivery and overall acceptability of food provided. RESULTS: The food intake of 67 patients with spinal cord injury (SCI) was recorded (64% response rate) and 166 evaluations (50% response rate) were returned. Twenty-nine patients (48%) consumed three full meals a day, 17 (26%) received oral nutritional supplements, 22 (34%) received vitamin/mineral supplements, and 23 (35%) required assistance to eat. Some patients and stakeholders expressed satisfaction with the current food provision: taste good: 25 versus 17% (for patients and stakeholders, respectively); appropriate texture: 22 versus 21%; appropriate temperature: 55 versus 72% (P = 0.002); well presented: 43 versus 28%; good choice: 49 versus 59%; received meal ordered: 65 versus 37% (P < 0.001); meal served on time: 71 versus 58%; and no interruption during mealtimes: 62 versus 46%. Principal component analyses of item scores identified three main factors (food quality, food presentation and food delivery (logistics). CONCLUSION: The present study identified some areas where there appeared to have been improvement in SCI hospital catering, but with much still to be achieved. Hospital-catering systems should be tailored to meet the demands of the different patient groups to optimise nutritional intake. Periodic quality control is essential to meet recommendations and patients' expectations.

A vesicular intermediate in the transport of hepatoma secretory proteins from the rough endoplasmic reticulum to the Golgi complex.

We have identified a vesicle fraction that contains alpha 1-antitrypsin and other human HepG2 hepatoma secretory proteins en route from the rough endoplasmic reticulum (RER) to the cis face of the Golgi complex. [35S]Methionine pulse-labeled cells were chased for various periods of time, and then a postnuclear supernatant fraction was resolved on a shallow sucrose-D2O gradient. This intermediate fraction has a density lighter than RER or Golgi vesicles. Most alpha 1-antitrypsin in this fraction (P1) bears N-linked oligosaccharides of composition similar to that of alpha 1-antitrypsin within the RER; mainly Man8GlcNac2 with lesser amounts of Man7GlcNac2 and Man9GlcNac2; this suggests that the protein has not yet reacted with alpha-mannosidase-I on the cis face of the Golgi complex. This light vesicle species is the first post-ER fraction to be filled by labeled alpha 1-antitrypsin after a short chase, and newly made secretory proteins enter this compartment in proportion to their rate of exit from the RER and their rate of secretion from the cells: alpha 1-antitrypsin and albumin faster than preC3 and alpha 1-antichymotrypsin, faster, in turn, then transferrin. Deoxynojirimycin, a drug that blocks removal of glucose residues from alpha 1-antitrypsin in the RER and blocks its intracellular maturation, also blocks its appearance in this intermediate compartment. Upon further chase of the cells, we detect sequential maturation of alpha 1-antitrypsin to two other intracellular forms: first, P2, a form that has the same gel mobility as P1 but that bears an endoglycosidase H-resistant oligosaccharide and is found in a compartment--probably the medial Golgi complex--of density higher than that of the intermediate that contains P1; and second, the mature sialylated form of alpha 1-antitrypsin.

A prospective evaluation assessing the effectiveness of the 'Dynamax' mandibular appliance in the management of obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) affects 4-6% of the middle-aged UK population and is responsible for significant partnership disharmony. Nasal CPAP therapy is effective but has poor compliance in less severe cases- bulky with poor portability and frequently deemed socially unacceptable. The 'Dynamax mandibular appliance (DMA) is a current treatment for Skeletal 11 malocclusion characterised by mandibular retrusion. It has the advantage of both maxillary expansion and mandibular advancement and is developed and tailored on an individual basis by orthodontic sculpture. These facilities are widely available in hospital-based orthodontic departments. For these reasons we have explored its use in the treatment of mild to moderate cases of OSAS. METHOD AND MATERIAL: 35 symptomatic patients (29 males) with mild to moderate OSAS, determined from sleep study analysis, had dental impressions taken and the 'Dynamax' appliance constructed. Following fitting and instructions for use, all patients were entered into the study. After two months, repeat overnight oximetry was undertaken for 16 patients and both an Epworth sleep score (ESS) and quality of life questionnaire completed. RESULTS: The mean age was 51 (range 29-71) years. The mean ESS pre-treatment was 12 (range 7-19) with a significant fall post-treatment by 7 (range 3-14) (p < 0.0001). Pre-treatment oximetry data confirmed typical tracings and patterns of OSAS with a mean low oxygen saturation (SaO2) of 83% (range 71-90%). Post-treatment oximetry was available in 16 patients and showed significant improvement in the number of hourly SaO2 desaturation dips and a mean increase of 4.7% in the lowest SaO2 recorded (p < 0.0001). Thirty (86%) patients found the appliance of 'great to moderate' benefit and 18 (60%) were able to tolerate it and be fully compliant within days. Of 10 patients who had previously experienced CPAP, 80% of them felt it was easier to tolerate the DA. Sixty-seven percent of these patients stated the appliance was more portable and acceptable to their bed partner. Twenty-one (70%) of bed partners reported softer and less frequent snoring. Ninety percent of the patients in this study wished to wear the DMA long-term. CONCLUSION: The DMA provides a satisfactory alternative therapy in the treatment of OSAS of'mild-moderate' severity. This oral device is conveniently small, readily portable and well tolerated by both patients and bed partners alike. It can be fashioned in orthodontic departments available in all district general hospitals and will enhance the provision and development of any local sleep service.

Use of antibiotics and the prevalence of antibiotic-associated diarrhoea in patients with spinal cord injuries: an international, multi-centre study.

BACKGROUND: Little is known about the use of antibiotics and the extent of antibiotic-associated diarrhoea (AAD) in patients with spinal cord injuries (SCIs). AIMS: To record the use of antibiotics, establish the prevalence of AAD and Clostridium difficile infection (CDI), and assess if there was any seasonal variation in antibiotic use and incidence of AAD in patients with SCIs. METHODS: A retrospective study was conducted in six European SCI centres between October 2014 and June 2015. AAD was defined as two or more watery stools (Bristol Stool Scale type 5, 6 or 7) over 24 h. FINDINGS: In total, 1267 adults (median age 54 years, 30.7% female) with SCIs (52.7% tetraplegia, 59% complete SCI) were included in this study. Among the 215 (17%) patients on antibiotics, the top three indications for antibiotics were urinary tract infections (UTIs), infected pressure ulcers and other skin infections. Thirty-two of these 215 (14.9%) patients developed AAD and two patients out of the total study population (2/1267; 0.16%) developed CDI. AAD was more common in summer than in spring, autumn or winter (30.3% vs 3.8%, 7.4% and 16.9%, respectively; P<0.01). AAD was associated with age ≥65 years, tetraplegia, higher body mass index, hypoalbuminaemia, polypharmacy, multiple antibiotic use and high-risk antibiotic use. Summer and winter seasons and male sex were identified as independent predictors for the development of AAD. CONCLUSION: This survey found that AAD is common in patients with SCIs, and UTI is the most common cause of infection. Summer and winter seasons and male sex are unique predictors for AAD. Both AAD and UTIs are potentially preventable; therefore, further work should focus on preventing the over-use of antibiotics, and developing strategies to improve hospital infection control measures.

Which factors are associated with quality of life in patients with Graves' orbitopathy presenting for orbital decompression surgery?

PURPOSE: Graves' orbitopathy (GO) is associated with changes in the appearance of the eyes and visual dysfunction. Patients report feeling socially isolated and unable to continue with day-to-day activities. This study aimed at investigating the demographic, clinical, and psychosocial factors associated with quality of life in patients presenting for orbital decompression surgery. METHODS: One-hundred and twenty-three adults with GO due for orbital decompression at Moorfields Eye Hospital London were recruited prospectively. Clinical measures including treatment history, exophthalmos, optic neuropathy, and diplopia were taken by an ophthalmologist. Participants completed psychosocial questionnaires, including the Graves' Ophthalmopathy Quality of Life Scale (GO-QOL), the Hospital Anxiety and Depression Scale, and the Derriford Appearance Scale. Hierarchical multiple regression analyses were used to identify predictors of quality of life. RESULTS: Higher levels of potential cases of clinical anxiety (37%) and depression (26%) were found in this study sample than in patients with other chronic diseases or facial disfigurements. A total of 55% of the variance in GO-QOL visual function scores was explained by the regression model; age, asymmetrical GO and depressed mood were significant unique contributors. In all, 75% of the variance in GO-QOL appearance scores was explained by the regression model; gender, appearance-related cognitions and depressed mood were significant unique contributors. CONCLUSION: Appearance-related quality of life and mood were particularly affected in this sample. Predominantly psychosocial characteristics were associated with quality of life. It is important when planning surgery for patients that clinicians be aware of factors that could potentially influence outcomes.

Changes in human plasma alpha-D-mannosidase activity during pregnancy.

There are significant and progressive increases in plasma acidic (pH optimum 4.2) and intermediate (pH optimum 5.6) alpha-mannosidase during pregnancy. The acidic alpha-mannosidase in plasma from pregnant women binds to concanavalin A and has the same apparent molecular weight as the acidic alpha-mannosidase in control plasma. The 2-3-fold increase in acidic alpha-mannosidase in pregnancy is due to an increase in the most negatively charged form of acidic alpha-mannosidase, B2, which is slightly more negatively charged than its counterpart in the control plasma. The intermediate alpha-mannosidase, which increases by approximately 50% during pregnancy, can be resolved by a combination of chromatography on concanavalin A and gel filtration into the same forms found in control plasma.

Plasma alpha-D-mannosidase in mucolipidosis II and mucolipidosis III.

There is a marked increase in the acidic alpha-D-mannosidase in the plasma of a patient with mucolipidosis II and of a patient with mucolipidosis III. A small proportion (3--4%) of this acidic alpha-D-mannosidase does not bind to concanavalin A-Sepharose, suggesting an alteration in the glycosylation and some of the enzyme in these disorders. A slight elevation in intermediate alpha-D-mannosidase was also demonstrated in these samples by using a differential assay for the acidic and intermediate alpha-D-mannosidase activities. A combination of chromatography on concanavalin A-Sepharose and Sephadex G-200 showed that intermediate alpha-D-mannosidase components I2 and I4, which account for approximately 80% of the intermediate activity in normal plasma, were also present in ML II and ML III plasma. The minor intermediate alpha-D-mannosidase components in normal plasma, I1 and I3 were either present in small amounts or not detected. These results suggest that a defect in intermediate alpha-D-mannosidase is unlikely to be the primary defect in these disorders.

Measurement of the alpha-mannosidase activities in human plasma by a differential assay.

A differential assay based on their difference in thermal stability has been used to measure the acidic and true intermediate alpha-mannosidases in the plasma of cntrols and individuals homozygous or heterozygous for mannosidosis. The intermediate activity was found to be independent of age, sex or mannosidosis genotype. The acidic alpha-mannosidase did not vary significantly with age or between sexes for groups of the same age. The concentrations of acidic and intermediate alpha-mannosidase showed a positive correlation for adults but not for children. The ratio of acidic to true intermediate alpha-mannosidase might therefore be a useful secondary test for the detection of adult heterozygotes for mannosidosis.

Transgenic expression of a variant of human tissue-type plasminogen activator in goat milk: purification and characterization of the recombinant enzyme.

A glycosylation variant of human tissue-type plasminogen activator (tPA) designated longer-acting tissue-type plasminogen activator (LAtPA) was extensively purified from the milk of a transgenic goat by a combination of acid fractionation, hydrophobic interaction chromatography and immunoaffinity chromatography. This scheme provided greater than 8,000-fold purification of the protein, a cumulative yield of 25% and purity greater than 98% as judged by SDS gel electrophoresis. SDS gel electrophoresis revealed that the transgenic enzyme was predominantly the "two chain" form of the protease. The specific activity of the purified transgenic protein, based on the average of the values obtained for three different preparations, was 610,000 U/mg as judged by amidolytic activity assay. This was approximately 84% of the value observed for the recombinant enzyme produced in mouse C127 cells. Analysis of the transgenic protein indicated that it had a significantly different carbohydrate composition from the recombinant enzyme produced in C127 cells. Molecular size analysis of the oligosaccharides from the transgenic and C127 cell-derived LAtPA preparations confirmed their differences and showed that the mouse cell-derived preparation contained larger, complex-type N-linked oligosaccharide structures than the material produced in goat mammary tissue.

Is undernutrition risk associated with an adverse clinical outcome in spinal cord-injured patients admitted to a spinal centre?

BACKGROUND/OBJECTIVES: To evaluate whether undernutrition risk measured using the Spinal Nutrition Screening Tool (SNST) and the Malnutrition Universal Screening Tool (MUST) is associated with worse clinical outcomes in respect of length of in-patient hospital stay (LOS) and mortality in the 12 months after admission to a spinal cord injuries (SCIs) centre. METHODS: A multicentre, prospective, cross-sectional observational study was conducted in four UK SCI centres (SCICs). A total of 150 SCI patients (aged 18-88 years (median: 44 years), 30.7% females) were studied between July 2009 and March 2010. LOS and mortality 12 months after admission to the SCIC was monitored. Multivariate regression analysis was used to identify unique predictors of the variance of LOS. RESULTS: The patients initially undernourished or at risk of undernutrition (44.6%) had a significantly longer LOS (median (days): 129 vs 85, P=0.012) and greater 12-month mortality (% deceased: 9.2% vs 1.4%, P=0.036). In addition, serum albumin and new admission to an SCIC were identified as independent predictors for long LOS. CONCLUSION: The present study suggests that undernutrition risk, as identified by the SNST, is associated with adverse clinical outcomes. Nutritional screening should be helpful in improving clinical outcomes if it promotes more appropriate and effective nutritional intervention.

Validation of the spinal nutrition screening tool (SNST) in patients with spinal cord injuries (SCI): result from a multicentre study.

BACKGROUND/OBJECTIVES: A disease-specific nutrition screening tool (NST): the spinal nutrition screening tool (SNST) has been developed for use in patients with spinal cord injury (SCI) but its reliability and agreement with other published tools requires investigation. The aims of this study were to assess the prevalence of malnutrition risk in SCI patients and to confirm the diagnostic accuracy of the SNST. SUBJECTS/METHODS: Patients' baseline clinical data, anthropometric measurements and NST scores were assessed. The validity of the SNST was assessed by (i) comparing with a full dietetic assessment (criterion validity); (ii) comparison with a generic NST: malnutrition universal screening tool (MUST) (concurrent validity); and (iii) completion of an additional SNST to assess inter- and intra-rater reliability. Agreement was assessed using Cohen's κ-statistics. RESULTS: Using the SNST, the prevalence of malnutrition risk ranged from 22 to 64% on admission to four SCI centres. The SNST had substantial agreement with MUST (κ: 0.723, 95% confidence interval (CI): 0.607-0.839) and dietitian assessment (κ: 0.567, 95% CI: 0.434-0.699). The SNST had a moderate to substantial reliability (inter-rater reliability: κ: 0.5, 95% CI: 0.2-0.8; intra-rater reliability: κ: 0.64, 95% CI: 0.486-0.802). When compared with dietetic assessment, the SNST had a numerically lower specificity (76.1% vs 80.4%) and similar agreement to MUST (κ: 0.57 vs 0.58) but SNST showed a numerically higher sensitivity (85.7% vs 80.4%) and a numerically higher negative predictive value (92% vs 89.2%) than MUST. CONCLUSIONS: This study shows that malnutrition is common in SCI patients. The SNST is an acceptable (valid and reliable) NST and may be a useful alternative to MUST in identifying SCI patients at risk of malnutrition.

Peak flow and voice pathology.

Lung function influences voice quality. The aim of this study was to determine if there was a link between subjective voice pathology and peak flow in patients newly presenting with voice problems. A prospective, multigroup study design was designed, with three groups: New voice pathology patients presenting to voice clinics or speech therapists; General patients from ear, nose, and throat clinics with no voice or hearing abnormality; and Asthmatics presenting to general practitioner surgeries or asthma groups for review of asthma treatment. Fifty general ENT patients, 50 voice pathology patients, and 26 asthmatics were included. Peak flow and Voice Handicap Index (VHI) were measured in all subjects. Analysis of the correlation between VHI and percentage of expected peak flow showed a small correlation between the two for voice pathology patients (r=-0.304, P=0.016). No significant correlation was found for the other two groups. These results do not justify the routine measurement of peak flow in all voice clinic patients, but suggest that peak flow measurement and optimization may have a place in those with the most severely impaired VHI.