Perth Royal Infirmary

OBJECTIVE: To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease. DESIGN: Multicentre, randomised, double blind, 2x2 factorial, placebo controlled trial. SETTING: 16 hospital centres in Scotland, supported by 188 primary care groups. PARTICIPANTS: 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. INTERVENTIONS: Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318). MAIN OUTCOME MEASURES: Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. RESULTS: No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89). CONCLUSION: This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53295293.

INTRODUCTION: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia. METHODS: The databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review. RESULTS: In 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer's disease and healthy controls. CONCLUSION: IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer.

A single case study of a patient with 'visual form agnosia' is presented. A severe visual recognition deficit was accompanied by impairments in discriminating shape, reflectance, and orientation, although visual acuity and colour vision, along with tactile recognition and intelligence, were largely preserved. Neuropsychological and behavioural investigations have indicated that the patient is able to utilize visual pattern information surprisingly well for the control of hand movements during reaching, and can even read many whole words, despite being unable to make simple discriminative judgements of shape or orientation. She seems to have no awareness of shape primitives through Gestalt grouping by similarity, continuity or symmetry. It is proposed that many of these perceptual disorders might be the combined result of (1) a selective loss of the cortical elaboration of the magnocellular visual processing stream, and (2) a selective output disconnection from a central processor of visual boundaries and shape primitives in the occipital cortex.

OBJECTIVE: To present estimates of maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean, and to discuss strategies to prevent these deaths. DESIGN: Retrospective review of all available data. SETTING: Database of the World Health Organization's Maternal Health and Safe Motherhood Programme. MAIN OUTCOME MEASURES: Estimates of the total maternal mortality and the proportions of deaths associated with hypertensive disorders of pregnancy. RESULTS: Estimates of mortality associated with hypertensive disorders of pregnancy were similar in Africa, Latin America and the Caribbean, despite considerably higher total mortality in Africa. Variations in both overall mortality and that associated with hypertensive disorders of pregnancy were greatest in Asia. Despite their limitations, these data suggest that between 10-15% of maternal deaths are associated with hypertensive disorders of pregnancy, and that 10% are associated with eclampsia. CONCLUSIONS: Where maternal mortality is relatively high, the excess is likely to be due to a high mortality associated with haemorrhage and infection and reductions are most likely to come from reductions in these deaths. Evidence from both developed and developing countries suggests that deaths associated with hypertensive disorders of pregnancy are the most difficult to prevent. More rigorous assessment of interventions designed to prevent these deaths is urgently required.

BACKGROUND AND OBJECTIVES: The effects of lifestyle interventions on cardio-metabolic outcomes in overweight children have not been reviewed systematically. The objective of the study was to examine the impact of lifestyle interventions incorporating a dietary component on both weight change and cardio-metabolic risks in overweight/obese children. METHODS: English-language articles from 1975 to 2010, available from 7 databases, were used as data sources. Two independent reviewers assessed articles against the following eligibility criteria: randomized controlled trial, participants overweight/obese and ≤18 years, comparing lifestyle interventions to no treatment/wait-list control, usual care, or written education materials. Study quality was critically appraised by 2 reviewers using established criteria; Review Manager 5.1 was used for meta-analyses. RESULTS: Of 38 eligible studies, 33 had complete data for meta-analysis on weight change; 15 reported serum lipids, fasting insulin, or blood pressure. Lifestyle interventions produced significant weight loss compared with no-treatment control conditions: BMI (-1.25kg/m(2), 95% confidence interval [CI] -2.18 to -0.32) and BMI z score (-0.10, 95% CI -0.18 to -0.02). Studies comparing lifestyle interventions to usual care also resulted in significant immediate (-1.30kg/m(2), 95% CI -1.58 to -1.03) and posttreatment effects (-0.92 kg/m(2), 95% CI -1.31 to -0.54) on BMI up to 1 year from baseline. Lifestyle interventions led to significant improvements in low-density lipoprotein cholesterol (-0.30 mmol/L, 95% CI -0.45 to -0.15), triglycerides (-0.15 mmol/L, 95% CI -0.24 to -0.07), fasting insulin (-55.1 pmol/L, 95% CI -71.2 to -39.1) and blood pressure up to 1 year from baseline. No differences were found for high-density lipoprotein cholesterol. CONCLUSIONS: Lifestyle interventions can lead to improvements in weight and cardio-metabolic outcomes. Further research is needed to determine the optimal length, intensity, and long-term effectiveness of lifestyle interventions.

BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) was reviewing its previous guidance on continuous subcutaneous insulin infusion (CSII). The review provided an assessment of evidence which had been published since the previous NICE appraisal (TA 151) in 2007. OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of using CSII to treat diabetes. To update the previous assessment report by reviewing evidence that has emerged since the last appraisal, and to take account of developments in alternative therapies, in particular the long-acting analogue insulins, which cause fewer problems with hypoglycaemia. DATA SOURCES: A systematic review of the literature and an economic evaluation were carried out. The bibliographic databases used were MEDLINE and EMBASE, 2002 to June 2007. The Cochrane Library (all sections), the Science Citation Index (for meeting abstracts only) and the website of the 2007 American Diabetes Association were also searched. REVIEW METHODS: The primary focus for type 1 diabetes mellitus (T1DM) was the comparison of CSII with multiple daily injection (MDI), based on the newer insulin analogues, but trials of neutral protamine Hagedorn (NPH)-based MDI that had been published since the last assessment were identified and described in brief. For type 2 diabetes mellitus (T2DM), all trials of MDI versus CSII were included, whether the long-acting insulin was analogue or not, because there was no evidence that analogue-based MDI was better than NPH-based MDI. Trials that were shorter than 12 weeks were excluded. Information on the patients' perspectives was obtained from four sources: the submission from the pump users group--Insulin Pump Therapy (INPUT); interviews with parents of young children who were members of INPUT; some recent studies; and from a summary of findings from the previous assessment report. Economic modelling used the Center for Outcomes Research (CORE) model, through an arrangement with the NICE and the pump manufacturers, whose submission also used the CORE model. RESULTS: The 74 studies used for analysis included eight randomised controlled trials (RCTs) of CSII versus analogue-based MDI in either T1DM or T2DM, eight new (since the last NICE appraisal) RCTs of CSII versus NPH-based MDI in T1DM, 48 observational studies of CSII, six studies of CSII in pregnancy, and four systematic reviews. The following benefits of CSII were highlighted: better control of blood glucose levels, as reflected by glycated haemoglobin (HbA1c) levels, with the size of improvement depending on the level before starting CSII; reduction in swings in blood glucose levels, and in problems due to the dawn phenomenon; fewer problems with hypoglycaemic episodes; reduction in insulin dose per day, thereby partly off-setting the cost of CSII; improved quality of life, including a reduction in the chronic fear of severe hypoglycaemia; more flexibility of lifestyle--no need to eat at fixed intervals, more freedom of lifestyle and easier participation in social and physical activity; and benefits for the patients' family. The submission from INPUT emphasised the quality of life gains from CSII, as well as improved control and fewer hypoglycaemic episodes. Also, there was a marked discrepancy between the improvement in social quality of life reported by successful pump users, and the lack of convincing health-related quality of life gains reported in the trials. With regard to economic evaluation, the main cost of CSII is for consumables, such as tubing and cannulas, and is about 1800-2000 pounds per year. The cost of the pump, assuming 4-year life, adds another 430-720 pounds per annum. The extra cost compared with analogue-based MDI averages 1700 pounds. Most studies, assuming a reduction in HbA1c level of 1.2%, found CSII to be cost-effective. LIMITATIONS: The most important weakness of the evidence was the very small number of randomised trials of CSII against the most modern forms of MDI, using analogue insulins. CONCLUSIONS: Based on the totality of evidence, using observational studies to supplement the limited data from randomised trials against best MDI, CSII provides some advantages over MDI in T1DM for both children and adults. However, there was no evidence that CSII is better than analogue-based MDI in T2DM or in pregnancy. Further trials with larger numbers and longer durations comparing CSII and optimised MDI in adults, adolescents and children are needed. In addition, there should be a trial of CSII versus MDI with similar provision of structured education in both arms. A trial is also needed for pregnant women with pre-existing diabetes, to investigate using CSII to the best effect.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

This paper explores spiritual and aesthetic cultural values associated with ecosystems. We argue that these values are not best captured by instrumental or consequentialist thinking, and they are grounded in conceptions of nature that differ from the ecosystem services conceptual framework. To support our case, we engage with theories of the aesthetic and the spiritual, sample the discourse of ‘wilderness’, and provide empirical evidence from the recent UK National Ecosystem Assessment Follow-on Phase. We observe that accounts of spiritual and aesthetic value in Western culture are diverse and expressed through different media. We recognise that humans do benefit from their aesthetic and spiritual experiences of nature. However, aesthetic and spiritual understandings of the value of nature lead people to develop moral responsibilities towards nature and these are more significant than aesthetic and spiritual benefits from nature. We conclude that aesthetic and spiritual values challenge economic conceptions of ecosystems and of value (including existence value), and that an analysis of cultural productions and a plural-values approach are needed to evidence them appropriately for decision-making.

IMPORTANCE: Critical illness results in disability and reduced health-related quality of life (HRQOL), but the optimum timing and components of rehabilitation are uncertain. OBJECTIVE: To evaluate the effect of increasing physical and nutritional rehabilitation plus information delivered during the post-intensive care unit (ICU) acute hospital stay by dedicated rehabilitation assistants on subsequent mobility, HRQOL, and prevalent disabilities. DESIGN, SETTING, AND PARTICIPANTS: A parallel group, randomized clinical trial with blinded outcome assessment at 2 hospitals in Edinburgh, Scotland, of 240 patients discharged from the ICU between December 1, 2010, and January 31, 2013, who required at least 48 hours of mechanical ventilation. Analysis for the primary outcome and other 3-month outcomes was performed between June and August 2013; for the 6- and 12-month outcomes and the health economic evaluation, between March and April 2014. INTERVENTIONS: During the post-ICU hospital stay, both groups received physiotherapy and dietetic, occupational, and speech/language therapy, but patients in the intervention group received rehabilitation that typically increased the frequency of mobility and exercise therapies 2- to 3-fold, increased dietetic assessment and treatment, used individualized goal setting, and provided greater illness-specific information. Intervention group therapy was coordinated and delivered by a dedicated rehabilitation practitioner. MAIN OUTCOMES AND MEASURES: The Rivermead Mobility Index (RMI) (range 0-15) at 3 months; higher scores indicate greater mobility. Secondary outcomes included HRQOL, psychological outcomes, self-reported symptoms, patient experience, and cost-effectiveness during a 12-month follow-up (completed in February 2014). RESULTS: Median RMI at randomization was 3 (interquartile range [IQR], 1-6) and at 3 months was 13 (IQR, 10-14) for the intervention and usual care groups (mean difference, -0.2 [95% CI, -1.3 to 0.9; P = .71]). The HRQOL scores were unchanged by the intervention (mean difference in the Physical Component Summary score, -0.1 [95% CI, -3.3 to 3.1; P = .96]; and in the Mental Component Summary score, 0.2 [95% CI, -3.4 to 3.8; P = .91]). No differences were found for self-reported symptoms of fatigue, pain, appetite, joint stiffness, or breathlessness. Levels of anxiety, depression, and posttraumatic stress were similar, as were hand grip strength and the timed Up & Go test. No differences were found at the 6- or 12-month follow-up for any outcome measures. However, patients in the intervention group reported greater satisfaction with physiotherapy, nutritional support, coordination of care, and information provision. CONCLUSIONS AND RELEVANCE: Post-ICU hospital-based rehabilitation, including increased physical and nutritional therapy plus information provision, did not improve physical recovery or HRQOL, but improved patient satisfaction with many aspects of recovery. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN09412438.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory condition that typically causes a symmetrical chronic arthritis. Timely use of disease-modifying antirheumatic drugs (DMARDs) is an essential aspect of disease management, but many patients may not respond even when conventional agents are used optimally. OBJECTIVE: To assess the clinical effectiveness and cost-effectiveness of adalimumab (ADA), etanercept (ETN), infliximab (IFX), rituximab (RTX) and abatacept (ABT) when used in patients with RA who have tried conventional agents and have failed to improve after trying a first tumour necrosis factor (TNF) inhibitor. DATA SOURCES: A systematic review of primary studies was undertaken. Databases searched included the Cochrane Library, MEDLINE (Ovid) and EMBASE up to July 2009. STUDY SELECTION: Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. STUDY APPRAISAL: Data from included studies were extracted by one reviewer and checked by a second. The quality of included studies was assessed independently by two reviewers, with any disagreements resolved by discussion and consultation with a third reviewer if necessary. RESULTS: Thirty-five studies were included in the systematic review: five randomised controlled trials (RCTs), one comparative study, one controlled study and 28 uncontrolled studies. One RCT (REFLEX) demonstrated the effectiveness of RTX. At 6 months significantly more patients treated with RTX achieved American College of Rheumatology (ACR) 20 [relative risk (RR) = 2.85, 95% confidence interval (CI) 2.08 to 3.91] and ACR70 (RR = 12.14, 95% CI 2.96 to 49.86) compared with those treated with the placebo. Differences between groups in favour of RTX were observed at 6 months for mean change from baseline in Disease Activity Score 28 (DAS28) (mean difference -1.50, 95% CI -1.74 to -1.26) and mean change from baseline in Health Assessment Questionnaire (HAQ) score (mean difference -0.30, 95% CI -0.40 to -0.20). One RCT (ATTAIN) demonstrated the effectiveness of ABT. At 6 months significantly more patients treated with ABT achieved ACR20 (RR = 2.56, 95% CI 1.77 to 3.69) and ACR70 (RR = 6.70, 95% CI 1.62 to 27.80) compared with those treated with placebo. Significant differences between groups in favour of ABT were observed at 6 months for mean change from baseline in DAS28 score (mean difference -1.27, 95% CI -1.62 to -0.93) and mean change from baseline in HAQ score (mean difference -0.34). Twenty-eight uncontrolled studies observed improvement of effectiveness compared with before switching, in patients who switched to ADA, ETN or IFX after discontinued previous TNF inhibitor(s). Four studies were included in the systematic review of cost-effectiveness. Independent economic evaluation undertaken by the assessment group showed that compared with DMARDs, the incremental cost-effectiveness ratios (ICERs) were £34,300 [per quality-adjusted life-year (QALY)] for ADA, £38,800 for ETN, £36,200 for IFX, £21,200 for RTX and £38,600 for ABT. RTX dominates the TNF inhibitors and the ICER for ABT compared with RTX is over £100,000 (per QALY). LIMITATIONS: Paucity of evidence from RCTs for assessing the clinical effectiveness of TNF inhibitors and an absence of head-to-head trials comparing the five technologies. CONCLUSIONS: Evidence from RCTs suggests that RTX and ABT are more effective than supportive care. Data from observational studies suggest that the use of an alternative TNF inhibitor in patients who exhibit an inadequate response to a first TNF inhibitor may offer some benefit, but there remain uncertainties with regard to the magnitude of treatment effects and their cost-effectiveness. Future research should include head-to-head trials comparing the clinical effectiveness and cost-effectiveness of the technologies against each other and emerging biologics. FUNDING: This study was funded by the Health Technology Assessment programme of the National Institute for Health Research.

OBJECTIVE: To examine the effect of β blockers in the management of chronic obstructive pulmonary disease (COPD), assessing their effect on mortality, hospital admissions, and exacerbations of COPD when added to established treatment for COPD. DESIGN: Retrospective cohort study using a disease specific database of COPD patients (TARDIS) linked to the Scottish morbidity records of acute hospital admissions, the Tayside community pharmacy prescription records, and the General Register Office for Scotland death registry. SETTING: Tayside, Scotland (2001-2010) Population 5977 patients aged >50 years with a diagnosis of COPD. MAIN OUTCOME MEASURES: Hazard ratios for all cause mortality, emergency oral corticosteroid use, and respiratory related hospital admissions calculated through Cox proportional hazard regression after correction for influential covariates. RESULTS: Mean follow-up was 4.35 years, mean age at diagnosis was 69.1 years, and 88% of β blockers used were cardioselective. There was a 22% overall reduction in all cause mortality with β blocker use. Furthermore, there were additive benefits of β blockers on all cause mortality at all treatment steps for COPD. Compared with controls (given only inhaled therapy with either short acting β agonists or short acting antimuscarinics), the adjusted hazard ratio for all cause mortality was 0.28 (95% CI 0.21 to 0.39) for treatment with inhaled corticosteroid, long acting β agonist, and long acting antimuscarinic plus β blocker versus 0.43 (0.38 to 0.48) without β blocker. There were similar trends showing additive benefits of β blockers in reducing oral corticosteroid use and hospital admissions due to respiratory disease. β blockers had no deleterious impact on lung function at all treatment steps when given in conjunction with either a long acting β agonist or antimuscarinic agent CONCLUSIONS: β blockers may reduce mortality and COPD exacerbations when added to established inhaled stepwise therapy for COPD, independently of overt cardiovascular disease and cardiac drugs, and without adverse effects on pulmonary function. NCT Number: NCT01221480

FOREWORD cells were later found to be conspicuously abundant.It was apparently this association of the dog's liver with the production of heparin, which first led Dr. Riley, and those who became associated with him, to consider the possi- bility that the mast cells might also be the source of the histamine; since the anaphylactic shock and analogous reactions, in the form characteristic of the dog, were known already to be due, essentially, to the effects of histamine and heparin poured into the general circulation, as the result of a primary reaction in the liver.Dr. Riley and his co-workers were thus led to make a more general survey of the relation between the abundance, on the one hand, of mast cells in different organs and tissues of a number of species, including examples of mast-cell tumours, and the yields, on the other hand, of histamine obtainable by extraction from the same normal and pathological sources.I do not doubt that any careful student of their results will find that the evidence here presented shows a highly significant correlation between the mast-cell content of solid organs and their yield of histamine to artificial extraction; and such a student will surely be impressed, as I am, with the reasonableness of the deduction that the mast cells in such tissues, and, indeed, the characteristic, basophile, meta- chromatically staining granules which occupy so much of the cytoplasm of those cells, are by far the most probable source of that histamine.It must be borne in mind, on the other hand, that this staining of the mast-cell granules does not, in itself, provide evidence for the presence in them of histamine.Histamine, on the contrary, being itself a base, has a special affinity for the acidic dyes, such as eosin and phloxin, with which it combines in vitro to form precipitates.Before the demonstration by Dr. Riley and his colleagues of the connexion between mast cells in a tissue and its yield of histamine, there had been highly suggestive evidence of a similar association between the yield of histamine from the blood of different animal species, including that of man, and its richness in white cells with an eosinophile granulation.In those of us who were familiar with these earlier observations, the news of the discovery that, in the tissues, the occurrence of histamine was associated with that of the basophile mast cells, produced, at first glance, a sense of paradox, or conflict of evidence.And it seems tp me that we have the more reason for gratitude to Dr. Riley and his co-workers for having gone steadily forward, undeterred by any such prejudice, to collect and assemble the data, which have now so abundantly confirmed their first observations.For my own part, I am expecting that the new association which they have so convincingly established, between histamine and the heparin-containing mast- cells of the tissues, will be found to have an increasing importance, for the assignment to histamine, and to the other amines, such as serotonin, now coming into view as mast-cell constituents, of their various functional roles in a range of physiological and pathological reactions.

IMPORTANCE: Diet and exercise represent the mainstays of obesity treatment. No systematic review has been conducted comparing the effect of dietary and exercise intervention in reducing metabolic risks in overweight children. OBJECTIVE: To compare the effects of diet-only intervention with those of diet plus exercise or exercise only on weight loss and metabolic risk reduction in overweight children. EVIDENCE REVIEW: English-language articles from 1975 to 2010 available from 7 databases were reviewed. One person searched the databases. Two independent reviewers assessed abstracts and articles against the following eligibility criteria: randomized controlled trials conducted in overweight and obese children aged 18 years or younger, comparing dietary intervention with a diet plus exercise program or an exercise-only program. Study quality was critically appraised by 2 reviewers using established criteria. The main outcome measures were body mass index, body fat percentage, lean body mass, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting glucose, and fasting insulin. FINDINGS: Fifteen studies were identified and included. Based on the small number of short-term trials currently available, both diet-only and diet plus exercise interventions resulted in weight loss and metabolic profile improvement. However, the addition of exercise to dietary intervention led to greater improvements in levels of high-density lipoprotein cholesterol (3.86 mg/dL [to convert to millimoles per liter, multiply by 0.0259]; 95% CI, 2.70 to 4.63), fasting glucose (-2.16 mg/dL [to convert to millimoles per liter, multiply by 0.0555]; 95% CI, -3.78 to -0.72), and fasting insulin (-2.75 μIU/mL [to convert to picomoles per liter, multiply by 6.945]; 95% CI, -4.50 to -1.00) over 6 months. The diet-only intervention caused greater reductions in levels of triglycerides (at the end of active intervention) and low-density lipoprotein cholesterol (at subsequent follow-up). CONCLUSIONS AND RELEVANCE: This review provides insights into the impact of dietary and exercise interventions on metabolic risk reduction in the pediatric population. However, further studies are required to confirm the evidence with rigorous design, appropriate sample size, longer duration of follow-up, and better strategies to improve compliance and achieve long-term sustainability.

The effects of ageing and dental state on the cross-sectional area and density of two jaw muscles, the masseter and medial pterygoid, were investigated using computed tomography. The study involved 84 male and 70 female subjects between the ages of 20 and 90 years. The cross-sectional area of both muscles showed a significant reduction with age; values for female subjects being found in the lower range of the distribution. When consideration was given to the presence or absence of a natural dentition, the cross-sectional area of both muscles in edentulous subjects showed a greater decrease throughout the age range studied. There was a significant decrease in the density of the muscles with increasing age. Previously, this has been interpreted to indicate a progressive increase in fat and fibrous tissue. Subject gender and the absence of teeth appeared to have little effect on this parameter. Changes in the cross-sectional area and density of these muscles would appear to be consistent with a general age related change of muscle tissue in the body as a whole and may specifically indicate a reduction in the masticatory forces which can be or are being utilised by ageing patients, many of whom have no remaining natural dentition.

Background: The care of older people with dementia is often complicated by physical comorbidity and polypharmacy, but the extent and patterns of these have not been well described. This paper reports analysis of these factors within a large, cross-sectional primary care data set. Methods: Data were extracted for 291,169 people aged 65 years or older registered with 314 general practices in the UK, of whom 10,258 had an electronically recorded dementia diagnosis. Differences in the number and type of 32 physical conditions and the number of repeat prescriptions in those with and without dementia were examined. Age–gender standardised rates were used to calculate odds ratios (ORs) of physical comorbidity and polypharmacy. Results: People with dementia, after controlling for age and sex, had on average more physical conditions than controls (mean number of conditions 2.9 versus 2.4; P < 0.001) and were on more repeat medication (mean number of repeats 5.4 versus 4.2; P < 0.001). Those with dementia were more likely to have 5 or more physical conditions (age–sex standardised OR [sOR] 1.42, 95% confidence interval (CI) 1.35–1.50; P < 0.001) and were also more likely to be on 5 or more (sOR 1.46; 95% CI 1.40–1.52; P < 0.001) or 10 or more repeat prescriptions (sOR 2.01; 95% CI 1.90–2.12; P < 0.001). Conclusions: People with dementia have a higher burden of comorbid physical disease and polypharmacy than those without dementia, even after accounting for age and sex differences. Such complex needs require an integrated response from general health professionals and multidisciplinary dementia specialists.

Measurements of tibial torsion using a tropometer were made in more than 1200 consecutive patients attending an adult knee clinic. In total 1672 readings from 836 patients in 11 diagnostic categories were analysed. Patients with either patellofemoral instability or Osgood-Schlatter disease had a significant increase in lateral tibial torsion. The most important finding was a significant reduction in this torsion in patients with panarticular disease.

Average muscle fiber conduction velocity, mean power frequency, and mean EMG voltage have been measured in human vastus lateralis during prolonged isometric knee extensions at 10, 20, 30, and 40% of the maximum knee extension force. During contractions at 10 and 20% of maximum force, conduction velocity and mean power frequency rose as the contraction progressed, whereas the conduction velocity and mean power frequency fell at 30 and 40% of the maximum force. The mean EMG voltage rose during the contractions, with steeper increases for higher forces. It is argued that two principal factors influence the EMG during prolonged submaximal contractions: firstly, the fatigue of current active motor units, and, secondly, recruitment of fresh motor units. These factors act in opposition to muscle fiber conduction velocity. Recruitment gives an increase in average conduction velocity, whereas fatigue provokes a slowing in conduction velocity.

This paper describes the patterns of pain induced from lumbar facet joints, from the posterior primary rami of L5, and from the medial articular branches of the posterior primary rami from T11 to L4 in patients undergoing diagnostic spinal infiltrations for chronic pain. No consistent segmental or sclerotomal pattern was found in 385 observations on 138 patients. Pain radiating to the buttock or trochanteric region occurred mostly from the L4 and L5 levels, while groin pain was produced from L2 to L5. The nerves supplying the facet joints gave rise to distal referral of pain significantly more commonly than the joints themselves.

BACKGROUND: The homozygous presence of the arginine-16 variant of the beta(2) adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting beta(2) agonists in asthmatic adults compared with the homozygous glycine-16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists. METHODS: A cross-sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004-5. The primary outcome measure was asthma exacerbations over the previous 6 months. RESULTS: There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group. CONCLUSIONS: The arginine-16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.

Abstract Rationale Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods The PHOSP–COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP–COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83–155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05–1.40), percent predicted Dl CO less than 80% (RR, 1.25; 95% CrI, 1.00–1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07–1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6–9.5), rising to 11.7% (95% CrI, 10.3–13.1) in the sensitivity analysis. Conclusions Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19–related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.