NHS Ayrshire and Arran

BACKGROUND: Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass. OBJECTIVES: To examine the effectiveness of exercise interventions in preventing bone loss and fractures in postmenopausal women. SEARCH STRATEGY: During the update of this review we updated the original search strategy by searching up to December 2010 the following electronic databases: the Cochrane Musculoskeletal Group's Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010 Issue 12); MEDLINE; EMBASE; HealthSTAR; Sports Discus; CINAHL; PEDro; Web of Science; Controlled Clinical Trials; and AMED. We attempted to identify other studies by contacting experts, searching reference lists and searching trial registers. SELECTION CRITERIA: All randomised controlled trials (RCTs) that met our predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Pairs of members of the review team extracted the data and assessed trial quality using predetermined forms. For dichotomous outcomes (fractures), we calculated risk ratios (RRs) using a fixed-effect model. For continuous data, we calculated mean differences (MDs) of the percentage change from baseline. Where heterogeneity existed (determined by the I(2) statistic), we used a random-effects model. MAIN RESULTS: Forty-three RCTs (27 new in this update) with 4320 participants met the inclusion criteria. The most effective type of exercise intervention on bone mineral density (BMD) for the neck of femur appears to be non-weight bearing high force exercise such as progressive resistance strength training for the lower limbs (MD 1.03; 95% confidence interval (CI) 0.24 to 1.82). The most effective intervention for BMD at the spine was combination exercise programmes (MD 3.22; 95% CI 1.80 to 4.64) compared with control groups. Fractures and falls were reported as adverse events in some studies. There was no effect on numbers of fractures (odds ratio (OR) 0.61; 95% CI 0.23 to 1.64). Overall, the quality of the reporting of studies in the meta-analyses was low, in particular in the areas of sequence generation, allocation concealment, blinding and loss to follow-up. AUTHORS' CONCLUSIONS: Our results suggest a relatively small statistically significant, but possibly important, effect of exercise on bone density compared with control groups. Exercise has the potential to be a safe and effective way to avert bone loss in postmenopausal women.

Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

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.

Objectives Compassion focused therapy ( CFT ) was developed to stimulate capacities for soothing and affiliation to self and others as a way to regulate the threat system. This feasibility study aimed to assess the safety, the acceptability, the potential benefits, and associated change processes of using group CFT with people recovering from psychosis. Design A prospective, randomized, open‐label, blinded end point evaluation design was used. Method Forty adult patients with a schizophrenia‐spectrum disorder were randomized to CFT plus treatment as usual ( TAU ; n = 22) or to TAU alone ( n = 18). Group CFT comprised 16 sessions (2 hr each, 1 x week). Participants were assessed prior to randomization and at the end of treatment. Assessments included semi‐structured interviews to elicit narratives of recovery from psychosis and self‐report measures. At the end of treatment, participants were rated on the Clinical Global Impression Scale. Narratives were coded using the Narrative Recovery Style Scale to provide measures of change in compassion and avoidance. Change processes were correlated with changes in depression, personal beliefs about illness, fear of recurrence, and positive and negative affect. Results Group CFT was associated with no adverse events, low attrition (18%), and high acceptability. Relative to TAU , CFT was associated with greater observed clinical improvement ( p &lt; 0.001) and significant increases in compassion ( p = 0.015) of large magnitude. Relative to TAU , increases in compassion in the CFT group were significantly associated with reductions in depression ( p = 0.001) and in perceived social marginalization ( p = 0.002). Discussion Findings support the feasibility of group CFT in psychosis and suggest that changes in compassion can be achieved, which appear to reduce depression in particular. This is the first randomized controlled evaluation of CFT . Conclusion Compassion focused therapy appears as a safe, acceptable, promising, and evolving intervention for promoting emotional recovery from psychosis. Practitioner Points Compassion focused therapy appears safe to use with people recovering from psychosis. Compassion focused therapy was associated with significantly greater clinical improvement than Treatment as Usual. Relative to TAU, CFT was associated with a significant increase in compassion of large magnitude. Relative to TAU, in the CFT group increases in compassion were significantly associated with reductions in depression and in perceived social marginalization.

BACKGROUND: Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. METHODS: Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. RESULTS: The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P=0.008). No significant between-group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. CONCLUSIONS: Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects. (Funded by Becton Dickinson; EudraCT number, 2012-000599-40 .).

BACKGROUND: The paper describes a randomized controlled trial of targeting cognitive behavioural therapy (CBT) during prodromal or early signs of relapse in schizophrenia. We hypothesized that CBT would result in reduced admission and relapse, reduced positive and negative symptoms, and improved social functioning. METHOD: A total of 144 participants with schizophrenia or a related disorder were randomized to receive either treatment as usual (TAU) (N = 72) or CBT+TAU (N = 72). Participants were prospectively followed up between entry and 12 months. RESULTS: At 12 months, 11 (15.3%) participants in the CBT group were admitted to hospital compared to 19 (26.4%) of the TAU group (hazard ratio = 0.53, P = 0.10, 95% CI 0.25, 1.10). A total of 13 (18.1%) participants in CBT relapsed compared to 25 (34.7%) in TAU (hazard ratio = 0.47, P < 0O05, 95% CI 0.24, 0.92). In addition, the CBT group showed significantly greater improvement in positive symptoms, negative symptoms, global psychopathology, performance of independent functions and prosocial activities. CONCLUSIONS: The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia. The results are discussed in context of the study's methodological limitations.

BACKGROUND: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo. METHODS/DESIGN: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study-Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. DISCUSSION: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013.

Journal Article Delusions of parasitosis Get access ALAN LYELL ALAN LYELL Craigallion, Skelmorlie, Ayrshire PA17 5DT, Scotland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 4, 1 April 1983, Pages 485–499, https://doi.org/10.1111/j.1365-2133.1983.tb04604.x Published: 01 April 1983

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).

Abstract Generalized bone loss within the femoral neck accounts for only 15% of the increase in intracapsular hip fracture risk between the ages of 60 and 80 years. Conventional histology has shown that there is no difference in cancellous bone area between cases of intracapsular fracture and age and sex-matched controls. Rather, a loss of cortical bone thickness and increased porosity is the key feature with the greatest change occurring in those regions maximally loaded during a fall (the inferoanterior [IA] to superoposterior [SP] axis). We have now reexamined this finding using peripheral quantitative computed tomography (pQCT) to analyze cortical and cancellous bone areas, density, and mass in a different set of ex vivo biopsy specimens from cases of intracapsular hip fracture (female, n = 16, aged 69-92 years) and postmortem specimens (female, n = 15, aged 58-95 years; male, n = 11, aged 56-86 years). Within-neck location was standardized by using locations at which the ratio of maximum to minimum external diameters was 1.4 and at more proximal locations. Cortical widths were analyzed using 72 radial profiles from the center of area of each of the gray level images using a full-width/half-maximum algorithm. In both male and female controls, cancellous bone mass increased toward the femoral head and the rate of change was gender independent. Cancellous bone mass was similar in cases and controls at all locations. Overall, cortical bone mass was significantly lower in the fracture cases (by 25%; p &amp;lt; 0.001) because of significant reductions in both estimated cortical area and density. These differences persisted at locations that are more proximal. The mean cortical width in the cases was significantly lower in the IA (22.2%; p = 0.002) and inferior regions (19%; p &amp;lt; 0.001). The SP region was the thinnest in both cases and controls. These data confirm that a key feature in the etiology of intracapsular hip fracture is the site-specific loss of cortical bone, which is concentrated in those regions maximally loaded during a fall on the greater trochanter. An important implication of this work is that the pathogenesis of bone loss leading to hip fracture must be by a mechanism that varies in its effect according to location within the femoral neck. Key candidate mechanisms would include those involving locally reduced mechanical loading. This study also suggests that the development of noninvasive methodologies for analyzing the thickness and estimated densities of critical cortical regions of the femoral neck could improve detection of those at risk of hip fracture.

AIMS: To profile site of stroke/cerebrovascular accident, type and extent of field loss, treatment options, and outcome. METHODS: Prospective multicentre cohort trial. Standardised referral and investigation protocol of visual parameters. RESULTS: 915 patients were recruited with a mean age of 69 years (SD 14). 479 patients (52%) had visual field loss. 51 patients (10%) had no visual symptoms. Almost half of symptomatic patients (n = 226) complained only of visual field loss: almost half (n = 226) also had reading difficulty, blurred vision, diplopia, and perceptual difficulties. 31% (n = 151) had visual field loss as their only visual impairment: 69% (n = 328) had low vision, eye movement deficits, or visual perceptual difficulties. Occipital and parietal lobe strokes most commonly caused visual field loss. Treatment options included visual search training, visual awareness, typoscopes, substitutive prisms, low vision aids, refraction, and occlusive patches. At followup 15 patients (7.5%) had full recovery, 78 (39%) had improvement, and 104 (52%) had no recovery. Two patients (1%) had further decline of visual field. Patients with visual field loss had lower quality of life scores than stroke patients without visual impairment. CONCLUSIONS: Stroke survivors with visual field loss require assessment to accurately define type and extent of loss, diagnose coexistent visual impairments, and offer targeted treatment.

The World Health Organization (WHO) stated that globally, dental caries is the most important oral condition. To develop effective prevention strategies requires an understanding of how this condition develops and progresses over time, but there are few longitudinal studies of caries onset and progression in children. The aim of the study was to establish the pattern of caries development from childhood into adolescence and to explore the role of potential risk factors (age, sex, ethnicity, and social deprivation). Of particular interest was the disease trajectory of dentinal caries in the permanent teeth in groups defined by the presence or absence of dentinal caries in the primary teeth. Intraoral examinations to assess oral health were performed at 4 time points by trained and calibrated dentist examiners using a standardized, national diagnostic protocol. Clinical data were available from 6,651 children. Mean caries prevalence (% D 3 MFT &gt; 0) was 16.7% at the first clinical examination (ages 7–9 y), increasing to 31.0%, 42.2%, and 45.7% at subsequent examinations. A population-averaged model (generalized estimating equations) was used to model the longitudinal data. Estimated mean values indicated a rising D 3 MFT count as pupils aged (consistent with new teeth emerging), which was significantly higher (4.49 times; 95% confidence interval, 3.90–5.16) in those pupils with caries in their primary dentition than in those without. This study is one of the few large longitudinal studies to report the development of dental caries from childhood into adolescence. Children who developed caries in their primary dentition had a very different caries trajectory in their permanent dentition compared to their caries-free contemporaries. In light of these results, caries-free and caries-active children should be considered as 2 separate populations, suggesting different prevention strategies are required to address their different risk profiles.

The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU’s). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU’s residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer “starts afresh” and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer.

The aim of the study was to establish the test–retest reliability, clinical significance and precision of four mobility and balance measures – the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale – in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended Disability Status Score 5–6.5) were assessed on four measures of mobility and balance. The Timed 25-Foot Walk, Six-minute Walk and Timed Up and Go mobility outcome measures and the Berg Balance Scale were assessed by one assessor one week apart. Intraclass correlation coefficient (ICC) analysis was carried out to determine reliability. Minimal detectable change values were calculated to determine clinical significance; the standard error of each measurement was calculated to assess precision. All four outcome measures were found to be reliable: Timed 25-Foot Walk ICC=0.94, Six-minute Walk Test ICC=0.96, Timed Up and Go ICC=0.97 and Berg Balance Scale ICC=0.96. Minimal detectable change values were as follows: Timed 25-Foot Walk=12.6 s, Six-minute Walk Test=76.2 m, Timed Up and Go=10.6 s and Berg Balance Scale=7 points. Standard errors of measurement were as follows: Timed 25-Foot Walk=4.56 s, Six-minute Walk Test=27.48 m, Timed Up and Go=3.81 s and Berg Balance Scale=3 points. The test–retest reliability of these four outcome measures was found to be good. The calculated clinical significance and precision of these measures highlight the problems of assessing a heterogeneous clinical population. Die vorliegende Studie sollte die Test-Retest-Reliabilität, klinische Signifikanz und Präzision von vier Mobilitäts- und Gleichgewichtsübungen – Timed 25-Foot-Walk (T25FW), 6-Minuten-Gehtest, Timed-Up-and-Go-Test (TUG) und Berg-Balance-Skala – bei Personen mit mäßigen Beeinträchtigungen durch multiple Sklerose beurteilen. Dazu wurden 24 Teilnehmer mit multipler Sklerose (und einem Score von 5–6.5 auf der Expanded Disability Status-Skala (EDSS)) anhand von vier Mobilitäts- und Gleichgewichtsübungen beurteilt. Die ergebnisorientierten Mobilitäts-Messgrößen des Timed 25-Foot-Walk, des 6-Minuten-Gehtests und des Timed-Up-and-Go-Tests sowie die Berg-Balance-Skala wurden von einem Assessor im Abstand von jeweils einer Woche beurteilt. Anhand der Intraclass-Korrelationskoeffizientenanalyse (ICC) wurde die Reliabilität ermittelt. Minimal nachweisbare Änderungswerte wurden berechnet, um die klinische Signifikanz zu ermitteln; der Standardfehler jeder Messung wurde berechnet, um die Präzision zu ermitteln. Alle vier ergebnisorientierten Messgrößen erwiesen sich als zuverlässig: Der Timed 25-Foot-Walk-ICC=0.94, der 6-Minuten-Gehtest-ICC=0.96, der Timed-Up-and-Go-ICC=0.97 und der Berg-Balance-Skala-ICC=0.96. Die minimal nachweisbaren Änderungswerte lauteten: Timed 25-Foot-Walk=12.6 s, 6-Minuten-Gehtest=76.2 m, Timed-Up-and-Go=10.6 s und Berg-Balance-Skala=7 Punkte. Die Standard-Messfehler betrugen: Timed 25-Foot-Walk=4.56 s, 6-Minuten-Gehtest=27.48 m, Timed-Up-and-Go=3.81 s und Berg-Balance-Skala=3 Punkte. Die Test-Retest-Reliabilität dieser vier ergebnisorientierten Messgrößen erwies sich als gut. Die berechnete klinische Signifikanz und Präzision dieser Messgrößen zeigen die Problematik bei der Beurteilung einer heterogenen klinischen Population auf. El objetivo de este estudio fue establecer la fiabilidad test-retest, la significancia clínica y la precisión de estas cuatro mediciones de movilidad y equilibrio: la prueba cronometrada de la marcha de 25 pies (Timed 25-Foot Walk), la prueba de los seis minutos marcha (Six-minute Walk), la prueba cronometrada de levántate y anda (Timed Up and Go) y la Escala de equilibrio de Berg, en individuos afectados por esclerosis múltiple moderada. Se realizaron cuatro mediciones de movilidad y equilibrio a veinticuatro participantes con esclerosis múltiple (Escala extendida del estado de incapacidad 5-6.5). Los resultados de movilidad de las mediciones de la prueba cronometrada de la marcha de 25 pies, de la prueba de los seis minutos marcha y de la prueba cronometrada de levántate y anda, así como de la Escala de equilibrio de Berg, fueron analizados por un evaluador una semana más tarde. Se llevó a cabo el análisis del coeficiente de correlación intraclase (CCI) con el fin de determinar la fiabilidad. Los valores del cambio mínimo detectable se calcularon con el objetivo de establecer la significancia clínica; el error estándar de cada medición se calculó para evaluar la precisión. Se demostró la fiabilidad de los resultados de las cuatro mediciones: CCI de la prueba cronometrada de la marcha de 25 pies=0.94; CCI de la prueba de los seis minutos marcha=0.96; CCI de la prueba cronometrada de levántate y anda=0.97; CCI de la Escala de equilibrio de Berg=0.96. Los valores del cambio mínimo detectable fueron los siguientes: prueba cronometrada de la marcha de 25 pies=12.6 s; prueba de los seis minutos marcha=76.2 m; prueba cronometrada de levántate y anda=10.6 s; Escala de equilibrio de Berg=7 puntos. Los errores estándar de las mediciones fueron los siguientes: prueba cronometrada de la marcha de 25 pies=4.56 s; prueba de los seis minutos marcha=27.48 m; prueba cronometrada de levántate y anda=3.81 s; Escala de equilibrio de Berg=3 puntos. Se observó una buena fiabilidad test-retest de los resultados de estas cuatro mediciones. El cálculo de la significancia clínica y de la precisión de estas mediciones refleja la existencia de problemas a la hora de evaluar una población clínica heterogénea. Cette étude avait pour objet d'établir la répétabilité des tests, la signification clinique et la précision de quatre mesures de mobilité et d'équilibre – la marche chronométrée sur 7.6 m (« Timed 25-Foot Walk »), la marche de six minutes, la mesure « Timed Up and Go » et l'échelle d'équilibre de Berg - chez les personnes modérément affectées par la sclérose en plaques. Vingt quatre participants souffrant de la sclérose en plaques (score de statut d'invalidité prolongée de 5–6.5) ont été évalués pour quatre mesures de mobilité et d'équilibre. Les résultats des mesures de mobilité Timed 25-Foot Walk, marche de six minutes et Timed Up and Go et de l'échelle d'équilibre de Berg ont été évalués à une semaine d'intervalle. Une analyse du coefficient de corrélation intraclasse (CCI) a été effectuée pour déterminer la fiabilité des mesures. Les valeurs de changement détectable minimales ont été calculées afin de déterminer la signification clinique; l'erreur-type de chaque mesure a été calculée pour évaluer la précision. Les quatre mesures de résultats se sont avérées fiables: CCI marche T25FW=0.94, CCI test de marche de six minutes=0.96, CCI TUG=0.97 et CCI échelle d'équilibre de Berg=0.96. Les valeurs de changement détectable minimales étaient les suivantes: Marche T25FW=12.6 s, test de marche de six minutes=76.2 m, TUG=10.6 et échelle d'équilibre de Berg=7 points. Les erreurs types de mesure étaient les suivantes: Marche T25FW=4.56 s, test de marche de six minutes=27.48 m, TUG=3.81 et échelle d'équilibre de Berg=3 points. La répétabilité des tests de ces quatre résultats de mesures a été jugée satisfaisante. La signification clinique calculée et la précision de ces mesures mettent en évidence les problèmes d'évaluation d'une population clinique hétérogène.

BACKGROUND: Cardiovascular disease is the most common cause of death globally. Traditionally, centre-based cardiac rehabilitation programmes are offered to individuals after cardiac events to aid recovery and prevent further cardiac illness. Home-based and technology-supported cardiac rehabilitation programmes have been introduced in an attempt to widen access and participation, especially during the SARS-CoV-2 pandemic. This is an update of a review previously published in 2009, 2015, and 2017. OBJECTIVES: To compare the effect of home-based (which may include digital/telehealth interventions) and supervised centre-based cardiac rehabilitation on mortality and morbidity, exercise-capacity, health-related quality of life, and modifiable cardiac risk factors in patients with heart disease SEARCH METHODS: We updated searches from the previous Cochrane Review by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) on 16 September 2022. We also searched two clinical trials registers as well as previous systematic reviews and reference lists of included studies. No language restrictions were applied. SELECTION CRITERIA: We included randomised controlled trials that compared centre-based cardiac rehabilitation (e.g. hospital, sports/community centre) with home-based programmes (± digital/telehealth platforms) in adults with myocardial infarction, angina, heart failure, or who had undergone revascularisation. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on predefined inclusion criteria. Disagreements were resolved through discussion or by involving a third review author. Two authors independently extracted outcome data and study characteristics and assessed risk of bias. Certainty of evidence was assessed using GRADE. MAIN RESULTS: We included three new trials in this update, bringing a total of 24 trials that have randomised a total of 3046 participants undergoing cardiac rehabilitation. A further nine studies were identified and are awaiting classification. Manual searching of trial registers until 16 September 2022 revealed a further 14 clinical trial registrations - these are ongoing. Participants had a history of acute myocardial infarction, revascularisation, or heart failure. Although there was little evidence of high risk of bias, a number of studies provided insufficient detail to enable assessment of potential risk of bias; in particular, details of generation and concealment of random allocation sequencing and blinding of outcome assessment were poorly reported. No evidence of a difference was seen between home- and centre-based cardiac rehabilitation in our primary outcomes up to 12 months of follow-up: total mortality (risk ratio [RR] = 1.19, 95% confidence interval [CI] 0.65 to 2.16; participants = 1647; studies = 12/comparisons = 14; low-certainty evidence) or exercise capacity (standardised mean difference (SMD) = -0.10, 95% CI -0.24 to 0.04; participants = 2343; studies = 24/comparisons = 28; low-certainty evidence). The majority of evidence (N=71 / 77 comparisons of either total or domain scores) showed no significant difference in health-related quality of life up to 24 months follow-up between home- and centre-based cardiac rehabilitation. Trials were generally of short duration, with only three studies reporting outcomes beyond 12 months (exercise capacity: SMD 0.11, 95% CI -0.01 to 0.23; participants = 1074; studies = 3; moderate-certainty evidence). There was a similar level of trial completion (RR 1.03, 95% CI 0.99 to 1.08; participants = 2638; studies = 22/comparisons = 26; low-certainty evidence) between home-based and centre-based participants. The cost per patient of centre- and home-based programmes was similar. AUTHORS' CONCLUSIONS: This update supports previous conclusions that home- (± digital/telehealth platforms) and centre-based forms of cardiac rehabilitation formally supported by healthcare staff seem to be similarly effective in improving clinical and health-related quality of life outcomes in patients after myocardial infarction, or revascularisation, or with heart failure. This finding supports the continued expansion of healthcare professional supervised home-based cardiac rehabilitation programmes (± digital/telehealth platforms), especially important in the context of the ongoing global SARS-CoV-2 pandemic that has much limited patients in face-to-face access of hospital and community health services. Where settings are able to provide both supervised centre- and home-based programmes, consideration of the preference of the individual patient would seem appropriate. Although not included in the scope of this review, there is an increasing evidence base supporting the use of hybrid models that combine elements of both centre-based and home-based cardiac rehabilitation delivery. Further data are needed to determine: (1) whether the short-term effects of home/digital-telehealth and centre-based cardiac rehabilitation models of delivery can be confirmed in the longer term; (2) the relative clinical effectiveness and safety of home-based programmes for other heart patients, e.g. post-valve surgery and atrial fibrillation.

Objectives The present review aimed to assess the quality, content and evidence of efficacy of universally delivered (to all pupils aged 5–16 years), school-based, mental health interventions designed to promote mental health/well-being and resilience, using a validated outcome measure and provided within the UK in order to inform UK schools-based well-being implementation. Design A systematic review of published literature set within UK mainstream school settings. Data sources Embase, CINAHL, MEDLINE, PsycINFO, PsychArticles, ASSIA and Psychological and Behavioural Sciences published between 2000 and April 2016. Eligibility criteria Published in English; universal interventions that aimed to improve mental health/emotional well-being in a mainstream school environment; school pupils were the direct recipients of the intervention; pre-post design utilised allowing comparison using a validated outcome measure. Data extraction and synthesis 12 studies were identified including RCTs and non-controlled pre-post designs (5 primary school based, 7 secondary school based). A narrative synthesis was applied with study quality check. 1 Results Effectiveness of school-based universal interventions was found to be neutral or small with more positive effects found for poorer quality studies and those based in primary schools (pupils aged 9–12 years). Studies varied widely in their use of measures and study design. Only four studies were rated ‘excellent’ quality. Methodological issues such as small sample size, varying course fidelity and lack of randomisation reduced overall study quality. Where there were several positive outcomes, effect sizes were small, and methodological issues rendered many results to be interpreted with caution. Overall, results suggested a trend whereby higher quality studies reported less positive effects. The only study that conducted a health economic analysis suggested the intervention was not cost-effective. Conclusions The current evidence suggests there are neutral to small effects of universal, school-based interventions in the UK that aim to promote emotional or mental well-being or the prevention of mental health difficulties. Robust, long-term methodologies need to be pursued ensuring adequate recording of fidelity, the use of validated measures sensitive to mechanisms of change, reporting of those lost to follow-up and any adverse effects. Further high-quality and large-scale research is required across the UK in order to robustly test any long-term benefits for pupils or on the wider educational or health system.

OBJECTIVE: To establish the effects of a 12-week, community-based group exercise intervention for people moderately affected with multiple sclerosis. DESIGN: Randomized controlled pilot trial. SETTING: Two community leisure centres. PARTICIPANTS: Thirty-two participants with multiple sclerosis randomized into intervention or control groups. INTERVENTION: The intervention group received 12 weeks of twice weekly, 60-minute group exercise sessions, including mobility, balance and resistance exercises. The control group received usual care. MAIN OUTCOME MEASURES: An assessor blinded to group allocation assessed participants at baseline, after eight weeks and after 12 weeks. The primary outcome measure was 25-foot (7.6 m) walk time, secondary outcomes assessed walking endurance, balance, physical function, leg strength, body mass index, activity levels, fatigue, anxiety and depression, quality of life and goal attainment. RESULTS: The intervention made no statistically significant difference to the results of participants' 25-foot walk time. However the intervention led to many improvements. In the intervention group levels of physical activity improved statistically between baseline and week 8 (P < 0.001) and baseline and week 12 (P = 0.005). Balance confidence results showed a significant difference between baseline and week 12 (P = 0.013). Good effect sizes were found for dynamic balance (d = 0.80), leg strength (d = 1.33), activity levels (d = 1.05) and perceived balance (d = 0.94). CONCLUSION: The results of the study suggest that community-based group exercise classes are a feasible option for people moderately affected with multiple sclerosis, and offer benefits such as improved physical activity levels, balance and leg strength.

The effect of adiposity is manifest in nearly every aspect of female reproductive life, whether as a metabolic or reproductive complication or as a technical problem affecting clinical issues such as ultrasonography or surgery. Indeed, obesity is present in 35% of maternal deaths in the United Kingdom. View this table: Potential effects of adiposity before and during pregnancy Such concerns are particularly important given recent evidence of a doubling in the prevalence of obesity in young women attending for antenatal care in maternity hospitals in the UK (in some places, almost one in five are now obese). In the United States, where obesity rates are generally even higher, the American College of Obstetricians and Gynecologists has issued guidance on the impact of obesity on pregnancy. Strong evidence shows that insulin resistance is an integral part of polycystic ovarian syndrome, especially in obese women. In most women with the syndrome, hyperinsulinaemia—driven or revealed by excess weight gain—promotes ovarian androgen secretion and abnormal follicular development, leading to dysfunctional ovarian and menstrual activity. Endocrine and clinical effects of obesity and insulin resistance in. Adapted from Harborne et al. Lancet 2003;361:1894-901 Androgens are carried in the circulation bound to sex hormone binding globulin (SHBG). Conditions of high androgen and insulin concentrations are associated with lower levels of SHBG, resulting in high free androgen activity. Thus, clinical manifestations of polycystic ovarian syndrome are associated with androgen activity and include hirsutism, acne, and alopecia, as well as oligomenorrhoea and ovulation failure. Medications that contain oestrogen (such as the combined contraceptive pill) or ovulation induction drugs (resulting in high levels of endogenous oestrogen) may be associated with an increased risk of venous thromboembolism in obese women. The combined effect of obesity and the combined contraceptive pill results in a 10-fold increased risk of venous thromboembolism in women with a body …

Here we report inherited dysregulation of protein phosphatase activity as a cause of intellectual disability (ID). De novo missense mutations in 2 subunits of serine/threonine (Ser/Thr) protein phosphatase 2A (PP2A) were identified in 16 individuals with mild to severe ID, long-lasting hypotonia, epileptic susceptibility, frontal bossing, mild hypertelorism, and downslanting palpebral fissures. PP2A comprises catalytic (C), scaffolding (A), and regulatory (B) subunits that determine subcellular anchoring, substrate specificity, and physiological function. Ten patients had mutations within a highly conserved acidic loop of the PPP2R5D-encoded B56δ regulatory subunit, with the same E198K mutation present in 6 individuals. Five patients had mutations in the PPP2R1A-encoded scaffolding Aα subunit, with the same R182W mutation in 3 individuals. Some Aα cases presented with large ventricles, causing macrocephaly and hydrocephalus suspicion, and all cases exhibited partial or complete corpus callosum agenesis. Functional evaluation revealed that mutant A and B subunits were stable and uncoupled from phosphatase activity. Mutant B56δ was A and C binding-deficient, while mutant Aα subunits bound B56δ well but were unable to bind C or bound a catalytically impaired C, suggesting a dominant-negative effect where mutant subunits hinder dephosphorylation of B56δ-anchored substrates. Moreover, mutant subunit overexpression resulted in hyperphosphorylation of GSK3β, a B56δ-regulated substrate. This effect was in line with clinical observations, supporting a correlation between the ID degree and biochemical disturbance.

Our study has determined the response of C-reactive protein (CRP) after total knee replacement (TKR). The peak level occurs on the second postoperative day and is significantly greater than that after total hip replacement (THR). The level returns to normal at similar times after both procedures. The physiological response to TKR as measured by the area under the CRP/time curve is significantly greater than that after THR. Rising CRP levels after the third postoperative day may indicate a complication of surgery such as infection.