Opportunities to engage health system leaders in whole systems approaches to physical activity in England.

BACKGROUND: Physical activity plays an important role in maintaining good health and wellbeing, non-communicable disease prevention and can improve healthcare outcomes. Some progress is being made on incorporating physical activity into routine care, but less on engaging health system leaders in the 'whole systems' approaches which are increasingly recognised as important for addressing complex public health challenges such as physical inactivity. This commentary builds upon the findings of a recent study and aims to identify opportunities for engaging National Health Service (NHS) systems leaders in whole systems approaches to physical activity. OPPORTUNITIES FOR ACTION IN ENGLAND: Pockets of good practice exist from which lessons can be learned, but there are systemic issues that discourage and create barriers, and a need for meaningful engagement, leadership and action at national, regional and local levels. National and regional actors like Sport England, NHS England, health professional bodies, Active Partnerships, the Local Government Association and the Office for Health Improvement and Disparities can encourage and support government and the NHS to change policy drivers, culture and practices. Emerging opportunities include the 2021 White Paper Integration and Innovation, development of local integrated care systems, leadership from health charities and investment in non-clinical interventions ('social prescribing'). At local level, public health and physical activity specialists and other organisations have a key role as champions and facilitators of local whole systems approaches and engagement of local NHS leaderships. Finally, although whole systems action is about collaborative leadership, individual champions of physical activity can make a difference in influencing NHS leaders at every level towards whole systems working.

General practice referral of 'at risk' populations to community leisure services: applying the RE-AIM framework to evaluate the impact of a community-based physical activity programme for inactive adults with long-term conditions.

BACKGROUND: In the UK a high proportion of adults with long-term conditions do not engage in regular physical activity. General practice (GP) referral to community-based physical activity is one strategy that has gained traction in recent years. However, evidence for the real-world effectiveness and translation of such programmes is limited. This study aimed to evaluate the individual and organisational impacts of the 'CLICK into Activity' programme - GP referral of inactive adults living with (or at risk of) long-term conditions to community-based physical activity. METHODS: A mixed methods evaluation using the RE-AIM framework was conducted with data obtained from a range of sources: follow-up questionnaires, qualitative interviews, and programme-related documentation, including programme cost data. Triangulation methods were used to analyse data, with findings synthesised across each dimension of the RE-AIM framework. RESULTS: A total of 602 individuals were referred to CLICK into Activity physical activity sessions. Of those referred, 326 individuals participated in at least one session; the programme therefore reached 30.2% of the 1080 recruitment target. A range of individual-, social-, and environmental-level factors contributed to initial physical activity participation. Positive changes over time in physical activity and other outcomes assessed were observed among participants. Programme adoption at GP surgeries was successful, but the GP referral process was not consistently implemented across sites. Physical activity sessions were successfully implemented, with programme deliverers and group-based delivery identified as having an influential effect on programme outcomes. Changes to physical activity session content were made in response to participant feedback. CLICK into Activity cost £175,000 over 3 years, with an average cost per person attending at least one programme session of £535. CONCLUSIONS: Despite not reaching its recruitment target, CLICK into Activity was successfully adopted. Positive outcomes were associated with participation, although low 6- and 12-month follow-up response rates limit understanding of longer-term programme effects. Contextual and individual factors, which may facilitate successful implementation with the target population, were identified. Findings highlight strategies to be explored in future development and implementation of GP referral to community-based physical activity programmes targeting inactive adults living with (or at risk of) long-term conditions.

Built and natural environment planning principles for promoting health: an umbrella review.

BACKGROUND: The built and natural environment and health are inextricably linked. However, there is considerable debate surrounding the strength and quality of the evidence base underpinning principles of good practice for built and natural environment design in promoting health. This umbrella review aimed to assess relationships between the built and natural environment and health, concentrating on five topic areas: neighbourhood design, housing, food environment, natural and sustainable environment, and transport. METHODS: A structured search was conducted for quantitative systematic reviews and stakeholder reviews published between January 2005 and April 2016. Seven databases and the websites of 15 relevant and respected stakeholder organisations known to publish review-level documentation were searched. Searches were limited to English-language publications and duplicate references were removed. Evidence quality and strength was appraised using validated techniques. Findings were used to develop a diagram for each topic area, illustrating relationships between built and natural environment planning principles and health-related outcomes. RESULTS: A total of 117 systematic reviews and review-level documents were eligible for inclusion. The quality of evidence was mixed; much of the evidence examined relied on findings from cross-sectional studies, making it difficult to draw clear causal links between built environment exposures and health-related impacts and outcomes. Fourteen actionable planning principles associated with positive health-related outcomes were identified across the five topic areas. For example, neighbourhoods that enhanced walkability, were complete and compact in design, and those which enhanced connectivity through safe and efficient infrastructure were associated with better health-related outcomes relating to physical activity, social engagement, mental health, perceptions of crime, and road traffic collisions. Evidence for the effectiveness of planning principles across different topic areas and on reducing health inequalities was sparse and inconclusive. CONCLUSIONS: Findings provide an up-to-date overview of relationships between the built and natural environment and health and present logical, evidence-based messages to aid communication between public health and planning professionals.

Employability and career experiences of international graduates of MSc Public Health: a mixed methods study.

OBJECTIVES: This article aims to describe the public health career experiences of international graduates of a Master of Science in Public Health (MSc PH) programme and to contribute to developing the evidence base on international public health workforce capacity development. STUDY DESIGN: A sequential mixed methods study was conducted between January 2017 and April 2017. METHODS: Ninety-seven international graduates of one UK university's MSc PH programme were invited to take part in an online survey followed by semistructured interviews, for respondents who consented to be interviewed. We computed the descriptive statistics of the quantitative data obtained, and qualitative data were thematically analysed. RESULTS: The response rate was 48.5%. Most respondents (63%) were employed by various agencies within 1 year after graduation. Others (15%) were at different stages of doctor of philosophy studies. Respondents reported enhanced roles after graduation in areas such as public health policy analysis (74%); planning, implementation and evaluation of public health interventions (74%); leadership roles (72%); and research (70%). The common perceived skills that were relevant to the respondents' present jobs were critical analysis (87%), multidisciplinary thinking (86%), demonstrating public health leadership skills (84%) and research (77%). Almost all respondents (90%) were confident in conducting research. Respondents recommended the provision of longer public health placement opportunities, elective courses on project management and advanced statistics, and 'internationalisation' of the programme's curriculum. CONCLUSIONS: The study has revealed the relevance of higher education in public health in developing the career prospects and skills of graduates. International graduates of this MSc PH programme were satisfied with the relevance and impact of the skills they acquired during their studies. The outcomes of this study can be used for curriculum reformation. Employers' perspectives of the capabilities of these graduates, however, need further consideration.

No evidence for parental age effects on offspring leukocyte telomere length in free-living Soay sheep.

In humans, the effect of paternal age at conception (PAC) on offspring leukocyte telomere length (LTL) is well established, with older fathers thought to pass on longer telomeres to their offspring in their sperm. Few studies have looked for PAC effects in other species, but it has been hypothesised that the effect will be exacerbated in polygamous species with higher levels of sperm competition and production. We test for maternal (MAC) and paternal age at conception effects on offspring LTL in Soay sheep, a primitive breed experiencing strong sperm competition. We use qPCR to measure relative telomere length in 389 blood samples (n = 318 individuals) collected from an unmanaged population of sheep on St Kilda, where individual age and parentage are known. We find no evidence that either MAC or PAC are associated with LTL in offspring across the age range, or when considering only young lambs (n = 164). This is the first study to test for parental age effects on offspring LTL in a wild mammal population, and the results contrast with the findings of numerous human studies that find a PAC effect, as well as predictions of a stronger PAC effect in polygamous species.

An audit of HIV treatment outcomes in a UK inner city cohort.

We describe the demographics and treatment outcomes of a HIV-infected cohort from Croydon University Hospital, London, UK. We showed that the Croydon Cohort had good viral load suppression (98.6% with viral load < 100 copies/ml and 99.0% with viral load < 200 copies/ml) despite being a potentially challenging cohort in a deprived area of London. The viral load outcomes are better than the Public Health England data from 2014 and the latest British HIV Association audit using data from 2009.

Process evaluation of the Bristol girls dance project.

BACKGROUND: The Bristol Girls Dance Project was a cluster randomised controlled trial that aimed to increase objectively measured moderate-to-vigorous physical activity (MVPA) levels of Year 7 (age 11-12) girls through a dance-based after-school intervention. The intervention was delivered in nine schools and consisted of up to forty after-school dance sessions. This paper reports on the main findings from the detailed process evaluation that was conducted. METHODS: Quantitative and qualitative data were collected from intervention schools. Dose and fidelity were reported by dance instructors at every session. Intervention dose was defined as attending two thirds of sessions and was measured by attendance registers. Fidelity to the intervention manual was reported by dance instructors. On four randomly-selected occasions, participants reported their perceived level of exertion and enjoyment. Reasons for non-attendance were self-reported at the end of the intervention. Semi-structured interviews were conducted with all dance instructors who delivered the intervention (n = 10) and school contacts (n = 9) in intervention schools. A focus group was conducted with girls who participated in each intervention school (n = 9). RESULTS: The study did not affect girls' MVPA. An average of 31.7 girls participated in each school, with 9.1 per school receiving the intervention dose. Mean attendance and instructors' fidelity to the intervention manual decreased over time. The decline in attendance was largely attributed to extraneous factors common to after-school activities. Qualitative data suggest that the training and intervention manual were helpful to most instructors. Participant ratings of session enjoyment were high but perceived exertion was low, however, girls found parts of the intervention challenging. CONCLUSIONS: The intervention was enjoyed by participants. Attendance at the intervention sessions was low but typical of after-school activities. Participants reported that the intervention brought about numerous health and social benefits and improved their dance-based knowledge and skills. The intervention could be improved by reducing the number of girls allowed to participate in each school and providing longer and more in-depth training to those delivering the intervention. TRIAL REGISTRATION: ISRCTN52882523 Registered 25th April 2013.

EEG Topographic Mapping of Visual and Kinesthetic Imagery in Swimmers.

This study investigated differences in QEEG measures between kinesthetic and visual imagery of a 100-m swim in 36 elite competitive swimmers. Background information and post-trial checks controlled for the modality of imagery, swimming skill level, preferred imagery style, intensity of image and task equality. Measures of EEG relative magnitude in theta, low (7-9 Hz) and high alpha (8-10 Hz), and low and high beta were taken from 19 scalp sites during baseline, visual, and kinesthetic imagery. QEEG magnitudes in the low alpha band during the visual and kinesthetic conditions were attenuated from baseline in low band alpha but no changes were seen in any other bands. Swimmers produced more low alpha EEG magnitude during visual versus kinesthetic imagery. This was interpreted as the swimmers having a greater efficiency at producing visual imagery. Participants who reported a strong intensity versus a weaker feeling of the image (kinesthetic) had less low alpha magnitude, i.e., there was use of more cortical resources, but not for the visual condition. These data suggest that low band (7-9 Hz) alpha distinguishes imagery modalities from baseline, visual imagery requires less cortical resources than kinesthetic imagery, and that intense feelings of swimming requires more brain activity than less intense feelings.

Na(v)1.7 sodium channel expression in human lingual nerve neuromas.

OBJECTIVE: Peripheral branches of the trigeminal nerve are often damaged during the removal of lower third molar teeth, and a small proportion of patients who sustain an injury develop persistent chronic pain. The cause of the pain is not clear and there are no satisfactory methods of treatment. The aim of the present study was to examine the expression of the sodium channel subtype Na(v)1.7 in damaged human lingual nerves, and to identify any association between Na(v)1.7 expression and reported symptoms of dysaesthesia. METHODS: Eleven neuromas-in-continuity (NICs) and 11 nerve-end neuromas (NENs) were studied, and were all obtained at the time of surgical repair of the damaged lingual nerve. Specimens were categorised as being obtained from patients with symptoms or without symptoms, according to the degree of pain, tingling or discomfort that had been experienced. The tissue was prepared and processed for indirect immunofluorescence, and image analysis was used to quantify the percentage area of PGP 9.5-labelled tissue that also contained Na(v)1.7. RESULTS: The results demonstrated that sodium channel Na(v)1.7 was expressed in human lingual nerve neuromas. There was no direct relationship between the level of expression of Na(v)1.7 and the patients' symptoms of dysaesthesia. However, in NICs there was found to be an inverse correlation between Na(v)1.7 and macrophage expression, and in symptomatic NICs a direct correlation was found between Na(v)1.7 expression and axonal apposition. CONCLUSIONS: These data suggest that Na(v)1.7 expression alone does not play a primary role in initiating the painful symptoms of dysaesthesia. The development of neuropathic pain may involve complex interactions including changes in ultrastructure and ion channel density.

Neuropeptide expression following ligation of the ferret lingual nerve.

Previous studies on the ferret inferior alveolar nerve found a close association between the spontaneous neural activity generated at a site of nerve injury, and the accumulation of neuropeptides in the injured axons. More recent electrophysiological studies on the lingual nerve revealed high levels of spontaneous activity 3 days after injury, a decline at 3 weeks and a late rise at 3 months. In the present study we have used immunocytochemical techniques to see whether this time course of spontaneous activity is again paralleled by an accumulation of neuropeptides. In 20 anaesthetised adult ferrets the left lingual nerve was ligated and sectioned distally, and the animals left to recover for 3 days, 3 weeks or 3 months. The tissue was processed using indirect immunofluorescence and image analysis was used to quantify levels of the neuropeptides; calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), enkephalin (ENK) and neuropeptide Y (NPY). Immunoreactivity to all of the neuropeptides was present proximal to the ligature 3 days after injury, and these high levels of expression had decreased considerably by 3 weeks. By 3 months ENK and NPY expression had almost disappeared proximal to the ligature, but levels of CGRP, SP, VIP and GAL had increased slightly. This was also accompanied by an accumulation of all of the neuropeptides, except NPY, in the portion of nerve immediately distal to the ligature. This late accumulation of certain neuropeptides coincides with the increase in spontaneous activity seen in our previous electrophysiological studies and supports the suggestion that neuropeptides may play a role in the aetiology of sensory disorders after nerve injury.

Remotivation therapy and Huntington's disease.

Huntington's disease (HD) is a genetic, autosomal dominant, neurodegenerative disorder for which there is no known cure. Because remotivation therapy (RmT) has been effective in other neurological conditions and because of the lack of current efficacious treatments for HD, RmT may be a beneficial therapy for persons suffering from the disease. By cultivating a more fertile environment, RmT leads to increased self-awareness, self-esteem, and an improved quality of life, even in late-stage HD. Two recent studies using animal models suggest that exposure of transgenic HD mice to a stimulating, enriched environment helped to prevent the loss of cerebral volume and delay the onset of motor disorders. Six case studies are presented that demonstrate improved physical, mental, and social functioning in persons with HD when a more stimulating environment is provided.

Quantitative neuropathological changes in presymptomatic Huntington's disease.

Morphometric studies of the tail of the caudate nucleus, the site where the pathology is first seen, were performed on 16 brain specimens collected from individuals at risk for inheriting Huntington's disease (HD). Medical records and information obtained from immediate family members indicated that all had died without symptoms of HD. Six individuals had 37 or more CAG repeats and were designated HD gene carriers, whereas 10 were determined to be non-carriers. Cell counts of the tail of the caudate nucleus revealed an increased density of oligodendrocytes among the presymptomatic HD gene carriers (mean cells/field: carriers = 40.0, noncarrier = 21.3; age, sex, repeated measure adjusted F[126] = 11.7, p = 0.0008). No statistically significant differences were found between HD carriers and noncarriers in the density of neurons (carriers = 16.9, noncarriers = 15.5), astrocytes (carriers = 27.8, noncarriers = 21.3) or microglial cells (carriers = 7.9, noncarriers = 5.6). Ubiquitin immunostaining performed in 3 gene carriers revealed intranuclear inclusions in all 3 cases, including 1, with 37 repeats, who died 3 decades before the expected age for onset of the clinical syndrome. Normal densities of other cell types and careful macroscopic examination suggest that the increase in oligodendroglial density is not a consequence of atrophy and may instead reflect a developmental effect of the HD gene.

Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.

The synthesis and structure-activity relationship (SAR) studies of a series of 4'-oxazolyl-N-(3,4-dimethyl-5-isoxazolyl)[1, 1'-biphenyl]-2-sulfonamide derivatives as endothelin-A (ET(A)) receptor antagonists are described. The data reveal a remarkable improvement in potency and metabolic stability when the 4'-position of the biphenylsulfonamide is substituted with an oxazole ring. Additional 2'-substitution of an acylaminomethyl group further increased the binding activity and provided one of the first subnanomolar ET(A)-selective antagonists in the biphenylsulfonamide series (17, ET(A) K(i) = 0.2 nM). Among the compounds described, 3 (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1, 1'-biphenyl]-2-sulfonamide; BMS-193884) had the optimum pharmacological profile and was therefore selected as a clinical candidate for studies in congestive heart failure.

Novel word acquisition in children with Down syndrome: does modality make a difference?

Signing is a commonly used intervention technique for children with cognitive impairments who have expressive language delays. Novel word learning in three conditions (signed only, spoken only, signed and spoken combined) was compared for children with Down syndrome (2;1 to 5;2) and mental-age matched control children (1;4 to 2;6). Spontaneous imitations and responses to production and comprehension probes were examined after 5, 10, and 15 word exposures. No group differences in frequency of imitations or productions were obtained. The frequency of imitations was highest in the combined condition. Probed productions were infrequent, although novel words were produced most often in spoken and combined conditions. For both imitated and probed productions in the combined condition, the spoken portion was almost exclusively produced. Across conditions, children with Down syndrome comprehended fewer words than did control children. The evidence for and explanations of the facilitative effect of signs and the advantage of dual-method presentation are discussed.

Predicting language production in children and adolescents with Down syndrome: the role of comprehension.

Predictors of language production skills in 12-minute narratives are investigated cross-sectionally in 48 children and adolescents with Down syndrome (trisomy 21), aged 5 to 20 years, in comparison to 48 control children aged 2 to 6 years matched statistically for nonverbal mental age and mother's years of education. Two models were evaluated by hierarchical regression analyses using predictors drawn from the domains of group membership, chronological age, cognition, socioeconomic status, and hearing screening status (Model I) and, additionally, comprehension performance (Model II). Results showed that Model II was more successful. In the DS group, it explained 68% of the variability in number of different words, 80% in MLU, and 32% in intelligibility. Corresponding percentages for the control group were 72%, 71%, and 26%. A mechanism linking comprehension of input to early stages of production practice through activation of the early speech motor area is proposed.

Evidence for the GluR6 gene associated with younger onset age of Huntington's disease.

Huntington's disease (HD) is attributed to a triplet CAG repeat mutation, and about half of the variation in onset age can be explained by the size of the repeat expansion. Recently, a TAA repeat polymorphism in close linkage to the kainate receptor, GluR6, was reported related to onset age in HD. We examined this polymorphism in 258 unrelated HD-affected persons (172 from a clinic sample and 86 from a postmortem series). This study confirms that the 155 allele is associated with younger onset age of HD and suggests that it is in linkage disequilibrium with a variant of the GluR6 gene or another gene in this region.

Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Language skills of children and adolescents with Down syndrome: II. Production deficits.

Hypotheses that children and adolescents with Down syndrome show (a) a specific expressive language impairment, (b) a "critical period" for language acquisition, (c) a "simple sentence syntactic ceiling" in production, and (d) deficit in grammatical morphology were investigated cross-sectionally. Conversational and narrative language samples from 47 children and adolescents with Down syndrome (Trisomy 21), aged 5 to 20 years, were compared to those from 47 control children aged 2 to 6 years matched statistically for nonverbal mental age. Children with Down syndrome appear to have a specific language impairment, compared to control children, in number of different words and total words (in the first 50 utterances) and in mean length of utterance (MLU). Total utterance attempts per minute were more frequent in the Down syndrome group. Narrative samples contained more word tokens, more word types, and longer MLU than conversation samples, for both groups. Intelligibility of narratives was significantly poorer for the Down syndrome group than controls. Analyses of narrative language sample by age sub-group showed no evidence of a critical period for language development ending at adolescence, nor of a "syntactic ceiling" at MLUs corresponding to simple sentences for the Down syndrome group. Omissions of word tokens and types were more frequent in the older Down syndrome than the younger control sample, matched on MLU.

Lymphoma presenting as parotid xanthogranulomatous sialadenitis.

We present a case of disseminated high-grade, T-cell-rich B-cell lymphoma in a 72-year-old white woman that presented as unilateral parotid swelling, and was initially diagnosed as xanthogranulomatous sialadenitis.

The role of oxybutynin in spinal cord injured patients with indwelling catheters.

PURPOSE: The long-term benefits of oral oxybutynin in spinal cord injured patients with indwelling catheters is unknown. We reviewed our experience with this population of men and present the results of our analysis. MATERIALS AND METHODS: A total of 109 male spinal cord injured patients at the Houston Veterans Affairs Medical Center have been treated with chronic indwelling catheters (80 transurethral and 29 suprapubic). Thirty-eight patients (35%) were identified as using oxybutynin on a regular basis. These patients were compared to those not using oxybutynin with regard to urodynamic parameters and upper tract deterioration. Specifically examined were bladder compliance, bladder leak point pressure, vesicoureteral reflux, hydronephrosis, urolithiasis, febrile urinary tract infections and serum creatinine greater than 2 mg./dl. RESULTS: The mean duration of indwelling catheter use was 11.9 years (12.4 without oxybutynin and 10.9 on oral oxybutynin). Of the 31 patients with normal compliance (greater than 20 ml./cm. water), 24 (77%) were using oxybutynin (p = 0.001). Bladder leak point pressures were abnormal (greater than 35 cm. water) in 5 of 32 patients (16%) on oxybutynin versus 34 of 60 (57%) without it (p <0.001). Hydronephrosis was present in 15 of 66 patients (23%) without oxybutynin versus 1 of 36 (3%) with oxybutynin (p = 0.009). Febrile urinary tract infections occurred in 4 of 35 patients (11%) versus 17 of 62 patients (27%) with or without oxybutynin, respectively (p = 0.077). No significant differences were found between the 2 groups with regard to reflux, renal scars, stones or elevated serum creatinine. CONCLUSIONS: It appears that regular use of oxybutynin may be beneficial in spinal cord injured patients who require chronic indwelling catheters for bladder management. Our analysis reveals that patients who take oxybutynin regularly have better bladder compliance, lower bladder leak point pressures and less hydronephrosis. Until a prospective, randomized trial reveals contradicting outcomes, empiric use of oxybutynin in all spinal cord injured patients requiring chronic indwelling catheters seems justified.