Political priorities and public health services in English local authorities: the case of tobacco control and smoking cessation services.

Background: Since 2013, local authorities in England have been responsible for public health including smoking cessation services. Methods: Online surveys of tobacco control leads in English local authorities were conducted in 2014 (76% response rate, n = 116), 2015 (82% response rate, n = 124) and 2016 (85% response rate, n = 129). Results: A high priority for tobacco control was reported in 17% of local authorities in 2014, rising to 27% in 2016. A low priority for tobacco control was reported in 4% of local authorities in 2014, rising to 11% in 2016. Budgets for smoking cessation services were cut in 16% of local authorities in 2014, 39% in 2015 and 59% in 2016. In 2016, budgets were cut in all local authorities where the priority given to tobacco control was perceived to be low and in 40% of the local authorities where it was perceived to be high. Cuts in smoking cessation budgets were principally due to cuts to the public health grant and wider cuts to local authority budgets. Conclusions: At a time of significant cost pressure, political support for tobacco control in English local authorities mitigates but does not remove the risk of cuts to budgets for smoking cessation services.

Primary synovial chondromatosis: a reassessment of malignant potential in 155 cases.

OBJECTIVE: Primary synovial chondromatosis (PSC) is a rare disorder characterised by cartilage formation in synovium-lined joints, tendon sheaths and bursae. It is thought that PSC cartilage arises from the proliferation of mesenchymal cells, which exhibit cartilaginous metaplasia in subintimal connective tissue. There are reports of transformation of PSC to chondrosarcoma, although the precise incidence and nature of this complication is uncertain. In this study we carried out a retrospective review PSC to determine the incidence of sarcomatous change in this condition, in addition to the clinical, radiological and pathological features that characterise this complication MATERIALS AND METHODS: We reviewed 155 cases of PSC and identified 4 cases (3 in the hip joint; 1 in the elbow joint) of aggressive behaviour and chondrosarcoma-like histology. RESULTS: Radiologically, these cases were all reported as showing features consistent with PSC and aggressive extra-articular soft tissue/bone involvement. Histologically, in addition to typical features of PSC, there was morphological evidence of peri-articular soft tissue and, in 2 cases, bone involvement by an infiltrating cartilaginous tumour. These tumours all behaved as locally aggressive neoplasms and did not give rise to metastasis. CONCLUSION: Our findings show that chondrosarcoma arises infrequently in PSC (approximately 2.5 %), and that this complication occurs most commonly in the hip joint (approximately 11 % of cases of hip PSC). These tumours behaved mainly as low-grade, locally aggressive tumours analogous to atypical cartilaginous tumour of bone/grade 1 chondrosarcoma of bone.

Relationships between impulse oscillometry, spirometry and dyspnoea in COPD.

BACKGROUND: Severity of chronic obstructive pulmonary disease (COPD) is based either on symptoms/disability or lung function, which have no discernible correlation. We hypothesised that impulse oscillometry (IOS), a non-effort-dependent measure of central and peripheral airway mechanics, could correlate to dyspnoea in COPD. METHODS: We analysed screening data from 57 COPD patients who had spirometry, IOS and Medical Research Council dyspnoea score (MRC) measurements. We searched for predictors or correlations of MRC from IOS, spirometry and demographics. RESULTS: MRC had no significant predictors or correlations from IOS, spirometry or demographics (possibly excepting smoking history, p=0.05). IOS correlated significantly with spirometry: FEV1 and FEF25-75 vs. R5-R20 (peripheral airway resistance), r= -0.499, p > 0.001 and r= -0.397, p= 0.002 respectively. CONCLUSION: MRC is not related to IOS or spirometry in COPD. IOS correlates well with spirometry, particularly peripheral airway resistance (R5-R20). IOS is useful, but does not provide a link between symptoms and pulmonary function measurements.

Prospective follow-up of novel markers of bone turnover in persistent asthmatics exposed to low and high doses of inhaled ciclesonide over 12 months.

CONTEXT: In asthmatic patients receiving long-term inhaled corticosteroid therapy, there are concerns regarding the potential for developing systemic adverse effects on bone metabolism, possibly even in the absence of adrenal suppression. OBJECTIVE: The aim of this study was to investigate whether exposure to inhaled ciclesonide at high vs. low doses over 1 yr causes any significant systemic adverse effect on sensitive biomarkers of bone turnover in asthmatic patients. DESIGN: Post hoc analysis of stored samples was performed in a subgroup of patients from a prospective, randomized parallel group trial with 1 yr follow-up. SETTING: We conducted a primary care study in Tayside, Scotland. PARTICIPANTS: A total of 164 mild-moderate persistent asthmatics aged 18-65 yr with evidence of airway hyperresponsiveness using mannitol bronchial challenge were enrolled into the original study. Of the 119 completed patients per protocol, 100 participants had bone marker samples available for analysis. INTERVENTIONS: Ciclesonide was titrated to control persistent asthma against either mannitol bronchial challenge [airway hyperresponsiveness (AHR) strategy] or a control group (based on symptoms, reliever use, and pulmonary function) over 1 yr. OUTCOME MEASURES: We measured markers of bone formation [amino-terminal propeptide of type I collagen (PINP), amino-terminal propeptide of type III collagen (PIIINP)], resorption [carboxy-terminal telopeptide of type I collagen (ICTP), type I collagen cross-linked C-telopeptide (CTx)], and adrenal suppression (overnight urinary cortisol/creatinine ratio) at 0 and 12 months. RESULTS: Mean ciclesonide doses after 12 months were: AHR, 507 µg/d (n = 50); and controls, 202 µg/d (n = 50) (P < 0.00001). There were no significant differences between AHR and control groups either at baseline or after 12 months in PINP, PIIINP, ICTP, or CTx; or in ratios of bone turnover as PINP/ICTP, PIIINP/CTx, or overnight urinary cortisol/creatinine ratio. CONCLUSION: Higher doses of inhaled ciclesonide do not adversely affect sensitive markers of bone turnover in persistent asthmatics over 12 months.

A survey detailing the calving performance of primiparous 2-year-old beef heifers and outcomes of assisted calving.

AIM: To examine via a survey the management at calving of primiparous, 2-year-old beef heifers on selected beef cattle farms in New Zealand and to investigate the causes and outcomes of assisted calving of these heifers. METHODS: An initial survey of beef cattle farmers identified that many beef breeding heifers were assisted at parturition in 2006. The outcome of assistance at parturition in the industry was not examined in that survey. A two-part questionnaire was sent to 204 respondents to the previous survey who had indicated a willingness to participate and had bred 15-month-old heifers in 2006. These respondents are unlikely to be a representative sample of all beef cattle farmers in New Zealand. A total of 127 responses were received to Part A, which encompassed mating and calving management and results and 107 responses were received to Part B, which addressed survival of calves and management of the replacement heifers. RESULTS: A total of 6726 heifers were joined with bulls in the respondents' herds in 2006. The percentage of calves born to primiparous, 2-year-old heifers present at marking was 83 (95% CI = 80-86)% of heifers joined with a bull. Overall assistance percentage was 9.7 (95% CI = 7.6-11.9)%, and 30 (95% CI = 25-35)% of 376 calves assisted at birth for which fate was reported were stillborn. The predominant cause of assisted calving was feto-maternal disproportion, and 11 (95% CI = 7-16)% of assisted heifers had died by 4 weeks postpartum. The most common time to first graze heifers with the mature cow herd was between first calving and second mating. Eighty-five (95% CI = 58-100)% of heifers that calved at 2 years of age in 2006 calved again in 2007 and this was not affected by stage of integration into the mixed-aged cow herd. Failure to conceive at second mating was the predominant reason for heifer attrition: 3.8 (95% CI = 0-16)% were culled after being diagnosed non-pregnant and a further 2.3 (95% CI = 0-18)% were carried over as empty 3-year-old heifers. CONCLUSIONS: The 85% retention of heifers as second-calving, 3-year-olds indicated that heifers were achieving adequate rebreeding rates after first calving. The survival of heifers and calves in the neonatal period could be increased by reducing the need for or improving the outcomes of assistance at parturition.

A survey of beef cattle farmers in New Zealand, examining management practices of primiparous breeding heifers.

AIM: To obtain an estimate of the incidence of assistance at calving in primiparous (first-calving) beef heifers and the prevalence of breeding heifers at 15 months of age in New Zealand in 2006, and to identify factors contributing to farmers' decisions regarding breeding strategies for heifers, using a survey of beef cattle farmers. METHODS: A questionnaire was sent to farmers listed in a Massey University database and to members of selected breed societies, as well as published in an industry newspaper; 331 valid responses were received. Information was gathered on the age and number of primiparous heifers, number of heifers assisted, and the importance of various reasons for and against breeding heifers at 15 months of age. Respondents were also required to outline the criteria used for selecting bulls to join with heifers, and the strategies used to manage dystocia in primiparous heifers. RESULTS: Sixty-five (95% CI=58-71)% of respondents had only 2-year-old primiparous heifers in 2006, whilst a further 11 (95% CI=8-16)% had both 2- and 3-year-old primiparous heifers. The mean reported incidence of assisted calving was 7.0 (95% CI=6.4-7.5)% for 2-year-old primiparous heifers and 1.7 (95% CI=1.2-2.2)% for 3-year-old primiparous heifers. The reported incidence of assistance at calving within individual herds ranged from 0 to 100% for 2-year-old heifers. Respondents with bull-breeding herds most commonly observed their primiparous 2-year-old heifers twice daily, whilst respondents with commercial herds most commonly observed them once daily during calving. The most important reason for breeding heifers at 15 months of age was increased profit, whereas the most important reason for not breeding them at that age was concern about rebreeding performance of 2-year-old heifers. Estimated breeding value (EBV) for birthweight was the factor considered most frequently when selecting bulls to join with maiden heifers; age of bull and body shape of bull were the next most frequently considered factors. Selection of an appropriate bull was the most common strategy used to manage dystocia in 2-year-old beef heifers. CONCLUSIONS: The majority of respondents calved their heifers at 2 years of age, and increased profit was the primary motivator. Concern about the rebreeding performance of 2-year-old heifers was the most important reason among the remainder of respondents for not breeding heifers at 15 months of age. Dystocia in 2-year-old heifers was not a problem or a minor problem in most herds, but there was much variation amongst herds.

The needs of people with HIV in the UK: findings from a national survey.

The aim of this study was to describe the needs of people living with HIV in the UK. A questionnaire addressing 17 areas of need was completed by 1821 people living with HIV in the UK. The core need indicator was a personal assessment of happiness with current state. A quarter of all respondents were happy with their current state across all needs. For each need, the following proportions were unhappy with their current state: sex, 40%; anxiety/depression, 33%; sleep, 32%; self-confidence, 32%; money, 28%; household chores and self-care, 18%; housing, 18%; appetite, eating and drinking, 17%; friendships, 17%; discrimination, 16%; mobility, 15%; dealing with health professionals, 15%; relationships, 14%; drugs and alcohol, 9%; taking treatments regularly, 5%; HIV treatment knowledge, 4%; looking after children, 2%. Although some people with HIV are coping well with minimal unmet need, the overall picture of need is dominated by personal, social and economic issues.

Coincidence of immune-mediated diseases driven by Th1 and Th2 subsets suggests a common aetiology. A population-based study using computerized general practice data.

BACKGROUND: The recent rise in the prevalence of immune-mediated diseases has been attributed to environmental factors such as a lack of microbial challenge, or dietary change, that deviate the overall balance between mutually antagonistic subsets of T helper (Th) cells. OBJECTIVE: An alternative proposal is that recent environmental changes have resulted in an immune system that is more likely to produce both Th1 and Th2 responses against benign antigens. The prediction of this hypothesis, that Th1 and Th2-mediated diseases are not mutually exclusive, and may be positively associated, is tested here in a whole population. METHODS: Data from General Practices participating in the Scottish Continuous Morbidity Recording (CMR) project were used to determine the coincidence of the major Th2-mediated atopic diseases; asthma, eczema and allergic rhinitis, with the Th1-mediated autoimmune conditions; type I diabetes, rheumatoid arthritis and psoriasis. We also identified the prescription rates of inhaled therapy for asthma in patients with Th1-mediated disease. RESULTS: There was a significant increase in the risk of presenting with a Th1-mediated autoimmune condition in patients with a history of allergic disease (standardized prevalence ratio (95% confidence interval) 1.28 (1.18-1.37)). Likewise, the standardized prevalence ratios of presenting with either eczema (1.67 (1.48-1.87)) or allergic rhinitis (1.22 (1.02-1.44)) were significantly increased in subjects with a history of Th1-mediated disease. There was a particularly strong association between current psoriasis and current eczema (standardized prevalence ratio ofpsoriasis in subjects with eczema 2.88, 95% confidence interval (CI) 2.38-3.45). There was also a significant increase in prescriptions for inhaled asthma therapy in patients with Th1 disease. CONCLUSION: It is concluded that Th1- and Th2-mediated diseases are significantly associated in a large General Practice population. This finding supports the proposal that autoimmune and atopic diseases share risk factors that increase the propensity of the immune system to generate both Th1- and Th2-mediated inappropriate responses to non-pathological antigens.

Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer's disease.

Amyloid beta(1-42), a major component of amyloid plaques, binds with exceptionally high affinity to the alpha 7 nicotinic acetylcholine receptor and accumulates intracellularly in neurons of Alzheimer's disease brains. In this study, we investigated the possibility that this binding plays a key role in facilitating intraneuronal accumulation of amyloid beta(1-42). Consecutive section immunohistochemistry and digital imaging were used to reveal the spatial relationship between amyloid beta(1-42) and the alpha 7 receptor in affected neurons of Alzheimer's disease brains. Results showed that neurons containing substantial intracellular accumulations of amyloid beta(1-42) invariably express relatively high levels of the alpha 7 receptor. Furthermore, this receptor is highly co-localized with amyloid beta(1-42) within neurons of Alzheimer's disease brains. To experimentally test the possibility that the binding interaction between exogenous amyloid beta(1-42) and the alpha 7 receptor facilitates internalization and intracellular accumulation of amyloid beta(1-42) in Alzheimer's disease brains, we studied the fate of exogenous amyloid beta(1-42) and its interaction with the alpha 7 receptor in vitro using cultured, transfected neuroblastoma cells that express elevated levels of this receptor. Transfected cells exhibited rapid binding, internalization and accumulation of exogenous amyloid beta(1-42), but not amyloid beta(1-40). Furthermore, the rate and extent of amyloid beta(1-42) internalization was related directly to the alpha 7 receptor protein level, since (1) the rate of amyloid beta(1-42) accumulation was much lower in untransfected cells that express much lower levels of this receptor and (2) internalization was effectively blocked by alpha-bungarotoxin, an alpha 7 receptor antagonist. As in neurons of Alzheimer's disease brains, the alpha 7 receptor in transfected cells was precisely co-localized with amyloid beta(1-42) in prominent intracellular aggregates. Internalization of amyloid beta(1-42) in transfected cells was blocked by phenylarsine oxide, an inhibitor of endocytosis. We suggest that the intraneuronal accumulation of amyloid beta(1-42) in Alzheimer's disease brains occurs predominantly in neurons that express the alpha 7 receptor. In addition, internalization of amyloid beta(1-42) may be facilitated by the high-affinity binding of amyloid beta(1-42) to the alpha 7 receptor on neuronal cell surfaces, followed by endocytosis of the resulting complex. This provides a plausible explanation for the selective vulnerability of neurons expressing the alpha 7 receptor in Alzheimer's disease brains and for the fact that amyloid beta(1-42) is the dominant amyloid beta peptide species in intracellular accumulations and amyloid plaques.

Telomere associations in interphase nuclei: possible role in maintenance of interphase chromosome topology.

The relative sizes of individual telomeres in cultured human cells under conditions of cell cycling, replicative quiescence, cell transformation and immortalization were determined using quantitative fluorescence in situ hybridization (Q-FISH) with a telomere-specific peptide nucleic acid (PNA) probe. Results obtained from analysis of telomere length profiles (TLPs), which display the distribution of relative telomere lengths for individual cells, confirmed telomere length heterogeneity at the single cell level and proportional shortening of telomere length during replicative aging of virus-transformed cells. TLPs also revealed that some telomeric ends of chromosomes are so closely juxtaposed within interphase nuclei that their fluorescent signals appear as a single spot. These telomeric associations (TAs) were far more prevalent in interphase nuclei of noncycling normal and virus-transformed cells than in their cycling counterparts. The number of interphase TAs per nucleus observed in late-passage E6/E7-transformed cells did not increase during progression to crisis, suggesting that telomere shortening does not increase the frequency of interphase TAs. Furthermore, interphase TAs were rarely observed in rapidly cycling, telomerase-positive, immortalized cells that exhibit somewhat shortened, but stabilized, telomere length through the activity of telomerase. Our overall results suggest that the number of interphase TAs is dependent more on whether or not cells are cycling than on telomere length, with TAs being most prominent in the nuclei of replicatively quiescent cells in which nonrandom (even preferred) chromosome spatial arrangements have been observed. We propose that interphase TAs may play a role in the generation and/or maintenance of nuclear architecture and chromosome positional stability in interphase nuclei, especially in cells with a prolonged G(1)/G(0) phase and possibly in terminally differentiated cells.

Dendritic alterations of cerebellar Purkinje neurons in postnatally lead-exposed kittens.

Many investigations have sought to determine the effect of lead exposure on the development of the cerebellum. This study addresses the effects of postnatal lead exposure in kittens on dendritic development of Purkinje cells. Golgi-Cox filled cells were used to measure dendritic branching patterns, spine density, height, width and distance from the cerebellar surface. The results revealed a significant increase in spine density and altered patterns of dendritic branching. Complex dendritic branching was evident with a progressive shift in peak branching peripherally. Lead-exposed Purkinje cells showed early sprouting with subsequent pruning. At 5 weeks of age dendritic branches on experimental cells were increased along the entire dendritic extent. Control Purkinje cells showed initial sprouting with subsequent pruning. Normal developmental growth spurts and lead-induced effects were evident on dendritic height, width and distance from the surface. Cerebella stained with hematoxylin and eosin and cresyl violet acetate showed no evidence of vascular damage or other pathologies. These findings corroborate the evidence of hyperspiny dendritic formation representing an important mechanism of neuronal plasticity. In regard to morphological effects of lead on rodents, the hyperspiny Purkinje cell dendrites and patterns of dendritic growth in lead-treated kittens offer an alternative interpretation of neurobehavioral findings of lead-burdened children. The results are discussed with reference to other aspects of lead exposure and neural development.

Childhood exposure to infection and risk of adult onset wheeze and atopy.

BACKGROUND: The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. METHODS: A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. RESULTS: The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. CONCLUSIONS: In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.

Radical radiotherapy for inoperable non-small cell lung cancer: what factors predict prognosis?

We set out to determine the factors that predict the outcome of conventional radical radiotherapy for inoperable non-small cell lung cancer. A retrospective casenote review was carried out of all 69 patients treated between 1986 and 1992 at the Northern Ireland Centre for Clinical Oncology, Belfast, with radical radiotherapy for inoperable non-small cell lung cancer. The tumour dose ranged from 45 Gy to 67.5 Gy, delivered in 15-30 fractions, 5 days per week over 3-6 weeks. All patients were followed up for 5 years. The disease was TNM Stage T1-T4N0-N2M0. The majority of tumours (51) were squamous. Overall survival was 63.8% (44-patients; 95% confidence interval (CT) 51.3-75.2) at one year; median survival was 16 months and 5-year survival was 13% (nine patients; 95% CI 6.1-23.3). Five-year survival for the 36 patients with stage T1 or T2 disease was 5.6% (2 patients). Five-year survival for the 33 patients with stage T3 or T4 disease, all with tumours at or near the carina, was 21.2% (seven patients). A WHO performance status of 0 or 1 (P = 0.03, Cox proportional hazards model) was associated with a better chance of survival.