Uteroplacental insufficiency leads to hypertension, but not glucose intolerance or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats

Growth restriction impacts on offspring development and increases their risk of disease in adulthood which is exacerbated with "second hits." The aim of this study was to investigate if blood pressure, glucose tolerance, and skeletal muscle mitochondrial biogenesis were altered in 12-month-old male and female offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel ligation induced uteroplacental insufficiency and growth restriction in offspring (Restricted). A sham surgery was also performed during pregnancy (Control) and some litters from sham mothers had their litter size reduced (Reduced litter), which restricted postnatal growth. Growth-restricted females only developed hypertension at 12 months, which was not observed in males. In Restricted females only homeostasis model assessment for insulin resistance was decreased, indicating enhanced hepatic insulin sensitivity, which was not observed in males. Plasma leptin was increased only in the Reduced males at 12 months compared to Control and Restricted males, which was not observed in females. Compared to Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males and females, suggesting that at 12 months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1α levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12 months of age. In summary, sex strongly impacts the cardiometabolic effects of growth restriction in 12-month-old rats and it is females who are at particular risk of developing long-term hypertension following growth restriction.

Collagen type III and VI turnover in response to long-term immobilization

BACKGROUND: Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarkers derived from turnover of collagen type III and type VI in a long-term immobilization and remobilization study. We also compared individual biomarker levels with Lean body Mass (LBM) and changes therein, hypothesizing that these biomarkers would be biomarkers of the remodeling processes associated with immobilization and/or remobilization. METHODS: In the Berlin bed rest study, 20 young men were recruited and randomly assigned to 8-week's strict bed rest with or without resistive vibration exercise countermeasure. We measured three neo-epitope ELISA kits in the serum samples of this study: Pro-C3, measured the synthesis of collagen type III; Pro-C6, measured the synthesis of collagen type VI; and C6M measured the degradation of collagen type VI induced by MMP-2 and MMP-9 cleavage. RESULTS: Pro-C3 and Pro-C6 biomarkers are up-regulated with both immobilization and remobilization, whereas C6M is hardly affected at all. We found that Pro-C3 and C6M levels are related to LBM at baseline and that high levels of Pro-C6 are associated with smaller changes in muscle mass during both immobilization and remobilization. CONCLUSION: The Pro-C3 and-C6 biomarkers change likely reflect remodeling changes in response to unloading or reloading, whereas C6M does not appear to respond to unloading. Pro-C3 and C6M levels correlate with LBM at baseline, while Pro-C6 is related to the anabolic and catabolic responses to unloading and reloading.

Changing guards: time to move beyond body mass index for population monitoring of excess adiposity

With the obesity epidemic, and the effects of aging populations, human phenotypes have changed over two generations, possibly more dramatically than in other species previously. As obesity is an important and growing hazard for population health, we recommend a systematic evaluation of the optimal measure(s) for population-level excess body fat. Ideal measure(s) for monitoring body composition and obesity should be simple, as accurate and sensitive as possible, and provide good categorization of related health risks. Combinations of anthropometric markers or predictive equations may facilitate better use of anthropometric data than single measures to estimate body composition for populations. Here, we provide new evidence that increasing proportions of aging populations are at high health-risk according to waist circumference, but not body mass index (BMI), so continued use of BMI as the principal population-level measure substantially underestimates the health-burden from excess adiposity.

Engaging patients, clinicians and health funders in weight management: the Counterweight Programme

Background. The Counterweight Programme provides an evidence based and effective approach for weight management in routine primary care. Uptake of the programme has been variable for practices and patients.

Aim. To explore key barriers and facilitators of practice and patient engagement in the Counterweight Programme and to describe key strategies used to address barriers in the wider implementation of this weight management programme in UK primary care.

Methods. All seven weight management advisers participated in a focus group. In-depth interviews were conducted with purposeful samples of GPs (n = 7) and practice nurses (n = 15) from 11 practices out of the 65 participating in the programme. A total of 37 patients participated through a mixture of in-depth interviews (n = 18) and three focus groups. Interviews and focus groups were analysed for key themes that emerged.

Results. Engagement of practice staff was influenced by clinicians’ beliefs and attitudes, factors relating to the way the programme was initiated and implemented, the programme content and organizational/contextual factors. Patient engagement was influenced by practice endorsement of the programme, clear understanding of programme goals, structured proactive follow-up and perception of positive outcomes.

Conclusions. Having a clear understanding of programme goals and expectations, enhancing self-efficacy in weight management and providing proactive follow-up is important for engaging both practices and patients. The widespread integration of weight management programmes into routine primary care is likely to require supportive public policy.

Empowering primary care to tackle the obesity epidemic: the Counterweight Programme

Subjects: Obese patients (body mass index greater than or equal to30 kg/m2) or BMIgreater than or equal to28 kg/m2 with obesity-related comorbidities in 80 general practices.

Intervention: The model consists of four phases: (1) audit and project development, (2) practice training and support, (3) nurse-led patient intervention, and (4) evaluation. The intervention programme used evidence-based pathways, which included strategies to empower clinicians and patients. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation.

Main outcome measures: Proportion of practices trained and recruiting patients, and weight change at 12 months.

Results: By March 2004, 58 of the 62 (93.5%) intervention practices had been trained, 47 (75.8%) practices were active in implementing the model and 1549 patients had been recruited. At 12 months, 33% of patients achieved a clinically meaningful weight loss of 5% or more. A total of 49% of patients were classed as 'completers' in that they attended the requisite number of appointments in 3, 6 and 12 months. 'Completers' achieved more successful weight loss with 40% achieving a weight loss of 5% or more at 12 months.

Conclusion: The Counterweight programme provides a promising model to improve the management of obesity in primary care.

Sponsorship: Educational grant-in-aid from Roche Products Ltd.

The Counterweight Programme: prevalence of CVD risk factors by body mass index and impact of a 10% weight change

Objectives

To examine relationships between body mass index (BMI), prevalence of physician-recorded cardiovascular disease (CVD) risk factors in primary care, and changes in risk with 10% weight change.

Methods

The Counterweight Project conducted a baseline cross-sectional survey of medical records of 6150 obese (BMI ≥ 30 kg/m2), 1150 age- and sex-matched overweight (BMI 25 to <30 kg/m2), and 1150 age- and sex-matched normal weight (BMI 18.5 to <25 kg/m2) controls, in primary care. Data were collected for the previous 18 months to examine BMI and disease prevalence, and then modelled to show the potential effect of 10% weight loss or gain on risk.

Results

Obese patients develop more CVD risk factors than normal weight controls. BMI ≥ 40 kg/m2 exhibits increased prevalence of type 2 diabetes mellitus (DM), odds ratio (OR) men: 6.16 (p < 0.001); women: 7.82 (p < 0.001) and hypertension OR men: 5.51 (p < 0.001); women: 4.16 (p < 0.001). Dyslipidaemia peaked around BMI 35 to <37.5 kg/m2, OR men: 3.26 (p < 0.001); women 3.76 (p < 0.001) and CVD at BMI 37.5 to <40 kg/m2 in men, OR 4.48 (p < 0.001) and BMI ≥ 40 kg/m2 in women, OR 3.98 (p < 0.001).

A 10% weight loss from the sample mean of 32.5 kg/m2 reduced the OR for type 2 DM by 30% and CVD by 20%, while 10% weight gain increased type 2 DM risk by more than 35% and CVD by 20%.

Conclusion

Obesity plays a fundamental role in CVD risk, which is reduced with weight loss. Weight management intervention strategies should be a public health priority to reduce the burden of disease in the population.

The impact of obesity on drug prescribing in primary care

Background

Healthcare costs attributable to obesity have previously involved estimations based on costs of diseases commonly considered as having obesity as an underlying factor.

Aim

To quantify the impact of obesity on total primary care drug prescribing.

Design of study

Review of computer generated and handwritten prescriptions to determine total prescribing volume for all drug classes.

Setting

Twenty-three general practice surgeries in the UK.

Method

Stratified random selection of 1150 patients who were obese (body mass index [BMI]>30 kg/m2) and 1150 age- and sex-matched controls of normal weight (BMI 18.5–<25 kg/m2). Retrospective review of medical records over an 18-month period.

Results

A higher percentage of patients who were obese, compared with those of normal weight, were prescribed at least one drug in the following disease categories: cardiovascular (36% versus 20%), central nervous system (46% versus 35%), endocrine (26% versus 18%), and musculoskeletal and joint disease (30% versus 22%). All of these categories had a P-value of <0.001. Other categories, such as gastrointestinal (24% versus 18%), infections (42% versus 35%), skin (24% versus 19%) had a P-value of <0.01, while respiratory diseases (18% versus 21%) had a P-value of <0.05. Total prescribing volume was significantly higher for the group with obesity and was increased in the region of two- to fourfold in a wide range of prescribing categories: ulcer healing drugs, lipid regulators, β-adrenoreceptor drugs, drugs affecting the rennin angiotensin system, calcium channel blockers, antibacterial drugs, sulphonylureas, biguanides, non-steroidal anti-inflammatories (NSAIDs) (P<0.001) and fibrates, angiotensin II antagonists, and thyroid drugs (P<0.05). The main impact on prescribing volumes is from numbers of patients treated, although in some areas there is an effect from greater dosage or longer treatment in those who are obese including calcium channel blockers, antihistamines, hypnotics, drugs used in the treatment of nausea and vertigo, biguanides, and NSAIDs (P<0.05) reflected in significantly increased defined daily dose prescribing.

Current approaches to obesity management in UK Primary Care: the Counterweight Programme

Background/Aims Primary care is expected to develop strategies to manage obese patients as part of coronary heart disease and diabetes national service frameworks. Little is known about current management practices for obesity in this setting. The aim of this study is to examine current approaches to obesity management in UK primary care and to identify potential gaps in care.

Method A total of 141 general practitioners (GPs) and 66 practice nurses (PNs) from 40 primary care practices participated in structured interviews to examine clinician self-reported approaches to obesity management. Medical records were also reviewed for 100 randomly selected obese patients from each practice [body mass index (BMI) ≥30 kg m−2, n = 4000] to review rates of diet counselling, dietetic or obesity centre referrals, and use of anti-obesity medication. Computerized medical records for the total practice population (n = 206 341, 18–75 years) were searched to examine the proportion of patients with a weight/BMI ever recorded.

Results Eighty-three per cent of GPs and 97% of PNs reported that they would raise weight as an issue with obese patients (P < 0.01). Few GPs (15%) reported spending up to 10 min in a consultation discussing weight-related issues, compared with PNs (76%; P < 0.001). Over 18 months, practice-based diet counselling (20%), dietetic (4%) and obesity centre (1%) referrals, and any anti-obesity medication (2%) were recorded. BMI was recorded for 64.2% of patients and apparent prevalence of obesity was less than expected.

Conclusion Obesity is under-recognized in primary care even in these 40 practices with an interest in weight management. Weight management appears to be based on brief opportunistic intervention undertaken mainly by PNs. While clinicians report the use of external sources of support, few patients are referred, with practice-based counselling being the most common intervention.

A new evidence-based approach to weight management in primary care: the Counterweight Programme

Background/Aims Obesity has become a global epidemic, and a major preventable cause of morbidity and mortality. Management strategies and treatment protocols are however poorly developed and evaluated. The aim of the Counterweight Programme is to develop an evidence-based model for the management of obesity in primary care.

Methods The Counterweight Programme is based on the theoretical model of Evidence-Based Quality Assessment aimed at improving the management of obese adults (18–75 years) in primary care. The model consists of four phases: (1) practice audit and needs assessment, (2) practice support and training, (3) practice nurse-led patient intervention, and (4) evaluation. Patient intervention consisted of screening and treatment pathways incorporating evidence-based approaches, including patient-centred goal setting, prescribed eating plans, a group programme, physical activity and behavioural approaches, anti-obesity medication and weight maintenance strategies. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. Eighty practices were recruited of which 18 practices were randomized to act as controls and receive deferred intervention 2 years after the initial audit.

Results By February 2004, 58 of the 62 (93.5%) intervention practices had been trained to run the intervention programme, 47 (75.8%) practices were active in implementing the model and 1256 patients had been recruited (74% female, 26% male, mean age 50.6 years, SD 14). At baseline, 75% of patients had at one or more co-morbidity, and the mean body mass index (BMI) was 36.9 kg/m2 (SD 5.4). Of the 1256 patients recruited, 91% received one of the core lifestyle interventions in the first 12 months. For all patients followed up at 12 months, 34% achieved a clinical meaningful weight loss of 5% or more. A total of 51% of patients were classed as compliant in that they attended the required level of appointments in 3, 6, and 12 months. For fully compliant patients, weight loss improved with 43% achieving a weight loss of 5% or more at 12 months.

Conclusion The Counterweight Programme is an evidence-based weight management model which is feasible to implement in primary care.

Long-term cost-effectiveness of weight management in primary care

Background:  As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively.

Methods:  Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain.

Results:  Mean weight changes in Counterweight attenders was −3 kg and −2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was £59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was ‘dominant’ (cost-saving) under ‘base-case scenario’, where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was £2017 where background weight gain was limited to 0.5 kg/year, and £2651 at 0.3 kg/year. Under a ‘best-case scenario’, where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained ‘dominant’ with background weight gains 1 kg, 0.5 kg or 0.3 kg/year.

Conclusion:  Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

Evaluation of the Counterweight Programme for obesity management in primary care: a starting point for continuous improvement

Background Evaluation for obesity management in primary care is limited, and successful outcomes are from intensive clinical trials in hospital settings.

Aim To determine to what extent measures of success seen in intensive clinical trials can be achieved in routine primary care. Primary outcome measures were weight change and percentage of patients achieving ≤5% loss at 12 and 24 months.

Design of study Prospective evaluation of a new continuous improvement model for weight management in primary care.

Setting Primary care, UK.

Method Primary care practice nurses from 65 UK general practices delivered interventions to 1906 patients with body mass index (BMI) ≥30 kg/m2 or ≥28 kg/m2 with obesity-related comorbidities.

Results Mean baseline weight was 101.2 kg (BMI 37.1 kg/m2); 25% of patients had BMI ≥40 kg/m2 and 74% had ≥1 major obesity-related comorbidity. At final data capture 1419 patients were in the programme for ≥12 months, and 825 for ≥24 months. Mean weight change in those who attended and had data at 12 months (n = 642) was −3.0 kg (95% CI = −3.5 to −2.4 kg) and at 24 months (n = 357) was −2.3 kg (95% CI = −3.2 to −1.4 kg). Among attenders at specific time-points, 30.7% had maintained weight loss of ≥5% at 12 months, and 31.9% at 24 months. A total of 761 (54%) of all 1419 patients who had been enrolled in the programme for >12 months provided data at or beyond 12 months.

Conclusion This intervention achieves and maintains clinically valuable weight loss within routine primary care.

Influence of body mass index on prescribing costs and potential cost savings of a weight management programme in primary care

Objectives Prescribed medications represent a high and increasing proportion of UK health care funds. Our aim was to quantify the influence of body mass index (BMI) on prescribing costs, and then the potential savings attached to implementing a weight management intervention.

Methods Paper and computer-based medical records were reviewed for all drug prescriptions over an 18-month period for 3400 randomly selected adult patients (18–75 years) stratified by BMI, from 23 primary care practices in seven UK regions. Drug costs from the British National Formulary at the time of the review were used. Multivariate regression analysis was applied to estimate the cost for all drugs and the ‘top ten’ drugs at each BMI point. This allowed the total and attributable prescribing costs to be estimated at any BMI. Weight loss outcomes achieved in a weight management programme (Counterweight) were used to model potential effects of weight change on drug costs. Anticipated savings were then compared with the cost programme delivery. Analysis was carried out on patients with follow-up data at 12 and 24 months as well as on an intention-to-treat basis. Outcomes from Counterweight were based on the observed lost to follow-up rate of 50%, and the assumption that those patients would continue a generally observed weight gain of 1 kg per year from baseline.

Results The minimum annual cost of all drug prescriptions at BMI 20 kg/m2 was £50.71 for men and £62.59 for women. Costs were greater by £5.27 (men) and £4.20 (women) for each unit increase in BMI, to a BMI of 25 (men £77.04, women £78.91), then by £7.78 and £5.53, respectively, to BMI 30 (men £115.93 women £111.23), then by £8.27 and £4.95 to BMI 40 (men £198.66, women £160.73). The relationship between increasing BMI and costs for the top ten drugs was more pronounced. Minimum costs were at a BMI of 20 (men £8.45, women £7.80), substantially greater at BMI 30 (men £23.98, women £16.72) and highest at BMI 40 (men £63.59, women £27.16). Attributable cost of overweight and obesity accounted for 23% of spending on all drugs with 16% attributable to obesity. The cost of the programme was estimated to be approximately £60 per patient entered. Modelling weight reductions achieved by the Counterweight weight management programme would potentially reduce prescribing costs by £6.35 (men) and £3.75 (women) or around 8% of programme costs at one year, and by £12.58 and £8.70, respectively, or 18% of programme costs after two years of intervention. Potential savings would be increased to around 22% of the cost of the programme at year one with full patient retention and follow-up.

Conclusion Drug prescriptions rise from a minimum at BMI of 20 kg/m2 and steeply above BMI 30 kg/m2. An effective weight management programme in primary care could potentially reduce prescription costs and lead to substantial cost avoidance, such that at least 8% of the programme delivery cost would be recouped from prescribing savings alone in the first year.

Renault do Brasil Automóveis S.A. : estudo de caso da estratégia operacional

Diante do novo cenário internacional globalizado e competitivo, as montadoras têm desenvolvido novas configurações de cadeias de suprimentos e estratégias operacionais, buscando atender às exigências da atual cadeia de valores deste segmento industrial. O objetivo do presente estudo é analisar a estratégia operacional e a cadeia de suprimentos de uma das novas montadoras que se instalou no Brasil, examinando prioritariamente como está definida e o porquê está assim definida. Para que o objetivo fosse atingido, foi estudada sua organização industrial, pois se percebeu que uma cadeia de suprimentos deve estar suportada por uma operação. O estudo realizado evidenciou que a montadora utiliza as melhores práticas operacionais desenvolvidas, porém no contexto local. Ela apresenta dimensões operacionais que vão do fordismo ao lean production, existindo dimensões que podem em um momento assumir uma característica puramente fordista e em outro momento apresentar características lean, sistema operacional baseado na flexibilidade. A cadeia de suprimentos da montadora em questão também se baseia nas melhores práticas de suprimentos. Ela não inova na questão dos modelos. Sua escolha é bastante conservadora, pois segmentou sua cadeia de suprimentos em três diferentes estratégias: outsourcing, just-in-time e gestão de estoques. Talvez aí esteja sua inovação, apresentar flexibilidade de implementar a melhor prática para o contexto econômico e social que encontrou no país. Como conclusão do estudo, foi possível determinar exatamente quais variáveis definem sua cadeia de suprimentos. Uma metodologia flexível, estruturada e consistente guia essa montadora em suas decisões operacionais estratégicas.

Qual é a identidade corporativa dos gerentes estratégicos da sede da E&P e o que isso implica na formação de um ambiente interno cooperativo e/ou competitivo?

Neste trabalho de dissertação busca-se descobrir qual é a identidade corporativa dos principais gerentes da área de Exploração e Produção da PETROBRAS, e analisar os limites e as possibilidades desta identidade na fonnação de um ambiente interno competitivo ou cooperativo. Para tanto, foi realizada pesquisa com base em dois extremos de identidade corporativa, um que representa a identidade corporativa de uma empresa com características de produção em massa e outro que representa uma empresa com características de produção enxuta.