Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma

Background: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target. Methods: In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells. Results: Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway. Conclusion: Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma

Poisoning of reintroduced red kites (Milvus Milvus) in England

Programmes to reintroduce predatory birds are resource intensive and expensive, yet there are few long-term studies on the health of these reintroduced birds following release. A total of 326 red kites (Milvus milvus) were released at four sites in England between 1989 and 2006 as part of efforts to reintroduce this species to England and Scotland, resulting in the establishment of several rapidly expanding populations in the wild. Detailed post-mortem examinations were carried out on 162 individuals found dead between 1989 and 2007, involving both released and wild-fledged birds. Toxicological analysis of one or more compounds was performed on 110 of the 162 birds. Poisoning was diagnosed in 32 of these 110 kites, 19 from second generation anticoagulant rodenticides, 9 from other pesticides and six from lead. Criteria for diagnosing anticoagulant rodenticide poisoning included visible haemorrhage on gross post-mortem examination and levels of anticoagulant rodenticide exceeding 100 ng/g, but levels were elevated above 100 ng/g in a further eight red kites without visible haemorrhages, suggesting poisoning may have occurred in more birds. The anticoagulant rodenticides difenacoum and bromadiolone were the most common vertebrate control agents involved during this period. Poisoning of red kites may be slowing their rate of population recovery and range expansion in England. Simple modifications of human activity, such as best practice in rodent control campaigns, tackling the illegal use of pesticides and the use of non-toxic alternatives to lead ammunition, can reduce our impact on red kites and probably other populations of predatory and scavenging species

The impact of obesity on time spent with the provider and number of medications managed during office-based physician visits using a cross-sectional, national health survey

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with morbidity, mortality, and increased health care costs. Few studies have examined the impact of obesity on outpatient office visits. The purpose of this study was to determine if outpatient visits by obese persons required more time with the provider and more prescription medication management compared to visits made by non-obese persons.</p> <p>Methods</p> <p>Obesity status was determined for 9,280 patient visits made by persons aged 18 years or older in the 2006 National Ambulatory Medical Care Survey. Multivariate analyses compared obese and non-obese visits, stratified by sex, for duration of the visit and the number of medications mentioned at the visit.</p> <p>Results</p> <p>Average duration of visit was higher among visits with patients determined to be obese. However, these differences were not considered significant after statistical testing. Visits made by obese female patients were significantly more likely to involve more than two prescription medications (OR 1.26, 95% CI 1.05 - 1.51) and visits made by obese male patients were significantly more likely to involve more than two prescription medications (OR 1.46, 95% CI 1.16 - 1.83) as compared to visits made by non-obese patients.</p> <p>Conclusion</p> <p>Time spent with the provider was found to be greater among visits with obese patients, but not significantly different from visits with non-obese patients. The number of medications for each visit was found to be significantly greater for visits where the patient was considered to be obese. Increased time for the visit and increased numbers of medication for each visit translate into increased costs. These findings document the impact of obesity on our health care system and have great implications on medical care cost and planning.</p

Many quality measurements, but few quality measures assessing the quality of breast cancer care in women: A systematic review

BACKGROUND: Breast cancer in women is increasingly frequent, and care is complex, onerous and expensive, all of which lend urgency to improvements in care. Quality measurement is essential to monitor effectiveness and to guide improvements in healthcare. METHODS: Ten databases, including Medline, were searched electronically to identify measures assessing the quality of breast cancer care in women (diagnosis, treatment, followup, documentation of care). Eligible studies measured adherence to standards of breast cancer care in women diagnosed with, or in treatment for, any histological type of adenocarcinoma of the breast. Reference lists of studies, review articles, web sites, and files of experts were searched manually. Evidence appraisal entailed dual independent assessments of data (e.g., indicators used in quality measurement). The extent of each quality indicator's scientific validation as a measure was assessed. The American Society of Clinical Oncology (ASCO) was asked to contribute quality measures under development. RESULTS: Sixty relevant reports identified 58 studies with 143 indicators assessing adherence to quality breast cancer care. A paucity of validated indicators (n = 12), most of which assessed quality of life, only permitted a qualitative data synthesis. Most quality indicators evaluated processes of care. CONCLUSION: While some studies revealed patterns of under-use of care, all adherence data require confirmation using validated quality measures. ASCO's current development of a set of quality measures relating to breast cancer care may hold the key to conducting definitive studies

Self-reported diabetes is associated with self-management behaviour: a cohort study

<p>Abstract</p> <p>Background</p> <p>The purposes of this cohort study were to establish how frequently people with physician-diagnosed diabetes self-reported the disease, to determine factors associated with self-reporting of diabetes, and to evaluate subsequent differences in self-management behaviour, health care utilisation and clinical outcomes between people who do and do not report their disease.</p> <p>Methods</p> <p>We used a registry of physician-diagnosed diabetes as a reference standard. We studied respondents to a 2000/01 population-based health survey who were in the registry (n = 1,812), and we determined the proportion who reported having diabetes during the survey. Baseline factors associated with self-report and subsequent behavioural, utilisation and clinical differences between those who did and did not self-report were defined from the survey responses and from linkage with administrative data sources.</p> <p>Results</p> <p>Only 75% of people with physician-diagnosed diabetes reported having the disease. People who did self-report were more likely to be male, to live in rural areas, to have longer disease duration and to have received specialist physician care. People who did not report having diabetes in the survey were markedly less likely to perform capillary blood glucose monitoring in the subsequent two years (OR 0.05, 95% CI 0.02 to 0.08). They were also less likely to receive specialist physician care (OR 0.55, 95% CI 0.37 to 0.86), and were less likely to require hospital care for hypo- or hyperglycaemia (OR 0.09, 95% CI 0.01 to 0.28).</p> <p>Conclusion</p> <p>Many people with physician-diagnosed diabetes do not report having the disease, but most demographic and clinical features do not distinguish these individuals. These individuals are much less likely to perform capillary glucose monitoring, suggesting that their diabetes self-management is inadequate. Clinicians may be able to use the absence of glucose monitoring as a screening tool to identify people needing a detailed evaluation of their disease knowledge.</p

Documentation of body mass index and control of associated risk factors in a large primary care network

<p>Abstract</p> <p>Background</p> <p>Body mass index (BMI) will be a reportable health measure in the United States (US) through implementation of Healthcare Effectiveness Data and Information Set (HEDIS) guidelines. We evaluated current documentation of BMI, and documentation and control of associated risk factors by BMI category, based on electronic health records from a 12-clinic primary care network.</p> <p>Methods</p> <p>We conducted a cross-sectional analysis of 79,947 active network patients greater than 18 years of age seen between 7/05 - 12/06. We defined BMI category as normal weight (NW, 18-24.9 kg/m²), overweight (OW, 25-29.9), and obese (OB, ≥ 30). We measured documentation (yes/no) and control (above/below) of the following three risk factors: blood pressure (BP) ≤130/≤85 mmHg, low-density lipoprotein (LDL) ≤130 mg/dL (3.367 mmol/L), and fasting glucose <100 mg/dL (5.55 mmol/L) or casual glucose <200 mg/dL (11.1 mmol/L).</p> <p>Results</p> <p>BMI was documented in 48,376 patients (61%, range 34-94%), distributed as 30% OB, 34% OW, and 36% NW. Documentation of all three risk factors was higher in obesity (OB = 58%, OW = 54%, NW = 41%, p for trend <0.0001), but control of all three was lower (OB = 44%, OW = 49%, NW = 62%, p = 0.0001). The presence of cardiovascular disease (CVD) or diabetes modified some associations with obesity, and OB patients with CVD or diabetes had low rates of control of all three risk factors (CVD: OB = 49%, OW = 50%, NW = 56%; diabetes: OB = 42%, OW = 47%, NW = 48%, p < 0.0001 for adiposity-CVD or diabetes interaction).</p> <p>Conclusions</p> <p>In a large primary care network BMI documentation has been incomplete and for patients with BMI measured, risk factor control has been poorer in obese patients compared with NW, even in those with obesity and CVD or diabetes. Better knowledge of BMI could provide an opportunity for improved quality in obesity care.</p

We should not forget the foot: relations between signs and symptoms, damage, and function in rheumatoid arthritis

We studied rheumatoid arthritis (RA) patients with foot complaints to address the associations between clinical signs and symptoms, radiographic changes, and function in connection with disease duration. Secondly, we describe the contribution of several foot segments to the clinical presentation and function. In 30 RA patients with complaints of their feet, attributed to either signs of arthritis and/or radiographic damage, we compared radiographic, ultrasound, clinical, and functional parameters of the feet and ankle. Pain and swelling of the ankle were correlated weakly but statistically significantly with limitation and disability (0.273 to 0.293) as measured on the 5-Foot Function Index (FFI). The clinical signs of the forefoot joints did not influence any of the functional outcome measures. Radiographic scores for both forefeet (SvdH) and hindfeet (Larsen) were correlated with the total Health Assessment Questionnaire Disability Index (HAQ DI) and the 5-FFI limitation subscale. Pain and disease duration, more than radiographic damage, influence the total HAQ DI significantly. With the progression of time, structural damage and function of the rheumatic foot worsen in RA patients. Pain and swelling of the ankle contribute more to disability than radiographic damage of the foot and ankle

Type D personality is associated with increased metabolic syndrome prevalence and an unhealthy lifestyle in a cross-sectional Dutch community sample

<p>Abstract</p> <p>Background</p> <p>People with Type D-Distressed-personality have a general tendency towards increased negative affectivity (NA), while at the same time inhibiting these emotions in social situations (SI). Type D personality is associated with an increased risk of adverse outcomes in patients with cardiovascular disease. Whether Type D personality is a cardiovascular risk factor in healthy populations remains to be investigated. In the present study, the relations between Type D personality and classical cardiovascular risk factors, i.e. metabolic syndrome and lifestyle were investigated in a Dutch community sample.</p> <p>Methods</p> <p>In a cross-sectional study 1592 participants were included, aged 20-80 years. Metabolic syndrome was defined by self-report, following the International Diabetes Federation-IDF-guidelines including an increased waist circumference, dyslipidemia, hypertension, and diabetes. In addition lifestyle factors smoking, alcohol use, exercise and dietary habits were examined. Metabolic syndrome prevalence was stratified by Type D personality (a high score on both NA and SI), lifestyle and confounders age, gender, having a partner, higher education level, cardiac history, family history of cardiovascular disease.</p> <p>Results</p> <p>Metabolic syndrome was more prevalent in persons with a Type D personality (13% vs. 6%). Persons with Type D personality made poorer lifestyle choices, adhered less to the physical activity norm (OR = 1.5, 95%CI = 1.1-2.0, <it>p </it>= .02), had a less varied diet (OR = 0.50, 95%CI = 0.40-0.70, <it>p </it>< .0005), and were less likely to restrict their fat intake (OR = 0.70, 95%CI = 0.50-0.90, <it>p </it>= .01). Type D personality was related to a twofold increased risk of metabolic syndrome (OR = 2.2, 95%CI = 1.2-4.0, <it>p </it>= .011), independent of lifestyle factors and confounders.</p> <p>Conclusions</p> <p>Type D personality is related to an increased prevalence of metabolic syndrome and unhealthy lifestyle, which suggests both behavioral and biological vulnerability for development of cardiovascular disorders and diabetes.</p

Discrepancies between the medical record and the reports of patients with acute coronary syndrome regarding important aspects of the medical history

<p>Abstract</p> <p>Background</p> <p>Many critical treatment decisions are based on the medical history of patients with an acute coronary syndrome (ACS). Discrepancies between the medical history documented by a health professional and the patient's own report may therefore have important health consequences.</p> <p>Methods</p> <p>Medical histories of 117 patients with an ACS were documented. A questionnaire assessing the patient's health history was then completed by 62 eligible patients. Information about 13 health conditions with relevance to ACS management was obtained from the questionnaire and the medical record. Concordance between these two sources and reasons for discordance were identified.</p> <p>Results</p> <p>There was significant variation in agreement, from very poor in angina (kappa < 0) to almost perfect in diabetes (kappa = 0.94). Agreement was substantial in cerebrovascular accident (kappa = 0.76) and hypertension (kappa = 0.73); moderate in cocaine use (kappa = 0.54), smoking (kappa = 0.46), kidney disease (kappa = 0.52) and congestive heart failure (kappa = 0.54); and fair in arrhythmia (kappa = 0.37), myocardial infarction (kappa = 0.31), other cardiovascular diseases (kappa = 0.37) and bronchitis/pneumonia (kappa = 0.31). The odds of agreement was 42% higher among individuals with at least some college education (OR = 1.42; 95% CI, 1.00 - 2.01, p = 0.053). Listing of a condition in medical record but not in the questionnaire was a common cause of discordance.</p> <p>Conclusion</p> <p>Discrepancies in aspects of the medical history may have important effects on the care of ACS patients. Future research focused on identifying the most effective and efficient means to obtain accurate health information may improve ACS patient care quality and safety.</p