Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects.

Type 2 diabetic subjects failing glyburide therapy were randomized to receive additional therapy with either metformin (2,550 mg/day) or troglitazone (600 mg/day) for 3-4 months. Biopsies of subcutaneous abdominal adipose tissue were obtained before and after therapy. Glycemic control was similar with both treatments. Metformin treatment increased insulin-stimulated whole-body glucose disposal rates by 20% (P < 0.05); the response to troglitazone was greater (44% increase, P < 0.01 vs. baseline, P < 0.05 vs. metformin). Troglitazone-treated subjects displayed a tendency toward weight gain (5 +/- 2 kg, P < 0.05), increased adipocyte size, and increased serum leptin levels. Metformin-treated subjects were weight-stable, with unchanged leptin levels and reduced adipocyte size (to 84 +/- 4% of control, P < 0.005). Glucose transport in isolated adipocytes from metformin-treated subjects was unaltered from pretreatment. Glucose transport in both the absence (321 +/- 134% of pre-Rx, P < 0.05) and presence of insulin (418 +/- 161%, P < 0.05) was elevated after troglitazone treatment. Metformin treatment had no effect on adipocyte content of GLUT1 or GLUT4 proteins. After troglitazone treatment, GLUT4 protein expression was increased twofold (202 +/- 42%, P < 0.05). Insulin-stimulated serine phosphorylation of Akt was augmented after troglitazone (170 +/- 34% of pre-Rx response, P < 0.05) treatment and unchanged by metformin. We conclude that the ability of troglitazone to upregulate adipocyte glucose transport, GLUT4 expression, and insulin signaling can contribute to its greater effect on whole-body glucose disposal.     

Economic evaluation of proton radiation therapy in the treatment of breast cancer.

BACKGROUND AND PURPOSE: Proton beam therapy offers potential clinical advantages compared with conventional radiation therapy for many cancer patients. The benefits are mainly a result of a more favourable dose distribution. The treatment cost with proton radiation is higher than for conventional radiation, mainly due to the large investment cost of building a proton therapy facility. It is therefore important to evaluate whether the medical benefits of proton therapy are large enough to justify the higher treatment costs, compared with conventional radiation therapy. PATIENTS AND METHODS: The cost-effectiveness of proton therapy in the treatment of 55-year old women with left-sided breast cancer was assessed. A Markov cohort simulation model was used to simulate the life of patients diagnosed with breast cancers and treated with radiation. Cost and quality adjusted life years (QALYs) were the primary outcome measures. RESULTS: The study found a cost per QALY gained of 67,000 Euro for the base case analysis of an average breast cancer patient. The cost per QALY gained would, however, be considerably lower if a population with high-risk of developing cardiac disease was treated. Sensitivity analyses showed that the results were stable and that the risk of cardiac disease was the most important parameter. CONCLUSIONS: The results indicate that proton therapy for breast cancer can be cost-effective if appropriate risk groups are chosen as targets for the therapy.     

Decreased Streptococcus pneumoniae susceptibility to oral antibiotics among children in rural Vietnam: a community study

Background  

Streptococcus pneumoniae is the most significant bacterial cause of community-acquired pneumonia among children under five years worldwide. Updated resistance information of S. pneumoniae among children is essential to adjust the recommendations for empirical treatment of community-acquired pneumonia, which will have immense implications for local and global health. This study investigated the prevalence of antibiotic resistance in isolated strains of S. pneumoniae and relationship with antibiotic use and demographic factors of children under five in rural Vietnam in 2007.     

Two years later: a prospective long-term follow-up of a training intervention in geriatric patients with a history of severe falls

OBJECTIVE: To study the long-term outcome of a physical training regimen of ambulant postward rehabilitation in community-dwelling geriatric patients with a history of injurious falls. DESIGN: Prospective 2-year follow-up of a randomized placebo-controlled intervention trial. SETTING: Postward rehabilitation in a geriatric hospital in Germany. PARTICIPANTS: Fifty-seven geriatric patients (mean age, 84.3+/-4.4 y) with a history of severe falls. INTERVENTION: Ambulatory training of strength, functional performance, and balance 3 times a week for 3 months for 31 patients versus placebo activities for 26 patients. MAIN OUTCOME MEASURES: Strength, functional performance, fall-related psychologic parameters, and physical activity assessed by standardized protocols 2 years after the training intervention, compared with baseline results. RESULTS: Motor performance decreased substantially in both groups. As patients in the intervention group declined from significantly improved motor performance levels achieved in the initial training intervention, differences between the groups were still significant in most functional performances 2 years later. Functional decline was greater in persons who were institutionalized or being cared for by family members. Physical activity, which increased during the exercise intervention, returned to low baseline levels. CONCLUSIONS: Improved functional performance in the training group did not lead to an increased level of physical activity after training, which might have preserved the functional improvements. In mobility-restricted, frail, geriatric patients such as our study population, training programs should continue to keep patients active and to prevent the decline in strength and functional performance that precedes loss of autonomy.     

Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case–control study

Standard sperm parameters have a limited power for prediction of the chance of natural conception. Recent studies have indicated that the sperm chromatin structure assay (SCSA) DNA fragmentation index (DFI), a measure for the fraction of sperms with DNA damage, is associated with fertility in vivo . The aim of this study was to evaluate the value of this parameter for prediction of infertility. One hundred and twenty-seven men from infertile couples with no known female factor and 137 men with proven fertility were included. Semen analysis was performed as recommended by the WHO. DFI was assessed using SCSA. Logistic binary regression was used to compute the odds ratios (OR) for infertility. As compared with men with a DFI <10%, men with a DFI between 10% and 20% had an increased risk for infertility (OR 2.5, 95% CI: 1.0–6.1). This was also true for men with a DFI >20% (OR 8.4; 95% CI: 3.0–23). In men with normal standard semen parameters (sperm concentration, motility and morphology) the OR for infertility was increased with DFI >20% (OR 5.1, 95% CI: 1.2–23), whereas if one of the standard semen parameters was abnormal, the OR for infertility was increased already at DFI above 10% (OR 16, 95% CI: 4.2–60). We conclude that SCSA DFI adds to the value of semen analysis in prediction of the chance of natural conception.     

Cost of disorders of the brain in Europe 2010

Background

The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.

Aims

To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.

Methods

The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27 + Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.

Results

The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.

Discussion

This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.

Recommendations

Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.