Obesity control and liver health in breast cancer: Normalized hepatic elasticity after ketogenic diet.

Most socially significant diseases, including breast cancer, are undeniably linked to obesity. Recently, a positive relationship between excessive weight and increased risk of breast cancer poor outcomes has been proved. Liver integrity is an essential point during chemotherapy. Consequently, a hepatic safe therapeutic approach for managing obesity in patients with breast cancer should be initiated. Our study aimed to assess the impact of the ketogenic diet on body mass index (BMI) and to evaluate its safety on liver function in female patients with breast cancer. The study comprised 520 women with ductal breast cancer who underwent a 60-day modified ketogenic diet. BMI, prothrombin time (PT), activated partial thromboplastin clotting time (aPTT), aspartate aminotransferase to platelet ratio index (APRI), and ultrasound liver elasticity was evaluated before and after the diet. The results showed a significant decrease in BMI and an improvement in ultrasound liver elasticity in all the participants after completing the diet. Before the KD, the participants' median BMI was 35.0 kg/m2, and after the 60-day diet, the median BMI was reduced to 30.0 kg/m2. No significant liver parameter changes were found after the diet. In conclusion, we can safely promote the keto diet amongst individuals with an increased chance of developing breast cancer for a better disease prevention.

Serum Levels of Incretin Hormones - GLP-1 and GIP in Patients with Type 1 Diabetes Mellitus.

BACKGROUND: The glucagon-like peptide-1 (GLP-1) and the glucose- dependent Insulinotropic peptide (GIP) are natural incretin hormones, which are secreted respectively by the L- and K-cells of the intestinal mucosa in response to the physiological gastrointestinal glucose absorption. In patients with type 2 diabetes mellitus, the incretin effect is reduced, whereas the results in type 1 diabetes mellitus (T1DM) are heterogeneous, in some patients normal incretin response is observed. AIM: Comparative analysis of the basal serum levels of the incretin hormones GLP-1 and GIP in patients with type 1 DM and in individuals without carbohydrate disorders. MATERIALS AND METHODS: The study included 27 patients with diagnosed T1DM and a control group of 39 individuals without carbohydrate disorders. All participants in the study were subjected to the following clinical measurements and laboratory tests - height, weight, bioimpedance analysis of body composition, fasting blood sugar (BS 0'), postprandial blood sugar (PPBS), glycated haemoglobin (HbA1c) in T1DM patients, total cholesterol (TC), HDL cholesterol (HDL chol), triglycerides (TG), transaminase (AST and ALT), basal serum levels of GLP-1 and GIP. RESULTS: The serum levels of GIP in the patients with type T1DM were significantly higher, compared to the individuals without carbohydrate disorders (P<0.05), while there was no statistically significant difference in the GLP-1 levels. CONCLUSION: The significantly higher GIP levels and the similar GLP-1 levels in our patients with type 1 DM, compared to the individuals without carbohydrate disorders, support the hypothesis of intact incretin effect in this type of diabetes mellitus Key Words: Glucagon-like peptide-1, Glucose-dependent insulinotropic peptide, Type 1 diabetes mellitus.

Adipokines and soluble cell adhesion molecules in insulin resistant and non-insulin resistant women with polycystic ovary syndrome.

INTRODUCTION: Insulin resistance (IR) is closely associated with increased atherogenic risk. OBJECTIVE: To investigate leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and their relationship with each other and metabolic parameters in women with polycystic ovary syndrome (PCOS). METHODS: The study included 76 PCOS women divided into insulin resistant and non-insulin resistant. Anthropometric parameters, glucose and lipid parameters, leptin, adiponectin, sICAM-1 and sVCAM-1 were determined. Homeostasis model of IR index(HOMA-IR), atherogenic index of plasma(AIP) and leptin/adiponectin ratio were calculated. HOMA-IR > 2.5 and/or fasting plasma glucose/immunoreactive insulin ratio < 0.333 were used as markers for IR. RESULTS: Non-insulin resistant PCOS had significantly higher adiponectin and sVCAM-1 levels. AIP was significantly higher in insulin resistant PCOS. Adiponectin showed a positive correlation with sVCAM-1 and sICAM-1. CONCLUSION: Insulin resistant PCOS women were at higher atherogenic risk compared to non-insulin resistant group. sVCAM-1 data confirms the necessity of further investigations for clarifying its role in IR.

Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis.

Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease.

Adipose tissue hormones and appetite and body weight regulators in insulin resistance.

Impaired sensitivity to insulin (the so called insulin resistance, IR) occurs in a number of genetic and acquired conditions, including obesity, non-insulin dependent diabetes mellitus, polycystic ovary syndrome (PCOS) and metabolic syndrome (MS). In this review we discuss the correlation between IR, the adipose tissue hormones and appetite and body weight regulators. Leptin acts as a major adipostat: it suppresses food intake and activates catabolic pathways associated with increased energy production. It improves the peripheral insulin sensitivity and affects beta-cell function. Adiponectin is the only adipocytokine discovered so far that has anti-atherogenic properties. There is a reverse correlation between the serum adiponectin levels and the degree of obesity, IR, impaired glucose tolerance, dyslipidemia and atherosclerosis. Ghrelin stimulates food intake; of all circulating orexigenic hormones ghrelin is the most thoroughly studied. Ghrelin levels are decreased in MS and PCOS patients as this hormone is negatively correlated with body mass. Resistin is a hormone secreted by adipose tissues; a growing body of evidence suggests that it might be implicated in the link between obesity and diabetes. It has been found that the hormone's levels are significantly higher in obese people than those in normal body mass people. The recently discovered adipose tissue hormones, vaspin, visfatin, omentin-1 and their effect on IR development, have been increasingly researched.

Adipocytokines, neuropeptide Y and insulin resistance in overweight women with gynoid and android type of adipose tissue distribution.

UNLABELLED: The AIM of the study was to compare the levels of certain adipose tissue hormones in women with the two main morphological types of obesity - android and gynoid obesity. MATERIALS AND METHODS: The study included 2 groups of age- and weight-matched women with android (n = 32) and gynoid (n = 27) type of obesity, and a group of age-matched healthy women (n = 24) with normal weight and body constitution. Leptin, resistin, tumour necrosis factor alpha (TNFalpha), neuropeptide Y (NPY), glucose and insulin were measured. HOMA index was calculated. RESULTS: Leptin levels in the women with gynoid obesity did not differ significantly from those in the controls and the women with android obesity. The controls had significantly lower leptin levels compared with the android obesity women. NPY was significantly higher in the control women compared to the women with android obesity and did not differ significantly between the two groups of obese women. TNFalpha levels in all groups were very similar. Resistin did not show significant differences between all groups but tended to have the lowest levels in the controls. In the women with android obesity, insulin was significantly higher than that in the women with gynoid obesity and the controls. Insulin resistance was found in the women with android obesity only. Basal insulin and HOMA index in the women with gynoid obesity did not differ significantly from the values in the control group. CONCLUSION: The results from this study contribute to understanding the association of adipose tissue hormones and insulin resistance in obesity. When adipose tissue is predominantly distributed in the abdominal area at similar amount and percentage of body fats, leptin production is higher and insulin resistance develops. In the gynoid type of adipose tissue predisposition, overt insulin resistance is not found, leptin levels does not differ significantly from those in the control group.

The burden of moderate to severe psoriasis: an overview.

Psoriasis is a chronic, immune-mediated skin disorder that affects 1-3% of the general population worldwide. While considered a non-life-threatening disease, psoriasis represents a social and financial burden for patients and the healthcare system. Individuals suffer from disfigurement and from social stigmatization. Because the disease is usually persistent, patients with a diagnosis of psoriasis usually need lifelong care, which also means a lifetime of expenses. We aimed to conduct a comprehensive review of the evidence available concerning the social burden and costs of psoriasis. A search for the keywords 'quality of life' (QOL) or 'burden' or 'stigmatization' or 'psychological factors' in PubMed up to January 2010 yielded a total of 817 studies. QOL was affected by psoriasis to a degree comparable with diabetes or cancer. A search for 'cost-of-illness analyses', in the same period, yielded only seven papers satisfying entry criteria. All the studies but one were performed before biologics became available for psoriasis treatment. Direct costs were higher than indirect costs, with hospitalization representing the most significant item. Treatment costs showed wide variations between different studies. Reasons for these discrepancies are manifold including differences in the selection of the sample, as well as in the methods for calculating costs. There is a need to harmonize methodologies. For a final conclusive judgement of the cost effectiveness of innovative therapies such as biological agents, long-term economic consequences have to be evaluated and long-term remission rates and complications considered.

Economic evaluation of human papilloma virus vaccination in the European Union: a critical review.

The human papilloma virus (HPV) vaccine is a new and expensive vaccine potentially effective in the prevention of a cancer. We reviewed the economic evaluations (EEs) on the vaccine in the EU to assess their potential contribution to public decision-making in a fairly homogeneous setting where HPV vaccination has been widely adopted. A literature search on PubMed selected EEs on HPV vaccines in the EU for the period 2007-2010 using the terms "HPV vaccines" and "Costs and cost analysis." Fifteen articles were eventually selected. All studies were based on modelling techniques, either "cohort" or "dynamic transmission": three were cost utility, three cost-effectiveness, and the remainder included both. The ten studies explicitly assessing one of the two vaccines were all sponsored by their manufacturer, while the five studies unrelated to the vaccine type were funded by public agencies. Apart from two studies, utility estimates were always obtained from three US sources. Direct costs were always vaccination, diagnosis and treatment of related pathologies. Incremental cost-effectiveness ratio (ICER) results were less favourable when life years gained were valued rather than quality-adjusted life years, genital warts were excluded, and booster doses and extension of vaccination to men were included in the base-case analysis. All but one of the sponsored EEs recommend in favour of the vaccination strategy, which is dominant in one English study. The ICER results were very sensitive to discount rates, followed by duration of protection and vaccine price. At such an early stage, when the vaccines' efficacy have been demonstrated by well-designed studies, it is not possible (and not even reasonable) to wait for several years to measure their effectiveness; public decision-makers might benefit more from EEs designed to indicate sustainable prices using realistic estimates of crucial variables like coverage rates, rather than referring to a large number of assumptions in order to show acceptable cost-effectiveness.

Influenza vaccine for healthy adult workers: an issue for health authorities or employers?

OBJECTIVE: To contribute to the debate whether extending public coverage of influenza vaccination to healthy workers is cost-effective, particularly in the perspective of EU countries. METHODS: First, we reviewed the recent international literature on the extension of vaccination to subjects aged 50-64 years in highly developed countries. Second, we estimated the broad economic impact of influenza vaccination on the Italian healthy adult working population. Finally, we ran a pilot observational study to assess the healthcare and labour outcomes of influenza vaccination on the employees of our organization. RESULTS: The methodological weaknesses of the studies reviewed, all built on models, undermine the credibility of their optimistic results. The more cautious the model design, the less favourable the final results, as our conservative analysis on the Italian setting confirmed. The only common result was a steady relationship between potential vaccination benefits and indirect costs of absenteeism from work. This "modelling-based evidence" was confirmed by our internal survey: vaccinated workers showed less tendency to stay at home during influenza-like illness episodes and their relapses. CONCLUSIONS: The economic advantage of extending public influenza vaccination to healthy adult workers is still uncertain and mainly relates to the indirect costs of productivity losses, making the extension strategy more a labour than a health issue.

Modeling in pharmacoeconomic studies: funding sources and outcomes.

OBJECTIVES: The prime objective of this study was to investigate whether sponsorship by the pharmaceutical industry affected the results of full economic evaluations (FEE) based on modeling. In particular, we focused on the flourishing literature based on Markov models, by far the most widely exploited tool for estimating lifetime costs and benefits. METHODS: We made a literature search of the international database PubMed to find all the studies on pharmacological treatments based on Markov models published in English in the period January 1, 2004 to June 30, 2009. We selected the FEEs focused on single drugs only, specifically cost-effectiveness and cost-utility analyses. Two hundred articles including FEEs based on Markov models were considered eligible. For the analysis, we classified the FEEs into two groups according to whether or not they had financial backing from the pharmaceutical industry. We then assessed the main conclusions, which were classified as (i) "favorable," (ii) "doubtful," and (iii) "unfavorable." RESULTS: Of the 200 articles, 138 (69 percent) were sponsored and 162 (81 percent) reached favorable conclusions. Sponsored studies were much more likely to report favorable conclusions than nonsponsored ones (95 percent and 50 percent, p < .001), the former even omitting unfavorable conclusions. CONCLUSIONS: The review found a substantial share of studies supported by the pharmaceutical industry, almost all concluding in favor of the drug studied, without any unfavorable conclusions at all. These results confirm also in the field of pharmacoeconomic studies that the best way of limiting confounding factors is by clearly distinguishing assessors from manufacturers and marketers of any new technology.

Daughters' stories: family memory and generational amnesia.

After World War II, most Bulgarian Jews emigrated legally to Israel. Those who stayed had to take part in the building of socialism and integrate in a monolithic "socialist nation." Thereby they had to "forget" their ethnic identity ("aided by the state in various ways) and to become "Homo politicus" rather than "Homo ethnicus." Since 1990, a revival of Jewish identity has begun in Bulgaria. Here I explore how the women of three generations from the same family reinvent their Jewish identity in their life stories. Drawing on this particular case, I suggest an approach to the question of the interplay of individual and collective memory. I focus on family and generation as different types of collectivities influencing individual memories and self-actualizations.

A critical review of the full economic evaluations of pharmacological treatments for glaucoma.

OBJECTIVE: This literature review aimed to critically assess the 'state of the art' of the full economic evaluations (FEEs) on glaucoma pharmacological treatments. This is the first review that tries to thoroughly assess both costs and consequences of pharmacoeconomic evaluations on glaucoma. METHODS: A literature search was done on the international databases PubMed and EMBASE, to find all the studies published in English on pharmacological treatments for glaucoma in the period 1997-2006. An economic and a clinical checklist were adopted to analyse FEEs and their clinical sources (CS). Finally, the reliability of the 33 FEEs included in the 15 articles selected was assessed from the health authorities' perspective by applying a critical appraisal checklist of 16 items derived from the economic and clinical variables previously analysed. RESULTS: The major weakness of the articles reviewed seemed to be the extensive recourse to expert panel opinions and assumptions at each phase of the economic analysis. About one-third of the FEEs even based their clinical efficacy on non-evidence-based sources. The critical appraisal of the CS methodological characteristics showed that their quality was not high either. CONCLUSION: This review showed that most FEEs on glaucoma suffer substantial methodological limits, mainly due to the scarce quality of available CSs, so public authorities should consider their results very cautiously for healthcare decision making.

Cost minimisation analysis of 12 or 24 weeks of peginterferon alfa-2b + ribavirin for hepatitis C virus.

BACKGROUND: Pegylated interferon and ribavirin are at present the standard treatment for chronic hepatitis C virus (HCV) patients. OBJECTIVE: The present economic evaluation compared 12 vs. 24 weeks of peginterferon alfa-2b + ribavirin treatments for HCV genotypes 2 or 3. Shortening the period of antiviral therapy is important in terms of adverse events and costs. METHODS: Clinical evidence was based on the results of a multicentre, randomised controlled clinical trial (RCCT) conducted in Italy, which found that the shorter course of therapy was as effective as the 24-week course for patients with HCV genotypes 2 or 3 responding to treatment at 4 weeks. A cost minimisation analysis was performed. The analysis took the Italian National Health Service (INHS) point of view, thus only healthcare costs (drugs, medical consultations, diagnostic tests, hospital admissions) were considered. Healthcare activities were estimated by the RCCT principal investigators and were priced by applying the INHS tariffs and prices. RESULTS: The total mean cost per patient was estimated at euro9,785 for the standard group and euro7,508 for the variable-duration group. Sensitivity analysis confirmed the robustness of the baseline results. CONCLUSIONS: This study showed that the variable-duration regimen can be recommended as an efficient use of resources for patients from the INHS perspective.

A critical review of the full economic evaluations of pharmacological treatments for colorectal cancer.

OBJECTIVE: This literature review makes a critical assessment of the methodology of the full economic evaluations (FEEs) conducted on colorectal cancer (CRC) pharmacological treatments. METHOD: A literature search of the international databases PubMed and EMBASE was carried out to find all the studies published in the English language on pharmacological treatments for CRC in the period 2001-2005. A checklist was adopted to analyse the 13 FEEs selected. Fourteen clinical trials were extracted from the references as sources of efficacy data and were reviewed separately according to a clinical checklist. Finally, the reliability of the 13 FEEs was assessed from the health authorities' perspective by applying a critical appraisal checklist of 16 items derived from the economic and clinical variables previously analysed. RESULTS: This review found that pharmacoeconomic studies on CRC showed important methodological weaknesses mainly regarding economic evaluation, whilst the sources of clinical evidence were of higher technical quality, although the clinical effectiveness of therapies was not fully sustained by their results.

Medical costs of glaucoma and ocular hypertension in Italian referral centres: a prospective study.

AIM: This study analyzes the resource utilization and costs of ocular hypertension and glaucoma (staged by severity) in Italian ophthalmology departments. METHODS: The project was a multi-centre observational study conducted in 17 Italian ophthalmology departments throughout the country. A total of 659 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, the patients were divided into 3 groups according to the severity at onset: ocular hypertension, glaucoma and advanced glaucoma. RESULTS: The subgroups differed significantly in the main demographic and clinical variables. As expected, greater severity was associated with older mean age and worse visual acuity, and with higher resource consumption and costs. The annual average cost per patient was EUR 788.7 and rose significantly with disease severity (EUR 572.0 for ocular hypertension, EUR 734.3 for glaucoma and EUR 1,054.9 for advanced glaucoma). Drugs and specialist consultations were by far the largest cost components. CONCLUSIONS: This study offers some information on the medical costs of glaucoma in Italy potentially useful for decision-making in the health care services. Health care resources and costs increased with disease severity.

Healthcare costs of COPD in Italian referral centres: a prospective study.

BACKGROUND: This study estimated the healthcare resource utilisation and costs of chronic obstructive pulmonary disease (COPD) patients, staged by severity, in the Italian pneumology departments (PDs). METHODS: The project was a multi-centre observational study conducted in 11 Italian PDs throughout the country. A total of 268 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, patients were divided into four groups according to the severity at onset: mild COPD (stage I)-postbronchodilator FEV1/FVC <70% and FEV1 >or=80% of predicted; moderate COPD (stage II)-postbronchodilator FEV1/FVC <70% and 50%

Medical costs of chronic musculoskeletal pain in Italy.

BACKGROUND AND OBJECTIVES: Musculoskeletal system problems are responsible for more than two-thirds of painful conditions in primary care. However, only one published study, conducted in Finland, has analysed the costs of managing musculoskeletal pain as a whole in primary care. This study analysed the costs of diagnosing and treating chronic musculoskeletal pain in primary care in Italy. A secondary aim of the study was to assess the impact of different drug treatment patterns on medical costs associated with musculoskeletal pain. METHODS: Chronic pain of musculoskeletal origin was defined as continuous or recurrent pain persisting over 3 months with involvement of the musculoskeletal system, i.e. arising from primary musculoskeletal disorders or from the late consequences of external events (injuries, medical care or surgery). A total of 52 general practitioners (GPs) recruited 581 patients. We focussed on the differences between patients treated (410) and not treated (171) with drugs. Within the treated group, we also analysed subgroups given non-selective NSAID-based therapy (subgroup A, 169 patients) or cyclo-oxygenase-2 (COX-2) inhibitor-based therapy (subgroup B, 52 patients). RESULTS: The annual average cost of treating a patient with chronic musculoskeletal pain was euro 212.60. Hospital admissions and GP consultations were the largest cost components, both accounting for around a quarter of the total cost. Not surprisingly, the treated group included older patients, who had more co-morbidities and more severe pain. This was associated with annual costs more than four times those of untreated patients (euro 274.50 vs euro 63.90, respectively). Subgroups A and B did not differ with respect to major demographic and clinical variables except in relation to mean age (63 vs 70 years, respectively; p=0.037). They had similar per-patient costs (euro 186.20 vs euro 172.90), although these totals comprised a different mix of components. CONCLUSION: The analysis showed that the annual average cost of treatment of chronic musculoskeletal pain in Italy varied considerably depending on whether drug treatment was used. COX-2 inhibitors and traditional NSAIDs had similar per-patient costs, although this similarity stemmed from a different mix of components.

Pain in primary care: an Italian survey.

BACKGROUND: Pain is a universal symptom of various pathologies and largely affects human well-being. Pain is therefore commonly observed by general practitioners (GPs) and its management is a useful indicator of quality. In our study we investigated the epidemiology and management of pain in Italian general practice. METHODS: Participating GPs were asked to record the first out of every two contacts with pain during two working weeks between November 2000 and February 2001. They entered information on type of pain, pain-related diagnosis, certainty of diagnosis and types of prescription. RESULTS: 89 GPs participated in the study. About one third of all reported contacts were with pain. The number of contacts analysed was 1432. Nearly half the cases were diagnosed as acute. The main complaints were of musculoskeletal and abdominal origin. Pain was 1.5 times more frequent in women than men and the female to male ratios for acute and chronic pain were 1.2:1 and 1.8:1 respectively. The most frequent site of pain was the limbs. 'Arthropathies and related disorders', 'dorsopathies' and 'rheumatism excluding the back' were the commonest groups of diagnoses. Approximately two thirds of contacts with pain led to a drug prescription. CONCLUSIONS: The study identified a high proportion of contacts with pain in Italian general practice, with widespread use of drugs. The distribution of chronic and acute pain was rather similar and musculoskeletal pain was the most frequent form. Most types of prescriptions were closely related to certainty of diagnosis.