The impact of non-communicable diseases (NCDs) in populations extends beyond ill-health and mortality with large financial consequences To systematically review and meta-analyze studies evaluating the impact of NCDs (including coronary heart disease, stroke, type 2 diabetes mellitus, cancer (lung, colon, cervical and breast), chronic obstructive pulmonary disease and chronic kidney disease) at the macro-economic level: healthcare spending and national income Medical databases (Medline, Embase and Google Scholar) up to November 6th 2014 For further identification of suitable studies, we searched reference lists of included studies and contacted experts in the field We included randomized controlled trials, systematic reviews, cohorts, case-control, cross-sectional, modeling and ecological studies carried out in adults assessing the economic consequences of NCDs on healthcare spending and national income without language restrictions All abstracts and full text selection was done by two independent reviewers Any disagreements were resolved through consensus or consultation of a third reviewer Data were extracted by two independent reviewers using a pre-designed data collection form Studies evaluating the impact of at least one of the selected NCDs on at least one of the following outcome measures: healthcare expenditure, national income, hospital spending, gross domestic product (GDP), gross national product, net national income, adjusted national income, total costs, direct costs, indirect costs, inpatient costs, outpatient costs, per capita healthcare spending, aggregate economic outcome, capital loss in production levels in a country, economic growth, GDP per capita (per capita income), percentage change in GDP, intensive growth, extensive growth, employment, direct governmental expenditure and non-governmental expenditure From 4,364 references, 153 studies met our inclusion criteria Most of the studies were focused on healthcare related costs of NCDs 30 studies reported the economic impact of NCDs on healthcare budgets and 13 on national income Healthcare expenditure for cardiovascular disease (12-165 %) was the highest; other NCDs ranged between 07 and 74 % NCD-related health costs vary across the countries, regions, and according to type of NCD Additionally, there is an increase in costs with increased severity and years lived with the disease Low- and middle-income (LMI) countries were the focus of just 16 papers, which suggests an information shortage concerning the true economic burden of NCDs in these countries NCDs pose a significant financial burden on healthcare budgets and nations' welfare, which is likely to increase over time However further work is required to standardize more consistently the methods available to assess the economic impact of NCDs and to involve (hitherto under-addressed) LMI populations across the globe

The global impact of non-communicable diseases on healthcare spending and national income: a systematic review

The use of oral anticancer drugs has increased during the last decade, because of patient preference, lower costs, proven efficacy, lack of infusion-related inconveniences, and the opportunity to develop chronic treatment regimens. Oral administration of anticancer drugs is, however, often hampered by limited bioavailability of the drug, which is associated with a wide variability. Since most anticancer drugs have a narrow therapeutic window and are dosed at or close to the maximum tolerated dose, a wide variability in the bioavailability can have a negative impact on treatment outcome. This review discusses mechanisms of low bioavailability of oral anticancer drugs and strategies for improvement. The extent of oral bioavailability depends on many factors, including release of the drug from the pharmaceutical dosage form, a drug’s stability in the gastrointestinal tract, factors affecting dissolution, the rate of passage through the gut wall, and the pre-systemic metabolism in the gut wall and liver. These factors are divided into pharmaceutical limitations, physiological endogenous limitations, and patient-specific limitations. There are several strategies to reduce or overcome these limitations. First, pharmaceutical adjustment of the formulation or the physicochemical characteristics of the drug can improve the dissolution rate and absorption. Second, pharmacological interventions by combining the drug with inhibitors of transporter proteins and/or pre-systemic metabolizing enzymes can overcome the physiological endogenous limitations. Third, chemical modification of a drug by synthesis of a derivative, salt form, or prodrug could enhance the bioavailability by improving the absorption and bypassing physiological endogenous limitations. Although the bioavailability can be enhanced by various strategies, the development of novel oral products with low solubility or cell membrane permeability remains cumbersome and is often unsuccessful. The main reasons are unacceptable variation in the bioavailability and high investment costs. Furthermore, novel oral anticancer drugs are frequently associated with toxic effects including unacceptable gastrointestinal adverse effects. Therefore, compliance is often suboptimal, which may negatively influence treatment outcome.

Oral anticancer drugs: mechanisms of low bioavailability and strategies for improvement.

The development of orally administrable gemcitabine prodrugs with d-enantiomer amino acids: Enhanced membrane permeability and enzymatic stability

Despite many advances in the treatment of breast cancer, it is still the second most common cause of death in women in the United States. It has been shown that inflammation plays a major role in the treatment of these cancers and inflammatory factors enhance tumor growth, invasion, metastasis, and vascularization. In this study, we would like to analyze peripheral blood neutrophil-lymphocyte ratio (NLR) in breast cancer patients and its correlation with disease staging. This cross-sectional analytic study was conducted in Imam Hospital, affiliated with Tehran University of Medical Sciences; a total of 195 female patients with breast cancer met the inclusion criteria. All of the patients had a complete blood count with leukocyte differential performed before chemotherapy. Medical records including pathology reports were also available. Data for all patients were collected prior to any surgical intervention. Exclusion criteria included clinical evidence of active infection, presence of hematological disorders, acute as well as chronic inflammatory or autoimmune diseases, or prior steroid therapy. Higher platelet count was significantly associated with the higher stage. The stage was not associated with the hemoglobin level. There was no association between the tumor size and age of patients with NLR. There was a significant relationship between NLR and IDC. There was a significant relationship between IDC and NLRs of less than 8.1 and greater than 3.3. There was a significant relationship between NLR and vascular invasion. There was no association between NLR and estrogen receptor and HER2. There was no significant relationship between the PLR and the cancer stage. In this study, NLR showed a significant relation with the disease staging. As the NLR increases the stage increases as well. Therefore, this ratio may be helpful in the preoperative evaluation of patients with breast cancer.

/pdf/neutrophil-lymphocyte-ratio-in-different-stages-of-breast-5d7pl8fcgs.pdf

Neutrophil-Lymphocyte Ratio in Different Stages of Breast Cancer

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) ‐positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, €642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy.

Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

Metastatic breast cancer: We do need primary cost data

Background: Immune checkpoint inhibitors (ICI) have revolutionized the treatment of many malignancies in recent years. However, immune-related adverse events (irAE) are a frequent concern in clinical practice. The safety profile of ICI for the treatment of malignancies in patients diagnosed with autoimmune liver disease (AILD) remains unclear. Due to this uncertainty, these patients were excluded from ICI clinical trials and ICI are withheld from this patient group. In this retrospective multicenter study, we assessed the safety of ICI in patients with AILD. Methods: We contacted tertiary referral hospitals for the identification of AILD patients under ICI treatment in Europe via the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Fourteen centers contributed data on AILD patients with malignancies being treated with ICI, another three centers did not treat these patients with ICI due to fear of irAEs. Results: In this study, 22 AILD patients under ICI treatment could be identified. Among these patients, 12 had primary biliary cholangitis (PBC), five had primary sclerosing cholangitis (PSC), four had autoimmune hepatitis (AIH), and one patient had an AIH-PSC variant syndrome. Eleven patients had hepatobiliary cancers and the other 11 patients presented with non-hepatic tumors. The applied ICIs were atezolizumab (n=7), durvalumab (n=5), pembrolizumab (n=4), nivolumab (n=4), spartalizumab (n=1), and in one case combined immunotherapy with nivolumab plus ipilimumab. Among eight patients who presented with grade 1 or 2 irAEs, three demonstrated liver irAEs. Cases with grades [≥] 3 irAEs were not reported. No significant changes in liver tests were observed during the first year after the start of ICI. Conclusions: This European multicenter study demonstrates that PD-1/PD-L1 inhibitors appear to be safe in patients with AILD. Further studies on the safety of more potent dual immune checkpoint therapy are needed. We conclude that immunotherapy should not categorically be withheld from patients with AILD.

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune liver disease

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Metastatic breast cancer: We do need primary cost data

PD-1/PD-L1 immune checkpoint therapy demonstrates favorable safety profile in patients with autoimmune liver disease