Estimating the money flow in the economy attributed to rotavirus disease and vaccination in the Netherlands using a Social Accounting Matrix (SAM) framework.

Background: The economics of rotavirus gastroenteritis in infants <5 years old is well-known within healthcare. The financial consequences for families, employers and authorities are not so well explored. The present study evaluates how vaccine prevention changes money flows among those involved in the management of disease, and its consequences. Methods: A Social Accounting Matrix (SAM) framework has been developed reflecting the distribution of income and spending at equilibrium affected by rotavirus disease among all those concerned for 1 year. The data came from official sources and published literature. A comparison of the financial equilibrium between with and without a national rotavirus immunization program has been conducted, along with sensitivity analysis for the results. Results: The total financial cost difference at equilibrium between presence and absence of rotavirus vaccination was +€26.758 million over one year as a net economic surplus. The payment of vaccination (€19.194 million) by the government was offset by the increase in tax revenue (€14.561 million) and by the lower spending in treatment care (€7.998 million). Conclusion: Studying the financial flows between different transacting agents can demonstrate the financial burden of a disease and the benefits of its prevention on agents' income and spending.

Access to anti-cancer drugs in India: is there a need to revise reimbursement policies?

BACKGROUND: The aim of this study was to examine the access of Indian cancer patients to optimum cancer care under selected government schemes by reviewing reimbursement schemes for cancer care in India. METHODS: All cancer care reimbursement schemes in India were identified and three highly utilized schemes (VAS, RAS, CMCHS) were selected. Quality of breast, colorectal, lung, head & neck, and gastric cancer care was reviewed with respect to NCCN guidelines. Direct medical costs and shortage of budget in reimbursed amounts were calculated for each listed chemotherapy regimen. RESULTS: Medical oncology practice following the schemes' formularies is inferior to recommendations by the NCCN guidelines. Innovative treatment (targeted therapies) like trastuzumab, pertuzumab (breast), bevacizumab, cetuximab, panitumumab (colorectal), erlotinib, gefitinib, crizotinib, and nivolumab (lung) are either not reimbursed (VAS, CMCHS) or partially reimbursed (RAS). Average shortage of budget was found to be 43% (breast), 55% (colorectal), 74% (lung), 7% (head & neck), and 51% (gastric cancer). CONCLUSIONS: Policy makers should consider addition of newer treatments, exclusion of sub-optimal treatments, increments in per patient budget and optimization of supportive care, which may contribute to improvements in survival and quality of life for Indian cancer patients.

Systematic review and meta-analysis of secondary prophylaxis for prevention of HIV-related toxoplasmic encephalitis relapse using trimethoprim-sulfamethoxazole.

A recent systematic literature and meta-analysis reported relative efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) for the treatment of toxoplasmic encephalitis (TE) in HIV-infected adults. Here, we estimated relapse rates during secondary prophylaxis with TMP-SMX, and further explored differences in relapse rates prior to introduction of highly active antiretroviral therapy (HAART) and the widespread adoption of HAART. A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials yielded 707 studies whereby 663 were excluded after abstract screening, and 38 were excluded after full review leaving 6 studies for extraction. We performed double data extraction with a third-party adjudicator. Study designs varied with only one randomized study, four prospective cohorts and one retrospective cohort. Relapse rates were transformed using the Freeman-Tukey method and pooled using both fixed-effect and random-effects meta-analysis models. The TMP-SMX relapse rate was 16.4% (95% CI = 6.2% to 30.3%) based on random-effects models. When the disaggregated pre-HAART studies (n = 4) were included, the relapse rate was 14.9% (random effects; 95% CI = 3.7% to 31.9%). Analysis of two post-HAART studies indicated a relapse rate of 19.2% (random effects; 95% CI = 2.8% to 45.6%). Comparing the relapse rates between pre- and post-HAART studies were contrary to what might be expected based on known benefits of HAART therapy in this population. Nevertheless, cautious interpretation is necessary considering the heterogeneity of the included studies and a limited number of subjects receiving TMP-SMX reported in the post-HAART era.

Rosiglitazone elicits in vitro relaxation in airways and precision cut lung slices from a mouse model of chronic allergic airways disease.

Rosiglitazone (RGZ), a peroxisome proliferator-activated receptor-γ (PPARγ) ligand, is a novel dilator of small airways in mouse precision cut lung slices (PCLS). In this study, relaxation to RGZ and ß-adrenoceptor agonists were compared in trachea from naïve mice and guinea pigs and trachea and PCLS from a mouse model of chronic allergic airways disease (AAD). Airways were precontracted with methacholine before addition of PPARγ ligands [RGZ, ciglitazone (CGZ), or 15-deoxy-(Δ12,14)-prostaglandin J2 (15-deoxy-PGJ2)] or ß-adrenoceptor agonists (isoprenaline and salbutamol). The effects of T0070907 and GW9662 (PPARγ antagonists) or epithelial removal on relaxation were assessed. Changes in force of trachea and lumen area in PCLS were measured using preparations from saline-challenged mice and mice sensitized (days 0 and 14) and challenged with ovalbumin (3 times/wk, 6 wk). RGZ and CGZ elicited complete relaxation with greater efficacy than ß-adrenoceptor agonists in mouse airways but not guinea pig trachea, while 15-deoxy-PGJ2 did not mediate bronchodilation. Relaxation to RGZ was not prevented by T0070907 or GW9662 or by epithelial removal. RGZ-induced relaxation was preserved in the trachea and increased in PCLS after ovalbumin-challenge. Although RGZ was less potent than ß-adrenoceptor agonists, its effects were additive with salbutamol and isoprenaline and only RGZ maintained potency and full efficacy in maximally contracted airways or after allergen challenge. Acute PPARγ-independent, epithelial-independent airway relaxation to RGZ is resistant to functional antagonism and maintained in both trachea and PCLS from a model of chronic AAD. These novel efficacious actions of RGZ support its therapeutic potential in asthma when responsiveness to ß-adrenoceptor agonists is limited.

Activation of WNT/ß-catenin signaling in pulmonary fibroblasts by TGF-ß1 is increased in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by abnormal extracellular matrix (ECM) turnover. Recently, activation of the WNT/ß-catenin pathway has been associated with abnormal ECM turnover in various chronic diseases. We determined WNT-pathway gene expression in pulmonary fibroblasts of individuals with and without COPD and disentangled the role of ß-catenin in fibroblast phenotype and function. METHODS: We assessed the expression of WNT-pathway genes and the functional role of ß-catenin, using MRC-5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. RESULTS: Pulmonary fibroblasts expressed mRNA of genes required for WNT signaling. Stimulation of fibroblasts with TGF-ß1, a growth factor important in COPD pathogenesis, induced WNT-5B, FZD8, DVL3 and ß-catenin mRNA expression. The induction of WNT-5B, FZD6, FZD8 and DVL3 mRNA by TGF-ß1 was higher in fibroblasts of individuals with COPD than without COPD, whilst basal expression was similar. Accordingly, TGF-ß1 activated ß-catenin signaling, as shown by an increase in transcriptionally active and total ß-catenin protein expression. Furthermore, TGF-ß1induced the expression of collagen1α1, α-sm-actin and fibronectin, which was attenuated by ß-catenin specific siRNA and by pharmacological inhibition of ß-catenin, whereas the TGF-ß1-induced expression of PAI-1 was not affected. The induction of transcriptionally active ß-catenin and subsequent fibronectin deposition induced by TGF-ß1 were enhanced in pulmonary fibroblasts from individuals with COPD. CONCLUSIONS: ß-catenin signaling contributes to ECM production by pulmonary fibroblasts and contributes to myofibroblasts differentiation. WNT/ß-catenin pathway expression and activation by TGF-ß1 is enhanced in pulmonary fibroblasts from individuals with COPD. This suggests an important role of the WNT/ß-catenin pathway in regulating fibroblast phenotype and function in COPD.