A macroeconomic approach to evaluating policies to contain antimicrobial resistance

Background

Antimicrobial resistance (AMR) is, at least in part, associated with high antimicrobial usage and causes increased morbidity, mortality and healthcare costs. However, policies to contain AMR focus on ‘micro’ interventions — typically in one institution (usually a hospital). Furthermore, in evaluating these interventions, economists tend to concentrate on the economic impact to the healthcare sector alone, which may give an incorrect estimation of the social costs and benefits of a disease or intervention.

Methods

This study outlines and illustrates a macroeconomic approach to tackling AMR through the evaluation of three ‘macro’ policies: regulation, permits and taxes/charges. In addition to effects on the healthcare sector, the effect of AMR (and these three policies to contain it) on labour productivity, GDP, household income, government transfers, tax revenues, unemployment, inflation and social services are estimated for the UK using the specific context of methicillin-resistant Staphylococcus aureus (MRSA).

Results

AMR is likely to have a far greater impact on the national economy than would be estimated by concentrating on the healthcare sector alone.

Conclusion

The permit system appears to offer the most efficient ‘solution’ to optimising antimicrobial consumption and, hence, reducing the development of resistance.     

Evaluation of the effect of age on treatment-related mortality and relapse in patients with high-risk primary breast cancer receiving high-dose chemotherapy

There are contradictory results regarding a potential increased responsiveness of younger women with high-risk primary breast cancer to high-dose compared with standard-dose chemotherapy. Observations from some, but not all, randomized trials, suggest that the potential benefit of high-dose treatment may be limited to younger patients. We analyzed, at median follow-up of 8 years, the prognostic effect of age in 264 patients enrolled in prospective phase II and III trials of high-dose chemotherapy, using a uniform regimen. Median age was 49 (range, 36-71). Among patients < or = 49 and > 49 years of age, the relapse rates were 27% and 25%, respectively (P = 0.7). In those age groups, the transplant-related mortality rates were 6.5% and 4%, respectively (P = 0.8). No age differences were observed between patients surviving transplant (median age 49) and those who experienced transplant-related mortality (median 47.5) (P = 0.9). Event-free survival (P = 0.3) and overall survival (P = 0.4) did not differ between patients < or = 49 and > 49 years of age. In conclusion, we did not detect a detrimental effect of older age on transplant-related mortality or relapse after high-dose chemotherapy for high-risk primary breast cancer at long-term follow-up. The debate about the age effect in this population remains unsettled.     

Pharmacokinetics and variation in the clearance of oxycodone and hydrocotarnine in patients with cancer pain

Compound injections of oxycodone and hydrocotarnine are currently used as one of the treatment options for some cases with cancer pain. However, there have been no reports examining the factors that influence oxycodone and hydrocotarnine clearance, so detailed examination is necessary. As for hydrocotarnine, there have been no reports examining the pharmacokinetics. Therefore in this study, we determined the pharmacokinetics of oxycodone and hydrocotarnine in patients with cancer pain. The study was conducted on 19 patients, in whom pain control was attempted by using the compound injections of oxycodone and hydrocotarnine. We used HPLC-electrochemical detector (ECD) to determine oxycodone and hydrocotarnine serum concentrations, and used the nonlinear least-squares method (MULTI) for calculation of the pharmacokinetic parameters. Furthermore, we examined the factors that influence the clearance of oxycodone and hydrocotarnine by multiple regression analysis (step wise method). The pharmacokinetic parameters were as follows: Oxycodone; V(d)=226.7+/-105.5 l (mean+/-S.D.), CL=37.9+/-25.1 l/h, t(1/2)=4.1+/-1.9 h. Hydrocotarnine; V(d)=276.8+/-237.2 l, CL=95.1+/-64.3 l/h, t(1/2)=2.0+/-0.7 h. The clearance of oxycodone represented by a regression formula was significantly correlated to the age, the presence or absence of within 7 d on the death or liver metastasis, or of the heart failure of the patients. The clearance of hydrocotarnine represented by a regression formula was significantly correlated to the presence or absence of within 7 d on the death or liver metastasis, or of the heart failure of the patients. The clearance also indicated that oxycodone concentration in the blood was likely to be higher in patients having these factors. Oxycodone/hydrocotarnine compound injections should be used with caution and dose reduction may be necessary in such populations.     

First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation

Despite prophylaxis with immunosuppressive agents or a variety of other approaches, many patients suffer from acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation. Although consensus has emerged supporting the use of high-dose methylprednisolone or prednisone for initial treatment of aGVHD, practices differ among centers with respect to the initial glucocorticoid dose, the use of additional immunosuppressive agents, and the approach to withdrawal of treatment after initial improvement. Despite many studies, practices vary considerably with respect to the selection of agents for treatment of glucocorticoid-resistant or refractory GVHD. Investigators and clinicians have recognized the lack of progress and lamented the absence of an accepted standard of care for secondary treatment of aGVHD. The American Society of Blood and Marrow Transplantation has developed recommendations for treatment of aGVHD to be considered by care providers, based on a comprehensive and critical review of published reports. Because the literature provides little basis for a definitive guideline, this review also provides a framework for the interpretation of previous results and the design of future studies.     

Regional variations in test requiring patterns of general practitioners in Spain

Objective

To analyze the requesting patterns for a range of laboratory tests ordered in 2009 from eight laboratories providing services to eight health areas, using appropriate indicators.

Design

Indicators measured every test request per 1,000 inhabitants, and indicators that measured the number of tests per related test requested by general practitioners were calculated. The savings generated, if each Health Care Department achieved the appropriate indicator standard, were also calculated. Laboratory Information System registers were collected, and indicators were calculated automatically in each laboratory using a data warehouse application.

Results

There was a large difference in demand for tests by health areas. The ratio of related tests also showed a great variability. The savings generated if each Health Care Department had achieved the appropriate indicator standard were €172,116 for free thyroxine, €18,289 for aspartate aminotransferase, and €62,678 for urea.

Conclusions

Considerable variability exists in general practitioners'' demand for laboratory tests.     

Management of Advanced and Relapsed/Refractory Extranodal Natural Killer T-Cell Lymphoma: An Analysis of Stem Cell Transplantation and Chemotherapy Outcomes

Background

Extra-Nodal natural killer/T-cell lymphoma (ENKL) is a rare lymphoma representing approximately 5-10% of T-cell non-Hodgkin lymphomas diagnosed in the United States each year. Patients with advanced stage III/IV ENKL and relapsed refractory ENKL have a poor prognosis even despite aggressive therapy and stem cell transplantation (SCT). We conducted a review of the management of 37 patients with advanced-stage and relapsed/refractory ENKL in a predominantly non-Asian cohort evaluating both chemotherapy and SCT outcomes.

IFN-gamma-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL

The current study explored our hypothesis that IFN-gamma-producing human T cells inhibit human osteoclast formation. Activated T cells derived from human PBMC were divided into IFN-gamma-producing T cells (IFN-gamma(+) T cells) and IFN-gamma-non-producing T cells (IFN-gamma(-) T cells). IFN-gamma(+) T cells were cultured with human monocytes in the presence of macrophage-CSF alone. The concentration of soluble receptor activator of NF-kappaB ligand (RANKL) and IFN-gamma, and the amount of membrane type RANKL expressed on T cells, were measured by ELISA. In the patients with early rheumatoid arthritis (RA) treated with non-steroidal anti-inflammatory drugs alone, CD4+ T cells expressing both IFN-gamma and RANKL were detected by flow cytometry. Surprisingly, IFN-gamma(+) T cells, but not IFN-gamma(-) T cells, induced osteoclastogenesis from monocytes, which was completely inhibited by adding osteoprotegerin and increased by adding anti-IFN-gamma antibodies. The levels of both soluble and membrane type RANKL were elevated in IFN-gamma(+) T cells. The ratio of CD4+ T cells expressing both IFN-gamma and RANKL in total CD4+ T cells from PBMC was elevated in RA patients. Contrary to our hypothesis, IFN-gamma(+) human T cells induced osteoclastogenesis through the expression of RANKL, suggesting that Th1 cells play a direct role in bone resorption in Th1 dominant diseases such as RA.