Projecting future drug expenditures--2003.

Drug expenditure projections for 2003 and factors likely to influence drug costs are discussed. The United States continues to face the challenge of increased growth in health expenditures, and drug expenditures are continuing to increase faster than the growth in total health care expenditures. These increases can be largely attributed to an increase in the average age of the U.S. population and technological advancement. On the basis of price inflation and non-price inflationary factors, including increases in volume, shifts in patient and therapeutic intensity, and expected approval of new drugs, a 10-12% increase in drug expenditures in 2003 for the inpatient setting and a 13.5-15.5% increase for ambulatory care settings are forecasted. While few new drugs are expected to greatly influence expenditures in 2003, the continued diffusion of recently approved drugs such as drotrecogin alfa and nesiritide will have a dramatic impact on total drug expenditures and must be carefully considered in the budgeting process. An agent likely to have a significant impact on HIV treatment is enfuvirtide, the first in a new class of antiretrovirals (fusion inhibitors), but its high cost ($10,000-$15,000 per year) may limit patients' access to this medication. An expanded user's guide is provided to assist the reader in appropriate application of this information in the drug budgeting process. Technological, demographic, and market-based changes and changes in public policy will continue to influence pharmaceutical expenditures in the coming year. An understanding of the overall drivers of medication expenditures and vigilance in monitoring pharmaceutical innovation are critical in the effective management of these resources.     

Patient outcomes after therapeutic interchange of dolasetron for granisetron.

The impact of using therapeutic interchange (TI) of dolasetron for granisetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) was evaluated. An outcomes evaluation was conducted in two cohorts of adult outpatients who had not previously received chemotherapy. Before the interchange, 20 patients were enrolled in a granisetron cohort, and after the interchange to dolasetron, 42 patients were matched to the initial cohort. Evaluations using the modified Functional Life Index--Emesis (MFLIE) compared changes in functional status before and after treatment. Nausea and vomiting frequency, satisfaction with antiemetics, reported adverse effects, changes in antiemetic therapy, and the use of antiemetics postchemotherapy were also evaluated. Success, defined as no vomiting and less than a 2.5-unit change in MFLIE score, was demonstrated in 45% of granisetron patients and 40% of dolasetron patients (p = 0.461). While functional status declined in both groups in response to chemotherapy, the changes in MFLIE scores did not differ between agents (-16.8 +/- 20.16 versus -19.39 +/- 26.36 in granisetron and dolasetron patients, respectively) (p = 0.650). Patients were equally satisfied with their prescribed antiemetic therapy, although less than half of patients achieved antiemetic success in the 72-hour study period. Self-reported adverse events attributed to serotonin type 3-receptor antagonist use were minimal and not significantly different between groups. The TI did not negatively affect patient outcomes and produced savings of $143,534 in the first year of the program. TI of dolasetron for granisetron for CINV did not affect functional status, nausea control, or patient satisfaction with antiemetic therapy.     

Use of qualitative and quantitative fluorescence techniques to assess dermal exposure

Fluorescent tracers provide a way of simultaneously assessing the mass of a contaminant hazardous substance on the surface of the skin of a worker and the area of skin exposed. These parameters, along with the duration of exposure and the estimated contaminant concentration in the skin contamination layer, can be used to calculate the likely uptake through the skin. Repeated assessment of the mass of tracer on a surface within a room or on the surface of the skin can also allow the net transfer of contaminant to that compartment to be estimated. Qualitative evaluation of transfer processes using fluorescent tracers can help identify important secondary sources of exposure.     

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

Is semi-closed endarterectomy of the superficial femoral artery combined with a short venous bypass in case of insufficient venous material an acceptable alternative for limb-threatening ischemia?

BACKGROUND: The aim of this study was to analyse the results of infragenual arterial revascularisation using semiclosed endarterectomy of the superficial femoral artery combined with a short venous bypass in patients with critical leg ischemia and insufficient venous material for a straightforward femorocrural reconstruction. METHODS: From December 1990 through December 1998 thirty patients were studied (22 males and 8 females; mean age 65 years, range 31-92 years). The mean follow-up was 26 months (range 1-96 months). Cumulative primary patency and limb salvage rates were calculated according to life-table analysis. RESULTS: The cumulative primary patency was 60.3% at 1 year and 48.4% at 3 years. The limb salvage rate was 68.6% at 1 and at 3 years. CONCLUSIONS: In patients with limb-threatening ischemia and lack of venous material for a straightforward venous femorocrural bypass, semi-closed endarterectomy of the superficial femoral artery combined with a short popliteo-crural bypass provides a good alternative.     

DNA vaccination using bacillus Calmette-Guerin-DNA as an adjuvant to enhance immune response to three kinds of swine diseases

In order to enhance the immune efficacy of DNA vaccination, experiments were conducted to investigate the regulating effects of Bacillus Calmette-Guerin （BCG）-DNA as an adjuvant on immune responses of mice against foot-and-mouth disease （FMD）, Aujeszky＇s disease （AID） and classical swine fever （CSF）. BCG-DNA was purified from BCG by ion-exchange chromatography. Three DNA vaccines （pVSG, pVgD and pVE2） against the respective infection were constructed, and BCGDNA was coimmunized to mice by muscle injection. The results showed that titres of specific immunoglobulin （Ig）G to the vaccines mounted remarkably in the sera of the adjuvant covaccinated mice （P〈0.01）. Antibody isotype IgG2a and IgG1 also increased, respectively, in mice coimmunized with BCG-DNA compared with those of the control groups （P〈0.01）. Cellular immune cytokine interferon-gamma and cytotoxic T lymphocytes were detected in coimmunized BCG-DNA groups （P〈0. 05）. Whereas interleukin-4, humoral immune cytokine, was not significant （P〉 0. 05）. These results suggest that codelivery of BCG-DNA with DNA vaccines against FMD, AjD and CSF can enhance the induction of antigen-specific, especially, cell-mediated immunity.     

Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study.

PURPOSE: At the time of diagnosis, metastatic dissemination of tumor cells via the lymphatic system has occurred in nearly all patients with inflammatory breast cancer (IBC). The objective of this study was twofold: (a) to determine which is the most suitable marker of lymph vessels in primary breast tumors and (b) to compare histomorphometric lymph vessel variables in IBC and non-IBC. EXPERIMENTAL DESIGN: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40, LYVE-1, podoplanin, and PROX-1. Relative lymph vessel area, lymph vessel perimeters, and counts and lymphatic endothelial cell proliferation (LECP) were then measured in D2-40/Ki-67 double-immunostained sections of 10 normal breast tissues, 29 IBCs, and 56 non-IBCs. RESULTS: D2-40 was the most suitable antibody for staining peritumoral and intratumoral lymph vessels. D2-40-stained intratumoral lymph vessels were present in 80% of non-IBCs and 82.8% of IBCs (P = 0.76). In non-IBC, lymph vessels located in the tumor parenchyma were smaller and less numerous than those at the tumor periphery (P < 0.0001) whereas in IBC, intratumoral and peritumoral variables were not significantly different. The mean relative tumor area occupied by lymph vessels was larger in IBC than in non-IBC (P = 0.01). LECP at the tumor periphery was higher in IBC than in non-IBC: median LECP was 5.74% in IBC versus 1.83% in non-IBC (P = 0.005). CONCLUSIONS: The high LECP in IBC suggests that lymphangiogenesis contributes to the extensive lymphatic spread of IBC.     

Pharmacy residency training in academic medical centers.

PURPOSE: A survey of U.S. academic medical centers (AMCs) was conducted to identify the most important and challenging issues in pharmacy residency training. METHODS: A questionnaire addressing program characteristics and residency training concerns was sent electronically to pharmacy directors at 130 AMCs that are members or associate members of the University HealthSystem Consortium (UHC). Residency coordinators for both pharmacy practice and specialized programs were asked to complete the questionnaire, with input from other pharmacists involved in the residency program. Respondents were asked to rate the importance and degree of challenge for all issues on a 5-point Likert scale, where 1 = least important or least challenging and 5 = most important or most challenging. RESULTS: Responses were received from hospitals representing over 60% of all residency positions offered by UHC member hospitals. Recruitment was rated the most important issue (mean importance score, 4.8) facing residency programs in AMCs, but with over 85% of budgeted positions filled, programs appear to be successful in overcoming this concern. The most challenging issue (mean challenge score, 4.2) was compliance with the evaluation and documentation elements of the ASHP Residency Learning System (RLS), a system often used to meet requirements for pharmacy practice residency accreditation. The completion of resident research requirements was ranked as both an important and a challenging issue (mean importance score, 4.5; mean challenge score, 3.9). CONCLUSION: A survey of AMCs showed that they offered a wide variety of pharmacy residency programs and filled most budgeted resident positions. Resident recruitment, the RLS, and research requirements are the most important and challenging residency concerns facing the respondents.     

Occupational exposure to diesel engine exhaust and serum cytokine levels

The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross‐sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM_2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)‐1, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐1β, and monocyte chemotactic protein (MCP)‐1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP‐1β were significantly reduced by ～37% in DEE exposed workers (P < 0.001) and showed a strong decreasing trend with increasing PM_2.5 concentrations in all subjects (P_trend < 0.001) as well as in exposed subjects only (P_trend = 0.001). Levels of IL‐8 and MIP‐1β were significantly lower in workers in the highest exposure tertile of PM_2.5 (>397 µg/m³) compared to unexposed controls. Further, significant inverse exposure‐response relationships for IL‐8 and MCP‐1 were also found in relation to increasing PM_2.5 levels among the DEE exposed workers. Given that IL‐8, MIP‐1β, and MCP‐1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM_2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144–150, 2018. © 2017 Wiley Periodicals, Inc.     

The potential role of lung microbiota in lung cancer attributed to household coal burning exposures

Bacteria influence site‐specific disease etiology and the host's ability to metabolize xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs). Lung cancer in Xuanwei, China has been attributed to PAH‐rich household air pollution from burning coal. This study seeks to explore the role of lung microbiota in lung cancer among never smoking Xuanwei women and how coal burning may influence these associations. DNA from sputum and buccal samples of never smoking lung cancer cases (n = 8, in duplicate) and controls (n = 8, in duplicate) in two Xuanwei villages was extracted using a multi‐step enzymatic and physical lysis, followed by a standardized clean‐up. V1‐V2 regions of 16S rRNA genes were PCR‐amplified. Purified amplicons were sequenced by 454 FLX Titanium pyrosequencing and high‐quality sequences were evaluated for diversity and taxonomic membership. Bacterial diversity among cases and controls was similar in buccal samples (P = 0.46), but significantly different in sputum samples (P = 0.038). In sputum, Granulicatella (6.1 vs. 2.0%; P = 0.0016), Abiotrophia (1.5 vs. 0.085%; P = 0.0036), and Streptococcus (40.1 vs. 19.8%; P = 0.0142) were enriched in cases compared with controls. Sputum samples had on average 488.25 species‐level OTUs in the flora of cases who used smoky coal (PAH‐rich) compared with 352.5 OTUs among cases who used smokeless coal (PAH‐poor; P = 0.047). These differences were explained by the Bacilli species (Streptococcus infantis and Streptococcus anginosus). Our small study suggests that never smoking lung cancer cases have differing sputum microbiota than controls. Further, bacteria found in sputum may be influenced by environmental exposures associated with the type of coal burned in the home. Environ. Mol. Mutagen. 55:643–651, 2014. © 2014 Wiley Periodicals, Inc.