Changes in plasma FGF23 in growth hormone deficient children during rhGH therapy.

BACKGROUND: Children with growth hormone deficiency (GHD) have increased renal phosphorus reabsorption during rhGH therapy, Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for this effect. METHODS: Prospective study in GHD children investigating changes in plasma C-terminal FGF23 (C-FGF23), markers of mineral metabolism, and insulin-like growth factor (IGF-1) in the first year of rhGH therapy. Normal stature children served as baseline controls. RESULTS: The two groups at baseline were similar, except GHD patients had lower baseline TmP/GFR vs. controls (p < 0.05). C-FGF23 in GHD patients trended upward at follow-up 1 (p = 0.058) and significantly increased at follow-up 2 (p = 0.0005) compared to baseline. TmP/GFR also rose at follow-up 1 (p = 0.002) and follow-up 2 (p = 0.027). The C-FGF23 rise persisted after adjusting for age, gender, sex, total calcium, and phosphorus (p < 0.01) but attenuated after adjusting for TmP/GFR or IGF-1. CONCLUSIONS: C-FGF23 rises during rhGH therapy in spite of increased Tmp/GFR, an unanticipated observation given the role of FGF23 as a phosphaturic factor. The C-FGF23 rise may be a secondary response during rhGH therapy.

Estimated effects of the National Breast and Cervical Cancer Early Detection Program on breast cancer mortality.

BACKGROUND: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) provides breast cancer screening to medically underserved, low-income women aged 40-64 years. No study has evaluated NBCCEDP's effect on breast cancer mortality. PURPOSE: This study estimates life-years saved by NBCCEDP breast cancer screening compared with screening in the absence of NBCCEDP and with no screening. METHODS: A breast cancer simulation model based on existing Cancer Intervention and Surveillance Modeling Network models was constructed. The screening module from these models was modified to reflect screening frequency for NBCCEDP participants. Screening data for uninsured women represented what would have happened without the program. Separate simulations were performed for women who received NBCCEDP (Program) screening, women who potentially received screening without the program (No Program), and women who received no screening (No Screening). The impact of NBCCEDP was estimated as the difference in life-years between the Program and No Program, and the Program and No Screening scenarios. The analysis was performed in 2008-2009. RESULTS: Among 1.8 million women who were screened between 1991 and 2006, the Program saved 100,800 life-years compared with No Program and 369,000 life-years compared with No Screening. Per woman screened, the Program saved 0.056 life-years (95% CI=0.031, 0.081) compared with No Program and 0.206 life-years (95% CI=0.177, 0.234) compared with No Screening. Per woman with invasive breast cancer and screen-detected invasive cancer, the Program saved 0.41 and 0.71 life-years, respectively, compared with No Program. CONCLUSIONS: These estimates suggest that NBCCEDP breast cancer screening has reduced mortality among medically uninsured and underinsured low-income women.

Cost of cervical cancer treatment: implications for providing coverage to low-income women under the Medicaid expansion for cancer care.

BACKGROUND: To date, no study has reported on the cost of treating cervical cancer among Medicaid beneficiaries younger than 65 years of age. This information is essential for assessing the cost effectiveness of screening interventions for low-income women and the funding required for treatment programs established by the Breast and Cervical Cancer Prevention and Treatment Act of 2000. METHODS: Administrative data from the North Carolina Medicaid program linked with cancer registry data were used to analyze total Medicaid costs for these patients and the incremental costs of cervical cancer care at 6 and 12 months from diagnosis. We compared 207 beneficiaries diagnosed with cancer during the years 2002 to 2004 with 414 controls. FINDINGS: Total Medicaid costs at 6 months after diagnosis were $3,807, $23,187, $35,853, and $45,028 for in situ, local, regional, and distant cancers, respectively. The incremental cost of cancer treatment for local and regional cancers was $13,935 and $26,174 and by 12 months increased to $15,868 and $30,917, respectively. CONCLUSION: Medicaid coverage may be required for many months after diagnosis to ensure the provision of comprehensive care, especially for women with late-stage cancers. Given the great differences in cost of early versus late-stage cancers, interventions aimed at increasing screening among low-income women are likely to be cost effective.

Meeting the cervical cancer screening needs of underserved women: the National Breast and Cervical Cancer Early Detection Program, 2004-2006.

OBJECTIVE: To examine the extent to which the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), has helped to meet the cervical cancer screening needs of underserved women. METHODS: Low-income, uninsured women 18-64 years of age are eligible for free cervical cancer screening services through NBCCEDP. We used data from the US Census Bureau to estimate the number of eligible women, based on insurance status and income. The estimates were adjusted for hysterectomy status using the National Health Interview Survey and the Behavioral Risk Factor Surveillance System. We used administrative data from NBCCEDP to obtain the number of women receiving NBCCEDP-funded Papanicolaou (Pap) tests. We then calculated the percentage of NBCCEDP-eligible women who received free cervical cancer screening through NBCCEDP. We also used the NHIS to calculate the percentage of NBCCEDP-eligible women screened nationally and the percentage unscreened. RESULTS: In 2004-2006, nearly 9% (775,312 of 8.9 million) of NBCCEDP-eligible women, received NBCCEDP-funded Pap test. Rates varied substantially by age groups, race, and ethnicity. NBCCEDP-eligible women 40-64 years of age had a higher screening rate (22.6%) than eligible women 18-39 years of age (2.3%). Non-Hispanic women had a higher screening rate (9.3%) than Hispanic women (7.3%). Among non-Hispanics, the screening rate was highest among American Indian and Alaska Native (AIAN) women (36.1%) and lowest among women of different race combinations (4.6%), The percentage of eligible women screened in each state ranged from 2.0 to 38.4%. CONCLUSIONS: Although NBCCEDP provided cervical cancer screening services to 775,312 low-income, uninsured women, this number represented a small percentage of those eligible. In 2005, more than 34% of NBCCEDP-eligible women (3.1 million women) did not receive recommended Pap tests from either NBCCEDP or other sources.

Effect of age on survival benefit of adjuvant chemotherapy in elderly patients with Stage III colon cancer.

OBJECTIVES: To estimate the modifying effect of age on the survival benefit associated with adjuvant chemotherapy receipt in elderly patients with a diagnosis of Stage III colon cancer. DESIGN: Observational, retrospective cohort study using two samples: an overall sample of 7,182 patients to provide externally valid analyses and a propensity score-matched sample of 3,016 patients to provide more internally valid analyses by reducing the presence of treatment endogeneity. An interval-censored survival model with a complementary log-log link was used. Hazard ratios and 95% confidence intervals were obtained for all regressions. SETTINGS: Data from the National Cancer Institute's Surveillance, Epidemiology and End Results database and the linked Medicare enrollment and claims database were used. PARTICIPANTS: Selected patients were aged 66 and older and had a diagnosis of Stage III colon cancer. Patients were followed from surgery to time of death or censorship. MEASUREMENTS: The outcome was colon cancer-specific death during the follow-up period. Receipt of adjuvant chemotherapy was measured according to the presence of a claim for 5-fluorouracil or leucovorin within 6 months after surgery. RESULTS: All elderly patients had a significant survival benefit associated with adjuvant chemotherapy receipt, although the survival benefit of adjuvant chemotherapy was not uniform across all age groups. CONCLUSION: These findings have important clinical and policy implications for the risk-benefit calculation induced by treatment in older patients with Stage III colon cancer. The results suggest that there is a benefit from chemotherapy, but the benefit is lower with older age.

Estimating personal costs incurred by a woman participating in mammography screening in the National Breast and Cervical Cancer Early Detection Program.

BACKGROUND: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) covers the direct clinical costs of breast and cervical cancer screening and diagnostic follow-up for medically underserved, low-income women. Personal costs are not covered. In this report, the authors estimated personal costs per woman participating in NBCCEDP mammography screening by race/ethnicity and also estimated lifetime personal costs (ages 50-74 years). METHODS: A decision analysis model was constructed and parameterized by using empiric data from a retrospective cohort survey of mammography rescreening among women ages 50 years to 64 years who participated in the NBCCEDP. Data from 1870 women were collected from 1999 to 2000. The model simulated the flow of resources incurred by a woman participating in the NBCCEDP. The analysis was stratified by annual income into 2 scenarios: Scenario 1, <$10,000; and Scenario 2, from $10,000 to <$20,000. Sensitivity analyses were conducted to appraise uncertainty, and all costs were standardized to 2000 U.S. dollars. RESULTS: In Scenario 1, for all races/ethnicities, a woman incurred a 1-time cost of $17 and a discounted lifetime cost of $108 for 10 screens and $262 for 25 screens; in Scenario 2, these amounts were $31 and from $197 to $475, respectively. In both scenarios, a non-Hispanic white woman incurred the highest cost. The sensitivity analyses revealed that >70% of cost incurred was attributable to opportunity cost. CONCLUSIONS: Capturing and quantifying personal costs will help ascertain the total cost (ie, societal cost) of providing mammography screening to a medically underserved, low-income woman participating in a publicly funded cancer screening program and, thus, will help determine the true cost-effectiveness of such programs.

Measurement of liver collagen synthesis by heavy water labeling: effects of profibrotic toxicants and antifibrotic interventions.

Enhanced production of collagen is central to fibrotic disorders such as hepatic cirrhosis and pulmonary fibrosis. We describe a sensitive, quantitative, and high-throughput technique for measuring hepatic collagen synthesis in vivo through metabolic labeling with heavy water ((2)H(2)O). Rats and mice received (2)H(2)O in drinking water for up to 35 days. Deuterium incorporation into collagen-bound amino acids (AA) alanine and hydroxyproline (OHP) was measured by gas chromatography-mass spectrometry. A threefold stimulation of collagen fractional synthesis was observed under the maximum dosage of carbon tetrachloride (CCl(4); 1.67 ml/kg). Deuterium enrichment was systematically 20% higher in AA from monomeric collagen relative to dimeric collagen, consistent with slower turnover of the latter. Administration of 1% griseofulvin to mice resulted in a significant, threefold increase in liver collagen synthesis, observable within 12 days and consistent with predicted interstrain differences (C57/Bl6J > BALB/c). Deuterium enrichments of OHP from total liver proteins correlated well with alanine or OHP from isolated collagen. Fibrogenesis subsided after withdrawal of CCl(4) exposure and was reduced to various degrees by coadministration of interferon-gamma, rosiglitazone, atorvastatin, or enalapril. Changes in isotopically measured collagen synthesis correlated with, but were more sensitive and reproducible than, standard histological staining (trichrome) for fibrosis. In summary, liver collagen synthesis can be measured sensitively and with high precision over a short time period, without radioactivity, thereby providing a relatively high-throughput in vivo strategy for rapidly measuring profibrotic activities of suspected hepatotoxicants and antifibrotic activities of drug candidates.

Local knowledge in community-based approaches to medicinal plant conservation: lessons from India.

BACKGROUND: Community-based approaches to conservation of natural resources, in particular medicinal plants, have attracted attention of governments, non governmental organizations and international funding agencies. This paper highlights the community-based approaches used by an Indian NGO, the Rural Communes Medicinal Plant Conservation Centre (RCMPCC). The RCMPCC recognized and legitimized the role of local medicinal knowledge along with other knowledge systems to a wider audience, i.e. higher levels of government. METHODS: Besides a review of relevant literature, the research used a variety of qualitative techniques, such as semi-structured, in-depth interviews and participant observations in one of the project sites of RCMPCC. RESULTS: The review of local medicinal plant knowledge systems reveals that even though medicinal plants and associated knowledge systems (particularly local knowledge) are gaining wider recognition at the global level, the efforts to recognize and promote the un-codified folk systems of medicinal knowledge are still inadequate. In country like India, such neglect is evident through the lack of legal recognition and supporting policies. On the other hand, community-based approaches like local healers' workshops or village biologist programs implemented by RCMPCC are useful in combining both local (folk and codified) and formal systems of medicine. CONCLUSION: Despite the high reliance on the local medicinal knowledge systems for health needs in India, the formal policies and national support structures are inadequate for traditional systems of medicine and almost absent for folk medicine. On the other hand, NGOs like the RCMPCC have demonstrated that community-based and local approaches such as local healer's workshops and village biologist program can synergistically forge linkages between local knowledge with the formal sciences (in this case botany and ecology) and generate positive impacts at various levels.