Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: a case for prospective economic analysis in cooperative group trials

BACKGROUND: Growth factor use has been shown to ameliorate chemotherapy-induced neutropenia, leading to shorter hospital stays and lower use of parenteral antibiotics, two costly areas of cancer treatment. Prior reports on pediatric patients have shown evidence of cost savings in some studies, but no such evidence in others. In this study a retrospective analysis compared the costs of inpatient supportive care for pediatric patients with T-cell leukemia and advanced lymphoblastic lymphoma enrolled in a Pediatric Oncology Group trial. PROCEDURE: Patients 1-22 years of age were randomized to receive either granulocyte colony-stimulating factor (G-CSF; n = 45) or no G-CSF (n = 43) following induction and two cycles of maintenance therapy. There were no significant differences in neutropenia-related outcomes during the induction phase. During maintenance therapy, G-CSF patients had significantly fewer days to an ANC >500 cells/microl and a trend towards fewer days of hospitalization. Data on resource utilization were tabulated from case report forms. Costs were imputed from national data on hospitalization costs, average wholesale prices of pharmaceuticals, and patient billing information from a single institution. RESULTS: Total median costs of supportive care were $34,190 for patients receiving G-CSF and $28,653 for patients not receiving G-CSF (P > 0. 05 for the cost difference). Sensitivity analyses demonstrated that the total cost difference was not statistically significant, even in scenarios that included reasonable variations in estimates of the range of the length of stay, antibiotic regimen, and dosage and cost of G-CSF. CONCLUSIONS: In the setting of pediatric leukemia, the cost of growth factor may offset potential savings from shorter hospital stays or lower antibiotic use, a finding consistent with that from the Children's Cancer Study Group.     

Treatment of phacolytic glaucoma with extracapsular cataract extraction

The treatment of choice for phacolytic glaucoma has been intracapsular cataract extraction (ICCE). The current study was undertaken to determine the efficacy of extracapsular cataract extraction (ECCE) as a definitive treatment for phacolytic glaucoma. Five cases of phacolytic glaucoma that occurred between 1984 and 1986 were studied after a retrospective chart review; ECCE (with placement of a posterior chamber intraocular lens [PC IOL]) was performed without complication and was curative in all five eyes. All patients (100%) maintained intraocular pressures (IOPs) of less than 20 mmHg, without medical therapy. The best-corrected visual acuity for all cases was 20/50 or better (80%, greater than or equal to 20/40) with 5 months to 3 years follow-up. These results suggest that ECCE is an effective alternative for the treatment of phacolytic glaucoma and allows surgeons the freedom to choose the procedure with which they are most comfortable. Additionally, implantation of a PC IOL is a safe and efficacious procedure in restoring visual function in these patients.     

Increased gonadotrophin stimulation does not improve IVF outcomes in patients with predicted poor ovarian reserve

Purpose

This retrospective study was carried out to evaluate whether increasing the starting dose of FSH stimulation above the standard dose of 150 IU/day in patients with low predicted ovarian reserve can improve IVF outcomes.

Method

A total of 122 women aged less than 36 years in their first cycle of IVF were identified as having likely low ovarian reserve based on a serum AMH measurement below 14 pmol/l. Thirty five women were administered the standard dose of 150 IU/day FSH, while the remaining 87 received a higher starting dose (200–300 IU/day FSH). There were no significant differences in age, BMI, antral follicle count, serum AMH, FSH or aetiology of infertility between the two dose groups.

Results

No significant improvement in oocyte and embryo yield or pregnancy rates was observed following an upward adjustment of FSH starting dose. While increasing the dose of FSH above 150 IU/day did not produce any adverse events such as OHSS, it did consume an extra 1,100 IU of FSH per IVF cycle.

Conclusion

The upward FSH dose adjustment in anticipation of low ovarian reserve can not be advocated as it is both expensive and of no proven clinical value.     

Repairing perineal hernia

The patient's pelvic structures repeatedly shifted out of place. Her physicians found a fix that helped.     

Population interconnectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here, we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density are explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also estimate the range of hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by our newly compiled dataset of dated archaeological sites. Finally, we show that genomic estimates of divergence times between CAHG groups match our ecological estimates of periods favoring population splits, and that recoveries of connectivity would have facilitated subsequent gene flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.

The evolutionary history of African hunter-gatherers may hold key insights into patterns and processes behind the evolution of modern human diversity. Recent genomic studies have revealed that these populations represent the oldest and most diverse human genetic lineages and have been genetically differentiated from one another since the origin of humans (1–3) (SI Appendix, Table S1). Therefore, a first question is whether their current ecological niches were also characteristic of early Homo sapiens populations. However, genetic data alone can neither determine the geographic distribution of hunter-gatherers in the past nor demonstrate a deep history of adaptation of hunter-gatherers to their current environments. In fact, various studies have proposed that farming expansions within the past 5,000 years (in particular by the ancestors of Bantu speakers) would have only recently displaced hunter-gatherers to marginalized regions less favorable to agriculture (such as rainforests and deserts) (4–7).For example, the central part of Africa, between latitudes 5°N and 5°S currently is inhabited by ∼20 scattered hunter-gatherer ethnic groups (8). These Central African hunter-gatherers (CAHG) form a genetic clade thought to have diverged from other African populations as far back as 120,000 to 200,000 years ago (2, 9). The lack of any major linguistic specificity between them is often implied to reflect extensive contacts with surrounding farmer populations (8, 10), and seen as evidence of recent displacement into marginal forest environments by expanding farming populations. However, anthropologists have remarked on the huge variability in lifestyle, habitat, techniques, and tools between CAHG (11), suggestive of long-term cultural diversification and adaptation to forest environments. Research on the drivers of demography and adaptation of CAHG populations remains extremely limited, which can be partially attributed to the lack of archaeological and osteological data resulting from a rapid disintegration of fossil remains in the rainforest’s acidic soils, in addition to social instability in the region (12). Therefore, we are still left with crucial questions regarding the time depth of occupation of Central Africa by hunter-gatherers, the breadth of the niche exploited by earlier populations in the region, and variations in levels of interconnectivity at different points in time.To address those questions, we first compiled ethnographic data on the distribution of 749 camps from 11 hunter-gatherer groups extending from West to East Central Africa. We used them as inputs for environmental niche models (ENMs) to determine the relative influence of several bioclimatic and ecological factors, as well as the presence of farming populations, on the distribution and abundance of CAHG (13, 14). Then, we used high-resolution paleoclimatic reconstructions and topographic maps to make continuous predictions about where CAHG could have lived over the past 120,000 years and the potential extension of their interaction networks. Next, we compiled all reliably dated archaeological assemblages ascribed to hunter-gatherer groups in the Congo Basin (n = 168) and confirmed the model’s ability to predict the location and date of the sites. We further contextualized genomic estimates of population divergences with changes in population densities and interpopulation connectivity predicted by our model. Last, we complemented these analyses with a detailed assessment of present and historical gene flow between nine CAHG populations (n = 265 individuals), which we used to assess recent interactions between previously diverged CAHG populations, after farming expansions. Our study therefore provides a causal link between past environmental changes and human population dynamics over evolutionary time, by predicting where and when populations across Central Africa could have exchanged genetic and/or cultural information throughout their evolutionary history.