Roadmap for Connecting Cancer Rehabilitation With Survivorship to Improve Patient Outcomes and Clinical Efficiency.

ABSTRACT: An evolved model of comprehensive cancer care is needed that begins at cancer diagnosis to proactively manage cancer treatment toxicities and optimize patient health, function, and well-being. Building new care models requires connecting oncology, primary care, and specialized clinicians from many disciplines including cancer rehabilitation. Having a vision for an evolved standard of comprehensive cancer care is a requirement, but it is not enough to bring an innovative clinical program to life and sustain it over the long term. To inform the development of new clinical programs, two example programs are presented that successfully integrate cancer rehabilitation services along with details of a three-step process these programs used to facilitate their success and build robust business models that ensure their sustainability. Following the roadmap for growth presented here, gaining input from stakeholders and ensuring their buy-in, leveraging existing programmatic priorities, as well as developing a strategic growth plan can help clinical innovators ensure that new programs anticipate and continually meet the needs of oncology, primary care, subspecialty care, and programs, while addressing the business needs of administrators and improving the experience for patients.

Effects of joint loading on the development of capital femoral epiphysis morphology.

INTRODUCTION: The deleterious influence of increased mechanical forces on capital femoral epiphysis development is well established; however, the growth of the physis in the absence of such forces remains unclear. The hips of non-ambulatory cerebral palsy (CP) patients provide a weight-restricted (partial weightbearing) model which can elucidate the influence of decreased mechanical forces on the development of physis morphology, including features related to development of slipped capital femoral epiphysis (SCFE). Here we used 3D image analysis to compare the physis morphology of children with non-ambulatory CP, as a model for abnormal hip loading, with age-matched native hips. MATERIALS AND METHODS: CT images of 98 non-ambulatory CP hips (8-15 years) and 80 age-matched native control hips were used to measure height, width, and length of the tubercle, depth, width, and length of the metaphyseal fossa, and cupping height across different epiphyseal regions. The impact of age on morphology was assessed using Pearson correlations. Mixed linear model was used to compare the quantified morphological features between partial weightbearing hips and full weightbearing controls. RESULTS: In partial weightbearing hips, tubercle height and length along with fossa depth and length significantly decreased with age, while peripheral cupping height increased with age (r > 0.2, P < 0.04). Compared to normally loaded (full weightbearing) hips and across all age groups, partially weightbearing hips' epiphyseal tubercle height and length were smaller (P < .05), metaphyseal fossa depth was larger (P < .01), and posterior, inferior, and anterior peripheral cupping heights were smaller (P < .01). CONCLUSIONS: Smaller epiphyseal tubercle and peripheral cupping with greater metaphyseal fossa size in partial weightbearing hips suggests that the growing capital femoral epiphysis requires mechanical stimulus to adequately develop epiphyseal stabilizers. Deposit low prevalence and relevance of SCFE in CP, these findings highlight both the role of normal joint loading in proper physis development and how chronic abnormal loading may contribute to various pathomorphological changes of the proximal femur (i.e., capital femoral epiphysis).

Smaller epiphyseal tubercle in hips with slipped capital femoral epiphysis compared to the uninvolved contralateral hip.

Recent investigations suggest that physeal morphologic features have a major role in the capital femoral epiphysis stability and slipped capital femoral epiphysis (SCFE) pathology, with a smaller epiphyseal tubercle and larger peripheral cupping of the femoral epiphysis being present in hips with progressive SCFE compared to healthy controls. Yet, little is known on the causal versus remodeling nature of these associations. This study aimed to use preoperative magnetic resonance imaging (MRI) of patients with unilateral SCFE to perform a comparison of the morphology of the epiphyseal tubercle, metaphyseal fossa, and peripheral cupping in hips with SCFE versus the contralateral uninvolved hips. Preoperative MRIs from 22 unilateral SCFE patients were used to quantify the morphological features of the epiphyseal tubercle (height, width, and length), metaphyseal fossa (depth, width, and length), and peripheral cupping height in three dimension. The quantified anatomical features were compared between hips with SCFE and the contralateral uninvolved side across the whole cohort and within SCFE severity subgroups using paired t-test. We found significantly smaller epiphyseal tubercle heights (p < 0.001) across all severities of SCFE when compared to their uninvolved contralateral side. There was a marginally smaller metaphyseal fossa length (p = 0.05) in SCFE hips compared to their contralateral uninvolved hips, with mild SCFE hips specifically having smaller fossa and epiphyseal lengths (p < 0.05) than their contralateral uninvolved side. There were no side-to-side differences in any other features of the epiphyseal tubercle, metaphyseal fossa and peripheral cupping across all severities (p > 0.05). These findings suggest a potential causal role of epiphyseal tubercle in SCFE pathogenesis.

Effects of native diversity, soil nutrients, and natural enemies on exotic invasion in experimental plant communities.

Many factors can promote exotic plant success. Three of these factors-greater pressure from natural enemies on natives, increased soil nutrient supply, and low native species richness-may interact during invasions. To test for independent and interactive effects of these drivers, we planted herbaceous perennial communities at two levels of native richness (monocultures and five-species polycultures). We then factorially manipulated soil nutrient supply and access to these communities by aboveground foliar enemies (fungal pathogens and insect herbivores), and allowed natural colonization to proceed for four years. We predicted that nutrient addition would increase exotic success, while enemy exclusion and increasing native richness would reduce exotic success. Additionally, we expected that enemy exclusion would reduce the benefits of nutrient addition to exotic species most in species-poor communities, and that this effect would be weaker in species-rich communities. In total, we found no evidence that nutrient supply, enemy access, and native richness interacted to influence exotic success. Furthermore, native richness had no effect on exotic success. Instead, nutrient addition increased, and enemy exclusion decreased, exotic success independently. As predicted, enemy exclusion reduced exotic success, primarily by slowing the decline in abundance of planted native species. Together, these results demonstrate that multiple drivers of exotic success can act independently within a single system.

Southern Phosphorus Indices, Water Quality Data, and Modeling (APEX, APLE, and TBET) Results: A Comparison.

Phosphorus (P) Indices in the southern United States frequently produce different recommendations for similar conditions. We compared risk ratings from 12 southern states (Alabama, Arkansas, Florida, Georgia, Kentucky, Louisiana, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, and Texas) using data collected from benchmark sites in the South (Arkansas, Georgia, Mississippi, North Carolina, Oklahoma, and Texas). Phosphorus Index ratings were developed using both measured erosion losses from each benchmark site and Revised Universal Soil Loss Equation 2 predictions; mostly, there was no difference in P Index outcome. The derived loss ratings were then compared with measured P loads at the benchmark sites by using equivalent USDA-NRCS P Index ratings and three water quality models (Annual P Loss Estimator [APLE], Agricultural Policy Environmental eXtender [APEX], and Texas Best Management Practice Evaluation Tool [TBET]). Phosphorus indices were finally compared against each other using USDA-NRCS loss ratings model estimate correspondence with USDA-NRCS loss ratings. Correspondence was 61% for APEX, 48% for APLE, and 52% for TBET, with overall P index correspondence at 55%. Additive P Indices (Alabama and Texas) had the lowest USDA-NRCS loss rating correspondence (31%), while the multiplicative (Arkansas, Florida, Louisiana, Mississippi, South Carolina, and Tennessee) and component (Georgia, Kentucky, and North Carolina) indices had similar USDA-NRCS loss rating correspondence-60 and 64%, respectively. Analysis using Kendall's modified Tau suggested that correlations between measured and calculated P-loss ratings were similar or better for most P Indices than the models.

Low Vitamin-D Levels Combined with PKP3-SIGIRR-TMEM16J Host Variants Is Associated with Tuberculosis and Death in HIV-Infected and -Exposed Infants.

BACKGROUND: This study examined the associations of 25-hydroxyvitamin D and specific host genetic variants that affect vitamin D levels or its effects on immune function, with the risk of TB or mortality in children. METHODS: A case-cohort sample of 466 South African infants enrolled in P1041 trial (NCT00080119) underwent 25-hydroxyvitamin D testing by chemiluminescent immunoassay. Single nucleotide polymorphisms (SNPs) that alter the effect of vitamin D [e.g. vitamin D receptor (VDR)], vitamin D levels [e.g. vitamin D binding protein (VDBP)], or toll like receptor (TLR) expression (SIGIRR including adjacent genes PKP3 and TMEM16J) were identified by real-time PCR. Outcomes were time to TB, and to the composite of TB or death by 192 weeks of follow-up. Effect modification between vitamin D status and SNPs for outcomes was assessed. FINDINGS: Median age at 25-hydroxyvitamin D determination was 8 months; 11% were breastfed, 51% were HIV-infected and 26% had low 25-hydroxyvitamin D (<32ng/mL). By 192 weeks, 138 incident TB cases (43 definite/probable, and 95 possible) and 26 deaths occurred. Adjusting for HIV status and potential confounders, low 25-hydroxyvitamin D was associated with any TB (adjusted hazard ratio [aHR] 1.76, 95% CI 1.01-3.05; p = 0.046) and any TB or death (aHR 1.76, 95% CI 1.03-3.00; p = 0.038). Children with low 25-hydroxyvitamin D and TMEM 16J rs7111432-AA or PKP3 rs10902158-GG were at increased risk for probable/definite TB or death (aHR 8.12 and 4.83, p<0.05) and any TB or death (aHR 4.78 and 3.26, p<0.005) respectively; SNPs in VDBP, VDR, and vitamin D precursor or hydroxylation genes were not. There was significant interaction between low 25-hydroxyvitamin D and, TMEM 16J rs7111432-AA (p = 0.04) and PKP3 rs10902158-GG (p = 0.02) SNPs. CONCLUSIONS: Two novel SNPs, thought to be associated with innate immunity, in combination with low vitamin D levels were identified as increasing a young child's risk of developing TB disease or death. Identifying high-risk children and providing targeted interventions such as vitamin D supplementation may be beneficial. TRIAL REGISTRATION: ClinicalTrials.gov NCT00080119.

Plant species' origin predicts dominance and response to nutrient enrichment and herbivores in global grasslands.

Exotic species dominate many communities; however the functional significance of species' biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental nutrient addition increases the cover and richness of exotic species, nutrients decrease native diversity and cover. Native and exotic species also differ in their response to vertebrate consumer exclusion. These results suggest that species origin has functional significance, and that eutrophication will lead to increased exotic dominance in grasslands.

Elevated CO2 spurs reciprocal positive effects between a plant virus and an arbuscular mycorrhizal fungus.

Plants form ubiquitous associations with diverse microbes. These interactions range from parasitism to mutualism, depending partly on resource supplies that are being altered by global change. While many studies have considered the separate effects of pathogens and mutualists on their hosts, few studies have investigated interactions among microbial mutualists and pathogens in the context of global change. Using two wild grass species as model hosts, we grew individual plants under ambient or elevated CO(2), and ambient or increased soil phosphorus (P) supply. Additionally, individuals were grown with or without arbuscular mycorrhizal inoculum, and after 2 wk, plants were inoculated or mock-inoculated with a phloem-restricted virus. Under elevated CO(2), mycorrhizal association increased the titer of virus infections, and virus infection reciprocally increased the colonization of roots by mycorrhizal fungi. Additionally, virus infection decreased plant allocation to root biomass, increased leaf P, and modulated effects of CO(2) and P addition on mycorrhizal root colonization. These results indicate that plant mutualists and pathogens can alter each other's success, and predict that these interactions will respond to increased resource availability and elevated CO(2). Together, our findings highlight the importance of interactions among multiple microorganisms for plant performance under global change.

Changes in superior mesenteric artery blood flow after oral, enteral, and parenteral feeding in humans.

OBJECTIVE: Alterations in splanchnic blood flow cause gut ischemia and may predispose to gut-derived sepsis. Increases in superior mesenteric artery (SMA) blood flow occur follow the oral ingestion of food, but the effects of enteral nutrition (EN) on splanchnic perfusion are poorly defined and those of parenteral nutrition (PN) are unknown in humans. The aim of this study was to investigate changes in SMA flow in healthy controls and patients receiving adjuvant nutrition. DESIGN: Qualitative before-after study. SETTING: Intensive care and general wards at Scarborough Hospital, Scarborough, United Kingdom. PATIENTS: Fourteen healthy volunteers and 20 consecutive hemodynamically stable patients receiving adjuvant nutrition. INTERVENTIONS: Oral, EN, or PN after an overnight fast. MEASUREMENTS AND MAIN RESULTS: Duplex ultrasonography was used to assess SMA flow after an overnight fast. Subjects were then rescanned 3 hrs later after commencement of the appropriate test feed so that postprandial flows could be determined. Of the 20 patients recruited, 10 were receiving EN (120 kcal) and 10 PN (175 kcal). Of the 14 volunteers, three received no feed before their second scan (controls), six received an oral meal (530 kcal), and five received EN (120 kcal). Changes in SMA flow within groups were assessed. The control (fasting) volunteers showed no change between the two scans (p = 1.000). All subjects fed intraluminally demonstrated significant increases in postprandial SMA blood flow. Conversely, all patients fed parenterally showed decreased postprandial SMA flows with a median (interquartile range) fasting SMA flow of 14.5 (4.8-24.8) mL/sec, which decreased to 6.1 (2.4-9.2) mL/sec postprandially (p = 0.013). CONCLUSIONS: Splanchnic flow is modulated by the route of feeding. The clinical significance of these findings requires further investigation as they may be important in the management of the critically ill patient, particularly in those with cardiovascular instability or any patient predisposed to gut ischemia.

Traditional practices and exposure to bodily fluids in Lusaka, Zambia.

OBJECTIVES: To ascertain if there are specific sociocultural and behavioural practices associated with the exposure to saliva, semen and vaginal fluids, particularly through child-rearing practices and the use of traditional medicine in Lusaka, Zambia. METHODS: We conducted 11 focus group discussions with men and women from diverse ethnic and socioeconomic backgrounds (n = 105) in Lusaka, Zambia in March 2004. We also conducted a brief sociodemographic survey of all focus group participants. RESULTS: Discussions indicated that saliva was used while engaging in home health care practices associated with childcare and the use of traditional medicine. Additionally, semen and vaginal fluids may be used in rituals associated with childcare and health care for children. Our survey indicated that the use of traditional medicine is associated with lower socioeconomic status. CONCLUSIONS: Population-based studies are needed to evaluate the relationship between traditional behavioural and sociocultural practices, which involve exchange of saliva and other bodily fluids and risk of infectious disease.