Mathematical model to predict individual survival for patients with renal cell carcinoma.

PURPOSE: To develop a multivariate model and mathematical formula capable of calculating personalized survival for renal cell carcinoma (RCC) patients with clinically available variables. PATIENTS AND METHODS: A total of 477 patients out of 661 undergoing nephrectomy at the University of California Los Angeles between 1989 and 1999 were eligible for evaluation and formed the analyzed cohort for this retrospective study. Time to death was the primary end point assessed. Univariate analysis for 14 to 20 variables was conducted, followed by a multivariate Cox analysis. The variables that provided independent information as to the time of death for metastatic and nonmetastatic patients were coded and incorporated into a function based on the Nadas equation principle. RESULTS: For nonmetastatic patients, the significant variables in the multivariate analysis were Fuhrman's grade and Eastern Cooperative Oncology Group performance status. For the metastatic patients, Fuhrman's grade, 1997 classification T stage, number of symptoms, nodal involvement, and immunotherapy were independent predictors for survival. These variables, based on the Cox multivariate regression model, were implanted into an exponential Nadas equation. The expected survival predicted by use of the Nadas equations faithfully describes the actual survival based on Kaplan-Meier curves. CONCLUSION: We have developed mathematical equations for estimating survival after radical nephrectomy for RCC. The resulting formulas are capable of better tailoring survival estimates for a specific patient and are based on widely accepted clinical prognostic variables. On validation with external data, this type of representation can be used as a tool for the determination of personalized prognosis and may be useful for patient education and counseling.     

Management principles of organic causes of childhood constipation.

Constipation is extremely common in the pediatric population; however, it is a symptom and not a disease. Organic causes of constipation include Hirschprung's disease, anorectal malformation, and spina bifida. This article also discusses constipation and urinary tract pathology and dysfunction. The function of the gastrointestinal and urinary tracts are intertwined, and this concept will assist the practitioner in managing patients accordingly. Children and adolescents who experience bowel dysfunction require patience and sensitive support from their health care providers so that they can live productive and emotionally healthy lives.     

Exploring multi-agency working in services to disabled children with complex healthcare needs and their families

Children with complex healthcare needs typically require technical and/or medical equipment in the home. This growing group of children and families need support that crosses agency and professional boundaries, necessitating effective multi-agency working. There are many examples of multi-agency working around the United Kingdom (UK), some specifically designed to meet the needs of children with complex healthcare needs and their families. Recent legislation and policy statements have highlighted the importance of joint planning and working. Currently no research exists that examines the impact of these initiatives on disabled children with complex healthcare needs and their families. The "Working Together" project is an ongoing research study based at the Norah Fry Research Centre, University of Bristol, Bristol, UK. The project aims to explore the impact of multi-agency work on children with complex healthcare needs and their families. This paper examines the literature on barriers to disabled children and the need for multi-agency working. It also considers the concept of multi-agency working and how different approaches to working together might be perceived by children and families.     

Family Formation Goals Among Sexual and Gender Minority Individuals in Urban India

Sexual and Gender Minority (SGM) individuals’ (nonheterosexual or noncisgender) desires and intentions to form families have been under‐researched. Further, research on family formation among SGM individuals is even more scant in India. Family formation, a significant milestone for many individuals, has important implications for overall health. Using data from interviews (n=25) and focus group discussions (8 participants) with SGM individuals in Bangalore, Chennai, and Kolkata, we explore desires and intentions related to parenting. Pressure to have children was ubiquitous, though participants’ parenting‐related desires varied. Participants considering parenting noted many priorities including their financial stability, relationships with partners, and the legality and legitimacy of their partnerships. Adoption and assisted biological reproduction (e.g., IVF) were the preferred methods of family formation. Experiences and expectations of stigma for themselves and their children shaped participants’ limited control over parenting‐related decisions. However, they exerted agency as they navigated achieving their ideals for family formation.     

Inhibiting activin‐A signaling stimulates bone formation and prevents cancer‐induced bone destruction in vivo

Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis (p < .01), promotes bone formation (p < .01) and increases bone mass in vivo (p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < .05) and suppression of bone formation (p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis (p < .01), prevents myeloma‐induced suppression of bone formation (p < .05), blocks the development of osteolytic bone lesions (p < .05), and increases survival (p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction (p < .001) and inhibits bone metastases (p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. © 2010 American Society for Bone and Mineral Research.     

Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases

Here, we investigated if TAR-DNA-binding protein-43 (TDP-43), the disease protein in frontotemporal lobar degeneration and ubiquitin inclusions with or without motor neuron disease as well as amyotrophic lateral sclerosis, also formed inclusions in Lewy body (LB) disorders including Parkinson’s disease (PD) without or with dementia (PDD), and dementia with LBs (DLB) alone or in association with Alzheimer’s disease (AD). Immunohistochemical analyses of TDP-43 in clinically well characterized and pathologically confirmed cases of DLB + AD, PD and PDD demonstrated TDP-43 pathology in the following percentage of cases: DLB + AD = 25/80 (31.3%); PD = 5/69 (7.2%); PDD = 4/21 (19%), while DLB and normal controls exhibited no (0/10, 0%) and one cases (1/33, 3%) presenting TDP-43 pathology, respectively. Significant differences in the prevalence of TDP-43 lesions were noted between disease versus normal brains (P < 0.001) as well as demented versus non-demented brains (P < 0.001). Statistical analyses revealed a positive relationship between TDP-43 lesions and several clinical and pathological parameters in these disorders suggesting the TDP-43 pathology may have co-morbid effects in LB diseases. This study expands the concept of TDP-43 proteinopathies by implicating TDP-43 lesions in mechanisms of neurodegeneration in LB disorders. Hanae Nakashima-Yasuda and Kunihiro Uryu are equally contributed first authors.     

Discrete choice experiments for complex health‐care decisions: does hierarchical information integration offer a solution?

This paper describes an application of hierarchical information integration (HII) discrete choice experiments. We assessed theoretical and construct validity, as well as internal consistency, to investigate whether HII can be used to investigate complex multi-faceted health-care decisions (objective 1). In addition, we incorporated recent advances in mixed logit modelling (objective 2). Finally, we determined the response rate and predictive ability to study the feasibility of HII to support health-care management (objective 3). The clinical subject was the implementation of the guideline for breast cancer surgery in day care, which is a complex process that involves changes at the organizational and management levels, as well as the level of health-care professionals and that of patients.We found good theoretical and construct validity and satisfactory internal consistency. The proposed mixed logit model, which included repeated measures corrections and subexperiment error scale variations, also performed well. We found a poor response, but the model had satisfactory predictive ability. Therefore, we conclude that HII can be used successfully to study complex multi-faceted health-care decisions (objectives 1 and 2), but that the feasibility of HII to support health-care management, in particular in challenging implementation projects, seems less favourable (objective 3).     

Familial occurrence of dementia with Lewy bodies.

OBJECTIVE: The authors investigated the validity of the designation "familial dementia with Lewy bodies (DLB)" by evaluating the clinical, neuropathological, and genetic characteristics of previously reported families exhibiting both familial parkinsonism and dementia. METHODS: Several families, including multiple individuals with parkinsonism as well as prominent dementia, were identified through a literature search. Selected families had at least one member with dementia with autopsy evidence of neocortical and/or limbic Lewy-body (LB) pathology. Clinical and neuropathological evidence from reports of families with prominent dementia as well as parkinsonism was reviewed to further define familial DLB. RESULTS: All selected families had at least one affected individual with dementia and autopsy-proven DLB. Therefore, these families might be considered examples of familial DLB. Individuals in the first six families typically presented with parkinsonian features, whereas cognitive decline did not appear until years later. In contrast, in the other six families, affected individuals typically presented with cognitive decline, and parkinsonism developed later. CONCLUSIONS: Families exist in which one or more persons meet both clinical and neuropathological criteria for DLB. They differ as to whether the signs of parkinsonism precede or follow signs of dementia. It remains to be determined whether this clinical distinction is biologically important. Susceptibility to developing LB pathology may be determined by the interaction between genetic predisposition and environmental risk factors.