Understanding bladder cancer death

BACKGROUND:

To the authors' knowledge, the extent to which death from bladder cancer is attributable to tumor biology or physician practice patterns is unknown. For this reason, the relative importance of broadening indications for aggressive therapy has unclear implications.

METHODS:

Patients whose deaths were caused directly by bladder cancer were identified using institutional (n = 126 patients) and administrative (n = 6326 patients) data sources. By using implicit review (clinical data, 2001‐2005) and explicit algorithms (Surveillance, Epidemiology, and End Results [SEER]‐Medicare, 1992‐2002), the authors estimated the proportion of potentially avoidable deaths from bladder cancer.

RESULTS:

After an implicit review of clinical data, 40 of 126 deaths (31.7%) were classified as potentially avoidable. Compared with those patients who were deemed unsalvageable, these patients generally presented with nonmuscle‐invasive disease (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder cancer deaths identified in the SEER‐Medicare data potentially were avoidable, depending on the survivorship threshold chosen. Patients whose deaths potentially were avoidable more commonly presented with nonmuscle‐invasive disease (66.7% vs 24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001).

CONCLUSIONS:

The greatest inroads into reducing death from bladder cancer likely hinge on earlier detection or improvement of systemic therapies. However, changing physician practice may translate into nontrivial reductions in bladder cancer mortality. Cancer 2009. © 2009 American Cancer Society.     

An overview of proteomic and metabolomic technologies and their application to pregnancy research

'Omic' technologies represent a strategy towards high-throughput, simultaneous analysis of thousands of biological molecules. Their development has been accelerated in the post-genomic era since these molecules represent the interaction of genes and environment or the 'functional genome'. Omic domains are of particular interest in the search for predictive disease biomarkers and have additional relevance in understanding pathophysiology and the development of molecularly targeted therapeutics. This review examines the fields of proteomics and metabolomics in the context of obstetrics and gynaecology, including a discussion of methodology, challenges, potential applications and current research.     

Orthodontic treatment for prominent upper front teeth in children

Background: Prominent upper front teeth are an important and potentially harmful type of orthodontic problem. This condition develops when the child’s permanent teeth erupt and children are often referred to an orthodontist for treatment with dental braces to reduce the prominence of the teeth. If a child is referred at a young age, the orthodontist is faced with the dilemma of whether to treat the patient early or to wait until the child is older and provide treatment in early adolescence. When treatment is provided during adolescence the orthodontist may provide treatment with various orthodontic braces, but there is currently little evidence of the relative effectiveness of the different braces that can be used. Objectives: To assess the effectiveness of orthodontic treatment for prominent upper front teeth, when this treatment is provided when the child is 7 to 9 years old or when they are in early adolescence or with different dental braces or both. Search strategy: The Cochrane Oral Health Group’s Trials Register, CENTRAL, MEDLINE and EMBASE were searched. The handsearching of the key international orthodontic journals was updated to December 2006. There were no restrictions in respect to language or status of publication. Date of most recent searches: February 2007. Selection criteria: Trials were selected if they met the following criteria:

• ? design – randomized and controlled clinical trials;
• ? participants – children or adolescents (age < 16 years) or both receiving orthodontic treatment to correct prominent upper front teeth;
• ? interventions – active: any orthodontic brace or head‐brace, control: no or delayed treatment or another active intervention;
• ? primary outcomes – prominence of the upper front teeth, relationship between upper and lower jaws;
• ? secondary outcomes: self esteem, any injury to the upper front teeth, jaw joint problems, patient satisfaction, number of attendances required to complete treatment.

Data collection and analysis: Information regarding methods, participants, interventions, outcome measures and results were extracted independently and in duplicate by two review authors. The Cochrane Oral Health Group’s statistical guidelines were followed and mean differences were calculated using random‐effects models. Potential sources of heterogeneity were examined. Main results: The search strategy identified 185 titles and abstracts. From this we obtained 105 full reports for the review. Eight trials, based on data from 592 patients who presented with Class II Division 1 malocclusion, were included in the review. Early treatment comparisons: Three trials, involving 432 participants, compared early treatment with a functional appliance with no treatment. There was a significant difference in final overjet of the treatment group compared with the control group of ?4.04 mm (95% CI ?7.47 to ?0.6, chi squared 117.02, 2 df, P < 0.00001, I2 = 98.3%). There was a significant difference in ANB (?1.35 mm; 95% CI ?2.57 to ?0.14, chi squared 9.17, 2 df, P = 0.01, I2 = 78.2%) and change in ANB (?0.55; 95% CI ?0.92 to ?0.18, chi squared 5.71, 1 df, P = 0.06, I2 = 65.0%) between the treatment and control groups. The comparison of the effect of treatment with headgear versus untreated control revealed that there was a small but significant effect of headgear treatment on overjet of ?1.07 (95% CI ?1.63 to ?0.51, chi squared 0.05, 1 df, P = 0.82, I2 = 0%). Similarly, headgear resulted in a significant reduction in final ANB of ?0.72 (95% CI ?1.18 to ?0.27, chi squared 0.34, 1 df, P = 0.56, I2 = 0%). No significant differences, with respect to final overjet, ANB, or ANB change, were found between the effects of early treatment with headgear and the functional appliances. Adolescent treatment (Phase II): At the end of all treatment we found that there were no significant differences in overjet, final ANB or PAR score between the children who had a course of early treatment, with headgear or a functional appliance, and those who had not received early treatment. Similarly, there were no significant differences in overjet, final ANB or PAR score between children who had received a course of early treatment with headgear or a functional appliance. One trial found a significant reduction in overjet (?5.22 mm; 95% CI ?6.51 to ?3.93) and ANB (?2.27 degrees; 95% CI ?3.22 to ?1.31, chi squared 1.9, 1 df, P = 0.17, I2 = 47.3%) for adolescents receiving one‐phase treatment with a functional appliance versus an untreated control. A statistically significant reduction of ANB (?0.68 degrees; 95% CI ?1.32 to ?0.04, chi squared 0.56, 1 df, P = 0.46, I2 = 0%) with the Twin Block appliance when compared to other functional appliances. However, there was no significant effect of the type of appliance on the final overjet. Authors’ conclusions: The evidence suggests that providing early orthodontic treatment for children with prominent upper front teeth is no more effective than providing one course of orthodontic treatment when the child is in early adolescence.     

Persistence of human multilineage, self-renewing lymphohematopoietic stem cells in chimeric sheep

We have previously reported the ability of uncharacterized human bone marrow (BM) cells to engraft into preimmune fetal sheep, thereby creating sheep-human chimera suitable for in vivo examination of the properties of human hematopoietic stem cells (HSC). Adult human bone marrow CD34+ HLA-DR- cells have been extensively characterized in vitro and have been demonstrated to contain a number of primitive hematopoietic progenitor cells (PHPC). However, the capacity of such highly purified populations of human marrow CD34+ HLA-DR- cells to undergo in vivo self-renewal and multipotential lymphohematopoietic differentiation has not been previously demonstrated. To achieve that, human CD34+ HLA-DR- cells were transplanted in utero into immunoincompetent fetal sheep to investigate the BM-populating potential of these cells. Long-term chimerism, sustained human hematopoiesis, and expression of human cells belonging to all human blood cell lineages were demonstrated in two animals for more than 7 months' posttransplantation. Chimeric BM contained erythroid, granulocytic/monocytic, and megakaryocytic hematopoietic progenitor cells, as well as the primitive high proliferative potential colony- forming cell (HPP-CFC). Under a variety of in vitro experimental conditions, chimeric BM cells gave rise to human T cells expressing T- lymphocyte-specific markers, human natural killer (NK) cells, and human IgG-producing B cells. In vivo expansion and possibly self-renewal of transplanted PHPC was confirmed by the detection in chimeric BM 130 days' posttransplantation of CD34+ HLA-DR- cells, the phenotype of human cells constituting the stem-cell graft. These studies demonstrate not only the BM-populating capacity, multipotential differentiation, and most likely self-renewal capabilities of human CD34+ HLA-DR- cells, but also that this BM population contains human HSC. Furthermore, it appears that this animal model of xenogeneic stem-cell transplantation is extremely useful for in vivo examination of human hematopoiesis and the behavioral and functional characteristics of human HSC.     

Genetic testing in familial AD and FTD: Mutation and phenotype spectrum in a Danish cohort

Autosomal dominantly transmitted Alzheimer's disease (AD) and frontotemporal dementia (FTD) are genetically heterogeneous disorders. To date, three genes have been identified in which mutations cause early-onset autosomal dominant inherited AD: APP, PSEN1 , and PSEN2. Mutations in two genes on chromosome 17, the MAPT and the PGRN genes, are associated with autosomal dominant inherited FTD. The aim of this study was to characterize the mutation spectrum and describe genotype-phenotype correlations in families with inherited dementia. The identification of novel mutations and/or atypical genotype-phenotype correlations contributes to further characterizing the disorders. DNA-samples from the 90 index cases from a Danish referral-based cohort representing families with presumed autosomal dominant inherited AD or FTD were screened for mutations in the known genes with sequencing, denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) techniques. Seven presumed pathogenic mutations (two PSEN1 , one PSEN2 , one APP , one MAPT , and two PGRN ) were identified, including a novel PSEN2 mutation (V393M). No dosage aberrations were identified.     

Factors influencing the adoption of home telecare by elderly or chronically ill people: a national survey

Aims and objectives. The primary aim is to provide insight into client characteristics and characteristics of home telecare contacts, which may influence the adoption of home telecare. Secondary aim is to examine the applicability of four perceived attributes in Rogers’ diffusion of innovations theory, which may influence the adoption: relative advantage, compatibility, complexity and observability. Background. Western countries face strongly increasing healthcare demands. At the same time, a growing nursing shortage exists. The use of home telecare may be instrumental in improving independence and safety and can provide support to older and chronically ill people, but a precondition for its uptake is that clients consider it as a useful and helpful technological tool. Design. A survey conducted among clients of seven home care organisations in the Netherlands connected to a home telecare system. Methods. In 2007, a postal questionnaire was distributed to 468 older or chronically ill clients: 254 responded (54%). The data were analysed by regression techniques, employing a theoretical model. Results. This study showed that clients’ perceived attributes – relative advantage, compatibility, complexity and observability – have a significant effect on adoption of home telecare explaining 61% of the variance. The chance of adoption is higher when a client already receives long‐term personal and/or nursing care, he/she lives alone and when there are fixed daily contacts via the home telecare system. The perception of possible benefits can still be enhanced. Conclusions. The concept of perceived attributes, derived from Rogers’ diffusion of innovation theory, has been useful to explain clients’ adoption of home telecare. Relevance to clinical practice. Home care organisations can best focus on clients already in care and people living alone, in offering home telecare. Nurses, who aim to enhance the client’s adoption of home telecare, have to take into account clients’ perceived attributes of such new technology.