‘They’re doing surgery on two people’: a meta‐ethnography of the influences on couples’ treatment decision making for prostate cancer

Background Current orthodoxy suggests that patients need to be provided with full information about their care and that treatment options should be discussed with patients and family members. This imperative is especially challenging when there is a lack of consensus about treatment effectiveness and equivocacy over different types of interventions. In the case of prostate cancer, evidence is contested as to the efficacy of different treatments. Thus, involving patients and their family members in treatment choices is complex and little is known about how patients and their partners process these decisions when there is uncertainty about different outcomes. This paper has reviewed the literature on the way couples approach such decision making in relation to treatment for prostate cancer. Objective A meta‐ethnographic synthesis of published qualitative papers that focused on the influences on patients’, and their partners’ treatment decision making for prostate cancer, was conducted in order to identify and understand barriers and facilitators which impact on this process. Results Our synthesis indicates that the couples’ relationship ‘dynamic’ provides a contextual background against which treatment decisions are negotiated and made. Discussion and conclusions We propose that the findings from this synthesis can enhance the potential for shared decision making for patients, and their partners, when facing a treatment decision for prostate cancer. By understanding the couples’ relationship dynamic pre‐diagnosis, clinicians may be able to tailor the communication and information provision to both patients and their partners, providing a personalized approach to treatment decision making.     

Endothelial activation and inflammation biomarkers in children and adolescents with sickle cell disease

Sickle cell disease pathogenesis is a complex interplay of multiple factors associated with vascular endothelial activation, intense oxidative stress, and increased sickle cell adhesion. The aim of this study was to determine and compare three panels of plasma circulating biomarkers at ‘steady state’ and during veno-occlusive crises (VOC) in a cohort of children and adolescents with SCD and healthy controls. The following biomarkers were assessed: acute phase reactants, endothelial factors, and adhesion molecules. Forty-one SCD pediatric patients and 28 healthy children were enrolled. Patients at ‘steady state’ presented significantly elevated plasma levels of endothelin-1 (ET-1), soluble-VCAM-1 (sVCAM-1), soluble P-selectin (sP-selectin), and d-dimers compared to the control group. ET-1, sP-selectin, platelet-derived growth factor (PDGF), von Willebrand factor (vWf), d-dimers, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) seems to represent additional, but not independent, prognostic markers of VOC crisis. Elevated plasma levels of sP-selectin, ET-1, and sVCAM-1 were associated with VOC frequency. The present study provides preliminary evidence of a possible association between these biomarkers and the endothelial activation at steady state and VOC in childhood SCD. Further prospective studies are required to confirm the potential independent prognostic value of these markers in different stages of pediatric SCD.     

Arm positioning alters lung volumes in subjects with COPD and healthy subjects

Subjects with chronic obstructive pulmonary disease (COPD) have difficulty performing arm exercise, particularly if the arms are unsupported and elevated. The purpose of this study was to evaluate the effect of arm position on static lung volumes in COPD and healthy subjects. Lung volumes were measured by plethysmography in nine COPD subjects (mean age +/- SD = 67.3 +/- 10.3 years; % pred FEV1 +/- SD = 39.7 +/- 10.9%) and nine healthy subjects (mean age +/- SD = 55.8 +/- 8.8 years; % pred FEV1 +/- SD = 102.9 +/- 12.2%) with the arms below 90 degrees shoulder flexion, at 90 degrees shoulder flexion and above 90 degrees shoulder flexion. In all subjects a significant increase in functional residual capacity (FRC) and reduction in inspiratory capacity (IC) was shown with arms above 90 degrees shoulder flexion when compared with both arms below 90 degrees shoulder flexion (mean increase in FRC (95% CI) was 0.17 L (0.06 to 0.27) for COPD and 0.29 L (0.11 to 0.47) for healthy subjects; mean reduction in IC (95% CI) was 0.24 L (0.1 to 0.38) for COPD and 0.45 L (0.22 to 0.68) for healthy subjects) and arms at 90 degrees shoulder flexion (mean increase in FRC (95% CI) was 0.15 L (0.01 to 0.29) for COPD and 0.22 L (0.11 to 0.34) for healthy subjects; mean reduction in IC (95% CI) was 0.14 L (0.01 to 0.26) for COPD and was 0.29 L (0.17 to 0.42) for healthy subjects). These changes may alter lung mechanics and, in COPD subjects, may affect their ability to perform arm exercise above shoulder height     

Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan

To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10,204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21-q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.     

The effect of orlistat-induced weight loss,without concomitant hypocaloric diet,on cardiovascular risk factors and insulin sensitivity in young obese Chinese subjects with or without type 2 diabetes

BACKGROUND: We examined the weight-losing effect of orlistat treatment on insulin sensitivity and cardiovascular risk factors in a group of severely obese young Chinese patients with or without type 2 diabetes mellitus. METHODS: Obese patients with diabetes (n = 33) and obese nondiabetic patients (n = 27) were given orlistat, 120 mg 3 times daily, without a concomitant hypocaloric diet for 6 months (body mass index [calculated as weight in kilograms divided by the square of height in meter; kg/m2] range, 27.8-47.4). The efficacy measures were (1) insulin sensitivity indices derived from the homeostasis model assessment and a composite measure of whole-body insulin sensitivity index; (2) glycemic control; (3) cardiovascular risk factors, including anthropometry, blood pressure, lipid profiles, and albuminuria; and (4) body composition determined by dual-energy x-ray absorptiometry. RESULTS: At baseline, patients with diabetes had lower body mass index and percentage of body fat but higher waist-hip ratios and were more insulin resistant. Orlistat therapy reduced body weight, waist and hip circumferences, percentage of total body fat, blood pressure, fasting plasma glucose and lipid levels, albuminuria, and insulin sensitivity indices in both groups (all, P<.05). Despite less weight reduction, we found a greater percentage of reduction from baseline in glycosylated hemoglobin level (-11.6% vs -3.6%; P<.001), fasting plasma glucose level (-18.2% vs -5.0%; P<.001), and systolic blood pressure (-7.1% vs -3.1%; P =.02) in patients with diabetes. Obese subjects without diabetes had greater improvements in triglyceride levels, albuminuria, and the homeostasis model assessment (all, P<.01). CONCLUSION: Short-term orlistat treatment without the use of a hypocaloric diet significantly improved insulin sensitivity and cardiovascular risk profiles in severely obese Chinese patients with or without type 2 diabetes.     

p21WAF-1/Cip-1 gene therapy as an adjunct to glaucoma filtration surgery

Glaucoma is a blinding eye disease characterized by elevated intraocular pressure (IOP). Glaucoma filtration surgery (GFS) is designed to reduce IOP, but wound healing responses to the procedure can result in surgical failure. Anti-metabolites used in conjunction with GFS are commonly employed to control the wound healing response, but have unwanted side effects. This review describes the therapeutic potential of ocular gene therapy using an adenovirus vector containing the human p21WAF-1/Cip-1 gene (rAd-p21) to control unwanted wound healing post-GFS. Here, we summarize encouraging preclinical data in relevant models, and propose rAd-p21 gene therapy as an alternative to the currently used methods of wound healing modulation.     

The mosaic genome structure of the Wolbachia wRi strain infecting Drosophila simulans

The obligate intracellular bacterium Wolbachia pipientis infects around 20% of all insect species. It is maternally inherited and induces reproductive alterations of insect populations by male killing, feminization, parthenogenesis, or cytoplasmic incompatibility. Here, we present the 1,445,873-bp genome of W. pipientis strain wRi that induces very strong cytoplasmic incompatibility in its natural host Drosophila simulans. A comparison with the previously sequenced genome of W. pipientis strain wMel from Drosophila melanogaster identified 35 breakpoints associated with mobile elements and repeated sequences that are stable in Drosophila lines transinfected with wRi. Additionally, 450 genes with orthologs in wRi and wMel were sequenced from the W. pipientis strain wUni, responsible for the induction of parthenogenesis in the parasitoid wasp Muscidifurax uniraptor. The comparison of these A-group Wolbachia strains uncovered the most highly recombining intracellular bacterial genomes known to date. This was manifested in a 500-fold variation in sequence divergences at synonymous sites, with different genes and gene segments supporting different strain relationships. The substitution-frequency profile resembled that of Neisseria meningitidis, which is characterized by rampant intraspecies recombination, rather than that of Rickettsia, where genes mostly diverge by nucleotide substitutions. The data further revealed diversification of ankyrin repeat genes by short tandem duplications and provided examples of horizontal gene transfer across A- and B-group strains that infect D. simulans. These results suggest that the transmission dynamics of Wolbachia and the opportunity for coinfections have created a freely recombining intracellular bacterial community with mosaic genomes.