The outcome of the functioning filter after subsequent cataract extraction

OBJECTIVE: To evaluate and compare the outcome of functioning filtration surgery followed by cataract surgery with posterior intraocular lens implantation by both phacoemulsification and extracapsular cataract extraction (ECCE) techniques in glaucomatous eyes. PATIENTS AND METHODS: We retrospectively evaluated the clinical course of 77 eyes (68 patients) that after successful trabeculectomy, underwent cataract surgery by either phacoemulsification or ECCE techniques. We determined the frequency of partial and absolute failure following cataract surgery by either phacoemulsification or ECCE in eyes with functioning trabeculectomies. Partial failure of intraocular pressure (IOP), control after cataract extraction was defined as the need for an increased number of antiglaucoma medications or argon laser trabeculoplasty to maintain IOP =21mm Hg. Complete failure of IOP control after cataract surgery was defined as an IOP >21 mm Hg on at least two consecutive measurements one or more weeks apart or the performance of additional filtration surgery. Failure rates were calculated using the Kaplan-Meier actuarial method. Failure rates between phacoemulsification and ECCE subgroups were compared using the log rank test. RESULTS: The probability of partial failure by the third postoperative year after cataract surgery was 39.5% in the phacoemulsification subgroup and 37.3% in the ECCE subgroup. This small difference is not statistically significant (P = 0.48). The probability of complete failure by the fourth postoperative year after cataract surgery was 12.0% in the phacoemulsification subgroup and 12.5% in the ECCE subgroup. This difference is also not statistically significant (P = 0.77). At the 6-month follow-up visit, visual acuity of both groups improved one or more lines in 87.0% of patients, and worsened one or more lines in 3.9% of patients. Sixty-one percent achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsular opacification requiring laser capsulotomy that occurred in 31.2% of patients. CONCLUSION: Cataract extraction by either phacoemulsification or ECCE following trabeculectomy surgery may be associated with a partial loss of the previously functioning filter and the need for more antiglaucoma medications to control IOP.

Molecular and clinicopathological markers of prognosis in breast cancer

A vast body of research in breast cancer prognostication has accumulated. Yet despite this, patients within current prognostic categories may have significantly different outcomes. There is a need to more accurately divide those cancer types associated with an excellent prognosis from those requiring more aggressive therapy. Gene expression array studies have revealed the numerous molecular breast cancer subtypes that are associated with differing outcomes. Furthermore, as next generation technologies evolve and further reveal the complexities of breast cancer, it is likely that existing prognostic approaches will become progressively refined. Future prognostication in breast cancer requires a morphomolecular, multifaceted approach involving the assessment of anatomical disease extent and levels of protein, DNA and RNA expression. One of the major challenges in prognostication will be the integration of potential assays into existing clinical systems and identification of appropriate patient subgroups for analysis.

Genetic and morphological characterization of Cladobotryum species causing cobweb disease of mushrooms

Cladobotryum dendroides (= Dactylium dendroides) has hitherto been regarded as the major causal agent of cobweb disease of the cultivated mushroom, Agaricus bisporus. Nucleotide sequence data for the internal transcribed spacer (ITS) regions of four Cladobotryum/Hypomyces species reported to be associated with cobweb disease, however, indicate that the most common pathogen is now C. mycophilum. This cobweb pathogen varies somewhat in conidial septation from published descriptions of C. mycophilum and lacks the distinctive colony odor. ITS sequencing revealed minor nucleotide variation which split isolates of the pathogen into three subgroups, two comprising isolates that were sensitive to methylbenzimidazole carbamate (MBC) fungicides and one comprising MBC-resistant isolates. The MBC-resistant isolates, which were only obtained from Ireland and Great Britain, clustered together strongly in randomly amplified polymorphic DNA (RAPD) PCR analysis, suggesting that they may be clonal. The MBC-sensitive isolates were more diverse. A RAPD fragment of 800 to 900 bp, containing a microsatellite and found in the MBC-resistant isolates, also indicated their clonal nature; the microsatellites of these isolates contained the same number of GA repeats. Smaller, polymorphic microsatellites, similarly comprising GA repeats, in the MBC-sensitive isolates in general correlated with their geographic origin.

Forensic analysis of architectural finishes using fourier transform infrared and raman spectroscopy, part II:White paint

White household paints are commonly encountered as evidence in the forensic laboratory but they often cannot be readily distinguished by color alone so Fourier transform infrared (FT-IR) microscopy is used since it can sometimes discriminate between paints prepared with different organic resins. Here we report the first comparative study of FT-IR and Raman spectroscopy for forensic analysis of white paint. Both techniques allowed the 51 white paint samples in the study to be classified by inspection as either belonging to distinct groups or as unique samples. FT-IR gave five groups and four unique samples; Raman gave seven groups and six unique samples. The basis for this discrimination was the type of resin and/ or inorganic pigments/extenders present. Although this allowed approximately half of the white paints to be distinguished by inspection, the other half were all based on a similar resin and did not contain the distinctive modifiers/pigments and extenders that allowed the other samples to be identified. The experimental uncertainty in the relative band intensities measured using FT-IR was similar to the variation within this large group, so no further discrimination was possible. However, the variation in the Raman spectra was larger than the uncertainty, which allowed the large group to be divided into three subgroups and four distinct spectra, based on relative band intensities. The combination of increased discrimination and higher sample throughput means that the Raman method is superior to FT-IR for samples of this type. © 2005 Society for Applied Spectroscopy.

Evaluation of an algorithm to guide patients with type 1 diabetes treated with continuous subcutaneous insulin infusion on how to respond to real-time continuous glucose levels:A randomized controlled trial

OBJECTIVE - To evaluate an algorithm guiding responses of continuous subcutaneous insulin infusion (CSII)-treated type 1 diabetic patients using real-time continuous glucose monitoring (RT-CGM). RESEARCH DESIGN AND METHODS - Sixty CSII-treated type 1 diabetic participants (aged 13-70 years, including adult and adolescent subgroups, with A1C =9.5%) were randomized in age-, sex-, and A1C-matched pairs. Phase 1 was an open 16-week multicenter randomized controlled trial. Group A was treated with CSII/RT-CGM with the algorithm, and group B was treated with CSII/RT-CGM without the algorithm. The primary outcome was the difference in time in target (4-10 mmol/l) glucose range on 6-day masked CGM. Secondary outcomes were differences in A1C, low (=3.9 mmol/l) glucose CGM time, and glycemic variability. Phase 2 was the week 16-32 follow-up. Group A was returned to usual care, and group B was provided with the algorithm. Glycemia parameters were as above. Comparisons were made between baseline and 16 weeks and 32 weeks. RESULTS - In phase 1, after withdrawals 29 of 30 subjects were left in group A and 28 of 30 subjects were left in group B. The change in target glucose time did not differ between groups. A1C fell (mean 7.9% [95% CI 7.7-8.2to 7.6% [7.2-8.0]; P <0.03) in group A but not in group B (7.8% [7.5-8.1] to 7.7 [7.3-8.0]; NS) with no difference between groups. More subjects in group A achieved A1C =7% than those in group B (2 of 29 to 14 of 29 vs. 4 of 28 to 7 of 28; P = 0.015). In phase 2, one participant was lost from each group. In group A, A1C returned to baseline with RT-CGM discontinuation but did not change in group B, who continued RT-CGM with addition of the algorithm. CONCLUSIONS - Early but not late algorithm provision to type 1 diabetic patients using CSII/RT-CGM did not increase the target glucose time but increased achievement of A1C =7%. Upon RT-CGM cessation, A1C returned to baseline. © 2010 by the American Diabetes Association.

Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups.

Methods: Protein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry.

Results: Analysis of variance analysis (P <= 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P =0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system.

Conclusions: The data indicates distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways which could influence pathological events at the joint level.

Identifying solutions to increase participation in physical activity interventions within a socio-economically disadvantaged community: a qualitative study

Background: There is an urgent need to increase population levels of physical activity, particularly amongst those who are socio-economically disadvantaged. Multiple factors influence physical activity behaviour but the generalisability of current evidence to such ‘hard-to-reach’ population subgroups is limited by difficulties in recruiting them into studies. Also, rigorous qualitative studies of lay perceptions and perceptions of community leaders about public health efforts to increase physical activity are sparse. We sought to explore, within a socio-economically disadvantaged community, residents’ and community leaders’ perceptions of physical activity (PA) interventions and issues regarding their implementation, in order to improve understanding of needs, expectations, and social/environmental factors relevant to future interventions.

Methods: Within an ongoing regeneration project (Connswater Community Greenway), in a socio-economically disadvantaged community in Belfast, we collaborated with a Community Development Agency to purposively sample leaders from public- and voluntary-sector community groups and residents. Individual semi-structured interviews were conducted with 12 leaders. Residents (n=113), of both genders and a range of ages (14 to 86 years) participated in focus groups (n=14) in local facilities. Interviews and focus groups were recorded, transcribed verbatim and analysed using a thematic framework.

Results: Three main themes were identified: awareness of PA interventions; factors contributing to intervention effectiveness; and barriers to participation in PA interventions. Participants reported awareness only of interventions in which they were involved directly, highlighting a need for better communications, both inter- and intra-sectoral, and with residents. Meaningful engagement of residents in planning/organisation, tailoring to local context, supporting volunteers, providing relevant resources and an ‘exit strategy’ were perceived as important factors related to intervention effectiveness. Negative attitudes such as apathy, disappointing experiences, information with no perceived personal relevance and limited access to facilities were barriers to people participating in interventions.

Conclusions: These findings illustrate the complexity of influences on a community’s participation in PA interventions and support a social-ecological approach to promoting PA. They highlight the need for cross-sector working, effective information exchange, involving residents in bottom-up planning and providing adequate financial and social support. An in-depth understanding of a target population’s perspectives is of key importance in translating PA behaviour change theories into practice.

Repackaging Prostate Cancer Support Group Research Findings: An e-KT Case Study

n the context of psychosocial oncology research, disseminating study findings to a range of knowledge “end-users” can advance the well-being of diverse patient subgroups and their families. This article details how findings drawn from a study of prostate cancer support groups were repackaged in a knowledge translation website—www.prostatecancerhelpyourself.ubc.ca—using Web 2.0 features. Detailed are five lessons learned from developing the website: the importance of pitching a winning but feasible idea, keeping a focus on interactivity and minimizing text, negotiating with the supplier, building in formal pretests or a pilot test with end-users, and completing formative evaluations based on data collected through Google™ and YouTube™ Analytics. The details are shared to guide the e-knowledge translation efforts of other psychosocial oncology researchers and clinicians.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Topology synthesis of three-legged spherical parallel manipulators employing Lie group theory

Driven by the requirements of the bionic joint or tracking equipment for the spherical parallel manipulators (SPMs) with three rotational degrees-of-freedom (DoFs), this paper carries out the topology synthesis of a class of three-legged SPMs employing Lie group theory. In order to achieve the intersection of the displacement subgroups, the subgroup characteristics and operation principles are defined in this paper. Mainly drawing on the Lie group theory, the topology synthesis procedure of three-legged SPMs including four stages and two functional blocks is proposed, in which the assembly principles of three legs are defined. By introducing the circular track, a novel class of three-legged SPMs is synthesized, which is the important complement to the existing SPMs. Finally, four typical examples are given to demonstrate the finite displacements of the synthesized three-legged SPMs.

Dimensionality, Reliability and Validity of the InterRAI Depression Rating Scale in a Canadian Palliative Care Population

A reliable and valid instrument is needed to screen for depression in palliative patients. The interRAI Depression Rating Scale (DRS) is based on seven items in the interRAI Palliative Care instrument. This study is the first to explore the dimensionality, reliability and validity of the DRS in a palliative population. Palliative home care patients (n = 5,175) residing in Ontario (Canada) were assessed with the interRAI Palliative Care instrument. Exploratory factor analysis and Mokken scale analysis were used to identify candidate conceptual models and evaluate scale homogeneity/performance. Confirmatory factor analysis compared models using standard goodness-of-fit indices. Convergent and divergent validity were investigated by examining polychoric correlations between the DRS and other items. The “known groups” test determined if the DRS meaningfully distinguished among client subgroups. The non-hierarchical two factor model showed acceptable fit with the data, and ordinal alpha coefficients of 0.83 and 0.82 were observed for the two DRS subscales. Omega hierarchical (ωh) was 0.78 for the bifactor model, with the general factor explaining three quarters of the common variance. Despite the multidimensionality evident in the factor analyses, bifactor modelling and the Mokken homogeneity coefficient (0.34) suggest that the DRS is a coherent scale that captures important information on sub-constructs of depression (e.g., somatic symptoms). Higher correlations were seen between the DRS and mood and psychosocial well-being items, and lower correlations with functional status and demographic variables. The DRS distinguished in the expected manner for known risk factors (e.g., social support, pain). The results suggest that the DRS is primarily unidimensional and reliable for use in screening for depression in palliative care patients.

Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: A prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial

Background: Primary results from the phase 3 ALSYMPCA trial showed that radium-223 dichloride (radium-223), a targeted α-emitter, improved overall survival compared with placebo and was well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases. We did a prespecified subgroup analysis from ALSYMPCA to assess the effect of previous docetaxel use on the efficacy and safety of radium-223. 

Methods: In the phase 3, randomised, double-blind ALSYMPCA trial, patients with symptomatic castration-resistant prostate cancer, at least two symptomatic bone metastases, no known visceral metastases, and who were receiving best standard of care were randomly assigned (2:1) via an interactive voice response system to receive six injections of radium-223 (50 kBq/kg intravenously) or matching placebo, with one injection given every 4 weeks. Patients had either received previous docetaxel treatment or were unsuitable for or declined docetaxel; previous docetaxel use (yes or no) was a trial stratification factor. We investigated the effect of previous docetaxel use on radium-223 treatment for the primary endpoint of overall survival, the main secondary efficacy endpoints, and safety. Efficacy analyses were done for the intention-to-treat population; safety analyses were done for the safety population. The trial has been completed and is registered with ClinicalTrials.gov, number NCT00699751. 

Findings: Randomisation took place between June 12, 2008, and Feb 1, 2011. 526 (57%) of 921 randomly assigned patients had received previous docetaxel treatment (352 in the radium-223 group and 174 in the placebo group) and 395 (43%) had not (262 in the radium-223 group and 133 in the placebo group). Radium-223 prolonged median overall survival compared with placebo, irrespective of previous docetaxel use (previous docetaxel use, hazard ratio [HR] 0·70, 95% CI 0·56-0·88; p=0·002; no previous docetaxel use, HR 0·69, 0·52-0·92; p=0·01). The benefit of radium-223 compared with placebo was seen in both docetaxel subgroups for most main secondary efficacy endpoints; risk for time to time to first symptomatic skeletal event was reduced with radium-223 versus placebo in patients with previous docetaxel use, but the difference was not significant in those with no previous docetaxel use. 322 (62%) of 518 patients previously treated with docetaxel had grade 3-4 adverse events, compared with 205 (54%) of 383 patients without docetaxel. Patients who had previously been treated with docetaxel had a higher incidence of grade 3-4 thrombocytopenia with radium-223 than with placebo (31 [9%] of 347 patients vs five [3%] of 171 patients), whereas the incidence was similar between treatment groups among patients with no previous docetaxel use (seven [3%] of 253 patients vs one [1%] of 130 patients). The incidences of grade 3-4 anaemia and neutropenia were similar between the radium-223 and placebo groups within both docetaxel subgroups. 

Interpretation: Radium-223 is effective and well tolerated in patients with castration-resistant prostate cancer and symptomatic bone metastases, irrespective of previous docetaxel use. 

Funding: Algeta ASA and Bayer HealthCare Pharmaceuticals.

Addressing inequalities in physical activity participation: Implications for public health policy and practice

OBJECTIVE: To investigate the characteristics of those doing no moderate-vigorous physical activity (MVPA) (0days/week), some MVPA (1-4days/week) and sufficient MVPA (≥5days/week) to meet the guidelines in order to effectively develop and target PA interventions to address inequalities in participation.

METHOD: A population survey (2010/2011) of 4653 UK adults provided data on PA and socio-demographic characteristics. An ordered logit model investigated the covariates of 1) participating in no PA, 2) participating in some PA, and 3) meeting the PA guidelines. Model predictions were derived for stereotypical subgroups to highlight important policy and practice implications.

RESULTS: Mean age of participants was 45years old (95% CI 44.51, 45.58) and 42% were male. Probability forecasting showed that males older than 55years of age (probability=0.20; 95% CI 0.11, 0.28), and both males (probability=0.31; 95% CI 0.17, 0.45) and females (probability=0.38; 95% CI 0.27, 0.50) who report poor health are significantly more likely to do no PA.

CONCLUSIONS: Understanding the characteristics of those doing no MVPA and some MVPA could help develop population-level interventions targeting those most in need. Findings suggest that interventions are needed to target older adults, particularly males, and those who report poor health.

Large panel-survey data demonstrated country-level and ethnic minority variation in consent for health record linkage

Objectives
To investigate individual, household and country variation in consent to health record linkage.

Study Design and Setting
Data from 50,994 individuals aged 16-74 years recruited to wave 1 of a large UK general purpose household survey (January 2009 – December 2010) were analysed using multi-level logistic regression models.

Results
Overall, 70.7% of respondents consented to record linkage. Younger age, marriage, tenure, car ownership and education were all significantly associated with consent, though there was little deviation from 70% in subgroups defined by these variables. There were small increases in consent rates in individuals with poor health when defined by self-reported long term limiting illness (adjusted OR 1.11; 95%CIs 1.06, 1.16), less so when defined by General Health Questionnaire score (adjusted OR=1.05; 95%CIs 1.00, 1.10), but the range in absolute consent rates between categories was generally less than 10%. Larger differences were observed for those of non-white ethnicity who were 38% less likely to consent (adjusted OR 0.62; 95%CIs 0.59, 0.66). Consent was higher in Scotland than England (adjusted OR 1.17; 95%CIs 1.06, 1.29) but lower in Northern Ireland (adjusted OR 0.56; 95%CIs 0.50, 0.63).

Conclusion
The modest overall level of systematic bias in consent to record linkage provides reassurance for record linkage potential in general purpose household surveys. However, the low consent rates amongst non-white ethnic minority survey respondents will further compound their low survey participation rates. The reason for the country-level variation requires further study.

Psychosocial interventions to improve quality of life and emotional wellbeing in newly diagnosed cancer patients

Title
Psychosocial interventions to improve quality of life and emotional wellbeing for recently diagnosed cancer patients.

Background
Despite clear guidelines recommending the provision of emotional support for cancer patients, we do not know how best to address psychological distress in this group.

Aim
To assess the effects of psychosocial interventions to improve quality of life (QoL) and general psychological distress newly diagnosed cancer patients.

Methods
We searched electronic sources for RCTs of psychosocial interventions or ‘talking therapies’ with individual newly diagnosed cancer patients. Only trials measuring QoL and general psychological distress were included. Meta-analyses examined subgroups by outcome measurement, mode of delivery and discipline of trained helper.

Results
Thirty trials met the criteria. No significant effects were observed for QoL at 6-months (SMD 0.11; 95% CI -0.00 to 0.22) except when using cancer-specific measures (SMD 0.16; 95% CI 0.02 to 0.30). Sub-group analyses revealed that psycho-educational, nurse-delivered interventions improved QoL (SMD 0.23; 95% CI 0.04 to 0.43). General psychological distress as assessed by ‘mood measures’ improved (SMD - 0.81; 95% CI -1.44 to -0.18), but heterogeneity was a factor.

Discussion and conclusion
Psychosocial interventions vary in format and content, raising concerns about heterogeneity, despite appearing to have a beneficial impact on cancer-specific QoL and mood. Future research should concentrate on screening for emotional support needs and identifying common elements within interventions that are of value. Authors should carefully select outcome measures that are appropriately sensitive to change.