Exploring the effectiveness of a fitness-app prototype for home care service users in Austria and Italy.

An infinite number of fitness apps are available on various app stores. However, hardly any of them are fitted to the needs and requirements of care-dependent people. This paper investigates the effectiveness of a customised fitness-app prototype for increasing physical activity in home care service users. Home care service users from Austria and Italy were randomly assigned to two groups. In total, 216 participants were involved in the field trial, 104 received a tablet with the fitness app and an activity tracker (treatment group), 112 did not (control group). Regularity of physical activity, frequency of fitness exercises and walking behaviour were self-reported by participants at baseline, after 4 months and after 8 months. In addition, the frequency of using the prototype was assessed based on the fitness app's logged usage data. We estimated multilevel mixed-effects ordered logistic models to examine the effects of the intervention. After 4 months, the intervention increased the home care users' probability of agreeing strongly with being physically active on a regular basis by 28 percentage points (p < 0.001; 95% CI: 0.20, 0.36) and their probability of reporting to exercise more than once a week by 45 percentage points (p < 0.001; 95% CI: 0.32, 0.57). Walking behaviour was not affected on group-level but improved for frequent users of the activity tracker. Frequent and regular users of the fitness app benefited most and effects persisted until the end of the 8 months controlled trial. Tailoring a fitness-app prototype to the needs of care-dependent people has the potential to support people with functional limitations to engage in a more active lifestyle. Future research is encouraged to seek further insights into how new technologies can support physical activities in people with long-term care needs.

Can self-reported pain characteristics and bedside test be used for the assessment of pain mechanisms? An analysis of results of neuropathic pain questionnaires and quantitative sensory testing.

Hyperalgesia and allodynia are frequent in neuropathic pain. Some pain questionnaires such as the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and the Neuropathic Pain Scale (NPS) include self-assessment or bedside testing of hyperalgesia/allodynia. The aim of this study was to determine to what extent LANSS and NPS data are congruent with findings on quantitative sensory testing (QST). Self-reported presence of dynamic mechanical allodynia (DMA) and descriptors of hot, cold, or deep ongoing pain (the NPS and LANSS) as well as bedside findings of mechanical allodynia (LANSS) were compared with signs of DMA and thermal hyperalgesia on QST in 617 patients with neuropathic pain. Self-reported abnormal skin sensitivity (LANSS) showed a moderate concordance with DMA during bedside test (67.9%, κ = 0.391) or QST (52.8%, κ = 0.165). Receiver operating curve analysis for self-reported DMA yielded similar area-under-the-curve values for the LANSS (0.65, confidence interval: 0.59%-0.97%) and NPS (0.71, confidence interval: 0.66%-0.75%) with high sensitivity but low specificity. Self-reported deep pain intensity was higher in patients with blunt pressure hyperalgesia, but not in patients with DMA or thermal hyperalgesia. No correlations were observed between self-reported hot or cold pain quality and thermal hyperalgesia on QST. Self-reported abnormal skin sensitivity has a high sensitivity to identify patients with DMA, but its low specificity indicates that many patients mean something other than DMA when reporting this symptom. Self-reported deep pain is related to deep-tissue hypersensitivity, but thermal qualities of ongoing pain are not related to thermal hyperalgesia. Questionnaires mostly evaluate the ongoing pain experience, whereas QST mirrors sensory functions. Therefore, both methods are complementary for pain assessment.

Comparing ranibizumab monotherapy and combination with single photodynamic therapy in wet AMD: retreatment and morphologic results.

PURPOSE: To evaluate retreatment indications/morphologic responses to ranibizumab monotherapy and combination with verteporfin photodynamic therapy (PDT). METHODS: A total of 40 patients received 3 monthly intravitreal ranibizumab 0.3 mg injections combined with either PDT or sham PDT at baseline (1:1) followed by as-needed ranibizumab based on predetermined vision/anatomical criteria. RESULTS: Retreatment criteria were visual acuity (VA) loss (59%/58%), central retinal thickness (CRT) increase (27%/26%), or both (14%/16%). One month before retreatment, intraretinal cysts (IRC) were present in 84%/74%, subretinal fluid (SRF) in 70%/63%, and at least one of them in 84%/89% of eyes. A significant decrease in mean leakage area, IRC, and SRF as well as a reduction in presence of hemorrhages and hard exudates occurred in both treatment groups at 12 months (compared to baseline). CONCLUSIONS: Retreatment indications were mostly based on VA loss, probably due to the quantitative optical coherence tomography criterion. Intraretinal cysts and SRF were earlier predictors for recurring choroidal neovascularization (CNV) activity than CRT/VA changes. Both treatment strategies were equally potent in reducing CNV activity.

Health targets in the Preventive Health Care Act and their importance for prevention reporting.

Experiences with the evaluation concept developed by the German forum gesundheitsziele.de (health targets) and the results obtained should be taken into consideration during the implementation of prevention reporting. Besides selecting and developing (sub-) targets, evaluating target achievement (impact evaluation) is an important aspect of the concept. This article discusses the methodological challenges for impact evaluation in addition to providing approaches to solve these issues.

Monetising the provision of informal long-term care by elderly people: estimates for European out-of-home caregivers based on the well-being valuation method.

Providing informal care can be both a burden and a source of satisfaction. To understand the welfare effect on caregivers, we need an estimate of the 'shadow value' of informal care, an imputed value for the non-market activity. We use data from the 2006-2007 Survey of Health Ageing and Retirement in Europe which offers the needed details on 29,471 individuals in Austria, Belgium, the Czech Republic, Denmark, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden and Switzerland. Of these, 9768 are unpaid non-co-resident caregivers. To estimate net costs, we follow the subjective well-being valuation method, modelling respondents' life satisfaction as a product of informal care provision, income and personal characteristics, then expressing the relation between satisfaction and care as a monetary amount. We estimate a positive net effect of providing mode rate amounts of informal care, equivalent to €93 for an hour of care/week provided by a caregiver at the median income. The net effect appears to turn negative for greater high care burdens (over 30 hours/week). Interestingly, the effects of differences in care situation are at least an order of magnitude larger. We find that carers providing personal care are significantly more satisfied than those primarily giving help with housework, a difference equivalent to €811 a year at the median income. The article makes two unique contributions to knowledge. The first is its quantifying a net benefit to moderately time-intensive out-of-home caregivers. The second is its clear demonstration of the importance of heterogeneity of care burden on different subgroups. Care-giving context and specific activities matter greatly, pointing to the need for further work on targeting interventions at those caregivers most in need of them.

Inter-individual variability contrasts with regional homogeneity in the human brain DNA methylome.

The possibility that alterations in DNA methylation are mechanistic drivers of development, aging and susceptibility to disease is widely acknowledged, but evidence remains patchy or inconclusive. Of particular interest in this regard is the brain, where it has been reported that DNA methylation impacts on neuronal activity, learning and memory, drug addiction and neurodegeneration. Until recently, however, little was known about the 'landscape' of the human brain methylome. Here we assay 1.9 million CpGs in each of 43 brain samples representing different individuals and brain regions. The cerebellum was a consistent outlier compared to all other regions, and showed over 16 000 differentially methylated regions (DMRs). Unexpectedly, the sequence characteristics of hypo- and hypermethylated domains in cerebellum were distinct. In contrast, very few DMRs distinguished regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable in these regions. These results lead to the surprising conclusion that, with the exception of cerebellum, DNA methylation patterns are more homogeneous between different brain regions from the same individual, than they are for a single brain region between different individuals. This finding suggests that DNA sequence composition, not developmental status, is the principal determinant of the human brain DNA methylome.

Ranibizumab plus verteporfin photodynamic therapy in neovascular age-related macular degeneration: 12 months of retreatment and vision outcomes from a randomized study.

PURPOSE: To investigate the injection frequency and visual acuity (VA) outcomes with combination therapy (ranibizumab plus verteporfin photodynamic therapy, PDT) versus monotherapy (ranibizumab). METHODS: A total of 40 patients with exudative age-related macular degeneration were randomized 1:1 to ranibizumab 0.3 mg plus single standard verteporfin PDT or ranibizumab 0.3 mg plus sham PDT. Ranibizumab was administered 3 times monthly followed by 'as needed' to month 12 based on predetermined vision/anatomical criteria. Retreatment rates, VA outcomes and safety were assessed. RESULTS: During months 3-12, combination therapy patients required fewer ranibizumab injections (mean 1.3) compared with monotherapy patients (2.8). Mean VA improved by 9.0 letters with combination therapy versus 7.5 letters in the monotherapy group at month 12. Both treatment regimens were well tolerated. CONCLUSION: The need for ranibizumab retreatment might be reduced by administering a single verteporfin PDT on the same day as the first ranibizumab injection, without compromising VA outcomes or safety.

Quantification of contrast recognizability in sequential epiretinal membrane removal and internal limiting membrane peeling in trypan blue-assisted macular surgery.

PURPOSE: To evaluate the selectivity and strength of intraoperative trypan blue staining during removal of epiretinal membranes (ERMs) and the internal limiting membrane. METHODS: Based on intraoperative videos, 51 consecutive chromovitrectomies in 51 patients with macular holes, macular pucker, vitreomacular traction syndromes, or persistent macular edema were retrospectively studied. Fifteen subjects underwent trypan blue, 14 indocyanine green, and 22 brilliant blue G chromovitrectomy. The main outcome measure was the color contrast between stained internal limiting membrane or ERM and the underlying unstained tissue by means of objective, quantitative, semiautomated chromaticity difference measurements. RESULTS: Trypan blue stains both ERM and the internal limiting membrane (average chromaticity scores 8.51 and 7.09, respectively; P = 0.48). Internal limiting membrane chromaticity scores were similar for trypan blue (7.09) and brilliant blue G (6.81; P = 0.71) but clearly higher for indocyanine green (15.81; P = 2.45 × 10). CONCLUSION: Under the premises of our study, trypan blue stains both ERM and the internal limiting membrane. Trypan blue's staining capacity of the internal limiting membrane is similar to that of brilliant blue G but significantly inferior compared with indocyanine green. Trypan blue, thus, represents a useful vital dye for chromovitrectomy, particularly in the presence of ERM, where it allows a sequential approach.

High frequency of MYC gene amplification is a common feature of radiation-induced sarcomas. Further results from EORTC STBSG TL 01/01.

Irradiation is a major causative factor among the small subgroup of sarcomas with a known etiology. The prognosis of radiation-induced sarcomas (RIS) is significantly worse than that of their spontaneous counterparts. The most frequent histological subtypes include undifferentiated pleomorphic sarcomas, angiosarcomas, and leiomyosarcomas. A high frequency of MYC amplifications in radiation-induced angiosarcomas, but not in primary angiosarcomas, has recently been described. To investigate whether MYC amplifications are also frequent in RIS other than angiosarcomas, we analyzed the MYC amplification status of 83 RIS and 192 sporadic sarcomas by fluorescence in situ hybridization. We found significantly higher numbers of MYC amplifications in RIS than in sporadic sarcomas (P < 0.0001), especially in angiosarcomas, undifferentiated pleomorphic sarcomas, and leiomyosarcomas. Angiosarcomas were special in that MYC amplifications were particularly frequent and always high level, while other RIS showed low-level amplifications. We conclude that MYC amplifications are a frequent feature of RIS as a group and may contribute to the biology of these tumors.

Informal eldercare and work-related strain.

OBJECTIVES: In light of an aging workforce, reconciling informal eldercare and paid work becomes increasingly pertinent. This article investigates the association between informal eldercare and work-related strain and tests for both the "competing demands" and "expansion" hypotheses. METHOD: The sample of 938 Austrian employees consisted of employees caring for older relatives and a control group of employees without eldercare obligations. We ran a Tobit regression model on work-related strain with different measures of informal eldercare as explanatory variables and controls for both personal and workplace characteristics. RESULTS: Accounting for different characteristics of eldercare within one estimation model revealed that informal eldercare was associated with work-related strain in 2 ways, that is, it increased with both care hours and subjective care burden. However, after controlling for these burdensome attributes of eldercare, the carer status as such was found to be negatively associated with work-related strain. In addition and independently of care commitments, work-related factors, such as advanced skills and job motivation, reduced work-related strain. DISCUSSION: This article lends support to both the "competing demands" and the "expansion" hypotheses. Commitment to eldercare can enhance work-related outcomes but entails work-related problems if care burden and time demands of eldercare are substantial. Thus, workers with eldercare responsibilities cannot be considered less productive from the outset. An individual assessment of their situation, considering the care and work setting, is required. Findings from this study support the design of workplace initiatives to uphold workers' productivity in general and bring specific attention to policies alleviating workers' eldercare burden.

"Do I stay or do I go?"--job change and labor market exit intentions of employees providing informal care to older adults.

UNLABELLED: This article examines whether providing informal eldercare to an older dependent person predicts employees' intentions to change jobs or exit the labor market and, if so, which particular aspects of both caregiving (e.g. time demands, physical/cognitive care burden) and their current work environment shape these intentions. We used data from a sample of 471 caring and 431 noncaring employees in Austria and split the analyses by gender. We found different aspects of informal caregiving to be associated with the intention to change jobs and with the anticipated labor market withdrawal of male and female workers. A time-based conflict between informal eldercare and paid work was significantly and positively related to the intended job change of female workers but not of their male counterparts. Flexible work arrangements were found to facilitate the attachment of female workers to their jobs and the labor market. Intentions to exit the labor market of male workers appeared to be triggered by a physical care burden rather than time demands. HIGHLIGHTS: We studied the effects of providing informal eldercare on the turnover intention of men and women in a group of workers who were also the main carers providing support to a dependent older person with substantial care needs. The intention of male and female workers to change jobs and exit the labor market is shaped by the different characteristics of informal caregiving. Time-based conflicts between informal care and paid work are associated with a higher relative risk of anticipating job changes for female workers. Flextime facilitates the job and labor market attachment of female workers with eldercare responsibilities. The intensity of personal care provided to an older relative is significantly positively related to male workers' relative risk of anticipated labor market exit. Care to an older person in need of supervision makes the labor market exit of female workers less likely, lending thus support to the idea of the respite effect of work.

Orphan CpG islands identify numerous conserved promoters in the mammalian genome.

CpG islands (CGIs) are vertebrate genomic landmarks that encompass the promoters of most genes and often lack DNA methylation. Querying their apparent importance, the number of CGIs is reported to vary widely in different species and many do not co-localise with annotated promoters. We set out to quantify the number of CGIs in mouse and human genomes using CXXC Affinity Purification plus deep sequencing (CAP-seq). We also asked whether CGIs not associated with annotated transcripts share properties with those at known promoters. We found that, contrary to previous estimates, CGI abundance in humans and mice is very similar and many are at conserved locations relative to genes. In each species CpG density correlates positively with the degree of H3K4 trimethylation, supporting the hypothesis that these two properties are mechanistically interdependent. Approximately half of mammalian CGIs (>10,000) are "orphans" that are not associated with annotated promoters. Many orphan CGIs show evidence of transcriptional initiation and dynamic expression during development. Unlike CGIs at known promoters, orphan CGIs are frequently subject to DNA methylation during development, and this is accompanied by loss of their active promoter features. In colorectal tumors, however, orphan CGIs are not preferentially methylated, suggesting that cancer does not recapitulate a developmental program. Human and mouse genomes have similar numbers of CGIs, over half of which are remote from known promoters. Orphan CGIs nevertheless have the characteristics of functional promoters, though they are much more likely than promoter CGIs to become methylated during development and hence lose these properties. The data indicate that orphan CGIs correspond to previously undetected promoters whose transcriptional activity may play a functional role during development.

Anatomical and functional outcome in brilliant blue G assisted chromovitrectomy.

PURPOSE: To evaluate the potential of brilliant blue G (BBG) for intraoperative staining of the inner limiting membrane (ILM) with respect to staining properties and surgical outcome. METHODS: In a retrospective, non-comparative clinical case series, we analysed 17 consecutive chromovitrectomy interventions for surgery of macular holes, ERMs, vitreoretinal traction syndromes and cystoid macular oedema. Following complete posterior vitreous detachment, BBG was injected into the vitreous cavity at a concentration of 0.25 mg/ml, followed by immediate washout. Main outcome measures were staining properties, visual acuity, central visual field testing and optical coherence tomography (OCT) measurements over a mean follow-up period of 3 months. RESULTS: ILM staining was somewhat less intensive for BBG than for average indocyanine green (ICG) chromovitrectomy. However, the ILM was removed successfully without additional ICG in 15/17 patients. Postoperative visual acuity was improved in 16/17 patients and remained unchanged in one patient. Central retinal OCT thickness showed a postoperative reduction, with values ranging from +7 to -295 microm (median -89 microm). Neither visual field defects nor any other adverse events were recorded. CONCLUSION: BBG permits sufficient staining for safe ILM removal. In this short-term study, good anatomical and functional results were achieved and no adverse events were observed.

Cell cycle/apoptosis molecule expression correlates with imatinib response in patients with advanced gastrointestinal stromal tumors.

PURPOSE: Altered expression of cell cycle/apoptosis key regulators may promote tumor progression, reflect secondary genetic/epigenetic events, and impair the effectiveness of therapy. Their expression pattern might then identify gastrointestinal stromal tumor (GIST) patient subgroups with different response to imatinib and elucidate novel therapeutic targets. EXPERIMENTAL DESIGN: Immunohistochemical evaluation of expression of p53, p16, p21, CHK2, CCND1, BCL2, CDK4, and MDM2 was done on 353 histologically validated GIST patients enrolled into a European/Australasian phase III trial. TP53 was screened for mutations in cases with presumptive nonfunctional protein; that is, high p53 and low expression of the two downstream molecules p21 and MDM2. Results were correlated with clinicopathologic data, KIT/PDGFRA mutation status, and imatinib dosage. RESULTS: Frequent impaired expression was found for BCL2 (78%), CHK2 (53%), p53 (50%), and p16 (47%). Stomach-originating GISTs showed significantly lower expression of p21, p16, and BCL2. KIT/PDGFRA wild-type GISTs had significant lower expression of CDK4. Eighty-eight percent of the high p53 expressers show low downstream target activation, indicating a nonfunctional p53 route. Of these high p53 expressers, 16.4% harbor a detectable TP53 mutation. Multivariate analysis, including previously identified markers, showed an independent effect of p53 and p16 on progression-free survival (PFS). Patients with high level of CHK2 and p21 showed significantly better PFS upon a high-dose regimen. CONCLUSIONS: Impaired p53, p16, BCL2, and CHK2 expression is common in advanced GISTs. Distinct patterns of expression correlate with tumor site, genotype, and PFS. Cell cycle/apoptosis maintenance is instrumental for optimal response to imatinib.

Prognostic value of cytokeratin-positive bone marrow cells of gastric cancer patients.

BACKGROUND: Epithelial cells in the bone marrow of patients with gastric cancer suggest tumor dissemination; however, their prognostic implications are controversial. We prospectively evaluated the correlation of bone marrow findings, recurrence rate, and disease-free survival after long-term follow-up. METHODS: Bone marrow were aspirated from both iliac crests and stained with monoclonal cytokeratin (CK)-18 antibody in 209 patients before their initial operation. Patients were followed up for a median of 56 months. RESULTS: Overall, 39 (19%) of 209 patients and 15 (14%) of 109 R0-resected patients had CK-positive cells. CK-positive patients had more local, regional, and distant recurrence than CK-negative patients (P < .05). We found a significantly shorter disease-free survival (P < .05) in the patients with >2 CK-positive cells per 2 x 10(6) bone marrow cells (mean, 35 months) than in patients with 2 CK-positive cells per 2 x 10(6) bone marrow cells was an independent prognostic factor for tumor-related death (P < .05). CONCLUSIONS: Not only the mere presence of CK-positive epithelial cells in bone marrow, but also the cell number, correlates with prognosis. Our findings suggest that classifying CK-positive bone marrow cells in these patients will facilitate future studies.

Gastric cancer surgery in elderly patients.

BACKGROUND: To investigate the value of individual risk-adapted therapy in geriatric patients, we performed a consecutive analysis of 363 patients undergoing potentially curative surgery for gastric cancer. PATIENTS AND METHODS: All patients underwent extensive preoperative workup to assess surgical risk. The following criteria were evaluated in 3 age groups (<60 years, 60-75 years, and >75 years): comorbidity, tumor characteristics, type of resection, postoperative morbidity and mortality, recurrence rate, overall survival, and disease-free survival. RESULTS: There was an increased rate of comorbidity in the higher age groups (51% vs 76% vs 83%; P<0.05). Cardiovascular and pulmonary diseases were most common. There was a decrease in the rate of both total gastrectomy (74%, 54%, 46%; P<0.05) and D2 lymphadenectomy (78%, 53%, 31%; P<0.05). The 30-day mortality in the 3 age groups was 0%, 1%, and 8%, respectively (P<0.05). There was only a slight difference in tumor recurrence rate (35%, 37%, and 27%; P=0.437), with no significant difference in 5-year cancer-related survival (61%, 53%, 61%; P=0.199). CONCLUSIONS: Patient selection and risk-adapted surgery in elderly patients can result in acceptable therapeutic results comparable to younger patients. Limited surgery in elderly gastric cancer patients with high comorbidity does not necessarily compromise oncological outcome.

Chorioretinal neovascularization after radial optic neurotomy for central retinal vein occlusion.

Radial optic neurotomy was recently introduced for the treatment of central retinal vein occlusion. Two patients developed chorioretinal neovascularization through the radial cut of the optic disc after pars plana vitrectomy, radial optic neurotomy, and endophotocoagulation. Patients undergoing radial optic neurotomy should be closely observed to minimize the risk of this complication.

Follow-up of gastro-intestinal stromal tumours (GIST) during treatment with imatinib mesylate by abdominal MRI.

Typical MRI findings for gastro-intestinal stromal tumours (GIST) under treatment with imatinib were evaluated. MRI was performed in 45 patients (25 responders, 20 non-responders) with metastatic or locally advanced, unresectable GIST. Target lesions were selected and re-evaluated after 2, 4, and 6 months of therapy with imatinib. The target tumour response (TTR) was classified according to RECIST criteria. TTR, signal intensity in the centre and border of the lesion and the presence and the extension of a hypervascular rim were analysed. The mean diameter of the marker lesions decreased significantly (P<0.001) from 7.1+/-2.6 cm to 5.9+/-2.3 cm after 6 months. Accuracy of RECIST criteria was 51%, 69% and 73% on MRI 2, 4 and 6 months for response assessment. In addition, responders had higher signal-to-noise ratios on T2-w images after 2 months (P<0.05) and a decrease of vascularised areas in the lesion 4 and 6 months after treatment (each P<0.01), when compared with non-responders. Beyond the size measurement for response assessment, MRI provides additional information of tumour response using SI of T2-w images and quantification of vascularised areas of GIST manifestations.

Effect of root canal dressings on the regeneration of inflamed periapical tissue.

The aim of this study was to evaluate the effects of chlorhexidine and calcium hydroxide on apical periodontitis in rats. Experimentally induced apical periodontitis was established on the mesial roots of maxillary molars of Wistar rats by leaving the root canals exposed to the oral cavity for 14 d. In the positive control group (n=10 teeth), the root canals were not further treated, but the coronal access openings were filled with composite. In the negative control group (n=10 teeth), partial pulpotomies were performed aseptically and the coronal access openings were sealed immediately. In a third control group (n=10 teeth) the canals were instrumented, left empty, and the coronal access openings were sealed. In the experimental groups, the root canals were instrumented and filled with either 2% chlorhexidine gel or calcium hydroxide paste (n=10 teeth per group). After 7 d all rats were killed and the histological sections were stained for microscopic analysis of periapical regeneration. The data of the subjective evaluation were analyzed with the Kruskal-Wallis test. Lesion sizes were measured and statistically analyzed using the ANOVA and post-hoc Scheffé test. The two treatment groups showed significantly lower average inflammatory scores and smaller lesion sizes than the positive and third control group (p<0.05). No statistically significant differences were obtained between the two treatment groups (p>0.05). Chlorhexidine used as an intra-canal medicament showed good periapical regeneration, suggesting that this may be an alternative to calcium hydroxide root canal dressing.