Assessment of GPs' beliefs relating to the care of people with intellectual disabilities: A Taiwan-based,opportunity-guided approach

Purpose. This study was designed to investigate general practitioners' (GPs) beliefs about the perceived importance of their role in, and their satisfaction with, providing healthcare to people with intellectual disabilities. The identification of healthcare issues with potential for improvement was assessed using gap analysis and an opportunity-guided method.

Method. A cross-sectional census survey by a mail-structured questionnaire recruited 331 GPs (response rate = 16%) who provided information on healthcare for people with intellectual disabilities in 2006 in Taiwan.

Results. The results indicated that GPs considered their role in providing healthcare for people with intellectual disabilities to be important (mean score 7.2 – 8.3). However, the respondents generally did not feel satisfied (mean score 4.6 – 5.5) with their achievements in treating patients with intellectual disabilities. We found that the gender and educational level of the respondents were statistically correlated to the perceived importance they considered their work to have, while the factors of age, medical practice setting and training experience in intellectual disability were statistically correlated to GPs' perceived satisfaction in providing healthcare to people with intellectual disabilities (p < 0.05). Those healthcare issues of ‘training and experience in intellectual disability’, ‘multi-disciplinary and multi-sectoral cooperation’, ‘adequate competence in disability diagnosis’, ‘genetic consulting services’, ‘duty of disease prevention and health promotion’, and ‘adequate medical consultation time’ were the five most promising areas to be improved in healthcare for people with intellectual disabilities according to the opportunity-guided analysis.

Conclusions. This study highlights that health professionals need to examine carefully healthcare issues pertaining to people with ID, and that much more effort is required to develop appropriate healthcare policies based on the opportunity-guided health issues identified here.     

Serum alpha-fetoprotein and clinical outcomes in patients with advanced hepatocellular carcinoma treated with ramucirumab

Background Post hoc analyses assessed the prognostic and predictive value of baseline alpha-fetoprotein (AFP), as well as clinical outcomes by AFP response or progression, during treatment in two placebo-controlled trials (REACH, REACH-2).Methods Serum AFP was measured at baseline and every three cycles. The prognostic and predictive value of baseline AFP was assessed by Cox regression models and Subpopulation Treatment Effect Pattern Plot method. Associations between AFP (≥ 20% increase) and radiographic progression and efficacy were assessed.Results Baseline AFP was confirmed as a continuous (REACH, REACH-2; p < 0.0001) and dichotomous (≥400 vs. <400 ng/ml; REACH, p < 0.01) prognostic factor, and was predictive for ramucirumab survival benefit in REACH (p = 0.0042 continuous; p < 0.0001 dichotomous). Time to AFP (hazard ratio [HR] 0.513; p < 0.0001) and radiographic (HR 0.549; p < 0.0001) progression favoured ramucirumab. Association between AFP and radiographic progression was shown for up to 6 (odds ratio [OR] 5.1; p < 0.0001) and 6–12 weeks (OR 1.8; p = 0.0065). AFP response was higher with ramucirumab vs. placebo (p < 0.0001). Survival was longer in patients with an AFP response than patients without (13.6 vs. 5.6 months, HR 0.451; 95% confidence interval, 0.354–0.574; p < 0.0001).Conclusions AFP is an important prognostic factor and a predictive biomarker for ramucirumab survival benefit. AFP ≥ 400 ng/ml is an appropriate selection criterion for ramucirumab.Clinical Trial Registration ClinicalTrials.gov, REACH ({"type":"clinical-trial","attrs":{"text":"NCT01140347","term_id":"NCT01140347"}}NCT01140347) and REACH-2 ({"type":"clinical-trial","attrs":{"text":"NCT02435433","term_id":"NCT02435433"}}NCT02435433).Subject terms: Oncology, Biomarkers     

Aging-like Spontaneous Epigenetic Silencing Facilitates Wnt Activation,Stemness, and BrafV600E-Induced Tumorigenesis

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Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response

Caffeine is an efficient inhibitor of cellular DNA repair, likely through its effects on ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) kinases. Here, we show that caffeine treatment causes a dose-dependent reduction in the total amount of HIV-1 and avian sarcoma virus retroviral vector DNA that is joined to host DNA in the population of infected cells and also in the number of transduced cells. These changes were observed at caffeine concentrations that had little or no effect on overall cell growth, synthesis, and nuclear import of the viral DNA, or the activities of the viral integrase in vitro. Substantial reductions in the amount of host-viral-joined DNA in the infected population, and in the number of transductants, were also observed in the presence of a dominant-negative form of the ATR protein, ATRkd. After infection, a significant fraction of these cells undergoes cell death. In contrast, retroviral transduction is not impeded in ATM-deficient cells, and addition of caffeine leads to the same reduction that was observed in ATM-proficient cells. These results suggest that activity of the ATR kinase, but not the ATM kinase, is required for successful completion of the viral DNA integration process and/or survival of transduced cells. Components of the cellular DNA damage repair response may represent potential targets for antiretroviral drug development.