Patients Know Best: Qualitative Study on How Families Use Patient-Controlled Personal Health Records.

BACKGROUND: Self-management technologies, such as patient-controlled electronic health records (PCEHRs), have the potential to help people manage and cope with disease. OBJECTIVE: This study set out to investigate patient families' lived experiences of working with a PCEHR. METHODS: We conducted a semistructured qualitative field study with patient families and clinicians at a children's hospital in the UK that uses a PCEHR (Patients Know Best). All families were managing the health of a child with a serious chronic condition, who was typically under the care of multiple clinicians. As data gathering and analysis progressed, it became clear that while much of the literature assumes that patients are willing and waiting to take more responsibility for and control over their health management (eg, with PCEHRs), only a minority of participants in our study responded in this way. Their experiences with the PCEHR were diverse and strongly shaped by their coping styles. Theory on coping identifies a continuum of coping styles, from approach to avoidance oriented, and proposes that patients' information needs depend on their style. RESULTS: We identified 3 groups of patient families and an outlier, distinguished by their coping style and their PCEHR use. We refer to the outlier as controlling (approach oriented, highly motivated to use PCEHR), and the 3 groups as collaborating (approach oriented, motivated to use PCEHR), cooperating (avoidance oriented, less motivated to use PCEHR), and avoiding (very avoidance oriented, not motivated to use PCEHR). CONCLUSIONS: The PCEHR met the needs of controller and collaborators better than the needs of cooperators and avoiders. We draw on the Self-Determination Theory to propose ways in which a PCEHR design might better meet the needs of avoidance-oriented users. Further, we highlight the need for families to also relinquish control at times, and propose ways in which PCEHR design might support a better distribution of control, based on effective training, ease of use, comprehensibility of data security mechanisms, timely information provision (recognizing people's different needs), personalization of use, and easy engagement with clinicians through the PCEHR.

Synthetic lethality between ATR and POLA1 reveals a potential new target for individualized cancer therapy.

The ATR-CHK1 pathway plays a fundamental role in the DNA damage response and is therefore an attractive target in cancer therapy. The antitumorous effect of ATR inhibitors is at least partly caused by synthetic lethality between ATR and various DNA repair genes. In previous studies, we have identified members of the B-family DNA polymerases as potential lethal partner for ATR, i.e. POLD1 and PRIM1. In this study, we validated and characterized the synthetic lethality between ATR and POLA1. First, we applied a model of ATR-deficient DLD-1 human colorectal cancer cells to confirm synthetic lethality by using chemical POLA1 inhibition. Analyzing cell cycle and apoptotic markers via FACS and Western blotting, we were able to show that apoptosis and S phase arrest contributed to the increased sensitivity of ATR-deficient cancer cells towards POLA1 inhibitors. Importantly, siRNA-mediated POLA1 depletion in ATR-deficient cells caused similar effects in regard to impaired cell viability and cumulation of apoptotic markers, thus excluding toxic effects of chemical POLA1 inhibition. Conversely, we demonstrated that siRNA-mediated POLA1 depletion sensitized several cancer cell lines towards chemical inhibition of ATR and its main effector kinase CHK1. In conclusion, the synthetic lethality between ATR/CHK1 and POLA1 might represent a novel and promising approach for individualized cancer therapy: First, alterations of POLA1 could serve as a screening parameter for increased sensitivity towards ATR and CHK1 inhibitors. Second, alterations in the ATR-CHK1 pathway might predict in increased sensitivity towards POLA1 inhibitors.

[Assessment of an e­learning platform for dermatosurgery]. / Beurteilung einer E­Learning-Plattform für Dermatochirurgie.

BACKGROUND: Dermatosurgical (DS) teaching is based on a combination of reading/understanding textbooks and applying surgical procedures (±â€¯supervision). Most textbooks are primarily text-centered. The text is visually supported by photos/sketches (S) and possibly videos (V). A learning goal of this teaching should be that the learner is confident to perform a procedure independently. METHODS: We have developed an online-based platform, the FlapFinder (FF; www.skin-surgery.org ), which teaches the user DS in the facial region primarily in the form of S + V. These are supported by a short text (T) and bonus material (B). B contains personal recommendations from the FF authors. A SurveyMonkey® (Survey Monkey, San Mateo, CA, USA) analysis should clarify how this is assessed by the user. RESULTS: In all, 62 participants completed the questionnaire in full. This was a heterogeneous group (27 dermatologists vs. 35 non-dermatologists; 32â€¯× clinic vs. 30â€¯× non-clinic) with different prior experience. The majority of users found that the combination of T + S + V helped them to understand (55/62; 88.7%), remember (53/62, 85.5%), and perform the procedures independently (43/62; 69.3%). While S + V were most frequently used (22/62; 35.5% and 27/62; 43.6%), users reported having benefited most from this (20/62; 32.3% and 24/62; 38.7%), T + B were used less (0/62, 0.0% and 2/62; 3.2%). Nevertheless, the majority would not want to do without either S, V, T, or B (49/62; 79%). CONCLUSION: The combination of S + V + T + B is rated positively by DS learners. S + V are rated as particularly helpful. Future studies must clarify whether the learning objective of the concrete practical performance of DS is changed by e­media.

The POLD1R689W variant increases the sensitivity of colorectal cancer cells to ATR and CHK1 inhibitors.

Inhibition of the kinase ATR, a central regulator of the DNA damage response, eliminates subsets of cancer cells in certain tumors. As previously shown, this is at least partly attributable to synthetic lethal interactions between ATR and POLD1, the catalytic subunit of the polymerase δ. Various POLD1 variants have been found in colorectal cancer, but their significance as therapeutic targets for ATR pathway inhibition remains unknown. Using CRISPR/Cas9 in the colorectal cancer cell line DLD-1, which harbors four POLD1 variants, we established heterozygous POLD1-knockout clones with exclusive expression of distinct variants to determine the functional relevance of these variants individually by assessing their impact on ATR pathway activation, DNA replication, and cellular sensitivity to inhibition of ATR or its effector kinase CHK1. Of the four variants analyzed, only POLD1R689W affected POLD1 function, as demonstrated by compensatory ATR pathway activation and impaired DNA replication. Upon treatment with ATR or CHK1 inhibitors, POLD1R689W strongly decreased cell survival in vitro, which was attributable at least partly to S phase impairment and apoptosis. Similarly, treatment with the ATR inhibitor AZD6738 inhibited growth of murine xenograft tumors, harboring the POLD1R689W variant, in vivo. Our POLD1-knockout model thus complements algorithm-based models to predict the pathogenicity of tumor-specific variants of unknown significance and illustrates a novel and potentially clinically relevant therapeutic approach using ATR/CHK1 inhibitors in POLD1-deficient tumors.