Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10-4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the PanCareLIFE project that has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of a website providing information on regional health care services for patients with rheumatoid arthritis: an observational study.

Studies on the effectiveness of information provision for patients with arthritis through the Internet are scarce. This study aimed to describe rheumatoid arthritis (RA) patients' knowledge and information needs before and after launching a website providing information on regional health care services for patients with rheumatic conditions. The intervention consisted of a weekly updated website comprising practical information on regional health care services for patients with arthritis. In addition, patients were offered information leaflets and an information meeting. Before (T1) and 24 months after (T2) the website was launched, a random sample of 400 RA patients filled in a questionnaire regarding knowledge and information need (scores 0-18) about accessibility and contents of 18 regional health care services. Two hundred and fifty-one patients returned the questionnaire (response rate 63%) at T1 and 200 patients (50%) at T2, respectively, with 160 paired observations (112 females (70%), mean age 60.4 years (SD 9.9)). The total score for insufficient knowledge about contents decreased from 9.3 (SD 4.9) to 8.5 (SD 4.8; p = 0.03) and for accessibility from 8.6 (SD 4.7) to 8.4 (SD 4.9; p = 0.59). Total score for information need about contents decreased from 4.2 (SD 4.5) to 1.9 (SD 2.9; p < 0.01) and for accessibility from 3.6 (SD 4.5) to 1.4 (SD 2.4; p < 0.01) (paired t-tests).After the administration of a website comprising practical health care information, RA patients' information need and to a lesser extent their perception of having insufficient knowledge on relevant regional health care services decreased significantly. The results of this descriptive study suggest that the use of the Internet to inform patients may be effective, although controlled studies are required to evaluate and optimize web-delivered information.

Internet-based physical activity interventions: a systematic review of the literature.

BACKGROUND: Nowadays people are extensively encouraged to become more physically active. The Internet has been brought forward as an effective tool to change physical activity behavior. However, little is known about the evidence regarding such Internet-based interventions. OBJECTIVE: The aim of the study was to systematically assess the methodological quality and the effectiveness of interventions designed to promote physical activity by means of the Internet as evaluated by randomized controlled trials. METHODS: A literature search was conducted up to July 2006 using the databases PubMed, Web of Science, EMBASE, PsycINFO, and Cochrane Library. Only randomized controlled trials describing the effectiveness of an Internet-based intervention, with the promotion of physical activity among adults being one of its major goals, were included. Data extracted included source and year of publication, country of origin, targeted health behaviors, participants' characteristics, characteristics of the intervention, and effectiveness data. In addition, the methodological quality was assessed. RESULTS: The literature search resulted in 10 eligible studies of which five met at least nine out of 13 general methodological criteria. The majority of the interventions were tailored to the characteristics of the participants and used interactive self-monitoring and feedback tools. Six studies used one or more theoretical models to compose the contents of the interventions. One study used an objective measure to assess the amount of physical activity (activity monitor), and six studies used multiple subjective measures of physical activity. Furthermore, half of the studies employed measures of physical fitness other than physical activity. In three studies, an Internet-based physical activity intervention was compared with a waiting list group. Of these three studies, two reported a significantly greater improvement in physical activity levels in the Internet-based intervention than in the control group. Seven studies compared two types of Internet-based physical activity interventions in which the main difference was either the intensity of contact between the participants and supervisors (4 studies) or the type of treatment procedures applied (3 studies). In one of these studies, a significant effect in favor of an intervention with more supervisor contact was seen. CONCLUSIONS: There is indicative evidence that Internet-based physical activity interventions are more effective than a waiting list strategy. The added value of specific components of Internet-based physical activity interventions such as increased supervisor contact, tailored information, or theoretical fidelity remains to be established. Methodological quality as well as the type of physical activity outcome measure varied, stressing the need for standardization of these measures.