Using Quality Improvement to Expand and Align State Public Health Long-Term Follow-up Data Collection Across Newborn Screening Conditions.

CONTEXT: Despite the undeniable success of newborn screening (NBS), numerous barriers exist regarding long-term follow-up (LTFU) of children with conditions included in NBS. Furthermore, there is a focus on condition-specific follow-up with no national guidelines for standard quality measures collected by state public health LTFU programs. PROGRAM: Minnesota Department of Health (MDH) Longitudinal Follow-up for NBS. IMPLEMENTATION: A state public health LTFU for NBS quality improvement (QI) project was carried out with collaboration between MDH project team members and a QI Steering Team who provided clinical, public health, education, caregiver, and community perspectives and expertise to MDH. Relevant measures were selected from existing data elements, and additional measures were developed based on exchange between MDH project team and the QI Steering Team. Potential data sources were explored and prioritized. Processes for querying existing data sources such as death records were refined, new sources such as electronic health records and paper/PDF health records were established, and data collection was piloted. The Minnesota Electronic Disease Surveillance System was modified, and an electronic data form was created to promote consistent data abstraction from sources. Throughout the project, progress was evaluated and shared. At project conclusion, MDH project team and the QI Steering Team reviewed project outcomes and approaches to evolve the project into ongoing surveillance. EVALUATION: Five common public health LTFU measures were determined. Overall, 77% of attempted measures were successfully collected. Primary and secondary data sources were adopted. In addition, collected data resulted in 7% of cases that were closed to further public health LTFU, often related to a move out of state. DISCUSSION: This project established the feasibility of state public health LTFU surveillance of outcomes and health care use by collecting a common data set applicable across NBS conditions.

Web-based physical activity promotion in young people with CF: a randomised controlled trial.

BACKGROUND: Physical activity levels are known to decline following hospitalisation for people with cystic fibrosis (pwCF). However, optimal physical activity promotion strategies are unclear. This study investigated the effect of a web-based application (ActivOnline) in promoting physical activity in young pwCF. METHODS: Multicentre randomised controlled trial with assessor blinding and qualitative evaluation. People with CF (12-35 years) admitted to hospital for a respiratory cause were eligible and randomised to the 12-week ActivOnline intervention (AO) or usual care (UC). The primary outcome was change in device-based time spent in moderate-to-vigorous physical activity (MVPA) from baseline to post-intervention. Follow-up was at 6 months from hospital discharge when qualitative evaluation was undertaken. RESULTS: 107 participants were randomised to AO (n=52) or UC (n=55). Sixty-three participants (59%) contributed to the intention-to-treat analysis. Mean (SD) age was 21 (6) years (n=46, <18 years). At baseline, physical activity levels were high in both groups (AO 102 (52) vs UC 127 (73) min/day). There was no statistically significant difference in MVPA between groups at either timepoint (post-intervention mean difference (95% CI) -14 mins (-45 to 16)). Uptake of the intervention was low with only 40% (n=21) of participants accessing the web application. CONCLUSION: A web-based application, including individualised goal setting, real-time feedback and motivation for behavioural change, was no better than usual care at promoting physical activity in young pwCF following hospital discharge. High levels of baseline physical activity levels in both groups, and limited engagement with the intervention, suggest alternative strategies may be necessary to identify and support young pwCF who would benefit from enhanced physical activity. TRIAL REGISTRATION NUMBER: ACTRN12617001009303, 13 July 13 2017.

A web-based intervention to promote physical activity in adolescents and young adults with cystic fibrosis: protocol for a randomized controlled trial.

BACKGROUND: Regular participation in physical activity by people with cystic fibrosis (CF) promotes positive clinical and health outcomes including reduced rate of decline in lung function, fewer hospitalizations and greater wellbeing. However adherence to exercise and activity programs is low, in part due to the substantial daily therapy burden for young people with CF. Strict infection control requirements limit the role of group exercise programs that are commonly used in other clinical groups. Investigation of methods to promote physical activity in this group has been limited. The Active Online Physical Activity in Cystic fibrosis Trial (ActionPACT) is an assessor-blinded, multi-centre, randomized controlled trial designed to compare the efficacy of a novel web-based program (ActivOnline) compared to usual care in promoting physical activity participation in adolescents and young adults with CF. METHODS: Adolescents and young adults with CF will be recruited on discharge from hospital for a respiratory exacerbation. Participants randomized to the intervention group will have access to a web-based physical activity platform for the 12-week intervention period. ActivOnline allows users to track their physical activity, set goals, and self-monitor progress. All participants in both groups will be provided with standardised information regarding general physical activity recommendations for adolescents and young adults. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and at 3-months followup. Healthcare utilization will be assessed at 12 months from intervention completion. The primary outcome is change in moderate-to-vigorous physical activity participation measured objectively by accelerometry. Secondary outcomes include aerobic fitness, health-related quality of life, anxiety and depression and sleep quality. DISCUSSION: This trial will establish whether a web-based application can improve physical activity participation more effectively than usual care in the period following hospitalization for a respiratory exacerbation. The web-based application under investigation can be made readily and widely available to all individuals with CF, to support physical activity and exercise participation at a time and location of the user's choosing, regardless of microbiological status. TRIAL REGISTRATION: Clinical trial registered on July 13, 2017 with the Australian and New Zealand Clinical Trials Register at (ACTRN12617001009303).

alpha-Melanocortin and endothelin-1 activate antiapoptotic pathways and reduce DNA damage in human melanocytes.

UV radiation is an important etiologic factor for skin cancer, including melanoma. Constitutive pigmentation and the ability to tan are considered the main photoprotective mechanism against sun-induced carcinogenesis. Pigmentation in the skin is conferred by epidermal melanocytes that synthesize and transfer melanin to keratinocytes. Therefore, insuring the survival and genomic stability of epidermal melanocytes is critical for inhibiting photocarcinogenesis, particularly melanoma, the most deadly form of skin cancer. The paracrine factors alpha-melanocortin and endothelin-1 are critical for the melanogenic response of cultured human melanocytes to UV radiation. We report that alpha-melanocortin and endothelin-1 rescued human melanocytes from UV radiation-induced apoptosis and reduced DNA photoproducts and oxidative stress. The survival effects of alpha-melanocortin and endothelin-1 were mediated by activation of the melanocortin 1 and endothelin receptors, respectively. Treatment of melanocytes with alpha-melanocortin and/or endothelin-1 before exposure to UV radiation activated the inositol triphosphate kinase-Akt pathway and increased the phosphorylation and expression of the microphthalmia-related transcription factor. Treatment with alpha-melanocortin and/or endothelin-1 enhanced the repair of cyclobutane pyrimidine dimers and reduced the levels of hydrogen peroxide induced by UV radiation. These effects are expected to reduce genomic instability and mutagenesis.

Melanin content and MC1R function independently affect UVR-induced DNA damage in cultured human melanocytes.

Malignant transformation of melanocytes leads to melanoma, the most fatal form of skin cancer. Ultraviolet radiation (UVR)-induced DNA photoproducts play an important role in melanomagenesis. Cutaneous melanin content represents a major photoprotective mechanism against UVR-induced DNA damage, and generally correlates inversely with the risk of skin cancer, including melanoma. Melanoma risk is also determined by susceptibility genes, one of which is the melanocortin 1 receptor (MC1R) gene. Certain MC1R alleles are strongly associated with melanoma. We hereby present experimental evidence for the role of two melanoma risk factors, constitutive pigmentation, as assessed by total melanin, eumelanin and pheomelanin contents, and MC1R genotype and function, in determining the induction and repair of DNA photoproducts in cultured human melanocytes after irradiation with increasing doses of UVR. We found that total melanin and eumelanin contents (MC and EC) correlated inversely with the extent of UVR-induced growth arrest, apoptosis and induction of cyclobutane pyrimidine dimers (CPD), but not with hydrogen peroxide release in melanocytes expressing functional MC1R. In comparison, melanocytes with loss-of-function MC1R, regardless of their MC or EC, sustained more UVR-induced apoptosis and CPD, and exhibited reduced CPD repair. Therefore, MC, mainly EC, and MC1R function are independent determinants of UVR-induced DNA damage in melanocytes.