Perspectives from primary health care providers on their roles for supporting adolescents and young adults transitioning from pediatric services.

BACKGROUND: Transitioning from pediatric care to adult-oriented care at age 18 (the age of transfer in most countries and jurisdictions) is a complex process for adolescents and young adults affected by chronic physical health and/or mental health conditions. The role of primary health care (PHC) providers for this population is poorly understood. Perspectives from these providers, such as family physicians and other members of the primary care team, have not been explored in depth. METHODS: A total of 18 participants (e.g., family physicians, social workers, nurses) were recruited from 6 Primary Care Networks in Calgary, Alberta, Canada. Semi-structured individual interviews were conducted, and transcribed verbatim. A qualitative description approach was used to analyze the data, and included thematic analysis. RESULTS: Five distinct, yet overlapping, roles of primary health care providers for adolescents and young adults transitioning to adult care resulted from our analysis: (1) being the "common thread" (continuous accessible care); (2) caring for the "whole patient" (comprehensive care); (3) "knowing families" (family-partnered care); (4) "empowering" adolescents and young adults to develop "personal responsibility" (developmentally-appropriate care); and (5) "quarterbacking" care (coordination of specialist and/or community-based care). Participants identified potential benefits of these roles for adolescents and young adults transitioning to adult care, and barriers in practice (e.g., lack of time, having minimal involvement in pediatric care). CONCLUSIONS: Input from family physicians, who follow their patients across the lifespan and provide the majority of primary care in Canada, are critical for informing and refining recommended transition practices. Our findings provide insights, from PHC providers themselves, to bolster the rationale for primary care involvement during transitions from pediatric specialty and community-based care for AYAs. Solutions to overcome barriers for integrating primary care and specialty care for adolescents and young adults need to be identified, and tested, with input from key stakeholders.

The 'Pounds for Pounds' weight loss financial incentive scheme: an evaluation of a pilot in NHS Eastern and Coastal Kent.

BACKGROUND: Financial incentive programmes have the potential to modify health-related behaviours, including those associated with achieving weight loss. This study evaluated a pilot NHS commissioned financial incentive weight loss programme, based on the commercial Weight Wins 'Pounds for Pounds' programme. METHODS: Participants chose a weight loss plan based on their target weight. Plans ranged from 15 lb (6.8 kg) weight loss over 3 months to 50 lb (22.7 kg) weight loss over 7 months, with optional additional 'maintenance' periods. Rewards, which were received after successful plan completion, ranged from £70 to £425 per year. RESULTS: Mean baseline weight for the 402 participants was 101.8 kg (SD 46.1 kg), with 77.4% having a BMI ≥30 kg/m(2). Clinically significant weight loss (≥5%) occurred in 44.8% [95% confidence interval (CI): 40.0-49.7%] of participants. Estimated mean weight loss at 12 months was 4.0 kg (95% CI: 2.4-5.6 kg) under the assumption of return-to-baseline weight for those who had left the programme before reporting a 12 month weight. CONCLUSIONS: The estimated mean 12 month weight loss of 4.0 kg at 12 months is comparable to other evaluations of other non-medical weight loss interventions. A randomized controlled trial is required to evaluate the clinical and cost-effectiveness of this financial incentive scheme.

Tetrandrine, a Compound Common in Chinese Traditional Medicine, Preferentially Kills Breast Cancer Tumor Initiating Cells (TICs) In Vitro.

Tetrandrine is a bisbenzylisoquinoline alkaloid found in Stephania tetrandra, a Chinese medicine commonly used as an anti-inflammatory. It has extensive pharmacological activity, including positive ion channel blockade and inhibition of multiple drug resistance proteins. These activities are very similar to that of salinomycin, a known drug targeting breast cancer initiation cells (TICs). Herein, we tested tetrandrine targeting of breast cancer TICs. SUM-149, an inflammatory breast cancer cell line and SUM-159, a non-inflammatory metaplastic breast cancer cell line were used in these studies. In proliferation assays using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), we found that the IC50 for inhibition of proliferation is 15.3 ± 4.1 µM for SUM-149 and 24.3 ± 2.1 µM for SUM-159 cells. Tetrandrine also inhibited mammosphere formation, a surrogate for breast cancer TICs growth in vitro with IC50 around 1 µM for SUM-149 and around 2 µM for SUM-159 cells. Tetrandrine has similar effects on the mammosphere formation from cells isolated from fresh patient sample. Moreover, tetrandrine decreases the aldehyde dehydrogenase (ALDH) positive population in SUM-159 by 45% ± 5.45% P = 0.005. In summary, tetrandrine demonstrates significant efficacy against in vitro surrogates for inflammatory and aggressive breast cancer TICs.

NQO1 and NQO2 regulation of humoral immunity and autoimmunity.

NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are cytosolic enzymes that catalyze metabolic reduction of quinones and derivatives. NQO1-null and NQO2-null mice were generated that showed decreased lymphocytes in peripheral blood, myeloid hyperplasia, and increased sensitivity to skin carcinogenesis. In this report, we investigated the in vivo role of NQO1 and NQO2 in immune response and autoimmunity. Both NQO1-null and NQO2-null mice showed decreased B-cells in blood, lower germinal center response, altered B cell homing, and impaired primary and secondary immune responses. NQO1-null and NQO2-null mice also showed susceptibility to autoimmune disease as revealed by decreased apoptosis in thymocytes and pre-disposition to collagen-induced arthritis. Further experiments showed accumulation of NADH and NRH, cofactors for NQO1 and NQO2, indicating altered intracellular redox status. The studies also demonstrated decreased expression and lack of activation of immune-related factor NF-kappaB. Microarray analysis showed altered chemokines and chemokine receptors. These results suggest that the loss of NQO1 and NQO2 leads to altered intracellular redox status, decreased expression and activation of NF-kappaB, and altered chemokines. The results led to the conclusion that NQO1 and NQO2 are endogenous factors in the regulation of immune response and autoimmunity.