Surgically Resectable Non-Small Cell Lung Cancer: A Contemporary Approach.

New treatment paradigms for resectable non-small cell lung cancer (NSCLC), with an emphasis on personalized care and a multidisciplinary approach, have significantly improved patient outcomes. The incorporation of immune checkpoint inhibitors into neoadjuvant, perioperative and adjuvant treatment algorithms is reshaping the standard of care for resectable NSCLC. Adjuvant targeted therapy trials have also paved the way for a much-needed personalized approach for patients with actionable genomic alterations. Innovative surgical techniques and judicious use of post operative radiotherapy may mitigate the toxicity associated with a multimodality approach. Amidst many new treatment options, questions remain about the best approach to consider for each patient. Measurement of minimal residual disease and achievement of pathologic complete response are emerging biomarkers of interest to help further refine treatment selection. This review summarizes the current management of resectable NSCLC, focusing on ongoing and recent advances in surgical approaches, the role of postoperative radiotherapy, and the rapidly changing field of systemic therapies.

Treating anaplastic lymphoma kinase (ALK) fusion-driven metastatic non-small cell lung cancer (NSCLC) with alectinib through pregnancy.

Management of cancer during pregnancy requires careful consideration of risks and benefits from maternal and fetal perspectives. For advanced lung adenocarcinomas, with no targetable driver mutations, there is evidence-based guidance on the use of carboplatin-paclitaxel chemotherapy after first trimester. In contrast, for epidermal growth factor receptor (EGFR)-mutated or anaplastic lymphoma kinase (ALK)-rearranged metastatic lung adenocarcinomas, there is a paucity of clinical data on the safety of EGFR and ALK tyrosine kinase inhibitors to mother and fetus for official guidelines to recommend the use of these otherwise-first-line therapies in pregnancy. Considering this knowledge gap, we present a case of a young gravida 1 para 0 (G1P0) woman who continued alectinib 300 mg oral two times per day for ALK-rearranged metastatic lung adenocarcinoma throughout all 36 weeks of her pregnancy and delivered a healthy baby at term via caesarean section (C-section).

Supporting cognitive catch-up: The effects of cluster-randomized psychosocial stimulation interventions on preterm low birthweight children in rural China.

Improved survival of preterm low birthweight (LBW) infants due to advances in neonatal care has brought issues such as postnatal development trajectories to the foreground. This study pools evidence from three cluster-randomized experiments evaluating community-based psychosocial stimulation programs conducted from 2014 to 2017 that included 3571 rural Chinese children aged 6-24 months (51.1% male, 96.2% Han Chinese). The risk of severe cognitive delay was found to be 26.5 percentage points higher for preterm LBW children than for their peers at age 2.5, with a prevalence rate of 48.3%. Results show that psychosocial stimulation interventions can improve child cognitive development at scale, with beneficial impacts on child cognition disproportionately larger for preterm LBW children, helping them to catch up developmentally.

A network analysis of positive developmental assets of Hong Kong school-age children during the Covid-19 pandemic.

The ongoing COVID19 pandemic is having detrimental effects on the mental and emotional well-being of many adults and children. It is relevant therefore to explore the combination of personal strengths and attributes that can help an individual develop resilience to such stress. Little is known about how psychological strength assets such as social connectedness, grit, hope, life meaning, and life satisfaction are inter-related, and if certain factors play a central role. This study involved a sample of 1,405 school-aged children in Hong Kong (50% female) from seven schools that participated in an online survey of psychological strengths. Data were analyzed by constructing a psychological network that found strength factors are inter-connected, and that 'school connectedness' and 'agency thinking' are central to the network. The information gained can be of value in any schools that are planning to provide strength-based interventions to help students maintain their psychological well-being during and after the COVID-19 pandemic.

An Intervention to Improve Chlamydia and Gonorrhea Testing Among Adolescents in Primary Care.

BACKGROUND AND OBJECTIVES: Rates of chlamydia and gonorrhea among adolescents continue to rise. We aimed to evaluate if a universal testing program for chlamydia and gonorrhea improved testing rates in an urban general pediatric clinic and an urban family medicine clinic within a system of federally qualified health care centers and evaluated the feasibility, cost, and logistic challenges of expanding implementation across 28 primary care clinics within a federally qualified health care centers system. METHODS: A universal testing quality improvement program for male and female patient 14 to 18 years old was implemented in a general pediatrics and family medicine clinic in Denver, Colorado. The intervention was evaluated by using a controlled pre-post quasi-experimental design. The difference in testing rates due to the intervention was assessed by using a difference-in-differences regression model weighted with the inverse probability of treatment. RESULTS: In total, 15 541 pediatric encounters and 5420 family medicine encounters were included in the analyses. In pediatrics, the unadjusted testing rates increased from 32.0% to 66.7% in the intervention group and from 20.9% to 28.9% in the comparison group. For family medicine, the rates increased from 38.5% to 49.9% in the intervention group and decreased from 26.3% to 24.8% in the comparison group. The intervention resulted in an adjusted increase in screening rates of 25.2% (P < .01) in pediatrics and 11.8% (P < .01) in family medicine. The intervention was well received and cost neutral to the clinic. CONCLUSIONS: Universal testing for chlamydia and gonorrhea in primary care pediatrics and family medicine is a feasible approach to improving testing rates .

Ang2 inhibitors and Tie2 activators: potential therapeutics in perioperative treatment of early stage cancer.

Anti-angiogenic drugs targeting the VEGF pathway are most effective in advanced metastatic disease settings of certain types of cancers, whereas they have been unsuccessful as adjuvant therapies of micrometastatic disease in numerous phase III trials involving early-stage (resectable) cancers. Newer investigational anti-angiogenic drugs have been designed to inhibit the Angiopoietin (Ang)-Tie pathway. Acting through Tie2 receptors, the Ang1 ligand is a gatekeeper of endothelial quiescence. Ang2 is a dynamically expressed pro-angiogenic destabilizer of endothelium, and its upregulation is associated with poor prognosis in cancer. Besides using Ang2 blockers as inhibitors of tumor angiogenesis, little attention has been paid to their use as stabilizers of blood vessels to suppress tumor cell extravasation and metastasis. In clinical trials, Ang2 blockers have shown limited efficacy in advanced metastatic disease settings. This review summarizes preclinical evidence suggesting the potential utility of Ang2 inhibitors or Tie2 activators as neoadjuvant or adjuvant therapies in the prevention or treatment of early-stage micrometastatic disease. We further discuss the rationale and potential of combining these strategies with immunotherapy, including immune checkpoint targeting antibodies.

Gonorrhea and Chlamydia Rates Among 12- to 24-Year-Old Patients in an Urban Health System.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection rates continue to rise. Screening guidelines have largely focused on sexually active female individuals and men who have sex with men populations. Health care system testing and infection rates, particularly among heterosexual male individuals, are poorly understood. Our aim was to evaluate CT and GC testing and prevalence among 12- to 24-year-old patients in an urban federally qualified health center system. METHODS: This retrospective study analyzed electronic health record data from 2017 to 2019 in a large system of federally qualified health centers in Denver, CO. Abstracted data included demographics, sexual activity, sexual orientation, and laboratory results. χ2 Tests were used to evaluate differences between groups. RESULTS: Of the 44,021 patients included, 37.6% were tested, 15.0% were positive for CT, and 3.4% were positive for GC. Heterosexual male patients had a testing rate of 22.8% and positivity rates of CT and GC at 13.1% and 3.0%, respectively. Among tested patients documented as not sexually active, 7.5% were positive for CT. Multiple or reinfections were detected in 29% of patients. CONCLUSIONS: This study shows low testing rates and high rates of CT and GC infections among all patients, including heterosexual male patients and those documented as not sexually active. Improved screening of these populations in the primary care setting may be key to combating the sexually transmitted disease epidemic.

Pre- and post-operative anti-PD-L1 plus anti-angiogenic therapies in mouse breast or renal cancer models of micro- or macro-metastatic disease.

BACKGROUND: There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic RCC; and in combination with chemotherapeutics as neoadjuvant (preoperative) therapies for resectable TNBC. METHODS: This study investigated these and similar clinically relevant drug combinations in highly translational preclinical models of micro- and macro-metastatic disease that spontaneously develop after surgical resection of primary kidney or breast tumours derived from orthotopic implantation of murine cancer cell lines (RENCAluc or EMT-6/CDDP, respectively). RESULTS: In the RENCAluc model, adjuvant sunitinib plus anti-PD-L1 improved overall survival compared to either drug alone, while the same combination was ineffective as early therapy for unresected primary tumours or late-stage therapy for advanced metastatic disease. In the EMT-6/CDDP model, anti-PD-L1 was highly effective as an adjuvant monotherapy, while its combination with paclitaxel chemotherapy (with or without anti-VEGF) was most effective as a neoadjuvant therapy. CONCLUSIONS: Our preclinical data suggest that anti-PD-L1 plus sunitinib may warrant further investigation as an adjuvant therapy for RCC, while anti-PD-L1 may be improved by combining with chemotherapy in the neoadjuvant but not the adjuvant setting of treating breast cancer.

A systematic review of burnout among doctors in China: a cultural perspective.

BACKGROUND: Numerous studies around the world has already suggested that burnout among doctors is a global phenomenon. However, studies for burnout in doctors are relatively limited in Chinese communities when compared to the West. As risk factors, barriers to intervention and strategies combatting burnout in different parts of the world can vary a lot due to different social culture and healthcare system, study with a focus at doctors in China from a cultural perspective is a worthful endeavor. METHODS: Systematic searches of databases were conducted for papers published in peer-reviewed journals from 2006 to 2016. Selection criteria included practicing doctors in Mainland China and publications written in English or Chinese. Keywords searched including "burnout", "doctors" and "China" in 3 electronic databases has been undergone. Traditional understanding of "work attitude" and "doctors' humanity" from ancient Chinese literature has also been retrieved. RESULTS: Eleven full papers, including 9302 participants, were included in this review. The overall prevalence of burnout symptoms among doctors in China ranged from 66.5 to 87.8%. The review suggested that negative impact of burnout include association with anxiety symptoms and low job satisfaction at the individual doctors' level, and prone to committing medical mistakes affecting patient safety and higher turnover intention at the society/organizational level. Burnout was higher among doctors who worked over 40 h/week, working in tertiary hospitals, on younger age group within the profession (at age 30-40), and with negative individual perception to work and life. CONCLUSIONS AND IMPLICATIONS: The overall prevalence and adverse impact of burnout among doctors in China echo with the findings from Western studies. Young doctors and doctors working in tertiary hospitals are more at risk of burnout, probably related to shift of social culture related to the loss of medical humanities and a weak primary healthcare system. Potential strategies of managing burnout in Chinese doctors should therefore take consideration from the Chinese cultural perspective, with renaissance of medical humanities and strengthening the primary healthcare system in China.

Evaluation of "Colorful Life": A Multi-Addiction Expressive Arts Intervention Program for Adolescents of Addicted Parents and Parents with Addiction.

This study evaluated an expressive arts intervention program ("Colorful Life") for adolescents with addicted parents and parents with addiction in Hong Kong. Different evaluation strategies were employed. Objective outcome evaluation adopting a one group pretest-posttest design showed positive changes in adolescents' (N = 43) beliefs about addiction. Both adolescents' and parents' (N = 21) psychosocial competencies were enhanced post-intervention. Subjective outcome evaluation from both adolescent (N = 47) and parent (N = 22) groups showed positive perceptions of the program content, implementers, and achievement of program objectives. Findings provided preliminary evidence to support and yielded practical implications for the adoption of the multi-addiction syndrome model, positive youth development, and expressive arts approaches in the development of interventions for high-risk adolescents and addictive parents.

The Social Indicators Movement: Progress, Paradigms, Puzzles, Promise and Potential Research Directions.

This paper is a response to the article entitled "Fifty years after the Social Indicators Movement: Has the promise been fulfilled?" by Ken Land and Alex Michalos (2015) which constitutes a careful review of the historical development of the Social Indicators Movement, utility of social indicators in shaping the concept of quality of life and subjective well-being, and issues deserving social indicators research in future. In this response paper, we join in the discussion by highlighting five issues-progress, paradigms, puzzles, promise, and potential research directions of social indicators research. In terms of progress, while we have accomplished many tasks proposed by Solomon et al. (The quality of life, Sage, London 1980), some of them are yet to be achieved. Regarding research paradigms surrounding social indicators, researchers have primarily used positivistic or post-positivistic orientation to conduct and interpret social indicators research, with relatively fewer studies using interpretive, constructionist or critical theory perspective. There are also several puzzles deserving consideration. These include (a) the use of "other types of evidence", particularly qualitative data; (b) evaluation of social programs; (c) feasibility of assessing "social progress"; (d) choice of social indicators; (e) interpretation of findings; (f) methodological debates; and (g) explanations for social change. Finally, the promise of social indicators research to promote quality of life and potential future research directions of social indicators research are discussed.

A 4-year Longitudinal Study of Well-being of Chinese University Students in Hong Kong.

The present longitudinal study explored the development of personal well-being in university students over 4 years. Personal well-being was indexed by multiple indicators including life satisfaction, positive youth development qualities, and university engagement. A sample of 434 students enrolled in the new 4-year undergraduate program in one university in Hong Kong was successfully followed up for 4 years since they started their university study in 2012-2013 academic year. Students completed an online survey on a yearly basis and four waves of data were collected. Results revealed significant changes in most well-being indicators over time with three main observations. First, students' life satisfaction remained at a stable level during 4 years. Second, most students' self-reported positive youth development competencies followed a U-shaped developmental trajectory, which was characterised by a dip in the second year and a continuous rebound in the third year and fourth year. Third, students' university engagement in different aspects showed significant increments in the third and fourth year of university study. The findings underscore the disparate developmental patterns of different aspects of student well-being during university study. This suggests that there is a need to take into account students' developmental characteristics and related challenges in different stages of university life when develop and implement programs in university to promote student well-being.

Teachers' views of a new general education program in Hong Kong: a qualitative study.

Under the new education reform in Hong Kong, The Hong Kong Polytechnic University (PolyU) has expanded its undergraduate education from 3 to 4 years since the 2012-2013 academic year. Along with the transition, the General University Requirements (GUR) has been developed as an integral part on general education of the new 4-year undergraduate curriculum of PolyU. The present study examined the implementation quality and effectiveness of the GUR in the 2012-2013 academic year based on focus group interviews with teachers. Twenty teachers who taught GUR subjects were interviewed for their perceptions and experiences about the GUR. Results revealed that the teachers generally had positive perceptions of the GUR in terms of its rationales, teaching and learning modes, and implementation quality. GUR subjects were also considered effective in helping students to develop in a holistic manner. The findings suggest that the first-year implementation of the GUR at PolyU was basically successful.

Qualitative evaluation of general university requirements in a new 4-year university curriculum: findings based on experiences of students.

Following the North American model, the length of undergraduate program in Hong Kong has been extended from 3 to 4 years since 2012. To maximize the impact of the additional year, The Hong Kong Polytechnic University (PolyU) has implemented a new general education framework entitled "General University Requirements (GUR)" aiming to cultivate students in a holistic manner. This study explored students' impressions of the GUR subjects using a survey collecting primarily qualitative data. Results from 163 students of eight faculties showed that students perceived the GUR subjects favorably. Having opportunities to make new friends from other departments and the teaching and learning methods, particularly experiential learning stimulated students' interest and enriched their learning experiences which were reportedly are unforgettable. Some of the obstacles encountered by students in several subjects were identified. The beneficial effects of the GUR subjects in different domains were voiced by the students.

Aflibercept and Ang1 supplementation improve neoadjuvant or adjuvant chemotherapy in a preclinical model of resectable breast cancer.

Phase III clinical trials evaluating bevacizumab (an antibody to the angiogenic ligand, VEGF-A) in breast cancer have found improved responses in the presurgical neoadjuvant setting but no benefits in the postsurgical adjuvant setting. The objective of this study was to evaluate alternative antiangiogenic therapies, which target multiple VEGF family members or differentially modulate the Angiopoietin/Tie2 pathway, in a mouse model of resectable triple-negative breast cancer (TNBC). Neoadjuvant therapy experiments involved treating established orthotopic xenografts of an aggressive metastatic variant of the MDA-MB-231 human TNBC cell line, LM2-4. Adjuvant therapies were given after primary tumor resections to treat postsurgical regrowths and distant metastases. Aflibercept ('VEGF Trap', which neutralizes VEGF-A, VEGF-B and PlGF) showed greater efficacy than nesvacumab (an anti-Ang2 antibody) as an add-on to neoadjuvant/adjuvant chemotherapy. Concurrent inhibition of Ang1 and Ang2 signaling (through an antagonistic anti-Tie2 antibody) was not more efficacious than selective Ang2 inhibition. In contrast, short-term perioperative BowAng1 (a recombinant Ang1 variant) improved the efficacy of adjuvant chemotherapy. In conclusion, concurrent VEGF pathway inhibition is more likely than Ang/Tie2 pathway inhibition (e.g., anti-Ang2, anti-Ang2/Ang1, anti-Tie2) to improve neoadjuvant/adjuvant chemotherapies for TNBC. Short-term perioperative Ang1 supplementation may also have therapeutic potential in conjunction with adjuvant chemotherapy for TNBC.

Efficacy of Cotargeting Angiopoietin-2 and the VEGF Pathway in the Adjuvant Postsurgical Setting for Early Breast, Colorectal, and Renal Cancers.

Antiangiogenic tyrosine kinase inhibitors (TKI) that target VEGF receptor-2 (VEGFR2) have not been effective as adjuvant treatments for micrometastatic disease in phase III clinical trials. Angiopoietin-2 (Ang2) is a proangiogenic and proinflammatory vascular destabilizer that cooperates with VEGF. The purpose of this study was to test whether CVX-060 (an Ang2-specific CovX-body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat postsurgical metastatic disease in multiple orthotopically implanted human tumor xenograft and syngeneic murine tumor models. In the MDA-MB-231.LM2-4 human breast cancer model, adjuvant sunitinib was ineffective, whereas adjuvant CVX-060 delayed the progression of pulmonary or distant lymphatic metastases; however, overall survival was only improved with the adjuvant use of a VEGF-A/Ang2-bispecific CovX-body (CVX-241) but not when CVX-060 is combined with sunitinib. Adjuvant CVX-241 also showed promise in the EMT-6/CDDP murine breast cancer model, with or without an immune checkpoint inhibitor (anti-PD-L1). In the RENCA model of mouse renal cancer, however, combining CVX-060 with sunitinib in the adjuvant setting was superior to CVX-241 as treatment for postsurgical lung metastases. In the HCT116 and HT29 xenograft models of colorectal cancer, both CVX-060 and regorafenib inhibited liver metastases. Overall, our preclinical findings suggest differential strategies by which Ang2 blockers can be successfully combined with VEGF pathway targeting in the adjuvant setting to treat micrometastatic disease-particularly, in combination with VEGF-A blockers (but not VEGFR2 TKIs) in resected breast cancer; in combination with VEGFR2 TKIs in resected kidney cancer; and as single agents or with VEGFR2 TKIs in resected colorectal cancer. Cancer Res; 76(23); 6988-7000. ©2016 AACR.

Development, implementation, and evaluation of a multi-addiction prevention program for primary school students in Hong Kong: the B.E.S.T. Teen Program.

Based on the evaluation findings of the B.E.S.T. Teen Program which aimed at promoting behavioral, emotional, social, and thinking competencies in primary school students, it is argued in this paper that promotion of psychosocial competence to prevent addiction in primary school students is a promising strategy. A total of 382 Primary 5 (Grade 5) and 297 Primary 6 (Grade 6) students from five primary schools in Hong Kong participated in the program. Different evaluation strategies were adopted to evaluate the program. First, objective outcome evaluation adopting a non-equivalent group pretest-posttest experimental-control group design was conducted to examine change in the students. Second, to gauge students' perceptions of the program, subjective outcome evaluation was conducted. The evaluation findings basically converged to tentatively suggest that young adolescents benefited from participating in the program. Implications on the development, implementation, and evaluation of addiction prevention programs for teenagers are discussed.

Evidence Implicating Immunological Host Effects in the Efficacy of Metronomic Low-Dose Chemotherapy.

Conventional chemotherapy drugs administered at a maximum tolerated dose (MTD) remains the backbone for treating most cancers. Low-dose metronomic (LDM) chemotherapy, which utilizes lower, less toxic, doses given on a close regular basis over prolonged periods, is an alternative and better tolerated potential strategy to improve chemotherapy. LDM chemotherapy has been evaluated preclinically and clinically and has shown therapeutic benefit, in both early and advanced stage metastatic disease, especially when used as a maintenance therapy. However, knowledge about the antitumor mechanisms by which LDM chemotherapy acts remain limited. Here we characterized the effects of LDM and MTD capecitabine therapy on tumor and host cells using high-throughput systems approaches involving mass spectrometry flow cytometry and automated cell imaging followed by in vivo analyses of such therapies. An increase in myeloid and T regulatory cells and a decrease in NK and T cytotoxic cells were found in MTD-capecitabine-treated tumors compared with LDM-capecitbine-treated tumors. Plasma from MTD capecitabine-treated mice induced a more tumorigenic and metastatic profile in both breast and colon carcinoma cells than plasma from mice treated with LDM capecitabine. These results correlated, in part, with in vivo studies using models of human or mouse advanced metastatic disease, where the therapeutic advantage of MTD capecitabine was limited despite a substantial initial antitumor activity found in the primary tumor setting. Overall these results implicate a possible contribution of immunologic host effects in accounting for the therapeutic limitations of MTD compared with LDM capecitabine. Cancer Res; 76(20); 5983-93. ©2016 AACR.

The Project P.A.T.H.S. in Hong Kong: Work Done and Lessons Learned in a Decade.

The Project Positive Adolescent Training through Holistic Social Programs is a positive youth development program initiated and financially supported by The Hong Kong Jockey Club Charities Trust. Since 2005, the project has gone through several phases, including the initial phase (2005-2012), school-based extension phase (2009-2016), and community-based extension phase (2013-2017). In the initial phase, with the involvement of academics from 5 universities in Hong Kong, the research team developed youth enhancement programs for junior secondary school students (20 hours per grade), trained the program implementers (20 hours per grade), assisted in the implementation in more than 250 schools, and evaluated the program using multiple evaluation strategies, including a 5-year longitudinal experimental study. In the school-based extension phase, the project was implemented for another cycle (2009-2010 and 2011-2012 school years) and a 6-year longitudinal study was conducted to understand the psychosocial development of Chinese adolescents in Hong Kong. In the community-based extension phase, the programs were administered by social workers in the community settings. Generally speaking, different evaluation findings showed that the programs in Project Positive Adolescent Training through Holistic Social Programs promoted positive development and reduced risk behavior in Chinese adolescents in Hong Kong. Positive youth development attributes and family functioning also have positive contributions to adolescent developmental outcomes over time.