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1.
Article in English | MEDLINE | ID: mdl-38736277

ABSTRACT

AIM: Integrated youth services (IYS) have been identified as a national priority in response to the youth mental health and substance use (MHSU) crisis in Canada. In British Columbia (BC), an IYS initiative called Foundry expanded to 11 physical centres and launched a virtual service. The aim of the study was to describe the demographics of Foundry clients and patterns of service utilization during this expansion, along with the impact of the COVID-19 pandemic. METHODS: Data were analysed for all youth (ages 12-24) accessing both in-person (April 27th, 2018-March 31st, 2021) and virtual (May 1st, 2020-March 31st, 2021) services. Cohorts containing all clients from before (April 27th, 2018-March 16th, 2020) and during (March 17th, 2020-March 31st, 2021) the COVID-19 pandemic were also examined. RESULTS: A total of 23 749 unique youth accessed Foundry during the study period, with 110 145 services provided. Mean client age was 19.54 years (SD = 3.45) and 62% identified as female. Over 60% of youth scored 'high' or 'very high' for distress and 29% had a self-rated mental health of 'poor', with similar percentages seen for all services and virtual services. These ratings stayed consistent before and during the COVID-19 pandemic. CONCLUSIONS: Foundry has continued to reach the target age group, with a 65% increase in number of clients during the study period compared with the pilot stage. This study highlights lessons learned and next steps to promote youth-centred data capture practices over time within an integrated youth services context.

2.
Orthopedics ; 47(1): 52-56, 2024.
Article in English | MEDLINE | ID: mdl-37216564

ABSTRACT

Cannabidiol (CBD)-containing supplements are used by children with cerebral palsy (CP), but the prevalence and efficacy of their use have not been studied. We sought to describe CBD use patterns and perceived efficacy in the pediatric population with CP, evaluating any association between CBD use and health-related quality of life. Patients with CP were prospectively enrolled, and caregivers were offered the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD) Questionnaire and a survey assessing CBD use. Of 119 participants, 20 (16.8%) endorsed CBD use (CBD+) and 99 (83.2%) denied it (CBD-). Participants in the CBD+ group had worse functional status (85% Gross Motor Function Classification System level IV-V for CBD+ vs 37.4% for CBD-, P<.001) and lower health-related quality of life (mean CPCHILD score of 49.3 for CBD+ vs 62.2 for CBD-, P=.001). Spasticity was the rationale most cited for CBD use (29%), followed by pain and anxiety (both 22.6%). CBD was perceived to be most effective for improving emotional health, spasticity, and pain. Fifty percent of the patients in the CBD+ group underwent surgery in the previous 2 years and most endorsed a general benefit in the postoperative setting. The most common side effects noted were fatigue and increased appetite (both 12%). Most participants endorsed no side effects (60%). CBD may serve as a useful adjunct for some children with CP, especially those with worse disease severity. Caregivers perceive CBD as offering some benefits, particularly in the domains of emotional health, spasticity, and pain. We found no evidence of severe adverse events in our small cohort. [Orthopedics. 2024;47(1):52-56.].


Subject(s)
Cannabidiol , Cerebral Palsy , Humans , Child , Quality of Life , Cannabidiol/therapeutic use , Cerebral Palsy/drug therapy , Cerebral Palsy/complications , Severity of Illness Index , Pain
3.
Cureus ; 15(11): e48575, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38073935

ABSTRACT

Background While there has been a growing emphasis on evaluating the patient's perspective of health outcomes, caregiver expectations of post-orthopedic procedure disability and pain in a pediatric population are yet to be investigated. This study evaluates whether caregivers' preoperative expectations of pain and function differ from their child's early outcomes after surgical orthopedic intervention. Methodology Patients eight to 18 years old undergoing elective orthopedic surgery were enrolled. The caregivers of consented patients completed a survey at the child's preoperative appointment to predict their postoperative pain and disability. The child was given the same survey during their postoperative visit four to six weeks after surgery to assess actual levels of functioning following the procedure. Scores were analyzed to study correlations between patient and caregiver responses (n = 48). Results Caregivers underestimated their child's postoperative psychosocial functioning, as evidenced by the Psychosocial Health Summary Score, and overestimated pain, as demonstrated by the Numeric Pain Rating Scale. The Pediatric Quality of Life Inventory scores showed caregivers had differing expectations of the impact surgery had across various aspects of the physical, emotional, social, and school functioning domains. Higher parental pain catastrophizing was associated with underestimated predictions of their child's psychosocial functioning after surgery. No significant difference was found in the patient's physical functioning, as shown by the Physical Health Summary Score. Conclusions Surgical intervention is a major event that can provoke anxiety for parents and caregivers. Understanding differences in caregiver perspectives and early postoperative patient outcomes provides physicians valuable insights. Explaining to caregivers that patient psychosocial factors and functional outcomes after surgery are commonly better than expected can alleviate anxiety and prevent catastrophizing. This knowledge can help guide caregiver expectations and plans for their child's postoperative pain control and functional recovery.

4.
Innov Pharm ; 14(2)2023.
Article in English | MEDLINE | ID: mdl-38025169

ABSTRACT

Background: Implementation of a clinical pharmacist in the primary care setting can offset provider time spent managing chronic diseases using Collaborative Practice Agreements (CPAs). The pharmacist-physician co-visit model presents an opportunity for pharmacists to increase patient access to their primary care provider (PCP). Studies of the co-visit model show that co-visits increase clinic efficiency by allowing the PCP to see additional patients and achieve more health care goals compared with independent visits1-4. Objectives: The aim of this study was to increase patient access to their PCP by utilizing a pharmacist-physician co-visit model at the Madsen Health Center Family Medicine (MHC FM) Clinic. The primary outcome was to identify the number of co-visits completed compared to the number of possible co-visits, and the number of appointment slots made available. The secondary outcomes were to track the time spent with patients and to obtain provider feedback via a survey. Methods: The co-visit model was implemented as a 4-month pilot study at the MHC FM Clinic. Complex care appointments lasting 40 minutes were selected based on inclusion and exclusion criteria. Potential co-visit appointments were identified one week prior then provider consent was obtained to change the appointment into two separate 20-minute visits. Schedules were reviewed to determine if the appointment slot opened by the co-visit was filled by another patient. Upon completion of the study, a survey was distributed to providers to collect feedback. Results: A total of five co-visits were completed out of a possible 19 (26%). All the appointments made available were filled by another patient. On average, the provider and pharmacist spent 15 and 14 minutes with the patient, respectively. Conclusion: Implementation of the physician-pharmacist co-visit model increased the availability of the PCP to see more patients without disrupting clinic workflow and provider schedules.

5.
CMAJ Open ; 11(5): E884-E893, 2023.
Article in English | MEDLINE | ID: mdl-37788865

ABSTRACT

BACKGROUND: Métis are a culturally unique and distinct population, yet little research has evaluated their health separate from the broader Indigenous population. We sought to explore current literature regarding the health of Métis Peoples in Canada and identify potential trends and gaps. METHODS: Using the Arksey-O'Malley, 5-stage, scoping review method, we searched PubMed, MEDLINE, iPortal Indigenous Articles Portal Research Tool and pertinent reference lists using the terms "Métis," "health" and "Canada." Two reviewers conducted the initial searches independently, including English articles from 2012 to 2022, and focused on only Métis populations' health within Canada. We described characteristics of the articles and themes for discussion. RESULTS: Of the 572 articles we identified, we included a total of 28 articles in this scoping review, of which 16 were quantitative, 9 were qualitative and 3 used mixed methods. Thirteen articles used consultation with Métis communities as part of their methods, and 8 extracted data from national surveys. One article focused on children, while all other articles focused on adults. Nine articles used data from across Canada, 6 were based in Ontario, 5 in Alberta and 4 each in British Columbia and Manitoba. Themes included health, well-being and spirituality; mental health and substance use; health conditions and risk factors; access to adequate health resources; and experiences in health care. INTERPRETATION: Métis-specific health research is lacking in Canada, with a gap in volume, subject matter and diversity in the demographics studied. This review illustrates the need for more research with strong community engagement to further explore Métis health and health service needs.

6.
PLoS One ; 18(10): e0292670, 2023.
Article in English | MEDLINE | ID: mdl-37847679

ABSTRACT

BACKGROUND: Mental health impacts of the COVID-19 pandemic have not been felt equally within populations. Parents with children living at home were early on identified as a population at heightened mental health risk, with concerns about the potential long-term impacts of the pandemic on parents' mental health, family functioning, and children's well-being. This study investigates impacts of the pandemic on parents' psychological distress, contextual sources of distress, and associations with family functioning nearly two years into the pandemic. METHODS AND FINDINGS: Data were drawn from a national cross-sectional survey of adults living in Canada in November and December 2021 that was representative by age, gender, household income, and region. Parents with children < 18 years old living at home (N = 553) reported their experiences of psychological distress, pandemic-related stressors, coping mechanisms, and family functioning (changes in parent-child interactions, children's anxiety). Chi-square tests, logistic regression, and linear regression analyses examined sociodemographic inequities in parents' levels of psychological distress, sources and mitigating mechanisms of distress, and associations between psychological distress and family functioning. Nearly two years into the pandemic, parents with children at home reported nearly double pre-pandemic population estimates of moderate to severe psychological distress. Psychological distress was more frequently reported among parents with pre-existing mental health conditions, disabilities, and financial stressors. Parents with greater psychological distress reported increases in negative parent-child interactions due to the pandemic and higher anxiety among their children. CONCLUSIONS: This study identifies sustained negative impacts of the pandemic on parents' mental health and family functioning in Canada nearly two years into the pandemic, despite high vaccine uptake and declining infection rates. Disparities in financial stress, social support structures, and pre-existing mental health were identified as underlying sources of psychological distress. These results highlight that meaningful responses to promote mental health among parents and families must address social and structural inequities.


Subject(s)
COVID-19 , Psychological Distress , Adult , Humans , Adolescent , Cross-Sectional Studies , COVID-19/epidemiology , Pandemics , Canada/epidemiology , Parents/psychology , Parent-Child Relations , Stress, Psychological/epidemiology
7.
Cancer Res ; 83(15): 2513-2526, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37311042

ABSTRACT

Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% of patients with NSCLC, with higher frequency in lung squamous carcinomas (LUSC). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy. Development of a Pten-null LUSC mouse model revealed that tumors with PTEN loss were refractory to antiprogrammed cell death protein 1 (anti-PD-1), highly metastatic and fibrotic, and secreted TGFß/CXCL10 to promote conversion of CD4+ lymphocytes into regulatory T cells (Treg). Human and mouse PTEN-low tumors were enriched in Tregs and expressed higher levels of immunosuppressive genes. Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGFß antibody aimed to alter this immunosuppressive microenvironment and led to tumor rejection and immunologic memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSCs by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically. SIGNIFICANCE: PTEN loss leads to the development of an immunosuppressive microenvironment in lung cancer that confers resistance to anti-PD-1 therapy, which can be overcome by targeting PTEN loss-mediated immunosuppression.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Drug Resistance, Neoplasm , Lung Neoplasms , PTEN Phosphohydrolase , T-Lymphocytes, Regulatory , Animals , Humans , Mice , B7-H1 Antigen/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Immunotherapy/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Tumor Microenvironment , Drug Resistance, Neoplasm/genetics , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use
8.
Spine Deform ; 11(5): 1057-1063, 2023 09.
Article in English | MEDLINE | ID: mdl-37166749

ABSTRACT

PURPOSE: The Scoliosis Research Society 22r Questionnaire(SRS-22r) is the standard for assessing health-related quality of life(HRQoL) in patients with adolescent idiopathic scoliosis. Here we investigate whether patients' perceptions of their HRQoL are influenced by knowledge of scoliosis and counseling by an orthopedic surgeon. METHODS: Patients ages 10-18 years referred for their first visit with an orthopaedic surgeon for scoliosis were enrolled from 9/30/19 to 10/22/20. Patients completed the SRS-22r pre- and post-visit. A Wilcoxon signed-rank test was used to analyze the SRS-22r scores. RESULTS: 52 patients participated in the study at a mean age of 14.3 years (95% CI 13.8-14.8 years) with an average major curve magnitude of 23.2 degrees (95% CI 19.4-27.0 degrees). SRS-22r scores were not correlated to curve magnitude pre- or post-visit. The SRS-22r Satisfaction with care domain exhibited a small increase from pre- to post-visit (pre: 3.3, post: 3.6). All other SRS-22r domains and total scores did not exhibit clinically significant differences. CONCLUSION: Among new adolescent referrals for scoliosis, it is unlikely that counseling by a surgeon influences perceptions of HRQoL as measured by the SRS-22r. LEVEL OF EVIDENCE: III.


Subject(s)
Kyphosis , Orthopedic Surgeons , Scoliosis , Humans , Adolescent , Quality of Life , Scoliosis/surgery , Referral and Consultation
9.
Subst Abuse Treat Prev Policy ; 17(1): 82, 2022 12 22.
Article in English | MEDLINE | ID: mdl-36550587

ABSTRACT

BACKGROUND: Concerns about youth alcohol and drug use have risen since the declaration of the global COVID-19 pandemic due to the pandemic's impact on known risk and protective factors for substance use. However, the pandemic's immediate and long-term impact on youths' substance use patterns has been less clear. Thus, this study sought to determine how the COVID-19 pandemic impacted alcohol or drug use and its risk and protective factors among youth accessing integrated youth services. METHODS: We conducted a repeated cross-sectional study of patient-reported outcomes data collected between May 2018 and February 2022 among youth (n = 6022) ages 10-24 accessing a provincial network of integrated youth services in Canada. The main exposure of interest was the COVID-19 pandemic (March 2020 - February 2022) compared with a pre-pandemic period (May 2018 - February 2020). As measured by the Global Appraisal of Individual Needs - Short Screener, outcomes included the average number of past month alcohol or drug use symptoms and past month likelihood of service need for alcohol/drug use (moderate/high vs. low need). Interrupted time series (ITS) examined change in average monthly alcohol/drug use symptoms between the pre- and pandemic periods. Stratified multivariable logistic regression investigated how the pandemic modified the effects of established risk/protective factors on likelihood of alcohol/drug use service need. RESULTS: Fifty-percent of youth met the criteria for moderate/high likelihood of alcohol/drug use service need, with the odds being 2.39 times (95% confidence interval = 2.04, 2.80) greater during the pandemic compared to the pre-pandemic period. Results from the ITS indicated significant immediate effects of the pandemic on monthly substance use symptoms (p = 0.01). Significant risk/protective factors for service need included exposure to violence, engagement in meaningful activities, and self-rated physical and mental health; and the direction of their effects remained consistent across pandemic and pre-pandemic periods. CONCLUSIONS: This study demonstrated that the COVID-19 pandemic corresponded with increased alcohol or drug use among youth accessing integrated services. This signals an urgent need for increased clinical capacity in existing youth services and policies that can respond to risk/protective factors for substance use earlier.


Subject(s)
COVID-19 , Substance-Related Disorders , Adolescent , Humans , Child , Young Adult , Adult , British Columbia/epidemiology , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , Ethanol , Substance-Related Disorders/epidemiology
10.
Article in English | MEDLINE | ID: mdl-36338797

ABSTRACT

The purpose of this study was to evaluate the impact of an 8-week remote summer program in supporting underrepresented students interested in orthopaedic surgery. Methods: We received 115 applications, and a total of 17 students participated in the program (14.8%). Nine faculty mentors were matched with 1 or 2 students each. The program delivered a curriculum from June-August 2021 consisting of (1) weekly instructional courses on research-related topics led by a content expert; (2) weekly faculty lectures discussing topics including orthopaedic topics, diversity in medicine, leadership, and work-life balance; and (3) a research experience paired with a faculty mentor and peer mentor. We surveyed students to measure skill progression, satisfaction, and overall program evaluation. Preprogram/postprogram evaluation, midprogram check-in, and student feedback surveys were collected. Results: Program participants represented a range of race and ethnic backgrounds, research experience levels, and various geographic locations across the United States. The cohort included a high rate of female (42%) and Black (35%) participants. On average, postprogram survey scores indicated that participants believed that the summer program improved their research skills (9.6 of 10), improved their orthopaedic interest (8.9 of 10), and improved mentorship and networking (9.1 of 10). For feedback surveys, 14 respondents of 15 total responses (93%) felt they were adequately matched to their faculty mentor. Twelve (80%) felt they had realistic deliverables for research projects within the 8-week program. Thirteen (87%) indicated they contributed to an abstract or manuscript as a coauthor. Conclusion: Our findings indicate that students improved their research skills, interest, and confidence to pursue orthopaedic residency and mentorship/networks in the field. The long-term goal is to improve the accessibility and quality of mentorship for underrepresented students in order to foster an equitable pathway into the field of orthopaedic surgery.

11.
J Pediatr Orthop ; 42(10): 600-607, 2022.
Article in English | MEDLINE | ID: mdl-36040069

ABSTRACT

BACKGROUND: Virtual Reality (VR) has been used as a distraction tool in various medical settings to reduce pain and anxiety associated with procedures. This study evaluates the effectiveness of VR as a distraction tool for decreasing fear, anxiety, and pain in pediatric patients undergoing common outpatient orthopaedic procedures. METHODS: A total of 210 patients were recruited from a single orthopaedic clinic between October 2017 and July 2019. Patients were randomized to the VR group or to the control group (standard of care). Outpatient procedures included cast and/or pin removals. Primary outcome measures were collected preprocedure and postprocedure using validated surveys, and included: fear (Children's Fear Scale), anxiety (Children's Anxiety Meter-State), and pain (Numerical Rating Scale). Patients and caregivers in the VR group completed a satisfaction survey at the end of their appointment. Fear, anxiety, and pain scores between the 2 groups were analyzed using multivariable linear regression models, and the satisfaction survey was analyzed using descriptive statistics. RESULTS: One hundred twenty nine patients were included in the final analysis, with 85 patients in the VR group and 44 patients in the control group. During the procedure, patients in the VR group reported significantly lower average fear scores ( P <0.001) and anxiety scores ( P =0.003) as compared with controls. There were no differences between the groups in fear and anxiety scores before and after the procedure, or pain scores before, during, or after the procedure. Overall, patients and caregivers in the VR group reported high satisfaction scores, with 97% of patients and 95% of caregivers recommending this intervention to others. CONCLUSION: VR technology was found to be an effective distraction tool to improve fear and anxiety during cast removal procedures. Findings build on a body of evidence that supports the use of distraction tools in clinics, specifically pediatric orthopaedics, to improve fear and anxiety. The distraction tools can be easily translated into current practices. LEVEL OF EVIDENCE: Level I.


Subject(s)
Orthopedics , Virtual Reality , Anxiety/prevention & control , Child , Fear , Humans , Pain , Pain Management/methods
12.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: mdl-35162988

ABSTRACT

Melanoma is an aggressive skin cancer that has become increasingly prevalent in western populations. Current treatments such as surgery, chemotherapy, and high-dose radiation have had limited success, often failing to treat late stage, metastatic melanoma. Alternative strategies such as immunotherapies have been successful in treating a small percentage of patients with metastatic disease, although these treatments to date have not been proven to enhance overall survival. Several melanoma antigens (Ags) proposed as targets for immunotherapeutics include tyrosinase, NY-ESO-1, gp-100, and Mart-1, all of which contain both human leukocyte antigen (HLA) class I and class II-restricted epitopes necessary for immune recognition. We have previously shown that an enzyme, gamma-IFN-inducible lysosomal thiol-reductase (GILT), is abundantly expressed in professional Ag presenting cells (APCs), but absent or expressed at greatly reduced levels in many human melanomas. In the current study, we report that increased GILT expression generates a greater pool of antigenic peptides in melanoma cells for enhanced CD4+ T cell recognition. Our results suggest that the induction of GILT in human melanoma cells could aid in the development of a novel whole-cell vaccine for the enhancement of immune recognition of metastatic melanoma.


Subject(s)
Melanoma , Sulfhydryl Compounds , Antigen Presentation , Antigens, Neoplasm , HLA Antigens , Humans , Lysosomes/metabolism , Oxidoreductases Acting on Sulfur Group Donors/metabolism , Peptides
13.
J Pediatr Orthop ; 42(1): 30-34, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34739431

ABSTRACT

BACKGROUND: The aim of the present study was to evaluate the effectiveness of the Bedside Entertainment and Relaxation Theater (BERT) on fear, anxiety, and pain outcomes in pediatric orthopaedic patients associated with cast removal and/or pin removal in the outpatient clinic setting. METHODS: A total of 66 pediatric patients between the ages of 2 and 6 undergoing clinic procedures were recruited for this study and randomized into the control group or the intervention (BERT) group. Patients in the control group received standard of care during the cast room procedure; patients in the BERT group were given headphones and watched a movie on a projector during the procedure. Fear, anxiety, and pain were measured before and after the procedure. Procedures included cast removal, pin removal, or a combination of the 2. RESULTS: Patients in the BERT group reported less fear and anxiety overall after the procedure than patients in the control group (P=0.009, 0.015). Adjusting for procedure type (ie, pin removal), patients in the BERT group reported a 0.67 point decrease (95% confidence interval: 0.04, 1.30) on the fear scale after the procedure (P=0.039) and a 1.81 point decrease (95% confidence interval: 0.04, 3.59) on the anxiety scale associated with the procedure (P=0.045), compared with the control group. Patients and caregivers reported high satisfaction with BERT. CONCLUSION: This randomized, controlled trial demonstrates an evidence-based distraction tool that can be implemented across medical centers for pediatric patients undergoing office based orthopaedic procedures. BERT can be used to reduce fear and anxiety associated with these procedures, and increase patient and parent satisfaction. LEVEL OF EVIDENCE: Level I.


Subject(s)
Orthopedics , Anxiety/etiology , Anxiety/prevention & control , Child , Child, Preschool , Fear , Humans , Outpatients , Pain
14.
Cancer Discov ; 11(7): 1736-1753, 2021 07.
Article in English | MEDLINE | ID: mdl-33707235

ABSTRACT

In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations; however, the extent to which these contribute to tumor growth and response to therapy in vivo remains largely unknown. By quantifying the effects of inactivating 10 putative tumor suppressor genes in a mouse model of EGFR-driven Trp53-deficient lung adenocarcinoma, we found that Apc, Rb1, or Rbm10 inactivation strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2-the strongest drivers of growth in a KRAS-driven model-reduced EGFR-driven tumor growth. These results are consistent with mutational frequencies in human EGFR- and KRAS-driven lung adenocarcinomas. Furthermore, KEAP1 inactivation reduced the sensitivity of EGFR-driven tumors to the EGFR inhibitor osimertinib, and mutations in genes in the KEAP1 pathway were associated with decreased time on tyrosine kinase inhibitor treatment in patients. Our study highlights how the impact of genetic alterations differs across oncogenic contexts and that the fitness landscape shifts upon treatment. SIGNIFICANCE: By modeling complex genotypes in vivo, this study reveals key tumor suppressors that constrain the growth of EGFR-mutant tumors. Furthermore, we uncovered that KEAP1 inactivation reduces the sensitivity of these tumors to tyrosine kinase inhibitors. Thus, our approach identifies genotypes of biological and therapeutic importance in this disease.This article is highlighted in the In This Issue feature, p. 1601.


Subject(s)
Acrylamides/therapeutic use , Adenocarcinoma of Lung/drug therapy , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Acrylamides/pharmacology , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Aniline Compounds/pharmacology , Animals , Antineoplastic Agents/pharmacology , Disease Models, Animal , Female , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Mice
15.
Orthop J Sports Med ; 8(10): 2325967120959725, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33195716

ABSTRACT

BACKGROUND: Investigations of the female athlete triad (Triad) in high school athletes have found that 36% had low energy availability, 54% had menstrual abnormalities, and 16% had low bone mineral density (BMD). Limited data are available showing the prevalence of these risk factors in high school distance runners or regarding best practice on screening for the Triad in the adolescent population. PURPOSE: To (1) evaluate the prevalence of Triad risk factors and iron supplementation in high school distance runners and (2) pilot a screening tool for Triad risk score. STUDY DESIGN: Descriptive epidemiology study. METHODS: The study population included female high school athletes who participated in cross-country/track. Participants completed a survey including questions regarding dietary habits, menstrual history, and bone stress injury (BSI) history. They then underwent evaluation of 25-hydroxyvitamin D, free triiodothyronine (T3), and dual-energy x-ray absorptiometry scan to measure body fat and BMD through use of age-, sex-, and ethnicity-matched Z scores. Triad scores were calculated. Relationships were analyzed using Spearman correlation coefficient. RESULTS: There were 38 study participants (mean age, 16.9 years). Average body mass index was 19.8 kg/m2. Disordered eating or eating disorders were reported in 76.3% of runners; in addition, 23.7% reported delayed menarche, 45.9% had a history of amenorrhea or oligomenorrhea, 42.1% had low BMD (Z score < -1.0), and 15.8% reported prior BSI. Low free T3 was significantly associated with higher Triad risk scores (r S = -0.36; P = .028). More than 42% of athletes were supplementing iron. CONCLUSION: The prevalence of Triad risk factors in high school distance runners was high. Free T3 was inversely associated with Triad score, which may serve as an indicator of low energy availability. Nearly half of the athletes were using iron supplementation.

16.
Int J Qual Health Care ; 32(10): 658-662, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32986101

ABSTRACT

OBJECTIVE: Identifying when and how often decisions are made based on high-quality evidence can inform the development of evidence-based treatment plans and care pathways, which have been shown to improve quality of care and patient safety. Evidence to guide decision-making, national guidelines and clinical pathways for many conditions in pediatric orthopedic surgery are limited. This study investigated decision-making rationale and quantified the evidence supporting decisions made by pediatric orthopedic surgeons in an outpatient clinic. DESIGN/SETTING/PARTICIPANTS/INTERVENTION(S)/MAIN OUTCOME MEASURE(S): We recorded decisions made by eight pediatric orthopedic surgeons in an outpatient clinic and the surgeon's reported rationale behind the decisions. Surgeons categorized the rationale for each decision as one or a combination of 12 possibilities (e.g. 'Experience/anecdote,' 'First principles,' 'Trained to do it,' 'Arbitrary/instinct,' 'General study,' 'Specific study'). RESULTS: Out of 1150 total decisions, the most frequent decisions were follow-up scheduling, followed by bracing prescription/removal. The most common decision rationales were 'First principles' (n = 310, 27.0%) and 'Experience/anecdote' (n = 253, 22.0%). Only 17.8% of decisions were attributed to scientific studies, with 7.3% based on studies specific to the decision. As high as 34.6% of surgical intervention decisions were based on scientific studies, while only 10.4% of follow-up scheduling decisions were made with studies in mind. Decision category was significantly associated with a basis in scientific studies: surgical intervention and medication prescription decisions were more likely to be based on scientific studies than all other decisions. CONCLUSIONS: With increasing emphasis on high value, evidence-based care, understanding the rationale behind physician decision-making can educate physicians, identify common decisions without supporting evidence and help create clinical care pathways in pediatric orthopedic surgery. Decisions based on evidence or consensus between surgeons can inform pathways and national guidelines that minimize unwarranted variation in care and waste. Decision support tools and aids could also be implemented to guide these decisions.


Subject(s)
Orthopedic Procedures , Orthopedics , Surgeons , Child , Clinical Decision-Making , Humans
18.
Cancer Epidemiol Biomarkers Prev ; 28(8): 1353-1363, 2019 08.
Article in English | MEDLINE | ID: mdl-31147314

ABSTRACT

BACKGROUND: Hispanics are the largest minority population in the United States (18%). They represent a heterogeneous and growing population. Cancer is the leading cause of death among Hispanics, yet few studies have described cancer mortality burden by specific Hispanic group nationwide. METHODS: Cancer-related deaths from U.S. death certificates for the years 2003-2012 were analyzed for decedents identifying as Mexican, Puerto Rican, Cuban, and Central or South American. We calculated descriptive statistics, including potential years of lives lost (PYLL), age-adjusted rates, standardized mortality ratios, and fitted JoinPoint regression models, to evaluate annual trends by Hispanic group, using non-Hispanic Whites (NHW) as the reference population. RESULTS: We identified 287,218 cancer-related deaths among Hispanics and 4,570,559 among NHWs. Mortality trends were heterogeneous across Hispanic groups. Female NHWs and male Puerto Ricans had the greatest rates of adjusted PYLL per 1,000 (NHWs, 19.6; Puerto Ricans, 16.5). Liver cancer was ranked among the top 5 cancer-related deaths for every Hispanic group, but not for NHWs. Stomach cancer mortality was twice as high for most Hispanic groups when compared with NHWs and especially high for Mexicans [male standardized mortality ratio (SMR), 2.07; 95% confidence interval (CI), 2.01-2.13; female SMR, 2.62; 95% CI, 2.53-2.71]. CONCLUSIONS: We observed marked heterogeneity in cancer mortality across Hispanic groups. Several cancers affect Hispanics disproportionately compared with NHWs. Screening programs in Hispanics should be considered for stomach and liver cancer. IMPACT: Disaggregated analysis of Hispanics is needed to fully understand cancer burden among the diverse Hispanic population and is critical for cancer prevention and control efforts.


Subject(s)
Hispanic or Latino/statistics & numerical data , Mexican Americans/statistics & numerical data , Neoplasms/ethnology , Neoplasms/mortality , Age Factors , Cuba/ethnology , Female , Humans , Incidence , Male , Mortality/trends , Neoplasms/epidemiology , Puerto Rico/ethnology , Risk Factors , Sex Factors , South America/ethnology , Survival Rate , United States/epidemiology
19.
Ethn Dis ; 29(2): 287-296, 2019.
Article in English | MEDLINE | ID: mdl-31057314

ABSTRACT

Objective: To determine the association between language and ideal cardiovascular health among Asian Americans and Latinos. Design/Study Participants: Cross-sectional study using 2011-2016 National Health and Nutrition Examination Survey of Asian Americans (n=2,009) and Latinos (n=3,906). Interventions: Participants were classified according to language spoken at home (only/mostly English spoken, both English and native language spoken equally, or mostly/only native language spoken). Outcomes: Ideal, intermediate and poor cardiovascular health status for smoking, blood pressure, glucose level, and total cholesterol. Results: The majority of Asian Americans and Latinos had ideal smoking status, but those who only/mostly spoke English were more likely to smoke compared with those who spoke only/mostly spoke their native language. Approximately one third of Asian Americans and Latinos had intermediate (ie, borderline or treated to goal) levels of cardiovascular health for blood pressure, glucose level and total cholesterol. In adjusted models, those who spoke only/mostly their native language were significantly less likely to have poor smoking or hypertension status than those who spoke only/mostly English. Among Latinos, only/mostly Spanish speakers were more likely to have poor/ intermediate glucose levels (PR=1.35, 95% CI =1.21, 1.49) than those who spoke only/ mostly English, becoming statistically non-significant after adjusting for education and income. Conclusion: We found significant variation in ideal cardiovascular health attainment by language spoken at home in two of the largest immigrant groups in the United States. Findings suggest the need for language and culturally tailored public health and clinical initiatives to reduce cardiovascular risk in diverse populations.


Subject(s)
Acculturation , Asian/statistics & numerical data , Hispanic or Latino/statistics & numerical data , Hypertension/etiology , Smoking/ethnology , Adult , Blood Pressure , Cardiovascular System , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , Nutrition Surveys , United States
20.
iScience ; 13: 339-350, 2019 Mar 29.
Article in English | MEDLINE | ID: mdl-30884311

ABSTRACT

The TAM receptor, Axl, has been implicated as a candidate entry receptor for Zika virus (ZIKV) infection but has been shown as inessential for virus infection in mice. To probe the role of Axl in murine ZIKV infection, we developed a mouse model lacking the Axl receptor and the interferon alpha/beta receptor (Ifnar-/-Axl-/-), conferring susceptibility to ZIKV. This model validated that Axl is not required for murine ZIKV infection and that mice lacking Axl are resistant to ZIKV pathogenesis. This resistance correlates to lower pro-interleukin-1ß production and less apoptosis in microglia of ZIKV-infected mice. This apoptosis occurs through both intrinsic (caspase 9) and extrinsic (caspase 8) manners, and is age dependent, as younger Axl-deficient mice are susceptible to ZIKV pathogenesis. These findings suggest that Axl plays an important role in pathogenesis in the brain during ZIKV infection and indicates a potential role for Axl inhibitors as therapeutics during viral infection.

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