Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.

Applications of the partial-order continual reassessment method in the early development of treatment combinations.

Combination therapy is increasingly being explored as a promising approach for improving cancer treatment outcomes. However, identifying effective dose combinations in early oncology drug development is challenging due to limited sample sizes in early-phase clinical trials. This task becomes even more complex when multiple agents are being escalated simultaneously, potentially leading to a loss of monotonic toxicity order with respect to the dose. Traditional single-agent trial designs are insufficient for this multi-dimensional problem, necessitating the development and implementation of dose-finding methods specifically designed for drug combinations. While, in practice, approaches to this problem have focused on preselecting combinations with a known toxicity order and applying single-agent designs, this limits the number of combinations considered and may miss promising dose combinations. In recent years, several novel designs have been proposed for exploring partially ordered drug combination spaces with the goal of identifying a maximum tolerated dose combination, based on safety, or an optimal dose combination, based on toxicity and efficacy. However, their implementation in clinical practice remains limited. In this article, we describe the application of the partial order continual reassessment method and its extensions for combination therapies in early-phase clinical trials. We present completed trials that use safety endpoints to identify maximum tolerated dose combinations and adaptively use both safety and efficacy endpoints to determine optimal treatment strategies. We discuss the effectiveness of the partial-order continual reassessment method and its extensions in identifying optimal treatment strategies and provide our experience with executing these novel adaptive designs in practice. By utilizing innovative dose-finding methods, researchers and clinicians can more effectively navigate the challenges of combination therapy development, ultimately improving patient outcomes in the treatment of cancer.

Disparities in Access to Mental Health Services Among Children Diagnosed with Anxiety and Depression in the United States.

Child and adolescent mental health are major public health concerns in the US. Overall, 20% of US children have a reported mental health condition, while an estimated 40% will be diagnosed with one by age 18. Despite these concerns, little is known about factors associated with access to mental health services among children and adolescents. We analyzed data from a sample of 6655 children (aged 6 to 17 years) with either anxiety and/or depression drawn from the 2020-2021 National Survey of Children's Health (NSCH). A multivariable logistic regression model was fit to investigate predisposing, enabling, and need factors associated with caregiver's (i.e., parent or other guardian) perceived access to mental health services for their children. Approximately 50.8% of caregivers perceived obtaining mental health services for their children to be somewhat difficult, very difficult, or impossible. Children meeting criteria for having a medical home had lower odds of experiencing such difficulties (adjusted [a]OR = 0.38; 95% CI: 0.30-0.49). Further, compared to children who sometimes or never had health insurance coverage for mental or behavioral health needs, children who were always insured (aOR: 0.19; 95% CI 0.14, 0.25) and those who usually had coverage (aOR: 0.38; 95% CI 0.28, 0.51) had lower odds of experiencing perceived difficulties in obtaining care. The results indicate several enabling and need predictors of perceived access to mental health services--highlighting potential structural barriers to care access. Efforts to address access challenges should adopt a multifaceted approach and be tailored to families living in poverty, those with limited health coverage, and minoritized children with less than optimal general health.

Food security status and breast cancer screening among women in the United States: Evidence from the Health and Retirement Study and Health Care and Nutrition Study.

PURPOSE: To assess the impact of food insecurity on biennial breast cancer screenings (i.e., mammography or breast X-ray) among older women in the United States (US). METHODS: Data from the 2014 and 2016 waves of the Health and Retirement Study and the 2013 Health Care and Nutrition Study were used. The analyses were limited to a nationally representative sample of 2,861 women between 50 and 74 years of age, residing in the US. We employed a propensity score weighting method to balance observed confounders between food-secure and food-insecure women and fit a binary logistic regression to investigate population-level estimates for the association between food security and breast cancer screening. RESULTS: Food insecurity was significantly associated with failure to obtain a mammogram or breast X-ray within the past two years. Food-insecure women had 54% lower odds of reporting breast cancer screening in the past 2 years (adjusted OR = 0.46; 95% CI 0.30-0.70, p-value < 0.001) as compared to food-secure women. Additional factors associated with a higher likelihood of receiving breast cancer screenings included greater educational attainment, higher household income, regular access to health care/advice, not smoking, and not being physically disabled or experiencing depressive symptoms. CONCLUSION: Results demonstrate a socioeconomic gradient existing in regard to the utilization of regular breast cancer screenings among women. Those who tend to have lower education, lower income, and lack of reliable healthcare access are more likely to be food insecure. Thus, more likely to face the financial, logistical, or environmental barriers in obtaining screening services that accompany food insecurity.

Systematic review of the management of brain metastases from hormone receptor positive breast cancer.

INTRODUCTION: Brain metastases are a common cause of morbidity and mortality in patients with breast cancer. Local central nervous system (CNS) directed therapies are usually the first line treatment for breast cancer brain metastases (BCBM), but those must be followed by systemic therapies to achieve long-term benefit. Systemic therapy for hormone receptor (HR+) breast cancer has evolved in the last 10 years, but their role when brain metastases occur is uncertain. METHODS: We performed a systematic review of the literature focused on management of HR+ BCBM by searching Medline/PubMed, EBSCO, and Cochrane databases. The PRISMA guidelines were used for systematic review. RESULTS: Out of 807 articles identified, 98 fulfilled the inclusion criteria in their relevance to the management of HR+ BCBM. CONCLUSIONS: Similar to brain metastases from other neoplasms, local CNS directed therapies are the first line treatment for HR+ BCBM. Although the quality of evidence is low, after local therapies, our review supports the combination of targeted and endocrine therapies for both CNS and systemic management. Upon exhaustion of targeted/endocrine therapies, case series and retrospective reports suggest that certain chemotherapy agents are active against HR+ BCBM. Early phase clinical trials for HR+ BCBM are ongoing, but there is a need for prospective randomized trials to guide management and improve patients' outcome.

Reducing Unnecessary Oophorectomies for Benign Ovarian Neoplasms in Pediatric Patients.

Importance: Although most ovarian masses in children and adolescents are benign, many are managed with oophorectomy, which may be unnecessary and can have lifelong negative effects on health. Objective: To evaluate the ability of a consensus-based preoperative risk stratification algorithm to discriminate between benign and malignant ovarian pathology and decrease unnecessary oophorectomies. Design, Setting, and Participants: Pre/post interventional study of a risk stratification algorithm in patients aged 6 to 21 years undergoing surgery for an ovarian mass in an inpatient setting in 11 children's hospitals in the United States between August 2018 and January 2021, with 1-year follow-up. Intervention: Implementation of a consensus-based, preoperative risk stratification algorithm with 6 months of preintervention assessment, 6 months of intervention adoption, and 18 months of intervention. The intervention adoption cohort was excluded from statistical comparisons. Main Outcomes and Measures: Unnecessary oophorectomies, defined as oophorectomy for a benign ovarian neoplasm based on final pathology or mass resolution. Results: A total of 519 patients with a median age of 15.1 (IQR, 13.0-16.8) years were included in 3 phases: 96 in the preintervention phase (median age, 15.4 [IQR, 13.4-17.2] years; 11.5% non-Hispanic Black; 68.8% non-Hispanic White); 105 in the adoption phase; and 318 in the intervention phase (median age, 15.0 [IQR, 12.9-16.6)] years; 13.8% non-Hispanic Black; 53.5% non-Hispanic White). Benign disease was present in 93 (96.9%) in the preintervention cohort and 298 (93.7%) in the intervention cohort. The percentage of unnecessary oophorectomies decreased from 16.1% (15/93) preintervention to 8.4% (25/298) during the intervention (absolute reduction, 7.7% [95% CI, 0.4%-15.9%]; P = .03). Algorithm test performance for identifying benign lesions in the intervention cohort resulted in a sensitivity of 91.6% (95% CI, 88.5%-94.8%), a specificity of 90.0% (95% CI, 76.9%-100%), a positive predictive value of 99.3% (95% CI, 98.3%-100%), and a negative predictive value of 41.9% (95% CI, 27.1%-56.6%). The proportion of misclassification in the intervention phase (malignant disease treated with ovary-sparing surgery) was 0.7%. Algorithm adherence during the intervention phase was 95.0%, with fidelity of 81.8%. Conclusions and Relevance: Unnecessary oophorectomies decreased with use of a preoperative risk stratification algorithm to identify lesions with a high likelihood of benign pathology that are appropriate for ovary-sparing surgery. Adoption of this algorithm might prevent unnecessary oophorectomy during adolescence and its lifelong consequences. Further studies are needed to determine barriers to algorithm adherence.

Factors Associated with E-Cigarette Quit Intention Among Adolescents in the United States.

Background: Given increasing use of e-cigarettes among adolescents in the United States and its potential for nicotine addiction, encouraging adolescents to quit using these products has become a public health priority. This study examined factors at various socio-ecological levels associated with e-cigarette quit intention (pre-contemplation, contemplation, or preparation) using the Stages of Change of the Trans-theoretical Model among the U.S. adolescents. Methods: We used cross-sectional data from the past 30-day adolescent exclusive e-cigarette users participating in Wave 4 of the Population Assessment of Tobacco and Health study (n = 349). Weighted adjusted multinomial logistic regression models were used to analyze the data. Results: Compared to pre-contemplators and contemplators, preparators were more likely to believe that nicotine in e-cigarettes was "very/extremely harmful" (vs. "not at all harmful") to health (p < 0.001) and people cause a "lot of harm" (vs. "no harm") to themselves when they use e-cigarettes (p < 0.001). In comparison to pre-contemplators, contemplators and preparators were more likely to report that their parents/guardians talked with them about not using e-cigarettes than those whose parents/guardians did not talk with them (p < 0.001). Additionally, contemplators and preparators were also more likely to report that they "often/very often" (vs. never) noticed health warnings on e-cigarette packages (p < 0.001). Conclusion: Our findings suggest that harm perception, influence of family, and e-cigarette health warnings are some of the important factors associated with the stages of change for intention to quit among adolescent e-cigarette users. This study will help public health practitioners and researchers design multi-level e-cigarette cessation interventions for adolescents.

Effectiveness of Interventions to Improve Oral Cancer Knowledge: a Systematic Review.

Oral cancer is prone to late-stage diagnosis, and subsequent low five-year survival rates. A small number of interventions or campaigns designed to enhance knowledge of risk factors and symptoms associated with oral cancer have been attempted in the UK, US, and some other countries. The purpose of this systematic review is to assess the effectiveness of interventions designed to improve oral cancer knowledge. We searched five databases to identify randomized controlled trials (RCTs) and non-randomized/quasi-experimental (NR/QE) studies targeting the general population or high-risk groups (tobacco users or alcohol consumers), aged ≥15 years, and reporting the outcomes of individual and/or community level interventions. Two co-authors independently identified relevant studies, extracted data, and assessed the risk of bias. Adhering to PRISMA guidelines, 27 (eight RCTs and 19 NR/QE studies) of the 551 studies identified from the five databases met the inclusion criteria. All RCTs and nine NR/QE studies used either printed materials, health education sessions, multimedia aids, or some combinations of these tools. The other ten NR/QE studies were community-based and used mass media campaigns to increase oral cancer awareness. Overall, the majority of studies significantly improved oral cancer knowledge; however, heterogeneity in study design and variation in measurement tools made it difficult to compare outcomes. Findings suggest that individual and/or community level interventions are generally effective in increasing knowledge of oral cancer risk factors, signs and symptoms, and/or its early diagnosis and prevention strategies among the general population or high-risk groups. However, the long-term benefits of these interventions are understudied.

Confirmation of Xp22.11 Duplication as a Germline Susceptibility Alteration in a Wilms Tumor Arising in Horseshoe Kidney.

BackgroundThere is strong evidence of a genetic contribution to Wilms tumor, such as WT1 gene variation or epigenetic changes at chromosome locus 11p15. A previous genome wide association study (GWAS) of Wilms tumor identified other significant association loci including Xp22. Case report: A 4-year-old girl developed a Wilms tumor of the left isthmus of a horseshoe kidney. Chromosomal microarray analysis (CMA) of peripheral blood showed a 563 kb copy number gain at Xp22.11 that included PRDX4 and ZFX. PRDX4 has been shown to play an active role in the tumorigenesis of malignant neoplasms in various organs. Beckwith-Wiedemann methylation analysis and WT1 sequencing were negative. Whole exome sequencing of peripheral blood revealed pathogenic variant in PMS2 gene (c.765C > A), which is consistent with Lynch syndrome. Conclusion: We report a case of Wilms tumor with germline Xp22.11 duplication which further supports this locus as germline susceptibility alteration for Wilms Tumor.

Factors Associated with Torsion in Pediatric Patients with Ovarian Masses.

BACKGROUND: Management of ovarian torsion has evolved toward ovarian preservation regardless of ovarian appearance during surgery. However, patients with torsion and an ovarian neoplasm undergo a disproportionately high rate of oophorectomy. Our objectives were to identify factors associated with ovarian torsion among females with an ovarian mass and to determine if torsion is associated with malignancy. METHODS: A retrospective review of females aged 2-21 y who underwent an operation for an ovarian cyst or neoplasm between 2010 and 2016 at 10 children's hospitals was performed. Multivariate logistic regression was used to assess factors associated with torsion. Imaging data were assessed for sensitivity, specificity, and predictive value in identifying ovarian torsion. RESULTS: Of 814 girls with an ovarian neoplasm, 180 (22%) had torsion. In risk-adjusted analyses, patients with a younger age, mass size >5 cm, abdominal pain, and vomiting had an increased likelihood of torsion (P < 0.01 for all). Patients with a mass >5 cm had two times the odds of torsion (odds ratio: 2.1; confidence interval: 1.2, 3.6). Imaging was not reliable at identifying torsion (sensitivity 34%, positive predictive value 49%) or excluding torsion (specificity 72%, negative predictive value 87%). The rates of malignancy were lower in those with an ovarian mass and torsion than those without torsion (10% versus 17%, P = 0.01). Among the 180 girls with torsion and a mass, 48% underwent oophorectomy of which 14% (n = 12) had a malignancy. CONCLUSIONS: In females with an ovarian neoplasm, torsion is not associated with an increased risk of malignancy and ovarian preservation should be considered.

Online Narratives of Methamphetamine Use and Risky Sexual Behavior: Can Shame-Free Guilt Aid in Recovery?

Methamphetamine (meth) use is a recurring public health challenge in the U.S. In 2016, approximately 1.6 million Americans reported using meth. Meth use is associated with a number of adverse outcomes, including those associated with users' sexual health. In particular, meth use is linked to an increased risk for sexually transmitted infections and unplanned pregnancies. While studies have examined associations between substance use of various types-including meth use, and shame and guilt-few studies have examined relationships among substance use, sexual risk behaviors, and shame and guilt. No qualitative studies, to our knowledge, have studied all three of these phenomena in a sample of meth users. The present qualitative study explored the sexual risk behaviors and associated feelings of shame and guilt in relation to meth use. It draws from anonymous letters and stories (N = 202) posted to an online discussion forum by meth users and their family members. A grounded theory analysis of these narratives identified four primary themes pertaining to meth use and sexual behaviors: (1) feeling heightened sexual arousal and stimulation on meth, (2) experiencing sexual dissatisfaction on meth, (3) responding to sexual arousal and dissatisfaction, and (4) feeling ashamed and/or guilty. Ultimately, the present findings indicate that feelings of shame and guilt may arise more from the consequences of sexual risk behaviors stemming from meth use rather than meth use itself. The emotional toll of meth-induced sexual risk behaviors, particularly shame and guilt over the loss of meaningful relationships and self-respect due to multiple sexual partners, may provide an important opportunity for interventionists.

Determination of locomotor qualities in elite Australian Football: A pragmatic approach.

The study examined the utility of surrogate measures of athletic performance to determine locomotor qualities (maximal aerobic velocity and peak velocity) in elite Australian Football (AF). 29 professional AF players undertook aerobic fitness (3km time-trial [TT] and 30-15 Intermittent Fitness Test [30-15 IFT]) and peak velocity (PV; 50 m maximal sprints using 10Hz GPS) assessments in pre-season. Characteristics of TT performance (mean velocity, 500m and 1km splits) were compared with a surrogate for maximal aerobic velocity (MAV; 80% of 30-15 IFT final velocity). PVs derived from sprint tests were compared to those attained in AF matches (10 Hz GPS). Higher Pearson correlations were observed between MAV versus the fastest 500m (r = 0.74) and 1km (r = 0.75) of the 3km TT, but they were not superior to mean velocity (r = 0.72; p ≥ 0.30) which also demonstrated the lowest bias (p ≤ 0.01) and equivalent typical errors (0.16-0.17 m.s-1). Peak velocity was higher across match observations (0.28, CI: ± 0.17 m.s -1, p = 0.017) versus sprint tests. There was no impact of playing position on the determination of locomotor qualities using surrogate measures of locomotor qualities. Locomotor qualities can be determined practically using 10Hz GPS devices during 3km time-trials and competitive matches (assuming appropriate signal quality), without additional fitness assessments.

The Association Between Substance Use and Violence: Results from a Nationally Representative Sample of High School Students in the United States.

With over 52% of high school students reporting that they have tried alcohol or illicit drugs, 16% carrying a weapon, and 23% engaging in a physical fight, substance use and youth violence remain critical public health challenges in the United States. Using data from the 2017 Youth Risk Behavior Survey, study results revealed that youth who reported heavy use of either alcohol, marijuana, or illicit drugs were three to ten times more likely to report carrying a weapon or engaging in a physical fight. Similarly, youth with heavy substance use were one and half times to 14 times more likely to be a victim of violence or sexual or dating violence. The SEM analysis indicated that substance use had a significant effect on all aspects of violence. School-based behavioral health specialists and community-based pediatricians may need to develop targeted messages to address the potential for violence among youth who use alcohol and/or illicit drugs.

Electrophoretic measurement of water charge density and ion hydration.

Water exchange between bulk water and water-ion complexes will be at equilibrium when the charge density of the complex surface equals the charge density of bulk water, producing a constant radius water-ion complex. This complex will migrate in an electric field at a velocity proportional to the complex radius. CE velocity is the sum of the complex charge-dependent velocity and the buffer electro-osmotic flow. Simultaneous use of both a base (1.07 mM imidazole) and an acid (1.5 mM MOPS) buffer negates EOF at pH 7.4. Electric fields below 300 V/cm (potassium, calcium) and 400 V/cm (magnesium) yield migration velocities with no dehydration of the water-ion complexes. The number of waters per complex increase with the ion charge density: K+ 1.90, Ca++ 5.90, Mg++ 6.59 waters/ion. The charge densities of the complexes are similar: K+ 1.24, Ca++ 1.43, Mg++ 1.21 e/nm2 , for an average bulk water charge density of 1.29 ± 0.11 (SD) e/nm2 . The addition of 0.1% Triton increases the number of waters for Mg++ to 25.33 and lowers the charge density to 0.497 e/nm2 . High electric field dehydration shows that calcium will be fully dehydrated at 638.3 V/cm and magnesium fully dehydrated at 925.5 V/cm, which occur at 6.15 and 5.78 nm from the membrane. Dehydrated magnesium will then bind to calcium channels leading to decreased smooth muscle activation.

Psychosocial interventions for informal caregivers of lung cancer patients: A systematic review.

OBJECTIVE: Caregivers of patients with lung cancer often face physical, emotional, and financial distress, which not only negatively affects the caregivers' mental health and quality of life but may also impact patients' well-being. The purpose of this systematic review is to examine the content, delivery, and efficacy of psychosocial interventions targeting caregivers of lung cancer patients. METHODS: Studies included in this systematic review assessed psychosocial interventions for caregivers of lung cancer patients that were published in English between January 2009 and December 2017. These interventions focused on burden, mental health, quality of life, self-efficacy, and/or coping as outcome measures. CINAHL, PubMed, PsycInfo, Science Direct, and Web of Science databases were searched using the terms (lung cancer OR lung neoplasms OR thoracic cancer) AND (caregiver OR caregiving) AND (intervention OR program) to systematically review the relevant literature on this topic. RESULTS: From the 22 studies included in this systematic review, interventions were classified into four categories: communication-based interventions, coping skills training interventions, multicomponent interventions, and stress reduction interventions. The majority of the interventions (especially communication-based and multicomponent) led to improvement, albeit not always statistically significant, in one or more outcomes; however, the most frequently reported improvements included, burden, distress, anxiety, depression, overall quality of life, self-efficacy, and coping abilities. CONCLUSIONS: The unmet needs of informal caregivers of lung cancer patients have a significant impact on their mental health and quality of life, but this burden can be alleviated by psychosocial interventions that offer appropriate support, education, and resources.

A Qualitative Exploration of "Mother First" Identity and Antiretroviral Adherence among African American Women Living with HIV in the Mid-South Region of the United States.

The majority of African American women living with HIV are of child-bearing age and large numbers of these women express a desire to have children. Extant research suggests that motherhood provides HIV-positive women with a sense of hope and normalcy and, in some cases, is associated with positive HIV-related health behaviors. Guided by the tenets of the culture-centered approach (CCA), this qualitative study sought to understand the relationship between motherhood identity and ART adherence among a sample of 50 African American women living with HIV in the Mid-South region of the United States. Our theoretically-informed thematic analysis of in-depth interviews with all 50 women produced three primary themes: (1) experiencing HIV through the lens of motherhood, (2) the physical and social realities of the "mother first" orientation while living with HIV, and (3) the impact of the "mother first" orientation on ART adherence and self-care. These findings identify how participants' "mother first" identity orientation interacts with their sociocultural environment to enable and constrain their attempts at ART adherence. The findings also provide empirical evidence to support the CCA's theorizing regarding the ways in which the materiality of structures interact with symbolic cultural meanings to (re)produce health inequalities.

Non-Neural (S-100 Negative) Bronchial Granular Cell Tumor Causing Acute Respiratory Failure.

Introduction: Endobronchial granular cell tumors are uncommon in the pediatric population. Case report: A 9-year-old female presented with respiratory failure due to an endobronchial tumor. After debulking and diagnosis, she underwent thoracotomy with right upper lobe resection and bronchoplasty. Pathology demonstrated an endobronchial S-100 negative granular cell tumor, which to our knowledge, is the first such report in the literature. Conclusion: Endobronchial granular cell tumors may cause obstructive respiratory failure, are amenable to surgery, and may be S-100 negative.

Cases and evidence for panel testing in cancer genetics: Is site-specific testing dead?

Historically in cancer genetic counseling, when a pathogenic variant is found which explains the cancers in the family, at risk family members are offered site-specific testing to identify whether or not they have the previously identified pathogenic variant. Factors such as turnaround times, cost, and insurance coverage all made site-specific testing the most appropriate testing option; however, as turnaround times and costs have substantially dropped and the recognition of double heterozygous families and families with nontraditional presentations has increased, the utility of site-specific testing should be questioned. We present four cases where ordering site-specific testing would have missed a clinically relevant pathogenic variant which raises the question of whether or not site-specific testing should be regularly used in cancer genetic testing.

"Gave me a line of ice and I got hooked": Exploring narratives of initiating methamphetamine use.

OBJECTIVE: This study explores factors associated with methamphetamine initiation based on the narratives from an online support group for methamphetamine users. METHODS: We conducted a qualitative study of 202 first-person narratives submitted to an anonymous, online support group for methamphetamine users. The narratives were analyzed in the Dedoose qualitative software using Charmaz's adaptations to Glaserian grounded theory methodology. RESULTS: Ten factors for initiating methamphetamine use emerged from our analysis and corresponded to three constructs from the Theory of Planned Behavior: attitude (needing energy to work, wishing to escape pain, wanting to have fun, and desiring a thinner body), subjective norms (ubiquity of methamphetamine use, yearning for closer relationships, and wanting to fit in), and perceived behavioral control (believing addiction is inevitable, feeling forced to fit in, and having no real control). Many participants described initiating methamphetamine use because they believed it would help them meet personal goals or needs. Other participants began using it out of curiosity, to develop relationships, and/or because of the drug's ubiquity in their social environments. Some users described how their perceived lack of control left them with limited ability to resist trying the drug. CONCLUSIONS: Results from this study may aid public health researchers and interventionists seeking theoretically informed methamphetamine prevention programs.

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

PURPOSE: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. PATIENTS AND METHODS: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. RESULTS: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. CONCLUSION: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. CLINICAL TRIAL: (NCT01305941).