Application of inverse weighting analysis to assess the association of youth perceptions with the age of initiation of tobacco products.

Introduction: To examine if perceptions of harmfulness and addictiveness of hookah and cigarettes impact the age of initiation of hookah and cigarettes, respectively, among US youth. Youth (12-17 years old) users and never users of hookah and cigarettes during their first wave of PATH participation were analyzed by each tobacco product (TP) independently. The effect of perceptions of (i) harmfulness and (ii) addictiveness at the first wave of PATH participation on the age of initiation of ever use of hookah was estimated using interval-censoring Cox proportional hazards models. Methods: Users and never users of hookah at their first wave of PATH participation were balanced by multiplying the sampling weight and the 100 balance repeated replicate weights with the inverse probability weight (IPW). The IPW was based on the probability of being a user in their first wave of PATH participation. A Fay's factor of 0.3 was included for variance estimation. Crude hazard ratios (HR) and 95% confidence intervals (CIs) are reported. A similar process was repeated for cigarettes. Results: Compared to youth who perceived each TP as "a lot of harm", youth who reported perceived "some harm" had younger ages of initiation of these tobacco products, HR: 2.53 (95% CI: 2.87-4.34) for hookah and HR: 2.35 (95% CI: 2.10-2.62) for cigarettes. Similarly, youth who perceived each TP as "no/little harm" had an earlier age of initiation of these TPs compared to those who perceived them as "a lot of harm", with an HR: 2.23 (95% CI: 1.82, 2.71) for hookah and an HR: 1.85 (95% CI: 1.72, 1.98) for cigarettes. Compared to youth who reported each TP as "somewhat/very likely" as their perception of addictiveness, youth who reported "neither likely nor unlikely" and "very/somewhat unlikely" as their perception of addictiveness of hookah had an older age of initiation, with an HR: 0.75 (95% CI: 0.67-0.83) and an HR: 0.55 (95% CI: 0.47, 0.63) respectively. Discussion: Perceptions of the harmfulness and addictiveness of these tobacco products (TPs) should be addressed in education campaigns for youth to prevent early ages of initiation of cigarettes and hookah.

Prospective study examining the impact of cerebral angiography on quantitative pupillometer values in the interventional radiology suite.

OBJECTIVES: The purpose of this pilot study was to obtain baseline quantitative pupillometry (QP) measurements before and after catheter-directed cerebral angiography (DCA) to explore the hypothesis that cerebral angiography is an independent predictor of change in pupillary light reflex (PLR) metrics. DESIGN: This was a prospective, observational pilot study of PLR assessments obtained using QP 30 min before and after DCA. All patients had QP measurements performed with the NPi-300 (Neuroptics) pupillometer. SETTING: Recruitment was done at a single-centre, tertiary-care academic hospital and comprehensive stroke centre in Dallas, Texas. PARTICIPANTS: Fifty participants were recruited undergoing elective or emergent angiography. Inclusion criteria were a physician-ordered interventional neuroradiological procedure, at least 18 years of age, no contraindications to PLR assessment with QP, and nursing transport to and from DCA. Patients with a history of eye surgery were excluded. MAIN OUTCOME MEASURES: Difference in PLR metric obtained from QP 30 min before and after DCA. RESULTS: Statistically significant difference was noted in the pre and post left eye readings for the minimum pupil size (a.k.a., pupil diameter on maximum constriction). The mean maximum constriction diameter prior to angiogram of 3.2 (1.1) mm was statistically larger than after angiogram (2.9 (1.0) mm; p<0.05); however, this was not considered clinically significant. Comparisons for all other PLR metrics pre and post angiogram demonstrated no significant difference. Using change in NPi pre and post angiogram (Δpre=0.05 (0.77) vs Δpost=0.08 (0.67); p=0.62), we calculated the effect size as 0.042. Hence, detecting a statistically significant difference in NPi, if a difference exists, would require a sample size of ~6000 patients. CONCLUSIONS: Our study provides supportive data that in an uncomplicated angiogram, even with intervention, there is no effect on the PLR.

Trends in the relationship between suicide behaviors and obesity among adolescents in the United States from 1999 to 2019.

Previous studies indicate that obesity is a risk factor of suicide behaviors among adolescents. Whether this association has remained consistent during the ongoing obesity epidemic remains unknown. The time trends of the obesity-suicide association were examined using the 1999-2019 biannual Youth Risk Behavior Survey data (n = 161,606). Prevalence odds ratio of suicide behaviors among adolescents with obesity (vs. adolescents with no obesity) for each survey year and time trends using National Cancer Institute Joinpoint regression analysis was calculated. For each year post-baseline, there was a significant increase of prevalence odds ratio of 1.4 (1.2-1.6)-1.6 (1.3-2.0) for suicide ideation, 1.3 (1.1-1.7) -1.7 (1.4-2.0) for plan, and 1.3 (1.0-1.7) -1.9 (1.5-2.4) for an attempt, except for the 2013 survey for attempt (1.19 [0.9-1.6]). Significant positive trends were found from1999 to 2019 for ideation and plan, with biannual %-changes of + 0.92 and + 1.22%, respectively. Adolescents with obesity have consistently higher odds of engaging in suicide behaviors than their peers without obesity since the beginning of the United States obesity epidemic, and this association grew stronger as the obesity epidemic continued.

Differences in Use of Clinical Decision Support Tools and Implementation of Aspirin, Blood Pressure Control, Cholesterol Management, and Smoking Cessation Quality Metrics in Small Practices by Race and Sex.

Importance: Practice-level evidence is needed to clarify the value of population-based clinical decision support (CDS) tools in reducing racial and sex disparities in cardiovascular care. Objective: To evaluate the association between CDS tools and racial and sex disparities in the aspirin use, blood pressure control, cholesterol management, and smoking cessation (ABCS) care quality metrics among smaller primary care practices. Design, Setting, and Participants: This cross-sectional study used practice-level data from the Agency for Healthcare Research and Quality-funded EvidenceNOW initiative. The national initiative from May 1, 2015, to April 30, 2021, spanned 12 US states and focused on improving cardiovascular preventive care by providing quality improvement support to smaller primary care practices. A total of 576 primary care practices in EvidenceNOW submitted both survey data and electronic health record (EHR)-derived ABCS data stratified by race and sex. Main Outcomes and Measures: Practice-level estimates of disparities between Black and White patients and between male and female patients were calculated as the difference in proportions of eligible patients within each practice meeting ABCS care quality metrics. The association between CDS tools (EHR prompts, standing orders, and clinical registries) and disparities was evaluated by multiply imputed multivariable models for each CDS tool, adjusted for practice rurality, ownership, and size. Results: Across the 576 practices included in the analysis, 219 (38.0%) had patient panels that were more than half White and 327 (56.8%) had panels that were more than half women. The proportion of White compared with Black patients meeting metrics for blood pressure (difference, 5.16% [95% CI, 4.29%-6.02%]; P < .001) and cholesterol management (difference, 1.49% [95% CI, 0.04%-2.93%] P = .04) was higher; the proportion of men meeting metrics for aspirin use (difference, 4.36% [95% CI, 3.34%-5.38%]; P < .001) and cholesterol management (difference, 3.88% [95% CI, 3.14%-4.63%]; P < .001) was higher compared with women. Conversely, the proportion of women meeting practice blood pressure control (difference, -1.80% [95% CI, -2.32% to -1.28%]; P < .001) and smoking cessation counseling (difference, -1.67% [95% CI, -2.38% to -0.95%]; P < .001) metrics was higher compared with men. Use of CDS tools was not associated with differences in race or sex disparities except for the smoking metric. Practices using CDS tools showed a higher proportion of men meeting the smoking counseling metric than women (coefficient, 3.82 [95% CI, 0.95-6.68]; P = .009). Conclusions and Relevance: The findings of this cross-sectional study suggest that practices using CDS tools had small disparities that were not statistically significant, but CDS tools were not associated with reductions in disparities. More research is needed on effective practice-level interventions to mitigate disparities.

Relationship between teacher fidelity to an early childhood obesity prevention program and the Child care center nutrition and physical activity environment.

Background: Child care centers (CCC) can be strategic settings to establish healthy lifestyle behaviors through obesity prevention programs. Fidelity to the implementation of such programs is a vital evaluation component, but is often not measured. This study assessed CCC teacher fidelity to the implementation of "Healthy Caregivers, Healthy Children (HC2)", a CCC-based obesity prevention intervention. Methods: CCCs serving low-resource, ethnically diverse families with ≥ 50 children ages 2-to-5 years old that were randomized to the HC2 intervention and that had teacher fidelity data collected (n = 9 CCC) were included in this analysis. The Environment and Policy Assessment and Observation (EPAO) tool assessed the CCC nutrition and physical activity (PA) environment at the beginning/end of the school year. Fidelity assessments were conducted in CCCs randomized to HC2 in Spring 2016 (n = 33 teachers) and 2017 (n = 39 teachers) by a trained observer. The relationship between teacher fidelity and EPAO was assessed via mixed models. Results: For every-one unit rise in teacher fidelity, EPAO nutrition increased 0.055 points (p =.006). No significant relationship was shown between teacher fidelity and EPAO PA score (p =.14). Conclusion: Teacher fidelity to obesity prevention program implementation may support a healthy CCC obesity prevention and nutrition environment but might require continued support for all components.

Incidence of and predictors for serious opioid-related adverse drug events.

PURPOSE: To determine the incidence of and predictors for serious opioid-related adverse drug events (ORADEs) in postoperative inpatients. METHODS: A retrospective cohort study design of serious ORADEs in surgical inpatients between 2015 and 2017, who were abstracted from the electronic health record, in an 800-bed academic medical health center. RESULTS: A total of 27,942 surgery patients met the inclusion criteria. Of those, 25,208 patients (90%) were exposed to opioids after surgery. A total of 25,133 (99.7%) patients exposed to opioids did not experience a serious ORADE while 75 (0.3%) patients did experience a serious ORADE and required naloxone. The predictors for ORADEs include age (OR = 1.040, P-value < .0001); gender (OR = 0.394, P-value = .0006); psychiatric disorder (OR = 4.440, CI: 2.435, 8.095); morphine level with respect to hydrocodone-acetaminophen (OR = 5.841, P-value = .0384); and were almost six times more likely to experience a serious ORADE when morphine is prescribed and 4.44 times more likely in patients with a psychiatric disorder (P-value < .0001). CONCLUSION: Once a baseline incidence is known, predictors for serious ORADEs in surgical inpatients are useful in guiding medical-surgical nurses' opioid safety practices, with more frequent focused respiratory assessments before opioid dosing and closer monitoring when opioids are prescribed postoperatively, especially in higher-risk surgical inpatients.

Cluster-randomised trial of the impact of an obesity prevention intervention on childcare centre nutrition and physical activity environment over 2 years.

OBJECTIVE: The prevalence of obesity among pre-school-aged children in the USA remains unacceptably high. Here, we examine the impact of Healthy Caregivers-Healthy Children (HC2) Phase 2, a childcare centre (CCC)-based obesity prevention intervention on changes in the CCC nutrition and physical activity environment over 2 school years. DESIGN: This was a cluster-randomised trial with twelve CCC receiving the HC2 intervention arm and twelve in the control arm. The primary outcome was change in the Environment and Policy Assessment and Observation (EPAO) tool over 2 school years (Fall 2015, Spring 2016 and Spring 2017). Changes in EPAO physical activity and nutrition score were analysed via a: (1) random effects mixed models and (2) mixed models to determine the effect of HC2 v. control. SETTING: The study was conducted in twenty-four CCC serving low-income, ethnically diverse families in Miami-Dade County. PARTICIPANTS: Intervention CCC received (1) teachers/parents/children curriculum, (2) snack, beverage, physical activity, and screen time policies, and (3) menu modifications. RESULTS: Two-year EPAO nutrition score changes in intervention CCC were almost twice that of control CCC. The EPAO physical activity environment scores only slightly improved in intervention CCC v. control CCC. Intervention CCC showed higher combined EPAO physical activity and nutrition scores compared to control CCC over the 2-year study period (ß = 0·09, P = 0·05). CONCLUSIONS: Obesity prevention programmes can have a positive impact on the CCC nutrition environment and can promote healthy weight in early childhood. CCC may need consistent support to improve the physical activity environment to ensure the policies remain intact.

Precise Estimation for the Age of Initiation of Tobacco Use Among U.S. Youth: Finding from the Population Assessment of Tobacco and Health (PATH) Study, 2013-2017.

Context: Youth tobacco use remains a prominent United States public health issue with a high economic and health burden. Method: We pooled never and ever users at youth's first wave of PATH participation (waves 1-3) to estimate age of initiation for hookah, e-cigarettes, cigarettes, traditional cigars, cigarillos, and smokeless tobacco prospectively (waves 2-4). Age of initiation of each tobacco product was estimated using weighted interval-censored survival analyses. Weighted interval censoring Cox-proportional hazards regression models were used to assess the association of ever use of the TP at the first wave of PATH participation, sex, and race/ethnicity on the age of initiation of ever use of each tobacco product. Sensitivity analyses were performed to understand the impact of the recalled age of initiation for the left-censored participants by replacing the recalled age of initiation with a uniform "6" years lower bound. Results: The proportion of those who ever used each tobacco product at the first wave of PATH participation ranged from 1.8% for traditional cigars to 10.4% for cigarettes. There was a significant increase in ever use of each tobacco product after the age of 14, with e-cigarettes and cigarettes showing the highest cumulative incidence of initiation by age 21, while smokeless and cigarillos recorded the lowest cumulative incidence by age 21. The adjusted Cox models showed boys initiated at earlier ages for all of these tobacco products except for hookah, which showed no difference. Similarly, apart from ever use of hookah, non-Hispanic White youth were more likely to initiate each tobacco product at earlier ages compared to Hispanic, non-Hispanic Black, and non-Hispanic Other youth. Conclusion: The increased sample size and the inclusion of ever users yielded greater precision for age of initiation of each tobacco product than analyses limited to never users at the first wave of PATH participation. These analyses can help elucidate population selection criteria for estimating the age of initiation of tobacco products.

Identificação da velocidade anormal da dilatação de pupila como biomarcador de lesão cerebral em pacientes neurocríticos / Identification of abnormal pupil dilation velocity as a biomarker of cerebral injury in neurocritically ill patients

RESUMO Objetivo: Calcular as velocidades médias da dilatação de pupila para classificar a gravidade da lesão derivada da escala de coma de Glasgow, estratificada por variáveis de confusão. Métodos: Neste estudo, analisaram-se 68.813 exames das pupilas para determinar a velocidade normal de dilatação em 3.595 pacientes com lesão cerebral leve (13 - 15), moderada (9 - 12) ou grave (3 - 8), segundo a escala de coma de Glasgow. As variáveis idade, sexo, raça, tamanho da pupila, tempo de permanência na unidade de terapia intensiva, pressão intracraniana, uso de narcóticos, classificação pela escala de coma de Glasgow e diagnóstico foram consideradas confundidoras e controladas para análise estatística. Empregou-se regressão logística com base em algoritmo de classificação com aprendizado de máquina para identificar os pontos de corte da velocidade de dilatação para as categorias segundo a escala de coma de Glasgow. Resultados: As razões de chance e os intervalos de confiança desses fatores se mostraram estatisticamente significantes em sua influência sobre a velocidade de dilatação. A classificação com base na área sob a curva mostrou que, para o grau leve, na escala de coma de Glasgow, o limite da velocidade de dilatação foi de 1,2mm/s, com taxas de falsa probabilidade de 0,1602 e 0,1902 e áreas sob a curva de 0,8380 e 0,8080, respectivamente, para os olhos esquerdo e direito. Para grau moderado na escala de coma de Glasgow, a velocidade de dilatação foi de 1,1mm/s com taxas de falsa probabilidade de 0,1880 e 0,1940 e áreas sob a curva de 0,8120 e 0,8060, respectivamente, nos olhos esquerdo e direito. Mais ainda, para o grau grave na escala de coma de Glasgow, a velocidade de dilatação foi de 0,9mm/s, com taxas de falsa probabilidade de 0,1980 e 0,2060 e áreas sob a curva de 0,8020 e 0,7940, respectivamente, nos olhos esquerdo e direito. Esses valores foram diferentes dos métodos prévios de descrição subjetiva e das velocidades de dilatação previamente estimadas. Conclusão: Observaram-se velocidades mais lentas de dilatação pupilar em pacientes com escores mais baixos na escala de coma de Glasgow, indicando que diminuição da velocidade pode indicar grau mais grave de lesão neuronal.

ABSTRACT Objective: To calculate mean dilation velocities for Glasgow coma scale-derived injury severity classifications stratified by multiple confounding variables. Methods: In this study, we examined 68,813 pupil readings from 3,595 patients to determine normal dilation velocity with brain injury categorized based upon a Glasgow coma scale as mild (13 - 15), moderate (9 - 12), or severe (3 - 8). The variables age, sex, race, pupil size, intensive care unit length of stay, intracranial pressure, use of narcotics, Glasgow coma scale, and diagnosis were considered as confounding and controlled for in statistical analysis. Machine learning classification algorithm-based logistic regression was employed to identify dilation velocity cutoffs for Glasgow coma scale categories. Results: The odds ratios and confidence intervals of these factors were shown to be statistically significant in their influence on dilation velocity. Classification based on the area under the curve showed that for the mild Glasgow coma scale, the dilation velocity threshold value was 1.2mm/s, with false probability rates of 0.1602 and 0.1902 and areas under the curve of 0.8380 and 0.8080 in the left and right eyes, respectively. For the moderate Glasgow coma scale, the dilation velocity was 1.1mm/s, with false probability rates of 0.1880 and 0.1940 and areas under the curve of 0.8120 and 0.8060 in the left and right eyes, respectively. Furthermore, for the severe Glasgow coma scale, the dilation velocity was 0.9mm/s, with false probability rates of 0.1980 and 0.2060 and areas under the curve of 0.8020 and 0.7940 in the left and right eyes, respectively. These values were different from the previous method of subjective description and from previously estimated normal dilation velocities. Conclusion: Slower dilation velocities were observed in patients with lower Glasgow coma scores, indicating that decreasing velocities may indicate a higher degree of neuronal injury.

Regression with a right-censored predictor using inverse probability weighting methods.

In a longitudinal study, measures of key variables might be incomplete or partially recorded due to drop-out, loss to follow-up, or early termination of the study occurring before the advent of the event of interest. In this paper, we focus primarily on the implementation of a regression model with a randomly censored predictor. We examine, particularly, the use of inverse probability weighting methods in a generalized linear model (GLM), when the predictor of interest is right-censored, to adjust for censoring. To improve the performance of the complete-case analysis and prevent selection bias, we consider three different weighting schemes: inverse censoring probability weights, Kaplan-Meier weights, and Cox proportional hazards weights. We use Monte Carlo simulation studies to evaluate and compare the empirical properties of different weighting estimation methods. Finally, we apply these methods to the Framingham Heart Study data as an illustrative example to estimate the relationship between age of onset of a clinically diagnosed cardiovascular event and low-density lipoprotein among cigarette smokers.

Parental Age of Onset of Cardiovascular Disease as a Predictor for Offspring Age of Onset of Cardiovascular Disease.

OBJECTIVE: The risk for cardiovascular disease (CVD) is higher for individuals with a first-degree relative who developed premature CVD (with a threshold at age 55 years for a male or 65 years for a female). However, little is known about the effect that each unit increase or decrease of maternal or paternal age of onset of CVD has on offspring age of onset of CVD. We hypothesized that there is an association between maternal and paternal age of onset of CVD and offspring age of onset of CVD. METHODS: We used the Framingham Heart Study database and performed conditional imputation for CVD-censored parental age (i.e. parents that didn't experience onset of CVD) and Cox proportional regression analysis, with offspring's age of onset of CVD as the dependent variable and parental age of onset of CVD as the primary predictor. Modifiable risk factors in offspring, such as cigarette smoking, body mass index (BMI), diabetes mellitus, systolic blood pressure (SBP), high-density lipoprotein (HDL) level, and low-density lipoprotein (LDL) level, were controlled for. Separate analyses were performed for the association between maternal age of onset of CVD and offspring age of onset of CVD and the association between paternal age of onset of CVD and offspring age of onset of CVD. RESULTS: Parental age of onset of CVD was predictive of offspring age of onset of CVD for maternal age of onset of CVD (P < .0001; N = 1401) and for paternal age of onset of CVD (P = 0.0134; N = 1221). A negative estimate of the coefficient of interest signifies that late onset of cardiovascular events in parents is protective of onset of CVD in offspring. Cigarette smoking and HDL level were important associated confounders. CONCLUSIONS: Offspring age of onset of cardiovascular disease is significantly associated with both maternal and paternal age of onset CVD. The incorporation of the parameters, maternal or paternal age of onset of CVD, into risk estimate calculators may improve accuracy of identification of high-risk patients in clinical settings.

Activity of azacitidine in chronic myelomonocytic leukemia.

BACKGROUND: Hypomethylating drugs are useful in the management of myelodysplastic syndrome (MDS). Two of these drugs, azacitidine and decitabine, have received FDA approval for the treatment of MDS and chronic myelomonocytic leukemia (CMML). However, phase 2 and 3 studies that assessed these agents in MDS included only a small number of patients with CMML. The objective of this study was to evaluate the efficacy and safety of azacitidine in the treatment of CMML. METHODS: The records of thirty-eight patients diagnosed with CMML and treated with azacitidine at our institution were reviewed. Azacitidine was administered at 75 mg/m(2) /day for 7 days or 100 mg/m(2) /day for 5 days every 4 weeks. Patients who received at least 1 cycle of the drug were considered evaluable for response. RESULTS: Response was assessed by the modified International Working Group (IWG) criteria. The overall response rate was 39% (14 of 36); complete response (CR) rate was 11% (4 of 36); partial response (PR) rate was 3% (1 of 36); hematologic improvement (HI) was 25% (9 of 36). The median overall survival was 12 months. There was a statistically significant overall survival advantage in responders compared with nonresponders: 15.5 months versus 9 months, respectively (P = .04). Treatment was generally well tolerated. One of 2 patients had complete resolution of a skin rash that was due to monocytic infiltration. CONCLUSIONS: Azacitidine is active in the treatment of CMML. The therapy-associated toxicity is acceptable. Our results support further investigation of azacitidine in CMML, particularly in combination with other agents.

Correlation of immunohistochemical expression of p53 with unamplified chromosome 17 polysomy in invasive breast carcinoma.

p53 functions as a tumor suppressor gene and is frequently mutated and inactivated in several human cancers. Some studies have shown p53 overexpression in breast cancer to be an independent prognostic indicator. A subset of breast cancers have chromosome 17 polysomy. Although p53 immunostaining has been found to correlate with chromosome 17 polysomy in nonsmall cell lung carcinomas, head and neck squamous cell carcinomas, and bladder carcinomas, its expression has not been correlated with chromosome 17 polysomy in breast carcinomas. In this study, we compared p53 expression by immunohistochemistry in cases of invasive breast carcinoma showing unamplified chromosome 17 polysomy (P) with cases showing HER2 amplification (A) and with those showing neither amplification nor polysomy (N). There was a significant overexpression of p53 in both cases with HER2 amplification and unamplified polysomy 17 compared with cases with neither amplification nor polysomy (7% of N, 25% of P, and 37% of A group were p53 positive). We have shown in an earlier study that invasive breast carcinoma with unamplified chromosome 17 polysomy is associated with several adverse prognostic indicators including a higher Nottingham score and greater estrogen receptor (ER) negativity with a trend toward the amplified group, in contrast to patients with neither amplification nor polysomy. In this study, we now show that p53 positivity in unamplified 17 polysomy identifies cases that are associated with an even higher Nottingham score and greater hormone receptor negativity that is similar to cases with HER2 amplification.

Poor prognostic significance of unamplified chromosome 17 polysomy in invasive breast carcinoma.

The human epidermal growth factor receptor 2 (HER2) oncoprotein is overexpressed in about 20% of breast cancers, with HER2 gene amplification responsible for protein overexpression in the vast majority of patients. A subset of breast cancers have chromosome 17 aneusomy, due to either 17 monosomy (a single copy of chromosome 17) or polysomy (increased copy numbers of chromosome 17). Although HER2 overexpression is an established adverse prognostic factor in breast cancer, the role of unamplified chromosome 17 polysomy is uncertain and there is a paucity of literature on the correlation of chromosome 17 aneusomy with important prognostic and predictive pathologic factors in invasive breast carcinoma. Furthermore, while patients showing HER2 amplification with or without polysomy 17 are treated with trastuzumab with or without other chemotherapy, treatment of patients with unamplified chromosome 17 polysomy is not well defined. Currently most of these patients are treated similar to patients with neither amplification nor 17 polysomy. The aim of this study was to compare some prognostic and predictive factors in invasive breast carcinoma in patients with unamplified chromosome 17 polysomy with that seen in cases with HER2 gene amplification and those with neither amplification or polysomy. We found that invasive breast carcinomas with unamplified chromosome 17 polysomy are associated with several adverse prognostic indicators such as a higher nuclear grade, mitotic activity, Nottingham score, histologic grade, tumor stage, and greater estrogen receptor negativity with a trend towards the amplified group, in contrast to patients with neither amplification or polysomy. Although most patients with unamplified 17 polysomy have a 2+ equivocal score on immunohistochemistry, a minority has a 3+ positive score. An increased adverse role for unamplified polysomy along with 3+ protein expression in some patients supports the idea that these patients should be considered for therapy with trastuzumab and/or anthracyclines.