Suitability of Goal Attainment Scaling in Older Adult Populations with Neurodegenerative Disease Experiencing Cognitive Impairment: A Systematic Review and Meta-Analysis.

INTRODUCTION: Identifying responsive outcome measures for assessing functional change related to cognition, communication, and quality of life for individuals with neurodegenerative disease is important for intervention design and clinical care. Goal Attainment Scaling (GAS) has been used as an outcome measure to formally develop and systematically measure incremental progress toward functional, patient-centered goals in clinical settings. Evidence suggests that GAS is reliable and feasible for use in older adult populations and in adult populations with cognitive impairment, but no review has assessed the suitability of GAS in older adults with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. This study conducted a systematic review to evaluate the suitability of GAS as an outcome measure for older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. METHODS: The review was registered with PROSPERO and performed by searching ten electronic scientific databases (PubMed, Medline OVID, CINAHL, Cochrane, Embase, Web of Science, PsycINFO, Scopus, OTSeeker, REHABDATA) and four registries (Clinicaltrials.gov, Grey Literature Report, Mednar, OpenGrey). A summary measure of responsiveness (post-intervention minus pre-intervention mean GAS T-score) was compared across eligible studies using a random-effects meta-analysis. Risk of bias in included studies was assessed using the NIH Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. RESULTS: 882 eligible articles were identified and screened by two independent reviewers. Ten studies met inclusion criteria for the final analysis. Of the ten included reports, 3 focus on all-cause dementia, 3 on multiple sclerosis, 1 on Parkinson's disease, 1 on mild cognitive impairment, 1 on Alzheimer's disease, and 1 on primary progressive aphasia. Responsiveness analyses showed pre- and post-intervention GAS goals were significantly different from zero (Z = 7.48, p < 0.001), with post-intervention GAS scores being higher than pre-intervention GAS scores. Three included studies showed a high risk of bias, 3 showed a moderate risk of bias, and 4 showed a low risk of bias. Overall risk of bias of included studies was rated as moderate. CONCLUSION: GAS showed an improvement in goal attainment across different dementia patient populations and intervention types. The overall moderate risk of bias suggests that while bias is present across included studies (e.g., small sample size, unblinded assessors), the observed effect likely represents the true effect. This suggests that GAS is responsive to functional change and may be suitable for use in older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment.

Follow-up approaches to a health literacy intervention to increase colorectal cancer screening in rural community clinics: A randomized controlled trial.

BACKGROUND: Significant disparities exist in colorectal cancer (CRC) screening rates among those of low socioeconomic status, with fewer years of education, lacking health insurance, or living in rural areas. METHODS: A randomized controlled trial was conducted to compare the effectiveness of 2 follow-up approaches to a health literacy intervention to improve CRC screening: automated telephone call or personal call. Patients aged 50 to 75 years residing in 4 rural community clinics in Louisiana were given a structured interview that assessed demographic, health literacy and CRC screening barriers, knowledge, and attitudes. All were given health literacy-informed CRC education, a patient-friendly CRC screening pamphlet, simplified fecal immunochemical test (FIT) instructions, and a FIT kit, and a "teach-back" method was used to confirm understanding. Patients were randomized to 1 of 2 telephone follow-up arms. If they did not mail their FIT kit within 4 weeks, they received a reminder call and were called again at 8 weeks if the test still was not received. RESULTS: A total of 620 patients were enrolled. Approximately 55% were female, 66% were African American, and 40% had limited literacy. The overall FIT completion rate was 68%: 69.2% in the automated telephone call arm and 67% in the personal call arm. Greater than one-half of the patients (range, 58%-60%) returned the FIT kit without receiving a telephone call. There was no difference noted with regard to the effectiveness of the follow-up calls; each increased the return rate by 9%. CONCLUSIONS: Providing FIT kits and literacy-appropriate education at regularly scheduled clinic visits with a follow-up telephone call when needed was found to increase CRC screening among low-income, rural patients. The lower cost automated call was just as effective as the personal call.

Labor Curves in Multiparous Women Related to Interbirth Intervals.

OBJECTIVE: Previous studies have shown that risk of cesarean section increases among multiparous women as interbirth interval increases. One possibility is that progress of labor may vary with interbirth interval, such that with longer intervals, labor curves of multiparas more closely resemble those of nulliparas. We sought to define labor curves among a cohort of multiparas with varying interbirth intervals. STUDY DESIGN: This was a retrospective cohort study of term multiparas with known interval from last delivery and only vaginal deliveries. Subjects were grouped by interval between the studied pregnancy and the most recent birth: 0 to 59, 60 to 119, and ≥120 months. Statistical analysis was performed using linear mixed effects model. Group slopes and intercepts were compared using model t-tests for individual effects. Length of second stage was compared using a Wilcoxon's rank-sum test. RESULTS: Groups did not differ significantly in demographic or obstetrical characteristics. Rate of dilation was similar between the 0 to 59 and 60 to 119 month groups (p = 0.38), but faster in the ≥120 month group compared with the 60 to 119 month group (p = 0.037). Median duration of second stage increased slightly with increased interbirth interval (p = 0.003). CONCLUSION: Prolonged interbirth interval is not associated with slower active phase of labor.

National evaluation of multidisciplinary quality metrics for head and neck cancer.

BACKGROUND: The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer. METHODS: The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality. RESULTS: In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83). CONCLUSIONS: Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society.

Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission.

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 µm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.

An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era.

The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Clinical features from 1650 adults with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2000-2010 at 7 NCCN cancer centers were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. Five predictors (age, lactate dehydrogenase (LDH), sites of involvement, Ann Arbor stage, ECOG performance status) were identified and a maximum of 8 points assigned. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5), and high (6-8). Compared with the IPI, the NCCN-IPI better discriminated low- and high-risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n = 1138), it also demonstrated enhanced discrimination for both low- and high-risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.

High Body Mass Index in Elderly Patients With DLBCL Treated With Rituximab-Containing Therapy Compensates for Negative Impact of Male Sex.

BACKGROUND: The impact of patient body habitus and sex on outcomes in diffuse large B-cell lymphoma (DLBCL) remains controversial. We investigated the impact of body mass index (BMI), body surface area (BSA), age, and sex on clinical outcomes in patients with DLBCL treated in the rituximab era. PATIENTS AND METHODS: Patients with de novo DLBCL (n=1,386) diagnosed between June 2000 and December 2010 treated with rituximab-containing chemotherapy were identified from the NCCN Oncology Outcomes Database for Non-Hodgkin's Lymphoma. Progression-free survival (PFS) and overall survival (OS) at 3 years were analyzed based on sex, age, and baseline BMI/BSA. RESULTS: High BMI was associated with a lower risk of disease progression or death than low or normal BMI, whereas male sex was associated with poor clinical outcomes, especially among elderly patients (age >60 years). Compared with elderly women, elderly men experienced worse PFS (3-year hazard ratio [HR], 1.5) and OS (3-year HR, 1.6), but these differences diminished with increases in BMI and BSA. In multivariable analysis, normal BMI compared with high BMI was independently associated with poor outcomes (3-year PFS HR, 1.5; OS HR, 1.6) after adjusting for sex. Notably, only 13% of elderly men had BMI less than 25 kg/m2 and only 26% had BSA less than 2 m2 CONCLUSIONS: Analysis of unselected patients with DLBCL treated with rituximab-containing chemotherapy confirmed an age-dependent disadvantage to male sex in treatment outcomes, but this effect is abrogated by higher levels of BMI and BSA in most North American men.

A comparative study of proliferative activity and tumor stage of pregnancy-associated melanoma (PAM) and non-PAM in gestational age women.

BACKGROUND: The influence of pregnancy on the development, progression, and prognosis of melanoma is controversial. OBJECTIVE: We sought to compare clinical characteristics, histologic features, and proliferative activity in pregnancy-associated melanoma (PAM) and melanoma in nonpregnant women of reproductive age (non-PAM). METHODS: In this retrospective cohort study, we reviewed medical records and pathology reports from women given a diagnosis of melanoma between 2006 and 2015. We also examined tumor proliferation rates using mitotic count and 2 immunohistochemical markers of proliferation, phosphohistone H3 and Ki-67. RESULTS: In 50 PAM and 122 non-PAM cases, a diagnosis of melanoma in situ was associated with PAM. Among invasive melanomas, there was no difference in proliferative activity between groups. Pregnancy status was also not associated with age at diagnosis, tumor site, Breslow depth, Clark level, ulceration, or overall stage. LIMITATIONS: This was a retrospective study with a small sample size of mostly patients with early-stage melanoma. CONCLUSIONS: In our study of primarily early-stage melanoma, pregnancy did not have a significant impact on tumor proliferation. Particularly for patients given a diagnosis of stage I melanoma who are undergoing close surveillance, a history of PAM should not outweigh traditional factors, such as advanced maternal age, in planning future pregnancies.

The utility of dermoscopy-guided histologic sectioning for the diagnosis of melanocytic lesions: A case-control study.

BACKGROUND: Dermoscopy allows for visualization of morphologic structures beyond the epidermis, including features that may indicate early malignant transformation. However, dermoscopic features are rarely considered during routine histologic sectioning, and areas of clinical concern may be missed during microscopic evaluation. OBJECTIVE: We assessed the diagnostic impact of a dermoscopy-guided micropunch score for the evaluation of melanocytic lesions. METHODS: In this case-control study, we evaluated 150 scored melanocytic lesions. Original tissue specimens were reprocessed to create a control group, in which a new score was introduced elsewhere in the lesion to guide an alternative plane of section. Slides were reviewed in a randomized, double-blinded manner to assess histologic features and render a diagnosis. Dermoscopy was also reviewed. RESULTS: The proportion of cases with a higher grade in the original, dermoscopy-guided section was statistically significant. Four invasive melanomas were exclusively identified using the scoring protocol. The presence of regression structures, negative pigment network, radial streaming or pseudopods, and irregular blotches were highly specific for a higher diagnostic grade. LIMITATIONS: This study is retrospective and reprocessing tissue does not perfectly mimic routine sectioning. CONCLUSION: Dermoscopy can identify important, histologically high-grade areas, and this information can be used to optimize the sectioning of melanocytic neoplasms.

Eye movements as probes of lexico-semantic processing in a patient with primary progressive aphasia.

Eye movement trajectories during a verbally cued object search task were used as probes of lexico-semantic associations in an anomic patient with primary progressive aphasia. Visual search was normal on trials where the target object could be named but became lengthy and inefficient on trials where the object failed to be named. The abnormality was most profound if the noun denoting the object could not be recognized. Even trials where the name of the target object was recognized but not retrieved triggered abnormal eye movements, demonstrating that retrieval failures can have underlying associative components despite intact comprehension of the corresponding noun.

Collagen matrix vs mitomycin-C in trabeculectomy and combined phacoemulsification and trabeculectomy: a randomized controlled trial.

BACKGROUND: Antifibrotic agents are commonly utilized to enhance the success rates of trabeculectomy. Novel approaches to further improve success rates and reduce the risks of complications are needed. The purpose of this study was to compare intraocular pressure (IOP)-lowering efficacy and safety of trabeculectomy or combined phacoemulsification and trabeculectomy with mitomycin-C (MMC) vs. Collagen Matrix (CM). METHODS: A prospective, multicenter, randomized controlled trial was performed. Ninety-five eyes of 94 patients with uncontrolled glaucoma despite medical therapy, without previous incisional glaucoma surgery underwent trabeculectomy (85 eyes) or combined phacoemulsification and trabeculectomy (10 eyes) and were randomized to MMC or CM. One eye of each subject was analyzed. Patients were followed for 24 months. The criteria for complete success were IOP >5 and ≤21 mmHg with at least a 20% reduction below medicated baseline without additional glaucoma surgery or medications. The main outcome measures were complete success rates at 24 months with Kaplan-Meier analysis and incidence of adverse events. RESULTS: The baseline IOPs were 20.4 ± 6.0 mmHg and 21.2 ± 6.1 (mean ± standard deviation, p = 0.49) on 3.2 ± 1.1 and 3.1 ± 1.0 medications (p = 0.53) compared to 11.8 ± 5.2 and 12.8 ± 3.7 (p = 0.36) on 0.5 ± 0.8 and 0.6 ± 1.0 medications (p = 0.63) at 2 years in the MMC and CM groups, respectively. Kaplan-Meier analysis demonstrated complete success rates were similar in both groups at 24 months: 38.4 ± 7.6% with MMC and 56.2 ± 7.9% with CM (mean ± standard error, p = 0.112, log rank test); however, a significantly higher incidence of failure due to persistent hypotony was observed with MMC (p = 0.002). CONCLUSIONS: Use of the CM implant at the time of trabeculectomy or combined phacoemulsification and trabeculectomy is associated with similar complete success rates compared to adjunctive MMC; however, the risk of persistent hypotony is higher with MMC. TRIAL REGISTRATION: ClinicalTrials.gov registration number NCT01440751 . Registered 9/14/11.

A cross-sectional study of carnitine deficiency and fatigue in pediatric cancer patients.

PURPOSE: Carnitine deficiency has been found in cancer patients and has been associated with fatigue. This study aimed to explore the prevalence of carnitine deficiency in pediatric cancer patients and its relationship with fatigue and other potential contributing factors. METHODS: Children with cancer or Langerhans cell histiocytosis who were receiving treatment or had completed therapy were eligible. Patients completed the Pediatric Functional Assessment of Chronic Illness-Fatigue, the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale, a numeric fatigue rating, and had carnitine levels obtained. Carnitine deficiency was defined as a total and/or free carnitine level less than normal for age or an acylcarnitine value higher than normal for age. RESULTS: Data from 142 children aged 8-17 were analyzed. Twenty-eight of 142 (19.7 %) had decreased total and 42.8 % (12/28) had decreased free carnitine levels. No patients had elevated acylcarnitine levels or elevated ratios. Patients with versus without carnitine deficiency differed by age (p = 0.043), treatment (p = 0.037), duration since last chemotherapy (p = 0.020), and body mass index (p = 0.010), but not fatigue, when all data were analyzed together. Yet, a negative relationship between fatigue and carnitine levels was found on a subgroup (off-therapy; fatigue worse than the norm). CONCLUSION: No significant association between fatigue and carnitine level was demonstrated when data from all patients were analyzed together; however, a significant yet unexpected relationship was found for patients who completed therapy and reported elevated fatigue. Given the small sample size, these results should be interpreted with caution. Future studies to explore impact upon excessive carnitine levels are warranted.

Psoriasis and Cardiometabolic Disease: A Brief, Focused, Educational Intervention on Cardiometabolic Risks.

BACKGROUND: To assess baseline knowledge and awareness of cardiometabolic comorbidities in subjects with psoriasis. To determine the impact of a verbal scripted educational intervention. METHODS: Fifty-six adults with a clinical diagnosis of moderate to severe psoriasis completed a 12-item questionnaire about psoriasis comorbidity awareness and knowledge at 2 time points: pre-intervention (PR-I) and post-intervention (PO-I). The PR-I questionnaire collected information on history of psoriasis and cardiometabolic disease. A 5-minute scripted educational intervention was administered during a single study visit to subjects immediately after PR-I but prior to PO-I questionnaires. Subjects also completed a final questionnaire at 2 months follow-up (2-MF). Responses were statistically analyzed using McNemar's test. RESULTS: Fifty-six subjects (26 females, 30 males, mean age 51 years, range 21 to 83 years) participated in the PR-I and PO-I and 46 (82%) participated in 2-MF. Significant improvements were noted for 10 of 11 questions between PR-I and PO-I, and 8 of the scores remained significantly improved (compared with baseline) at 2-MF (P<0.05). At 2-MF, 65% of subjects had seen a primary care physician within the 2-month interval from PO-I to 2-MF, and another 26% planned to visit a primary care physician in the near future. Furthermore, 85% had checked their blood pressure in the past 2 months. CONCLUSIONS: Measures of knowledge and awareness of psoriasis and cardiometabolic comorbidities were significantly improved at PO-I and retained for most measures at 2-MF. An educational intervention, as utilized in this study, warrants consideration to enhance cardiometabolic-based knowledge and awareness in patients with psoriasis.

J Drugs Dermatol. 2016;15(10):1176-1180.

The Effectiveness of a Physician-Only and Physician-Patient Intervention on Colorectal Cancer Screening Discussions Between Providers and African American and Latino Patients.

BACKGROUND: Physician recommendation of colorectal cancer (CRC) screening is a critical facilitator of screening completion. Providing patients a choice of screening options may increase CRC screening completion, particularly among racial and ethnic minorities. OBJECTIVE: Our purpose was to assess the effectiveness of physician-only and physician-patient interventions on increasing rates of CRC screening discussions as compared to usual care. DESIGN: This study was quasi-experimental. Clinics were allocated to intervention or usual care; patients in intervention clinics were randomized to receipt of patient intervention. PARTICIPANTS: Patients aged 50 to 75 years, due for CRC screening, receiving care at either a federally qualified health care center or an academic health center participated in the study. INTERVENTION: Intervention physicians received continuous quality improvement and communication skills training. Intervention patients watched an educational video immediately before their appointment. MAIN MEASURES: Rates of patient-reported 1) CRC screening discussions, and 2) discussions of more than one screening test. KEY RESULTS: The physician-patient intervention (n = 167) resulted in higher rates of CRC screening discussions compared to both physician-only intervention (n = 183; 61.1 % vs.50.3 %, p = 0.008) and usual care (n = 153; 61.1 % vs. 34.0 % p = 0.03). More discussions of specific CRC screening tests and discussions of more than one test occurred in the intervention arms than in usual care (44.6 % vs. 22.9 %,p = 0.03) and (5.1 % vs. 2.0 %, p = 0.036), respectively, but discussion of more than one test was uncommon. Across all arms, 143 patients (28.4 %) reported discussion of colonoscopy only; 21 (4.2 %) reported discussion of both colonoscopy and stool tests. CONCLUSIONS: Compared to usual care and a physician-only intervention, a physician-patient intervention increased rates of CRC screening discussions, yet discussions overwhelmingly focused solely on colonoscopy. In underserved patient populations where access to colonoscopy may be limited, interventions encouraging discussions of both stool tests and colonoscopy may be needed.

Comparing the Performance of the S-TOFHLA and NVS Among and Between English and Spanish Speakers.

Given the growing body of evidence demonstrating the significant implications of health literacy on a myriad of outcomes, researchers continue to incorporate health literacy metrics in studies. With this proliferation in measurement of health literacy in research, it has become increasingly important to understand how various health literacy tools perform in specific populations. Our objective was to compare the performance of two widely used tests, the Short Test of Functional Health Literacy in Adults (S-TOFHLA) and the Newest Vital Sign (NVS) among and between a sample of English and Spanish-speaking patients. Adults (N = 402) ages 50-75 years participating in a trial to promote colorectal cancer screening completed in-person interviews which included both measures of health literacy. In the full sample, the tests were moderately correlated (r = 0.69, p < .0001); however, there was a stronger correlation among those completing the test in Spanish (r = 0.83) as compared with English (r = 0.58, p < .0001). English speakers more often were categorized as having adequate literacy by the S-TOFHLA as compared with the NVS, whereas Spanish speakers scored consistently low on both instruments. These findings indicate that the categorization of participants into levels of literacy is likely to vary, depending on whether the NVS or S-TOFHLA is used for assessment, a factor which researchers should be aware of when selecting literacy assessments.

The Yale Pharyngeal Residue Severity Rating Scale: An Anatomically Defined and Image-Based Tool.

The Yale Pharyngeal Residue Severity Rating Scale was developed, standardized, and validated to provide reliable, anatomically defined, and image-based assessment of post-swallow pharyngeal residue severity as observed during fiberoptic endoscopic evaluation of swallowing (FEES). It is a five-point ordinal rating scale based on residue location (vallecula and pyriform sinus) and amount (none, trace, mild, moderate, and severe). Two expert judges reviewed a total of 261 FEES evaluations and selected a no residue exemplar and three exemplars each of trace, mild, moderate, and severe vallecula and pyriform sinus residue. Hard-copy color images of the no residue, 12 vallecula, and 12 pyriform sinus exemplars were randomized by residue location for hierarchical categorization by 20 raters with a mean of 8.3 years of experience (range 2-27 years) performing and interpreting FEES. Severity ratings for all images were performed by the same 20 raters, 2 weeks apart, and with the order of image presentations randomized. Intra-rater test-retest reliability, inter-rater reliability, and construct validity were determined by pooled multi-category multi-rater kappa statistics. Residue ratings were excellent for intra-rater reliability for vallecula (kappa = 0.957 ± 0.014) and pyriform sinus (kappa = 0.854 ± 0.021); very good to excellent for inter-rater reliability for vallecula (kappa = 0.868 ± 0.011) and pyriform sinus (kappa = 0.751 ± 0.011); and excellent for validity for vallecula (kappa = 0.951 ± 0.014) and pyriform sinus (kappa = 0.908 ± 0.017). Clinical uses include accurate classification of vallecula and pyriform sinus residue severity patterns as none, trace, mild, moderate, or severe for diagnostic purposes, determination of functional therapeutic change, and precise dissemination of shared information. Scientific uses include tracking outcome measures, demonstrating efficacy of interventions to reduce pharyngeal residue, investigating morbidity and mortality in relation to pharyngeal residue severity, and improving training and accuracy of FEES interpretation by students and clinicians. The Yale Pharyngeal Residue Severity Rating Scale is a reliable, validated, anatomically defined, and image-based tool to determine residue location and severity based on FEES.

The changing landscape of phase II/III metastatic NSCLC clinical trials and the importance of biomarker selection criteria.

Over the last decade, new cytotoxic treatments and targeted therapies have altered treatment paradigms for patients with metastatic non-small cell lung cancer (NSCLC). We sought to analyze the impact of histology and biomarker selection criteria on outcomes of clinical trials in metastatic NSCLC reported over the last decade at the American Society of Clinical Oncology (ASCO) Annual Meeting. Data were collected from ASCO abstracts of Phase II-IV clinical trials for patients with metastatic NSCLC from 2004-2014. 770 of 2,989 identified metastatic NSCLC category abstracts met selection criteria. Despite a decline in the number of abstracts from 107 to 46 abstracts annually over this period, the proportion of trials with positive progression free survival (PFS) and overall survival (OS) outcomes has increased significantly. Trials with histology selection (6%) or molecular biomarker (15%) criteria were more likely to result in an improvement in PFS than those without selection criteria (21% vs. 8%, p = 0.0001 and 31% vs. 10%, p < 0.0001, respectively). These data demonstrate profound changes in the clinical trial landscape over the last 10 years with significantly increasing proportion of trials with positive outcomes. These changes are likely attributed to the use of histology and biomarker selection criteria in clinical trial design.

F-18 FDG-PET predicts outcomes for patients receiving total lymphoid irradiation and autologous blood stem-cell transplantation for relapsed and refractory Hodgkin lymphoma.

Total lymphoid irradiation (TLI) followed by high-dose chemotherapy and autologous haematopoietic stem cell transplant (aHSCT) is an effective strategy for patients with relapsed/refractory classical Hodgkin lymphoma (HL). We report outcomes for patients with relapsed/refractory HL who received TLI followed by high-dose chemotherapy and aHSCT. Pre-transplant fludeoxyglucose positron emission tomography (FDG-PET) studies were scored on the 5-point Deauville scale. Of 51 patients treated with TLI and aHSCT, 59% had primary refractory disease and 63% had active disease at aHSCT. The 10-year progression-free survival (PFS) and overall survival (OS) for all patients was 56% and 54%, respectively. Patients with complete response (CR) by PET prior to aHSCT had a 5-year PFS and OS of 85% and 100% compared to 52% and 48% for those without CR (P = 0·09 and P = 0·007, respectively). TLI and aHSCT yields excellent disease control and long-term survival rates for patients with relapsed/refractory HL, including those with high-risk disease features. Achievement of CR with salvage therapy is a powerful predictor of outcome.

Clinical benefits of above-standard dose of octreotide LAR in patients with neuroendocrine tumors for control of carcinoid syndrome symptoms: a multicenter retrospective chart review study.

BACKGROUND: Octreotide LAR is used in patients for control of carcinoid syndrome (CS) and other symptoms of hormone hypersecretion. The aim of this study was to examine reasons for octreotide LAR dose escalation and observe CS symptom improvement in patients with neuroendocrine tumors (NETs) who underwent octreotide LAR dose escalation at three cancer referral centers. METHODS: Medical records for patients with diagnosis of carcinoid or pancreatic NET who had received one dose or more of octreotide LAR above 30 mg every 4 weeks from 2000 to 2012 were reviewed. Reasons for dose escalation and symptomatic outcomes were abstracted for each patient 3 months prior to and up to 12 months following the dose escalation. RESULTS: Of the evaluated 239 NET patients, 53% were male, mean age at first dose escalation was 60 years (standard deviation [SD]: 11 years), and mean time from octreotide LAR initiation to first dose escalation was 1.7 years (SD: 2.0 years). The primary reasons reported for dose escalation were carcinoid or hormonal syndrome (62%) or radiographic progression (28%). The most common dose changes at the first dose escalation were 40 mg every 4 weeks (71%) and 60 mg every 4 weeks (18%). Of 90 patients in whom flushing was reported prior to first dose escalation, 73 (81%) were reported to have experienced improvement or resolution of their symptoms following the dose escalation. Of 107 patients who were reported to have experienced diarrhea before the first dose escalation, 85 (79%) were reported to have experienced improvement or resolution after first dose escalation. CONCLUSION: The goal of improved symptom control is a common reason for dose escalation of octreotide LAR. This study suggests that escalation to above the standard dose of octreotide LAR of 30 mg every 4 weeks may result in improved CS symptom control.

Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: involvement of the RB-microRNA axis.

BACKGROUND: The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription. Recent studies suggest that Smurf2 functions as a tumor suppressor in mice. However, no inactivating mutation of SMURF2 has been reported in human, and information about Smurf2 expression in human cancer remains limited or complicated. Here we demonstrate that Smurf2 expression is downregulated in human breast cancer tissues, especially of the triple-negative subtype, and address the mechanism of Smurf2 downregulation in triple-negative breast cancer cells. METHODS: Human breast cancer tissues (47 samples expressing estrogen receptor (ER) and 43 samples with triple-negative status) were examined by immunohistochemistry for the expression of Smurf2. Ten widely-studied human breast cancer cell lines were examined for the expression of Smurf2. Furthermore, microRNA-mediated regulation of Smurf2 was investigated in triple-negative cancer cell lines. RESULTS: Immunohistochemical analysis showed that benign mammary epithelial cells expressed high levels of Smurf2, so did cells in ductal carcinomas in situ. In contrast, invasive ductal carcinomas showed focal or diffuse decrease in Smurf2 expression, which was observed more frequently in triple-negative tumors than in ER-positive tumors. Consistently, human triple-negative breast cancer cell lines such as BT549, MDA-MB-436, DU-4475 and MDA-MB-468 cells showed significantly lower expression of Smurf2 protein, compared to ER + or HER2+ cell lines. Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in the expression of the microRNAs. CONCLUSIONS: This study provides evidence of posttranscriptional downregulation of Smurf2 in triple-negative breast cancers, and demonstrates that the loss of RB function is involved in microRNA-mediated interference with Smurf2 translation. The new link from RB inactivation to Smurf2 downregulation is likely to play a role in malignant phenotypes of triple-negative breast cancer cells.