Protocol for a cluster-randomized trial of a school-based skin cancer preventive intervention for adolescents.

BACKGROUND: Adolescents infrequently use sun protection and engage in intentional tanning more frequently compared to other age groups, leading to increased ultraviolet radiation (UVR) exposure that heightens skin cancer risk across the lifespan. High schools are therefore an ideal setting for offering skin cancer preventive interventions. Yet, there are limited UVR protection interventions for high school students, especially those that are personalized, tested using randomized designs, and include long-term outcome assessment to determine the durability of intervention effects. METHOD: The Sun-safe Habits Intervention and Education (SHINE) cluster-randomized trial will test a novel, personalized intervention that targets high school adolescents' sun protection and tanning behaviors, and tracks their outcomes for up to one year following intervention. Enrolled high schools will be randomized to receive either the personalized SHINE intervention, which includes facial UVR photographs and sun protection action planning, or standard education using publicly available materials. Students in both conditions will receive information about skin cancer, sun protection, and skin self-examination. Outcome variables will include students' sun protection and tanning behaviors and sunburn occurrence. Potential moderators (e.g., race/ethnicity) and mediators (e.g., self-efficacy) will also be assessed and tested. CONCLUSIONS: This trial examines the efficacy of a personalized intervention targeting sun protection and tanning of high school students. The project will lead to new scientific understanding of the theoretical mechanisms underlying outcomes and moderators of the intervention effects, which will inform future intervention tailoring to meet the needs of vulnerable subgroups.

Low-Value Prostate Cancer Screening Among Young Men With Private Insurance.

INTRODUCTION: No professional society guidelines recommend PSA screening in men younger than age 40; however, data suggest testing occurs at meaningful rates in this age group. The purpose of this study was to identify the rate of PSA testing in men under 40. METHODS: This is a population-based, retrospective cohort study from 2008 to 2017. Using the MarketScan database, rates of testing for the sum of the annual population of men at risk were evaluated. Descriptive statistics and statistical analyses were performed in men continuously enrolled in the database for at least 5 year. Results were stratified by receipt of PSA testing and by age group. The association of diagnoses and Charlson Comorbidity Index with receipt of PSA test was evaluated using multivariable logistic regression models. RESULTS: We identified 3,230,748 men ages 18 to 39 who were enrolled for at least 5 years. The rate of ever receiving PSA testing was 0.6%, 1.7%, 8.5%, and 9.1% in men less than 25, 25 to 29, 30 to 34, and 35 to 39 years, respectively. Multivariable logistic regression showed that relative to all men 18 to 39, patients who received PSA testing had higher odds of a diagnosis of hypogonadism (OR 11.77) or lower urinary tract symptoms (OR 4.19). CONCLUSIONS: This study found a remarkable number of young men receive PSA testing, with a strong association with diagnoses of lower urinary tract symptoms and hypogonadism. Clinicians need to be educated that assessment and management guidelines for other urologic diagnoses now defer PSA testing to prostate cancer screening guidelines.

Impact of choosing wisely on imaging in men with newly diagnosed prostate cancer.

INTRODUCTION: Encouraging the appropriate use of staging imaging in patients with newly diagnosed prostate cancer remains a challenge. Assessing the effects of national efforts may help guide future initiatives in curtailing low-value care. The purpose of this study was to determine the impact of the Choosing Wisely campaign on imaging utilization among men with prostate cancer. METHODS: Surveillance, Epidemiology, and End Results - Medicare data were used to complete a longitudinal population-based study of men diagnosed with prostate cancer from 2007 to 2015. An interrupted time series analysis evaluated the impact of the Choosing Wisely campaign on trends of imaging utilization. RESULTS: From 2007 to 2015 imaging utilization in low-risk patients decreased, with computed tomography (CT) usage declining from 45.0% to 34.4% (P<0.001) and nuclear medicine bone scan (NMBS) from 27.8% to 11.7% (P<0.001). Choosing Wisely likely contributed to an absolute reduction of 2.9% (P=0.03) in utilization of NMBS in the low-risk population. Imaging usage for all modalities increased in the high-risk population, but with 32.8% continuing to not receive guideline-supported imaging. CONCLUSIONS: In 2012, the Choosing Wisely campaign sought to decrease inappropriate staging imaging for men with low-risk prostate cancer and encourage stewardship of medical resources. Overall decreases in staging imaging trends suggest a move towards higher value care. However, this study found that the Choosing Wisely recommendations had a modest impact on utilization of NMBS, but not CT or PET scans. These results may help inform future efforts to promote guideline concordant imaging.

Implementation and outcomes of a clinician-directed intervention to improve antibiotic prescribing for acute respiratory tract infections within the Veterans' Affairs Healthcare System.

OBJECTIVE: To determine whether a clinician-directed acute respiratory tract infection (ARI) intervention was associated with improved antibiotic prescribing and patient outcomes across a large US healthcare system. DESIGN: Multicenter retrospective quasi-experimental analysis of outpatient visits with a diagnosis of uncomplicated ARI over a 7-year period. PARTICIPANTS: Outpatients with ARI diagnoses: sinusitis, pharyngitis, bronchitis, and unspecified upper respiratory tract infection (URI-NOS). Outpatients with concurrent infection or select comorbid conditions were excluded. INTERVENTION(S): Audit and feedback with peer comparison of antibiotic prescribing rates and academic detailing of clinicians with frequent ARI visits. Antimicrobial stewards and academic detailing personnel delivered the intervention; facility and clinician participation were voluntary. MEASURE(S): We calculated the probability to receive antibiotics for an ARI before and after implementation. Secondary outcomes included probability for a return clinic visits or infection-related hospitalization, before and after implementation. Intervention effects were assessed with logistic generalized estimating equation models. Facility participation was tracked, and results were stratified by quartile of facility intervention intensity. RESULTS: We reviewed 1,003,509 and 323,023 uncomplicated ARI visits before and after the implementation of the intervention, respectively. The probability to receive antibiotics for ARI decreased after implementation (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78-0.86). Facilities with the highest quartile of intervention intensity demonstrated larger reductions in antibiotic prescribing (OR, 0.69; 95% CI, 0.59-0.80) compared to nonparticipating facilities (OR, 0.89; 95% CI, 0.73-1.09). Return visits (OR, 1.00; 95% CI, 0.94-1.07) and infection-related hospitalizations (OR, 1.21; 95% CI, 0.92-1.59) were not different before and after implementation within facilities that performed intensive implementation. CONCLUSIONS: Implementation of a nationwide ARI management intervention (ie, audit and feedback with academic detailing) was associated with improved ARI management in an intervention intensity-dependent manner. No impact on ARI-related clinical outcomes was observed.

Cardiovascular disease risk in long-term breast cancer survivors: A population-based cohort study.

BACKGROUND: Breast cancer survival is increasing, making late effects such as cardiovascular disease (CVD) more relevant. The purpose of this study was to evaluate incident CVD following breast cancer diagnosis among long-term survivors and to investigate possible risk factors for CVD. METHODS: A population-based cohort of 6641 breast cancer survivors diagnosed between 1997 and 2009 who survived at least 10 years was identified within the Utah Cancer Registry. In addition, 36,612 cancer-free women from the general population, matched by birth year and state, were identified within the Utah Population Database. Cox proportional hazards models were used to calculate CVD hazard ratios (HRs) for >10 to 15 and >15 years. RESULTS: Long-term breast cancer survivors had an increased risk of newly diagnosed diseases of the circulatory system (HR, 1.32; 99% confidence interval [CI], 1.00-1.75) from 10 to 15 years following cancer diagnosis compared with the general population. No increased CVD risks were observed after 15 years. Breast cancer survivors with Charlson Comorbidity Index score ≥2 had a significantly higher risk of diseases of the circulatory system (HR, 2.64; 95% CI, 1.08-6.45) beyond 10 years following breast cancer diagnosis. Similarly, older age, obesity, lower education, and family history of CVD and breast cancer were risk factors for heart and circulatory system diseases among long-term breast cancer survivors. CONCLUSION: Risk of CVD compared to the general population was moderate among this cohort of long-term breast cancer survivors between 10 to 15 years since cancer diagnosis. Awareness of CVD risks is important for breast cancer survivors.

Characteristics and Outcomes of US Patients Hospitalized With COVID-19.

BACKGROUND: Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. OBJECTIVE: To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. METHODS: A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. RESULTS: Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. CONCLUSIONS: In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

A time-varying model of the dynamics of smoking lapse.

OBJECTIVE: The majority of smokers who make a quit attempt experience their first lapse within the first week of quitting, yet limited research to date has examined how the strength and direction of the relationship between smoking risk factors and lapse may change over longer periods of time. Time-varying effect modeling (TVEM) was used to address this gap. METHOD: A diverse sample (N = 325) of adult smokers completed ecological momentary assessments of risk factors for lapse for 28 days after quitting. TVEM was used to examine the relationship between risk factors (abstinence self-efficacy, positive affect, positive coping expectancies, smoking expectancies, motivation, negative affect, stress, and urge) and lapse for 28 days postquit. RESULTS: Some associations were stable (e.g., negative affect, motivation), whereas others varied over time. Abstinence self-efficacy, positive affect, and positive coping expectancies were most strongly associated with lapse between Days 3 and 8 postquit. The association of urge with lapse was strongest between Days 4 and 10, as well as near the end of the quit attempt. Stress was also most strongly associated with lapse near the beginning and end of the postquit period and was the only predictor associated with lapse on quit date. The strength of the association between smoking expectancies and lapse increased over time. CONCLUSION: There may be periods during a quit attempt when certain risk factors are more strongly related to lapse. This work has relevance for tailoring interventions designed to deliver intervention components in particular contexts or times of need. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Applying economic incentives to increase effectiveness of an outpatient weight loss program (TRIO) - A randomized controlled trial.

The prevalence of overweight and obesity has more than doubled in the past three decades, leading to rising rates of non-communicable diseases. This study tests whether adding a payment/rewards (term reward) program to an existing evidence-based weight loss program can increase weight loss and weight loss maintenance. We conducted a parallel-group randomized controlled trial from October 2012 to October 2015 with 161 overweight or obese individuals randomized to either control or reward arm in a 1:2 ratio. Control and reward arm participants received a four month weight loss program at the LIFE (Lifestyle Improvement and Fitness Enhancement) Centre at Singapore General Hospital. Those in the reward arm paid a fee of S$165.00 (1US$ = 1.35S$) to access a program that provided rewards of up to S$660 for meeting weight loss and physical activity goals. Participants could choose to receive rewards as guaranteed cash payments or a lottery ticket with a 1 in 10 chance of winning but with the same expected value. The primary outcome was weight loss at months 4, 8, and 12. 161 participants were randomized to control (n = 54) or reward (n = 107) arms. Average weight loss was more than twice as great in the reward arm compared to the control arm at month 4 when the program concluded (3.4 kg vs 1.4 kg, p < 0.01), month 8 when rewards concluded (3.3 kg vs 1.8 kg, p < 0.05), and at month 12 (2.3 kg vs 0.8 kg, p < 0.05). These results reveal that a payment/rewards program can be used to improve weight loss and weight loss maintenance when combined with an evidence-based weight loss program. Future efforts should attempt to replicate this approach and identify how to cost effectively expand these programs to maximize their reach. This study is registered at www.clinicaltrials.gov (Identifier: NCT01533454).

Effectiveness of activity trackers with and without incentives to increase physical activity (TRIPPA): a randomised controlled trial.

BACKGROUND: Despite the increasing popularity of activity trackers, little evidence exists that they can improve health outcomes. We aimed to investigate whether use of activity trackers, alone or in combination with cash incentives or charitable donations, lead to increases in physical activity and improvements in health outcomes. METHODS: In this randomised controlled trial, employees from 13 organisations in Singapore were randomly assigned (1:1:1:1) with a computer generated assignment schedule to control (no tracker or incentives), Fitbit Zip activity tracker, tracker plus charity incentives, or tracker plus cash incentives. Participants had to be English speaking, full-time employees, aged 21-65 years, able to walk at least ten steps continuously, and non-pregnant. Incentives were tied to weekly steps, and the primary outcome, moderate-to-vigorous physical activity (MVPA) bout min per week, was measured via a sealed accelerometer and assessed on an intention-to-treat basis at 6 months (end of intervention) and 12 months (after a 6 month post-intervention follow-up period). Other outcome measures included steps, participants meeting 70 000 steps per week target, and health-related outcomes including weight, blood pressure, and quality-of-life measures. This trial is registered at ClinicalTrials.gov, number NCT01855776. FINDINGS: Between June 13, 2013, and Aug 15, 2014, 800 participants were recruited and randomly assigned to the control (n=201), Fitbit (n=203), charity (n=199), and cash (n=197) groups. At 6 months, compared with control, the cash group logged an additional 29 MVPA bout min per week (95% CI 10-47; p=0·0024) and the charity group an additional 21 MVPA bout min per week (2-39; p=0·0310); the difference between Fitbit only and control was not significant (16 MVPA bout min per week [-2 to 35; p=0·0854]). Increases in MVPA bout min per week in the cash and charity groups were not significantly greater than that of the Fitbit group. At 12 months, the Fitbit group logged an additional 37 MVPA bout min per week (19-56; p=0·0001) and the charity group an additional 32 MVPA bout min per week (12-51; p=0·0013) compared with control; the difference between cash and control was not significant (15 MVPA bout min per week [-5 to 34; p=0·1363]). A decrease in physical activity of -23 MVPA bout min per week (95% CI -42 to -4; p=0·0184) was seen when comparing the cash group with the Fitbit group. There were no improvements in any health outcomes (weight, blood pressure, etc) at either assessment. INTERPRETATION: The cash incentive was most effective at increasing MVPA bout min per week at 6 months, but this effect was not sustained 6 months after the incentives were discontinued. At 12 months, the activity tracker with or without charity incentives were effective at stemming the reduction in MVPA bout min per week seen in the control group, but we identified no evidence of improvements in health outcomes, either with or without incentives, calling into question the value of these devices for health promotion. Although other incentive strategies might generate greater increases in step activity and improvements in health outcomes, incentives would probably need to be in place long term to avoid any potential decrease in physical activity resulting from discontinuation. FUNDING: Ministry of Health, Singapore.

A Fit-Fat Index for Predicting Incident Diabetes in Apparently Healthy Men: A Prospective Cohort Study.

BACKGROUND: The purpose of this study was to examine the impact of combined cardiorespiratory fitness and waist-to-height ratio in the form of a fit-fat index on incident diabetes risk. Additionally, the independent predictive performance of cardiorespiratory fitness, waist-to-height ratio, and body mass index also were estimated and compared. METHODS: This was a prospective cohort study of 10,381 men who had a normal electrocardiogram and no history of major chronic disease at baseline from 1979 to 2005. Random survival forest models and traditional Cox proportional hazards models were used to predict diabetes at 5-, 10-, and 15-year incidence horizons. RESULTS: Overall, 4.8% of the participants developed diabetes. Receiver operating characteristic curve analyses for incidence risk demonstrated good discrimination using random survival forest models across fitness and fatness measures; Cox models were poor to fair. The differences between fitness and fatness measures across horizons were clinically negligible. Smoothed random survival forest estimates demonstrated the impact of each fitness and fatness measure on incident diabetes was intuitive and graded. CONCLUSIONS: Although fitness and fatness measures showed a similar discriminative ability in predicting incident diabetes, unique to the study was the ability of the fit-fat index to demonstrate a better indication of incident risk when compared to fitness or fatness alone. A single index combining cardiorespiratory fitness and waist-to-height ratio may be more useful because it can indicate improvements in either or both of the measures.

Design and baseline characteristics of participants in the TRial of Economic Incentives to Promote Physical Activity (TRIPPA): a randomized controlled trial of a six month pedometer program with financial incentives.

Non-communicable diseases (NCDs) are emerging as the predominant global health challenge of this century. Physical inactivity is one of the primary risk factors for NCDs. Therefore, increasing physical activity levels is a public health imperative. The arrival of affordable wearable technologies, such as wireless pedometers, provides one strategy for encouraging walking. However, the effectiveness of these technologies in promoting sustained behavior change has not been established. Insights from economics suggest that incentives may be a useful strategy for increasing maintenance and effectiveness of behavior change interventions, including physical activity interventions that rely on wearable technologies. The aim of this trial is to test the effectiveness of a common wireless pedometer with or without one of two types of incentives (cash or donations to charity) for reaching weekly physical activity goals. We present here the design and baseline characteristics of participants of this four arm randomized controlled trial. 800 full-time employees (desk-bound office workers) belonging to 15 different worksites (on average, 53 (sd: 37) employees at each worksite) were successfully randomized to one of four study arms. If shown to be effective, wearable technologies in concert with financial incentives may provide a scalable and affordable health promotion strategy for governments and employers seeking to increase the physical activity levels of their constituents.

Lamina cribrosa visibility using optical coherence tomography: comparison of devices and effects of image enhancement techniques.

PURPOSE: To compare the visibility of the lamina cribrosa (LC) in optic disc images acquired from 60 glaucoma and 60 control subjects using three optical coherence tomography (OCT) devices, with and without enhanced depth imaging (EDI) and adaptive compensation (AC). METHODS: A horizontal B-scan was acquired through the center of the disc using two spectral-domain (Spectralis and Cirrus; with and without EDI) and a swept-source (DRI) OCT. Adaptive compensation was applied post acquisition to improve image quality. To assess LC visibility, four masked observers graded the 1200 images in a randomized sequence. The anterior LC was graded from 0 to 4, the LC insertions from 0 to 2, and the posterior LC either 0 or 1. The effect of EDI, AC, glaucoma severity, and other clinical/demographic factors on LC visibility was assessed using generalized estimating equations. RESULTS: The anterior LC was the most detectable feature, followed by the LC insertions. Adaptive compensation improved anterior LC visibility independent of EDI. Cirrus+EDI+AC generated the greatest anterior LC visibility grades (2.79/4). For LC insertions visibility, DRI+AC was the best method (1.10/2). Visibility of the posterior LC was consistently poor. Neither glaucoma severity nor clinical/demographic factors consistently affected LC visibility. CONCLUSIONS: Adaptive compensation is superior to EDI in improving LC visibility. Visibility of the posterior LC remains poor suggesting impracticality in using LC thickness as a glaucoma biomarker.

Presence of and correction for interviewer error on an instrument assessing cognitive function of older adults.

AIM: To determine the extent of interviewer error on the Short Portable Mental Status Questionnaire (SPMSQ), the association between interviewer-level variables and SPMSQ score, compare the prevalence of SPMSQ cognitive status categories before and after correction for interviewer error, and identify SPMSQ items prone to interviewer error. METHODS: Data of 4542 older adults from a national survey in Singapore were utilized. Multilevel models, which adjusted for respondent-level variables known to be associated with cognitive status, were utilized to determine the intraclass correlation on the SPMSQ, association of interviewer-level variables (age, ethnicity, education and number of interviews carried out) with SPMSQ and identify SPMSQ items prone to interviewer error. RESULTS: The intraclass correlation, after adjusting for respondent-level variables, was 0.265. Interviewer educational status was associated with SPMSQ score. Correction for interviewer error resulted in an "improvement" in cognitive status of a substantial proportion of those initially classified as moderately or severely impaired. Two of the SPMSQ items, "Please count backward from 20 by 3" and "When were you born?" were particularly prone to interviewer error. CONCLUSIONS: Investigators using the SPMSQ, and potentially, other instruments, for assessing cognitive function in surveys of older adults and using face-to-face interviews for data collection should be cognizant of the sensitivity of such instruments to interviewer error. Intensive training of interviewers to standardize instrument administration as well as assessment for interviewer error and its correction, using appropriate statistical models, such as multilevel models, is warranted.

Development of a score and probability estimate for detecting angle closure based on anterior segment optical coherence tomography.

PURPOSE: To develop a score along with an estimated probability of disease for detecting angle closure based on anterior segment optical coherence tomography (AS OCT) imaging. DESIGN: Cross-sectional study. METHODS: A total of 2047 subjects 50 years of age and older were recruited from a community polyclinic in Singapore. All subjects underwent standardized ocular examination including gonioscopy and imaging by AS OCT (Carl Zeiss Meditec). Customized software (Zhongshan Angle Assessment Program) was used to measure AS OCT parameters. Complete data were available for 1368 subjects. Data from the right eyes were used for analysis. A stepwise logistic regression model with Akaike information criterion was used to generate a score that then was converted to an estimated probability of the presence of gonioscopic angle closure, defined as the inability to visualize the posterior trabecular meshwork for at least 180 degrees on nonindentation gonioscopy. RESULTS: Of the 1368 subjects, 295 (21.6%) had gonioscopic angle closure. The angle closure score was calculated from the shifted linear combination of the AS OCT parameters. The score can be converted to an estimated probability of having angle closure using the relationship: estimated probability = e(score)/(1 + e(score)), where e is the natural exponential. The score performed well in a second independent sample of 178 angle-closure subjects and 301 normal controls, with an area under the receiver operating characteristic curve of 0.94. CONCLUSIONS: A score derived from a single AS OCT image, coupled with an estimated probability, provides an objective platform for detection of angle closure.

Non-communicable diseases and injuries in Pakistan: strategic priorities.

Non-communicable diseases, including cardiovascular diseases, cancers, respiratory diseases, diabetes, and mental disorders, and injuries have become the major causes of morbidity and mortality in Pakistan. Tobacco use and hypertension are the leading attributable risk factors for deaths due to cardiovascular diseases, cancers, and respiratory diseases. Pakistan has the sixth highest number of people in the world with diabetes; every fourth adult is overweight or obese; cigarettes are cheap; antismoking and road safety laws are poorly enforced; and a mixed public-private health-care system provides suboptimum care. Furthermore, almost three decades of exposure to sociopolitical instability, economic uncertainty, violence, regional conflict, and dislocation have contributed to a high prevalence of mental health disorders. Projection models based on the Global Burden of Disease 2010 data suggest that there will be about 3·87 million premature deaths by 2025 from cardiovascular diseases, cancers, and chronic respiratory diseases in people aged 30-69 years in Pakistan, with serious economic consequences. Modelling of risk factor reductions also indicate that Pakistan could achieve at least a 20% reduction in the number of these deaths by 2025 by targeting of the major risk factors. We call for policy and legislative changes, and health-system interventions to target readily preventable non-communicable diseases in Pakistan.

Classification algorithms based on anterior segment optical coherence tomography measurements for detection of angle closure.

OBJECTIVE: A recent study found that a combination of 6 anterior segment optical coherence tomography (ASOCT) parameters (anterior chamber area, volume, and width [ACA, ACV, ACW], lens vault [LV], iris thickness at 750 µm from the scleral spur, and iris cross-sectional area) explain >80% of the variability in angle width. The aim of this study was to evaluate classification algorithms based on ASOCT measurements for the detection of gonioscopic angle closure. DESIGN: Cross-sectional study. PARTICIPANTS: We included 2047 subjects aged ≥50 years. METHODS: Participants underwent gonioscopy and ASOCT (Carl Zeiss Meditec, Dublin, CA). Customized software (Zhongshan Angle Assessment Program, Guangzhou, China) was used to measure ASOCT parameters in horizontal ASOCT scans. Six classification algorithms were considered (stepwise logistic regression with Akaike information criterion, Random Forest, multivariate adaptive regression splines, support vector machine, naïve Bayes' classification, and recursive partitioning). The ASOCT-derived parameters were incorporated to generate point and interval estimates of the area under the receiver operating characteristic (AUC) curves for these algorithms using 10-fold cross-validation as well as 50:50 training and validation. MAIN OUTCOME MEASURES: We assessed ASOCT measurements and angle closure. RESULTS: Data on 1368 subjects, including 295 (21.6%) subjects with gonioscopic angle closure were available for analysis. The mean (±standard deviation) age was 62.4±7.5 years and 54.8% were females. Angle closure subjects were older and had smaller ACW, ACA, and ACV; greater LV; and thicker irides (P<0.001 for all). For both, the 10-fold cross-validation and the 50:50 training and validation methods, stepwise logistic regression was the best algorithm for detecting eyes with gonioscopic angle closure with testing set AUC of 0.954 (95% confidence interval [CI], 0.942-0.966) and 0.962 (95% CI, 0.948-0.975) respectively, whereas recursive partitioning had relatively the poorest performance with testing set AUC 0.860 (95% CI, 0.790-0.930) and 0.905 (95% CI, 0.876-0.933), respectively. This algorithm performed similarly well (AUC, 0.957) in a second independent sample of 200 angle closure subjects and 302 normal controls. CONCLUSIONS: A classification algorithm based on stepwise logistic regression that used a combination of 6 parameters obtained from a single horizontal ASOCT scan identified subjects with gonioscopic angle closure>95% of the time. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Expert estimates of caregiver hours for older Singaporeans with dementia.

AIM: To obtain experts' estimates of the number of non-medical care hours required by older Singaporeans at different stages of ageing-related dementia, with low or high behavioural features. METHODS: Experts on dementia in Singapore attended one of two meetings where they provided estimates of the number of care hours required for individuals at mild, moderate and severe levels of dementia with either low or high behavioural features. The experts were shown the collated responses, given an opportunity to discuss as a group, and then polled again. RESULTS: The estimated mean care hours varied by dementia severity and the level of behavioural features. There was no interaction between dementia severity and behavioural features. CONCLUSION: Estimated care hours needed by individuals with dementia is independently influenced by severity of dementia and behavioural features. These estimates may be useful for policy-makers in projecting the impact of caregiving.

Cetuximab in the first-line treatment of K-ras wild-type metastatic colorectal cancer: the choice and schedule of fluoropyrimidine matters.

BACKGROUND: Cetuximab, a monoclonal antibody against the epidermal growth factor receptor, inconsistently improves response rates (RR), progression-free survival (PFS) and overall survival (OS) in the first-line treatment of advanced colorectal cancer patients with K-ras wild-type (WT) tumors. METHODS: We performed a meta-analysis of four trials where K-ras WT Pts received a fluoropyrimidine (infusional vs. bolus 5-fluorouracil (5-FU) vs. capecitabine) and oxaliplatin or irinotecan with and without cetuximab (CRYSTAL, OPUS, COIN and NORDIC VII trials) and two trials, where K-ras WT and mutant patients received cetuximab and a fluoropyrimidine (capecitabine in a German AIO study and infusional 5-FU in the CECOG study) with oxaliplatin versus irinotecan. We sought to determine whether the choice of fluoropyrimidine or of oxaliplatin versus irinotecan affects the response to cetuximab. Meta-analysis was performed in the context of a mixed effects model with a random effect for each study. RESULTS: Only patients treated with infusional 5-FU-based chemotherapy derived benefit from cetuximab. Relative to infusional 5-FU, patients treated with capecitabine/bolus 5-FU-based doublet chemotherapy had a 42 % (95 % CI 21-58 %; p < 0.001) decrease in response probability and a 52 % (95 % CI 20-93 %; p < 0.001) and 33 % (95 % CI 7-65 %; p = 0.012) increase, respectively, in risk of progression and death. The choice of oxaliplatin or irinotecan did not affect benefit from cetuximab. CONCLUSION: The lack of benefit for cetuximab with capecitabine/bolus 5-FU regimens is unexpected. Cetuximab should only be used with infusional 5-FU regimens in the first-line treatment of K-ras WT colorectal cancer patients. Further study is urgently needed to elucidate the basis of this observation.

Gefitinib vs. chemotherapy as first-line therapy in advanced non-small cell lung cancer: meta-analysis of phase III trials.

BACKGROUND: Gefitinib is an oral tyrosine kinase inhibitor against the epidermal growth factor receptor (EGFR). It has been shown to be active in patients with advanced non-small cell lung cancer (NSCLC) whose tumors contain EGFR mutations. METHODS: We performed a meta-analysis of four randomized studies that compared gefitinib with chemotherapy in the first-line treatment of patients with advanced NSCLC: IPASS, North-East Japan, West Japan and first-SIGNAL studies. Patients were selected either on the basis of known EGFR mutations or based on clinicopathologic criteria - non-smokers with adenocarcinomas - associated with increased likelihood of EGFR mutations. RESULTS: Nearly 2000 patients were enrolled on these four trials. Median ages ranged from 57 to 64years. Seventy-six percent were women and 86% were non-smokers. Overall, gefitinib was associated with significantly less toxicity than chemotherapy and improved quality-of-life. Gefitinib also produced higher response rates in the EGFR mutation-positive patients (72% vs. 38%, odds ratio 4.04, p<10(-15)), as well as improved progression-free survival (PFS; hazard ratio 0.45, p<10(-16)). Overall survival (OS) was not significantly different between treatment groups (p=0.35). CONCLUSIONS: This meta-analysis confirms the results of each individual study and narrows the confidence intervals of these results. In patients with known EGFR mutations or whose tumors are likely to harbor a mutation, upfront gefitinib or chemotherapy are associated with similar OS. Gefitinib is associated with less fatigue, myelosuppression and nausea than chemotherapy (but produces more skin rash, diarrhea and pneumonitis). Patients receiving gefitinib have improved quality-of-life compared to those receiving chemotherapy, making it an appropriate first-line choice.

Clinical and MRI findings associated with false-positive knee MR diagnoses of medial meniscal tears.

OBJECTIVE: The objective of our study was to determine if false-positive MR diagnoses of a medial meniscal tear are more common with specific clinical variables, tear type or location, or MRI findings of a longitudinal tear. MATERIALS AND METHODS: We reviewed the records of 559 patients who underwent knee MR examinations and arthroscopy. We compared the positive predictive values (PPVs) of an MR diagnosis of a medial meniscal tear for differences in tear location or type, delay between knee injury and MRI, delay between MRI and arthroscopy, and the presence of an anterior cruciate ligament (ACL) tear. We also retrospectively reviewed the MR examinations of 50 longitudinal tears to compare the PPVs of various MRI findings of a longitudinal tear. RESULTS: There was no association between either the delay between injury and MRI or the delay between MRI and arthroscopy and false-positive diagnoses. The PPV of 64% (32/50) for longitudinal tears was lower than the values of 83% (15/18) to 100% (116/116) for other types of medial meniscal tears. False-positive diagnoses of medial meniscal tears were more common in patients who had a prior episode of acute trauma (p = 0.004) or an ACL tear (p < 0.0001). Review of longitudinal tears revealed a decreased PPV when MRI showed signal contacting only the superior surface (p = 0.016) or when MRI showed signal contacting the surface at the meniscocapsular junction (p = 0.004). Four of the 18 menisci with a false-positive diagnosis of a longitudinal tear had a healed ACL tear noted at arthroscopy. CONCLUSION: False-positive MR diagnoses of medial meniscal tears are more common for longitudinal tears than other tear types and are also more common with MR abnormalities at either the superior surface or the meniscocapsular junction. Spontaneous healing of longitudinal tears accounts for some false-positive MR diagnoses.