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Diabetic retinopathy has become an increasingly important cause of blindness. Nevertheless, vision loss can be prevented from early detection of diabetic retinopathy and monitor with regular examination. Common automatic detection of retinal abnormalities is for microaneurysms, hemorrhages, hard exudates, and cotton wool spot. However, there is a worse case of retinal abnormality, but not much research was done to detect it. It is neovascularization where new blood vessels grow due to extensive lack of oxygen in the retinal capillaries. This paper shows that various combination of techniques such as image normalization, compactness classifier, morphology-based operator, Gaussian filtering, and thresholding techniques were used in developing of neovascularization detection. A function matrix box was added in order to classify the neovascularization from natural blood vessel. A region-based neovascularization classification was attempted as a diagnostic accuracy. The developed method was tested on images from different database sources with varying quality and image resolution. It shows that specificity and sensitivity results were 89.4% and 63.9%, respectively. The proposed approach yield encouraging results for future development. [ABSTRACT FROM AUTHOR]

In this paper, we present an effective method to determine the reference point of symphysis pubis (SP) in an axial stack of CT images to facilitate image registration for pelvic cancer treatment. In order to reduce the computational time, the proposed method consists of two detection parts, the coarse detector, and the fine detector. The detectors check each image patch whether it contains the characteristic structure of SP. The coarse detector roughly determines the location of the reference point of SP using three types of information, which are the location and intensity of an image patch, the SP appearance, and the geometrical structure of SP. The fine detector examines around the location found by the coarse detection to refine the location of the reference point of SP. In the experiment, the average location error of the propose method was 2.23 mm, which was about the side length of two pixels. Considering that the average location error by a radiologist is 0.77 mm, the proposed method finds the reference point quite accurately. Since it takes about 10 s to locate the reference point from a stack of CT images, it is fast enough to use in real time to facilitate image registration of CT images for pelvic cancer treatment. [ABSTRACT FROM AUTHOR]

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner. [ABSTRACT FROM AUTHOR]

Descending neural pathways in the mammalian auditory system are known to modulate the function of the peripheral auditory system. These pathways include the medial olivocochlear (MOC) efferent innervation to outer hair cells (OHCs) and the acoustic reflex pathways mediating middle ear muscle (MEM) contractions. Based on measurements in humans (Marks and Siegel, companion paper), we applied a sensitive method to attempt to differentiate MEM and MOC reflexes using contralateral acoustic stimulation in mice under different levels of anesthesia. Separation of these effects is based on the knowledge that OHC-generated transient evoked otoacoustic emissions (TEOAE) are delayed relative to the stimulus, and that the MOC reflex affects the emission through its innervation of OHC. In contrast, the MEM-mediated changes in middle ear reflectance alter both the stimulus (with a short delay) and the emission. Using this approach, time averages to transient stimuli were evaluated to determine if thresholds for a contralateral effect on the delayed emission, indicating potential MOC activation, could be observed in the absence of a change in the stimulus pressure. This outcome was not observed in the majority of cases. There were also no statistically significant differences between MEM and putative MOC thresholds, and variability was high for both thresholds regardless of anesthesia level. Since the two reflex pathways could not be differentiated on the basis of activation thresholds, it was concluded that the MEM reflex dominates changes in TEOAEs induced by contralateral noise. This result complicates the identification of purely MOC-induced changes on OAEs in mice unless the MEM reflex is inactivated surgically or pharmacologically. [ABSTRACT FROM AUTHOR]

Background: Latino immigrants face a higher burden of colorectal cancer (CRC) and screening rates are low.Objective: To assess the effectiveness of a multilevel intervention in increasing the rate of CRC screening among Latino immigrants.Design: A randomized controlled trial, with randomization at the physician level.Participants: Pairs of 65 primary care physicians and 65 Latino immigrant patients participated, 31 in the intervention and 34 in the control group.Intervention: CRC educational video in Spanish on a portable personal digital video display device accompanied by a brochure with key information for the patient, and a patient-delivered paper-based reminder for their physician.Measurements: Completed CRC screening, physician recommendation for CRC screening, and patient adherence to physician recommended CRC screening.Results: The overall rate of completed screening for CRC was 55% for the intervention and 18% for the control group (p = 0.002). Physicians recommended CRC screening for 61% of patients in the intervention group versus 41% in the control group (p = 0.08). Of those that received a recommendation, 90% in the intervention group adhered to it versus 26% in the control group (p = 0.007).Conclusions: The intervention was successful in increasing rates of completed CRC screening primarily through increasing adherence after screening was recommended. Additional efforts should focus on developing new strategies to increase physician recommendation for CRC screening, while employing effective patient adherence interventions. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) and the other low-grade non-Hodgkin lymphomas are among the most common lymphoid malignancies. Recent studies suggest that more than 4% of the general population over age 40 harbor a population of clonal B cells with the phenotype of either CLL or another B-cell malignancy, a condition now designated monoclonal B-cell lymphocytosis (MBL). Although all cases of CLL appear to be preceded by MBL, the majority of individuals with MBL will not develop a hematologic malignancy. The biologic characteristics and clinical implications of MBL appear to differ based on whether it is identified during the diagnostic evaluation of lymphocytosis or incidentally discovered through screening of individuals with normal lymphocyte counts as part of research studies using highly sensitive detection methods. In this paper, we provide a state of the art review on the prevalence, nomenclature, biology, natural history and clinical management of MBL. [ABSTRACT FROM AUTHOR]

Background: Overuse of antibiotics in the treatment of acute respiratory tract infection (ARI) contributes to the growing problem of antibiotic-resistant infections.Objective: To identify factors that influence community practitioners to prescribe antibiotics and examine how they differ from the recommendations of the Centers for Disease Control and Prevention (CDC) guideline for treatment of ARI.Design: Paper case vignette study using a fractional factorial design.Participants: One hundred one community practitioners and eight faculty members.Main Measurements: We asked community practitioners to estimate how likely they would be to prescribe antibiotics in each of 20 cases of ARI and then used multiple regression to infer the importance weights of each of nine clinical findings. We then compared practitioners' weights with those of a panel of eight faculty physicians who evaluated the cases following the CDC guidelines rather than their own judgments.Main Results: Practitioners prescribed antibiotics in 44.5% of cases, over twice the percentage treated by the panel using the CDC guidelines (20%). In deciding to prescribe antibiotic treatment, practitioners gave little or no weight to patient factors such as whether the patients wanted antibiotics. Although weighting patterns differed among practitioners, the majority (72%) gave the greatest weight to duration of illness. When illness duration was short, the rate of prescribing (20.1%) was the same as the rate of the faculty panel (20%).Conclusions: Based on hypothetical cases of ARI, community practitioners prescribed antibiotics at twice the rate of faculty following CDC practice guidelines. Practitioners were most strongly influenced by duration of illness. The effect of duration was strongest when accompanied by fever or productive cough, suggesting that these situations would be important areas for practitioner education and further clinical studies. [ABSTRACT FROM AUTHOR]

Background: Many older adults in the U.S. do not receive appropriate colorectal cancer (CRC) screening. Although primary care physicians' recommendations to their patients are central to the screening process, little information is available about their recommendations in relation to guidelines for the menu of CRC screening modalities, including fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), colonoscopy, and double contrast barium enema (DCBE). The objective of this study was to explore potentially modifiable physician and practice factors associated with guideline-consistent recommendations for the menu of CRC screening modalities.Methods: We examined data from a nationally representative sample of 1266 physicians in the U.S. surveyed in 2007. The survey included questions about physician and practice characteristics, perceptions about screening, and recommendations for age of initiation and screening interval for FOBT, FS, colonoscopy and DCBE in average risk adults. Physicians' screening recommendations were classified as guideline consistent for all, some, or none of the CRC screening modalities recommended. Analyses used descriptive statistics and polytomous logit regression models.Results: Few (19.1%; 95% CI:16.9%, 21.5%) physicians made guideline-consistent recommendations across all CRC screening modalities that they recommended. In multivariate analysis, younger physician age, board certification, north central geographic region, single specialty or multi-specialty practice type, fewer patients per week, higher number of recommended modalities, use of electronic medical records, greater influence of patient preferences for screening, and published clinical evidence were associated with guideline-consistent screening recommendations (p < 0.05).Conclusions: Physicians' CRC screening recommendations reflect both overuse and underuse, and few made guideline-consistent CRC screening recommendations across all modalities they recommended. Interventions that focus on potentially modifiable physician and practice factors that influence overuse and underuse and address the menu of recommended screening modalities will be important for improving screening practice. [ABSTRACT FROM AUTHOR]

Otitis media is the leading cause of hearing loss in children. It is commonly associated with fluid in the ear, which can result in up to 45 dB of hearing loss for extended periods of time during a child's most important developmental years. Accurate assessment of middle ear effusions is an important part of understanding otitis media. Current technologies used to diagnose otitis media with effusion are pneumatic otoscopy, tympanometry, and acoustic reflectometry. While all of these techniques can reasonably diagnose the presence of an effusion, they provide limited information about the infection present behind the tympanic membrane.We have developed a technique based on low-coherence interferometry-a non-invasive optical ranging technique capable of sensing depth-resolved microscopic scattering features through the eardrum-to quantify eardrum thickness and integrity, as well as detect any effusion, purulence, or biofilm behind the tympanic membrane. In this manuscript, the technique is coupled with a pneumatic otoscope to measure minute deflections of the tympanic membrane from insufflation pressure stimuli. This results in quantitative measurements of tympanic membrane mobility, which may be used to gain a better understanding of the impact of infection on the membrane dynamics. A small pilot study of 15 subjects demonstrates the ability of pneumatic low-coherence interferometry to quantitatively differentiate normal ears from ears with effusions present. Analysis of the strengths and weaknesses of the technique, as well as focus areas of future research, is also discussed. [ABSTRACT FROM AUTHOR]

Background: Primary care providers and health systems have prominent roles in guiding effective cancer screening.Objective: To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests.Design: Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.Participants: Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years).Intervention: Breast, colorectal, or cervical cancer screening.Main Measures: Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up.Key Results: There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7  % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %).Conclusions: Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities. [ABSTRACT FROM AUTHOR]

Background: For more than a decade, the presence of diabetes has been considered a coronary heart disease (CHD) "risk equivalent". Objective: The objective of this study was to revisit the concept of risk equivalence by comparing the risk of subsequent CHD events among individuals with or without history of diabetes or CHD in a large contemporary real-world cohort over a period of 10 years (2002 to 2011). Design: Population-based prospective cohort analysis. Participants: We studied a cohort of 1,586,061 adult members (ages 30-90 years) of Kaiser Permanente Northern California, an integrated health care delivery system. Main Measurements: We calculated hazard ratios (HRs) from Cox proportional hazard models for CHD among four fixed cohorts, defined by prevalent (baseline) risk group: no history of diabetes or CHD (None), prior CHD alone (CHD), diabetes alone (DM), and diabetes and prior CHD (DM + CHD). Key Results: We observed 80,012 new CHD events over the follow-up period (~10,980,800 person-years). After multivariable adjustment, the HRs (reference: None) for new CHD events were as follows: CHD alone, 2.8 (95% CI, 2.7-2.85); DM alone 1.7 (95% CI, 1.66-1.74); DM + CHD, 3.9 (95% CI, 3.8-4.0). Individuals with diabetes alone had significantly lower risk of CHD across all age and sex strata compared to those with CHD alone (12.2 versus 22.5 per 1000 person-years). The risk of future CHD for patients with a history of either DM or CHD was similar only among those with diabetes of long duration (≥10 years). Conclusions: Not all individuals with diabetes should be unconditionally assumed to be a risk equivalent of those with prior CHD. [ABSTRACT FROM AUTHOR]

Background: Changes to national guidelines for breast and cervical cancer screening have created confusion and controversy for women and their primary care providers.Objective: To characterize women's primary health care provider attitudes towards screening and changes in practice in response to recent revisions in guidelines for breast and cervical cancer screening.Design, Setting, Participants: In 2014, we distributed a confidential web and mail survey to 668 women's health care providers affiliated with the four clinical care networks participating in the three PROSPR (Population-based Research Optimizing Screening through Personalized Regimens) consortium breast cancer research centers (385 respondents; response rate 57.6 %).Main Measures: We assessed self-reported attitudes toward breast and cervical cancer screening, as well as practice changes in response to the most recent revisions of the U.S. Preventive Services Task Force (USPSTF) recommendations.Key Results: The majority of providers believed that mammography screening was effective for reducing cancer mortality among women ages 40-74 years, and that Papanicolaou (Pap) testing was very effective for women ages 21-64 years. While the USPSTF breast and cervical cancer screening recommendations were widely perceived by the respondents as influential, 75.7 and 41.2 % of providers (for mammography and cervical cancer screening, respectively) reported screening practices in excess of those recommended by USPSTF. Provider-reported barriers to concordance with guideline recommendations included: patient concerns (74 and 36 % for breast and cervical, respectively), provider disagreement with the recommendations (50 and 14 %), health system measurement of a provider's screening practices that use conflicting measurement criteria (40 and 21 %), concern about malpractice risk (33 and 11 %), and lack of time to discuss the benefits and harms with their patients (17 and 8 %).Conclusions: Primary care providers do not consistently follow recent USPSTF breast and cervical cancer screening recommendations, despite noting that these guidelines are influential. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Listeners with normal audiometric thresholds can still have suprathreshold deficits, for example, in the ability to discriminate sounds in complex acoustic scenes. One likely source of these deficits is cochlear neuropathy, a loss of auditory nerve (AN) fibers without hair cell damage, which can occur due to both aging and moderate acoustic overexposure. Since neuropathy can affect up to 50 % of AN fibers, its impact on suprathreshold hearing is likely profound, but progress is hindered by lack of a robust non-invasive test of neuropathy in humans. Reduction of suprathreshold auditory brainstem responses (ABRs) can be used to quantify neuropathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy is selective for AN fibers with high thresholds, and because phase locking to temporal envelopes is particularly strong in these fibers, the envelope following response (EFR) might be a more robust measure. We compared EFRs to sinusoidally amplitude-modulated tones and ABRs to tone-pips in mice following a neuropathic noise exposure. EFR amplitude, EFR phase-locking value, and ABR amplitude were all reduced in noise-exposed mice. However, the changes in EFRs were more robust: the variance was smaller, thus inter-group differences were clearer. Optimum detection of neuropathy was achieved with high modulation frequencies and moderate levels. Analysis of group delays was used to confirm that the AN population was dominating the responses at these high modulation frequencies. Application of these principles in clinical testing can improve the differential diagnosis of sensorineural hearing loss. [ABSTRACT FROM AUTHOR]

Background: The increasing incidence of testicular germ cell tumour (TGCT) combined with its strong heritable basis suggests that stratified screening for the early detection of TGCT may be clinically useful. We modelled the efficiency of such a personalised screening approach, based on genetic risk profiling in combination with other diagnostic tools.Methods: We compared the number of cases potentially detectable in the population under a number of screening models. The polygenic risk scoring (PRS) model was assumed to have a log-normal relative risk distribution across the 19 currently known TGCT susceptibility variants. The diagnostic performance of testicular biopsy and non-invasive semen analysis was also assessed, within a simulated combined screening programme.Results: The area under the curve for the TGCT PRS model was 0.72 with individuals in the top 1% of the PRS having a nine-fold increased TGCT risk compared with the population median. Results from population-screening simulations only achieved a maximal positive predictive value (PPV) of 60%, highlighting broader clinical factors that challenge such strategies, not least the rare nature of TGCT. In terms of future improvements, heritability estimates suggest that a significant number of additional genetic risk factors for TGCT remain to be discovered, identification of which would potentially yield improvement of the PPV to 80-90%.Conclusions: While personalised screening models may offer enhanced TGCT risk discrimination, presently the case for population-level testing is not compelling. However, future advances, such as more routine generation of whole genome data is likely to alter the landscape. More targeted screening programs may plausibly then offer clinical benefit, particularly given the significant survivorship issues associated with the successful treatment of TGCT. [ABSTRACT FROM AUTHOR]

Background: Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients.Methods: A DiAcSpm/cutoff ratio (DASr) was established for 260 NSCLC patients, 99 benign lung disease patients, and 140 healthy volunteers, using colloidal gold aggregation methods. The DASr was compared between patients and healthy controls, and the prognostic significance of DASr was examined.Results: The median urinary DASr of NSCLC patients was significantly higher than that of healthy controls (0.810 vs 0.534, P<0.001). The DASr was higher in squamous cell carcinoma (SqCC) patients than in adenocarcinoma patients (1.18 vs 0.756, respectively, P=0.039). An increased urinary DASr value was significantly associated with pathological stage, other histological invasive factors and unfavourable outcomes in patients with completely resected NSCLC. Multivariate Cox regression analysis showed that increased urinary DASr was an independent prognostic factor (hazard ratio=4.652, 95% confidence interval (CI), 2.092-10.35; P<0.001).Conclusions: Urinary DASr was significantly increased in NSCLC, especially in SqCC. Urinary DASr was an independent poor prognostic indicator in patients with completely resected NSCLC. The DASr could be a useful biomarker for detecting malignancies and predicting prognosis. [ABSTRACT FROM AUTHOR]

Background: It is important to understand which components of successful multifaceted interventions are responsible for study outcomes, since some components may be more important contributors to the intervention effect than others.Objective: We conducted a mediation analysis to determine which of seven factors had the greatest effect on change in systolic blood pressure (BP) after 6 months in a trial to improve hypertension control.Design: The study was a preplanned secondary analysis of a cluster-randomized clinical trial. Eight clinics in an integrated health system were randomized to provide usual care to their patients (n = 222), and eight were randomized to provide a telemonitoring intervention (n = 228).Participants: Four hundred three of 450 trial participants completing the 6-month follow-up visit were included.Interventions: Intervention group participants received home BP telemonitors and transmitted measurements to pharmacists, who adjusted medications and provided advice to improve adherence to medications and lifestyle modification via telephone visits.Main Measures: Path analytic models estimated indirect effects of the seven potential mediators of intervention effect (defined as the difference between the intervention and usual care groups in change in systolic BP from baseline to 6 months). The potential mediators were change in home BP monitor use, number of BP medication classes, adherence to BP medications, physical activity, salt intake, alcohol use, and weight.Key Results: The difference in change in systolic BP was 11.3 mmHg. The multivariable mediation model explained 47 % (5.3 mmHg) of the intervention effect. Nearly all of this was mediated by two factors: an increase in medication treatment intensity (24 %) and increased home BP monitor use (19 %). The other five factors were not significant mediators, although medication adherence and salt intake improved more in the intervention group than in the usual care group.Conclusions: Most of the explained intervention effect was attributable to the combination of self-monitoring and medication intensification. High adherence at baseline and the relatively low intensity of resources directed toward lifestyle change may explain why these factors did not contribute to the improvement in BP. [ABSTRACT FROM AUTHOR]

Differentiation of malignant and benign pulmonary nodules is of paramount clinical importance. Texture features of pulmonary nodules in CT images reflect a powerful character of the malignancy in addition to the geometry-related measures. This study first compared three well-known types of two-dimensional (2D) texture features (Haralick, Gabor, and local binary patterns or local binary pattern features) on CADx of lung nodules using the largest public database founded by Lung Image Database Consortium and Image Database Resource Initiative and then investigated extension from 2D to three-dimensional (3D) space. Quantitative comparison measures were made by the well-established support vector machine (SVM) classifier, the area under the receiver operating characteristic curves (AUC) and the p values from hypothesis t tests. While the three feature types showed about 90 % differentiation rate, the Haralick features achieved the highest AUC value of 92.70 % at an adequate image slice thickness, where a thinner or thicker thickness will deteriorate the performance due to excessive image noise or loss of axial details. Gain was observed when calculating 2D features on all image slices as compared to the single largest slice. The 3D extension revealed potential gain when an optimal number of directions can be found. All the observations from this systematic investigation study on the three feature types can lead to the conclusions that the Haralick feature type is a better choice, the use of the full 3D data is beneficial, and an adequate tradeoff between image thickness and noise is desired for an optimal CADx performance. These conclusions provide a guideline for further research on lung nodule differentiation using CT imaging. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the method of the combination of radiological and textural features for the differentiation of malignant from benign solitary pulmonary nodules by computed tomography. Features including 13 gray level co-occurrence matrix textural features and 12 radiological features were extracted from 2,117 CT slices, which came from 202 (116 malignant and 86 benign) patients. Lasso-type regularization to a nonlinear regression model was applied to select predictive features and a BP artificial neural network was used to build the diagnostic model. Eight radiological and two textural features were obtained after the Lasso-type regularization procedure. Twelve radiological features alone could reach an area under the ROC curve (AUC) of 0.84 in differentiating between malignant and benign lesions. The 10 selected characters improved the AUC to 0.91. The evaluation results showed that the method of selecting radiological and textural features appears to yield more effective in the distinction of malignant from benign solitary pulmonary nodules by computed tomography. [ABSTRACT FROM AUTHOR]

A new restoration methodology is proposed to enhance mammographic images through the improvement of contrast features and the simultaneous suppression of noise. Denoising is performed in the first step using the Anscombe transformation to convert the signal-dependent quantum noise into an approximately signal-independent Gaussian additive noise. In the Anscombe domain, noise is filtered through an adaptive Wiener filter, whose parameters are obtained by considering local image statistics. In the second step, a filter based on the modulation transfer function of the imaging system in the whole radiation field is applied for image enhancement. This methodology can be used as a preprocessing module for computer-aided detection (CAD) systems to improve the performance of breast cancer screening. A preliminary assessment of the restoration algorithm was performed using synthetic images with different levels of quantum noise. Afterward, we evaluated the effect of the preprocessing on the performance of a previously developed CAD system for clustered microcalcification detection in mammographic images. The results from the synthetic images showed an increase of up to 11.5 dB ( p = 0.002) in the peak signal-to-noise ratio. Moreover, the mean structural similarity index increased up to 8.3 % ( p < 0.001). Regarding CAD performance, the results suggested that the preprocessing increased the detectability of microcalcifications in mammographic images without increasing the false-positive rates. Receiver operating characteristic analysis revealed an average increase of 14.1 % ( p = 0.01) in overall CAD performance when restored image sets were used. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy.Methods: Two-dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich α-2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers.Results: We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase.Conclusion: These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) type 16 is associated with oropharyngeal carcinomas (OPC). Antibodies (Abs) to HPV16 E6 and E7 oncoproteins have been detected in patient sera; however, Abs to other early HPV-derived proteins have not been well explored.Methods: Antibodies to the HPV16 proteome were quantified using a novel multiplexed bead assay, using C-terminal GST-fusion proteins captured onto Luminex beads. Sera were obtained from untreated patients with OPC (N=40), partners of patients with HPV16+ OPC (N=11), and healthy controls (N=50).Results: Oropharyngeal carcinomas patients with known virus-like capsid particle+ Abs had elevated serum Abs to HPV16 E1, E2, E4, E6, and E7, and L1 antibody levels, but not E5. The ratios of specific median fluorescence intensity to p21-GST compared with controls were E1: 50.7 vs 2.1; E4: 14.6 vs 1.3; E6: 11.3 vs 2.4; E7: 43.1 vs 2.6; and L1: 10.3 vs 2.6 (each P≤0.01). In a validation cohort, HPV16 E1, E2, and E7 antibody levels were significantly elevated compared with healthy control samples (P≤0.02) and partners of OPC patients (P≤0.01).Conclusion: Patients with HPV16+ OPC have detectable Abs to E1, E2, and E7 proteins, which are potential biomarkers for HPV-associated OPC. [ABSTRACT FROM AUTHOR]

Background: Previous studies have noted a high (41%) prevalence and poor discharge summary communication of pending laboratory (lab) tests at the time of hospital discharge for general medical patients. However, the prevalence and communication of pending labs within a high-risk population, specifically those patients discharged to sub-acute care (i.e., skilled nursing, rehabilitation, long-term care), remains unknown.Objective: To determine the prevalence and nature of lab tests pending at hospital discharge and their inclusion within hospital discharge summaries, for common sub-acute care populations.Design: Retrospective cohort study.Participants: Stroke, hip fracture, and cancer patients discharged from a single large academic medical center to sub-acute care, 2003-2005 (N = 564)Main Measures: Pending lab tests were abstracted from the laboratory information system (LIS) and from each patient's discharge summary, then grouped into 14 categories and compared. Microbiology tests were sub-divided by culture type and number of days pending prior to discharge.Key Results: Of sub-acute care patients, 32% (181/564) were discharged with pending lab tests per the LIS; however, only 11% (20/181) of discharge summaries documented these. Patients most often left the hospital with pending microbiology tests (83% [150/181]), particularly blood and urine cultures, and reference lab tests (17% [30/181]). However, 82% (61/74) of patients' pending urine cultures did not have 24-hour preliminary results, and 19% (13/70) of patients' pending blood cultures did not have 48-hour preliminary results available at the time of hospital discharge.Conclusions: Approximately one-third of the sub-acute care patients in this study had labs pending at discharge, but few were documented within hospital discharge summaries. Even after considering the availability of preliminary microbiology results, these omissions remain common. Future studies should focus on improving the communication of pending lab tests at discharge and evaluating the impact that this improved communication has on patient outcomes. [ABSTRACT FROM AUTHOR]

Research on neighborhoods and health has been growing. However, studies have not investigated the association of specific neighborhood measures, including socioeconomic and built environments, with cancer incidence or outcomes. We developed the California Neighborhoods Data System (CNDS), an integrated system of small area-level measures of socioeconomic and built environments for California, which can be readily linked to individual-level geocoded records. The CNDS includes measures such as socioeconomic status, population density, racial residential segregation, ethnic enclaves, distance to hospitals, walkable destinations, and street connectivity. Linking the CNDS to geocoded cancer patient information from the California Cancer Registry, we demonstrate the variability of CNDS measures by neighborhood socioeconomic status and predominant race/ethnicity for the 7,049 California census tracts, as well as by patient race/ethnicity. The CNDS represents an efficient and cost-effective resource for cancer epidemiology and control. It expands our ability to understand the role of neighborhoods with regard to cancer incidence and outcomes. Used in conjunction with cancer registry data, these additional contextual measures enable the type of transdisciplinary, "cells-to-society" research that is now being recognized as necessary for addressing population disparities in cancer incidence and outcomes. [ABSTRACT FROM AUTHOR]

Background: The United Kingdom NHS Breast Screening Programme was established in 1988, and women aged between 50 and 70 are routinely invited at three yearly intervals. Expected United Kingdom interval cancer rates have been calculated previously, but this is the first publication from an exercise to collate individual-based interval cancer data at a national level.Methods: Interval cancer case ascertainment is achieved by the regular exchange of data between Regional Breast Screening Quality Assurance Reference Centres and Cancer Registries. The present analysis includes interval cancers identified in women screened between 1st April 1997 and 31st March 2003, who were aged between 50 and 64 at the time of their last routine screen.Results: In the periods >0-<12 months, 12-<24 months and 24-<36 months after a negative screen, we found overall interval cancer rates and regional ranges of 0.55 (0.43-0.76), 1.13 (0.92-1.47) and 1.22 (0.93-1.57) per 1000 women screened, respectively. Rates in the period 33-<36 months showed a decline, possibly associated with early re-screening or delayed presentation.Conclusions: Interval cancer rates were higher than the expected rates in the 24-month period after a negative screen, but were similar to published results from other countries. Increases in background incidence may mean that the expected rates are underestimated. It is also possible that, as a result of incomplete case ascertainment, interval cancers rates were underestimated in some regions in which rates were less than the expected. [ABSTRACT FROM AUTHOR]

Background: The debate continues regarding the best management for women with low-grade abnormal cervical cytology attending colposcopy. We compared psychosocial outcomes of alternative management policies in these women.Methods: In all, 989 women, aged 20-59 years, with low-grade abnormal cytology, were randomised to immediate large loop excision (LLETZ) or two to four targeted punch biopsies taken immediately with recall for LLETZ if these showed cervical intra-epithelial neoplasia 2/3. At 6 weeks after the last procedure, women completed the hospital anxiety and depression scale (HADS) and the impact of event scale (IES). At 12, 18, 24 and 30 months post recruitment, women completed the HADS and process outcome specific measure (POSM). Prevalence of significant depression (≥ 8), significant anxiety (≥ 11) and distress (≥ 9) and median POSM scores were compared between arms. Multivariate odds ratios (ORs) for immediate LLETZ vs biopsy and recall were computed.Results: Over the entire follow-up, there was no significant difference between arms in cumulative prevalence or risk of significant depression (OR=0.78, 95% CI 0.52-1.17) or significant anxiety (OR=0.83, 95% CI 0.57-1.19). At 6 weeks post procedure, distress did not differ significantly between arms. At later time points, 8-11% had significant depression and 14-16% had significant anxiety but with no differences between arms. The POSM scores did not differ between the arms.Conclusions: There is no difference in long- or short-term psychosocial outcomes of immediate LLETZ and punch biopsies with selective recall. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening can be administered through tests with varied characteristics and is a preference-sensitive decision.Objective: To assess patient experiences with a Maximum Differences Scaling (MDS) tool for eliciting values about CRC screening test characteristics and determine whether patients vary in how they prioritize test characteristics and whether this variation relates to test preferences.Design: MDS survey to elicit patients' values for characteristics related to fecal occult blood testing, sigmoidoscopy, colonoscopy, CT colonography and colon capsule endoscopy.Participants: 92 patients enrolled in primary care clinics at a VA hospital and associated university.Results: Patients reported that the tool was easy to use (95%). On completion 62% would choose colonoscopy, 23% colon capsule endoscopy and 10% CT colonography. Of the attributes evaluated, patients valued sensitivity, risk of tear and need for a second test most. Sensitivity was more important to those choosing colonoscopy than those choosing other tests (median importance = 21.5 versus 19.6, p < 0.01). Concern with complications and sedation was positively associated with age (p < 0.001 and p < 0.001), whereas concern with colon preparation and missing work was negatively associated with age (p < 0.009 and p < 0.03). Patients with fair or poor health status were less concerned with sensitivity than patients in good to excellent health (median importance = 19.3 versus 21.4, p < 0.008).Conclusions: This pilot study suggests that patients vary in how they prioritize colorectal cancer screening test attributes; this variation is associated with test preferences, and this MDS tool is feasible to use and may help patients construct their preferences. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B and hepatitis B-associated liver cancer is a major health disparity among Vietnamese Americans, who have a chronic hepatitis B prevalence rate of 7-14% and an incidence rate for liver cancer six times that of non-Latino whites.Objective: Describe factors associated with hepatitis B testing among Vietnamese Americans.Design: A population-based telephone survey conducted in 2007-2008.Participants: Vietnamese Americans age 18-64 and living in the Northern California and Washington, DC areas (N = 1,704).Main Measures: Variables included self-reports of sociodemographics, health care factors, and hepatitis B-related behaviors, knowledge, beliefs, and communication with others. The main outcome variable was self-reported receipt of hepatitis B testing.Key Results: The cooperation rate was 63.1% and the response rate was 27.4%. Only 62% of respondents reported having received a hepatitis B test and 26%, hepatitis B vaccination. Only 54% knew that hepatitis B could be transmitted by sexual intercourse. In multivariable analyses, factors negatively associated with testing included: age 30-49 years, US residence for >10 years, less Vietnamese fluency, lower income, and believing that hepatitis B can be deadly. Factors positively associated with testing included: Northern California residence, having had hepatitis B vaccination, having discussed hepatitis B with family/friends, and employer requested testing. Physician recommendation of hepatitis B testing (OR 4.46, 95% CI 3.36, 5.93) and respondent's request for hepatitis B testing (OR 8.37, 95% CI 5.95, 11.78) were strongly associated with test receipt.Conclusion: Self-reports of hepatitis B testing among Vietnamese Americans remain unacceptably low. Physician recommendation and patient request were the factors most strongly associated with test receipt. A comprehensive effort is needed to promote hepatitis B testing in this population, including culturally-targeted community outreach, increased access to testing, and physician education. [ABSTRACT FROM AUTHOR]

Background: There are no universally accepted guidelines for the follow-up of individuals with cutaneous melanoma. Furthermore, to date, there have been no randomised controlled trials of different models of melanoma follow-up care. This randomised controlled trial was conducted to evaluate the effects of GP-led melanoma follow-up on patient satisfaction, follow-up guideline compliance, anxiety and depression, as well as health status.Methods: A randomised controlled trial of GP-led follow-up of cutaneous melanoma was conducted over a period of 1 year with assessment by self-completed questionnaires and review of general practice-held medical records at baseline and 12 months later. It took place in 35 general practices in North-east Scotland. Subjects were 142 individuals (51.4% women 48.6% men; mean (s.d.) age 59.2 (15.2) years previously treated for cutaneous melanoma and free of recurrent disease. The intervention consisted of protocol-driven melanoma reviews in primary care, conducted by trained GPs and supported by centralised recall, rapid access pathway to secondary care and a patient information booklet. The main outcome measure was patient satisfaction measured by questionnaire. Secondary outcomes were adherence to guidelines, health status measured by Short Form-36 and the Hospital Anxiety and Depression Scale.Results: There were significant improvements in 5 out of 15 aspects of patient satisfaction during the study year in those receiving GP-led melanoma follow-up (all PConclusions: GP-led follow-up is feasible, engenders greater satisfaction in those patients who receive it, permits closer adherence to guidelines and does not result in adverse effects on health status or anxiety and depression when compared with traditional hospital-based follow-up for melanoma. [ABSTRACT FROM AUTHOR]

Objective: To determine if the relationship between obesity and usage of colorectal cancer (CRC) screening in women varies when stratifying by race.Methods: Using nationally representative data from the 2005 National Health Interview Survey, we examined the relationship between obesity and CRC screening for white and African-American women aged 50 and older. Screening usage variables indicated if a woman was up-to-date for any CRC screening test, colonoscopy, or FOBT. We used multivariable logistic regression models that included interaction terms to determine if race moderates the obesity-screening relationship. We also calculated adjusted up-to-date colonoscopy rates using direct standardization to model covariates.Results: The relationship between obesity and screening differed by race for any CRC screening test (P = 0.04 for interaction) and for colonoscopy (P = 0.01 for interaction), but not for FOBT. Obese white women had a lower adjusted colonoscopy rate (30.2%, 95% CI 25.9-34.8) than non-obese white women (39.1%, 95% CI 36.1-42.2). Obese African-American women, on the other hand, had a higher adjusted colonoscopy rate (41.2%, 95% CI 31.6-51.4) than their non-obese counterparts (35.6%, 95% CI 28.3-43.6). Overall, adjusted colonoscopy rates were lowest among obese white women.Conclusions: Obesity is associated with lower CRC screening rates in white, but not African-American women. [ABSTRACT FROM AUTHOR]

Background: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status.Methods: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received.Results: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity.Conclusions: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men. [ABSTRACT FROM AUTHOR]

Background: The National Health Service (NHS) bowel cancer screening programme (BCSP) was initiated across England in April 2006. To determine the feasibility of using national cancer registration data to assess the impact of the BCSP on stage-specific incidence, we studied trends in the incidence rates of colon (ICD10 C18) and rectosigmoid junction and rectum (ICD10 C19-C20) cancers and the completeness of data on Dukes stage in England.Methods: Data were obtained from all nine cancer registries for the period 1996-2004, before the introduction of the BCSP, in men and women aged 50-79 years.Results: Overall, incidence rates declined by 1% per year in the 9 years before the introduction of the BCSP (P<0.001). Dukes stage was recorded for 60% of all registrations but this varied between regions and over time. Only four registries had completeness of 74% or more. Registrations with unknown Dukes stage decreased from 1996 to 2000, and then increased during 2001-2004 affecting trends in stage-specific incidence.Conclusion: To study the impact of the BCSP on stage-specific incidence, regional variations in data completeness need to be addressed. [ABSTRACT FROM AUTHOR]

Background: Although modest improvements in colorectal cancer (CRC) screening utilization have occurred, rates remain low among Latinos. It is unclear whether acculturation plays a role in the utilization of CRC screening.Objective: This study aimed to examine the relationships between acculturation and CRC screening among older Mexican, Puerto-Rican and Cuban adults.Design: Cross-sectional observational study.Subjects: Latinos 50 years and older, never diagnosed with CRC, and who were surveyed in the 2000, 2003 and 2005 National Health Interview Survey (NHIS).Measures: We measured acculturation with US nativity and language of interview, and examined three different CRC screening outcomes: fecal occult blood test (FOBT) in the past year, up-to-date endoscopy and any up-to-date CRC screening. Logistic regression models were adjusted for predisposing, enabling and health-care need factors consistent with the behavioral model of health-care utilization.Main Results: In adjusted analyses, US nativity was positively associated with up-to-date endoscopy among Mexicans (OR: 1.5; 95% CI: 1.1, 2.2), but negatively associated with FOBT in the past year among Puerto Ricans (OR: 0.3; 95% CI: 0.2, 0.7). In contrast to this latter finding among Puerto Ricans, English language interview was positively associated with FOBT in the past year (OR: 2.5; 95% CI: 1.1, 5.4).Conclusion: Results underscore the importance of stratification by national origin in studies of acculturation and cancer screening and of targeting less acculturated adults to promote CRC screening. Clinicians, however, should consider the complexity of acculturation and treat US nativity and language preference as independent dimensions among their Latino patients. [ABSTRACT FROM AUTHOR]

Treatment decisions after diagnosis of clinically localised prostate cancer are difficult due to variability in tumour behaviour. We therefore examined one of the most promising biomarkers in prostate cancer, Ki-67, in a cohort of 808 patients diagnosed with prostate cancer between 1990 and 1996 and treated conservatively. Ki-67 expression was assessed immunohistochemically, in two laboratories, by two different scoring methods and the results compared with cancer-specific and overall survival. The power of the biomarker was compared with Gleason score and initial serum prostate-specific antigen (PSA). Both methods showed that Ki-67 provided additional prognostic information beyond that available from Gleason score and PSA: for the semi-quantitative method, Deltachi(2) (1 d.f.)=24.6 (P<0.0001), overall survival chi(2)=20.5 (P<0.0001), and for the quantitative method, Deltachi(2) (1 d.f.)=15.1 (P=0.0001), overall survival chi(2)=10.85 (P=0.001). Ki-67 is a powerful biomarker in localised prostate cancer and adds to a model predicting the need for radical or conservative therapy. As it is already in widespread use in routine pathology, it is confirmed as the most promising biomarker to be applied into routine practice. [ABSTRACT FROM AUTHOR]

The introduction of thalidomide, bortezomib and lenalidomide has dramatically changed the treatment paradigm of multiple myeloma (MM). In patients eligible for autologous stem cell transplant (ASCT), combinations including thalidomide/dexamethasone (Thal/Dex) or bortezomib/dexamethasone (Bort/Dex) or lenalidomide/dexamethasone (Rev/Dex) have been introduced as induction regimens in patients eligible for ASCT. New induction regimens have significantly increased complete response rate before and after ASCT with a positive impact on progression-free survival. Maintenance therapy with thalidomide, under investigation with lenalidomide, may further prolong remission duration. In patients not eligible for ASCT, randomized studies have shown that melphalan, prednisone, thalidomide (MPT) and melphalan, prednisone and bortezomib (MPV) are both superior to melphalan and prednisone (MP), and are now considered standard of care. Ongoing trials will soon assess if MP plus lenalidomide may be considered an attractive option. More complex regimens combining thalidomide or bortezomib or lenalidomide with cyclophosphamide or doxorubicin have been also tested. In small cohorts of patients bortezomib or lenalidomide may overcome the poor prognosis induced by deletion 13 or translocation t(4;14) or deletion 17p13. If these data will be confirmed, a cytogenetically risk-adapted strategy might become the most appropriate strategy. [ABSTRACT FROM AUTHOR]

Tamoxifen remains an important adjuvant therapy to reduce the rate of breast cancer recurrence among patients with oestrogen-receptor-positive tumours. Cytochrome P-450 2D6 metabolizes tamoxifen to metabolites that more readily bind the oestrogen receptor. This enzyme also metabolizes selective serotonin reuptake inhibitors (SSRI), so these widely used drugs - when taken concurrently - may reduce tamoxifen's prevention of breast cancer recurrence. We studied citalopram use in 184 cases of breast cancer recurrence and 184 matched controls without recurrence after equivalent follow-up. Cases and controls were nested in a population of female residents of Northern Denmark with stages I-III oestrogen-receptor-positive breast cancer 1985-2001 and who took tamoxifen for 1, 2, or most often for 5 years. We ascertained prescription histories by linking participants' central personal registry numbers to prescription databases from the National Health Service. Seventeen cases (9%) and 21 controls (11%) received at least one prescription for the SSRI citalopram while taking tamoxifen (adjusted conditional odds ratio=0.85, 95% confidence interval=0.42, 1.7). We also observed no reduction of tamoxifen effectiveness among regular citalopram users (>or=30% overlap with tamoxifen use). These results suggest that concurrent use of citalopram does not reduce tamoxifen's prevention of breast cancer recurrence. [ABSTRACT FROM AUTHOR]

A fluorescence in situ hybridisation (FISH) assay has been used to screen for ETV1 gene rearrangements in a cohort of 429 prostate cancers from patients who had been diagnosed by trans-urethral resection of the prostate. The presence of ETV1 gene alterations (found in 23 cases, 5.4%) was correlated with higher Gleason Score (P=0.001), PSA level at diagnosis (P=<0.0001) and clinical stage (P=0.017) but was not linked to poorer survival. We found that the six previously characterised translocation partners of ETV1 only accounted for 34% of ETV1 re-arrangements (eight out of 23) in this series, with fusion to the androgen-repressed gene C15orf21 representing the commonest event (four out of 23). In 5'-RACE experiments on RNA extracted from formalin-fixed tissue we identified the androgen-upregulated gene ACSL3 as a new 5'-translocation partner of ETV1. These studies report a novel fusion partner for ETV1 and highlight the considerable heterogeneity of ETV1 gene rearrangements in human prostate cancer. [ABSTRACT FROM AUTHOR]

Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7 vs 65.3 years) and is associated with longer median overall survival (11.1 vs 1.3 months; P<0.001). 14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM. Both show ubiquitous inactivation of TP53 (pPCL 56%; sPCL 83%) by coding mutation or 17p13 deletion; complemented by p14ARF epigenetic silencing in sPCL (29%). Both show frequent N-RAS or K-RAS mutation. Poor survival in pPCL was predicted by MYC translocation (P=0.006). Survival in sPCL was consistently short. Overall pPCL and sPCL are different disorders with distinct natural histories, genetics and survival. [ABSTRACT FROM AUTHOR]

The Prostate Cancer Risk Management Programme (PCRMP) launched in November 2002 provides guidelines for general practitioners (GPs) on age-specific prostate-specific antigen (PSA) cutoff levels in asymptomatic men. The impact of the PCRMP on GP referrals is unknown. This study investigates whether there was a change in the proportion of asymptomatic men with raised PSA levels (> or =3 ng ml(-1)) who were referred to urologists since the launch of the guidelines. Sixty-nine general practices in four areas of England and the main pathology laboratory in each area, which had participated in our previous research, were asked to provide data. Forty-eight practices (70%) provided retrospective data on urological referrals in men who had a PSA test taken in the periods 1 December 2001 to 31 May 2002 (pre-launch) and 1 December 2003 to 31 May 2004 (post-launch). Data on referrals were completed for 709 (79%) out of 898 and 1040 (90%) out of 1157 raised records pre- and post-launch, respectively. The percentage of men with raised PSA levels who were asymptomatic was similar in both time periods (19-20%) and the proportion referred to urologists according to the PCRMP guidelines did not increase significantly over time (24% pre-launch and 29% post-launch, P=0.42). The referral rate was lower than expected if the guidelines had been followed. The influence of the guidelines seems to have been low. At the time of data collection, 56% (112 out of 200) of GP partners reported that they were aware of receiving the PCRMP pack. To ensure future, effective implementation of guidelines requires evaluation. [ABSTRACT FROM AUTHOR]

There is a high and rising prevalence of prostate cancer (PRCA) within the male population of the United Kingdom. Although the relative risk of PRCA is higher in male BRCA2 and BRCA1 mutation carriers, the histological characteristics of this malignancy in these groups have not been clearly defined. We present the histopathological findings in the first UK series of BRCA1 and BRCA2 mutation carriers with PRCA. The archived histopathological tissue sections of 20 BRCA1/2 mutation carriers with PRCA were collected from histopathology laboratories in England, Ireland and Scotland. The cases were matched to a control group by age, stage and serum PSA level of PRCA cases diagnosed in the general population. Following histopathological evaluation and re-grading according to current conventional criteria, Gleason scores of PRCA developed by BRCA1/2 mutation carriers were identified to be significantly higher (Gleason scores 8, 9 or 10, P=0.012) than those in the control group. Since BRCA1/2 mutation carrier status is associated with more aggressive disease, it is a prognostic factor for PRCA outcome. Targeting screening to this population may detect disease at an earlier clinical stage which may therefore be beneficial. [ABSTRACT FROM AUTHOR]

Background: Despite the documented benefits of colorectal cancer screening, patient participation rates remain low. Physician recommendation has been identified as a significant predictor of screening completion.Objective: The aim of this study is to investigate how primary care physicians perceive colorectal cancer screening communication tasks, as well as to explore the form and content of actual screening discussions.Design: The research design includes a mailed physician survey and a separate observational study in a sample of videotaped medical encounters. PARTICIPANTS AND DATA SOURCES: The participants were 270 primary care physicians who completed a mailed questionnaire (57.9% response rate) and 18 physician-patient encounters that included discussions of colorectal cancer screening.Measurement: The questionnaire focused on perceived importance and accomplishment of communication tasks relevant to colorectal cancer screening. Two of the authors reviewed transcripts of videotaped physician encounters to determine whether the same communication tasks assessed in the survey were accomplished. Interrater reliability was high across all of the mutually exclusive coding categories (Kappa > .90).Results: Physicians rated colonoscopy as the most important screening option to discuss; self-reports indicate that colonoscopy (84.8%) is more frequently mentioned than fecal occult blood test (FOBT; 49.4%), flexible sigmoidoscopy (34.1%), or computed tomography (CT) imaging (18.1%). Explaining benefits and risks, describing test procedure and frequency, eliciting patient preferences, and making a plan for screening were all viewed as very important. Self-reported accomplishment of these communication tasks was considerably higher than that observed in our separate videotape sample.Conclusion: Most physicians recognize and espouse the importance of recommending colorectal cancer screening to eligible patients. However, findings from both the physician survey and observational study suggest that physicians tend to overestimate the extent of discussions about screening. Interventions may be warranted to improve clinical practice. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer screening (PCS) is controversial. Ideally, patients should understand the risks and benefits of screening before undergoing PSA testing. This study assessed whether primary care physicians routinely discuss PCS and explored the barriers to and facilitators of these discussions.Methods: Qualitative pilot study involving in-depth, semistructured interviews with 18 purposively sampled, academic and community-based primary care physicians. Barriers and facilitators of PCS discussions were ascertained using both interviews and chart-stimulated recall--a technique utilizing patient charts to probe recall and provide context to physician decision-making during clinic encounters. Analysis was performed using consensus conferences based on grounded theory techniques.Results: All 18 participating physicians reported that they generally discussed PCS with patients, though 6 reported sometimes ordering PSA tests without discussion. A PCS discussion occurred in only 16 (36%) of the 44 patient-physician encounters when patients were due for PCS that also met criteria for chart-stimulated recall. Barriers to PCS discussion were patient comorbidity, limited education/health literacy, prior refusal of care, physician forgetfulness, acute-care visits, and lack of time. Facilitators of PCS discussion included patient-requested screening, highly educated patients, family history of prostate cancer, African-American race, visits for routine physicals, review of previous PSA results, extra time during encounters, and reminder systems.Conclusions: PCS discussions sometimes do not occur. Important barriers to discussion are inadequate time for health maintenance, physician forgetfulness, and patient characteristics. Future research should explore using educational and decision support interventions to involve more patients in PCS decisions. [ABSTRACT FROM AUTHOR]

Background: Provider attitudes about issues pertinent to patient safety may be related to errors and adverse events. We know of no instruments that measure safety-related attitudes in the outpatient setting.Objective: To adapt the safety attitudes questionnaire (SAQ) to the outpatient setting and compare attitudes among different types of providers in the outpatient setting.Methods: We modified the SAQ to create a 62-item SAQ-ambulatory version (SAQ-A). Patient care staff in a multispecialty, academic practice rated their agreement with the items using a 5-point Likert scale. Cronbach's alpha was calculated to determine reliability of scale scores. Differences in SAQ-A scores between providers were assessed using ANOVA.Results: Of the 409 staff, 282 (69%) returned surveys. One hundred ninety (46%) surveys were included in the analyses. Cronbach's alpha ranged from 0.68 to 0.86 for the scales: teamwork climate, safety climate, perceptions of management, job satisfaction, working conditions, and stress recognition. Physicians had the least favorable attitudes about perceptions of management while managers had the most favorable attitudes (mean scores: 50.4 +/- 22.5 vs 72.5 +/- 19.6, P < 0.05; percent with positive attitudes 18% vs 70%, respectively). Nurses had the most positive stress recognition scores (mean score 66.0 +/- 24.0). All providers had similar attitudes toward teamwork climate, safety climate, job satisfaction, and working conditions.Conclusion: The SAQ-A is a reliable tool for eliciting provider attitudes about the ambulatory work setting. Attitudes relevant to medical error may differ among provider types and reflect behavior and clinic operations that could be improved. [ABSTRACT FROM AUTHOR]

Background: Low literacy influences cervical cancer screening knowledge, and is a possible contributor to racial disparities in cervical cancer.Objective: To examine the hypothesis that literacy predicts patient adherence to follow-up recommendations after an abnormal Pap smear.Design: A prospective, continuity clinic-based study.Participants: From a sample of 538 women undergoing literacy testing at the time of Pap smear screening, we studied 68 women with abnormal Pap smear diagnoses.Measurements: Literacy was assessed using the Rapid Evaluation of Adult Literacy in Medicine (REALM). We also measured other proxies for literacy, including educational attainment and physician estimates of patients' literacy level. Outcome measures included on-time and 1-year follow-up and duration of time to follow-up after an abnormal Pap smear.Results: Only one-third of the cohort adhered to follow-up recommendations. At 1 year, 25% of the women had not returned at all. Patients with inadequate literacy (as assessed by the REALM) were less likely to follow up within 1 year, although this result was not statistically significant (adjusted odds ratio [OR]=3.8, 95% confidence interval [CI]: 0.8 to 17.4). Patients subjectively assessed by their physician to have low literacy skills were significantly less likely to follow up within 1 year (adjusted OR=14, 95% CI: 3 to 65). Less than high school education (hazard ratio (HR)= 2.3; 95% CI: 1.2, 4.6) and low physician-estimated literacy level (HR=3.4, 95% CI: 1.4, 8.2), but not objective literacy level, were significant predictors of duration of time to follow-up, adjusting for recommended days to follow-up and other factors.Conclusions: Among women with an abnormal Pap smear, those perceived by their physician to have low literacy were significantly more likely to fail to present for follow-up. [ABSTRACT FROM AUTHOR]

Objective: The Patient Health Questionnaire depression scale (PHQ-9) is a well-validated, Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) criterion-based measure for diagnosing depression, assessing severity and monitoring treatment response. The performance of most depression scales including the PHQ-9, however, has not been rigorously evaluated in different racial/ethnic populations. Therefore, we compared the factor structure of the PHQ-9 between different racial/ethnic groups as well as the rates of endorsement and differential item functioning (DIF) of the 9 items of the PHQ-9. The presence of DIF would indicate that responses to an individual item differ significantly between groups, controlling for the level of depression.Measurements: A combined dataset from 2 separate studies of 5,053 primary care patients including non-Hispanic white (n=2,520), African American (n=598), Chinese American (n=941), and Latino (n=974) patients was used for our analysis. Exploratory principal components factor analysis was used to derive the factor structure of the PHQ-9 in each of the 4 racial/ethnic groups. A generalized Mantel-Haenszel statistic was used to test for DIF.Results: One main factor that included all PHQ-9 items was found in each racial/ethnic group with alpha coefficients ranging from 0.79 to 0.89. Although endorsement rates of individual items were generally similar among the 4 groups, evidence of DIF was found for some items.Conclusions: Our analyses indicate that in African American, Chinese American, Latino, and non-Hispanic white patient groups the PHQ-9 measures a common concept of depression and can be effective for the detection and monitoring of depression in these diverse populations. [ABSTRACT FROM AUTHOR]

The lead time and over-detection associated with prostate-specific antigen (PSA) screening, and generational improvements in all-cause mortality, make prostate cancer outcome studies from the pre-PSA era difficult to interpret in a contemporary setting. We developed a competing-risks hazard model to estimate the natural history of screen-detected prostate cancer, and the impact of radical treatment on overall survival. The model of hazard of mortality was fitted to clinical outcome data from the pre-PSA era, and the effects of screening, generational mortality improvements and radical treatment were incorporated. Sensitivities to the choice of baseline data and values of key parameters were assessed. Lead-time estimates in men diagnosed aged 55-59 years were 14.1, 9.3 and 5.0 years for men with Gleason scores <7, 7 and >7, respectively, assuming biennial screening with 100% attendance. Central estimates of 15-year prostate cancer mortality for conservative management of screen-detected prostate cancer ranged from 0 to 2% for Gleason scores <7, 9 to 31% for Gleason score 7 and 28-72% for Gleason scores >7. For men aged 55-59 years at diagnosis, the predicted absolute 15-year survival benefit from curative treatment was 0, 12 and 26% for men with Gleason scores <7, 7 and >7, respectively. Estimates of the survival benefit of radical treatment were relatively insensitive to values of key parameters. The case for curative treatment, rather than conservative management, of screen-detected localised prostate cancer is strongest in men with high-grade disease. This conclusion contrasts with current patterns of care. [ABSTRACT FROM AUTHOR]

This study examined factors that predict psychological morbidity and screening adherence in first-degree relatives (FDRs) taking part in a familial PSA screening study. Prostate cancer patients (index cases - ICs) who gave consent for their FDRs to be contacted for a familial PSA screening study to contact their FDRs were also asked permission to invite these FDRs into a linked psychosocial study. Participants were assessed on measures of psychological morbidity (including the General Health Questionnaire; Cancer Worry Scale; Health Anxiety Questionnaire; Impact of Events Scale); and perceived benefits and barriers, knowledge; perceived risk/susceptibility; family history; and socio-demographics. Of 255 ICs, 155 (61%) consented to their FDRs being contacted. Of 207 FDRs approached, 128 (62%) consented and completed questionnaires. Multivariate logistic regression revealed that health anxiety, perceived risk and subjective stress predicted higher cancer worry (P = 0.05). Measures of psychological morbidity did not predict screening adherence. Only past screening behaviour reliably predicted adherence to familial screening (P = 0.05). First-degree relatives entering the linked familial PSA screening programme do not, in general, have high levels of psychological morbidity. However, a small number of men exhibited psychological distress. [ABSTRACT FROM AUTHOR]

We evaluated prediagnosis predictors of breast cancer survival among 717 premenopausal breast cancer patients enrolled in a population-based case-control study and followed for 10.4 years. Using Cox's proportional hazards models, lifetime exercise, weight, and height were not associated with survival. Higher body mass index (trend P=0.21) and recent exercise activity (trend P=0.31) were weakly associated with longer survival. [ABSTRACT FROM AUTHOR]

Objectives: This study compared the relative efficiency of lumbar x-ray and rapid magnetic resonance (MR) imaging for diagnosing cancer-related low back pain (LBP) in primary care patients.Design: We developed a decision model with Markov state transitions to calculate the cost per case detected and cost per quality-adjusted life year (QALY) of rapid MR imaging. Model parameters were estimated from the medical literature. The costs of x-ray and rapid MR were calculated in an activity-based costing study.Setting and Patients: A hypothetical cohort of primary care patients with LBP referred for imaging to exclude cancer as the cause of their pain.Main Results: The rapid MR strategy was more expensive due to higher initial imaging costs and larger numbers of patients requiring conventional MR and biopsy. The overall sensitivity of the rapid MR strategy was higher than that of the x-ray strategy (62% vs 55%). However, because of low pre-imaging prevalence of cancer-related LBP, this generates <1 extra case per 1,000 patients imaged. Therefore, the incremental cost per case detected using rapid MR was high ($213,927). The rapid MR strategy resulted in a small increase in quality-adjusted survival (0.00043 QALYs). The estimated incremental cost per QALY for the rapid MR strategy was $296,176.Conclusions: There is currently not enough evidence to support the routine use of rapid MR to detect cancer as a cause of LBP in primary care patients. [ABSTRACT FROM AUTHOR]