Methylation markers differentiate thyroid cancer from benign nodules.

PURPOSE: The incidence of thyroid cancer (TC) is increasing. Cytology by itself cannot distinguish TC from some benign nodules especially in certain subtypes of TC. Our immediate goal is to identify DNA methylation markers for early detection of TC and to molecularly differentiate TC subtypes from benign nodules. METHODS: Promoter methylation status of 21 candidate genes was examined on formalin-fixed paraffin-embedded tissue (FFPE) utilizing quantitative methylation-specific polymerase chain reaction (QMSP) in a retrospective cohort of 329 patients (56% white, 29% African American, 61% female) comprising 71 normal thyroid, 83 benign nodules [follicular adenomas (FA)], 90 follicular TC (FTC) and 85 papillary TC (PTC). All genes were analyzed individually (Kruskal-Wallis and Wilcoxon rank sum tests) and in combination (logistic regression models) to identify genes whose methylation levels might best separate groups. RESULTS: Combination gene panels TPO and UCHL1 (ROC = 0.607, sensitivity 78%) discriminated FTC from FA, and RASSF1 and TPO (ROC = 0.881, sensitivity 78%) discriminated FTC from normal. Methylation of TSHR distinguished PTC from FTC (ROC = 0.701, sensitivity 84%) and PTC from FA (ROC = 0.685, sensitivity 70%). The six gene panel of TIMP3, RARB2, SERPINB5, RASSF1, TPO and TSHR, which differentiates PTC from normal thyroid, had the best combination sensitivity (91%) and specificity (81%) of the panels addressing discrimination of cancer tissue. CONCLUSIONS: Aberrant gene methylation used in combination panels may be useful clinically in differentiating FTC and PTC from benign nodules. If confirmed in additional studies, these findings could help reduce the over diagnosis of thyroid cancer and surgeries related to over diagnosis.

Diagnostic performance of HbA1c for diabetes in Arab vs. European populations: a systematic review and meta-analysis.

AIM: To examine differences in the performance of HbA1c for diagnosing diabetes in Arabs compared with Europeans. METHODS: The PubMed, Embase and Cochrane library databases were searched for records published between 1998 and 2015. Estimates of sensitivity, specificity and log diagnostic odds ratios for an HbA1c cut-point of 48 mmol/mol (6.5%) were compared between Arabs and Europeans, using a bivariate linear mixed-model approach. For studies reporting multiple cut-points, population-specific summary receiver operating characteristic (SROC) curves were constructed. In addition, sensitivity, specificity and Youden Index were estimated for strata defined by HbA1c cut-point and population type. Database searches yielded 1912 unique records; 618 full-text articles were reviewed. Fourteen studies met the inclusion criteria; hand-searching yielded three additional eligible studies. Three Arab (N = 2880) and 16 European populations (N = 49 127) were included in the analysis. RESULTS: Summary sensitivity and specificity for a HbA1c cut-point of 48 mmol/mol (6.5%) in both populations were 42% (33-51%), and 97% (95-98%). There was no difference in area under SROC curves between Arab and European populations (0.844 vs. 0.847; P = 0.867), suggesting no difference in HbA1c diagnostic accuracy between populations. Multiple cut-point summary estimates stratified by population suggest that Arabs have lower sensitivity and higher specificity at a HbA1c cut-point of 44 mmol/mol (6.2%) compared with European populations. Estimates also suggest similar test performance at cut-points of 44 mmol/mol (6.2%) and 48 mmol/mol (6.5%) for Arabs. CONCLUSIONS: Given the low sensitivity of HbA1c in the high-risk Arab American population, we recommend a combination of glucose-based and HbA1c testing to ensure an accurate and timely diagnosis of diabetes.

Incidence of cardiovascular and cerebrovascular events associated with sirolimus use after liver transplantation.

BACKGROUND: Sirolimus (SRL) is an immunosuppressant often used in liver transplantation (LT) to mitigate renal insufficiency associated with calcineurin inhibitors. Sirolimus can cause hyperlipidemia, but its association with coronary artery disease (CAD) and cerebrovascular accidents (CVAs) is unclear. The purpose of this study was to assess the risk of CAD and CVAs with the use of SRL in LT recipients. METHODS: We retrospectively reviewed all of our LT recipients from 2000 to 2011. Patients with multiorgan transplant, multiple liver transplants, everolimus therapy, or survival <3 months were excluded. The 803 remaining patients were divided into 3 groups: 1) 134 patients who received and tolerated SRL; 2) 604 patients who never received SRL; and 3) 65 patients who started but discontinued SRL. The primary outcome was the development of CAD or CVA beyond 4 months after transplantation with the use of time-dependent Kaplan-Meier analysis. RESULTS: In group 1, there were 6 CAD and 2 CVA events; in group 2, 27 CAD and 16 CVA events; and in group 3, 10 CAD and 2 CVA events. The event-free survival for CAD/CVA at 1, 3, and 5 years was 100%, 98.1%, and 97.2% respectively for group 1; 99.7%, 98.4%, and 96.1% for group 2; and 92.3%, 92.3%, and 85.6% for group 3. On an unadjusted basis, compared with group 2, there was no difference in CAD/CVA rates in group 1 (hazard ratio [HR] 0.92; not significant), but there was an increase in group 3 (HR 2.94; P = .0019). However, on multivariate analysis, only age at transplantation (HR 1.06; P = .001) and diabetes before transplantation (P = .011) were associated with increased CAD/CVA risk. CONCLUSIONS: Our analysis showed that patients receiving SRL after LT had no increased risk of CAD/CVA events compared with patients maintained on a calcineurin inhibitor. The risk of CAD/CVA should not be a factor in avoiding SRL.

Serum non-coding RNAs as biomarkers for osteoarthritis progression after ACL injury.

OBJECTIVE: The aim of this study was to examine serum non-coding RNAs as potential biomarkers for cartilage damage associated with anterior cruciate ligament (ACL) injury. METHODS: Serum was obtained from 80 patients 1 year after surgery for ACL injury and 60 normal donors without overt skeletal injury. Total serum RNA was isolated, small non-coding RNAs profiled by TaqMan array MicroRNA (miRNA) analysis and individual small RNA assays performed by quantitative TaqMan RT-PCR (qPCR). Semi-quantitative magnetic resonance imaging (MRI) analysis was performed using Whole Organ Magnetic Resonance Knee Score (WORMS) scoring for analysis of cartilage damage. RESULTS: Initial TaqMan array miRNA profiling showed an increased serum concentration of a small nucleolar RNA (snoRNA), U48, in five patients with cartilage damage compared with that in five patients without cartilage damage and six normal donors. Independent qPCR analysis of snoRNAs in serum from all patients and normal donors showed a strong association between the serum level of another snoRNA, U38, and cartilage damage in ACL injury patients and together with snoRNA, U48, clear distinction between ACL injury patients and normal donors. CONCLUSION: SnoRNAs U38 and U48 are significantly elevated in the serum of patients developing cartilage damage at 1 year after ACL injury. Serum levels of U38 have the potential to facilitate early diagnosis of patients with cartilage damage after ACL injury. This study suggests serum non-coding RNAs may serve as novel noninvasive biomarkers for the detection and assessment of cartilage damage after ACL injury.

A national study of pain in the bleeding disorders community: a description of haemophilia pain.

UNLABELLED: The National Pain Study was a prospective, computer-based, descriptive survey of the pain experience of persons with a bleeding disorder conducted in the United States over a 28 month period from 2007 to 2009. The aim of this study was to (i) determine the language used by patients to describe and differentiate acute and persistent pain, (ii) describe pharmacological and non-pharmacological strategies utilized to control pain, (iii) assess the perceived effectiveness of current pain management on quality of life and, (iv) to determine who provides pain management to this population. One thousand, one hundred and four surveys were received. Only the responses of the 764 respondents who reported having hemophilia A or B were evaluated for this paper. Thirty nine percent of participants reported their pain was not well treated. The average acute pain score associated with a bleed reported was 5.97/10 while the average persistent pain score reported was 4.22/10. The most frequently reported word descriptors for acute pain were: throbbing, aching, sharp, tender and miserable. The most frequently reported word descriptors for persistent pain were aching, nagging, tiring, sharp, and tender. The most frequently reported pain strategies for acute and persistent pain included factor, rest, ice, elevation, and compression. Alcohol and illicit drugs were reportedly used to manage both acute pain as well as persistent pain. Primarily, short-acting opioids and acetaminophen were reported to treat both acute and persistent pain. Hematologists and primary care providers provide the majority of pain management for persons with hemophilia (PWH). Quality of life (QOL) scores were lowest in the domains of pain, energy/fatigue and physical problems indicating disruption of QOL. This substantiates under-recognition and under-treatment of pain in the hemophilia population when combined with the 39% of respondents who felt their pain was not well treated and literature in the general pain population of wide spread under-treatment of pain. RECOMMENDATIONS: The NPS is an initial step in recognizing the prevalence and description of pain in PWH. HTC providers should educate themselves in pain management techniques to better serve this population. Further research is necessary to develop specific pain management guidelines for the bleeding disorders population that include multimodal holistic treatment plans.

Assessment of acute and persistent pain management in patients with haemophilia.

A descriptive survey was conducted in Region V-E of the United States to bridge the gap in available information on pain issues in the bleeding disorders population. The aim of this study was to a) determine language used by patients to describe and differentiate acute and persistent pain, b) describe pharmacological and non-pharmacological strategies utilized to control pain, c) determine the providers of pain management to this population and d) evaluate quality of life incorporating the SF-36 QOL tool. A total of 202 surveys were returned. For the purposes of this paper, it was decided to analyse only haemophilia data (n = 114). Average persistent daily pain levels were 5/10 (P < 0.001). The three most common word descriptors for both acute and persistent pain were the same - achy, throbbing and tender; the most utilized pain medications were NSAIDs and acetaminophen. Factor replacement was used for what respondents described as acute pain management 79% of the time and for persistent pain management 38% of the time. Participants described acute and persistent pain with the same pain descriptors leading to the conclusion that patients have difficulty distinguishing between acute and persistent pain. This lack of differentiation was further displayed by the use of factor replacement to treat persistent pain associated with arthritic discomfort (38%) which would be viewed as inappropriate, as well as lack of factor replacement use by 21% of respondents who identified pain as from an acute bleed. Opportunities exist to improve pain management through patient and provider-directed educational programs.

Survival after liver transplantation in patients who develop renal insufficiency.

BACKGROUND: Renal insufficiency (RI) after liver transplantation (OLT) is associated with worse outcomes but the actual survival after RI ensues is not well described. We examined the survival of OLT recipients who developed moderate or severe RI or end-stage renal disease (ESRD), seeking to identify variables associated with these outcomes. METHODS: Between 1993 and 2007, 731 patients underwent OLT. After excluding patients undergoing retransplantation, combined kidney-liver grafts, and those who died within 1 year, we had a cohort of 527 subjects whose basic demographic data were obtained. Glomerular filtration rate (GFR) calculated (by MDRD4-Modification of Diet in Renal Disease 4-formula) at 3-month intervals in the first year and then at 6-month intervals. Moderate RI was defined as a GFR < 60 mL/min/1.73 m(2); severe RI, GFR < 30; and ESRD by need for dialysis or renal transplantation. We determined survival from the point of developing RI. An analysis determined factors associated with survival. RESULTS: Among 527 patients, 251 developed moderate (47.6%) and 40 (7.6%) severe RI as well as 40 (7.6%) with ESRD. Once RI ensued, the 5-year survivals for patients with moderate RI, severe RI or ESRD were 84.0%, 67.7%, and 48.5%, respectively. Five-year survival, for patients receiving a renal transplant was 100%. On multivariate Cox regression analysis, the only variables associated with time to death for patients with any RI were higher age at transplant (hazard ratio [HR] = 1.04, P = .02), higher creatinine at transplant (HR = 1.25, P = .01), pretransplant diabetes (HR = 2.34, P = .008), and transplantation in the Model for End-stage Liver Disease (MELD) era (HR = 0.15, P = .002). CONCLUSION: Development of severe RI or ESRD correlated with diminished survival. For patients with RI, age and creatinine at transplant, pretransplant diabetes, and transplantation in the pre-MELD era were associated with lower survival rates. Five-year survival for dialysis patients was somewhat higher than that previously reported but worse than that of subjects treated by renal transplantation.

The impact of donor race on recurrent hepatitis C after liver transplantation.

BACKGROUND: Several studies have demonstrated mixed results regarding the influence of donor race on patient and graft survival in patients infected with hepatitis C virus (HCV) after liver transplant. However, few studies have looked at the impact of donor race on recurrent HCV. This study is a retrospective analysis of the influence of patient and donor race on the severity of recurrent HCV at a single center. METHODS: Of patients transplanted at our center between 2000 and 2006, 222 were infected with HCV. Of these, 165 were eligible to be evaluated for recurrent HCV after transplant. We excluded those with patient and graft loss within 1 year that was not related to recurrent HCV, patients with advanced fibrosis from other causes, those who did not undergo posttransplant liver biopsy, and those lost to follow-up. Patients were given a recurrent HCV score of 1, 2, or 3. A score of 1 was assigned if the patient had no more than mild portal fibrosis at 1 year and no bridging fibrosis at any point. A score of 2 was defined as moderate portal fibrosis or focal bridging fibrosis at 1 year or bridging fibrosis or cirrhosis after 3 years. A score of 3 was defined as bridging fibrosis, cirrhosis, or graft loss from HCV within 3 years. Baseline characteristics including donor and recipient age, race, sex, body mass index, ischemia time, hypertension, and diabetes were recorded. Analysis was performed with ordinal multivariate logistic regression modeling. RESULTS: Of the 165 patients with a recurrent HCV score, 105 (64%) had a score of 1, 29 patients (17%) had a score of 2, and 31 patients (19%) had a score of 3. In all, 132 recipients (80%) had white donors, and 26 (16%) had African American donors, 115 patients (70%) were white and 40 (24%) were African American. The mean recurrent HCV scores for the patient donor and recipient race combinations are as follows: white donor and white recipient, 1.54; white donor and African American recipient, 1.89; African American donor and white recipient, 1.18; and African American donor and African American recipient, 1.23. Having a white donor also significantly associated with a higher recurrent HCV score regardless of recipient race (odds ratio 2.93, P = .044) in African American patients, having a white donor had an odds ratio of 4.62 (P = .046). After adjusting for donor age and sex and patient age and sex, having a white donor was still found to be associated with a higher recurrent HCV score (4.48, P = .0275) on multivariate analysis. For all 222 patients, donor race was not associated with overall patient and graft survival. CONCLUSION: Patients receiving white donor grafts had significantly worse recurrent HCV than those receiving grafts from African American donors regardless of recipient race. This difference was especially marked in African American recipients and persisted on multivariate analysis. These data suggest a graft from a white donor is potentially one more important variable in identifying patients at risk for more aggressive recurrent HCV after orthotopic liver transplant.

Incidental hepatocellular carcinoma after liver transplantation: population characteristics and outcomes.

We combined data from two liver transplant centers to determine the tumor characteristics and outcomes of 51 patients transplanted with incidental hepatocellular carcinoma (iHCC) compared with 143 patients transplanted for previously known HCC (pkHCC). There were no differences in age, gender, or frequency of hepatitis C infection. Patients with iHCC were more likely to be African-American (22% vs 10%; P = .016), more likely to be screened by ultrasound (38% vs 9%; P < .001), had a lower alpha-fetoprotein (83.9 +/- 258.1 vs 572.4 +/- 2376.4 ng/mL; P = .005), and had a higher model for end-stage liver disease (MELD) score (14.3 +/- 4.1 vs 11.8 +/- 4.7; P < .001). The liver explants of patients with iHCC had smaller total tumor burden than patients with pkHCC (3.1 +/- 3.5 vs 4.1 +/- 2.6 cm; P < .001), but a similar percentage of single lesions (66% vs 65%) and tumors that met Milan criteria (76% vs 65%). Patients with iHCC had 1-, 3-, and 5-year survivals of 78%, 67%, and 58%, and 1-, 3-, and 5-year recurrence-free survivals of 90%, 87%, and 87% compared with the 1-, 3-, and 5-year survivals of 90%, 82%, and 70%, and the 1-, 3-, and 5-year tumor-free survivals of 91%, 84%, and 78% in patients with pkHCC. We concluded that patients with iHCC were more likely to be African-American, to be screened by ultrasound, to have a lower alpha-fetoprotein, and a higher MELD score. Ultrasound is not a sensitive modality for screening patients for HCC. Patients with iHCC do not have an advantage in survival over those with pkHCC.

Impact of model for end-stage liver disease on patient survival and disease-free survival in patients receiving liver transplantation for hepatocellular carcinoma.

We combined data from two transplant centers to determine the impact of the model for end-stage liver disease (MELD) allocation system on outcomes in patients undergoing liver transplantation for hepatocellular carcinoma (HCC). We compared 55 patients listed before MELD to 117 patients in the MELD era. Patients before MELD were less likely to receive a transplant (67% vs 91%) and waited a median of 127 days vs 20 days (P < .001). On an intention to treat (ITT) basis, the 1-, 3-, and 5-year survivals for patients before MELD were 79%, 60%, and 48%, and in the MELD era were 84%, 73%, and 73% (P = .055). On an ITT basis, the 1-, 3-, and 5-year tumor-free survivals before MELD were 58%, 58%, and 55% vs 83%, 74%, and 70% in the MELD era (P = .018). In patients who received a transplant, however, there were no differences in overall or tumor-free survival. In these patients, the 1-, 3-, and 5-year patient survivals were 92%, 84%, and 67% before MELD, and 90%, 81%, and 81% in the MELD era (P = .57). In transplanted patients, the 1-, 3-, and 5-year tumor-free survivals before MELD were 88%, 88%, and 83% vs 92%, 83%, and 78% in the MELD era (P = .403). On explant, patients listed before MELD had lower grade tumors (P = .046). We concluded that patients with HCC listed in the MELD era had higher and more rapid rates of transplantation with improvements in survival. However, the more efficacious rates of transplantation did not result in lower rates of tumor recurrence.

Prevalence of vitamin D depletion among subjects seeking advice on osteoporosis: a five-year cross-sectional study with public health implications.

UNLABELLED: We assessed vitamin D nutritional status in unselected consecutive patients seeking advice on osteoporosis. The prevalence of vitamin D depletion ranged from 15-72% depending upon the cut-off levels used for serum 25-hydroxyvitamin D, and the prevalence did not change over the 5 years of the study. INTRODUCTION: Vitamin D depletion is a significant public health problem and has been studied in different populations using different cut-off levels, but the optimal level is yet to be established. METHODS: In a cross-sectional study of 2,924 patients seen for osteoporosis advice we determined the prevalence of vitamin D depletion, as assessed by 25-hydroxyvitamin D (25-OHD), using three different cut-off levels stratified by gender, race and the year of the study over 5 years. RESULTS: Mean age was 68.3 +/- 10.0 years; 90% women and 88% white. Mean 25-OHD level was 24.6 +/- 10 ng/ml and mean PTH was 48.4 +/- 32 pg/ml. The prevalence of vitamin D depletion was 15% with a cut-off level of <15 ng/ml, and rose to 32% and 72% with cut-off levels <20 ng/ml and <30 ng/ml, respectively. The prevalence was higher in men and blacks and remained constant over 5 years, regardless of the cut-off level. The expected inverse relationship between 25-OHD and PTH was observed irrespective of gender or ethnicity. CONCLUSIONS: The prevalence of vitamin D depletion in patients seeking advice for osteoporosis is high and did not change over the 5 years of the study.

Influence of hepatitis C on renal function after liver transplantation.

Liver transplantation (OLT) is often complicated by renal failure. Hepatitis C (HCV) is said to be a risk factor for renal failure after OLT, but few studies have analyzed this directly. We evaluated all patients who received a liver transplant from 1995 through 2003. There were 147 patients infected with HCV and 202 not infected. Patients with HCV were further divided into 114 patients with benign HCV and 33 patients with severe HCV defined by bridging fibrosis or cirrhosis. The groups were evaluated for the development of renal insufficiency defined as a creatinine above 1.8 mg/dL on three consecutive occasions or renal failure as defined by the need for dialysis or renal transplant. The incidence of renal failure in patients with HCV was 10.2% and in patients without HCV was 3.5% (P = .004). Patients with severe HCV had an incidence of 12.1% vs 9.7% for patients with mild HCV. The linear trend in renal failure from non-HCV to mild HCV to severe HCV was significant (P = .012). The incidence of renal insufficiency was 23.4% in patients with HCV and 14.9% in patients without HCV (P = .080). The incidence was 32.3% in patients with severe HCV and 20.6% in patients with mild HCV. The trend in renal insufficiency across the three groups was mildly significant (P = .042). On multivariate analysis, HCV was a risk factor for renal failure with a relative risk of 2.58 (P = .045). The study suggests that HCV and the severity of recurrent HCV are risk factors for renal dysfunction after liver transplantation.

Long-term ovariectomy decreases ovine compact bone viscoelasticity.

Changes in bone mineral density associated with estrogen depletion in humans do not account for all of the associated change in fracture risk, and it is possible that some of this variation may lie in changes of other aspects of bone quality. The purpose of this study was to investigate changes in viscoelastic behavior of compact bone that may be associated with estrogen depletion. Changes in compact bone viscoelastic properties associated with three years of ovariectomy were investigated with dynamic mechanical analysis (low-amplitude 3-point bending at frequencies of 1-20 Hz) using beams milled from the diaphysis of the ovine radius. The viscoelastic storage modulus was significantly (5.2%) lower at the higher frequencies for the ovariectomized animals. The general anatomic variation in storage modulus, in which cranial sectors had higher values than caudal sectors, did not change with ovariectomy. The loss tangent (tandelta, a measure of damping) was also greatly decreased (up to 83%) at high frequencies in the ovariectomized animals. Anatomic variation in tandelta at low (6-12 Hz) frequencies (cranial and caudal sectors having higher values than lateral or medial sectors) was enhanced with ovariectomy. Changes in viscoelastic properties associated with long-term estrogen depletion could be responsible for a significant reduction in the toughness or strength of a bone without concomitant changes in screening modalities used to evaluate bone quality (e.g., DXA, QCT, QUA).

Determinants of ovine compact bone viscoelastic properties: effects of architecture, mineralization, and remodeling.

Significant decreases in ovine compact bone viscoelastic properties (specifically, stress-rate sensitivity, and damping efficiency) are associated with three years of ovariectomy and are particularly evident at higher frequencies [Proc. Orthop. Res. Soc. 27 (2002) 89]. It is unclear what materials or architectural features of bone are responsible for either the viscoelastic properties themselves, or for the changes in those properties that were observed with estrogen depletion. In this study, we examined the relationship between these viscoelastic mechanical properties and features involving bone architecture (BV/TV), materials parameters (ash density, %mineralization), and histologic evidence of remodeling (%remodeled, cement line interface). The extent of mineralization was inversely proportional to the material's efficiency in damping stress oscillations. The damping characteristics of bone material from ovariectomized animals were significantly more sensitive to variation in mineralization than was bone from control animals. At low frequencies (6 Hz or less), increased histologic evidence of remodeling was positively correlated with increased damping efficiency. However, the dramatic decreases in stress-rate sensitivity that accompanied 3-year ovariectomy were seen throughout the bone structure and occurred even in areas with little or no secondary Haversian remodeling as well as in areas of complete remodeling. Taken together, these data suggest that, while the mineral component may modify the viscoelastic behavior of bone, the basic mechanism underlying bone viscoelastic behavior, and of the changes in that behavior with estrogen depletion, reside in a non-mineral component of the bone that can be significantly altered in the absence of secondary remodeling.

Provider type and the receipt of general and diabetes-related preventive health services among patients with diabetes.

OBJECTIVE: Using a measure of provider type that includes "shared care" to determine the contribution of provider type on receipt of general and diabetes-related preventive health services. METHODS: Automated clinical and administrative data were used to identify adult patients with type 1 and 2 diabetes receiving care from a multispecialty, salaried group practice and enrolled in a large health maintenance organization between 3/97 and 2/98 (n = 10,991). Logistic regression models were fit using generalized estimating equation approaches to evaluate the contribution of provider type on service receipt. MEASURES: Preventive service receipt included receipt of glycated hemoglobin and lipid testing, retinal examinations, pneumococcal vaccines, Papanicolaou (Pap) smears, and mammograms. Multivariable analyses adjusted for age, sex, race, marital status, household income, diabetes-related comorbidities and complications, prescription drug use, laboratory testing results, and frequency of medical care contact. RESULTS: Patients seeing an endocrinologist and primary care physician (PCP) were more likely than those seeing endocrinologists alone to receive glycated hemoglobin testing (OR, 1.42), lipid testing (OR, 1.72), mammograms (OR, 2.12), and Pap smears (OR, 2.36), and more likely than those seeing PCPs alone to receive glycated hemoglobin testing (OR, 1.79), lipid testing (OR, 1.54), retinal examinations (OR, 1.33), and mammograms (OR, 1.43). Compared with patients seeing PCPs only, patient's seeing endocrinologists only were more likely to receive retinal examinations (OR, 1.37) and less likely to receive Pap smears (OR, 0.46). CONCLUSIONS: Care delivered by no one single provider type is associated with greater receipt of all recommended services. Instead, patients seeing both an endocrinologist and a PCP are most likely to receive recommended services.

A Web-based diabetes care management support system.

BACKGROUND: Because of the often asymptomatic nature of diabetes and the long period between sustained hyperglycemia and observable complications, appropriate diabetes care relies on a long-term program of secondary prevention. Yet routine monitoring and screening among patients with diabetes is less than optimal. To support the provision of routine care to patients with diabetes, the Center for Health Services Research, Henry Ford Health System (Detroit), developed a Web-based Diabetes Care Management Support System (DCMSS). A nonrandomized, longitudinal study was conducted (January 1, 1998-October 31, 1999) with 13,325 health maintenance organization patients with diabetes who were aligned to 190 primary care providers practicing in 31 primary care clinics. RESULTS: Three DCMSS features--clinical practice guidelines, patient registries, and performance reports--were made available via a corporate intranet within an existing electronic medical record. The effect of DCMSS usage frequency was evaluated on the likelihood of a patient's receipt of glycated hemoglobin testing, lipid profile testing, and retinal examinations. Logistic regression models controlling for patient sociodemographic and clinical characteristics, and the testing history of the patient, the primary care physician, and the primary care clinic, were fit using generalized estimating equation methods. The more often a physician used DCMSS, the more likely his or her patients were to receive lipid profile testing (OR [odds ratio] = 1.01, 95% CI [confidence interval] = 1.01-1.02). Compared with patients of physicians who never used the system, patients of physicians who initiated 12 sessions were an estimated 19% more likely (95% CI = 7%-33%) to receive lipid profile testing. The analyses also suggested that the likelihood of a patient receiving a retinal exam was associated with system usage (OR = 1.01, 95% CI = 1.01-1.01). No relationship was found between system use and glycated hemoglobin testing. CONCLUSIONS: Computerized systems of clinical practice guidelines, patient registries, and performance feedback may help improve the rate of routine testing among patients with diabetes.

Two-color, cytokeratin-labeled dna flow cytometric analysis of 332 breast cancers: lack of prognostic value with 12-year follow-up.

CONTEXT: DNA flow cytometry of breast cancer is a proposed tumor marker of prognostic significance that is of controversial clinical utility because of lack of standardization and confirmatory studies. OBJECTIVE: To evaluate the prognostic significance of the more informative technique of multiparametric 2-color DNA flow cytometry as recommended by the 1992 DNA Cytometry Consensus Conference. DESIGN: Three hundred thirty-two breast carcinomas with 7 to 12 years of follow-up were prospectively analyzed as fresh tumors that were mechanically dissociated into whole cell suspensions. These suspensions were dual fluorescence-labeled with propidium iodide (DNA) and antibodies to cytokeratin (epithelium) and leukocyte common antigen (internal leukocyte control) for gated analysis of subpopulations. Multicycle software with histogram-dependent algorithms employing background, aggregate, and debris correction were used in DNA and cell-cycle quantitation. Data were analyzed according to the DNA Flow Cytometry Consensus Conference recommendations. RESULTS: DNA ploidy and proliferation stratified into 3 categories were not predictive of overall or disease-free survival. Sixty-five percent of tumors were nondiploid, and 35.4% were diploid. Two hundred six tumors were able to be evaluated for synthesis-phase fraction (SPF) analysis, with 74 of 206 cases in the low range (<13.4%), 36.4% in the intermediate range (>13.5 to <25.4%), and 27.6% in the high SPF (>25.5%) category. Aneuploid tumors tended to have a higher SPF. Univariate survival analysis showed prognostic significance of the following: tumor size, stage, TNM components, vascular invasion, nuclear grade, and histologic grade. Only T classification, presence of positive axillary lymph nodes, and distant metastases were significant independent predictors of survival in multivariate Cox regression models. Age and hormone receptor status showed no prognostic significance. Synthesis-phase fraction was significantly correlated with tumor size, stage, T classification, nuclear and histologic grade, presence of estrogen or progesterone receptors, and axillary lymph node status. None of the histologic parameters showed any significant association with DNA aneuploidy, except for high nuclear and histologic grade and the absence of estrogen receptors. CONCLUSIONS: Despite the use of state-of-the-art processing and flow cytometry analytic techniques, DNA ploidy and proliferation measurements were not predictive of survival in any stage of breast cancer. However, select histopathologic parameters and TNM stage were significant predictors of survival in univariate and multivariate analyses. We conclude that DNA ploidy and proliferation measurements do not provide significant prognostic information for clinicians to integrate into therapeutic decision making for patients with breast cancer.

Magnetization transfer MRI: application to treatment of middle cerebral artery occlusion in rat.

The temporal profiles of MRI parameters which use quantitative estimates of magnetization transfer were measured in 22 male Wistar rats subjected to middle cerebral artery occlusion, with and without therapeutic intervention with an anti-ICAM-1 monoclonal antibody. Two measures were used: the value of a magnetization transfer-related parameter in a predetermined region of interest, and the area of damage, as measured by changes in this parameter. In both groups, the value and area of damage of the inverse of the apparent forward transfer rate for magnetization transfer (1/k(fa)) significantly increased from the preischemic values (P < 0.05), as did T1 under an off-resonance partial saturation of the macromolecular pool (T1sat), and T1 (P < 0.05). Moreover, the increase in the value and total area of damage, as measured by 1/k(fa), T1, and T1sat in the treated group, was smaller compared to that of the untreated group, with significant differences detected between groups at 5, 24, and 48 hours. Our data suggest that a quantitative measure of MT may provide a sensitive and early method to detect the efficacy of therapeutic intervention in experimental stroke.

Predictive modeling techniques in prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.