Type 2 diabetes impairs annulus fibrosus fiber deformation and rotation under disc compression in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.

Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing disc degeneration. We used synchrotron small-angle X-ray scattering to investigate how changes to collagen behavior contribute to alterations in the disc's ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats ( n=7) and diabetic obese University of California Davis type 2 diabetes mellitus (UCD-T2DM) rats ( n=6, diabetic for 68±7 days) were compressed during simultaneous synchrotron scanning to measure collagen strain at the nanoscale (beamline 7.3.3 of the Advanced Light Source). After compression, the annulus fibrosus was assayed for nonenzymatic cross-links. In discs from lean rats, resistance to compression involved two main energy-dissipation mechanisms at the nanoscale: (1) rotation of the two groups of collagen fibrils forming the annulus fibrosus and (2) straightening (uncrimping) and stretching of the collagen fibrils. In discs from diabetic rats, both mechanisms were significantly impaired. Specifically, diabetes reduced fibril rotation by 31% and reduced collagen fibril strain by 30% (compared to lean discs). The stiffening of collagen fibrils in the discs from diabetic rats was consistent with a 31% higher concentration of nonenzymatic cross-links and with evidence of earlier onset plastic deformations such as fibril sliding and fibril-matrix delamination. These findings suggest that fibril reorientation, stretching, and straightening are key deformation mechanisms that facilitate whole-disc compression, and that type 2 diabetes impairs these efficient and low-energy elastic deformation mechanisms, thereby altering whole-disc behavior and inducing the earlier onset of plastic deformation.

Comparing CSF biomarkers and brain MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease.

We assessed the diagnostic utility of 3 CSF biomarkers-14-3-3 protein, total tau (T-tau), and neuron-specific enolase (NSE)-from the same lumbar puncture to distinguish between participants with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease (sCJD, n = 57) and controls with nonprion rapidly progressive dementia (npRPD, n = 41). Measures of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, as well as logistic regression and area under the receiver operator curve (AUC), were used to assess the ability of these CSF biomarkers, alone or concomitantly, to predict diagnosis. In a subcohort with available MRI (sCJD n = 57, npRPD = 32), we compared visual assessment of diffusion-weighted imaging MRI sequences to these CSF biomarkers. MRI was the best predictor, with an AUC of 0.97 (confidence interval [CI] 0.92-1.00) and a diagnostic accuracy of 97% (CI 90%-100%). Of the CSF biomarkers, T-tau had a higher diagnostic accuracy (79.6%) than 14-3-3 (70.4%, CI for difference 8.7%, 9.7%; p = 0.048) or NSE (71.4%, CI for difference 7.6%, 8.7%; p = 0.03).

Health-Related Quality of Life in Patients with MPS II.

Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a chronic and progressive X-linked lysosomal disease that mainly affects males. The National MPS Society (2013) reports that MPS II affects 1 in 100,000 to 1 in 150,000 males worldwide. Two distinct forms of the disease are based on age of onset and clinical course: attenuated and severe. MPS II affects many organ systems including the nervous, cardiovascular, gastrointestinal and respiratory systems. Clinical manifestations can include progressive hearing loss, mental impairment, and enlarged liver and spleen. This study focuses on the health-related quality of life of individuals (HRQOL) with MPS II as measured by the parent and self-report versions of the Pediatric Quality of Life Inventory (PedsQL™). Both parents of patients with MPS II as well as patients themselves reported lower scores on all domains of the PedsQL™ (physical, emotional, social and school functioning) indicating that children with MPS II have an overall lower HRQOL when compared to a healthy sample. When compared with patients with other chronic illnesses (cancer, MSUD, galactosemia,), the MPS II sample had significantly lower scores on a number of PedsQL™ scales, suggesting an overall lower HRQOL. No significant relationships were found using scores from parent or self report PedsQL™ measures and length of time on ERT.

Renal outcomes of simultaneous liver-kidney transplantation compared to liver transplant alone for candidates with renal dysfunction.

It is unclear whether a concomitant kidney transplant grants survival benefit to liver transplant (LT) candidates with renal dysfunction (RD). We retrospectively studied LT candidates without RD (n = 714) and LT candidates with RD who underwent either liver transplant alone (RD-LTA; n = 103) or simultaneous liver-kidney transplant (RD-SLKT; n = 68). RD was defined as renal replacement therapy (RRT) requirement or modification of diet in renal disease (MDRD)-glomerular filtration rate (GFR) <25 mL/min/1.73 m(2) . RD-LTAs had worse one-yr post-transplant survival compared to RD-SLKTs (79.6% vs. 91.2%, p = 0.05). However, RD-LTA recipients more often had hepatitis C (60.2% vs. 41.2%, p = 0.004) and more severe liver disease (MELD 37.9 ± 8.1 vs. 32.7 ± 9.1, p = 0.0001). Twenty RD-LTA recipients died in the first post-transplant year. Evaluation of the cause and timing of death relative to native renal recovery revealed that only four RD-LTA recipients might have derived survival benefit from RD-SLKT. Overall, 87% of RD-LTA patients recovered renal function within one month of transplant. One yr after RD-LTA or RD-SLKT, serum creatinine (1.5 ± 1.2 mg/dL vs. 1.4 ± 0.5 mg/dL, p = 0.63) and prevalence of stage 4 or 5 chronic kidney disease (CKD; 5.9% vs. 6.8%, p = 0.11) were comparable. Our series provides little evidence that RD-SLKT would have yielded substantial short-term survival benefit to RD-LTA recipients.

Association of empathy of nursing staff with reduction of seclusion and restraint in psychiatric inpatient care.

OBJECTIVE: Disruptive behavior leading to seclusion or restraint increases with patients in a high-acuity stage of mental illness who have histories of aggressive behavior. The study examined whether greater nursing staff empathy skills and motivation reduced use of seclusion and restraint and whether empathy training can further this effect. METHODS: In 1,098 nursing shifts in 2 six-month periods one year apart, hierarchical analyses examined the effects of nursing shift and patient characteristics, the effect for each shift of nurses' skill and motivation to use empathy, and whether empathy training reduced use of seclusion and restraint. RESULTS: With controls for shift, patient, and other staffing variables, analyses showed that the presence of more nursing staff with above-average empathy ratings was strongly associated with reduced use of seclusion and restraint but empathy training showed no further benefit. CONCLUSIONS: Recruiting and retaining empathic nursing staff may be the best way to reduce the use of seclusion and restraint.

NIH EXAMINER: conceptualization and development of an executive function battery.

Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals.

Intimate partner violence and condom and diaphragm nonadherence among women in an HIV prevention trial in southern Africa.

BACKGROUND: We longitudinally examined the effect of intimate partner violence (IPV) on condom and diaphragm nonadherence among women in the Methods for Improving Reproductive Health in Africa study, a phase III HIV prevention trial in southern Africa. METHODS: Recent IPV (fear of violence, emotional abuse, physical violence, or forced sex, in past 3 months), condom nonadherence, and diaphragm nonadherence were assessed at baseline, 12 month, and exit visits (up to 24 months). The association between IPV and (1) condom nonadherence or (2) diaphragm nonadherence across visits was modeled using Generalized Estimating Equations adjusting for potential confounders. RESULTS: Of 4505 participants, 55% reported recent IPV during their trial participation. Women reported fearing violence (41%), emotional abuse (38%), being physically assaulted (16%), and forced sex (15%) by their regular male partner. IPV was associated with condom nonadherence in both study arms [adjusted odds ratio (AOR): 1.41, 95% confidence interval (CI): 1.24 to 1.61 (control arm) and AOR: 1.47, 95% CI: 1.28 to 1.69, (intervention arm)] and with diaphragm nonadherence (AOR 1.24, 95% CI: 1.06 to 1.45) adjusting for age, study sites, number of sex partners, and knowledge of male partner infidelity. Modeling effects of each form of IPV separately on nonadherence outcomes yielded similar results. CONCLUSIONS: Prevalence of recent IPV was high and associated with condom and diaphragm nonadherence during the trial. Counseling in prevention trials should proactively address IPV, for its own sake, and in product and risk-reduction counseling. Strategies to encourage men's positive involvement in product use and prevent IPV perpetration should be considered.

Lack of association of BRAF mutation with negative prognostic indicators in papillary thyroid carcinoma: the University of California, San Francisco, experience.

IMPORTANCE: Papillary thyroid carcinoma (PTC) is the most common endocrine neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative prognostic indicator in PTC, and patients harboring it should receive more aggressive initial therapy. OBJECTIVE: To assess the significance of BRAF V600E mutation in PTC in the largest US sample to date. DESIGN: We identified patients from our institution's pathology archives diagnosed as having PTC and meeting criteria for BRAF mutation testing. Medical records were analyzed for BRAF status (positive or negative) and a list of standardized clinicopathologic features. PARTICIPANTS: A total of 429 patients with PTC at an academic medical center. MAIN OUTCOMES AND MEASURES: Clinicopathologic features in patients with PTC with and without BRAF mutation. RESULTS: Of 429 cases with PTC, 314 (73.2%) were positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was significantly associated with tumor margin positivity (P = .03) and lymph node metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2), total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis. CONCLUSIONS AND RELEVANCE: BRAF V600E mutation has been extensively studied in relation to negative prognostic indicators in PTC, with no consistent relationship emerging. Two recent meta-analyses showed an overall association between BRAF status and aggressive disease features and called for tailoring treatment plans in patients accordingly. In this, the largest US study to date, BRAF status was not significantly associated with most clinicopathologic features suggestive of more aggressive disease.

Interrater reliability of the new criteria for behavioral variant frontotemporal dementia.

OBJECTIVE: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD). METHODS: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by κ statistics for multiple raters with categorical ratings. RESULTS: The mean κ value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; κ = 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; κ = 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy. CONCLUSIONS: The FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important.

The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia.

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).

The New York policy on smoking in addiction treatment: findings after 1 year.

OBJECTIVES: We assessed changes in smoking prevalence and other measures associated with the July 2008 New York Office of Alcoholism and Substance Abuse Services tobacco policy, which required that all publicly funded addiction treatment programs implement smoke-free grounds, have "no evidence" of smoking among staff, and make tobacco dependence treatment available for all clients. METHODS: In a random sample of 10 programs, staff and clients were surveyed before the policy and 1 year later. Measures included tobacco-related knowledge, attitudes, and practices used by counselors and received by clients. RESULTS: Client smoking decreased from 69.4% to 62.8% (P = .044). However, response to the policy differed by program type. Outpatient programs showed no significant changes on any of the staff and client survey measures. In methadone programs, staff use of tobacco-related practices increased (P < .01), client attitudes toward tobacco treatment grew more positive (P < .05), and clients received more tobacco-related services (P < .05). Residential clients were more likely to report having quit smoking after policy implementation (odds ratio = 4.7; 95% confidence interval = 1.53, 14.19), but they reported less favorable attitudes toward tobacco treatment (P < .001) and received fewer tobacco-related services from their program (P < .001) or their counselor (P < .001). CONCLUSIONS: If supported by additional research, the New York policy may offer a model that addiction treatment systems can use to address smoking in a population where it has been prevalent and intractable. Additional intervention or policy supports may be needed in residential programs, which face greater challenges to implementing tobacco-free grounds.

Impact of learning HIV status on contraceptive use in the MIRA trial.

BACKGROUND AND METHODOLOGY: We examined the effect of becoming HIV-positive on contraceptive practices in a Phase III randomised controlled trial of the diaphragm for HIV prevention. We coded self-reported contraceptive use into seven categories of methods in order of effectiveness. We compared the proportion using each category of contraception at baseline and last visit between women who did and did not become HIV-positive. We compared changes in the proportion using each category of contraception from baseline to last visit and calculated the percentage of women that moved to a more or less effective method category or stayed the same. We examined immediate and long-term changes in contraceptive use category after learning HIV-positive status. RESULTS: A total of 4645 women remained HIV-negative and 309 became HIV-positive. The proportion using each category of contraception was similar between groups at baseline and last visit. In both groups approximately one-fifth changed to a less effective method category between baseline and last visit. Few women reported using long-acting methods. Among HIV-positive women, shorter-term changes in the proportion using each category of contraception were similar to longer-term changes, though somewhat more women were using a method in the same category 3 months after seroconversion. DISCUSSION AND CONCLUSIONS: Learning about HIV-positive status did not appear to significantly change patterns of use of effective contraceptives or the probability of switching to a more or less effective method. Information about, and access to, long-acting methods should receive more attention and be a routine part of family planning programmes and prevention trials.

Contraception use and effectiveness among women in a trial of the diaphragm for HIV prevention.

BACKGROUND: There is little data on contraceptive effectiveness or use patterns from sub-Saharan Africa. STUDY DESIGN: We analyzed data from women at risk of pregnancy (n=4905) in the Methods for Improving Reproductive Health in Africa trial of the diaphragm for HIV prevention. We described reported contraceptive method use and calculated rates of pregnancy by contraceptive method. We compared time to first pregnancy by study arm (condoms or condoms plus diaphragm), and estimated a Cox proportional hazards model to identify predictors of pregnancy. RESULTS: Condoms (25.8%), injectables (25.4%) and OC (21.6%) were the most commonly used methods; long-acting method use was rare. During the trial, 51.6% of women used the same method, 27.4% switched to a more effective method and 20.9% switched to a less effective method; 21.4% of women became pregnant. Pregnancy rates by contraceptive group mirrored published estimates; frequency of study product use was not associated with pregnancy. CONCLUSION: Long-acting methods of contraception should be made available in HIV prevention trials and to women in Southern Africa.

Smoking prevalence in addiction treatment: a review.

INTRODUCTION: This review explores whether smoking prevalence in addiction treatment samples exceeds that shown in epidemiological data for persons with alcohol or other drug use disorders and whether smoking may have decreased over time in the addiction treatment population as it has done in the general population. METHODS: English language papers published between 1987 and 2009 were searched electronically. Forty papers reporting smoking prevalence for addiction treatment samples in the United States were identified, and key predictor variables were abstracted. Random logistic models were used to assess relationships between each individual predictor (year, treatment modality, primary drug treated, government status, and public/private funding status) and smoking prevalence. RESULTS: The lowest smoking prevalence aggregated for studies reported in any single year was 65%, well above epidemiological estimates reported among those with alcohol use and drug use disorders. The odds of smoking were higher in methadone maintenance programs (odds ratio [OR] = 2.25, CI = 1.08, 4.68) as compared with outpatient programs. No other variables in the model were significant. Reanalysis omitting recent studies that may represent outliers or confounding with type of treatment showed a small but significant decrease in smoking over time (OR = 0.9891, CI = 0.9888, 0.9893). CONCLUSIONS: The very high smoking rates reported in addiction treatment samples warrant significant, organized, and systemic response from addiction treatment systems, from agencies that fund and regulate those systems, and from agencies concerned with tobacco control.

A Randomized Trial of Probation Case Management for Drug-Involved Women Offenders.

This paper reports findings from a clinical trial of a probation case management (PCM) intervention for drug-involved women offenders. Participants were randomly assigned to either PCM (n=92) or standard probation (n=91), and followed for 12 months using measures of substance abuse, psychiatric symptoms, social support and service utilization. Arrest data were collected from administrative datasets. The sample (N=183) included mostly African American (57%) and White (20%) women, with a mean age of 34.7 (SD = 9.2) and mean education of 11.6 years (SD = 2.1). Cocaine and heroin were the most frequently reported drugs of abuse, 86% reported prior history of incarceration, and 74% had children. Women assigned to both PCM and standard probation showed change over time in the direction of clinical improvement on 7 of 10 outcomes measured. However, changes observed for the PCM group were no different than those observed for the standard probation group. Higher levels of case management, drug abuse treatment, and probationary supervision may be required to achieve improved outcomes in this population.

A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder.

We conducted a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children ages 3-8 with autism spectrum disorder (ASD). After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (± 4.8) points in the omega-3 group compared to 0.3 (± 7.2) points in the placebo group (p = 0.40; effect size = 0.38). Correlations were found between decreases in five fatty acid levels and decreases in hyperactivity, and the treatment was well tolerated. Although this pilot study did not find a statistically significant benefit from omega-3 fatty acids, the small sample size does not rule out small to moderate beneficial effects.

Incidence of stricturing and penetrating complications of Crohn's disease diagnosed in pediatric patients.

BACKGROUND: The development of disease complications is poorly characterized in pediatric patients with Crohn's disease (CD). METHODS: We retrospectively determined the cumulative incidence of stricturing and penetrating complications of CD prior to first surgery utilizing data from 989 consecutively enrolled CD patients (age 0-17 years at diagnosis) collected between January 2000 and November 2003 and stored in the Pediatric IBD Consortium Registry. RESULTS: Mean age at diagnosis was 11.5 +/- 3.8 (standard deviation) years. Median follow-up time was 2.8 years. Prior to first surgery, the cumulative incidence of stricturing or penetrating complications was 27% at 5 years and 38% at 10 years from the diagnosis of inflammatory bowel disease. The cumulative incidence of complicated disease was lowest in isolated colonic disease (P = 0.009). Penetrating complications that followed stricturing complications prior to first surgery occurred within 2 years of stricturing complications (cumulative incidence was 13% at 2 years from diagnosis of stricturing disease). Stricturing complications that followed penetrating complications prior to first surgery occurred within 8 years of penetrating complications (cumulative incidence was 26% at 8 years from diagnosis of penetrating complications). CONCLUSIONS: Strictures, abscesses, and fistulas are common in pediatric CD. Earlier aggressive management may be indicated. Prospective study is required to identify genetic and serologic markers that predict a patient's risk for the development of complicated disease and to determine optimal treatment regimens.

Association of attitudes and beliefs towards antiretroviral therapy with HIV-seroprevalence in the general population of Kisumu, Kenya.

BACKGROUND: Since antiretroviral therapy (ART) became available in the developed world, the prevalence of unprotected sex and the incidence of sexually transmitted infections (STIs) and HIV have increased. We hypothesized that a similar phenomenon may be occurring in sub-Saharan Africa concomitant with the scale-up of HIV treatment. METHODS: We conducted a general population-based survey in Kisumu, Kenya. Participants completed an interview that included demographics as well as ART-related attitudes and beliefs (AB) and then underwent HIV serological testing. Exploratory and confirmatory factor analyses of AB about ART indicated two factors: 1) ART-related risk compensation (increased sexual risk taking now that ART is available); and 2) a perception that HIV is more controllable now that ART is available. Logistic regression was used to determine associations of these factors with HIV-seroprevalence after controlling for age. FINDINGS: 1,655 (90%) of 1,844 people aged 15-49 contacted, including 749 men and 906 women, consented to participate in the study. Most participants (n = 1164; 71%) had heard of ART. Of those who had heard of ART, 23% believed ART was a cure for HIV. ART-related risk compensation (Adjusted (A)OR = 1.45, 95% CI 1.16-1.81), and a belief that ART cures HIV (AOR = 2.14, 95% CI 1.22-3.76) were associated with an increased HIV seroprevalence in men but not women after controlling for age. In particular, ART-related risk compensation was associated with an increased HIV-seroprevalence in young (aged 15-24 years) men (OR = 1.56; 95% CI 1.12-2.19). CONCLUSIONS: ART-related risk compensation and a belief that ART cures HIV were associated with an increased HIV seroprevalence among men but not women. HIV prevention programs in sub-Saharan Africa that target the general population should include educational messages about ART and address the changing beliefs about HIV in the era of greater ART availability.

Alcohol use and prostate cancer: a meta-analysis.

Past reviews have concluded that there is no association between alcohol use and prostate cancer incidence. We performed a meta-analysis of existing epidemiological studies finding, in contrast, evidence to suggest that prostate incidence is positively linearly associated with heavier alcohol use. This finding was largely due to the contribution of population case-control studies and those measuring men recruited before age 60. No relationship between alcohol consumption and prostate cancer was found for cohort and hospital case-control studies. Analyses of design effects modestly suggests that population case-control studies were probably better suited to identify potential alcohol-prostate cancer relationships due to the close temporal proximity of the measurement of level of alcohol consumption to diagnosis. Future efforts should be made to exclude all ill subjects from control groups/baseline samples in addition to accounting for changes in consumption with advancing age and the onset of illness. The alcohol-prostate cancer association remained significant despite controlling for the degree to which studies endeavored to eliminate false negatives from their control groups.

Presentation and disease course in early- compared to later-onset pediatric Crohn's disease.

BACKGROUND: The relationship between the age at diagnosis and disease course is poorly defined in children with Crohn's disease (CD). We examined the presentation and course of disease in patients 0-5 compared to 6-17 yr of age at diagnosis. METHODS: We analyzed uniform data from 989 consecutive CD patients collected between January 2000 and November 2003, and stored in the Pediatric IBD Consortium Registry. The statistical tests account for the length of follow-up of each patient. RESULTS: In total, 98 patients (9.9%) were of 0-5 yr of age at diagnosis. The mean follow-up time was 5.6 +/- 5.0 yr in the younger group and 3.3 +/- 2.8 yr in the older group (P < 0.001). Race/ethnicity differed by the age group (P= 0.015); a larger proportion of the younger group was Asian/Pacific Islander or Hispanic, and a larger proportion of the older group was African American. The initial classification as ulcerative colitis or indeterminate colitis was more common among the 0-5 yr of age group (P < 0.001). The 6-17 yr of age patients presented with more abdominal pain (P < 0.001), weight loss (P= 0.001), or fever (P= 0.07), while the 0-5 yr of age patients presented with more rectal bleeding (P= 0.008). The 6-17 yr of age patients were more likely to be treated with antibiotics (P < 0.001), 6-mercaptopurine/azathioprine (P < 0.001), infliximab (P= 0.001), or corticosteroids (P= 0.0006). The 6-17 yr of age patients had a higher cumulative incidence of treatment with 5-aminosalicylates (P= 0.009) or methotrexate (P= 0.04). The risk for developing an abscess (P= 0.001), a fistula (P= 0.02), a stricture (P= 0.05), or a perianal fissure (P= 0.06) was greater in the 6-17 yr of age patients. CONCLUSIONS: The 6-17 yr of age patients with CD appear to have a more complicated disease course compared to 0-5 yr of age children. The 0-5 yr of age group may represent a unique disease phenotype and benefit from different approaches to management. Long-term prospective studies are required to validate these findings.