Right ventricular outflow reconstruction with cryopreserved homografts in pediatric patients: Intermediate-term follow-up with serial echocardiographic assessment

AbstractObjectives. This study was performed to assess by echocardiography the intermediate-term outcome of cryopreserved homografts employed in pulmonary outflow reconstruction in children and to validate the reliability of Doppler echocardiography in their evaluation.Background. Cryopreserved homografts have become the most widely used pulmonary conduits. Previous reports have shown the occurrence of homograft regurgitation in the immediate postoperative period and the propensity of regurgitation to progress. Although Doppler echocardiography has been useful in assessing extracardiac valved conduit stenosis, its reliability in assessing a large series of cryopreserved homografts has not been documented.Methods. Echocardiograms of 41 patients (43 homografts) who underwent operations between December 1986 and October 1992 were retrospectively reviewed. The median age of patients at operation was 37.5 months (range 3 to 333), and the median duration of follow-up was 28.5 months (range 1 to 68). Homograft regurgitation was classified on a scale of 0 to 4+. Pressure gradients across the homografts measured in 23 catheterizations were correlated with corresponding echocardiographic gradients.Results. Regurgitation: Homograft regurgitation occurred in 100% of patients at follow-up. Progression of severity >2 grades occurred during follow-up in 35% and was associated with operation before age 18 months (p < 0.002) and stenosis progression (p < 0.05) but not with homograft type (aortic or pulmonary). These data predict that 50% of patients operated on before 18 months of age will have severe regurgitation by 15 months postoperatively compared with only 15% operated on after 18 months. Stenosis: At follow-up, 51% of homografts had a stenotic gradient ≥25 mm Hg predominantly at the distal anastomosis, and stenosis progression was related to young age at operation (<18 months, p < 0.005) and small conduit size (p < 0.01). Fifty percent of conduits implanted before age 18 months could be predicted to stenose by 21.8 months compared with only 5% of those implanted after age 18 months. The gradient measured from Doppler echocardiography correlated well with the catheterization gradient (r = 0.86).Conclusions. Cryopreserved homograft dysfunction is frequent and progressive. Young age at operation (<18 months) predicts more rapid deterioration. Doppler echocardiography is reliable in assessing the systolic gradients across homografts. Serial echocardiographic assessment in the follow-up of these patients accurately characterizes these problems

Physician decision making in selection of second-line treatments in immune thrombocytopenia in children.

Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Genome-wide Association Study Identifies Two Susceptibility Loci for Osteosarcoma

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. In order to better understand the genetic etiology of osteosarcoma, we performed a multi-stage genome-wide association study (GWAS) consisting of 941 cases and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: rs1906953 at 6p21.3, in the glutamate receptor metabotropic 4 [GRM4] gene (P = 8.1 ×10-9), and rs7591996 and rs10208273 in a gene desert on 2p25.2 (P = 1.0 ×10-8 and 2.9 ×10-7). These two susceptibility loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma

Is the prevalence of psychiatric disorders associated with urbanization?

Objectives In many countries, the total rate of psychiatric disorders tends to be higher in urban areas than in rural areas. The relevance of this phenomenon is that it may help in identifying environmental factors that are important in the pathogenesis of mental disorders. Moreover, urban preponderance suggests that the allocation of funds and services should take urbanization levels into account. Method The Netherlands Mental Health Survey and Incidence Study (NEMESIS) used the Composite International Diagnostic Interview (CIDI) to determine the prevalence of DSM-III-R disorders in a sample of 7,076 people aged 18–64. The sample was representative of the population as a whole. The study population was assigned to five urbanization categories defined at the level of municipalities. The association between urbanization and 12-month prevalence rates of psychiatric disorders was studied using logistic regression taking several confounders into account. Results The prevalence of psychiatric disorders gradually increased over five levels of urbanization. This pattern remained after adjustment for a range of confounders. Comorbidity rates also increased with level of urbanization. Conclusion This study confirms that psychiatric disorders are more common and more complex in more urbanized areas. This should be reflected in service allocation and may help in identifying environmental factors of importance for the aetiology of mental disorders. j Key words population survey – psychiatric epidemiology – mental disorders – urbanizatio

Moving Towards the Post p < 0.05 Era via the Analysis of Credibility

It is now widely accepted that the techniques of null hypothesis significance testing (NHST) are routinely misused and misinterpreted by researchers seeking insight from data. There is, however, no consensus on acceptable alternatives, leaving researchers with little choice but to continue using NHST, regardless of its failings. I examine the potential for the Analysis of Credibility (AnCred) to resolve this impasse. Using real-life examples, I assess the ability of AnCred to provide researchers with a simple but robust framework for assessing study findings that goes beyond the standard dichotomy of statistical significance/nonsignificance. By extracting more insight from standard summary statistics while offering more protection against inferential fallacies, AnCred may encourage researchers to move toward the post p < 0.05 era

Dietary factors impact on the association between CTSS variants and obesity related traits.

Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors--increased by high protein, glycemic index and energy diets

Surface processes recorded by rocks and soils on Meridiani Planum, Mars: Microscopic Imager observations during Opportunity's first three extended missions

The Microscopic Imager (MI) on the Mars Exploration Rover Opportunity has returned images of Mars with higher resolution than any previous camera system, allowing detailed petrographic and sedimentological studies of the rocks and soils at the Meridiani Planum landing site. Designed to simulate a geologist's hand lens, the MI is mounted on Opportunity's instrument arm and can resolve objects 0.1 mm across or larger. This paper provides an overview of MI operations, data calibration, and analysis of MI data returned during the first 900 sols (Mars days) of the Opportunity landed mission. Analyses of Opportunity MI data have helped to resolve major questions about the origin of observed textures and features. These studies support eolian sediment transport, rather than impact surge processes, as the dominant depositional mechanism for Burns formation strata. MI stereo observations of a rock outcrop near the rim of Erebus Crater support the previous interpretation of similar sedimentary structures in Eagle Crater as being formed by surficial flow of liquid water. Well-sorted spherules dominate ripple surfaces on the Meridiani plains, and the size of spherules between ripples decreases by about 1 mm from north to south along Opportunity's traverse between Endurance and Erebus craters

Development and validation of the Diabetes Numeracy Test (DNT)

<p>Abstract</p> <p>Background</p> <p>Low literacy and numeracy skills are common. Adequate numeracy skills are crucial in the management of diabetes. Diabetes patients use numeracy skills to interpret glucose meters, administer medications, follow dietary guidelines and other tasks. Existing literacy scales may not be adequate to assess numeracy skills. This paper describes the development and psychometric properties of the Diabetes Numeracy Test (DNT), the first scale to specifically measure numeracy skills used in diabetes.</p> <p>Methods</p> <p>The items of the DNT were developed by an expert panel and refined using cognitive response interviews with potential respondents. The final version of the DNT (43 items) and other relevant measures were administered to a convenience sample of 398 patients with diabetes. Internal reliability was determined by the Kuder-Richardson coefficient (KR-20). An <it>a priori </it>hypothetical model was developed to determine construct validity. A shortened 15-item version, the DNT15, was created through split sample analysis.</p> <p>Results</p> <p>The DNT had excellent internal reliability (KR-20 = 0.95). The DNT was significantly correlated (p < 0.05) with education, income, literacy and math skills, and diabetes knowledge, supporting excellent construct validity. The mean score on the DNT was 61% and took an average of 33 minutes to complete. The DNT15 also had good internal reliability (KR-20 = 0.90 and 0.89). In split sample analysis, correlations of the DNT-15 with the full DNT in both sub-samples was high (rho = 0.96 and 0.97, respectively).</p> <p>Conclusion</p> <p>The DNT is a reliable and valid measure of diabetes related numeracy skills. An equally adequate but more time-efficient version of the DNT, the DNT15, can be used for research and clinical purposes to evaluate diabetes related numeracy.</p