The Autism–Tics,ADHD and other Comorbidities inventory (A-TAC): previous and predictive validity

Background

Reliable and easy to administer screening instruments focusing on neurodevelopmental disorders and associated conditions are scarce. The Autism–Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated and reporting good– excellent validity for several disorders. This article aims to expand these findings by including more conditions in a substantially larger sample augmented with the Swedish National Patient Register (NPR).

Methods

Since 2004 parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden, CATSS. The CATSS is linked to the NPR which includes data from in- and outpatient care. Data on neurodevelopmental disorders (A-TAC) collected in CATSS were compared with diagnoses from the NPR. We investigated diagnoses that had been made both before (previous validity) and after (predictive validity) the interview.

Results

Sensitivity and specificity of A-TAC scores for predicting earlier or later clinical diagnoses were mostly good–excellent, with values of the area under the curve for a clinical diagnosis of autism spectrum disorder (ASD) of .98, attention deficit hyperactivity disorder (ADHD) .93, learning disorder (LD) .92, and oppositional defiant disorder (ODD) .99, with small differences in terms of previous and predictive analyses. A-TAC provided little validity for eating disorders.

Conclusion

The result support previous claims: A-TAC is a broad screening instrument with a particular strength in assessing ASD, ADHD, LD, and ODD at ages 9 and 12, and also provides phenotypic information about other child psychiatric disorders.

     

Pitfalls and major issues in the histologic diagnosis of peripheral T‐cell lymphomas: results of the central review of 573 cases from the T‐Cell Project,an international,cooperative study

Peripheral T‐cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post‐thymic lymphoid cells at different stages of differentiation with different morphological patterns, phenotypes and clinical presentations. PTCLs are highly diverse, reflecting the diverse cells from which they can originate and are currently sub‐classified using World Health Organization (WHO) 2008 criteria. In 2006 the International T‐Cell Lymphoma Project launched the T‐Cell Project, building on the retrospective study previously carried on by the network, with the aim to prospectively collect accurate data to improve knowledge on this group of lymphomas. Based on previously published reports from International Study Groups it emerged that rendering a correct classification of PTCLs is quite difficult because the relatively low prevalence of these diseases results in a lack of confidence by most pathologists. This is the reason why the T‐Cell Project requested the availability of diagnostic material from the initial biopsy of each patient registered in the study in order to have the initial diagnosis centrally reviewed by expert hematopathologists. In the present report the results of the review process performed on 573 cases are presented. Overall, an incorrect diagnosis was centrally recorded in 13.1% cases, including 8.5% cases centrally reclassified with a subtype eligible for the project and 4.6% cases misclassified and found to be disorders other than T‐cell lymphomas; 2.1% cases were centrally classified as T‐Cell disorders not included in the study population. Thus, the T‐Cell Project confirmed the difficulties in providing an accurate classification when a diagnosis of PTCLs is suspected, singled out the major pitfalls that can bias a correct histologic categorization and confirmed that a centralized expert review with the application of adequate diagnostic algorithms is mandatory when dealing with these tumours. Copyright © 2016 John Wiley & Sons, Ltd.     

Surface dose measurements in and out of field: Implications for breast radiotherapy with megavoltage photon beams

This study examines the difference in surface dose between flat and flattening filter free (FFF) photon beams in the context of breast radiotherapy. The surface dose was measured for 6 MV, 6 MV FFF, 10 MV, 10 MV FFF and 18 MV photon beams using a thin window ionisation chamber for various field sizes. Profiles were acquired to ascertain the change in surface dose off-axis. Out-of-field measurements were included in a clinically representative half beam block tangential breast field. In the field centres of FFF beams the surface dose was found to be increased for small fields and decreased for large fields compared to flat beams. For FFF beams, surface dose was found to decrease off-axis and resulted in lower surface dose out-of-field compared to flat beams.     

IgM myeloma: A multicenter retrospective study of 134 patients

IgM myeloma is a rare hematologic malignancy for which the clinicopathological features and patient outcomes have not been extensively studied. We carried out a multicenter retrospective study in patients with diagnosis of IgM myeloma defined by >10% marrow involvement by monoclonal plasma cells, presence of an IgM monoclonal paraproteinemia of any size, and anemia, renal dysfunction, hypercalcemia, lytic lesions and/or t(11;14) identified by FISH. A total of 134 patients from 20 centers were included in this analysis. The median age at diagnosis was 65.5 years with a male predominance (68%). Anemia, renal dysfunction, elevated calcium and skeletal lytic lesions were found in 37, 43, 19, and 70%, respectively. The median serum IgM level was 2,895 mg dL^?1 with 19% of patients presenting with levels >6,000 mg dL^?1. International Staging System (ISS) stages 1, 2, and 3 were seen in 40 (33%), 54 (44%), and 29 (24%) of patients, respectively. The malignant cells expressed CD20 (58%) and cyclin D1 (67%), and t (11;14) was the most common cytogenetic finding (39%). The median overall survival (OS) was 61 months. Higher ISS score was associated with worse survival (P = 0.02). Patients with IgM myeloma present with similar characteristics and outcomes as patients with more common myeloma subtypes.     

Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids

The lymphoid tyrosine phosphatase (Lyp, PTPN22) is a critical negative regulator of T cell antigen receptor (TCR) signaling. A single-nucleotide polymorphism (SNP) in the ptpn22 gene correlates with the incidence of various autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and systemic lupus erythematosus. Since the disease-associated allele is a more potent inhibitor of TCR signaling, specific Lyp inhibitors may become valuable in treating autoimmunity. Using a structure-based approach, we synthesized a library of 34 compounds that inhibited Lyp with IC(50) values between 0.27 and 6.2 μM. A reporter assay was employed to screen for compounds that enhanced TCR signaling in cells, and several inhibitors displayed a dose-dependent, activating effect. Subsequent probing for Lyp's direct physiological targets by immunoblot analysis confirmed the ability of the compounds to inhibit Lyp in T cells. Selectivity profiling against closely related tyrosine phosphatases and in silico docking studies with the crystal structure of Lyp yielded valuable information for the design of Lyp-specific compounds.     

Synthesis and significant cytostatic activity of 7-hetaryl-7-deazaadenosines

A series of 7-aryl- and 7-hetaryl-7-deazaadenosines was prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes, or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro antiproliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells. Intracellular conversion to triphosphates has been detected with active compounds. The triphosphate metabolites showed only a weak inhibitory effect on human RNA polymerase II, suggesting potentially other mechanisms for the inhibition of RNA synthesis and quick onset of apoptosis. Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model.     

A randomised trial of endobronchial ultrasound guided sampling in peripheral lung lesions

Aim

The aim of the study was to evaluate endobronchial ultrasound (EBUS) for peripheral lung lesions and to find the most cost effective combination of sampling techniques.

Materials

264 patients with lesions suspicious of malignancy were recruited in Bergen and Aalesund, Norway from 2005 to 2008.

Methods

The study was a prospective randomised cohort study. EBUS was performed with a 1.7 mm rotating probe. X-ray fluoroscopy was used in both arms. The different sampling techniques were evaluated in a cost-effectiveness analysis.

Results

The detection rate for cancer was 36% in the EBUS group, 44% in the non-EBUS group (ns). Lesions below 3 cm and lesions assumed difficult to reach had significant lower detection rates in the EBUS group. Lesions visualised by EBUS had a higher detection rate for cancer than lesions not visualised by EBUS (62% vs. 19%, p < 0.01). The cost of one additional positive sample was 1211 euro when brushing was added to biopsy. It was not cost effective to add washing or TBNA.

Conclusion

EBUS did not increase the detection rate for cancer in peripheral lung lesions when bronchoscopy was performed by bronchoscopists at all levels of expertise. Biopsy and brushing was the most cost effective combination of sampling techniques.