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David Atkins

Publications and source records attributed to David Atkins.

At least 19 recordsLinked to original sources
PubMed2025

Improving Community-Based Care for Adolescents with ADHD: a Randomized Controlled Trial of Artificial Intelligence-Assisted Fidelity Supports.

Cognitive-behavioral treatments (CBTs) for adolescents with ADHD demonstrate promise of long-term effects on outcome. However, their implementation in routine care community clinics faces barriers that impact quantity, efficiency, and quality of delivery, as well as client outcomes. This study is a randomized controlled trial designed to evaluate the impact of an AI-assisted service delivery model on therapist implementation of Supporting Teens' Autonomy Daily (STAND), a CBT blended with Motivational Interviewing (MI) for adolescents with ADHD. Adolescents with ADHD (N = 51), who were clients at three community mental health agencies, received treatment from 23 therapists. There was randomization of adolescents and therapists to AI-assisted or standard implementation supports. In addition to standard supports (i.e., training, standard facilitation resources, technical assistance, case supervision), AI-assisted support package included digitized facilitation resources housed in a clinical dashboard (Care4), feedback on content fidelity, and AI-generated feedback on MI implementation quality. The AI-assisted group was associated with more efficient treatment delivery and lower number of appointments attended by the adolescent. There was also a significant decrement in MI quality over time in the AI-assisted group compared to the standard support group. Feedback in focus groups indicated that therapists perceived a task-oriented mindset to be associated with receipt of the AI-assisted support package, leading therapists to prioritize efficiency over relational aspects of therapy. Following the results of this trial, a future, larger RCT should examine the impact of the AI-assisted implementation model on mental health outcomes and cost savings to organizations, third party payers, and clients. Trial registration number: NCT05135065; https://www.clinicaltrials.gov ; Registered September 2021.

Humans↗
PubMed2006

Genes associated with breast cancer metastatic to bone.

PURPOSE: The biology of tumors relapsing to bone is poorly understood. In this study, we initiated a search for genes that are implicated in tumors relapsing to bone in breast cancer. PATIENTS AND METHODS: We analyzed 107 primary breast tumors in patients who were all lymph node negative at the time of diagnosis and all had experienced relapse. Total RNA isolated from frozen tumor samples was used to gather gene expression data using oligo microarrays. RESULTS: A panel of 69 genes was found significantly differentially expressed between patients who experienced relapse to bone versus those who experienced relapse elsewhere in the body. The most differentially expressed gene, TFF1, was confirmed by quantitative reverse transcriptase polymerase chain reaction in an independent cohort (n = 122; P = .0015). Our differentially expressed genes, combined with a recently reported gene set relevant to tumors relapsing to bone in an animal model system, pointed to the involvement of the fibroblast growth factor receptor signaling pathway in preference of tumor cells that relapse to bone. Given that patients who experience relapse to bone may benefit from bisphosphonate therapy, we developed a classifier of 31 genes, which in an independent validation set correctly predicts all tumors relapsing to bone with a specificity of 50%. CONCLUSION: Our study identifies a panel of genes relevant to bone metastasis in breast cancer. The subsequently developed classifier of tumors relapsing to bone could, after thorough confirmation on an extended number of independent samples, and in combination with our previously developed high-risk profile, provide a diagnostic tool for the recommendation of adjuvant bisphosphonate therapy in addition to endocrine therapy or chemotherapy.

Adult↗
PubMed2006

Multicenter validation of a gene expression-based prognostic signature in lymph node-negative primary breast cancer.

PURPOSE: We previously identified in a single-center study a 76-gene prognostic signature for lymph node-negative (LNN) breast cancer patients. The aim of this study was to validate this gene signature in an independent more diverse population of LNN patients from multiple institutions. PATIENTS AND METHODS: Using custom-designed DNA chips we analyzed the expression of the 76 genes in RNA of frozen tumor samples from 180 LNN patients who did not receive adjuvant systemic treatment. RESULTS: In this independent validation, the 76-gene signature was highly informative in identifying patients with distant metastasis within 5 years (hazard ratio, [HR], 7.41; 95% CI, 2.63 to 20.9), even when corrected for traditional prognostic factors in multivariate analysis (HR, 11.36; 95% CI, 2.67 to 48.4). The actuarial 5- and 10-year distant metastasis-free survival were 96% (95% CI, 89% to 99%) and 94% (95% CI, 83% to 98%), respectively, for the good profile group and 74% (95% CI, 64% to 81%) and 65% (53% to 74%), respectively for the poor profile group. The sensitivity for 5-yr distant metastasis-free survival was 90%, and the specificity was 50%. The positive and negative predictive values were 38% (95% CI, 29% to 47%) and 94% (95% CI, 86% to 97%), respectively. The 76-gene signature was confirmed as a strong prognostic factor in subgroups of estrogen receptor-positive patients, pre- and postmenopausal patients, and patients with tumor sizes 20 mm or smaller. The subgroup of patients with estrogen receptor-negative tumors was considered too small to perform a separate analysis. CONCLUSION: Our data provide a strong methodologic and clinical multicenter validation of the predefined prognostic 76-gene signature in LNN breast cancer patients.

Adult↗
PubMed2006

A quantitative reverse transcriptase-polymerase chain reaction assay to identify metastatic carcinoma tissue of origin.

Identifying the primary site in patients with metastatic carcinoma of unknown primary origin can enable more specific therapeutic regimens and may prolong survival. Twenty-three putative tissue-specific markers for lung, colon, pancreatic, breast, prostate, and ovarian carcinomas were nominated by querying a gene expression profile database and by performing a literature search. Ten of these marker candidates were then selected based on validation by reverse transcriptase-polymerase chain reaction (RT-PCR) on 205 formalin-fixed, paraffin-embedded metastatic carcinoma specimens originating from these six and from other cancer types. Next, we optimized the RNA isolation and quantitative RT-PCR methods for these 10 markers and applied the quantitative RT-PCR assay to a set of 260 metastatic tumors. We then built a gene-based algorithm that predicted the tissue of origin of metastatic carcinomas with an overall leave-one-out cross-validation accuracy of 78%. Lastly, our assay demonstrated an accuracy of 76% when tested on an independent set of 48 metastatic samples, 37 of which were either a known primary or initially presented as carcinoma of unknown primary but were subsequently resolved.

Algorithms↗
PubMed2005

Left behind.

Explore the source record for details and available documents.

Communication↗
PubMed2005

Novel genes associated with malignant melanoma but not benign melanocytic lesions.

PURPOSE: Cutaneous melanoma is a common, aggressive cancer with increasing incidence. The identification of melanoma-specific deregulated genes could provide molecular markers for lymph node staging assays and further insight into melanoma tumorigenesis. EXPERIMENTAL DESIGN: Total RNA isolated from 45 primary melanoma, 18 benign skin nevi, and 7 normal skin tissue specimens were analyzed on an Affymetrix Hu133A microarray containing 22,000 probe sets. RESULTS: Hierarchical clustering revealed a distinct separation of the melanoma samples from the benign and normal specimens. Novel genes associated with malignant melanoma were identified. Differential gene expression of two melanoma-specific genes, PLAB and L1CAM, were tested by a one-step quantitative reverse transcription-PCR assay on primary malignant melanoma, benign nevi, and normal skin samples, as well as on malignant melanoma lymph node metastasis and melanoma-free lymph nodes. The performance of the markers was compared with conventional melanoma markers such as tyrosinase, gp100, and MART1. CONCLUSION: Our study systematically identified novel melanoma-specific genes and showed the feasibility of using a combination of PLAB and L1CAM in a reverse transcription-PCR assay to differentiate clinically relevant samples containing benign or malignant melanocytes.

Adolescent↗
PubMed2005

Better information for better health care: the Evidence-based Practice Center program and the Agency for Healthcare Research and Quality.

To provide decision makers with the best available evidence, the Agency for Healthcare Research and Quality established a network of Evidence-based Practice Centers across North America. The centers perform systematic reviews on important questions posed by partner organizations about clinical, organizational, and policy interventions in healthcare. The Agency works closely with partners and other decision maker s to help translate that evidence into practice or policy. In this paper, we review important lessons we have learned over the past 7 years about how to increase the efficiency and impact of systematic reviews. Lessons concern selecting the right topics and scope, working effectively with partners, and balancing consistency and flexibility in methods. We examine continuing evolutions of the program and the impact of planned work on comparative effectiveness performed as part of the Medicare Modernization Act of 2003.

Evidence-Based Medicine↗
PubMed2005

Challenges in using nonrandomized studies in systematic reviews of treatment interventions.

Randomized, controlled trials (RCTs) are firmly established as the standard for determining which medical treatments are effective. In some areas of health care, however, among them surgery, public health, and the organization of health care delivery, most evidence addressing the effectiveness of clinical or policy interventions rests on nonrandomized studies. We examine the use of study designs other than RCTs in Evidence-based Practice Center reports addressing questions of the effectiveness of treatment interventions. These reports offer the opportunity to examine the approaches used and the challenges faced by reviewers when nonrandomized studies are included and their quality assessed. We then offer recommendations for using these studies in systematic reviews of treatment interventions.

Clinical Trials as Topic↗
PubMed2005

Systems for grading the quality of evidence and the strength of recommendations II: pilot study of a new system.

BACKGROUND: Systems that are used by different organisations to grade the quality of evidence and the strength of recommendations vary. They have different strengths and weaknesses. The GRADE Working Group has developed an approach that addresses key shortcomings in these systems. The aim of this study was to pilot test and further develop the GRADE approach to grading evidence and recommendations. METHODS: A GRADE evidence profile consists of two tables: a quality assessment and a summary of findings. Twelve evidence profiles were used in this pilot study. Each evidence profile was made based on information available in a systematic review. Seventeen people were given instructions and independently graded the level of evidence and strength of recommendation for each of the 12 evidence profiles. For each example judgements were collected, summarised and discussed in the group with the aim of improving the proposed grading system. Kappas were calculated as a measure of chance-corrected agreement for the quality of evidence for each outcome for each of the twelve evidence profiles. The seventeen judges were also asked about the ease of understanding and the sensibility of the approach. All of the judgements were recorded and disagreements discussed. RESULTS: There was a varied amount of agreement on the quality of evidence for the outcomes relating to each of the twelve questions (kappa coefficients for agreement beyond chance ranged from 0 to 0.82). However, there was fair agreement about the relative importance of each outcome. There was poor agreement about the balance of benefits and harms and recommendations. Most of the disagreements were easily resolved through discussion. In general we found the GRADE approach to be clear, understandable and sensible. Some modifications were made in the approach and it was agreed that more information was needed in the evidence profiles. CONCLUSION: Judgements about evidence and recommendations are complex. Some subjectivity, especially regarding recommendations, is unavoidable. We believe our system for guiding these complex judgements appropriately balances the need for simplicity with the need for full and transparent consideration of all important issues.

Comprehension↗
PubMed2005

Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis.

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.

Biomarkers, Tumor↗
PubMed2004

Systems for grading the quality of evidence and the strength of recommendations I: critical appraisal of existing approaches The GRADE Working Group.

BACKGROUND: A number of approaches have been used to grade levels of evidence and the strength of recommendations. The use of many different approaches detracts from one of the main reasons for having explicit approaches: to concisely characterise and communicate this information so that it can easily be understood and thereby help people make well-informed decisions. Our objective was to critically appraise six prominent systems for grading levels of evidence and the strength of recommendations as a basis for agreeing on characteristics of a common, sensible approach to grading levels of evidence and the strength of recommendations. METHODS: Six prominent systems for grading levels of evidence and strength of recommendations were selected and someone familiar with each system prepared a description of each of these. Twelve assessors independently evaluated each system based on twelve criteria to assess the sensibility of the different approaches. Systems used by 51 organisations were compared with these six approaches. RESULTS: There was poor agreement about the sensibility of the six systems. Only one of the systems was suitable for all four types of questions we considered (effectiveness, harm, diagnosis and prognosis). None of the systems was considered usable for all of the target groups we considered (professionals, patients and policy makers). The raters found low reproducibility of judgements made using all six systems. Systems used by 51 organisations that sponsor clinical practice guidelines included a number of minor variations of the six systems that we critically appraised. CONCLUSIONS: All of the currently used approaches to grading levels of evidence and the strength of recommendations have important shortcomings.

Advisory Committees↗
PubMed2004

Microarray analysis reveals genetic pathways modulated by tipifarnib in acute myeloid leukemia.

BACKGROUND: Farnesyl protein transferase inhibitors (FTIs) were originally developed to inhibit oncogenic ras, however it is now clear that there are several other potential targets for this drug class. The FTI tipifarnib (ZARNESTRA, R115777) has recently demonstrated clinical responses in adults with refractory and relapsed acute leukemias. This study was conducted to identify genetic markers and pathways that are regulated by tipifarnib in acute myeloid leukemia (AML). METHODS: Tipifarnib-mediated gene expression changes in 3 AML cell lines and bone marrow samples from two patients with AML were analyzed on a cDNA microarray containing approximately 7000 human genes. Pathways associated with these expression changes were identified using the Ingenuity Pathway Analysis tool. RESULTS: The expression analysis identified a common set of genes that were regulated by tipifarnib in three leukemic cell lines and in leukemic blast cells isolated from two patients who had been treated with tipifarnib. Association of modulated genes with biological functional groups identified several pathways affected by tipifarnib including cell signaling, cytoskeletal organization, immunity, and apoptosis. Gene expression changes were verified in a subset of genes using real time RT-PCR. Additionally, regulation of apoptotic genes was found to correlate with increased Annexin V staining in the THP-1 cell line but not in the HL-60 cell line. CONCLUSIONS: The genetic networks derived from these studies illuminate some of the biological pathways affected by FTI treatment while providing a proof of principle for identifying candidate genes that might be used as surrogate biomarkers of drug activity.

Acute Disease↗
PubMed2004

Grading quality of evidence and strength of recommendations.

Users of clinical practice guidelines and other recommendations need to know how much confidence they can place in the recommendations. Systematic and explicit methods of making judgments can reduce errors and improve communication. We have developed a system for grading the quality of evidence and the strength of recommendations that can be applied across a wide range of interventions and contexts. In this article we present a summary of our approach from the perspective of a guideline user. Judgments about the strength of a recommendation require consideration of the balance between benefits and harms, the quality of the evidence, translation of the evidence into specific circumstances, and the certainty of the baseline risk. It is also important to consider costs (resource utilisation) before making a recommendation. Inconsistencies among systems for grading the quality of evidence and the strength of recommendations reduce their potential to facilitate critical appraisal and improve communication of these judgments. Our system for guiding these complex judgments balances the need for simplicity with the need for full and transparent consideration of all important issues.

Cost-Benefit Analysis↗
PubMed2004

Gene expression profiles and molecular markers to predict recurrence of Dukes' B colon cancer.

PURPOSE: The 5-year survival rate of patients with Dukes' B colon cancer is approximately 75%. Identification of the patients at high risk of recurrence in this group would allow better staging and more informed use of adjuvant chemotherapy. In this study, we used DNA chip technology to systematically identify new prognostic markers for tumor relapse in Dukes' B patients. PATIENTS AND METHODS: Using Affymetrix U133a GeneChip containing approximately 22,000 transcripts (Affymetrix, Santa Clara, CA), RNA samples from 74 patients with Dukes' B colon cancer were analyzed. Thirty-one patients developed tumor relapse in less than 3 years, whereas 43 patients remained disease-free for more than 3 years after surgery. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. A multivariate Cox model was built to predict recurrence. RESULTS: Gene expression profiling identified a 23-gene signature that predicts recurrence in Dukes' B patients. This signature was validated in 36 independent patients. The overall performance accuracy was 78%. Thirteen of 18 relapse patients and 15 of 18 disease-free patients were predicted correctly, giving an odds ratio of 13 (95% CI, 2.6 to 65; P =.003). The log-rank test indicated a significant difference in disease-free time between the predicted relapse and disease-free patients (P =.0001). CONCLUSION: The clinical value of these markers is that the patients at a high predicted risk of relapse (13-fold risk) could be upstaged to receive adjuvant therapy, similar to Dukes' C patients. Our data highlight the feasibility of a prognostic assay that could focus more intensive treatment for localized colon cancer.

Algorithms↗