Biomedical subjects

John Fox

Publications and source records attributed to John Fox.

8 recordsLinked to original sources

PubMed2026

Real-World Actionability Analysis of Comprehensive Genomic Profiling Versus Single/Small-Gene Panels.

INTRODUCTION: Comprehensive genomic profiling (CGP) enables identification of patients eligible for targeted treatments, making it essential in the management of advanced cancer. This retrospective real-world study compared actionable mutations in CGP-tested patients with advanced/metastatic solid tumors to those who received single-gene/small-panel (SP) tests. METHODS: Patients aged > 18 years with advanced/metastatic solid tumors (including non-small cell lung cancer (NSCLC), colorectal cancer, prostate cancer, breast cancer, or melanoma) with a CGP or SP test reported between 1 January 2018, and 31 December 2022, were included. OncoKB-derived actionability was compared between the two cohorts. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline characteristics. A weighted generalized linear model with log link was used to report actionability ratio (AR) and 95% confidence intervals (CI). RESULTS: Among 406 patients (CGP-tested cohort: 202, SP-tested cohort: 204), approximately half were diagnosed with NSCLC. After adjusting for baseline characteristics, CGP testing detected more actionable alterations than SP: OncoKB level 1 (50.0% versus 31.4%; AR 1.76 [95% CI: 1.24, 2.51]; p = 0.002), OncoKB level 2 (22.8% versus 10.3%; AR 2.53 [95% CI: 1.17, 5.48]; p = 0.018), and OncoKB level 1 or level 2 or level R1 (55.9% versus 41.2%; AR 1.5 [95% CI: 1.11, 2.01]; p = 0.008). CONCLUSIONS: CGP testing identified more actionable genetic alterations compared with SP testing methods for patients with advanced/metastatic NSCLC, colorectal cancer, prostate cancer, breast cancer, or melanoma. Expanding reimbursement and coverage for CGP testing as well as expanding CGP use can facilitate equitable treatment access for patients with advanced/metastatic cancer.

Actionable mutations↗

PubMed2003

Evaluation of adjunctive HPV testing by Hybrid Capture II in women with minor cytological abnormalities for the diagnosis of CIN2/3 and cost comparison with colposcopy.

BACKGROUND: As a proportion of high grade cervical intraepithelial neoplasia (CIN2/3) are associated with equivocal cervical smears, which show borderline or mild dyskaryosis, follow up with repeat smears, colposcopy and biopsy is required. Since infection with oncogenic Human Papilloma Virus (HR HPV) has been found to be associated with the development of cervical cancer, HRHPV testing appears to be an alternative. OBJECTIVE: The present study assesses if HRHPV testing can predict CIN2/3 in women referred for mild dyskaryosis and borderline cytological changes in an health authority with a referral policy to colposcopy after one single mild dyskaryotic Pap smear. STUDY DESIGN: The HPV DNA Hybrid Capture II (Digene/Abbott, Maidenhead) was evaluated on 110 consenting women with mild dyskaryosis and 23 women with persistent borderline changes, who were referred for colposcopy between May and November 2001. A cost comparison between two referral policies was performed. RESULTS: CIN2/3 was diagnosed histologically in 30 of 133 women (22%) with minor cytological abnormalities. As the Receiver Operator Characteristics plot suggested a cut-off of 3 pg/ml the HRHPV HCII was evaluated at 3 RLU (relative light units) and at the manufacturer's recommendation of 1 RLU. At both cut-offs sensitivity and negative predictive value were high at 97%. Specificity was low at 37% at a cut-off of 1 pg/ml and 46% at a cut-off of 3 RLU. To remain cost neutral in comparison to immediate colposcopy the costs for one HR HPV HC II must not exceed pound 34.37 per test at a cut off of 3 pg/ml. CONCLUSION: The negative likelihood ratio (NLR) was of good diagnostic value with 0.089 at 1 RLU and 0.072 at 3 RLU, which reduces the post-test probability for CIN2/3 to 2% in this population. Women with minor cytological disorders can be excluded from colposcopy on a negative HR HPV result.Specificity can be improved by restricting HR HPV testing to women with persistent borderline cytological changes or to women over 30 years.

Colposcopy↗

PubMed2003

The syntax and semantics of the PROforma guideline modeling language.

PROforma is an executable process modeling language that has been used successfully to build and deploy a range of decision support systems, guidelines, and other clinical applications. It is one of a number of recent proposals for representing clinical protocols and guidelines in a machine-executable format (see ). In this report, the authors outline the task model for the language and provide an operational semantics for process enactment together with a semantics for expressions, which may be used to query the state of a task during enactment. The operational semantics includes a number of public operations that may be performed on an application by an external agent, including operations that change the values of data items, recommend or make decisions, manage tasks that have been performed, and perform any task state changes that are implied by the current state of the application. Disclosure: PROforma has been used as the basis of a commercial decision support and guideline technology Arezzo (Infermed, London, UK; details in text).

Decision Support Systems, Clinical↗

PubMed2003

Minimally invasive mitral valve repair suggests earlier operations for mitral valve disease.

OBJECTIVE: We began minimally invasive mitral valve surgery in August, 1996, to reduce hospital costs, to improve patient recovery, cosmetic appearance, and to decrease trauma, yet maintain the same quality of surgery. To validate this approach we reviewed our entire experience through May 2002. METHODS: From August 1996 to May 2002, we performed 413 minimally invasive mitral valve operations including 51 mitral valve replacements and 362 mitral valve repairs. Excluding 4 robotically assisted repairs, we evaluated 358 patients, using the mitral valve repairs as the basis for this retrospective survey. These operations were performed through a 6- to 8-cm minimally invasive incision, beginning with parasternal and, most recently, lower ministernotomy (181 patients). The mitral valve reparative techniques include repair of 94 prolapsed anterior leaflets, posterior leaflet resection, leaflet advancement, commissuroplasty, Polytetrafluoroethylene (PTFE; Gore-Tex, W. L. Gore & Associates, Inc, Flagstaff, Ariz) chordal placement, and ring annuloplasty. Cannulation sites varied but primarily utilized a miniaturized system of 24F catheters in both the inferior and superior venae cavae with assisted venous suction. The Cosgrove ring was used in 95% of the patients undergoing this procedure. RESULTS: The operative mortality was 0/358. Perioperative morbidity included a 26% incidence of new atrial fibrillation, 2% incidence of pacemaker implantation, 0.5% incidence of deep sternal wound infection, and 1.9% incidence of stroke after an operation. There were 10 arterial and 3 venous complications. The mean length of stay was 6 days and 208 patients stayed < or =5 days. Only 25% of the patients underwent homologous blood transfusion. The mean follow-up was 36 months with 1.4% lost to follow-up. There were 12 late deaths and a survival at 5 years of 95%. There were 21 valves requiring reoperation for structural valve failure of 5.8%. The probability of freedom from reoperation at 5 years was 92%. CONCLUSION: This study documents the safety of minimally invasive mitral valve repair surgery in 358 patients. It also documents a low incidence of homologous blood use, requirement for post-hospital rehabilitation, and general morbidity.

Adolescent↗

PubMed2002

Developments in parathyroid hormone and related peptides as bone-formation agents.

Osteoporosis is a major and growing healthcare concern. When administered by daily injection, parathyroid hormone (PTH) and its N-terminal fragments and analogs are potent bone-formation agents. Teriparatide, recombinant human PTH(1-34), is likely to be the first anabolic agent approved for treating osteoporosis, despite inducing osteosarcomas in rats. Native PTH and other PTH fragments and analogs are also in development. N-terminal fragments sometimes differ in activity from the native hormone, however, and the C-terminal region of PTH, acting through a receptor different from the classical PTH-1 receptor, initiates a variety of distinct biological activities. In particular, the C-terminal region of PTH, by promoting bone-cell apoptosis, may be important in opposing the anti-apoptotic effects of teriparatide in these cells, thereby maintaining normal bone-cell turnover. Because of these differences, care must be taken to consider the effects of native PTH and N-terminal PTH fragments and analogs separately.

Animals↗

PubMed2002

Clinical decision support systems: a discussion of quality, safety and legal liability issues.

Developers of Clinical Decision Support Systems (CDSSs) have to date been more concerned with the efficacy of systems (e.g. measurable improvements in clinical outcomes) than with safety (e.g. potential for harmful side-effects). In future CDSS developers will be required (by the courts etc.) to acknowledge a "duty of care" covering all aspects of design, development and deployment. Experience in the transport, power and other safety-critical industries has led to a range of quality and safety assurance methods whose adoption may be needed before CDSSs can safely become an integral part of routine patient care, and before the trust of healthcare professionals, patients and other stakeholders can be gained. No single method will be sufficient for safe development and deployment; a range of techniques will be needed and used selectively. This paper is a contribution to discussion of quality, safety and legal liability issues in the medical informatics community.

Decision Support Systems, Clinical↗

PubMed2000

Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats.

The secondary hyperparathyroidism that develops in rats with chronic renal insufficiency (CRI) can be totally prevented by activation of the parathyroid Ca(2+) receptor with a calcimimetic compound, when treatment is initiated before parathyroid cell hyperplasia and increased circulating parathyroid hormone levels develop. In clinical practice, however, secondary hyperparathyroidism is usually manifest by the time CRI is diagnosed. This study examined the effects of daily oral gavage or continuous subcutaneous infusion for 8 wk of the calcimimetic NPS R-568 on the progression of established mild or moderate-to-severe secondary hyperparathyroidism in rats with CRI induced by 5/6 nephrectomy. Both oral and infused NPS R-568 completely prevented further hyperplasia but did not reduce total parathyroid cell number below that present at the initiation of treatment. This prevention of cellular proliferation occurred despite increases in plasma phosphate and decreases in Ca(2+) and 1, 25-dihydroxyvitamin D levels, and supports the view that the Ca(2+) receptor is the dominant regulator of parathyroid cell hyperplasia in addition to parathyroid hormone secretion. The clinical implications of these findings suggest that controlling Ca(2+) receptor activity with calcimimetic compounds could be sufficient to manage secondary hyperparathyroidism in CRI.

Analysis of Variance↗

PubMedDate not supplied

Comparing computer-interpretable guideline models: a case-study approach.

OBJECTIVES: Many groups are developing computer-interpretable clinical guidelines (CIGs) for use during clinical encounters. CIGs use "Task-Network Models" for representation but differ in their approaches to addressing particular modeling challenges. We have studied similarities and differences between CIGs in order to identify issues that must be resolved before a consensus on a set of common components can be developed. DESIGN: We compared six models: Asbru, EON, GLIF, GUIDE, PRODIGY, and PROforma. Collaborators from groups that created these models represented, in their own formalisms, portions of two guidelines: American College of Chest Physicians cough guidelines [correction] and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. MEASUREMENTS: We compared the models according to eight components that capture the structure of CIGs. The components enable modelers to encode guidelines as plans that organize decision and action tasks in networks. They also enable the encoded guidelines to be linked with patient data-a key requirement for enabling patient-specific decision support. RESULTS: We found consensus on many components, including plan organization, expression language, conceptual medical record model, medical concept model, and data abstractions. Differences were most apparent in underlying decision models, goal representation, use of scenarios, and structured medical actions. CONCLUSION: We identified guideline components that the CIG community could adopt as standards. Some of the participants are pursuing standardization of these components under the auspices of HL7.

Decision Support Systems, Clinical↗