Strategies to improve implementation of cascade testing in hereditary cancer syndromes: a systematic review.

Hereditary cancer syndromes constitute approximately 10% of all cancers. Cascade testing involves testing of at-risk relatives to determine if they carry the familial pathogenic variant. Despite growing efforts targeted at improving cascade testing uptake, current literature continues to reflect poor rates of uptake, typically below 30%. This study aims to systematically review current literature on intervention strategies to improve cascade testing, assess the quality of intervention descriptions and evaluate the implementation outcomes of listed interventions. We searched major databases using keywords and subject heading of "cascade testing". Interventions proposed in each study were classified according to the Effective Practice and Organization of Care (EPOC) taxonomy. Quality of intervention description was assessed using the TIDieR checklist, and evaluation of implementation outcomes was performed using Proctor's Implementation Outcomes Framework. Improvements in rates of genetic testing uptake was seen in interventions across the different EPOC taxonomy strategies. The average TIDieR score was 7.3 out of 12. Items least reported include modifications (18.5%), plans to assess fidelity/adherence (7.4%) and actual assessment of fidelity/adherence (7.4%). An average of 2.9 out of 8 aspects of implementation outcomes were examined. The most poorly reported outcomes were cost, fidelity and sustainability, with only 3.7% of studies reporting them. Most interventions have demonstrated success in improving cascade testing uptake. Uptake of cascade testing was highest with delivery arrangement (68%). However, the quality of description of interventions and assessment of implementation outcomes are often suboptimal, hindering their replication and implementation downstream. Therefore, further adoption of standardized guidelines in reporting of interventions and formal assessment of implementation outcomes may help promote translation of these interventions into routine practice.

Diagnosis and biomarkers for ocular tuberculosis: From the present into the future.

Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis (Mtb) and can manifest both pulmonary and extrapulmonary disease, including ocular tuberculosis (OTB). Accurate diagnosis and swift optimal treatment initiation for OTB is faced by many challenges combined with the lack of standardized treatment regimens this results in uncertain OTB outcomes. The purpose of this study is to summarize existing diagnostic approaches and recently discovered biomarkers that may contribute to establishing OTB diagnosis, choice of anti-tubercular therapy (ATT) regimen, and treatment monitoring. The keywords ocular tuberculosis, tuberculosis, Mycobacterium, biomarkers, molecular diagnosis, multi-omics, proteomics, genomics, transcriptomics, metabolomics, T-lymphocytes profiling were searched on PubMed and MEDLINE databases. Articles and books published with at least one of the keywords were included and screened for relevance. There was no time limit for study inclusion. More emphasis was placed on recent publications that contributed new information about the pathogenesis, diagnosis, or treatment of OTB. We excluded abstracts and articles that were not written in the English language. References cited within the identified articles were used to further supplement the search. We found 10 studies evaluating the sensitivity and specificity of interferon-gamma release assay (IGRA), and 6 studies evaluating that of tuberculin skin test (TST) in OTB patients. IGRA (Sp = 71-100%, Se = 36-100%) achieves overall better sensitivity and specificity than TST (Sp = 51.1-85.7%; Se = 70.9-98.5%). For nuclear acid amplification tests (NAAT), we found 7 studies on uniplex polymerase chain reaction (PCR) with different Mtb targets, 7 studies on DNA-based multiplex PCR, 1 study on mRNA-based multiplex PCR, 4 studies on loop-mediated isothermal amplification (LAMP) assay with different Mtb targets, 3 studies on GeneXpert assay, 1 study on GeneXpert Ultra assay and 1 study for MTBDRplus assay for OTB. Specificity is overall improved but sensitivity is highly variable for NAATs (excluding uniplex PCR, Sp = 50-100%; Se = 10.5-98%) as compared to IGRA. We also found 3 transcriptomic studies, 6 proteomic studies, 2 studies on stimulation assays, 1 study on intraocular protein analysis and 1 study on T-lymphocyte profiling in OTB patients. All except 1 study evaluated novel, previously undiscovered biomarkers. Only 1 study has been externally validated by a large independent cohort. Future theranostic marker discovery by a multi-omics approach is essential to deepen pathophysiological understanding of OTB. Combined these might result in swift, optimal and personalized treatment regimens to modulate the heterogeneous mechanisms of OTB. Eventually, these studies could improve the current cumbersome diagnosis and management of OTB.

Successful Treatment of Recurrent Thrombosis Associated with Malignancy with Apixaban and Follow-up for 1 Year.

This case report aims to highlight a successful example of using novel oral anticoagulants (NOACs), such as apixaban, to prevent recurrent venous thromboembolism (VTE) in patients with solid-organ malignancy, as an alternative to low-molecular weight heparin (LMWH). Discussed is the case of a 67-year-old woman diagnosed with recurrent thrombosis in the upper-right limb and malignancy of right breast with metastasis to the axillary lymph nodes. Over a follow-up period of more than 1 year, there was no recurrence of VTE and D-dimer decreased, illuminating the possibility of apixaban as an alternative form of treatment for recurrent VTE in patients with malignancy. This appears to be one of the first case reports in Singapore.