Cost-effectiveness of a mailed educational reminder to increase colorectal cancer screening

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) screening rates are low in many areas and cost-effective interventions to promote CRC screening are needed. Recently in a randomized controlled trial, a mailed educational reminder increased CRC screening rates by 16.2% among U.S. Veterans. The aim of our study was to assess the costs and cost-effectiveness of a mailed educational reminder on fecal occult blood test (FOBT) adherence.</p> <p>Methods</p> <p>In a blinded, randomized, controlled trial, 769 patients were randomly assigned to the usual care group (FOBT alone, n = 382) or the intervention group (FOBT plus a mailed reminder, n = 387). Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group. Primary outcome was number of returned FOBT cards after 6 months. The costs and incremental cost-effectiveness ratio (ICER) of the intervention were assessed and calculated respectively. Sensitivity analyses were based on varying costs of labor and supplies.</p> <p>Results</p> <p>At 6 months after card distribution, 64.6% patients in the intervention group returned FOBT cards compared with 48.4% in the control group (P < 0.001). The total cost of the intervention was $962 or$2.49 per patient, and the ICER was $15 per additional person screened for CRC. Sensitivity analysis based on a 10$13.50 to $16.50 per additional patient screened for CRC.</p> <p>Conclusions</p> <p>A simple mailed educational reminder increases FOBT card return rate at a cost many health care systems can afford. Compared to other patient-directed interventions (telephone, letters from physicians, mailed reminders) for CRC screening, our intervention was more effective and cost-effective.</p

Clinical aspects of sentinel node biopsy

Sentinel lymph node (SLN) biopsy requires validation by a backup axillary dissection in a defined series of cases before becoming standard practice, to establish individual and institutional success rates and the frequency of false negative results. At least 90% success in finding the SLN with no more than 5-10% false negative results is a reasonable goal for surgeons and institutions learning the technique. A combination of isotope and dye to map the SLN is probably superior to either method used alone, yet a wide variety of technical variations in the procedure have produced a striking similarity of results. Most breast cancer patients are suitable for SLN biopsy, and the large majority reported to date has had clinical stage T1-2N0 invasive breast cancers. SLN biopsy will play a growing role in patients having prophylactic mastectomy, and in those with 'high-risk' duct carcinoma in situ, microinvasive cancers, T3 disease, and neoadjuvant chemotherapy. SLN biopsy for the first time makes enhanced pathologic analysis of lymph nodes logistically feasible, at once allowing greater staging accuracy and less morbidity than standard methods. Retrospective data suggest that micrometastases identified in this way are prognostically significant, and prospective clinical trials now accruing promise a definitive answer to this issue

Analysis of urinary oligosaccharides in lysosomal storage disorders by capillary high-performance anion-exchange chromatography–mass spectrometry

Many lysosomal storage diseases are characterized by an increased urinary excretion of glycoconjugates and oligosaccharides that are characteristic for the underlying enzymatic defect. Here, we have used capillary high-performance anion-exchange chromatography (HPAEC) hyphenated to mass spectrometry to analyze free oligosaccharides from urine samples of patients suffering from the lysosomal storage disorders fucosidosis, α-mannosidosis, GM1-gangliosidosis, GM2-gangliosidosis, and sialidosis. Glycan fingerprints were registered, and the patterns of accumulated oligosaccharides were found to reflect the specific blockages of the catabolic pathway. Our analytical approach allowed structural analysis of the excreted oligosaccharides and revealed several previously unpublished oligosaccharides. In conclusion, using online coupling of HPAEC with mass spectrometric detection, our study provides characteristic urinary oligosaccharide fingerprints with diagnostic potential for lysosomal storage disorders

Cardiac disease in patients with mucopolysaccharidosis: presentation, diagnosis and management

The mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders caused by the absence of functional enzymes that contribute to the degradation of glycosaminoglycans (GAGs). The progressive systemic deposition of GAGs results in multi-organ system dysfunction that varies with the particular GAG deposited and the specific enzyme mutation(s) present. Cardiac involvement has been reported in all MPS syndromes and is a common and early feature, particularly for those with MPS I, II, and VI. Cardiac valve thickening, dysfunction (more severe for left-sided than for right-sided valves), and hypertrophy are commonly present; conduction abnormalities, coronary artery and other vascular involvement may also occur. Cardiac disease emerges silently and contributes significantly to early mortality

Characterising chromosome rearrangements: recent technical advances in molecular cytogenetics

Genomic rearrangements can result in losses, amplifications, translocations and inversions of DNA fragments thereby modifying genome architecture, and potentially having clinical consequences. Many genomic disorders caused by structural variation have initially been uncovered by early cytogenetic methods. The last decade has seen significant progression in molecular cytogenetic techniques, allowing rapid and precise detection of structural rearrangements on a whole-genome scale. The high resolution attainable with these recently developed techniques has also uncovered the role of structural variants in normal genetic variation alongside single-nucleotide polymorphisms (SNPs). We describe how array-based comparative genomic hybridisation, SNP arrays, array painting and next-generation sequencing analytical methods (read depth, read pair and split read) allow the extensive characterisation of chromosome rearrangements in human genomes

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC