Advanced practice occupational therapy led triage and treatment clinic for patients with carpal tunnel syndrome in an Irish public hospital.

INTRODUCTION: A pilot CTS Triage and Treat clinic led by an Advanced Practice Occupational Therapist was established to address the CTS wait list at a large urban hospital. The aims of this pilot were to develop a clinical triage and screening protocol to inform the stratification of patients for suitable treatment options and to reduce waiting time. METHODS: A cross sectional study with follow up was conducted, patients on the wait list at time of commencement of the pilot and subsequent referrals over a 1-year period were recruited. Triage consisted of tests of sensibility, self-rating measures, provocative tests and detailed patient to inform the subsequent treatment stratification, conservative, injection, surgery, or further investigation. Nonparametric analyses were used to test relationships between the test scores and to complete subgroup comparisons. RESULTS: Eighty-nine patients were triaged over the pilot period, 62 (70%) had a positive Phalen's at triage. Following triage 48 (54%) patients were stratified for conservative management, injection (n = 23, 26%) and surgery/differential diagnosis (n = 18, 20%). Statistically significant differences in BCTQ (SSS and FSS) and Q-DASH scores were noted across the three outcome groups, with lower scores among those commenced on conservative management. BCTQ (SSS) scores were aligned with the Semmes Weinstein Monofilaments sensibility thresholds. Wait times showed a marked decrease from 10 to 2 months over the period of the pilot. DISCUSSION: Findings highlight the positive impact of occupational therapy led triage and treat approach in the reduction of wait time for assessment and treatment for patients with CTS.

The pruritus severity scale-a novel tool to assess itch in burns patients.

BACKGROUND: Pruritus assessment is difficult due to the varying subjective nature of the experience. There have been several validated tools described to quantify the severity of itch, however these tools fail to provide a comprehensive assessment or are too cumbersome and therefore lack usability. Our novel burn assessment tool, "The Pruritus Severity Scale" (PSS) allows for accurate quantification of itch components. The aim of this study was to assess its use in the burns population. METHODS: A prospective observational study was conducted on all patients over five years of age with a burn injury over a six month period. Patients underwent subjective evaluation of their itch as determined by two validated scores, the Visual Analogue Scale (VAS) and the Itch Man scale (IMS) and in addition to the PSS. The pruritus severity scale was correlated with the previously validated scoring methods using bi-variate correlations. RESULTS: Twenty-two patients were included in the study. The most common cause of injury was due to flame burn. The mean total body surface area was 6.5% (range: 1-26%). Both the IMS and the VAS positively correlated well with the PSS. The Spearman Coefficient for the PSS vs IMS was 0.81, R2 = 0.65 (P<0.05). The Spearman Coefficient for the PSS vs VAS was 0.87 (R2 = 0.76 (P<0.01)). There is a positive linear relationship between our novel scoring methods and the currently validated methods, indicating its validity as a burn assessment too. CONCLUSION: The Pruritus Severity Scale was shown to be an accurate, objective tool that was able to effectively record the patient's experience of itch. We believe that this novel score is quick, easy to use and allows for more comprehensive assessment than other short assessment tools.

Preoperative measurement of cutaneous melanoma and nevi thickness with photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging biomedical imaging technology, which can potentially be used in the clinic to preoperatively measure melanoma thickness and guide biopsy depth and sample location. We recruited 27 patients with pigmented cutaneous lesions suspicious for melanoma to test the feasibility of a handheld linear-array photoacoustic probe in imaging lesion architecture and measuring tumor depth. The probe was assessed in terms of measurement accuracy, image quality, and ease of application. Photoacoustic scans included single wavelength, spectral unmixing, and three-dimensional (3-D) scans. The photoacoustically measured lesion thickness gave a high correlation with the histological thickness measured from resected surgical samples ([Formula: see text], [Formula: see text] for melanomas, [Formula: see text], [Formula: see text] for nevi). Thickness measurements were possible for 23 of 26 cases for nevi and all (6) cases for melanoma. Our results show that handheld, linear-array PAI is highly reliable in measuring cutaneous lesion thickness in vivo, and can potentially be used to inform biopsy procedure and improve patient management.

A germline mutation in the BRCA1 3'UTR predicts Stage IV breast cancer.

BACKGROUND: A germline, variant in the BRCA1 3'UTR (rs8176318) was previously shown to predict breast and ovarian cancer risk in women from high-risk families, as well as increased risk of triple negative breast cancer. Here, we tested the hypothesis that this variant predicts tumor biology, like other 3'UTR mutations in cancer. METHODS: The impact of the BRCA1-3'UTR-variant on BRCA1 gene expression, and altered response to external stimuli was tested in vitro using a luciferase reporter assay. Gene expression was further tested in vivo by immunoflourescence staining on breast tumor tissue, comparing triple negative patient samples with the variant (TG or TT) or non-variant (GG) BRCA1 3'UTR. To determine the significance of the variant on clinically relevant endpoints, a comprehensive collection of West-Irish breast cancer patients were tested for the variant. Finally, an association of the variant with breast screening clinical phenotypes was evaluated using a cohort of women from the High Risk Breast Program at the University of Vermont. RESULTS: Luciferase reporters with the BRCA1-3'UTR-variant (T allele) displayed significantly lower gene expression, as well as altered response to external hormonal stimuli, compared to the non-variant 3'UTR (G allele) in breast cancer cell lines. This was confirmed clinically by the finding of reduced BRCA1 gene expression in triple negative samples from patients carrying the homozygous TT variant, compared to non-variant patients. The BRCA1-3'UTR-variant (TG or TT) also associated with a modest increased risk for developing breast cancer in the West-Irish cohort (OR=1.4, 95% CI 1.1-1.8, p=0.033). More importantly, patients with the BRCA1-3'UTR-variant had a 4-fold increased risk of presenting with Stage IV disease (p=0.018, OR=3.37, 95% CI 1.3-11.0). Supporting that this finding is due to tumor biology, and not difficulty screening, obese women with the BRCA1-3'UTR-variant had significantly less dense breasts (p=0.0398) in the Vermont cohort. CONCLUSION: A variant in the 3'UTR of BRCA1 is functional, leading to decreased BRCA1 expression, modest increased breast cancer risk, and most importantly, presentation with stage IV breast cancer, likely due to aggressive tumor biology.

The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer.

PURPOSE: A germline microRNA binding site-disrupting variant, the KRAS-variant (rs61764370), is associated with an increased risk of developing several cancers. Because this variant is most strongly associated with ovarian cancer risk in patients from hereditary breast and ovarian families (HBOC), and with the risk of premenopausal triple negative breast cancer, we evaluated the association of the KRAS-variant with women with personal histories of both breast and ovarian cancer, referred to as double primary patients. EXPERIMENTAL DESIGN: Germline DNA from double primary patients was tested for the KRAS-variant (n = 232). Confirmation of pathologic diagnoses, age of diagnoses, interval between ovarian cancer diagnosis and sample collection, additional cancer diagnoses, and family history were obtained when available. All patients were tested for deleterious BRCA mutations. RESULTS: The KRAS-variant was significantly enriched in uninformative (BRCA negative) double primary patients, being found in 39% of patients accrued within two years of their ovarian cancer diagnosis. Furthermore, the KRAS-variant was found in 35% of uninformative double primary patients diagnosed with ovarian cancer post-menopausally, and was significantly associated with uninformative double primary patients with a positive family history. The KRAS-variant was also significantly enriched in uninformative patients who developed more then two primary cancers, being found in 48% of women with two breast primaries plus ovarian cancer or with triple primary cancers. CONCLUSIONS: These findings further validate the importance of the KRAS-variant in breast and ovarian cancer risk, and support the association of this variant as a genetic marker for HBOC families previously considered uninformative.

A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis.

BACKGROUND: We previously identified a functional variant in a let-7 microRNA (miRNA) complementary site in the 3'-untranslated region of the KRAS oncogene (rs61764370) which is associated with cancer. We aimed to investigate the association of this KRAS variant with breast cancer and tumour biology. METHODS: We assessed frequency distributions of the KRAS variant in 415 patients with histologically confirmed breast cancer and 457 controls from Connecticut, USA (study group 1) and association of this variant with breast-cancer subtypes in 690 Irish women with known oestrogen receptor (ER), progesterone receptor (PR), and HER2 statuses, and 360 controls (study group 2). We pooled data for study groups 1 and 2 with a cohort of 140 women with triple-negative breast cancer and 113 controls to assess the association of the KRAS variant with triple-negative breast cancer risk, and genome-wide mRNA and specific miRNA expression in patients with triple-negative breast cancer. FINDINGS: Although frequency distributions of the KRAS variant in study group 1 did not differ between all genotyped individuals, eight (33%) of 24 premenopausal women with ER/PR-negative cancer had the KRAS variant, compared with 27 (13%) of 201 premenopausal controls (p=0.015). In study group 2, the KRAS variant was significantly enriched in women with triple-negative breast cancer (19 [21%] of 90 cases) compared with 64 (13%) of 478 for luminal A, 13 (15%) of 87 for luminal B, and two (6%) of 35 for HER2-positive subgroups (p=0.044). Multivariate analysis in the pooled study groups showed that the KRAS variant was associated with triple-negative breast cancer in premenopausal women (odds ratio 2.307, 95% CI 1.261-4.219, p=0.0067). Gene-expression analysis of triple-negative breast-cancer tumours suggested that KRAS-variant positive tumours have significantly altered gene expression, and are enriched for the luminal progenitor and BRCA1 deficiency signatures. miRNA analysis suggested reduced levels of let-7 miRNA species in KRAS-variant tumours. INTERPRETATION: The KRAS variant might be a genetic marker for development of triple-negative breast cancer in premenopausal women, and altered gene and miRNA expression signatures should enable molecular and biological stratification of patients with this subgroup of breast cancer. FUNDING: US National Institutes of Health.