Validity, reliability, responsiveness, and clinically meaningful change threshold estimates of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16).

BACKGROUND: Breast cancer is one of the most common cancers in women. Patient-reported outcome measures are used to evaluate patients' health-related quality of life in clinical breast cancer studies. This study evaluated the structure, validity, reliability, and responsiveness of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) subscales in a clinical trial featuring patients with advanced/metastatic breast cancer (aBC), and estimated NFBSI-16 meaningful change thresholds. METHODS: Data from 101 patients with aBC enrolled in a phase II trial (Xenera-1) were included for psychometric evaluation of the NFBSI-16. Subscale structure was evaluated by assessing inter-item correlations, item-total correlations, and internal consistency (cycles 2 and 5). Validity was assessed using scale-level convergent validity (cycles 2 and 5) and known-groups (Baseline). Reliability was analysed via test-retest at cycles 3-4, and responsiveness to improvement and worsening was evaluated at cycles 5, 7, and 9. Meaningful change thresholds were estimated using anchor-based methods (supported by distribution-based methods) at cycles 5, 7, and 9. RESULTS: NFBSI-16 internal consistency was acceptable, but item-total correlations suggested that its subscales and the GP5 item (side-effect of treatment) scores may be preferred over a total score. Convergent and known-groups evidence supported NFBSI-16 validity. Test-retest reliability was good to excellent for Total and DRS-P (disease-related symptoms: physical) scales, and moderate for the GP5 item. Responsiveness to worsening was generally demonstrated, but responsiveness to improvement could not be demonstrated due to limited observed improvement. Anchor-based meaningful change thresholds were estimated for DRS-P and Total scores. CONCLUSION: This study provides evidence that the NFBSI-16 has desirable psychometric properties for use in clinical studies in aBC. It also provides estimates of group- and individual-level meaningful change thresholds to facilitate score interpretation in future aBC research.

A Mixed-Methods Study to Better Measure Patient-Reported Pain and Fatigue in Soft Tissue Sarcoma.

INTRODUCTION: Pain and fatigue are commonly reported by patients with soft tissue sarcoma (STS) as distressing symptoms, yet no patient-reported outcome (PRO) measures have been validated or developed specifically for STS. This study aimed to develop novel PRO scales using existing item banks to measure pain and fatigue in STS. METHODS: A three-stage mixed-methods approach was used. Stage 1: a literature review examined the development and validation of the European Organization for Research and Treatment of Cancer (EORTC) library, Patient-Reported Outcomes Measurement Information System (PROMIS) pain/fatigue item banks, Functional Assessment of Cancer Therapy-General, and FACIT-Fatigue. Conceptual models were developed for pain and fatigue. Stage 2: semi-structured interviews were conducted with clinical experts (n = 3) and STS patients (n = 28) to ensure conceptual coverage and cognitively debrief the selected PRO items. Stage 3: exploratory Rasch measurement theory (RMT) analyses were performed to examine the measurement properties of the proposed scales. RESULTS: Stage 1: The conceptual model for fatigue was organized into two overarching domains: fatigability and fatigue, further split into two subdomains: symptoms and impact. The conceptual model for pain had one overarching domain split into two subdomains: descriptors and impact. Pain (n = 56) and fatigue (n = 40) items were selected from the EORTC item library. Stage 2: qualitative findings ensured conceptual coverage, provided insight into the relevance and comprehension of the items, and informed subsequent item reduction. Stage 3: The total item number was reduced to 43 (pain n = 18, fatigue n = 25). Exploratory RMT analyses supported the final scales' psychometric properties. CONCLUSIONS: This mixed-methods research generated important information on the experience of pain and fatigue in specific subtypes of STS. Five novel PRO scales have been developed through careful item selection in consultation with experts and supported by qualitative and quantitative evidence. These scales may be of value to future clinical trials for STS.

Development of a disease conceptual model of patient experience with metastatic colorectal cancer: identification of the most salient symptoms and impacts.

PURPOSE: Patients with metastatic colorectal cancer (mCRC) experience multiple symptoms and impacts affecting their health-related quality of life. However, there is limited data on self-reported experience of the most relevant and bothersome aspects of patients living with mCRC. METHODS: Semi-structured interviews were conducted in patients with mCRC to identify and understand the signs, symptoms and impacts experienced. Patients were also asked to rate the level of bothersomeness for each concept reported on a scale ranging from 0 ("not bothersome at all") to 10 ("extremely bothersome"). Verbatim transcripts were analysed following a thematic analysis approach. The most salient concepts were identified (i.e. reported by > 50% of patients with a bothersome rating ≥ 5 out of 10). RESULTS: Twenty-five patients (USA; age: 26 to 72 years old) were interviewed. Patients reported 58 signs and symptoms, amongst which 8 were considered salient: fatigue, nausea, neuropathy, diarrhoea, loss of appetite, constipation, weight loss, and abdominal pain; 35 impacts were identified, and 7 were considered salient: reduced ability to work, interference with daily activities, impact on cognitive functioning, financial impact, sleep changes, impact on social life and walking difficulties. The concepts identified helped refine a literature-based disease conceptual model of patient experience with mCRC. CONCLUSIONS: The interviews provided insights into the most bothersome and salient signs, symptoms and impacts affecting the HRQoL of patients living with mCRC. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to improve clinical strategies for future clinical development and inform clinical practice decision-making for mCRC survivors.

The impact of continuous positive airway pressure treatment on retinal vascular changes in obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) was recently shown to be associated with quantifiable retinal vascular changes, which correlate with disease severity. This follow-up study examines the response of retinal vascular changes in patients with OSA receiving continuous positive airway pressure (CPAP) treatment. METHODS: This prospective cohort study recruited adult patients undergoing diagnostic polysomnography at a tertiary sleep clinic in Sydney, Australia, stratified into 4 groups by the apnea-hypopnea index; control patients and patients with mild, moderate, and severe OSA. At baseline and follow-up approximately 24 months later, static retinal vascular calibers were derived from fundus photographs, and dynamic vascular pulsation amplitudes were measured on video fundoscopy. A proportion of patients started CPAP therapy after baseline assessment. RESULTS: Seventy-nine patients participated in this follow-up study: 9 control patients and 18 patients with mild OSA, 21 patients with moderate OSA, and 31 patients with severe OSA. Twenty-five patients started CPAP after baseline. In the severe group, patients not on treatment showed progressive narrowing of retinal arteries from baseline, whereas those on CPAP showed a slight improvement (mean, 171.3-165.1 and 171.2-174.0 µm, respectively; P = .012). Arterio-venous ratio was also significantly reduced in the nontreatment group compared to the treatment group in those with severe OSA (0.836-0.821 and 0.837-0.855, respectively; P = .031). CPAP did not seem to have a significant impact on venous caliber or vascular pulsatility. CONCLUSIONS: This study shows that patients with severe untreated OSA demonstrate progressive retinal arterial narrowing, whereas CPAP treatment may be protective.

Obstructive Sleep Apnea in Neuro-Ophthalmology.

BACKGROUND: Obstructive sleep apnea (OSA) is a common pulmonary disorder with many systemic sequelae. Its association with diseases seen in neuro-ophthalmology is being increasingly recognized. Treatment of OSA with continuous positive airway pressure (CPAP) may reverse the pathology in some eye diseases. EVIDENCE ACQUISITION: We conducted a search of the literature using the Ovid Medline database and Google Scholar, focusing on articles that explored the association between OSA and ophthalmic conditions. These included hypertensive retinopathy, diabetic retinopathy, central serous retinopathy (CSR), retinal vein occlusion (RVO), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, idiopathic intracranial hypertension (IIH), papilledema, and stroke. RESULTS: There is evidence of an independent association between OSA, and both hypertension and Type 2 diabetes mellitus, as well as the retinopathy associated with each disease. Evidence also suggests a link between OSA and CSR, NAION, and stroke. The evidence remains controversial or insufficient for convincing causative association with RVO, glaucoma, and IIH. However, in patients presenting with CSR, and IIH, underlying OSA is a common finding. CPAP reverses some pathological changes, but the evidence is limited. CONCLUSIONS: OSA is associated with many diseases seen in neuro-ophthalmology clinics. More studies are required to assess the real ability of CPAP to reverse pathological changes. Ophthalmologists can screen for undiagnosed OSA in patients presenting with certain eye diseases.

The learning curve, interobserver, and intraobserver agreement of endoscopic confocal laser endomicroscopy in the assessment of mucosal barrier defects.

BACKGROUND AND AIMS: Confocal laser endomicroscopy can dynamically assess intestinal mucosal barrier defects and increased intestinal permeability (IP). These are functional features that do not have corresponding appearance on histopathology. As such, previous pathology training may not be beneficial in learning these dynamic features. This study aims to evaluate the diagnostic accuracy, learning curve, inter- and intraobserver agreement for identifying features of increased IP in experienced and inexperienced analysts and pathologists. METHODS: A total of 180 endoscopic confocal laser endomicroscopy (Pentax EC-3870FK; Pentax, Tokyo, Japan) images of the terminal ileum, subdivided into 6 sets of 30 were evaluated by 6 experienced analysts, 13 inexperienced analysts, and 2 pathologists, after a 30-minute teaching session. Cell-junction enhancement, fluorescein leak, and cell dropout were used to represent increased IP and were either present or absent in each image. For each image, the diagnostic accuracy, confidence, and quality were assessed. RESULTS: Diagnostic accuracy was significantly higher for experienced analysts compared with inexperienced analysts from the first set (96.7% vs 83.1%, P < .001) to the third set (95% vs 89.7, P = .127). No differences in accuracy were noted between inexperienced analysts and pathologists. Confidence (odds ratio, 8.71; 95% confidence interval, 5.58-13.57) and good image quality (odds ratio, 1.58; 95% confidence interval, 1.22-2.03) were associated with improved interpretation. Interobserver agreement κ values were high and improved with experience (experienced analysts, 0.83; inexperienced analysts, 0.73; and pathologists, 0.62). Intraobserver agreement was >0.86 for experienced observers. CONCLUSION: Features representative of increased IP can be rapidly learned with high inter- and intraobserver agreement. Confidence and image quality were significant predictors of accurate interpretation. Previous pathology training did not have an effect on learning.

Herpes zoster (shingles) at a large New Zealand general practice: incidence over 5 years.

AIM: The objective of this study, in a large group practice in Lower Hutt with a stable population of around 19,000 patients, was to describe the retrospective incidence of shingles over a 5-year period so that it could be compared to international data. METHOD: The practice database was interrogated for patients whose disease code indicated they suffered shingles, herpes zoster, or post herpetic neuralgia between January 1 2009 and December 31 2013. The charts of the identified patients were reviewed to assess whether the diagnosis was confirmed, to ascertain that onset occurred within the specified time period, to describe the site of the rash and the age, sex and ethnicity of the patients. Rates of disease were calculated using a denominator derived from a comparison of patients registered during the 5 years studied. RESULTS: The results indicate that incidence of shingles rose with age, females were more frequently affected than males and that the thorax was the commonest site. CONCLUSION: The incidence at this New Zealand medical centre was similar to that reported internationally.