Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios

Influence of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes in patients with chronic pain: cross-sectional study protocol

Published 08.09.17Background: Fear of pain and coping strategies are emotional-behavioral responses to pain and are known to play an important role in the development and maintenance of pain. It is highly likely that fear of pain and coping strategies influence each other, potentially affecting the course of chronic pain. To our knowledge, the relationship between pain, fear of pain and coping strategies, and how they influence patient-anticipated outcomes and health-related quality of life, have not been investigated. Objective: The aims of this study are to test (1) if both fear of pain and/or coping strategies are sufficient causes for maintaining pain; and (2) whether fear of pain influences coping strategies and pain intensity. The study will also examine the impact of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Methods: The cross-sectional study will be conducted using an online survey. The Fear of Pain Questionnaire-III (FPQ-III), the Brief Coping Inventory (COPE), and EuroQoL-5d (EQ-5D) validated questionnaires will be used to collect data. Information pertaining to demographic factors, pain-related factors, and patient-anticipated outcomes will also be collected. The study has ethics approval from the Human Research Ethics Committee of the University of Adelaide. Study participants will be individuals aged 18 years and above who are experiencing chronic pain (ie, pain lasting more than 6 months). Effect measure modification technique (EMMM) will be used to examine if fear of pain acts as a moderator or mediator between coping strategies and pain. Simple and multinomial logistic regression analysis will be used to examine the effect of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Results: Recruitment began July 2017 and it is anticipated that data collection will be completed by October 2017. Findings from this study will help to extend our understanding of fear of pain and coping strategies, their interaction, and their impact on health-related quality of life and patient-anticipated outcomes. Conclusions: Fear of pain and coping strategies have significant influence on the experience of chronic pain and its course. This study will help enhance our understanding of the relationship between fear of pain and coping strategies, which may help in developing patient-centered care practices.Manasi Murthy Mittinty, David S Brennan, Cameron L Randall, Daniel W McNeil, Murthy N Mittinty, Lisa Jamieso

Prevalence, awareness and risk factors of hypertension in a large cohort of Iranian adult population

Background: There is considerable variation in hypertension prevalence and awareness, and their correlates, across different geographic locations and ethnic groups. We performed this cross-sectional analysis on data from the Golestan Cohort Study (GCS). Methods: Enrollment in this study occurred in 2004-2008, and included 50 045 healthy individuals from Golestan Province in northeastern Iran. Hypertension was defined as a SBP at least 140 mmHg, a DBP at least 90 mmHg, a prior diagnosis of hypertension, or the use of antihypertensive drugs. Potential correlates of hypertension and its awareness were analyzed by logistic regression adjusted for sex, age, BMI, place of residence, literacy, ethnicity, physical activity, smoking, black and green tea consumption and wealth score. Results: Of the total cohort participants, 21 350 (42.7) were hypertensive. Age-standardized prevalence of hypertension, using the 2001 WHO standard world population, was 41.8 (95 confidence interval: 38.3-45.2). Hypertension was directly associated with female sex, increased BMI, Turkmen ethnicity, and lack of physical activity, and inversely associated with drinking black tea and wealth score. Among hypertensive patients, 46.2 were aware of their disease, 17.6 were receiving antihypertensive medication, and 32.1 of the treated patients had controlled hypertension. Hypertension awareness was greater among women, the elderly, overweight and obese patients, and those with a higher wealth score. Conclusion: Hypertension is highly prevalent in rural Iran, many of the affected individuals are unaware of their disease, and the rate of control by antihypertensive medications is low. Increasing hypertension awareness and access to health services, especially among less privileged residents are recommended. © Lippincott Williams and Wilkins

Evaluation of pathologic staging using number of nodes in p16-negative head and neck cancer

Objectives: The 8th edition AJCC staging guidelines for head and neck squamous cell carcinoma (HNSCC) recently introduced pathologic staging criteria for nodal disease among p16-positive patients. In this study we evaluate pathologic staging in p16-negative HNSCC. Materials and Methods: We compared pathologic staging to the 7th and 8th edition AJCC staging systems using a statewide population-based cohort. All M0 p16-negative surgical patients were included. The outcome was five-year overall survival. Results: Of 304 patients identified, 113 were N0, 157 had 1–4 positive nodes, and 34 had ≥4 nodes. Survival was 71% (95% CI 61–78%) with no nodes, 48% (36%−60%) for 1–4 nodes, and 24% (11 – 39%) for > 4 nodes. When compared to the AJCC systems, the pathologic staging yielded a larger total survival gradient, more montonic survival, better consistency across primary sites, and a slightly lower Bayesian information criterion (1510 vs 1538). After adjusting for disease characteristics, demographics, and tobacco use, hazard ratios for survival were similar using pathologic and AJCC criteria. Conclusion: In this cohort, pathological staging was more prognostic than AJCC staging. This is the first study to evaluate pathologic staging in p16-negative cancer; if these findings are verified, a universal nodal staging system could be introduced

The CCAP knowledgebase:Linking protistan and cyanobacterial biological resources with taxonomic and molecular data

Peer reviewedPublisher PD

The future for follow-up of gynaecological cancer in Europe. Summary of available data and overview of ongoing trials

After completing treatment, most patients follow a pre-determined schedule of regular hospital outpatient appointments, which includes clinical examinations, consultations and routine tests. After several years of surveillance, patients are transferred back to primary care. However, there is limited evidence to support the effectiveness and efficiency of this approach. This paper examines the current rationale and evidence base for hospital-based follow-up after treatment for gynaecological cancer. We investigate what alternative models of care have been formally evaluated and what research is currently in progress in Europe, in order to make tentative recommendations for a model of follow-up. The evidence base for traditional hospital based follow-up is limited. Alternative models have been reported for other cancer types but there are few evaluations of alternative approaches for gynaecological cancers. We identified five ongoing European studies; four were focused on endometrial cancer patients and one feasibility study included all gynaecological cancers. Only one study had reached the reporting stage. Alternative models included nurse-led telephone follow-up and comparisons of more intensive versus less intensive regimes. Outcomes included survival, quality of life, psychological morbidity, patient satisfaction and cost effectiveness of service. More work is needed on alternative strategies for all gynaecological cancer types. New models will be likely to include risk stratification with early discharge from secondary care for early stage disease with fast track access to specialist services for suspected cancer recurrence or other problems

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.

Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies

Spectrum of pheochromocytoma in the 131 I-MIBG era

131 I-metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy allows for both functional diagnosis and anatomical localization of pheochromocytoma. The spectrum of pheochromocytoma since the routine use of preoperative 131 I-MIBG scan was studied. From 1980 to 1986, a total of 34 patients were primarily diagnosed and treated at the University of Michigan Medical Center, Ann Arbor, Michigan, U.S.A. There were 16 males and 18 females. The mean age was 38 years and 4 patients (11.8%) were under 18 years of age. Six patients (17.6%) had family history of pheochromocytoma or multiple endocrine neoplasia (MEN) II syndrome. The presenting symptoms were hypertension in 29 patients (85.3%); attacks of headache, palpitation, sweating, and flushing in 4 (11.8%), and 1 patient presented with a neck mass. Plasma catecholamines were elevated in 97% of patients while urinary catecholamines and metabolites were elevated in 93.5%. 131 I-MIBG was accurate in 82.3%, partly positive in 11.8%, and false-negative in 5.9% of patients. CT scan was accurate in 80%, partly positive in 10%, but failed to show the tumor in another 10% of patients. At operation, extraadrenal lesions were found in 38.2% of the patients and among these, one-third were extraabdominal. Multiple tumors occurred in 5 (14.7%), and bilateral adrenal lesions occurred in 4 patients (11.8%). Malignancy was diagnosed in 3 patients (8.8%) after an average follow-up period of 2 years. We conclude that the use of routine preoperative 131 I-MIBG scanning improves localization of pheochromocytoma and earlier diagnosis is possible in patients with MEN II syndrome. Multiple tumors, extraadrenal and extraabdominal lesions occur more often than commonly believed. The low rate of confirmed malignancy is probably related to the short period of follow-up. La scintigraphie à l' 131 I-MIBG permet de diagnostiquer et de localiser les phéochromocytomes. Toute la gamme de types de phéochromocytomes reconnu depuis l'utilisation préopératoire systématique de la scintigraphie à l' 131 I-MIBG est présentée. Entre 1980 et 1986, 34 patients ont été explorés et traités au Centre Médical de l'Université de Michigan, Ann Arbor, Michigan. Il y avait 16 hommes et 18 femmes. L'âge moyen était de 38 ans, et 4 patients (11.8%) avaient moins de 18 ans. Six patients (17.6%) avaient des antécédents familiaux de phéochromocytome ou de néoplasmes endocrines multiples (MEN) du type II. Les symptômes amenant à consulter étaient l'hypertension chez 29 patients (85.3%), des crises de céphalées, des palpitations et un flush chez 4 patients (11.8%); un patient présentait une masse cervicale. Les catécholamines plasmatiques étaient élevées chez 97% des patients alors que les catécholamines et leurs métabolites étaient en quantité élevée chez 93.5% des patients. La scintigraphie à l' 131 I-MIBG était positive chez 82.3%, partiellement positive chez 11.8%, et faussement négative chez 5.9% des patients. La tomodensitométrie était positive chez 80%, partiellement positive chez 10%, et faussement négative chez 10% des patients. A l'intervention, des lésions extra-surrénales étaient présentes dans 38.2% des cas, et parmi celles-ci, un tiers étaient extra-abdominales. Les tumeurs étaient multiples dans 5 cas (14.7%), et bilatérales surrénales dans 4 cas (11.8%). Une tumeur maligne était diagnostiquée chez 3 patients (8.8%), après une période de suivi de 2 ans en moyenne. Nous concluons que l'utilisation systématique de la scintigraphie à l' 131 I-MIBG améliore la localisation des phéochromocytomes, permettant un diagnostic plus précoce chez les patients présentant un syndrome MEN II. La multiplicité tumorale et les localisations extra-médullosurrénales ou extra-abdominales se voient beaucoup plus fréquemment qu'on le pensait auparavant. Le taux de malignité peu élevé était probablement en rapport avec la courte période de suivi. La escintigrafía con 131 I-MIBG permite tanto la localización anatómica como el diagnóstico funcional del feocromocitoma. Las características o espectro del feocromocitoma a partir del uso rutinario de 131 I-MIBG han sido estudiadas.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41282/1/268_2005_Article_BF01655447.pd

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529