[JAPANESE TRANSLATION AND LINGUISTIC VALIDATION OF THE RECAP OF ATOPIC ECZEMA (RECAP)].

BACKGROUND: The Recap of atopic eczema (RECAP), a new core outcome of the atopic dermatitis trial, was translated into Japanese and linguistically validated. METHODS: Translation into Japanese was accomplished according to the ISPOR (International Society for Pharmacoeconomics and Outcome Research) guidelines and the basic guidelines for scale translation. The translation process included two forward translations, reconciliation with native English speakers, third-party back translation, cognitive debriefing, review and harmonization by the original authors. Twenty-seven atopic dermatitis and pediatric specialists from 21 centers in Japan participated in the translation process. Cognitive debriefing was conducted through face-to-face interviews using a think-aloud method with the interview guide including questions about comprehensibility, relevance, comprehensiveness, recall period and suggested improvements, based on the COSMIN methodology. RESULTS: No linguistic or cultural problems were encountered in the translation into Japanese. Cognitive debriefings were conducted with 10 adult patients and 10 parents of pediatric patients. Some minor modifications were made following discussion and approval by the research team and the original authors. The Japanese version of RECAP was considered to be understandable, comprehensive and relevant for adult patients and families of pediatric patients. CONCLUSION: The Japanese version of the RECAP, which has been validated as linguistically equivalent to the original version, is now available. Further evaluation of the measurement properties is needed in the future.

Assessing health outcomes, quality of life, and healthcare use among school-age children with asthma.

OBJECTIVE: Asthma affects six million children in the United States. Most people can control their asthma symptoms with effective care, management, and appropriate medical treatment. Information on the relationship between asthma control and quality of life indicators and health care use among school-age children is limited. METHODS: Using the 2006-2010 combined Behavior Risk Factor Surveillance System Asthma Call-back Survey child data, we examined asthma control and asthma attack status among school-age (aged 5-17 years) children with asthma from 35 states and the District of Columbia. Multivariable logistic regression models were used to assess if having uncontrolled asthma and having ≥1 asthma attacks affect quality of life (activity limitation and missed school days) and healthcare use (emergency department [ED] visits and hospitalizations). RESULTS: About one-third (36.5%) of the 8,484 respondents with current asthma had uncontrolled asthma and 56.8% reported ≥1 asthma attack in the past year. Having uncontrolled asthma and having ≥1 asthma attack were significantly associated with activity limitation (aPR = 1.43 and 1.74, respectively), missed school (1.45 and 1.68), ED visits (2.05 and 4.78), and hospitalizations (2.38 and 3.64). Long-term control (LTC) medication use was higher among respondents with uncontrolled asthma (61.3%) than respondents with well-controlled asthma (33.5%). CONCLUSIONS: Having uncontrolled asthma is associated with reduced quality of life and increased health care use. However, only 61.3% of respondents with uncontrolled asthma use LTC medications. Increasing use of LTC medications among children with uncontrolled asthma could help improve quality of life and reduce health care use.

Use of Haddenham Venex armsleeve for lymphoedema management in clinical practice.

Lymphoedema of the upper limb can be an unwelcome side effect of treatment for breast cancer, some skin cancers, as well as having non-cancer-related causes. Treatment focuses on patient self-management, and involves skin care, exercise, lymphatic drainage massage and compression. Lymphoedema is a chronic, life-long condition, and the correct choice of garment will influence treatment outcomes, enhancing concordance and improving quality of life. This article examines how, following recent improvements to the comfort and overall fit of the Haddenham Venex lymphoedema sleeve, patient feedback informed the implementation of further modifications, and how gaining feedback from patients has empowered them to manage and monitor their own condition. By taking ownership for their own care, long-term control of the condition is improved and self-management is enhanced.

Spontaneous nasal cerebrospinal fluid leaks: management of 24 patients over 11 years.

PURPOSE: Most cases of non-traumatic nasal cerebrospinal fluid (CSF) leaks occur spontaneously without any obvious reason. Severe and life-threatening complications are possible consequences. Endoscopic repair is considered the gold standard; however, diagnosis and therapy of these CSF leaks stay challenging. METHODS: In this retrospective analysis, patients who presented with spontaneous nasal CSF leaks from 2006 to 2017 were included. Symptoms, diagnostics, localization of the skull base defect, surgical method, outcome, and postoperative treatment were recorded. RESULTS: Twenty four patients were included. 8 patients presented with symptoms of meningitis. The skull base defects were most commonly located in the anterior ethmoid roof-especially in the cribriform plate-and in the lateral part of the sphenoid sinus. 21 patients had a BMI above 25. In only 13 cases the defect could be detected preoperatively via computed tomography or additional magnetic resonance imaging. In all patients intraoperative visualization of the CSF leak was possible using intrathecal application of sodium-fluorescein. Endoscopic repair was the initial surgical method for all patients and proved to be successful in 80% of the cases. In most cases surgical revision was performed endoscopically; however, in two patients an open transpterygoidal approach was necessary. CONCLUSIONS: Spontaneous nasal CSF leaks often initially present with symptomatic meningitis. Imaging does not always clearly identify the skull base defect. Common localizations are the anterior ethmoid roof and the lateral sphenoid sinus. Obesity seems to be a predisposing factor. In most cases, endoscopic repair with low morbidity is possible; however, an individualized approach is necessary.

Measuring long-term disease control in patients with atopic dermatitis: A validation study of well-controlled weeks.

BACKGROUND: Because atopic dermatitis (AD) is a relapsing remitting disease, assessing long-term control is important. Well-controlled weeks (WCWs) have been used to assess asthma long-term control but have never been validated for AD. OBJECTIVES: We sought to assess the feasibility, validity, and interpretability of WCWs in patients with AD. METHODS: Three studies of patients with moderate-to-severe AD, including 4 to 6 months of daily/weekly symptom and treatment use data, were evaluated (study A, n = 336; study B, n = 60; and study C, n = 224). WCWs were defined by worsening symptoms and increased medication use. Feasibility, construct validity, and interpretability of WCWs were determined by assessing missing data, association with validated AD outcomes, and floor and ceiling effects. Analysis used linear and logistic regression. RESULTS: WCWs were feasible to collect: 95.2% (study A) and 94.7% (study B) contributed data for at least half of the weekly data points, and 93.2% and 88.7% contributed to all data points up to 4 months. WCWs were significantly associated with validated AD severity instruments, including patient-orientated outcome measures and objective signs (Eczema Area and Severity Index, Three Item Severity Score, and Six Signs, Six Areas Atopic Dermatitis Scale). The odds of experiencing a WCW if AD severity was clear/mild was 5.8 (95% CI, 3.5-9.7), 1.9 (95% CI, 0.8-4.4), and 8.1 (95% CI, 4.5-14.6) in studies A, B, and C, respectively. WCWs were associated with ceiling effects: 31.6% (study A) and 37.5% (study B) of participants had no WCWs more than 90% of the time. CONCLUSIONS: WCWs are valid and feasible for measuring long-term control in AD trials. However, ceiling effects and burden of data collection can limit use.

A Long-Term Control of Intramedullary Thoracic Spinal Cord Metastasis from Small Cell Lung Cancer.

Radiotherapy with systemic corticosteroid therapy has been used to treat intramedullary spinal cord metastasis (ISCM), but recovery of function and long-term survival of these patients has been rarely observed. We report herein a small cell lung cancer (SCLC) patient with recurrent thoracic ISCM, who was successfully treated with radiotherapy and systemic corticosteroid therapy. A 70-year-old man, who was diagnosed as having SCLC seven months previously, developed thoracic ISCM. Soon after the detection of the lesion, the patient received radiotherapy with systemic corticosteroid therapy. Sensory disturbance in both extremities and neurogenic bladder and bowel dysfunction was recovered. The patient could walk after irradiation again. The patient received additional chemotherapy and survived 20 months after the diagnosis of ISCM recurrence. Prompt diagnosis and appropriate treatment for ISCM and effective chemotherapy for recurrent SCLC might be the favorable factors for such patients. Further studies will be required to define a favorable subset of patients most likely to benefit from a conventional approach.

Strategies used for measuring long-term control in atopic dermatitis trials: A systematic review.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardized methods for capturing long-term control of AD. OBJECTIVE: We sought to identify how long-term control has been captured in published randomized controlled trials (RCTs). Results will initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. METHODS: We conducted a systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of 3 months or longer, at least 1 outcome measure recorded at 3 or more time points, full article available, and published in English. RESULTS: In all, 101 of 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%), and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly used for trials including flare data (21/52). Medication use was recorded based on quantity, potency, and frequency of application. LIMITATIONS: We included RCT data only. CONCLUSION: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.

Long-Term Disease Control After locoregional Pelvic Chemoradiation in Patients with Advanced Anal Squamous Cell Carcinoma.

Introduction: The incidence of metastatic squamous cell carcinoma of the anus (SCCA) is increasing. Even if systemic docetaxel, cisplatin, and 5-Fluorouracil (DCF) provide a high rate of long-term remission, the role of pelvic chemoradiation (CRT) is unknown in this setting. We reported the safety and efficacy of local CRT in patients with synchronous metastatic SCCA who achieved objective response after upfront DCF. Methods: Patients included in Epitopes HPV01 or Epitopes HPV02 or SCARCE trials and treated with DCF followed by pelvic CRT were included. Concurrent chemotherapy was based on mitomycin (MMC) (10 mg/m² for two cycles) and fluoropyrimidine (capecitabine 825 mg/m² twice a day at each RT treatment day or two cycles of intra-venous 5FU 1000 mg/m² from day 1 to day 4). Primary endpoints were safety, local complete response rate, and local progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and metastasis-free survival (MFS). Results: From 2013 to 2018, 16 patients received DCF followed by a complementary pelvic CRT for advanced SCCA. Median follow-up was 42 months [range, 11-71]. All patients received the complete radiation dose. Compliance to concurrent CT was poor. Overall, 13/15 of the patients (87%) had at least one grade 1-2 acute toxicity and 11/15 of the patients (73%) had at least one grade 3-4 toxicity. There was no treatment-related death. The most frequent grade 3-4 adverse effects were neutropenia (36%), dermatitis (40%), and anitis (47%). Eleven patients (73%) had at least one chronic grade 1 or 2 toxicity. One patient had a grade 4 chronic rectitis (7%). Complete local response rate was 81% at first evaluation and 62.5% at the end of the follow-up. Median local PFS was not reached and the 3-year local PFS was 77% (95%CI 76.8-77). Conclusions: In patients with metastatic SCCA who had a significant objective response after upfront DCF, local CRT was feasible with high complete local response rate. The good local control rate, despite interruptions due to toxicities and low CT compliance, underline the role of pelvic RT. The high rate of toxicity prompts the need to adapt CRT regimen in the metastatic setting.

Long-term outcomes of patients with unresectable benign meningioma treated with proton beam therapy.

This study aimed to evaluate the long-term efficacy of proton beam therapy (PBT) for unresectable benign meningiomas at the University of Tsukuba, Japan. From 1986-1998, 10 patients were treated at the Particle Radiation Medical Science Center (PRMSC) with a relative biological effectiveness (RBE) value of 1.0 using an accelerator built for physics experiments. The total dose was compensated with an X-ray in three patients. Following that, from 2002-2017, 17 patients were treated with a RBE value of 1.1 at the Proton Medical Research Center (PMRC) which was built for medical use. At the PRMSC, the total dose ranged from 50.4-66 Gy (median: 54 Gy). During the follow-up, which lasted between 3.8 and 31.6 years (median: 25.1 years), the 5-, 10-, 15-, 20- and 30-year local control rates were 100%, and the 5-, 10-, 15-, 20- and 30-year survival rates were 90, 80, 70, 70 and 36%, respectively. One patient died of brainstem radiation necrosis 5.1 years after PBT. At PMRC, the total dose ranged from 45.0-61.2 GyE, with a median of 50.4 GyE. During the follow-up, which lasted between 3 and 17 years with a median of 10.5 years, the 5-, 10- and 15-year local control rates were 94.1%, and the 5-, 10- and 15-year survival rates were 100, 100 and 88.9%, respectively. Neither malignant transformation nor secondary malignancy was observed, indicating that fractionated PBT may be effective and safely control benign unresectable meningioma even for the lifelong period of time.

The German RECAP questionnaire: linguistic validation and cognitive debriefing in German adults with self-reported atopic eczema and parents of affected children.

BACKGROUND: Recap of atopic eczema (RECAP) is a patient-reported outcome measure (PROM) assessing eczema control. Long-term control of eczema is one of the four core outcome domains for atopic eczema trials. This instrument has been recently developed in the UK. OBJECTIVE: This study aimed to translate the English RECAP into German and test its content validity in a German population with self-reported atopic eczema. METHODS: A six-step procedure including two forward and one backward translations, two consensus decisions and an expert review was performed to obtain a German version of RECAP. We conducted semi-standardized cognitive interviews with adults with atopic eczema (n = 7) and parents having children affected by this disease (n = 5). A "think-aloud" method was used and aspects of comprehensibility, comprehensiveness and relevance according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria were examined. Interviews were coded using qualitative content analysis. RESULTS: No particular linguistic problems were encountered during forward-backward translation. Minor wording changes were made as required. The title was adjusted to a more familiar German term of the disease (which is 'Neurodermitis'). The recall period was rephrased from 'over the last week' to 'over the last seven days' since there was a different cultural understanding of the time frame. Regarding content validity, the items of the German RECAP were considered to be comprehensible, comprehensive and relevant for the participants and parents of affected children. The participants understood the instruction and considered the one-week recall period and the response options as appropriate. CONCLUSIONS: A German version of RECAP that is linguistically equivalent to the original version is now available but further assessment of its measurement properties is needed.

Review: Control of feed intake by hepatic oxidation in ruminant animals: integration of homeostasis and homeorhesis.

Feed intake is controlled through a combination of long- and short-term mechanisms. Homeorhetic mechanisms allow adaptation to changes in physiological states in the long term, whereas homeostatic mechanisms are important to maintain physiological equilibrium in the short term. Feed intake is a function of meal size and meal frequency that are controlled by short-term mechanisms over the timeframe of minutes that are modulated by homeorhetic signals to adapt to changes in the physiological state. Control of feed intake by hepatic oxidation likely integrates these mechanisms. Signals from the liver are transmitted to brain feeding centers via vagal afferents and are affected by the hepatic oxidation of fuels. Because fuels oxidized in the liver are derived from both the diet and tissues, the liver is able to integrate long- and short-term controls. Whereas multiple signals are integrated in brain feeding centers to ultimately determine feeding behavior, the liver is likely a primary sensor of energy status.

A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis: study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial.

BACKGROUND: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. METHODS: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. DISCUSSION: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.

Usefulness of a topical combination of dinotefuran and pyriproxyfen for long-term control of clinical signs of allergic dermatitis in privately-owned cats in Ile-de-France region.

BACKGROUND: The present study assessed the activity of a combination of dinotefuran and pyriproxyfen (Vectra® Felis) for long-term control (3 months) of allergic dermatitis (AD) in privately-owned cats under common household conditions in Ile-de-France region. METHODS: This was an open pre-treatment vs post-treatment study. Twenty-eight client-owned cats with clinical signs of AD were enrolled in the study. They received topical application of the combination of dinotefuran and pyriproxyfen on days 0, 28, 56 and 84. Two parameters (clinical signs and pruritus severity) were used to assess the animals' condition on days 0, 28 and 84. Fleas were counted if they were observed. RESULTS: Of the 28 cats initially enrolled, 26 were presented on day 28 and 20 for the final evaluation on day 84. A significant improvement in clinical signs and pruritus was observed in cats for which fleas and/or flea feces were detected on day 0. Globally, the post-treatment AD clinical scores on days 28 and 84 were different from that of the pre-treatment on day 0, with a reduction of 30% and 71%, respectively. For cats with fleas and/or flea feces, the reduction on days 28 and 84 was 33% and 85%, respectively. The improvement of clinical signs and pruritus was not significant in cats with no visible fleas and no flea feces at the beginning of the trial (n = 8). CONCLUSIONS: The present study indicated that the treatment with a combination of dinotefuran and pyriproxyfen should be considered as useful in controlling fleas on cats without additional environmental treatment and useful for long-term control of clinical signs and pruritus in allergic cats.

Open field study on the efficacy of oral fluralaner for long-term control of flea allergy dermatitis in client-owned dogs in Ile-de-France region.

BACKGROUND: Fluralaner is the first orally administered isoxazoline to provide 12 weeks of activity against fleas and ticks after a single administration. As a result of its potent anti-flea activity, oral fluralaner may be proposed as a component of a strategy for the control of flea allergy dermatitis (FAD) in dogs. The open field study reported here assessed the efficacy of fluralaner for long-term control (up to 6 months) of FAD in affected client-owned dogs maintained under common household conditions in the Ile-de-France region. METHODS: This was an open pre-treatment versus post-treatment study. Client-owned dogs with clinical signs of FAD were recruited and treated with oral fluralaner (Bravecto®) at 25-56 mg/kg body weight on days 0 and 84. The dogs' condition was assessed at each visit (on days 0, 28, 84 and 168) using the following three parameters: (i) extent of skin lesions based on the scoring system for canine FAD; (ii) pruritus severity based on the pruritus visual analog scale; (iii) presence or absence of fleas or flea feces. RESULTS: Of the 26 dogs initially enrolled, 23 were presented on day 28, 20 on day 84 and 16 for the final evaluation on day 168. Eighteen out of 20 dogs (90 %) presented on day 84 and 15 out of 16 dogs (94 %) presented on day 168 showed a complete clinical resolution. The post-treatment FAD clinical scores on days 28, 84 and 168 were significantly different from that of the pre-treatment with a reduction of 89.8 %, 98.8 % and 99.8 %, respectively. The post-treatment pruritus index values on days 28, 84 and 168 were significantly different from that of the pre-treatment with a reduction of 45.2 %, 71.2 % and 80.8 %, respectively. CONCLUSIONS: The present study confirmed that oral fluralaner treatment should be considered as effective for long-term control of clinical signs in FAD affected dogs.