Development and validation of the Flare-OA questionnaire for measuring flare in knee and hip osteoarthritis.

OBJECTIVE: Ability to assess flares in osteoarthritis (OA) of the knee and hip (KHOA) is important in clinical care and research. Using mixed methods, we developed a self-reported instrument measuring flare and assessed its psychometric properties. METHODS: We constructed questionnaire items from semi-structured interviews and a focus group (patients, clinicians) by using a dual-language (English-French) approach. A Delphi consensus method was used to select the most relevant items. Patients with OA from Australia, France and the United States completed the preliminary Flare-OA, HOOS, KOOS and Mini-OAKHQOL questionnaires online. We used a factor analysis and content approach to reduce items and determine structural validity. We tested the resulting questionnaire (score 0-100) for internal consistency, convergent and known-groups validity. RESULTS: Initially, 180 statements were generated and reduced to 33 items in five domains (response 0 = not at all, to 10 = absolutely) by Delphi consensus (50 patients, 116 professionals) and an expert meeting. After 398 patients (mean [SD] age 64 [8.5] years, 70.4% female, 86.7% knee OA) completed the questionnaire, it was reduced to 19 items by factor analysis and a content approach (RMSEA = 0.06; CFI = 0.96; TLI = 0.94). The Cronbach's alpha was >0.9 for the five domains and the whole questionnaire. Correlation coefficients between Flare-OA and other instrument scores were as predicted, supporting construct validity. The difference in Flare-OA score between patients with and without flare (31.8) largely exceeded 2 SEM (10.2). CONCLUSION: Flare-OA is a valid and reliable patient-reported instrument for assessing the occurrence and severity of flare in patients with KHOA in clinical research.

Co-occurring medical and behavioural conditions in children with Down syndrome with or without ADHD symptom presentation.

BACKGROUND: Co-occurring attention deficit hyperactivity disorder (ADHD) is a challenge to characterise in the presence of other medical conditions commonly present in children with Down syndrome (DS). The current study examined differences among children with DS with or without ADHD symptomatology in terms of demographics, developmental level, co-occurring medical conditions, and parent and teacher ratings of behaviour and executive functioning. METHODS: Parents and teachers of 108 school-age children with DS provided ratings of ADHD symptoms, behaviour problems and executive functioning skills. Children with DS and ADHD symptom presentation, as identified by a scoring algorithm, were compared with those without ADHD symptom presentation on demographic characteristics, developmental level, co-occurring medical conditions and parent-report and teacher-report measures of behaviours and executive functioning. RESULTS: Sleep disorders, disruptive behaviour disorder, allergies and seizures were more common in children with DS and ADHD symptom presentation than in children without ADHD symptom presentation. After controlling for ADHD medication use, children with DS and ADHD symptom presentation had poorer performance than those without ADHD symptom presentation on parent behaviour ratings, teacher behaviour ratings and parent but not teacher ratings of executive functioning. No significant group differences in demographic characteristics or developmental level were identified. CONCLUSIONS: Higher rates of co-occurring medical conditions present in children with DS and ADHD symptom presentation support the need for thorough differential diagnoses. The different pattern of group differences between parent-report and teacher-report has implications for diagnostic practices across settings as well as for treatment.

An algorithm to determine the date when the McDonald criteria are met for the diagnosis of relapsing-remitting multiple sclerosis.

BACKGROUND: A patient is diagnosed with multiple sclerosis once they meet the McDonald criteria of dissemination in space and time. Studies of cohorts of patients with multiple sclerosis need a reproducible way to determine an accurate date of diagnosis. We developed an automatic data-driven algorithm to determine the date when the MacDonald criteria are met, which we validated with the Registre Lorrain des Scleroses en Plaques (ReLSEP), a regional French registry of patients with multiple sclerosis. METHODS: We developed an algorithm to determine the date of diagnosis based on clinical and paraclinical data adapted from the four versions of the McDonald criteria. For validation, the dates of diagnosis generated by the algorithm were compared with those determined by an expert physician using the patients' files as the gold standard. We calculated the sensitivity and specificity of the algorithm to provide a date, then we tested the equivalence between the dates of the gold standard and the algorithm (two-one-sided-t-test). RESULTS: The algorithm used every possibility of determining dissemination in space and time according to the four sets. The sensitivity of the algorithm was 100% for the four sets, and specificity ranged between 95 and 100%. The difference between the dates of diagnosis found by the physician and the algorithm was usually less than 2 weeks (equivalence test P<0.0001). CONCLUSION: The algorithm appears to be an efficient surrogate to accurately determine dates of diagnosis of multiple sclerosis in datasets of patients.

Evaluation of the quality of the care pathway for patients with multiple sclerosis in France: Results of an original study of a cohort of 700 patients.

INTRODUCTION: Evaluating the quality of the care pathway for patients with chronic diseases, such as multiple sclerosis (MS), is an important issue. Process indicators are a recognized method for evaluating professional practices. However, these tools have been little developed in the field of MS, and few data are available. The aim of this study was to describe, retrospectively, with validated indicators, the quality of the care pathway in a population-based cohort of 700 patients with the first manifestations of the disease occurring between January 1, 2000 and December 31, 2001 and during the first 10 years of disease. METHOD: This assessment was based on 48 indicators specific to MS. The information required for the calculation of each indicator was collected from the source files of the 700 patients of the cohort. RESULTS: Data for the 10 years of follow-up were collected for 80% of the patients. In total, 36 indicators were calculated. These results reveal that there is room for improvement, particularly in terms of the initial assessment, access to ophthalmological evaluation, employment, obtaining an evaluation of the need for rehabilitation and access to such care. CONCLUSION: The results of this survey provide access to unprecedented new data in France, that professionals and patients can appropriate to improve the targeting of actions, to improve the quality of care further for patients with MS in France. We propose to continue this process by submitting, for discussion, a targeted list of updated indicators relating to changes in guidelines, and in issues concerning the quality of patient management.

Cystic papillary adenoma of the seminal vesicle.

BACKGROUND: Primary Seminal Vesicle (SV) tumours are a rare entity, with most SV masses representing invasion of the SV by malignancy originating in an adjacent organ, most often the prostate. Previously reported primary SV epithelial tumours have included adenocarcinoma and cystadenoma, with limited prior reports of inracystic papillary structures. CASE PRESENTATION: A 35-year-old male presented with azoospermia, intermittent macroscopic haematuria, and mild right iliac fossa and groin pain. A papillary appearing seminal vesicle mass was found on imaging and seminal vesicoscopy. The mass was robotically excised with diagnosis of benign cystic papillary adenoma made. CONCLUSION: In this manuscript we describe a rare case of a benign cystic papillary adenoma of the seminal vesicle, a unique histological entity differentiated from cystadenoma of the Seminal Vesicle by its papillary component.

Optimizing DyNaChron instrument for assessing chronic nasal dysfunction symptoms by Rasch analysis.

BACKGROUND: The DyNaChron (Dysfonctionnement Nasal Chronique) questionnaire is a self-reporting 78-item instrument assessing six symptoms and their consequences of chronic nasal dysfunction. Patients complete items of a symptom domain only when it is present but in case the patient presents several or all symptoms, its length can limit its use. Here, we aimed to optimize, or shorten, the DyNaChron for clinical use. METHODS: A total of 640 patients in 14 rhinology outpatient clinics all over France completed the original DyNaChron questionnaire before the first rhinologic clinic and 15 days later. The optimization process involved Rasch analysis and then qualitative content analyses. Rasch analysis flagged items with a floor/ceiling effect or with important differential item functioning and an expert committee decided whether to retain the flagged items on the basis of clinical importance and statistical characteristics. The psychometric properties of the optimized version were studied according to classical test theory and Rasch analysis. RESULTS: Rasch analysis revealed 4 items with underfit, 6 with an extreme score, 2 that were highly locally dependent and 16 with differential item functioning which 5 of these 16 items were retained after content analysis. In total, 19 flagged items were removed. Factorial analysis confirmed the preservation of the initial instrument structure in the optimized scale; psychometrics properties and scale calibration were the same as or better than the original version. CONCLUSION: The shortened DyNaChron optimizes the quality of assessment by deleting redundant items and reduces the burden on respondents; the structure is preserved and the psychometrics properties are improved.

Comparison of a video versus paper questionnaire on functional limitation in lower limb osteoarthritis.

INTRODUCTION: The video Animated Activity Questionnaire (AAQ) was developed to assess the impact of lower limb osteoarthritis (OA) on daily functional activities. The objective of the study was to compare the video and the HOOS/KOOS paper questionnaires and to assess the effect of order of administration. MATERIAL AND METHODS: Patients recruited in the KHOALA cohort were randomized in two groups: AAQ questionnaire first (AAQ-first group) and HOOS (hip)/KOOS (knee) questionnaire first (H/KOOS-first group). Within group differences between AAQ and HOOS/KOOS scores were compared using a Student t-test. The Spearman correlation coefficient between AAQ score and HOOS/KOOS score was calculated in each group then compared, using Fisher z-transformation. RESULTS: Among 200 randomized patients, 188 (65.8 years, 66.0% women) completed the questionnaires: 99 in the AAQ-first group and 89 in the H/KOOS-first group. The AAQ score was 85.9 (SD: 13.7) in the AAQ-first versus 87.8 (SD: 13.1) in the H/KOOS-first group (p = 0.34). The H/KOOS score was 72.5 (SD: 21.2) in the AAQ-first versus 73.5 (SD: 18.4) in the H/KOOS-first group (p = 0.71). The Spearman correlation coefficient between AAQ and H/KOOS in the AAQ-first was 0.84[0.77-0.89] and 0.73[0.61-0.81] in H/KOOS-first group. These correlations differed between groups significantly (p = 0.02). CONCLUSION: This study found video AAQ and paper HOOS/KOOS questionnaire highly correlated, with a moderate but significant effect of order administration of video and paper questionnaires evidencing a stronger correlation when the videos were viewed first.

Clinical follow-up of 411 patients with relapsing and progressive multiple sclerosis 10 years after discontinuing mitoxantrone treatment: a real-life cohort study.

BACKGROUND AND PURPOSE: Mitoxantrone (MITOX) has been used to treat patients with aggressive multiple sclerosis (MS) for decades. We aimed to describe the effectiveness and adverse events over 10 years post-MITOX in patients with relapsing and progressive MS from an exhaustive real-life database. METHODS: Data from patients who received MITOX before 1 January 2006 were collected from the MS Lorraine registry. Expanded Disability Status Scale (EDSS) scores and annual relapse rates (ARRs) year by year during follow-up and the year prior to MITOX were compared. Time to the first relapse and a 1-point increase in EDSS score were used in Cox multivariate models to find associations with potential predictive factors. RESULTS: A total of 411 patients were included. The ARR for the 155 relapsing patients had decreased from 2.0 (SD 1.20) the year before treatment to 0.3 (SD 0.31) by year 10 (P < 0.0001). The EDSS score increased from 2.8 (SD 1.44) to 4.8 (SD 1.90) by year 10 (P < 0.0001). A high ARR at MITOX initiation was associated with a longer time to a 1-point increase in EDSS score (hazard ratio, 0.81; 95% confidence interval, 0.67-0.99; P = 0.04). The EDSS score in 256 progressive patients increased from 5.0 (SD 1.33) to 6.5 (SD 1.26) by year 10 (P < 0.0001). We identified four cases of acute myeloid leukemias. CONCLUSIONS: Patients with the most active forms of MS are the most likely to benefit from MITOX in the long term.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Links between sleep and daytime behaviour problems in children with Down syndrome.

BACKGROUND: In the general population, sleep problems have an impact on daytime performance. Despite sleep problems being common among children with Down syndrome, the impact of sleep problems on daytime behaviours in school-age children with Down syndrome is an understudied topic. Our study examined the relationship between parent-reported and actigraphy-measured sleep duration and sleep quality with parent and teacher reports of daytime behaviour problems among school-age children with Down syndrome. METHOD: Thirty school-age children with Down syndrome wore an actigraph watch for a week at home at night. Their parent completed ratings of the child's sleep during that same week. Their parent and teacher completed a battery of measures to assess daytime behaviour. RESULTS: Parent reports of restless sleep behaviours on the Children's Sleep Habits Questionnaire, but not actigraph-measured sleep efficiency, was predictive of parent and teacher behavioural concerns on the Nisonger Child Behaviour Rating Form and the Vanderbilt ADHD Rating Scales. Actigraph-measured sleep period and parent-reported sleep duration on the Children's Sleep Habits Questionnaire was predictive of daytime parent-reported inattention. Actigraph-measured sleep period was predictive of parent-reported hyperactivity/impulsivity. CONCLUSION: The study findings suggest that sleep problems have complex relationships to both parent-reported and teacher-reported daytime behaviour concerns in children with Down syndrome. These findings have implications for understanding the factors impacting behavioural concerns and their treatment in school-age children with Down syndrome.

Estimating the potential cost of a high dose immune tolerance induction (ITI) therapy relative to the cost of a combined therapy of a low dose ITI therapy with bypassing agent prophylaxis.

INTRODUCTION: The International Immune Tolerance Study (I-ITI) demonstrated comparable success rates between low (FVIII 50 IU/kg/TIW) and high dose (FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time-to-treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis (BAP) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI. AIM AND METHODS: An economic model was developed to compare high dose ITI to low dose ITI with BAP. All model inputs were derived from clinical trials. The I-ITI study indicated a median time to negative inhibitor titre of 4.6 and 9.2 months and average number of bleeds/patient of 4.2 and 9.9 for the high and low dose regimens respectively. Based on the BAP trials, aPCC (85 U/kg/TIW) and rFVIIa (90 µg/kg/day) achieved a 62% and 45% reduction in bleeding frequency respectively. Cost analysis was from a US third party payer perspective and limited to drug costs. One-way, two-way and probabilistic sensitivity analyses were performed. RESULTS: Costs of low dose ITI with aPCC prophylaxis until negative inhibitor titre is achieved was 24.0% less compared to high dose ITI. Low dose ITI with rFVIIa prophylaxis cost 46.5% more compared to high dose ITI. Model results were robust in the majority of the sensitivity analyses. CONCLUSION: A low dose ITI regimen with aPCC prophylaxis may be cost saving compared to a high dose ITI regimen with the potential to reduce morbidity by lowering the risk for breakthrough bleeds.

Viral discovery as a tool for pandemic preparedness.

Emerging diseases are frequently caused by novel or previously unrecognised zoonotic viral pathogens, which tend to originate in and emerge from wildlife. When human or animal cases are first recognised, molecular or serological diagnostic assays specific to them do not yet exist, causing a delay in the identification of an outbreak's aetiologic agent as well as its source. Preparing for the next virus to emerge is a major public health challenge, impeded by a poor understanding of the diversity of potential candidates that exist in wildlife reservoirs. Characterising the diversity of viruses in key wildlife species will help to reduce the time between detection and response in an outbreak situation, and inform public health strategies that reduce the risk of spillover from animal reservoirs. Pathogen discovery techniques such as consensus polymerase chain reaction (cPCR) and next-generation sequencing (NGS) have been used to identify known and novel viruses in animals and humans, but have not been widely used in surveillance programmes. Metagenomic studies have identified novel viruses, new strains of known viruses, and have characterised host microbiomes. While NGS represents an unbiased approach to viral sequence detection, it is constrained by lower sensitivity than conventional PCR, requires substantial bioinformatics capabilities, and is cost prohibitive and therefore not widely available in the regions of the world that are most vulnerable to zoonotic disease emergence. In contrast, consensus PCR uses standard and widely available technologies, has greater sensitivity than NGS, and has also been used to identify novel viruses in wildlife, livestock and humans, though it is limited to detecting target genetic sequences conserved across known groups of viruses. The use of cPCR, in combination, if possible, with NGS and serology, can offer a powerful approach to rapidly identifying aetiologic agents in an outbreak and characterising the virome of key wildlife known to carry zoonotic viruses. Here, the authors review pathogen discovery techniques currently being used in human and animal surveillance programmes and the challenges of using viral discovery to identify novel zoonotic pathogens.

Les maladies émergentes sont souvent causées par des virus nouveaux ou précédemment inconnus, de portée zoonotique, qui ont généralement leur source dans la faune sauvage, à partir de laquelle s'effectue leur émergence. Lorsque le premier cas d'infection par un virus de ce type est détecté chez l'homme ou chez les animaux, il n'existe encore aucune épreuve moléculaire ou sérologique de détection de l'agent étiologique, ce qui retarde son identification ainsi que l'élucidation de la source du foyer. La préparation aux futures émergences virales est un véritable défi de santé publique et se voit entravée par les lacunes des connaissances sur la diversité des virus potentiellement candidats. La caractérisation des différents virus qui affectent les principales espèces sauvages permettra de réduire le délai entre le moment où un nouveau foyer est détecté et celui où une réponse lui est apportée, et d'élaborer en connaissance de cause des stratégies de santé publique visant à limiter le risque d'un franchissement d'espèce à partir des réservoirs animaux. Les techniques de découverte d'agents pathogènes, par exemple l'amplification en chaîne par polymérase (PCR) pan-générique ou consensus et le séquençage de nouvelle génération (SNG) sont utilisées pour identifier des virus connus ou nouveaux chez l'homme et l'animal, mais ne sont pas d'une utilisation courante dans les programmes de surveillance. Les études métagénomiques permettent d'identifier des virus nouveaux ainsi que les souches nouvelles de virus connus et servent également à caractériser le microbiome de l'hôte. Le SNG constitue une méthode de détection des séquences virales exempte de biais mais sa sensibilité moindre que celle des PCR classiques, les capacités bio-informatiques considérables qu'il requiert et son coût prohibitif sont des contraintes importantes qui en limitent l'utilisation dans les régions du monde les plus vulnérables à l'émergence des maladies zoonotiques. En revanche, la PCR consensus fait appel à des technologies normalisées et largement disponibles, tout en présentant une meilleure sensibilité que le SNG ; elle permet également d'identifier des virus nouveaux présents dans la faune sauvage, chez les animaux domestiques ou chez l'homme, bien qu'elle ne détecte que des séquences génétiques cibles conservées d'un groupe connu de virus à l'autre. Le recours à la PCR consensus, si possible associé aux techniques de SNG et à la sérologie se révèle une stratégie puissante qui permet d'identifier rapidement les agents responsables d'un foyer et de caractériser le virome d'espèces sauvages jouant un rôle majeur en tant que réservoirs de virus zoonotiques. Après avoir passé en revue les techniques de découverte d'agents pathogènes actuellement utilisées dans les programmes de surveillance des maladies animales et humaines, les auteurs font le point sur les enjeux de ces techniques pour l'identification de nouveaux agents pathogènes zoonotiques.

La causa de las enfermedades emergentes reside muchas veces en virus zoonóticos de aparición reciente o hasta entonces no descritos, que en general se originan y surgen en animales salvajes. Cuando se detectan los primeros casos en personas o animales aún no existen pruebas específicas de diagnóstico, ya sea molecular o serológico, y ello retrasa la identificación del agente etiológico del brote y la determinación de su origen. Prepararse para el próximo virus que vaya a aparecer es un gran objetivo de salud pública, lastrado en la práctica por el escaso conocimiento de la gran diversidad de posibles candidatos que moran en los reservorios de la fauna salvaje. La caracterización de los diversos virus que existen en las principales especies de animales salvajes ayudará a reducir el lapso que media entre la detección y la respuesta en caso de brote y a fundamentar a partir de ahí estrategias de salud pública que reduzcan el riesgo de diseminación desde los reservorios animales. Hasta ahora las técnicas de descubrimiento de patógenos, como la reacción en cadena de la polimerasa (PCR) de consenso (PCRc) o la secuenciación de próxima generación, han servido para identificar virus nuevos o ya conocidos en personas y animales, pero no se han aplicado de forma generalizada a los programas de vigilancia. Gracias a estudios de metagenómica se han podido detectar virus recién aparecidos o nuevas cepas de virus ya conocidos y caracterizar los microbiomas de los organismos anfitriones. Aunque la secuenciación de próxima generación constituye un método exento de sesgos para detectar secuencias víricas, adolece de una menor sensibilidad que la PCR convencional, exige una considerable capacidad de gestión informática de datos biológicos y tiene un costo prohibitivo, por lo que no suele aplicarse en las regiones del mundo que están más expuestas a la aparición de enfermedades zoonóticas. La PCR de consenso, en cambio, reposa en técnicas habituales y muy extendidas, ofrece mayor sensibilidad que la secuenciación de próxima generación y también ha sido utilizada para identificar virus nuevos en personas o animales salvajes y domésticos, si bien solo permite detectar las secuencias genéticas «diana¼ conservadas de entre todos los grupos conocidos de virus. El uso de la PCRc, combinado con la secuenciación de próxima generación y técnicas serológicas cuando sea posible, puede ofrecer un potente método para identificar con rapidez los agentes etiológicos de un brote y caracterizar el viroma de los principales animales salvajes de los que se sabe que son portadores de virus zoonóticos. Los autores pasan revista a las técnicas de descubrimiento de patógenos que se utilizan actualmente en los programas de vigilancia sanitaria y zoosanitaria y exponen las dificultades que presenta el uso del descubrimiento de virus para identificar nuevos patógenos zoonóticos.

Obstructive sleep apnoea and the need for its introduction into dental curricula.

Obstructive sleep apnoea (OSA) is a major health problem which causes blood oxygen desaturation that may initiate a cascade of events via inflammatory cytokines and adrenocorticotrophic hormone that may have impact upon quality of life and lead to potential life-threatening events. Even though OSA affects an increasing number of individuals, the role of dental practitioners in recognition, screening and management has not developed accordingly. The goal of this article was to provide updated information to dental practitioners on pathophysiology, consequences and treatment options of OSA with a focused discussion on oral appliance (OA) therapy, as this topic is not routinely included in current dental curricula of many dental schools. Additionally, we present a template dental curriculum for predoctoral and/or postdoctoral students in education regarding sleep disordered breathing.

Abdominoplasty and simultaneous laparoscopic ventral hernia repair. Clinical study about 45 patients.

INTRODUCTION: Abdominoplasty procedures sometimes reveal the presence of ventral hernias (umbilical or trocar-site hernias). Our objective is then to deal with the excess abdominal skin and fat tissue at the same time as the ventral hernia. This can be done with a single surgical procedure combining abdominoplasty with umbilical transposition and laparoscopic ventral hernia repair (LVHR) with mesh. The main objective of our study is to assess the outcome of the combined procedure of abdominoplasty and LVHR with mesh, compared to abdominoplasty alone. MATERIALS AND METHODS: A retrospective single-centre cohort study was conducted, including patients operated on with the combined method (ABDO-LVHR group) and patients who underwent abdominoplasty alone (ABDO group). We noted major and minor complications, with infection issues as our main concern. RESULTS: We included 15 patients in the ABDO-LVHR group and 30 in the ABDO group. The results show no statistically significant difference for infectious complications in the ABDO-LVHR group compared to the ABDO group (20% vs 3.3%; P=0.100). There was no instance of complete umbilical necrosis. Other major and minor complications occurred at the rates typically described in the literature without difference between the two groups. CONCLUSION: There was no significant difference between our two groups in terms of infectious complications. LVHR carried out at the same time as abdominoplasty with umbilical transposition is a positive combination of procedures. Further studies are necessary to confirm that the risk in terms of infectious complications is no higher than for abdominoplasty alone. LEVEL OF EVIDENCE: III.

Modeling complete removal of risk assessment questions in the USA predicts the risk of HIV exposure in blood recipients could increase despite the use of nucleic acid testing.

BACKGROUND AND OBJECTIVES: The safety of the blood supply in a number of countries is achieved by interventions that include behaviour-based time-limited or indefinite deferrals and screening of donated units for transfusion-transmitted infections. The relatively high sensitivity of nucleic acid testing (NAT) used in blood donor screening has raised the question of whether such time-based deferrals can be eliminated in favour of individual risk assessment. MATERIALS AND METHODS: Data on the annual number of incident human immunodeficiency virus (HIV) infections associated with various behaviours and on the performance characteristics of NAT applied to donor screening were used to model the number of potentially infected units that might escape detection in the worst-case scenario in which individual risk assessment was implemented, but was not effective as a screening tool, and donors did not otherwise self-select for lower risk. RESULTS: In the absence of effective individual risk-based screening or donor self-selection, the model predicts that in the United States, an additional 39 (95% CI 35-43) HIV-infected units would escape detection by nucleic acid testing, potentially capable of exposing approximately 68 (95% CI 61-75) individuals to the risk of HIV infection through the administration of prepared blood components. CONCLUSION: Despite some inherent uncertainty, the worst-case scenario of completely ineffective individual risk assessment, absence of donor self-selection and increased reliance on NAT for blood screening is estimated to be associated with an approximately fourfold increase in the risk of HIV exposure through transfusion in the United States.

[The 2014 consensus conference of the ISUP on Gleason grading of prostatic carcinoma]. / Konsenskonferenz 2014 der ISUP zur Gleason-Graduierung des Prostatakarzinoms.

In 2005 the International Society of Urological Pathology (ISUP) held a concensus conference on Gleason grading in order to bring this grading system up to the current state of contemporary practice; however, it became clear that further modifications on the grading of prostatic carcinoma were necessary. The International Society of Urological Pathology therefore held a further consensus conference in 2014 to clarify these points. This article presents the essential results of the Chicago grading meeting.

Health-related quality of life assessment in haemophilia patients on prophylaxis therapy: a systematic review of results from prospective clinical trials.

INTRODUCTION: Prophylaxis is effective in reducing the number of bleeding episodes in patients with severe or moderately severe haemophilia A and B, including those with inhibitors. However, data, predominantly from observational studies, suggest more equivocal effects on health-related quality of life (HRQoL). AIM: To examine the impact of prophylaxis on HRQoL from prospective clinical trials. METHODS: We performed a systematic literature review of clinical trials evaluating the efficacy of prophylaxis with factor VIII, FIX or bypassing agents. Trials assessing HRQoL via validated instruments were selected and summarized. RESULTS: Thirteen trials (haemophilia A [n = 8]; haemophilia B [n = 2]; inhibitors [n = 3]) met all inclusion criteria. HRQoL instruments included the EQ-5D, SF-36, Haem-QoL-A, Haem-A-QoL, Haemo-QoL and CHO-KLAT. Improvements in HRQoL following prophylaxis were observed with the EQ-VAS, SF-36 and haemophilia-specific instruments in adult patients and were associated with reduced pain, fewer restrictions in physical activities and better general health. Prophylaxis led to statistically significant or clinically meaningful HRQoL improvement in six trials and non-significant improvement in four trials; two trials found no improvement and one reported no data. Despite study differences, consistent trends suggested that patients previously treated solely on-demand and those who experienced marked reductions in the frequency of bleeding with prophylaxis had a greater improvement in HRQoL. CONCLUSION: Contrary to findings of observational studies, the results from the majority of prospective trials using validated instruments showed positive trends for improved HRQoL with prophylaxis in adults.

Toluidine blue aids in detection of dysplasia and carcinoma in suspicious oral lesions.

OBJECTIVES: Accurate clinical identification of 'higher-risk' oral premalignant lesions or 'higher-risk' areas within lesions is important. Assessment methods that predict their presence have great utility. SUBJECTS AND METHODS: A cross-sectional, observational study enrolled a consecutive sample of consenting patients diagnosed with oral leukoplakia, erythroleukoplakia, or erythroplakia. Medical history, visual oral examination, ViziLite(®) examination, toluidine blue staining (TBlue(®) ), and finally a biopsy were completed in a single clinic visit. Seventy-seven of 100 examined lesions in 43 patients were biopsied. Sensitivity, specificity, and positive and negative predictive values were computed for visual examination, ViziLite(®) , and TBlue(®) using biopsy results as the gold standard. RESULTS: The sensitivity of TBlue(®) in detecting high-risk lesions (carcinoma in situ or carcinoma) was 94 (71-100, P < 0.0003) and specificity 45 (32-58, P < 0.53), while for carcinoma, sensitivity was 100 (54-100, P < 0.032) and specificity 39 (28-52, P < 0.097). The results of ViziLite(®) testing either by itself or in combination with the information from toluidine blue testing revealed low sensitivity for the detection of high-risk lesions. CONCLUSIONS: Clinical examination of leukoplakia, erythroplakia, or erythroleukoplakia lesions combined with toluidine blue staining may aid in the identification of severe dysplasia (carcinoma in situ) or carcinoma. This may help in determining whether, when, and where (the site within a lesion) a biopsy should be taken.

Recent advances in the pathophysiology and management of eosinophilic oesophagitis.

Eosinophilic oesophagitis is an increasingly recognized allergic gastrointestinal disease, which is becoming more common. Although the average age at diagnosis is 30-50 years, it often affects very young children and carries significant long-term morbidity. While our understanding of its pathophysiology is accumulating, the precise pathways by which the disease arises remain unclear. There are inconsistencies in its diagnosis and definition, and a drive towards international standardization is underway. Current methods for diagnosis and monitoring are relatively invasive, and controversies surround their interpretation. Management strategies are imperfect and involve burdensome long-term dietary exclusions, or drug treatments with uncertain efficacy or serious side-effects. It is the focus of a rapidly increasing body of research, the latest insights from which are systematically presented in this review.

Prophylaxis with anti-inhibitor coagulant complex improves health-related quality of life in haemophilia patients with inhibitors: results from FEIBA NF Prophylaxis Study.

The Pro-FEIBA study reported health-related quality of life (HRQoL) improved following 6-month of Factor Eight Inhibitor Bypassing Activity (FEIBA) prophylaxis. This study investigates whether 12-month of FEIBA prophylaxis improved HRQoL in haemophilia patients with inhibitors. Thirty-six subjects in a 1-year prospective, randomized, open-label, parallel-design study were randomized to prophylaxis (85 ± 15 U kg(-1) every other day) or on-demand treatment. HRQoL was assessed at screening, 6 and 12-month termination using the EQ-5D, Haem-A-QoL, Haemo-QoL and a general pain visual analog scale (VAS). To evaluate changes, paired t-tests and criteria for minimally important differences were applied. Repeated measures regression tested the association between annualized bleeding rate (ABR) and physical HRQoL. At 6 and 12 months, prophylaxis subjects reported clinically meaningful improvement in EQ-5D index (mean improvement, 0.10 and 0.08, respectively) and both clinically meaningful and statistically significant improvements in EQ-VAS scores (16.9 and 15.7, respectively; P < 0.05) vs. baseline. General pain was significantly reduced during prophylaxis at each follow-up (mean improvement, 20.3 and 23.2, respectively; both P <0.05). At 12 months, prophylaxis subjects achieved significant improvements in Haem-A-QoL Total Score and in four domains: Physical Health, Feeling, View, and Work and School (all P < 0.05). No statistically significant changes, except for Haem-A-QoL Physical Health at 6 months, were observed with on-demand treatment. ABR was decreased by 72.5% with prophylaxis vs. on-demand treatment (P = 0.0003) and reduced ABR was associated with better physical HRQoL (P < 0.05). FEIBA prophylaxis significantly reduced ABR and improved HRQoL in inhibitor patients. Subjects with lower ABR reported better physical HRQoL.