Characterization of functioning in multiple sclerosis using the ICF

The objective of this study was to explore whether it is possible to describe based on the International Classification of Functioning, Disability and Health (ICF) relevant aspects of functioning and disability affected in multiple sclerosis (MS) as well as environmental factors relevant to persons with MS. The specific aim was to identify most relevant 'Body functions', 'Body structures', 'Activities and participation', as well as 'Environmental factors' in patients with MS using the ICF. Additionally, different MS forms were compared with respect to the identified problems. A multi-centre study was conducted in an empirical cross-sectional design. Data from 205 individuals with MS were collected in rehabilitation centres: disease related data, socio-demographic data, single interviews based on the Extended ICF Checklist and a patient questionnaire including ratings on general health and functioning status, Beck Depression Inventory II (BDI-II) and Comorbidity Questionnaire (SCQ). The 129 ICF categories identified represent a comprehensive classification of functioning in MS from the clinical perspective. Differences between MS forms were observed for several ICF categories, EDSS, general health and functioning status, but not for BDI and SCQ. The study showed that it is possible to describe based on the ICF the spectrum in functioning and disability affected in MS as well as environmental factors relevant to persons with MS.

Reticulate eruptions: Part 2. Historical perspectives, morphology, terminology and classification

Reticulate eruptions of vascular origin may represent an underlying arterial, venous, microvascular or combined pathology. In the presence of arterial pathology, individual rings are centred around ascending arterial vessels that supply the corresponding area of skin within an arterial hexagon that clinically presents with a blanched centre. Confluence of multiple arterial hexagons generates a stellate (star-like) pattern. In the presence of a primary venous pathology, individual rings correspond to the underlying reticular veins forming multiple venous rings. Focal involvement of a limited number of vessels presents with a branched (racemosa) configuration while a generalized involvement forms a reticulate (net-like) pattern. 'Livedo' refers to the colour and not the pattern of the eruption. Primary livedo reticularis (Syn. cutis marmorata) is a physiological response to cold and presents with a diffuse blanchable reticulate eruption due to vasospasm of the feeding arteries and sluggish flow and hyperviscosity in the draining veins. Livedo reticularis may be secondary to underlying conditions associated with hyperviscosity of blood. Livedo racemosa is an irregular, branched eruption that is only partially-blanchable or non-blanchable and always signifies a pathological process. Retiform purpura may be primarily inflammatory with secondary haemorrhage or thrombohaemorrhagic, as seen in disseminated intravascular coagulopathy.

IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival

BACKGROUND Low-grade gliomas (LGGs) are rare brain neoplasms, with survival spanning up to a few decades. Thus, accurate evaluations on how biomarkers impact survival among patients with LGG require long-term studies on samples prospectively collected over a long period. METHODS The 210 adult LGGs collected in our databank were screened for IDH1 and IDH2 mutations (IDHmut), MGMT gene promoter methylation (MGMTmet), 1p/19q loss of heterozygosity (1p19qloh), and nuclear TP53 immunopositivity (TP53pos). Multivariate survival analyses with multiple imputation of missing data were performed using either histopathology or molecular markers. Both models were compared using Akaike's information criterion (AIC). The molecular model was reduced by stepwise model selection to filter out the most critical predictors. A third model was generated to assess for various marker combinations. RESULTS Molecular parameters were better survival predictors than histology (ΔAIC = 12.5, P< .001). Forty-five percent of studied patients died. MGMTmet was positively associated with IDHmut (P< .001). In the molecular model with marker combinations, IDHmut/MGMTmet combined status had a favorable impact on overall survival, compared with IDHwt (hazard ratio [HR] = 0.33, P< .01), and even more so the triple combination, IDHmut/MGMTmet/1p19qloh (HR = 0.18, P< .001). Furthermore, IDHmut/MGMTmet/TP53pos triple combination was a significant risk factor for malignant transformation (HR = 2.75, P< .05). CONCLUSION By integrating networks of activated molecular glioma pathways, the model based on genotype better predicts prognosis than histology and, therefore, provides a more reliable tool for standardizing future treatment strategies.

Classification and pharmacological treatment of preschool wheezing: changes since 2008.

Since the publication of the European Respiratory Society Task Force report in 2008, significant new evidence has become available on the classification and management of preschool wheezing disorders. In this report, an international consensus group reviews this new evidence and proposes some modifications to the recommendations made in 2008. Specifically, the consensus group acknowledges that wheeze patterns in young children vary over time and with treatment, rendering the distinction between episodic viral wheeze and multiple-trigger wheeze unclear in many patients. Inhaled corticosteroids remain first-line treatment for multiple-trigger wheeze, but may also be considered in patients with episodic viral wheeze with frequent or severe episodes, or when the clinician suspects that interval symptoms are being under reported. Any controller therapy should be viewed as a treatment trial, with scheduled close follow-up to monitor treatment effect. The group recommends discontinuing treatment if there is no benefit and taking favourable natural history into account when making decisions about long-term therapy. Oral corticosteroids are not indicated in mild-to-moderate acute wheeze episodes and should be reserved for severe exacerbations in hospitalised patients. Future research should focus on better clinical and genetic markers, as well as biomarkers, of disease severity.

Analysis of caesarean section rates over time in a single Swiss centre using a ten-group classification system.

OBJECTIVE Caesarean section (CS) rates have risen over the past two decades. The aim of this observational study was to identify time-dependent variations in CS and vaginal delivery rates over a period of 11 years. METHOD All deliveries (13,701 deliveries during the period 1999-2009) at the University Women's Hospital Bern were analysed using an internationally standardised and approved ten-group classification system. Caesarean sections on maternal request (CSMR) were evaluated separately. RESULTS We detected an overall CS rate of 36.63% and an increase in the CS rate over time (p <0.001). Low-risk profile groups were the two largest populations and displayed low CS rates, with significantly decreasing relative size over time. The relative size of groups with induced labour increased significantly, but this did not have an impact on the overall CS rate. Pregnancies complicated by breech position, multiple pregnancies and abnormal lies did not have an impact on overall CS rate. The biggest contributor to a high CS rate was preterm delivery and the existence of a uterine scar from a previous CS. CSMR was 1.45% and did not have an impact on the overall CS rate. CONCLUSION The observational study identified wide variations in caesarean section and vaginal delivery rates across the groups over time, and a shift towards high-risk populations was noted. The biggest contributors to high CS rates were identified; namely, previous uterine scar and preterm delivery. Interventions aiming to reduce CS rates are planned.

Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.

BACKGROUND Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. METHODS We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. RESULTS During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. CONCLUSION NaHB is a highly effective and safe treatment that needs further controlled studies.

Towards the introduction of the 'Immunoscore' in the classification of malignant tumours.

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

The comprehensiveness of the ESHRE/ESGE classification of female genital tract congenital anomalies: a systematic review of cases not classified by the AFS system.

STUDY QUESTION How comprehensive is the recently published European Society of Human Reproduction and Embryology (ESHRE)/European Society for Gynaecological Endoscopy (ESGE) classification system of female genital anomalies? SUMMARY ANSWER The ESHRE/ESGE classification provides a comprehensive description and categorization of almost all of the currently known anomalies that could not be classified properly with the American Fertility Society (AFS) system. WHAT IS KNOWN ALREADY Until now, the more accepted classification system, namely that of the AFS, is associated with serious limitations in effective categorization of female genital anomalies. Many cases published in the literature could not be properly classified using the AFS system, yet a clear and accurate classification is a prerequisite for treatment. STUDY DESIGN, SIZE AND DURATION The CONUTA (CONgenital UTerine Anomalies) ESHRE/ESGE group conducted a systematic review of the literature to examine if those types of anomalies that could not be properly classified with the AFS system could be effectively classified with the use of the new ESHRE/ESGE system. An electronic literature search through Medline, Embase and Cochrane library was carried out from January 1988 to January 2014. Three participants independently screened, selected articles of potential interest and finally extracted data from all the included studies. Any disagreement was discussed and resolved after consultation with a fourth reviewer and the results were assessed independently and approved by all members of the CONUTA group. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the 143 articles assessed in detail, 120 were finally selected reporting 140 cases that could not properly fit into a specific class of the AFS system. Those 140 cases were clustered in 39 different types of anomalies. MAIN RESULTS AND THE ROLE OF CHANCE The congenital anomaly involved a single organ in 12 (30.8%) out of the 39 types of anomalies, while multiple organs and/or segments of Müllerian ducts (complex anomaly) were involved in 27 (69.2%) types. Uterus was the organ most frequently involved (30/39: 76.9%), followed by cervix (26/39: 66.7%) and vagina (23/39: 59%). In all 39 types, the ESHRE/ESGE classification system provided a comprehensive description of each single or complex anomaly. A precise categorization was reached in 38 out of 39 types studied. Only one case of a bizarre uterine anomaly, with no clear embryological defect, could not be categorized and thus was placed in Class 6 (un-classified) of the ESHRE/ESGE system. LIMITATIONS, REASONS FOR CAUTION The review of the literature was thorough but we cannot rule out the possibility that other defects exist which will also require testing in the new ESHRE/ESGE system. These anomalies, however, must be rare. WIDER IMPLICATIONS OF THE FINDINGS The comprehensiveness of the ESHRE/ESGE classification adds objective scientific validity to its use. This may, therefore, promote its further dissemination and acceptance, which will have a positive outcome in clinical care and research. STUDY FUNDING/COMPETING INTERESTS None.