Disease Severity Scoring System Research Articles

A study on the efficacy of APACHE-IV for predicting mortality and length of stay in an intensive care unit in Iran.

Background: Clinical assessment of disease severity is an important part of medical practice for prediction of mortality and morbidity in Intensive Care Unit (ICU). A disease severity scoring system can be used as guidance for clinicians for objective assessment of disease outcomes and estimation of the chance of recovery. This study aimed to evaluate the hypothesis that the mortality and length of stay in emergency ICUs predicted by APACHE-IV is different to the real rates of mortality and length of stay observed in our emergency ICU in Iran. Methods: This was a retrospective cohort study conducted on the data of 839 consecutive patients admitted to the emergency ICU of Nemazi Hospital, Shiraz, Iran, during 2012-2015. The relevant variables were used to calculate APACHE-IV. Length of stay and death or discharge, Glasgow coma score, and acute physiology score were also evaluated. Moreover, the accuracy of APACHE-IV for mortality was assessed using area under the Receiver Operator Characteristic (ROC) curve. Results: Of the studied patients, 157 died and 682 were discharged (non-survivors and survivors, respectively). The length of stay in the ICU was 10.98±14.60, 10.22 ± 14.21 and 14.30±15.80 days for all patients, survivors, and non-survivors, respectively. The results showed that APACHE-IV model underestimated length of stay in our emergency ICU (p<0.001). In addition, the overall observed mortality was 17.8%, while the predicted mortality by APACHE-IV model was 21%. Therefore, there was an overestimation of predicted mortality by APACHE-IV model, with an absolute difference of 3.2% (p=0.036). Conclusion: The findings showed that APACHE-IV was a poor predictor of length of stay and mortality rate in emergency ICU. Therefore, specific models based on big sample sizes of Iranian patients are required to improve accuracy of predictions.

Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency

Autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to serine 32 and serine 36 or N-terminal truncations in IκBα that impair its phosphorylation and degradation and thus activation of the canonical nuclear factor κ light chain enhancer of activated B cells (NF-κB) pathway. The outcome of hematopoietic stem cell transplantation is poor in patients with AD EDA-ID despite achievement of chimerism. Mice heterozygous for the serine 32I mutation in IκBα have impaired noncanonical NF-κB activity and defective lymphorganogenesis. We sought to establish genotype-phenotype correlation in patients with AD EDA-ID. A disease severity scoring system was devised. Stability of IκBα mutants was examined in transfected cells. Immunologic, biochemical, and gene expression analyses were performed to evaluate canonical and noncanonical NF-κB signaling in skin-derived fibroblasts. Disease severity was greater in patients with IκBα point mutations than in those with truncation mutations. IκBα point mutants were expressed at significantly higher levels in transfectants compared with truncation mutants. Canonical NF-κB-dependent IL-6 secretion and upregulation of the NF-κB subunit 2/p100 and RELB proto-oncogene, NF-κB subunit (RelB) components of the noncanonical NF-κB pathway were diminished significantly more in patients with point mutations compared with those with truncations. Noncanonical NF-κB-driven generation of the transcriptionally active p100 cleavage product p52 and upregulation of CCL20, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1), which are important for lymphorganogenesis, were diminished significantly more in LPS plus α-lymphotoxin β receptor-stimulated fibroblasts from patients with point mutations compared with those with truncations. IκBα point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical andnoncanonical NF-κB activity in patients with AD EDA-ID.

A new framework for evaluating the health impacts of treatment for Gaucher disease type 1

BackgroundThe Disease Severity Scoring System (DS3) is a validated measure for evaluating Gaucher disease type 1 (GD1) severity. We developed a new framework, consisting of health states, transition probabilities between those states, and preferences for those states (utilities) based on the DS3 to predict long-term outcomes of patients starting treatment. We defined nine mutually exclusive (alive) health states based on three DS3 categories: mild (0 ≤ DS3 ≤ 3.5) without symptoms of bone disease; mild with bone pain, mild with severe skeletal complications (SSC) defined as lytic lesions, avascular necrosis, or fracture; moderate (3.5 < DS3 ≤ 6.5) without SSC; moderate with SSC; marked (6.5 < DS3 ≤ 9.5) without SSC; marked with SSC; severe (9.5 < DS3 ≤ 19) without SSC; and severe with SSC. Health-state transition probabilities and utilities were estimated from a longitudinal sample of patients with GD1 who started enzyme replacement therapy (the DS3 Score Study). Age dependent GD1-specific mortality was derived from published data. We used a Markov state-transition model to illustrate how to estimate time spent in each health state.ResultsThe average predicted utilities for each health state ranged from 0.76 for mild disease with no clinical symptoms of bone disease to 0.52 with severe disease with SSC. Transition probabilities depended on disease severity (DS3 score) at treatment initiation and whether patients had undergone a total splenectomy or had an intact spleen/partial splenectomy prior to starting treatment. Patients who started treatment with intact or residual spleens spent more time in better health states than those who started treatment with total splenectomy.ConclusionsThis new framework, which is based on the DS3, can be used to project the long-term outcomes of GD1 patients starting treatment. The framework could also be used to compare the long-term outcomes of different GD1 treatment options.Trial registrationNCT01136304. Registered: May 31, 2010 (retrospectively registered).

Dissecting Parameters Associated with Sheath Rot (&lt;i&gt;Sarocladium oryzae&lt;/i&gt; [(Sawada) W. Gams &amp; D. Hawksw]) Disease in Rice (&lt;i&gt;Oryza sativa&lt;/i&gt; L.

Accurate measurement of parameters contributing to diseases and their symptoms is important for identification of resistant genotypes. Present sheath rot scoring system such as disease incidence scoring system accounts for only percentage of disease incidence and not the disease severity. Disease severity scoring system is based on combined features of panicle exertion and lesion size, very laborious and less accurate in field condition. Existing disease index requires assigning of incidence-severity scores for each and every tillers in a plant and has greater difficulties in evaluation of large number of plants or breeding pools. Hence, we propose phenotypic parameters such as proportion of panicle exertion, proportion of diseased and healthy sheath and modified disease severity scoring system for accurate measurement of disease. A high-throughput and simple disease indices (severity index, lesion index, detached lesion index and panicle discolouration index) are proposed for accurate identification of resistant-susceptible genotypes.

Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease.

Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients.

FAbry STabilization indEX (FASTEX): an innovative tool for the assessment of clinical stabilization in Fabry disease.

Two disease severity scoring systems, the Mainz Severity Score Index (MSSI) and Fabry Disease Severity Scoring System (DS3), have been validated for quantifying the disease burden of Fabry disease. We aimed to develop a dynamic mathematical model [the FASTEX (FAbry STabilization indEX)] to assess the clinical stability. A multidisciplinary panel of experts in Fabry disease first defined a novel score of severity [raw score (RS)] based on three domains with a small number items in each domain (nervous system domain: pain, cerebrovascular events; renal domain: proteinuria, glomerular filtration rate; cardiac domain: echocardiography parameters, electrocardiograph parameters and New York Heart Association class) and evaluated the clinical stability over time. The RS was tested in 28 patients (15 males, 13 females) with the classic form of Fabry disease. There was good statistical correlation between the newly established RS and a weighted score (WS), with DS3 and MSSI (R2 = 0.914, 0.949, 0.910 and 0.938, respectively). In order to refine the RS further, a WS, which was expressed as a percentage value, was calculated. This was based on the relative clinical significance of each item within the domain with the panel agreeing on the attribution of a different weight of clinical damage to a specific organ system. To test the variation of the clinical burden over time, the RS was repeated after 1 year. The panel agreed on a cut-off of a 20% change from baseline as the clinical WS to define clinical stability. The FASTEX model showed good correlation with the clinical assessment and with clinical variation over time in all patients.

Development of a new disease severity scoring system for patients with non-transfusion-dependent thalassemia

BackgroundPatients with non-transfusion-dependent thalassemia (NTDT) present with a spectrum of disease severities. Since there are multiple pathophysiologies in such patients, tailoring treatment remains essential. Therefore, one simple, reliable tool would be beneficial to assess disease severity and tailor therapy, particularly for internal medicine specialists who may treat a variety of NTDT patients with a multitude of complications. This would allow for standardization of assessments leading to timely interventions and prevention of complications. MethodsA working group of NTDT experts was formed to develop a new disease severity scoring system for adult and pediatric patients with NTDT, based on parameters considered to be most pertinent in defining disease severity. Results20 parameters were selected for inclusion in the disease severity scoring system. An additional six parameters, largely related to growth and development, were selected specifically for pediatric patients (≤16years of age). Consensus of expert opinion was used to establish the selected methods of assessment for each parameter, based on feasibility and availability of technology, cost containment, and avoidance of patient risk. ConclusionWe propose that this new disease severity scoring system for adult and pediatric NTDT patients could be developed into a practical tool for widespread clinical use.

Evaluation of disease burden and response to treatment in adults with type 1 gaucher disease using a validated disease severity scoring system (DS3)

BackgroundGD1-DS3 is an integrated assessment of type 1 Gaucher disease (GD1) burden based on bone, hematologic and visceral domains. We investigated this disease severity scoring system (DS3) methodology for initial assessment, long-term follow-up and evaluation of treatment responses.MethodsWe enrolled 133 treated adult GD1 patients. Baseline DS3 scores were calculated near the initial treatment date and patients stratified by severity as marked (DS3 6.00-19.00), moderate (DS3 3.00-5.99), mild (DS3 < 3.00). Follow-up scores were calculated annually. Minimal clinically important improvement (MCII), is defined as ΔDS3 of -3.1.ResultsPatient characteristics: N370S was the most common allele (118 patients had at least one), 52 were N370S/N370S (48/52 were Ashkenazi Jews), N370S/L444P was the most common genotype among non-Jews. Median age of treatment: 45 years; median follow-up: 14 years. Baseline DS3 scores: Patients with marked disease (N = 58; median 7.84) were least likely to be N370S homozygous (19 %) and most likely to have had splenectomy (53 %), early age at diagnosis (median 18 years) and major pre-treatment bone pathology (76 %). Among patients with moderate disease (N = 53; median 4.33), 49 % were N370S/N370S, 15.1 % had splenectomy and 17 % had major bone disease. Median age at diagnosis: 32 years. No patient with mild disease (N = 22; median 2.4) had splenectomy or major skeletal disease. Median age at diagnosis: 40 years. 68 % were N370S homozygous. Response to treatment: Health-state transitions occurred primarily during the early treatment years. At Year 5, among 48 evaluable patients with marked baseline disease, eight were unchanged in severity status whereas 40 had MCII of varying degrees with 11 scored as mild. Among 42 evaluable moderate patients, none worsened, 16 remained moderate and 26 improved to mild. Among 16 evaluable mild patients, 14 remained so and 2 had DS3 scores in the low moderate range.ConclusionsDS3 is effective for assessing disease burden in GD1 and for monitoring response. ERT was associated with MCII in DS3 scores in patients with high severity. Nevertheless, despite better DS3 scores with treatment, GD1 patients especially those with splenectomy and pre-treatment bone pathology, continued to have bone complications.

Severity Assessment of Chronic Liver Disease in Children

Introduction: Chronic liver disease and cirrhosis are the most important causes of growth failure, morbidity and mortality in children. Cirrhosis consists of a variety of congenital, genetic, metabolic, and infectious causes in children. Models for predicting of chronic liver disease severity, survival, and transplantation are useful for decision-making as well as medical interventions. The most important application of this model is to estimate the true mortality rate at a specific time. Therefore, it helps the correct selection of patients for liver transplantation. In this study, we examined the relationship between disease severity and pediatric end-stage liver disease (PELD) scoring system in children with chronic liver diseases. Materials and Methods: This cross–sectional study conducted on 106 children with chronic liver diseases from 2011 to 2012 admitted to Ghaem Hospital, Mashhad, Iran. We used the clinical files of the patients to determine PELD score and recorded all information on a special form. Following that, PELD/MELD (model for end-stage liver disease) scores were calculated. SPSS software version 18 was performed for the analysis of the data applying independent t-test. Results: A total of 106 patients, 53% females and 47% males with the mean age of 68.3±41.8 months participated. The most common clinical finding was hepatomegaly (76%), followed by jaundice and splenomegaly. Jaundice, hepatopulmonary syndrome, cirrhosis and splenomegaly were clearly correlated with PELD score. The increasing of PELD/MELD (model for end-stage liver disease) scores were in line with the high level of liver alkaline phosphatase enzyme and there was a significant relation between them (P<0.05). Conclusion: In our study, all the results showed that the scoring system had the reasonable efficiency in the prognosis and morbidity of chronic liver diseases in children, which has been demonstrated in previous studies. Keywords: Chronic liver disease, MELD score, PELD score.

Engage: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multi-center Study To Investigate The Efficacy and Safety Of Eliglustat In Adults With Gaucher Disease Type 1: 9 Month Results

BackgroundGaucher disease type 1 is one of the most common lysosomal storage disorders. Deficiency of the lysosomal enzyme acid-β-glucosidase leads to accumulation of glucosylceramide (GL-1) in the spleen, liver, and bone marrow. Enzyme replacement therapy has been the mainstay of therapy for the last 20 years. Substrate reduction therapy is another treatment approach that inhibits GL-1 synthase and ultimately restores the balance between synthesis and degradation of the substrate. Eliglustat is a novel oral substrate reduction therapy that is currently in development for the treatment of Gaucher disease type 1. ENGAGE (NCT00891202) is a randomized, double-blind, placebo-controlled, Phase 3 trial sponsored by Genzyme, a Sanofi company investigating the efficacy and safety of eliglustat in untreated adults with Gaucher disease type 1. MethodForty patients (mean age: 31.8 years; 20 males) with splenomegaly and thrombocytopenia and/or anemia were stratified by spleen volume and randomized 1:1 to receive eliglustat (50 or 100 mg BID depending on plasma levels) or placebo for 9 months. The primary efficacy endpoint was percent change in spleen volume (multiples of normal). Other efficacy measures included hemoglobin, liver volume, and platelets. Bone endpoints included bone marrow burden (BMB) scores and bone mineral density changes (DXA). Quality of life assessments included the Gaucher Disease Severity Scoring System (DS3). Safety monitoring included adverse event reporting, and lab and electrocardiogram evaluations. ResultsIn patients receiving eliglustat vs. placebo, mean spleen volume decreased (-28% vs. +2%, P<0.0001), mean hemoglobin increased (0.69 vs. -0.54 g/dL, P<0.0006), liver volume decreased (-5.20% vs. +1.44%, P<0.0072), and platelets increased (+32% vs. -9.06%, P<0.0001). Significant improvements (eliglustat vs. placebo) were observed for total (-1.1 vs. 0.0, p=0.002), spine (-0.6 vs. 0.1, p=0.002), and femur (-0.5 vs. 0.0, p=0.026) BMB scores. Although patients with symptomatic bone disease were excluded, absolute change in total spine DXA Z-scores approached significance (least square mean treatment difference=0.2, p=0.06). Burden of disease, as measured by the Gaucher DS3, was significantly reduced following treatment with eliglustat vs. placebo (least square mean treatment difference=-0.3, p=0.0452). No patients discontinued due to an adverse event, all of which were classified as mild to moderate, and 39/40 patients transitioned into the ongoing open-label trial. Arthralgia and nasopharyngitis occurred in >10% of eliglustat vs. placebo patients. ConclusionENGAGE met its primary and secondary efficacy endpoints. Significant effects on bone marrow and a trend toward BMD improvement in spine were observed. Eliglustat treatment was effective and well-tolerated in untreated adults with Gaucher disease type 1. Disclosures:Shankar:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lukina:Genzyme, a Sanofi company: Consultancy, Honoraria, Speakers Bureau. Amato:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Packman:Genzyme, a Sanofi company: Consultancy, Research Funding. Pastores:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Balwani:Genzyme, a Sanofi company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Mistry:Genzyme, a Sanofi company: Consultancy, Honoraria, Research Funding. Ross:Genzyme, a Sanofi company: Employment. Marulkar:Genzyme, a Sanofi company: Employment. Peterschmitt:Genzyme, a Sanofi company: Employment.

A disease severity scoring system for children with type 1 Gaucher disease

A disease severity scoring system for children with type 1 Gaucher disease

Assessment of clinical benefit and quality of life in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for management of peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) is a challenging problem with poor prognosis. Survival even with the current standard chemotherapy is dismal. Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) in appropriately selected patients may offer significant survival benefit. In the review article entitled “Assessment of Clinical benefit and quality of life in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for management of peritoneal carcinomatosis” authors provide a comprehensive review of the available data related to the morbidity, mortality, survival and quality of life with CRS and HIPEC for the management of peritoneal carcinomatosis (1). Several retrospective studies have shown the feasibility and benefit of CRS and HIPEC in the management of various peritoneal surface malignancies (2,3). Although clinical utility of CRS and HIPEC in the management of mesothelioma and peritoneal dissemination of appendiceal malignancies is widely accepted, its role in colorectal cancer peritoneal carcinomatosis has been heavily debated. Randomized controlled trial by Veerwal et al. demonstrated a survival benefit of 9 months for patients with colorectal peritoneal carcinomatosis treated with CRS and HIPEC followed by 5-FU chemotherapy compared to palliative surgery and 5-FU chemotherapy (4). Furthermore, patients who underwent complete cytoreduction had a 5-year survival rate of 45%, which favorably compares to the reported survival for colorectal hepatic metastasectomy. Despite these promising results skepticism still exists, as the patients in the control arm of the trial did not receive current standard chemotherapy. However, recent studies utilizing current standard chemotherapy with or without biologic agents have reported a median overall survival of 10-15 months in patients with colorectal peritoneal carcinomatosis (5,6). These results underscore the decreased efficacy of systemic treatment in the setting of PC, when feasible CRS and HIPEC should be considered as the standard treatment for patients with colorectal cancer peritoneal carcinomatosis. As described in the review article cytoreductive surgery is a major surgical procedure with significant morbidity. However, in appropriately selected patients the risk-benefit ratio favors an aggressive treatment approach. Extent of peritoneal dissemination, measured as peritoneal cancer index (PCI) and the completeness of cytoreduction have been indisputably shown to be major predictors of outcome (7). Patient selection is a challenging task, as the risk-benefit ratio is influenced by multiple factors. In addition, the ability to accurately estimate the extent of peritoneal dissemination and predicting the chances of complete cytoreduction is far from perfect. Esquivel and Pelz have proposed a peritoneal surface disease severity (PSDS) scoring system based on symptoms, extent of disease and histology to stratify patients with colon cancer peritoneal carcinomatosis into different prognostic groups that may aid in patient selection for different treatment (8). The risk-benefit ratio for CRS and HIPEC not only depends on the ability to achieve complete cytoreduction but on the biologic aggressiveness of the tumor, which is heavily weighed into the PSDS score. Multi-institutional prospective validation studies are required to assess the clinical utility of the PSDS scoring system. Finally, the importance of measurement of health related quality of life (HRQoL) cannot be overemphasized in patients undergoing CRS and HIPEC. The authors have provided a comprehensive review of the available scoring systems and the data for QoL. Most studies report a decrease in the quality of life up to six months after CRS and HIPEC, with improvement in majority of patients at one year. This should be taken into consideration while counseling patients about the outcomes of CRS and HIPEC. In summary, management of patients with peritoneal carcinomatosis is complex and requires a multidisciplinary approach. Proper patient selection for CRS and HIPEC based on favorable risk-benefit ratio is of utmost importance. Management should focus on both cancer-specific outcomes and quality of life.

Small fibre neuropathy in Fabry disease

Fabry disease is an X-linked inherited lysosomal storage disorder associated with glycosphingolipid accumulation in organs and vascular endothelium [1]. Neuropathic pain is common in Fabry disease and is associated with small fibre neuropathy [2, 3]. The diagnosis of small fibre neuropathy is based on symptoms like paresthesias, dysesthesias and pain and clinical signs with abnormal pin prick sensation, quantitative sensory testing (QST) and skin biopsy [4]. Corneal confocal microscopy examination of patients with diabetes mellitus as well as Fabry disease has demonstrated a reduction in sub-basal nerve density, also reflecting small fibre neuropathy [5–7]. In the present study we have compared these tests in patients with Fabry disease. Fifteen patients (five males with mean age of 16.2 years and 10 females with mean age of 33.8 years) with Fabry disease, all verified by mutation analysis, were recruited from the Bergen Fabry cohort at Haukeland University Hospital, Bergen, Norway (2004–2009). Blood levels of alpha-galactosidase varied from 2.2 to 37.8 lkat/kg protein (N: 17.7–26.4). All patients had episodes of neuropathic pain aggravated by heat. Eleven sexand age-matched healthy individuals served as controls for the assessment of small fibre affection. The disease severity scoring system (DS3) was used to measure the general neurological, cardiovascular and renal symptoms and signs in the Fabry patients [8]. Age was positively correlated with the DS3 total score (r = 0.68, p = 0.005; Pearson’s test), while it was negatively associated with the DS3 peripheral nervous system (PNS) score (r = -0.52, p = 0.045; Pearson’s test). Males had higher DS3 PNS score than females (p = 0.043; t test), but there was no sex association with DS3 total score (p = 0.73; t test). The alpha-galactosidase levels were not associated with the DS3 PNS score (r = 0.40, p = 0.135; Pearson’s test). Routine clinical and neurological examination, nerve conduction studies, electromyography, and QST (vibrametry and thermotests) were performed. A slit scanning confocal microscope (Confoscan 3, Nidek Technologies, Vigonza, Italy) was used to measure the sub-basal cornea nerve fibre length (CNFL) (mm/mm) in the central cornea of one eye of each subject. Skin-punch biopsy from the A. K. Bertelsen J. Aarseth C. A. Vedeler (&) Department of Neurology, Haukeland University Hospital, Bergen, Norway e-mail: christian.vedeler@helse-bergen.no

A disease severity scoring system for children with type 1 Gaucher disease

Almost half of patients with Gaucher disease are diagnosed by the age of 10 years, and approximately two thirds are diagnosed by the age of 20 years. Besides symptomatic children, some presymptomatic children are being diagnosed through community screening programs and because of affected siblings. In addition, it is anticipated that in the near future, newborn screening for lysosomal diseases such as Gaucher disease will be introduced in the USA, identifying additional pre/nonsymptomatic children. Currently, there is no severity scoring system for children. A validated disease severity scoring system in the pediatric Gaucher population will be essential for classifying disease severity in these children, monitoring their disease progression, making decisions about when to treat them, and monitoring disease improvement with therapy. A severity scoring system will also be helpful in comparing therapeutic options as new therapies are designed. Therefore, a Pediatric Gaucher Severity Scoring System (PGS3) was devised using expert opinion and validated in 26 patients with type 1 Gaucher disease. The PGS3 correlates well with disease severity in patients at diagnosis and over time. A practical system that will help clinical management, based on signs and symptoms in children with type 1 Gaucher disease, is presented.

The prognostic value of initial blood lactate concentration measurements in very low birthweight infants and their use in development of a new disease severity scoring system

The prognostic value of initial blood lactate concentration measurements in very low birthweight infants and their use in development of a new disease severity scoring system

The prognostic value of initial blood lactate concentration measurements in very low birthweight infants and their use in development of a new disease severity scoring system

ObjectivesTo investigate the predictive value of the Clinical Risk Index for Babies (CRIB) score in current practise, the predictive value of blood lactate concentrations ([L]) and to develop a new...

Relationship Between MELD Severity Score and the Distance Walked and Respiratory Muscle Strength in Candidates for Liver Transplantation

The model end-stage liver disease (MELD) severity scoring system is used in the allocation of organs for liver transplantation. However, there is no evidence of its relationship with the functionality and respiratory muscle strength in these patients. The aim of this study was to analyze the correlation of MELD with distance walked and respiratory muscle strength in patients awaiting liver transplantation. We performed a cross-sectional analysis of 24 individuals (16 male and 8 female) with mean age of 51.8 ± 10.4 years. The MELD score inversely correlated with the 6-minute walking test (6MWT) ( r = −0.85; P < .001) and with the maximal inspiratory pressure (MIP) ( r = −0.69; P < .001). In addition, there was a correlation between 6MWT and MIP ( r = 0.77; P < .001). Thus, MELD scores can be considered to be effective tools to predict the functional capacity and respiratory muscle strength in candidates for liver transplantation.

Interobserver variability of clinical scores in hidradenitis suppurativa is low

Hidradenitis suppurativa (HS) is a chronic recurrent disease with scars and sinus tract formation that causes substantial impact on quality of life. For evaluation of HS and treatment results, a scoring system for disease severity (Hidradenitis Suppurativa Score, HSS) has been proposed. To describe the interobserver reliability of the HSS and further to document its correlation with risk factors and other measures of disease severity. Sixty-one consecutive patients with HS, referred to a clinical centre with special interest in the disease, were scored according to the HSS protocol: eight patients by four dermatologists together, 23 patients by all four observers independently and 30 patients by a single observer. Interobserver variability in HSS between the four observers was investigated in the group of 23 patients. Patients' reports of weight and height, smoking habits etc., were collected, as well as Dermatology Life Quality Index (DLQI) questionnaires. The interobserver concordance of HSS was 0·95. Median (interquartile range, IQR) HSS for all patients was 40 (18-73); women 39 (16-68); men 60·5 (30-95). Median (IQR) HSS for nonsmokers was 26 (12-65); former smokers 30 (10-56); smokers 44 (26-108). Median (IQR) HSS for normal weight patients was 12 (10-30); overweight 43 (25-58); obese 51 (24-95). Mean ± SD DLQI for all patients was 11·3 ± 8·6. HSS is simple to use and shows low interobserver variability. The score correlates with suggested risk factors, indicating that it reflects a valid estimation of disease severity.

140. A validated disease severity scoring system for Fabry disease

140. A validated disease severity scoring system for Fabry disease

A validated disease severity scoring system for adults with type 1 Gaucher disease

PurposeA validated disease severity scoring system (DS3) for Gaucher disease type 1 (GD1) is needed to standardize patient monitoring and to define patient cohorts in clinical studies. MethodsDS3 domains were established by an expert physician group using the nominal group technique of consensus formation. Items were selected by 36 GD1 physicians. The expert group determined appropriate measurement techniques for each item. Measurements were weighted considering contributions to GD1 morbidity and mortality. Consensus Clinical Global Impression Severity scores for sample cases were compared with average DS3 scores. A minimal clinically important difference in GD1 DS3 score was calculated. ResultsThe GD1 DS3 includes bone (42% of score), hematologic (32%), and visceral domains (26%); individual items use routine assessments, including medical history, blood chemistry, organ volume measurements, and bone evaluations (magnetic resonance imaging and dual x-ray absorptiometry). The maximum score is 19. Interrater reliability was 0.97 (Cohen's kappa). DS3 scores were highly correlated with Clinical Global Impression Severity scores (r2 = 0.89). The minimal clinically important difference was −3.2 improvement and +3.9 deterioration. ConclusionThis DS3 accurately quantifies GD1 status and intrapatient change over time. Testing of reliability and validity will continue to allow eventual implementation of the DS3 in clinical studies and routine practice.