The Mainz Severity Score Index (MSSI): development and validation of a system for scoring the signs and symptoms of Fabry disease

Fabry disease is a rare lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α-galactosidase A. The resultant storage of undegraded glycolipids leads to the progressive development of potentially life-threatening manifestations affecting multiple organ systems in the body. This paper describes the development of the Mainz Severity Score Index (MSSI), a scoring system for patients with Fabry disease.
Conclusion: The MSSI score has been proven to be representative in patients with 'classic' Fabry disease and may be useful for monitoring clinical improvement in patients receiving enzyme replacement therapy.     

Clinico-epidemiological profile and validation of symptoms and signs of severe illness in young infants (< 60 days) reporting to a district hospital

OBJECTIVES: To describe the clinical and epidemiological profile of infants less than 2 months of age reporting to a district hospital and to assess the ability of simple clinical symptoms and signs used by health workers to detect severe illness warranting hospital admission. METHODS: It was an observational study done at a general district hospital at Chandigarh, North India. Infants less than 2 months of age presenting to this hospital were enrolled. All infants were first evaluated by an auxiliary nurse midwife (ANM) to record a pre-determined set of symptoms and signs. A pediatrician who was blinded to the findings of the ANM did an independent assessment for severe illness needing urgent hospitalization. RESULTS: A total of 1268 infants were enrolled. Of these, 356 (28%) were below 7 days of age. Overall, regurgitation, vomiting and stool problems (25%) were the most common presenting complaints in the first 2 months of life, followed by jaundice (22%) and respiratory symptoms (15%). 112 (8.8%) infants were classified as having "severe illness requiring urgent hospital management" by the pediatrician. Nearly half (46%) of the admissions were because of jaundice while 17% each were due to sepsis and pneumonia / lower respiratory tract infection (LRTI). A history of not feeding well (OR 14.7, 8.0 and 11.3 in 0-6, 7-27 and 28-59 days age groups, respectively) and a respiratory rate >60/min (OR 21.5, 6.2 and 10.5 in 0-6, 7-27 and 28-59 days age groups, respectively) had significant positive predictive value to predict severe illness (except jaundice) in all the 3 age groups studied. In the second month of life, severe chest in-drawing (OR 4.6) was also a significant predictor. CONCLUSIONS: Simple clinical signs are useful in hands of health worker for identifying neonates with serious illness warranting hospital admission. These will be of use in the further development of clinical algorithms for the national integrated management of childhood illnesses.     

Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey

AIM: Mutations of the gene (GLA) encoding alpha-galactosidase A are implicated in Fabry disease, a progressive, X-chromosomal inherited lysosomal storage disorder. FOS--the Fabry Outcome Survey - was established as a long-term surveillance study to describe the natural course of Fabry disease and its response to enzyme replacement therapy in a large cohort of European patients. Clinical phenotype, age of onset and course of Fabry disease are very variable, even within the same family, which makes it difficult to define a genotype-phenotype relationship by analysing individual patients. The FOS database contains detailed medical information on a large cohort of patients and thus has the potential to provide important information to address this question. METHODS: At the time of analysis, information on 545 patients belonging to 157 families from nine European countries had been entered into the FOS database. A GLA mutation has been reported in 365 individuals (65% and 68% of all males and females, respectively) in FOS. These data were used to analyse the relationship between genotype and phenotype in Fabry disease. RESULTS: A highly significant positive correlation was found between the age at entry into FOS and the FOS Severity Index in male patients with GLA missense mutations (p < 0.001) as well as in those carrying other types of mutations (p < 0.001). A positive correlation was also found between the age at entry into FOS and the number of affected organs in male patients with missense mutations, irrespective of whether the change in the amino acid side chain predicted in the alpha-galactosidase A protein was classified as a conservative or non-conservative change. CONCLUSION: The data presented here suggest that there is a correlation between genotype and clinical severity.     

Genotype and phenotype in Fabry disease: analysis of the Fabry Outcome Survey

Aim: Mutations of the gene ( GLA ) encoding α-galactosidase A are implicated in Fabry disease, a progressive, X-chromosomal inherited lysosomal storage disorder. FOS – the Fabry Outcome Survey – was established as a long-term surveillance study to describe the natural course of Fabry disease and its response to enzyme replacement therapy in a large cohort of European patients. Clinical phenotype, age of onset and course of Fabry disease are very variable, even within the same family, which makes it difficult to define a genotype–phenotype relationship by analysing individual patients. The FOS database contains detailed medical information on a large cohort of patients and thus has the potential to provide important information to address this question. Methods: At the time of analysis, information on 545 patients belonging to 157 families from nine European countries had been entered into the FOS database. A GLA mutation has been reported in 365 individuals (65% and 68% of all males and females, respectively) in FOS. These data were used to analyse the relationship between genotype and phenotype in Fabry disease. Results: A highly significant positive correlation was found between the age at entry into FOS and the FOS Severity Index in male patients with GLA missense mutations ( p <0.001) as well as in those carrying other types of mutations ( p <0.001). A positive correlation was also found between the age at entry into FOS and the number of affected organs in male patients with missense mutations, irrespective of whether the change in the amino acid side chain predicted in the α-galactosidase A protein was classified as a conservative or non-conservative change.
Conclusion: The data presented here suggest that there is a correlation between genotype and clinical severity.     

The Medical Home Index: development and validation of a new practice-level measure of implementation of the Medical Home model.

OBJECTIVE: The Medical Home is a clinical practice concept that sets new standards for pediatric primary care. This study describes the development and validation of a tool to measure the Medical Home. METHODOLOGY: The Medical Home Index (MHI) consists of 25 themes arranged among 6 domains of primary care office activity. A national panel of experts on the Medical Home reviewed a prototype of the instrument. Pediatric primary care offices completed the MHI and participated in 90-minute on-site interviews with two of the authors (J.W.M., K.S.). The study examined interrater reliability between the 2 project staff and between the practices and project staff and the internal consistency of MHI domains and themes. RESULTS: On a 100-point scale, 43 practices demonstrated a range of MHI summary scores from 18.9 to 75.4, with a mean of 43.9. Kappa coefficients of interrater reliability between two Center for Medical Home Improvement project staff were above.50 for all 25 themes. Kappa scores comparing each staff member and the practice sites' self-assessment found 80% of the themes at.65 or better for one interviewer (J.W.M.) and 60% of the themes at.65 or better for the second interviewer (K.S.). Intraclass correlation coefficients between the summary scores of the interviewers were.98 and between the scores of the two interviewers and the scores of the practices was.97. The internal consistency reliability standardized alpha coefficients across the 6 domains of the MHI ranged from.81 to.91, and the overall standardized alpha coefficient was.96. CONCLUSIONS: In the sample of practices studied, the MHI was an internally consistent instrument with acceptable reliability and validity for pediatric primary care practices to assess their implementation of the Medical Home concept. Further work is needed to study its correlation with other process and outcome measures and its performance in a wider range of practices.     

Profile of neonates admitted in pediatric ICU and validation of Score for Neonatal Acute Physiology (SNAP)

A retrospective study was conducted in the Pediatric Intensive Care Unit (PICU) of a tertiary care hospital in northern India to profile neonatal admissions and to assess the validity of the Score for Neonatal Acute Physiology (SNAP) in predicting the outcome in terms of mortality and length of hospital stay (LOS). Neonatal sepsis (51%) and birth asphyxia (11.2%) were the commonest indications for admission. Thirty-seven (38.1%) of the neonates died. The mean SNAP score in babies who died was 18.8 +/- 9.8 and 10.1 +/- 6.4 in survivors (P<0.001). There was no correlation between SNAP score and mean length of stay in hospital (P=0.5). We conclude that SNAP correlates well with mortality in neonates admitted to the PICU.     

Pediatric Functional Constipation Questionnaire-Parent Report (PedFCQuest-PR): development and validation

ObjectiveDeveloping and validating a disease-specific instrument in the Brazilian Portuguese language to assess the Health-Related Quality of Life of children with functional constipation, applied to parents/caregivers.MethodsThe process of developing the questionnaire was carried out in the following steps: items generation concerning functional constipation; elaboration of the preliminary questionnaire; assessment by health professionals; identifying problems or inconsistencies by the researchers; improvement of the questions; obtaining a final questionnaire named Pediatric Functional Constipation Questionnaire-Parent Form (PedFCQuest-PR) with 26 questions divided into four domains. Responses options use a Likert scale based on the events of the last four weeks. The process of validation was an observational, cross-sectional study in a sample of 87 parents/caregivers of children from 5 to 15 years of age diagnosed with Functional constipation according to the Rome IV Criteria. The questionnaire was applied simultaneously to the Pediatric Quality of Life Inventory 4.0 (PedsQL TM 4.0) as a control.ResultsThe questionnaire validation included 87 parents/caregivers. The children's median age was 8.2 years, with a long time of constipation symptoms associated with fecal incontinence in approximately two-thirds. Internal consistency reliability for the Total Scale Score of PedFCQuest-PR by Coefficient Alpha of Cronbach score was 0.86. Convergent and divergent validity of PedFCQuest-PR was demonstrated by correlating the domains of both questionnaires.ConclusionThis study provides evidence that PedFCQuest-PR is a reliable instrument. The results showed a high degree of internal consistency and validity of the instrument for future applications.     

The Apgar cycle: a new view of a familiar scoring system

Apgar scores are universally recorded, but they should no longer be used to guide resuscitation; thus, some authorities have suggested that the scores should be abandoned. However, the physiological relationships underlying the elements of the Apgar scoring system can be conceptualised as a cycle, wherein the five functions are linked by cardiorespiratory reflexes and metabolically supported by the oxygen pathway. Respiratory effort represents both the main input into the system and its functional output (sustained respirations). The progressive deterioration of functions during asphyxia, and their recovery during resuscitation, are readily understood within the sequence. This depiction helps in learning concepts such as primary and secondary apnoea and bradycardia. The visual model harmonises the pedagogical and practical values of the Apgar scoring system, by placing the rapid assessment of respirations, heart rate and colour during neonatal resuscitation (as taught in the Neonatal Resuscitation Program) in its broader physiological context. The understanding imparted by the Apgar cycle may directly enhance patient care during resuscitation, apart from the attribution of numerical scores.     

INCLEN diagnostic tool for attention deficit hyperactivity disorder (INDT-ADHD): development and validation

Objective

To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD).

Design

Diagnostic test evaluation by cross sectional design. Setting: Tertiary care pediatric centers.

Participants

156 children aged 65–117 months.

Methods

After randomization, INDT-ADHD and Connor’s 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria.

Main outcome measures

Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.

Results

INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner’s Parents Rating Scale was moderate (r =0.73, P= 0.001).

Conclusions

INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.     

Multidimensional measure for gastroesophageal reflux disease (MM-GERD) symptoms in children: a population-based study

BACKGROUND: Gastroesophageal reflux disease (GERD) symptoms are very common in children with major presenting symptoms of abdominal pain, heartburn and regurgitation. The presence of GERD symptoms often result in an impaired health-related quality of life for both the patients and their parents. Evaluation of children with GERD symptoms continues to challenge physicians due to the lack of a validated measure for GERD symptoms. AIMS: To develop and test a multidimensional measure for GERD symptoms in children and to evaluate the responses of the measure among children attending pediatric gastroenterology (GI) clinics. METHODS: We conducted a cross-sectional study that enrolled children with GERD symptoms from pediatric GI clinic. All children and parents received a standardized questionnaire concerning socio-economic parameters, GERD symptoms, duration, frequency, intensity and missed activities due to GERD symptoms. Each child and parent pair was interviewed by a physician to complete baseline information for the multidimensional measure that consisted of four scales: symptoms scale (10 items), pain intensity scale (3 items); disability scale (3 items) and satisfaction scale (2 items). RESULTS: One hundred and thirty-three children participated in the study; 59% girls, ages 4 to 18 years, mean age = 10 +/- 3, 50%, 10 years and younger. There was an excellent correlation between the four-scales measure among children 7 years and younger (R = 0.70, p = 0.0001) and children >7 years (R = 0.74, p = 0.0001). The inter-item consistency (Cronbach's co-efficient alpha) for the symptoms items, pain intensity items, disability items and satisfaction items were 0.71, 0.74, 0.78 and 0.60, respectively, demonstrating adequate reliability of the measure. CONCLUSION: Children with GERD symptoms have good responses to the multidimensional measure for GERD symptoms, showing that the measure performed well across populations. The measure is reliable and specific for assessing the symptoms of GERD in children and is an appropriate outcomes measure for clinical trials involving GERD symptoms in children.     

Predictors of mortality in pediatric trauma: experiences of a level 1 trauma center and an assessment of the International Classification Injury Severity Score (ICISS)

Objectives

Injury severity scoring tools allow systematic comparison of outcomes in trauma research and quality improvement by indexing an expected mortality risk for certain injuries. This study investigated the predictive value of the empirically derived ICD9-derived Injury Severity Score (ICISS) compared to expert consensus-derived scoring systems for trauma mortality in a pediatric population.

Methods

1935 consecutive trauma patients aged <18 years from 1/2000 to 12/2012 were reviewed. Mechanism of injury (MOI), Injury Severity Score (ISS), Revised Trauma Score (RTS), Trauma Score ISS (TRISS), and ICISS were compared using univariate and multivariate logistic regression analysis and receiver operator characteristic analysis.

Results

The population was a median age of 11 ± 6 year, 70 % male, and 76 % blunt injury. Median ISS 13 ± 12 and overall mortality 3.5 %. Independent predictors of mortality were initial hematocrit [odds ratio (OR) 0.83 (0.73–0.95)], HCO3 [OR 0.82 (0.67–0.98)], Glasgow Coma Scale score [OR 0.75 (0.62–0.90)], and ISS [OR 1.10 (1.04–1.15)]. TRISS was superior to ICISS in predicting survival [area under receiver operator curve: 0.992 (0.982–1.000) vs 0.888 (0.838–0.938)].

Conclusions

ICISS was inferior to existing injury scoring tools at predicting mortality in pediatric trauma patients.

     

Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants. Correlation with a scoring system for severity of sequelae.

OBJECTIVES--To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population. DESIGN--A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years. Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated. Data obtained on admission to the hospital were used to calculate HTPS. SETTING--Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska. STUDY SUBJECTS--51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988. One child was infected with both organisms, producing a total of 64 cases for study. SELECTION PROCEDURES--Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control. MEASUREMENTS AND RESULTS--Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States. After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States. Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype. Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis. The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae. Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission. CONCLUSIONS--Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts. The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center.