Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

Epidemiological surveillance of West Nile neuroinvasive diseases in Italy, 2008 to 2011.

Binary file ES_Abstracts_Final_ECDC.txt matche

Different trajectories in upper limb and gross motor function in spinal muscular atrophy

INTRODUCTION: The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) have been widely used in natural history studies and clinical trials. Our aim was to establish how the scales relate to each other at different age points in spinal muscular atrophy (SMA) type 2 and 3, and to describe their coherence over 12 mo. METHODS: The study was performed by cross-sectional and longitudinal reanalysis of previously published natural history data. The longitudinal analysis of the 12-mo changes also included the analysis of concordance between scales with changes grouped as stable (±2 points), improved (>+2) or declined (>−2). RESULTS: Three hundred sixty-four patients were included in the cross-sectional analysis, showing different trends in score and point of slope change for the two scales. For type 2, the point of slope change was 4.1 y for the HFMSE and 5.8 for the RULM, while for type 3, it was 6 y for the HFMSE and 7.3 for the RULM. One-hundred-twenty-one patients had at least two assessments at 12 mo. Full concordance was found in 57.3% of the assessments, and in 40.4% one scale remained stable and the other changed. Each scale appeared to be more sensitive to specific age or functional subgroups. DISCUSSION: The two scales, when used in combination, may increase the sensitivity to detect clinically meaningful changes in motor function in patients with SMA types 2 and 3

Age-Period-Cohort Analysis of 1990–2003 Incidence Time Trends of Childhood Diabetes in Italy: The RIDI Study

OBJECTIVE - To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0-14 years in Italian registries. RESEARCH DESIGN AND METHODS - This report is based on 5,180 incident cases in the period 1990-2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS - The incidence rate was 12.26 per 100,000 personyears and significantly higher in boys (13.13 [95% CI 12.66-13.62]) than in girls (11.35 [10.90-11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22-3.67]). With respect to the calendar period 1990-1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987-1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54-0.73) in the 1975-1981 cohort to 1.38 (1.06-1.80) in the 1999-2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS - Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort

Clinical variability in spinal muscular atrophy type III

Objective: We report natural history data in a large cohort of 199 patients with spinal muscular atrophy (SMA) type III assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish the annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number, and functional status. Methods: HFMSE longitudinal changes were assessed using piecewise linear mixed‐effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12‐month assessments. Results: A break point at age 7 years was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type, and ambulatory status were significantly associated with changes in mean HFMSE score, whereas gender and SMN2 copy number were not. The increase in response before the break point of age 7 years is significant only for SMA IIIA (β = 1.79, p < 0.0001). After the break point, the change in the rate of HFMSE score significantly decrease for both SMA IIIA (β = −1.15, p < 0.0001) and IIIB (β = −0.69, p = 0.002). Interpretation: Our findings contribute to the understanding of the natural history of SMA type III and will be helpful in the interpretation of the real‐world data of patients treated with commercially available drugs. ANN NEUROL 2020;88:1109–111

Development and psychometric properties of the “Suicidality: Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales” in adolescents

Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity—the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test–retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS—the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = −&nbsp;0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents

Development and psychometric properties of the “Suicidality:Treatment Occurring in Paediatrics (STOP) Risk and Resilience Factors Scales” in adolescents

Suicidality in the child and adolescent population is a major public health concern. There is, however, a lack of developmentally sensitive valid and reliable instruments that can capture data on risk, and clinical and psychosocial mediators of suicidality in young people. In this study, we aimed to develop and assess the validity of instruments evaluating the psychosocial risk and protective factors for suicidal behaviours in the adolescent population. In Phase 1, based on a systematic literature review of suicidality, focus groups, and expert panel advice, the risk factors and protective factors (resilience factors) were identified and the adolescent, parent, and clinician versions of the STOP-Suicidality Risk Factors Scale (STOP-SRiFS) and the Resilience Factors Scale (STOP-SReFS) were developed. Phase 2 involved instrument validation and comprised of two samples (Sample 1 and 2). Sample 1 consisted of 87 adolescents, their parents/carers, and clinicians from the various participating centres, and Sample 2 consisted of three sub-samples: adolescents (n = 259) who completed STOP-SRiFS and/or the STOP-SReFS scales, parents (n = 213) who completed one or both of the scales, and the clinicians who completed the scales (n = 254). The STOP-SRiFS demonstrated a good construct validity—the Cronbach Alpha for the adolescent (α = 0.864), parent (α = 0.842), and clinician (α = 0.722) versions of the scale. Test–retest reliability, inter-rater reliability, and content validity were good for all three versions of the STOP-SRiFS. The sub-scales generated using Exploratory Factor Analysis (EFA) were the (1) anxiety and depression risk, (2) substance misuse risk, (3) interpersonal risk, (4) chronic risk, and (5) risk due to life events. For the STOP-SRiFS, statistically significant correlations were found between the Columbia-Suicide Severity Rating Scale (C-SSRS) total score and the adolescent, parent, and clinical versions of the STOP-SRiFS sub-scale scores. The STOP-SRiFS showed good psychometric properties. This study demonstrated a good construct validity for the STOP-SReFS—the Cronbach Alpha for the three versions were good (adolescent: α = 0.775; parent: α = 0.808; α = clinician: 0.808). EFA for the adolescent version of the STOP-SReFS, which consists of 9 resilience factors domains, generated two factors (1) interpersonal resilience and (2) cognitive resilience. The STOP-SReFS Cognitive Resilience sub-scale for the adolescent was negatively correlated (r = −&nbsp;0.275) with the C-SSRS total score, showing that there was lower suicidality in those with greater Cognitive Resilience. The STOP-SReFS Interpersonal resilience sub-scale correlations were all negative, but none of them were significantly different to the C-SSRS total scores for either the adolescent, parent, or clinician versions of the scales. This is not surprising, because the items in this sub-scale capture a much larger time-scale, compared to the C-SSRS rating period. The STOP-SReFS showed good psychometric properties. The STOP-SRiFS and STOP-SReFS are instruments that can be used in future studies about suicidality in children and adolescents

Psychosocial risk factors for suicidality in children and adolescents

Suicidality in childhood and adolescence is of increasing concern. The aim of this paper was to review the published literature identifying key psychosocial risk factors for suicidality in the paediatric population. A systematic two-step search was carried out following the PRISMA statement guidelines, using the terms ‘suicidality, suicide, and self-harm’ combined with terms ‘infant, child, adolescent’ according to the US National Library of Medicine and the National Institutes of Health classification of ages. Forty-four studies were included in the qualitative synthesis. The review identified three main factors that appear to increase the risk of suicidality: psychological factors (depression, anxiety, previous suicide attempt, drug and alcohol use, and other comorbid psychiatric disorders); stressful life events (family problems and peer conflicts); and personality traits (such as neuroticism and impulsivity). The evidence highlights the complexity of suicidality and points towards an interaction of factors contributing to suicidal behaviour. More information is needed to understand the complex relationship between risk factors for suicidality. Prospective studies with adequate sample sizes are needed to investigate these multiple variables of risk concurrently and over time

Specific Immunoassays Confirm Association of Mycobacterium avium Subsp. paratuberculosis with Type-1 but Not Type-2 Diabetes Mellitus

Mycobacterium avium subspecies paratuberculosis (MAP) is a versatile pathogen with a broad host range. Its association with type-1 diabetes mellitus (T1DM) has been recently proposed. Rapid identification of infectious agents such as MAP in diabetic patients at the level of clinics might be helpful in deciphering the role of chronic bacterial infection in the development of autoimmune diseases such as T1DM.We describe use of an ELISA method to identify live circulating MAP through the detection of a cell envelope protein, MptD by a specific M13 phage--fMptD. We also used another ELISA format to detect immune response to MptD peptide. Both the methods were tested with blood plasma obtained from T1DM, type-2 diabetes (T2DM) patients and non-diabetic controls. Our results demonstrate MptD and fMptD ELISA assays to be accurate and sensitive to detect MAP bacilli in a large fraction (47.3%) of T1DM patients as compared to non-diabetic controls (12.6%) and those with confirmed T2DM (7.7%). Comparative analysis of ELISA assays performed here with 3 other MAP antigen preparations, namely HbHA, Gsd and whole cell MAP lysates confirmed comparable sensitivity of the MptD peptide and the fMptD based ELISA assays. Moreover, we were successful in demonstrating positive bacterial culture in two of the clinical specimen derived from T1DM patients.The MptD peptide/fMptD based ELISA or similar tests could be suggested as rapid and specific field level diagnostic tests for the identification of MAP in diabetic patients and for finding the explanations towards the occurrence of type-1 or type-2 diabetes in the light of an active infectious trigger