Introduction: The objective of this study was to better understand the clinical profiles of child... more Introduction: The objective of this study was to better understand the clinical profiles of children with hypophosphatasia (HPP) prior to treatment with enzyme replacement therapy (ERT). Methods: Pretreatment demographics and medical histories of ERT-treated children (aged <18 years) enrolled in the Global HPP Registry (2015–2020) were analyzed overall, by age at first HPP manifestation (<6 months vs. 6 months to 18 years), and by geographic region (USA/Canada, Europe, and Japan). Results: Data from 151 children with HPP were analyzed. Sex distribution was balanced overall (52.3% female; 47.7% male) but differed in Japan (63.0% female; 37.0% male). Prior to ERT initiation, common manifestations were skeletal (67.5%) and extraskeletal, with the foremost types being muscular (48.3%), constitutional/metabolic (47.0%), and neurologic (39.7%). A high proportion of children who first presented at <6 months of age (perinatal/infantile period) had a history of bone deformity (59.3%...
Abstract Underdeveloped economies and limited resources for clean water and sanitation influence ... more Abstract Underdeveloped economies and limited resources for clean water and sanitation influence environmental hazards in many tropical countries. Major hazards include air pollution, poor water supplies including presence of arsenic, lack of adequate sanitation and hygiene, lead poisoning, pesticides, mold and food impurities, and heat and UV radiation. The impacts of climate change are of special concern, as it is expected to exacerbate many existing environmental health hazards and place further strain on already limited resources and infrastructures. Recognition of occupational and environmental health hazards requires adequate training and awareness by health care providers, public health professionals, and education of workers and communities. Hazard control methods vary and may require policies, guidelines, and engineering or administrative controls. Global actions for sustainable development, including equitable access to safe water, and combat of climate change are critical for protecting and promoting environmental health in the tropics.
Objectives: The present systematic review examined the literature focusing on psychosocial functi... more Objectives: The present systematic review examined the literature focusing on psychosocial functioning and health-related quality of life (HRQOL) in young people with inflammatory bowel disease (IBD). It aimed to critique the methodological quality of the identified studies, discuss the implications of their findings, and make recommendations for future research. Patients and Methods: Relevant articles (January 1990-December 2009) were subject to strict inclusion and exclusion criteria. Identified papers were rated for methodological quality using SIGN 50 and Critical Appraisal Skills Programme guidelines before data extraction. Results: Of 2141 articles initially identified, 278 were screened in detail, leaving 12 articles for inclusion in the review: 3 having ''acceptable'' and 9 having ''good''quality rating scores. These 12 studies yielded a combined total of 5330 participants including 790 with IBD and 4540 controls (ages 4-18 years). Five main outcomes-self-esteem, HRQOL, anxiety and depression, social competence, and behavioural functioning-were examined. Three of the 4 controlled studies addressing self-reported HRQOL found it to be significantly lower in the participants with IBD. The evidence for lowered self-esteem, self-reported symptoms of depression and anxiety, impaired social competence, and behavioural problems were conflicting. Methodological heterogeneity was noted in terms of areas of functioning addressed, measures used, sample size, and use of control groups. Conclusions: HRQOL is lower in patients with IBD, but conflicting results and methodological flaws limit conclusions on other aspects of psychosocial functioning. Future research should present data on effect sizes, avoid confounding findings by not combining across age groups or disease severity indices, and consider investigating body image disturbance.
Journal of Occupational and Environmental Medicine, Oct 1, 2009
Objective-To investigate the association between PM 2.5 and urinary 8-hydroxy-2′deoxyguanosine (8... more Objective-To investigate the association between PM 2.5 and urinary 8-hydroxy-2′deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals. Methods-Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM 2.5 was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG. Results-Exposure to PM 2.5 was associated with a decrease in 8-OHdG in hypertensives compared to an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day. Conclusions-Results suggest modification of the association between PM 2.5 exposure and urinary 8-OHdG by hypertension status. Antioxidant activity present in antihypertensive medications may play a role or PM 2.5 exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation.
Background and aims: Toenail metal concentrations may capture exposure to welding fume components... more Background and aims: Toenail metal concentrations may capture exposure to welding fume components. We sought to identify the association between toenail metal and previous work activity, including ...
Journal of Occupational and Environmental Medicine, Mar 1, 2016
Objective-To investigate whether associations of Acceleration Capacity (AC) and Deceleration Capa... more Objective-To investigate whether associations of Acceleration Capacity (AC) and Deceleration Capacity (DC) with metal-PM 2.5 are mediated by inflammation. Methods-We obtained PM 2.5, CRP, IL-6, 8 and 10; and electrocardiograms to compute AC and DC, from 45 male welders. Mediation analyses were performed using linear mixed models to assess associations between PM 2.5 exposure, inflammatory mediator, and AC or DC; controlling for covariates. Results-The proportion of total effect of PM 2.5 on AC or DC (indirect effect) mediated through IL-6 on AC was 4% at most. Controlling for IL-6 (direct effect), a 1 mg/m 3 increase of PM 2.5 was associated with a decrease of 2.16 (95% CI: −0.36, 4.69) msec in AC and a decrease of 2.51 (95% CI: −0.90, 5.93) msec in DC.
Journal of the Canadian Association of Gastroenterology, Mar 1, 2021
BackgroundLysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused ... more BackgroundLysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused by pathogenic variants in the LIPA gene. Lysosomal accumulation of cholesteryl esters and triglycerides leads to cirrhosis and dyslipidemia across a clinical spectrum, and affect both infants and children/adults.AimsAn international registry ({"type":"clinical-trial","attrs":{"text":"NCT01633489","term_id":"NCT01633489"}}NCT01633489; Alexion Pharmaceuticals, Inc.; 2013–ongoing) was established to better understand the natural history of lysosomal acid lipase deficiency (LAL-D) and to evaluate long-term treatment outcomes.MethodsBaseline findings for patients enrolled through July 1, 2019 are presented. Of 190 patients enrolled, 35 were excluded from this analysis (LIPA carrier, deceased at enrollment, unconfirmed LAL-D diagnosis); 155 patients with confirmed LAL-D diagnosis were included (12 infants, 143 children/adults). LAL enzyme activity analysis was performed for 145/154 patients (94%) and genetic testing for 128/154 patients (83%).ResultsOf 105 children/adults with reported LIPA mutations, 39 were homozygous and 34 were compound heterozygous for the common LIPA mutation E8SJM (c.894G>A); 6 infants with reported LIPA mutations were homozygotes and 2 were compound heterozygotes. Of the 155 patients, 62% were <18 years, 52% were male, and 85% were white. Median (range) age at clinical onset was 0.2 years (0.0–0.7) among infants and 6.0 years (0.0–41.3) among 133 children/adults with data; median (range) age at diagnosis was 0.2 years (−0.1 to 1.2) among infants and 10.8 years (0.2–53.6) among 135 children/adults with data. Manifestations that raised suspicion of LAL-D were reported in 149/155 patients. Infants (12 with data) presented predominantly with hepatomegaly (75%), splenomegaly (58%), nausea/vomiting (58%), and diarrhea (50%), and 50% had a known family history of LAL-D. Children/adults (n=143) presented predominantly with elevated alanine aminotransferase levels (67%), hepatomegaly (66%), and elevated aspartate aminotransferase levels (65%). Of 74 children/adults with baseline liver biopsy, 58% had microvesicular steatosis, 16% had micro- and macrovesicular steatosis, and 32% had lobular inflammation. Of the 155 patients, 6% had a medical history of cirrhosis. Analyses exploring the genotype-phenotype relationship will be presented.ConclusionsRegistry data of >150 LAL-D patients demonstrate early symptom onset, variable clinical manifestations, and a significant diagnostic delay in children/adults.Funding AgenciesAlexion Pharmaceuticals, Inc.
Background: Inflammation may be associated with macular pigment optical density (MPOD) degradatio... more Background: Inflammation may be associated with macular pigment optical density (MPOD) degradation. Objectives: The relationship between inflammation and MPOD is evaluated using inflammatory biomarkers, including high sensitivity C-reactive protein (hsCRP), lipid level and ratio, waist circumference (WC), and body mass index (BMI). Method: In this cross-sectional design, 62 hypertensive patients were recruited between January 6 and January 8, 2022, at a primary care unit. The MPOD was measured using the Macular pigment screener II. Blood tests for hsCRP, lipid profile, WC measurement, BMI calculation, and completing a questionnaire were conducted, and statistical analysis was done by using Microsoft Excel 2019 and Stata version 16.1. Spearman's rank correlation test was used to evaluate correlations. Multivariate analysis for adjusting confounders was done by logistic regression. Result: There was a significant negative correlation between hsCRP >3 and MPOD (r =-0.26, P = 0.04). Conclusion: Inflammation was linked to MPOD. Anti-inflammatory agents may be beneficial in preventing MPOD degradation.
Journal of Occupational and Environmental Medicine, Mar 1, 2016
Objective-To clarify if long-term metal particulates affect cardiac acceleration capacity (AC), d... more Objective-To clarify if long-term metal particulates affect cardiac acceleration capacity (AC), deceleration capacity (DC) or both. Methods-We calculated Chronic Exposure Index (CEI) for PM 2.5 over the work life of 50 boilermakers and obtained their resting AC and DC. Linear regression was used to assess the associations between CEI PM 2.5 exposure and each of AC and DC, controlling for age, acute effects of welding exposure, and diurnal variation. Results-Mean (SD) CEI for PM 2.5 exposure was 1.6 (2.4)mg/m 3-workyears and ranged from 0.001-14.6mg/m 3-workyears. In our fully adjusted models, a 1 mg/m 3-workyear increase in CEI for PM 2.5 was associated with a decrease of 1.03 (95% CI: 0.10, 1.96)msec resting AC, and a decrease of 0.67 (95% CI: −0.14, 1.49)msec resting DC.
Selumetinib (ARRY-142886, AZD6244) is an oral, allosteric MEK1/2 inhibitor approved in the US for... more Selumetinib (ARRY-142886, AZD6244) is an oral, allosteric MEK1/2 inhibitor approved in the US for children aged ≥2 years with NF1 and symptomatic, inoperable PN, based on results from the pivotal SPRINT study. Aims of the US Selumetinib Registry study [NCT05683678] include understanding treatment practices and assessing short- and long-term safety and effectiveness outcomes of selumetinib treatment in children with NF1-PN in real-world US practice. Clinical and non-clinical factors affecting outcomes will also be explored. This observational registry study of pediatric patients with NF1-PN will be conducted in up to 22 US centers. Eligible patients will be 2–18 years old at the time of selumetinib initiation (on/after April 10, 2020), and not currently participating in a clinical trial. Patients will be divided into three cohorts: Cohort 1 – treatment discontinued before enrollment, Cohort 2 – treatment initiated before enrollment and currently on treatment, Cohort 3 – treatment ini...
Objective: Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineral... more Objective: Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children. Design: Data from children (aged <18 ¬¬years¬) with hypophosphatasia were analyzed from the observational Global Hypophosphatasia Registry. Methods: Anthropometric parameters were evaluated by age group (<2 years and ≥2 years) at assessment. Frequency of hypophosphatasia manifestations were compared between children with short stature (<3rd percentile) and those with normal stature. Results: This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged <2 years and 20.4% of those aged ≥2 years at assessment. Among those with available data (n=62), height was below the target height (mean: -0.66 standard deviations). Substantial worsening of grow...
Background The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stag... more Background The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient’s symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately. Results A total ...
Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherit... more Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherited, metabolic disorder characterized by reduced enzymatic activity of tissue nonspecific alkaline phosphatase. The natural history of these calcifications is poorly understood. Using data from the Global HPP Registry, a cross-sectional, observational analysis was conducted to better understand the prevalence of nephrocalcinosis and eye calcifications in patients with HPP in the absence of treatment with the enzyme replacement therapy, asfotase alfa. The association between hypercalcemia (serum calcium ≤10.3 mg/dL [normal]; 10.4–11.9 mg/dL [mild hypercalcemia]; ≥12.0 mg/dL [moderate to severe hypercalcemia]) and ectopic calcification was also evaluated. Of the patients in the study population with renal ultrasound data (n=327), 11.0% had nephrocalcinosis; no patients had severe nephrocalcinosis. In children (aged <18 years; n=174), 13.2% had nephrocalcinosis, and the median age at the ...
Presented at the 57th Annual Meeting of the European Society for Paediatric Endocrinology, Septem... more Presented at the 57th Annual Meeting of the European Society for Paediatric Endocrinology, September 27–29, 2018, Athens, Greece. Disease Burden and Systemic Manifestations of HPP in Children Enrolled in the Global HPP Registry Wolfgang Högler, MD1*; Craig Langman, MD2; Hugo Gomes Da Silva, MD3; Shona Fang, ScD3; Agnès Linglart, MD, PhD4; Keiichi Ozono, MD, PhD5; Anna Petryk, MD3; Cheryl Rockman-Greenberg, MD, CM6; Lothar Seefried, MD7; Priya S. Kishnani, MD8 1Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, and Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 2Feinberg School of Medicine, Northwestern University, and Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 3Alexion Pharmaceuticals, Inc., Boston, MA, USA; 4APHP, Bicêtre Paris-Sud, University Paris-Saclay, Le Kremlin Bicêtre, Paris, France; 5Department of Pediatrics, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan; 6University of Manito...
Introduction: The objective of this study was to better understand the clinical profiles of child... more Introduction: The objective of this study was to better understand the clinical profiles of children with hypophosphatasia (HPP) prior to treatment with enzyme replacement therapy (ERT). Methods: Pretreatment demographics and medical histories of ERT-treated children (aged <18 years) enrolled in the Global HPP Registry (2015–2020) were analyzed overall, by age at first HPP manifestation (<6 months vs. 6 months to 18 years), and by geographic region (USA/Canada, Europe, and Japan). Results: Data from 151 children with HPP were analyzed. Sex distribution was balanced overall (52.3% female; 47.7% male) but differed in Japan (63.0% female; 37.0% male). Prior to ERT initiation, common manifestations were skeletal (67.5%) and extraskeletal, with the foremost types being muscular (48.3%), constitutional/metabolic (47.0%), and neurologic (39.7%). A high proportion of children who first presented at <6 months of age (perinatal/infantile period) had a history of bone deformity (59.3%...
Abstract Underdeveloped economies and limited resources for clean water and sanitation influence ... more Abstract Underdeveloped economies and limited resources for clean water and sanitation influence environmental hazards in many tropical countries. Major hazards include air pollution, poor water supplies including presence of arsenic, lack of adequate sanitation and hygiene, lead poisoning, pesticides, mold and food impurities, and heat and UV radiation. The impacts of climate change are of special concern, as it is expected to exacerbate many existing environmental health hazards and place further strain on already limited resources and infrastructures. Recognition of occupational and environmental health hazards requires adequate training and awareness by health care providers, public health professionals, and education of workers and communities. Hazard control methods vary and may require policies, guidelines, and engineering or administrative controls. Global actions for sustainable development, including equitable access to safe water, and combat of climate change are critical for protecting and promoting environmental health in the tropics.
Objectives: The present systematic review examined the literature focusing on psychosocial functi... more Objectives: The present systematic review examined the literature focusing on psychosocial functioning and health-related quality of life (HRQOL) in young people with inflammatory bowel disease (IBD). It aimed to critique the methodological quality of the identified studies, discuss the implications of their findings, and make recommendations for future research. Patients and Methods: Relevant articles (January 1990-December 2009) were subject to strict inclusion and exclusion criteria. Identified papers were rated for methodological quality using SIGN 50 and Critical Appraisal Skills Programme guidelines before data extraction. Results: Of 2141 articles initially identified, 278 were screened in detail, leaving 12 articles for inclusion in the review: 3 having ''acceptable'' and 9 having ''good''quality rating scores. These 12 studies yielded a combined total of 5330 participants including 790 with IBD and 4540 controls (ages 4-18 years). Five main outcomes-self-esteem, HRQOL, anxiety and depression, social competence, and behavioural functioning-were examined. Three of the 4 controlled studies addressing self-reported HRQOL found it to be significantly lower in the participants with IBD. The evidence for lowered self-esteem, self-reported symptoms of depression and anxiety, impaired social competence, and behavioural problems were conflicting. Methodological heterogeneity was noted in terms of areas of functioning addressed, measures used, sample size, and use of control groups. Conclusions: HRQOL is lower in patients with IBD, but conflicting results and methodological flaws limit conclusions on other aspects of psychosocial functioning. Future research should present data on effect sizes, avoid confounding findings by not combining across age groups or disease severity indices, and consider investigating body image disturbance.
Journal of Occupational and Environmental Medicine, Oct 1, 2009
Objective-To investigate the association between PM 2.5 and urinary 8-hydroxy-2′deoxyguanosine (8... more Objective-To investigate the association between PM 2.5 and urinary 8-hydroxy-2′deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals. Methods-Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM 2.5 was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG. Results-Exposure to PM 2.5 was associated with a decrease in 8-OHdG in hypertensives compared to an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day. Conclusions-Results suggest modification of the association between PM 2.5 exposure and urinary 8-OHdG by hypertension status. Antioxidant activity present in antihypertensive medications may play a role or PM 2.5 exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation.
Background and aims: Toenail metal concentrations may capture exposure to welding fume components... more Background and aims: Toenail metal concentrations may capture exposure to welding fume components. We sought to identify the association between toenail metal and previous work activity, including ...
Journal of Occupational and Environmental Medicine, Mar 1, 2016
Objective-To investigate whether associations of Acceleration Capacity (AC) and Deceleration Capa... more Objective-To investigate whether associations of Acceleration Capacity (AC) and Deceleration Capacity (DC) with metal-PM 2.5 are mediated by inflammation. Methods-We obtained PM 2.5, CRP, IL-6, 8 and 10; and electrocardiograms to compute AC and DC, from 45 male welders. Mediation analyses were performed using linear mixed models to assess associations between PM 2.5 exposure, inflammatory mediator, and AC or DC; controlling for covariates. Results-The proportion of total effect of PM 2.5 on AC or DC (indirect effect) mediated through IL-6 on AC was 4% at most. Controlling for IL-6 (direct effect), a 1 mg/m 3 increase of PM 2.5 was associated with a decrease of 2.16 (95% CI: −0.36, 4.69) msec in AC and a decrease of 2.51 (95% CI: −0.90, 5.93) msec in DC.
Journal of the Canadian Association of Gastroenterology, Mar 1, 2021
BackgroundLysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused ... more BackgroundLysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease caused by pathogenic variants in the LIPA gene. Lysosomal accumulation of cholesteryl esters and triglycerides leads to cirrhosis and dyslipidemia across a clinical spectrum, and affect both infants and children/adults.AimsAn international registry ({"type":"clinical-trial","attrs":{"text":"NCT01633489","term_id":"NCT01633489"}}NCT01633489; Alexion Pharmaceuticals, Inc.; 2013–ongoing) was established to better understand the natural history of lysosomal acid lipase deficiency (LAL-D) and to evaluate long-term treatment outcomes.MethodsBaseline findings for patients enrolled through July 1, 2019 are presented. Of 190 patients enrolled, 35 were excluded from this analysis (LIPA carrier, deceased at enrollment, unconfirmed LAL-D diagnosis); 155 patients with confirmed LAL-D diagnosis were included (12 infants, 143 children/adults). LAL enzyme activity analysis was performed for 145/154 patients (94%) and genetic testing for 128/154 patients (83%).ResultsOf 105 children/adults with reported LIPA mutations, 39 were homozygous and 34 were compound heterozygous for the common LIPA mutation E8SJM (c.894G>A); 6 infants with reported LIPA mutations were homozygotes and 2 were compound heterozygotes. Of the 155 patients, 62% were <18 years, 52% were male, and 85% were white. Median (range) age at clinical onset was 0.2 years (0.0–0.7) among infants and 6.0 years (0.0–41.3) among 133 children/adults with data; median (range) age at diagnosis was 0.2 years (−0.1 to 1.2) among infants and 10.8 years (0.2–53.6) among 135 children/adults with data. Manifestations that raised suspicion of LAL-D were reported in 149/155 patients. Infants (12 with data) presented predominantly with hepatomegaly (75%), splenomegaly (58%), nausea/vomiting (58%), and diarrhea (50%), and 50% had a known family history of LAL-D. Children/adults (n=143) presented predominantly with elevated alanine aminotransferase levels (67%), hepatomegaly (66%), and elevated aspartate aminotransferase levels (65%). Of 74 children/adults with baseline liver biopsy, 58% had microvesicular steatosis, 16% had micro- and macrovesicular steatosis, and 32% had lobular inflammation. Of the 155 patients, 6% had a medical history of cirrhosis. Analyses exploring the genotype-phenotype relationship will be presented.ConclusionsRegistry data of >150 LAL-D patients demonstrate early symptom onset, variable clinical manifestations, and a significant diagnostic delay in children/adults.Funding AgenciesAlexion Pharmaceuticals, Inc.
Background: Inflammation may be associated with macular pigment optical density (MPOD) degradatio... more Background: Inflammation may be associated with macular pigment optical density (MPOD) degradation. Objectives: The relationship between inflammation and MPOD is evaluated using inflammatory biomarkers, including high sensitivity C-reactive protein (hsCRP), lipid level and ratio, waist circumference (WC), and body mass index (BMI). Method: In this cross-sectional design, 62 hypertensive patients were recruited between January 6 and January 8, 2022, at a primary care unit. The MPOD was measured using the Macular pigment screener II. Blood tests for hsCRP, lipid profile, WC measurement, BMI calculation, and completing a questionnaire were conducted, and statistical analysis was done by using Microsoft Excel 2019 and Stata version 16.1. Spearman's rank correlation test was used to evaluate correlations. Multivariate analysis for adjusting confounders was done by logistic regression. Result: There was a significant negative correlation between hsCRP >3 and MPOD (r =-0.26, P = 0.04). Conclusion: Inflammation was linked to MPOD. Anti-inflammatory agents may be beneficial in preventing MPOD degradation.
Journal of Occupational and Environmental Medicine, Mar 1, 2016
Objective-To clarify if long-term metal particulates affect cardiac acceleration capacity (AC), d... more Objective-To clarify if long-term metal particulates affect cardiac acceleration capacity (AC), deceleration capacity (DC) or both. Methods-We calculated Chronic Exposure Index (CEI) for PM 2.5 over the work life of 50 boilermakers and obtained their resting AC and DC. Linear regression was used to assess the associations between CEI PM 2.5 exposure and each of AC and DC, controlling for age, acute effects of welding exposure, and diurnal variation. Results-Mean (SD) CEI for PM 2.5 exposure was 1.6 (2.4)mg/m 3-workyears and ranged from 0.001-14.6mg/m 3-workyears. In our fully adjusted models, a 1 mg/m 3-workyear increase in CEI for PM 2.5 was associated with a decrease of 1.03 (95% CI: 0.10, 1.96)msec resting AC, and a decrease of 0.67 (95% CI: −0.14, 1.49)msec resting DC.
Selumetinib (ARRY-142886, AZD6244) is an oral, allosteric MEK1/2 inhibitor approved in the US for... more Selumetinib (ARRY-142886, AZD6244) is an oral, allosteric MEK1/2 inhibitor approved in the US for children aged ≥2 years with NF1 and symptomatic, inoperable PN, based on results from the pivotal SPRINT study. Aims of the US Selumetinib Registry study [NCT05683678] include understanding treatment practices and assessing short- and long-term safety and effectiveness outcomes of selumetinib treatment in children with NF1-PN in real-world US practice. Clinical and non-clinical factors affecting outcomes will also be explored. This observational registry study of pediatric patients with NF1-PN will be conducted in up to 22 US centers. Eligible patients will be 2–18 years old at the time of selumetinib initiation (on/after April 10, 2020), and not currently participating in a clinical trial. Patients will be divided into three cohorts: Cohort 1 – treatment discontinued before enrollment, Cohort 2 – treatment initiated before enrollment and currently on treatment, Cohort 3 – treatment ini...
Objective: Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineral... more Objective: Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children. Design: Data from children (aged <18 ¬¬years¬) with hypophosphatasia were analyzed from the observational Global Hypophosphatasia Registry. Methods: Anthropometric parameters were evaluated by age group (<2 years and ≥2 years) at assessment. Frequency of hypophosphatasia manifestations were compared between children with short stature (<3rd percentile) and those with normal stature. Results: This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged <2 years and 20.4% of those aged ≥2 years at assessment. Among those with available data (n=62), height was below the target height (mean: -0.66 standard deviations). Substantial worsening of grow...
Background The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stag... more Background The clinical signs and symptoms of hypophosphatasia (HPP) can manifest during any stage of life. The age at which a patient’s symptoms are reported can impact access to targeted treatment with enzyme replacement therapy (asfotase alfa), as this treatment is indicated for patients with pediatric-onset HPP in most countries. As such, many patients reported to have adult-onset HPP typically do not receive treatment. Comparison of the disease in treated and untreated adult patients is confounded by the approved indication. To avoid this confounding factor, a comparison between baseline disease manifestations prominent among treated versus untreated adult patients was limited to those with pediatric-onset HPP using data collected from the Global HPP Registry. The hypothesis was that treated adults will have a greater disease burden at baseline than untreated adults. The analysis of disease manifestations in adults with adult-onset HPP was conducted separately. Results A total ...
Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherit... more Ectopic calcifications have been observed in patients with hypophosphatasia (HPP)—a rare, inherited, metabolic disorder characterized by reduced enzymatic activity of tissue nonspecific alkaline phosphatase. The natural history of these calcifications is poorly understood. Using data from the Global HPP Registry, a cross-sectional, observational analysis was conducted to better understand the prevalence of nephrocalcinosis and eye calcifications in patients with HPP in the absence of treatment with the enzyme replacement therapy, asfotase alfa. The association between hypercalcemia (serum calcium ≤10.3 mg/dL [normal]; 10.4–11.9 mg/dL [mild hypercalcemia]; ≥12.0 mg/dL [moderate to severe hypercalcemia]) and ectopic calcification was also evaluated. Of the patients in the study population with renal ultrasound data (n=327), 11.0% had nephrocalcinosis; no patients had severe nephrocalcinosis. In children (aged <18 years; n=174), 13.2% had nephrocalcinosis, and the median age at the ...
Presented at the 57th Annual Meeting of the European Society for Paediatric Endocrinology, Septem... more Presented at the 57th Annual Meeting of the European Society for Paediatric Endocrinology, September 27–29, 2018, Athens, Greece. Disease Burden and Systemic Manifestations of HPP in Children Enrolled in the Global HPP Registry Wolfgang Högler, MD1*; Craig Langman, MD2; Hugo Gomes Da Silva, MD3; Shona Fang, ScD3; Agnès Linglart, MD, PhD4; Keiichi Ozono, MD, PhD5; Anna Petryk, MD3; Cheryl Rockman-Greenberg, MD, CM6; Lothar Seefried, MD7; Priya S. Kishnani, MD8 1Department of Endocrinology and Diabetes, Birmingham Children’s Hospital, and Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK; 2Feinberg School of Medicine, Northwestern University, and Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 3Alexion Pharmaceuticals, Inc., Boston, MA, USA; 4APHP, Bicêtre Paris-Sud, University Paris-Saclay, Le Kremlin Bicêtre, Paris, France; 5Department of Pediatrics, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan; 6University of Manito...
Uploads
Papers by Shona Fang