Displaying publications 21 - 40 of 117 in total

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  1. Watts GF, Gidding S, Wierzbicki AS, Toth PP, Alonso R, Brown WV, et al.
    Eur J Prev Cardiol, 2015 Jul;22(7):849-54.
    PMID: 24776375 DOI: 10.1177/2047487314533218
    Familial hypercholesterolaemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL) cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected and current treatment is often suboptimal.To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment and management of FH in adults and children, and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of non-cholesterol risk factors and safe and effective use of LDL lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed.This international guidance acknowledges evidence gaps, but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be employed to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.
  2. Uma E, Nieminen P, Mani SA, John J, Haapanen E, Laitala ML, et al.
    Healthcare (Basel), 2021 Oct 20;9(11).
    PMID: 34828454 DOI: 10.3390/healthcare9111408
    Social media use among students has infiltrated into dental education and offers benefits but may also cause problems. The aim of this study was to explore and compare current social media usage among dental undergraduate students from two countries-Malaysia and Finland. A self-administered structured online questionnaire was used. WhatsApp, YouTube, Instagram, Facebook and Snapchat were the services that were most familiar to the respondents from both countries. There were differences between the students from the two countries among the most preferred platforms. The most frequently used applications were WhatsApp (91.1% of students in Malaysia and 96.1% in Finland used it very frequently) and Instagram (74.3% of students in Malaysia and 70.0% in Finland used it very frequently). Students in Malaysia spent significantly more hours per week using the platforms as study tools than students in Finland. Over 80% of the Finnish dental students reported that lack of knowledge was not an issue in social media usage, while 85% of Malaysian students felt that lack of knowledge prevented them from using social media platforms frequently. The findings offer evidence that dental students used social media extensively.
  3. Md Bohari NF, Kruger E, John J, Tennant M
    Int Dent J, 2019 Jun;69(3):223-229.
    PMID: 30565655 DOI: 10.1111/idj.12454
    OBJECTIVE: The aim of this study was to analyse, in detail, the distribution of primary dental clinics in relation to the Malaysian population and relative population wealth, to test the hypothesis that an uneven distribution of dental services exists in Malaysia.

    METHOD: This 2016 study located every dental practice in Malaysia (private and public) and mapped these practices against population, using Geographic Information Systems (GIS) tools. Population clusters within 5, 10 and 20 km of a dental clinic were identified, and clinic-to-population ratios were ascertained. Population data were obtained from the Population and Housing Census of Malaysia 2010. Population relative wealth was obtained from the 2014 Report on Household Income and Basic Amenities Survey for Malaysia. The physical address for each dental practice in Malaysia was gathered from the Official Portal of Ministry of Health Malaysia. All data for analysis were extracted from the integrated database in Quantum GIS (QGIS) into Microsoft Excel.

    RESULT: The population of Malaysia (24.9 million) was distributed across 127 districts, with 119 (94%) having at least one dental clinic. Sixty-four districts had fewer than 10 dental clinics, and 11.3% of Malaysians did not reside in the catchment of 20 km from any dental clinic. The total dental clinic-to-population ratio was 1:9,000: for public dental clinics it was 1:38,000 and for private clinics it was 1:13,000.

    CONCLUSION: Dental services were distributed relative to high population density, were unevenly distributed across Malaysia and the majority of people with the highest inaccessibility to a dental service resided in Malaysian Borneo.

  4. Nhu VH, Mohammadi A, Shahabi H, Ahmad BB, Al-Ansari N, Shirzadi A, et al.
    PMID: 32650595 DOI: 10.3390/ijerph17144933
    We used AdaBoost (AB), alternating decision tree (ADTree), and their combination as an ensemble model (AB-ADTree) to spatially predict landslides in the Cameron Highlands, Malaysia. The models were trained with a database of 152 landslides compiled using Synthetic Aperture Radar Interferometry, Google Earth images, and field surveys, and 17 conditioning factors (slope, aspect, elevation, distance to road, distance to river, proximity to fault, road density, river density, normalized difference vegetation index, rainfall, land cover, lithology, soil types, curvature, profile curvature, stream power index, and topographic wetness index). We carried out the validation process using the area under the receiver operating characteristic curve (AUC) and several parametric and non-parametric performance metrics, including positive predictive value, negative predictive value, sensitivity, specificity, accuracy, root mean square error, and the Friedman and Wilcoxon sign rank tests. The AB model (AUC = 0.96) performed better than the ensemble AB-ADTree model (AUC = 0.94) and successfully outperformed the ADTree model (AUC = 0.59) in predicting landslide susceptibility. Our findings provide insights into the development of more efficient and accurate landslide predictive models that can be used by decision makers and land-use managers to mitigate landslide hazards.
  5. Nhu VH, Shirzadi A, Shahabi H, Singh SK, Al-Ansari N, Clague JJ, et al.
    PMID: 32316191 DOI: 10.3390/ijerph17082749
    Shallow landslides damage buildings and other infrastructure, disrupt agriculture practices, and can cause social upheaval and loss of life. As a result, many scientists study the phenomenon, and some of them have focused on producing landslide susceptibility maps that can be used by land-use managers to reduce injury and damage. This paper contributes to this effort by comparing the power and effectiveness of five machine learning, benchmark algorithms-Logistic Model Tree, Logistic Regression, Naïve Bayes Tree, Artificial Neural Network, and Support Vector Machine-in creating a reliable shallow landslide susceptibility map for Bijar City in Kurdistan province, Iran. Twenty conditioning factors were applied to 111 shallow landslides and tested using the One-R attribute evaluation (ORAE) technique for modeling and validation processes. The performance of the models was assessed by statistical-based indexes including sensitivity, specificity, accuracy, mean absolute error (MAE), root mean square error (RMSE), and area under the receiver operatic characteristic curve (AUC). Results indicate that all the five machine learning models performed well for shallow landslide susceptibility assessment, but the Logistic Model Tree model (AUC = 0.932) had the highest goodness-of-fit and prediction accuracy, followed by the Logistic Regression (AUC = 0.932), Naïve Bayes Tree (AUC = 0.864), ANN (AUC = 0.860), and Support Vector Machine (AUC = 0.834) models. Therefore, we recommend the use of the Logistic Model Tree model in shallow landslide mapping programs in semi-arid regions to help decision makers, planners, land-use managers, and government agencies mitigate the hazard and risk.
  6. Mani SA, Naing L, John J, Samsudin AR
    Int J Paediatr Dent, 2008 Sep;18(5):380-8.
    PMID: 18284472 DOI: 10.1111/j.1365-263X.2007.00890.x
    BACKGROUND: Numerous methods of age estimation have been proposed. The Demirjian method is the most frequently used, which was first applied in a French Canadian population in 1973. The Willems method is a modification of the above and was applied in a Belgian population in 2002.
    OBJECTIVES: The objectives of this study were to test the applicability of the two methods, namely Demirjian and Willems, for age estimation in a Malay population, and to find the correlation between body mass index and the difference between the dental age and the chronological age.
    MATERIALS AND METHODS: A cross-sectional study involving 214 boys and 214 girls, selected by a simple stratified random sampling method was carried out. The orthopantomograph was used to score the seven left mandibular teeth, and the calculated maturity score was used to obtain the Demirjian dental age. Willems dental age was estimated using the tables proposed in the Willems method. Results. The Demirjian method overestimated the age by 0.75 and 0.61 years, while the Willems method overestimated the age by 0.55 and 0.41 years among boys and girls, respectively. In boys, the body mass index was significantly correlated to the difference in age using the Willems method.
    CONCLUSION: Further modification of either method is indicated for dental age estimation among the Malay population.
  7. Hamzaid H, Talib RA, Azizi NH, Maamor N, Reilly JJ, Wafa SW
    Int J Pediatr Obes, 2011 Oct;6(5-6):450-4.
    PMID: 21767214 DOI: 10.3109/17477166.2011.590206
    BACKGROUND:Quality of life (QoL) is impaired in childhood obesity, but the literature on this is all from Western countries. Aim. To test for impairment of QoL in obese children in Malaysia, using parent-reported and child-reported QoL.
    METHODS:Health-related Quality of Life was measured using the Paediatric Quality of Life Inventory version 4.0. Comparison of QoL between a community sample of 90 obese children (as defined by US CDC and Cole-IOTF definitions), median age 9.5 y (interquartile range [IQR] 8.6, 10.5 y) and 90 control children of healthy weight (BMI less than the 85th centile of US reference data), median age 10.0 y (IQR 9.6, 10.5 y). Children were matched pair-wise for age, gender, and ethnic group, and controls were recruited from schools in the same area as obese participants.
    RESULTS:For child self-report, the healthy weight group had significantly higher QoL for the physical (median 82.9, IQR 65.7, 90.6), and psychosocial domains (median, 73.3, IQR 64.4, 83.3), and total QoL (median 76.1, IQR 64.1, 84.8) compared to the obese group (median 67.2, IQR 59.4, 81.3; median 62.5, IQR 53.3, 75.4; median 60.9, IQR 50.8, 73.9; all p < 0.001). There were no significant differences between the obese and healthy weight group for parent-reported physical health, psychosocial health, or total QoL.
    CONCLUSION:Obese children in Malaysia have markedly poorer QoL than their peers, but this is not evident when parent reports of QoL are used.
    Study name: Malaysian Childhood Obesity Treatment Trial (MASCOT)
    Study site: Two primary schools, Kuala Lumpur, Malaysia
  8. Wafa SW, Talib RA, Hamzaid NH, McColl JH, Rajikan R, Ng LO, et al.
    Int J Pediatr Obes, 2011 Jun;6(2-2):e62-9.
    PMID: 21604965 DOI: 10.3109/17477166.2011.566340
    CONTEXT: Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world.
    AIM: To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia.
    METHODS: Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days).
    RESULTS: The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group.
    CONCLUSIONS: Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes.
  9. May LW, John J, Seong LG, Abidin ZZ, Ibrahim N, Danaee M, et al.
    J Indian Prosthodont Soc, 2021 5 4;21(2):198-203.
    PMID: 33938871 DOI: 10.4103/jips.jips_41_21
    Aim: To investigate the effect of different cooling methods on denture base adaptation of rapid heat-cured acrylic resin using 3D superimposition technique.

    Setting and Design: In vitro - Comparative study.

    Materials and Methods: Denture base adaptation of two different rapid heat-cured polymethyl methacrylate acrylic resins using five different cooling methods were compared. Forty maxillary edentulous stone cast were prepared to produce the denture bases with standardized thickness. The specimens were divided into five groups (n = 8) according to type of materials and cooling methods. The master stone cast and all forty denture bases were scanned with 3Shape E1 laboratory scanner. The scanned images of each of the denture bases were superimposed over the scanned image of the master cast using Materialize 3-matic software. Three dimensional differences between the two surfaces were calculated and color surface maps were generated for visual qualitative assessment.

    Statistical Analysis Used: Generalized Linear Model Test, Bonferroni Post Hoc Analysis.

    Results: All bench-cooled specimens showed wide green-colored area in the overall palatal surface, while the rapid cooled specimens presented with increased red color areas especially at the palate and post dam area. Generalized Linear Model test followed by Bonferroni post hoc analysis showed significant difference in the root mean square values among the specimen groups.

    Conclusion: Samples that were bench cooled, demonstrated better overall accuracy compared to the rapid cooling groups. Regardless of need for shorter denture processing time, bench cooling of rapid heat-cured PMMA is essential for acceptable denture base adaptation.

  10. Lewiecki EM, Binkley N, Morgan SL, Shuhart CR, Camargos BM, Carey JJ, et al.
    J Clin Densitom, 2016 Apr-Jun;19(2):127-40.
    PMID: 27020004 DOI: 10.1016/j.jocd.2016.03.003
    Dual-energy X-ray absorptiometry (DXA) is a technology that is widely used to diagnose osteoporosis, assess fracture risk, and monitor changes in bone mineral density (BMD). The clinical utility of DXA is highly dependent on the quality of the scan acquisition, analysis, and interpretation. Clinicians are best equipped to manage patients when BMD measurements are correct and interpretation follows well-established standards. Poor-quality acquisition, analysis, or interpretation of DXA data may mislead referring clinicians, resulting in unnecessary diagnostic evaluations, failure to evaluate when needed, inappropriate treatment, or failure to provide medical treatment, with potentially ineffective, harmful, or costly consequences. Misallocation of limited healthcare resources and poor treatment decisions can be minimized, and patient care optimized, through meticulous attention to DXA instrument calibration, data acquisition and analysis, interpretation, and reporting. This document from the International Society for Clinical Densitometry describes quality standards for BMD testing at DXA facilities worldwide to provide guidance for DXA supervisors, technologists, interpreters, and clinicians. High-quality DXA testing is necessary for correct diagnostic classification and optimal fracture risk assessment, and is essential for BMD monitoring.
  11. Watts GF, Gidding S, Wierzbicki AS, Toth PP, Alonso R, Brown WV, et al.
    J Clin Lipidol, 2014 Mar-Apr;8(2):148-72.
    PMID: 24636175 DOI: 10.1016/j.jacl.2014.01.002
    Familial hypercholesterolemia (FH) is a dominantly inherited disorder present from birth that markedly elevates plasma low-density lipoprotein cholesterol and causes premature coronary heart disease. There are at least 20 million people with FH worldwide, but the majority remains undetected, and current treatment is often suboptimal. To address this major gap in coronary prevention we present, from an international perspective, consensus-based guidance on the care of FH. The guidance was generated from seminars and workshops held at an international symposium. The recommendations focus on the detection, diagnosis, assessment, and management of FH in adults and children and set guidelines for clinical purposes. They also refer to best practice for cascade screening and risk notifying and testing families for FH, including use of genetic testing. Guidance on treatment is based on risk stratification, management of noncholesterol risk factors, and the safe and effective use of low-density lipoprotein-lowering therapies. Recommendations are given on lipoprotein apheresis. The use of emerging therapies for FH is also foreshadowed. This international guidance acknowledges evidence gaps but aims to make the best use of contemporary practice and technology to achieve the best outcomes for the care of FH. It should accordingly be used to inform clinical judgment and be adjusted for country-specific and local healthcare needs and resources.
  12. Samuvel DJ, Nguyen NT, Jaeschke H, Lemasters JJ, Wang X, Choo YM, et al.
    J Nat Prod, 2022 Jul 22;85(7):1779-1788.
    PMID: 35815804 DOI: 10.1021/acs.jnatprod.2c00324
    Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. Platanosides (PTSs) isolated from the American sycamore tree (Platanus occidentalis) represent a potential new four-molecule botanical drug class of antibiotics active against drug-resistant infectious disease. Preliminary studies have suggested that PTSs are safe and well tolerated and have antioxidant properties. The potential utility of PTSs in decreasing APAP hepatotoxicity in mice in addition to an assessment of their potential with APAP for the control of infectious diseases along with pain and pyrexia associated with a bacterial infection was investigated. On PTS treatment in mice, serum alanine aminotransferase (ALT) release, hepatic centrilobular necrosis, and 4-hydroxynonenal (4-HNE) were markedly decreased. In addition, inducible nitric oxide synthase (iNOS) expression and c-Jun-N-terminal kinase (JNK) activation decreased when mice overdosed with APAP were treated with PTSs. Computational studies suggested that PTSs may act as JNK-1/2 and Keap1-Nrf2 inhibitors and that the isomeric mixture could provide greater efficacy than the individual molecules. Overall, PTSs represent promising botanical drugs for hepatoprotection and drug-resistant bacterial infections and are effective in protecting against APAP-related hepatotoxicity, which decreases liver necrosis and inflammation, iNOS expression, and oxidative and nitrative stresses, possibly by preventing persistent JNK activation.
  13. Sharif R, Chong KH, Zakaria NH, Ong ML, Reilly JJ, Wong JE, et al.
    J Phys Act Health, 2016 11;13(11 Suppl 2):S201-S205.
    PMID: 27848721 DOI: 10.1123/jpah.2016-0404
    BACKGROUND: The 2016 Malaysia Active Healthy Kids Report Card aims to collect, assess, and grade current and comprehensive data on physical activity (PA) and associated factors in Malaysian children and adolescents aged 5 to 17 years.
    METHODS: This report card was developed following the Active Healthy Kids Canada Report Card protocol. The Research Working Group identified the core matrices, assessed the key data sources, and evaluated the evidence gathered for grade assignments. A grade was assigned to each indicator by comparing the best available evidence against relevant benchmark using a standardized grading scheme.
    RESULTS: Overall Physical Activity, Active Transportation, and Sedentary Behavior were assigned the D grade. The lowest grade of F was assigned to Diet, while School and Government Strategies and Investments were graded higher with a B. Five indicators were assigned INC (incomplete) due to a lack of representative data.
    CONCLUSIONS: The report card demonstrates that Malaysian children and adolescents are engaging in low levels of PA and active commuting, high levels of screen time, and have extremely low compliance with dietary recommendations. More efforts are needed to address the root causes of physical inactivity while increasing the opportunities for children and adolescents to be more physically active.
    MESH: screen time
  14. John J, Ann Mani S, Palaniswamy K, Ramanathan A, Razak AA
    J Prosthodont, 2015 Apr;24(3):233-8.
    PMID: 24976147 DOI: 10.1111/jopr.12191
    PURPOSE: The purpose of this preliminary study was to evaluate the flexural properties of poly(methyl methacrylate) (PMMA) reinforced with oil palm empty fruit bunch (OPEFB) fiber.

    MATERIALS AND METHODS: The flexural strength and flexural modulus of three OPEFB fiber-reinforced PMMA were compared with a conventional and a commercially available reinforced PMMA. The three test groups included OPEFB fibers of 0.5 mm thickness, 2.0 mm thickness, and OPEFB cellulose.

    RESULTS: All test group specimens demonstrated improved flexural strength and flexural modulus over conventional PMMA. Reinforcement with OPEFB cellulose showed the highest mean flexural strength and flexural modulus, which were statistically significant when compared to the conventional and commercially reinforced PMMA used in this study. OPEFB fiber in the form of cellulose and 0.5 mm thickness fiber significantly improved flexural strength and flexural modulus of conventional PMMA resin. Further investigation on the properties of PMMA reinforced with OPEFB cellulose is warranted.

    CONCLUSIONS: Natural OPEFB fibers, especially OPEFB in cellulose form, can be considered a viable alternative to existing commercially available synthetic fiber reinforced PMMA resin.

  15. Rahaman Ali AAA, John J, Mani SA, El-Seedi HR
    J Prosthodont, 2020 Aug;29(7):611-616.
    PMID: 30637856 DOI: 10.1111/jopr.13018
    PURPOSE: To assess the impact of thermal cycling on flexural properties of denture base acrylic resin reinforced with microcrystalline cellulose (MCC) derived from oil palm empty fruit bunch (OPEFB).

    MATERIALS AND METHODS: The flexural strength and flexural modulus, following thermal cycling (5000 cycles of 5-55°C) of 3 MCC-reinforced poly methyl methacrylate (PMMA) specimens were compared with the conventional and commercially available high-impact PMMA. The 3 test groups were represented by addition of various weight combinations of MCC and acrylic powders.

    RESULTS: All 3 test groups with the addition of MCC demonstrated improved flexural strength and flexural modulus compared to the conventional resin, without and after thermal cycling. The highest mean flexural strength corresponded to the specimens reinforced with 5% MCC followed by 2% MCC.

    CONCLUSION: Addition of MCC derived from OPEFB to PMMA may be a viable alternative to the existing, commercially available synthetic reinforced PMMA resins. The potential application of natural fillers in the fabrication of a reinforced denture base resin needs further study.

  16. Amanat MA, John J, Pin TM, Danaee M, Malhotra V, Abbas SA, et al.
    J Public Health (Oxf), 2020 May 26;42(2):304-311.
    PMID: 30796789 DOI: 10.1093/pubmed/fdz014
    BACKGROUND: Poor oral health affects not only dietary choices but overall well-being. This study explores the influence of lifestyle, socio-demographics and utilization of dental services on the dentition status of an older urban Malaysian population.

    METHODS: A total of 1210 participants 60 years and above, representing the three main ethnic groups were recruited from a larger cohort study. Weighted factors valued for comparison included socio demographics and health status. Knowledge of and attitude and behaviour towards personal oral health were also assessed. Dentition status, adapted from WHO oral health guidelines, was the dependent variable investigated. Data were analysed using descriptive chi square test and multivariate binary logistic regression.

    RESULTS: Overall, 1187 respondents completed the study. The dentition status and oral health related knowledge, attitude and behaviour varied between the three ethnic groups. The Chinese were significantly less likely to have ≥13 missing teeth (OR = 0.698, 95% CI: 0.521-0.937) and ≥1 decayed teeth (0.653; 0.519-0.932) compared to the Malays, while the Indians were significantly less likely than the Malays to have ≥1 decayed teeth (0.695; 0.519-0.932) and ≥2 filled teeth (0.781; 0.540-1.128).

    CONCLUSION: Ethnic differences in dentition outcome are related to oral health utilization highlighting the influence of cultural differences and the need for culturally sensitivity interventions.

  17. Mwase-Vuma TW, Janssen X, Okely AD, Tremblay MS, Draper CE, Florindo AA, et al.
    J Sci Med Sport, 2022 Dec;25(12):1002-1007.
    PMID: 36270900 DOI: 10.1016/j.jsams.2022.10.003
    OBJECTIVES: To validate parent-reported child habitual total physical activity against accelerometry and three existing step-count thresholds for classifying 3 h/day of total physical activity in pre-schoolers from 13 culturally and geographically diverse countries.

    DESIGN: Cross-sectional validation study.

    METHODS: We used data involving 3- and 4-year-olds from 13 middle- and high-income countries who participated in the SUNRISE study. We used Spearman's rank-order correlation, Bland-Altman plots, and Kappa statistics to validate parent-reported child habitual total physical activity against activPAL™-measured total physical activity over 3 days. Additionally, we used Receiver Operating Characteristic Area Under the Curve analysis to validate existing step-count thresholds (Gabel, Vale, and De Craemer) using step-counts derived from activPAL™.

    RESULTS: Of the 352 pre-schoolers, 49.1 % were girls. There was a very weak but significant positive correlation and slight agreement between parent-reported total physical activity and accelerometer-measured total physical activity (r: 0.140; p = 0.009; Kappa: 0.030). Parents overestimated their child's total physical activity compared to accelerometry (mean bias: 69 min/day; standard deviation: 126; 95 % limits of agreement: -179, 316). Of the three step-count thresholds tested, the De Craemer threshold of 11,500 steps/day provided excellent classification of meeting the total physical activity guideline as measured by accelerometry (area under the ROC curve: 0.945; 95 % confidence interval: 0.928, 0.961; sensitivity: 100.0 %; specificity: 88.9 %).

    CONCLUSIONS: Parent reports may have limited validity for assessing pre-schoolers' level of total physical activity. Step-counting is a promising alternative - low-cost global surveillance initiatives could potentially use pedometers for assessing compliance with the physical activity guideline in early childhood.

  18. Stein EA, Dann EJ, Wiegman A, Skovby F, Gaudet D, Sokal E, et al.
    J Am Coll Cardiol, 2017 Aug 29;70(9):1162-1170.
    PMID: 28838366 DOI: 10.1016/j.jacc.2017.06.058
    BACKGROUND: Homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder, is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and accelerated atherosclerotic cardiovascular disease. Statin treatment starts at diagnosis, but no statin has been formally evaluated in, or approved for, HoFH children.

    OBJECTIVES: The authors sought to assess the LDL-C efficacy of rosuvastatin versus placebo in HoFH children, and the relationship with underlying genetic mutations.

    METHODS: This was a randomized, double-blind, 12-week, crossover study of rosuvastatin 20 mg versus placebo, followed by 12 weeks of open-label rosuvastatin. Patients discontinued all lipid-lowering treatment except ezetimibe and/or apheresis. Clinical and laboratory assessments were performed every 6 weeks. The relationship between LDL-C response and genetic mutations was assessed by adding children and adults from a prior HoFH rosuvastatin trial.

    RESULTS: Twenty patients were screened, 14 randomized, and 13 completed the study. The mean age was 10.9 years; 8 patients were on ezetimibe and 7 on apheresis. Mean LDL-C was 481 mg/dl (range: 229 to 742 mg/dl) on placebo and 396 mg/dl (range: 130 to 700 mg/dl) on rosuvastatin, producing a mean 85.4 mg/dl (22.3%) difference (p = 0.005). Efficacy was similar regardless of age or use of ezetimibe or apheresis, and was maintained for 12 weeks. Adverse events were few and not serious. Patients with 2 defective versus 2 negative LDL receptor mutations had mean LDL-C reductions of 23.5% (p = 0.0044) and 14% (p = 0.038), respectively.

    CONCLUSIONS: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added to ezetimibe and/or apheresis. The LDL-C response in children and adults was related to underlying genetic mutations. (A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia [HYDRA]; NCT02226198).

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