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The prevention of mother-to-child transmission of HIV cascade analysis tool: supporting health managers to improve facility-level service delivery. - BMC research notes
The objective of the prevention of Mother-to-Child Transmission (pMTCT) cascade analysis tool is to provide frontline health managers at the facility level with the means to rapidly, independently and quantitatively track patient flows through the pMTCT cascade, and readily identify priority areas for clinic-level improvement interventions. Over a period of six months, five experienced maternal-child health managers and researchers iteratively adapted and tested this systems analysis tool for pMTCT services. They prioritized components of the pMTCT cascade for inclusion, disseminated multiple versions to 27 health managers and piloted it in five facilities. Process mapping techniques were used to chart PMTCT cascade steps in these five facilities, to document antenatal care attendance, HIV testing and counseling, provision of prophylactic anti-retrovirals, safe delivery, safe infant feeding, infant follow-up including HIV testing, and family planning, in order to obtain site-specific knowledge of service delivery.Seven pMTCT cascade steps were included in the Excel-based final tool. Prevalence calculations were incorporated as sub-headings under relevant steps. Cells not requiring data inputs were locked, wording was simplified and stepwise drop-offs and maximization functions were included at key steps along the cascade. While the drop off function allows health workers to rapidly assess how many patients were lost at each step, the maximization function details the additional people served if only one step improves to 100% capacity while others stay constant.Our experience suggests that adaptation of a cascade analysis tool for facility-level pMTCT services is feasible and appropriate as a starting point for discussions of where to implement improvement strategies. The resulting tool facilitates the engagement of frontline health workers and managers who fill out, interpret, apply the tool, and then follow up with quality improvement activities. Research on adoption, interpretation, and sustainability of this pMTCT cascade analysis tool by frontline health managers is needed.ClinicalTrials.gov NCT02023658, December 9, 2013.
From bedside to cell biology: a century of history on lysosomal dysfunction. - Gene
Lysosomal storage disorders (LSDs) are a group of rare genetic diseases, generally caused by a deficiency of specific lysosomal enzymes, which results in abnormal accumulation of undegraded substrates. The first clinical reports describing what were later shown to be LSDs were published more than a hundred years ago. In general, the history and pathophysiology of LSDs has impacted on our current knowledge of lysosomal biology. Classically, depending on the nature of the substrates, LSDs can be divided into different subgroups. The mucopolysaccharidoses (MPSs) are those caused by impaired degradation of glycosaminoglycans (GAGs). Amongst LSDs, the MPSs are a major group of pathologies with crucial historical relevance, since their study has revealed important biological pathways and highlighted interconnecting pathological cascades which are still being unveiled nowadays. Here we review the major historical discoveries in the field of LSDs and their impact on basic cellular knowledge and practical applications. Attention will be focused on the MPSs, with occasional references to other LSDs. We will show as studies on the metabolic basis of this group of diseases have increased our knowledge of the complex degradative pathways associated with the lysosome and established the basis to the development of specific therapeutic approaches aiming at correcting or, at least ameliorating their associated phenotypes.Copyright Â© 2014 Elsevier B.V. All rights reserved.
Factors associated with recruitment and retention of diverse children with asthma. - Children's health care : journal of the Association for the Care of Children's Health
This study examines factors associated with recruitment and retention of Latino, Dominican (DR) and mainland Puerto Rican (PR), and non-Latino white (NLW) families into a pediatric asthma study. Over eleven hundred (n=1185) families were screened, and 489 (n= 174 NLW, n= 160 DR, n= 155 PR) were enrolled. Rates of recruitment by source of recruitment and rates of retention differed by ethnic group. Families whose caregiver had never married had lower odds of completing the study. The findings highlight the need for further study to examine the effectiveness of specific recruitment and retention strategies with Latino and non-Latino white families.
Prenatal skeletal dysplasia phenotype in severe MLII alpha/beta with novel GNPTAB mutation. - Gene
We report a neonate who was diagnosed as a case of skeletal dysplasia during pregnancy, and was subsequently diagnosed as a case of MLII alpha/beta on the basis of clinical and radiological findings and molecular testing of the parents. A novel GNPTAB mutation c.1701delC [p.F566LfsX5] was identified in the father. The case reiterates the severe prenatal phenotype of MLII alpha/beta which mimics skeletal dysplasia and illustrates the utility of molecular genetic analysis in confirmation of diagnosis and subsequent genetic counselling.Copyright Â© 2014 Elsevier B.V. All rights reserved.
What does high and low have to do with it? Performance classification to identify health system factors associated with effective prevention of mother-to-child transmission of HIV delivery in Mozambique. - Journal of the International AIDS Society
Efforts to implement and take to scale highly efficacious, low-cost interventions to prevent mother-to-child HIV transmission (pMTCT) have been a cornerstone of reproductive health services in sub-Saharan Africa for over a decade. Yet efforts to increase access and utilization of these services remain far from optimal. This study developed and applied an approach to systematically classify pMTCT performance to identify modifiable health system factors associated with pMTCT performance which may be replicated in other pMTCT systems.Facility-level performance measures were collected at 30 sites over a 12-month period and reviewed for consistency. Five combinations of three indicators (1. HIV testing; 2. CD4 testing; 3. antiretroviral prophylaxis and combined antiretroviral therapy initiation) were compared including a composite of all three, a combination of 1. and 3., and each individually. Approaches were visually assessed to describe facility performance, focusing on rank order consistency across high, medium and low categories. Modifiable and non-modifiable factors were ascertained at each site and ranking process was reviewed to estimate association with facility performance through unadjusted Chi-square tests and logistic regression. After describing factors associated with high versus low performing pMTCT clinics, the effect of inclusion of the 10 middle performers was assessed.The indicator most consistently associated with the reference composite indicator (HIV testing, antiretroviral prophylaxis and combined antiretroviral therapy) was the single measure of antiretroviral prophylaxis and combined antiretroviral therapy. Lower performing pMTCT clinics ranked consistently low across measurement strategies; high and middle performing clinics demonstrated more variability. Association between clinic characteristics and high pMTCT performance varied markedly across ranking strategies. Using the reference composite indicator, larger catchment area, higher number of institutional deliveries, onsite CD4 point-of-care capacity, and higher numbers of nurses and doctors were associated with high clinic performance while clinic location, NGO support, women's support group, community linkages patient-tracking systems and stock-outs were not associated with high performance.Classifying high and low performance provided consistent results across ranking measures, though granularity was improved by aggregating middle performers with either high or low performers. Human resources, catchment size and utilization were positively associated with effective pMTCT service delivery.
Mucolipidosis II-related mutations inhibit the exit from the endoplasmic reticulum and proteolytic cleavage of GlcNAc-1-phosphotransferase precursor protein (GNPTAB). - Human mutation
Mucolipidosis (ML) II and MLIII alpha/beta are two pediatric lysosomal storage disorders caused by mutations in the GNPTAB gene, which encodes an Î±/Î²-subunit precursor protein of GlcNAc-1-phosphotransferase. Considerable variations in the onset and severity of the clinical phenotype in these diseases are observed. We report here on expression studies of two missense mutations c.242G>T (p.Trp81Leu) and c.2956C>T (p.Arg986Cys) and two frameshift mutations c.3503_3504delTC (p.Leu1168GlnfsX5) and c.3145insC (p.Gly1049ArgfsX16) present in severely affected MLII patients, as well as two missense mutations c.1196C>T (p.Ser399Phe) and c.3707A>T (p.Lys1236Met) reported in more mild affected individuals. We generated a novel Î±-subunit-specific monoclonal antibody, allowing the analysis of the expression, subcellular localization, and proteolytic activation of wild-type and mutant Î±/Î²-subunit precursor proteins by Western blotting and immunofluorescence microscopy. In general, we found that both missense and frameshift mutations that are associated with a severe clinical phenotype cause retention of the encoded protein in the endoplasmic reticulum and failure to cleave the Î±/Î²-subunit precursor protein are associated with a severe clinical phenotype with the exception of p.Ser399Phe found in MLIII alpha/beta. Our data provide new insights into structural requirements for localization and activity of GlcNAc-1-phosphotransferase that may help to explain the clinical phenotype of MLII patients.Â© 2013 WILEY PERIODICALS, INC.
Sortilin and the risk of cardiovascular disease. - Revista portuguesa de cardiologia : orgÃ£o oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology
Plasma low-density lipoprotein cholesterol (LDL-C) levels are a key determinant of the risk of cardiovascular disease, which is why many studies have attempted to elucidate the pathways that regulate its metabolism. Novel latest-generation sequencing techniques have identified a strong association between the 1p13 locus and the risk of cardiovascular disease caused by changes in plasma LDL-C levels. As expected for a complex phenotype, the effects of variation in this locus are only moderate. Even so, knowledge of the association is of major importance, since it has unveiled a new metabolic pathway regulating plasma cholesterol levels. Crucial to this discovery was the work of three independent teams seeking to clarify the biological basis of this association, who succeeded in proving that SORT1, encoding sortilin, was the gene in the 1p13 locus involved in LDL metabolism. SORT1 was the first gene identified as determining plasma LDL levels to be mechanistically evaluated and, although the three teams used different, though appropriate, experimental methods, their results were in some ways contradictory. Here we review all the experiments that led to the identification of the new pathway connecting sortilin with plasma LDL levels and risk of myocardial infarction. The regulatory mechanism underlying this association remains unclear, but its discovery has paved the way for considering previously unsuspected therapeutic targets and approaches.Copyright Â© 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier EspaÃ±a. All rights reserved.
Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy. - Circulation. Cardiovascular imaging
Transthyretin familial amyloid polyneuropathy is a hereditary form of amyloidosis characterized by sensorimotor and autonomic neuropathy, cardiac conduction defects, and infiltrative cardiomyopathy. Previous studies have suggested that myocardial sympathetic denervation assessed by 123-iodine metaiodobenzylguanidine (MIBG) imaging occurs early in disease progression. However, its prognostic significance was never evaluated. We aimed to study the long-term prognostic value of myocardial sympathetic denervation detected by MIBG imaging in transthyretin familial amyloid polyneuropathy.A total of 143 individuals with V30M transthyretin mutation underwent Holter, ambulatory blood pressure monitoring, echocardiography, and MIBG imaging. Time to all-cause death was compared with late heart-to-mediastinum MIBG uptake ratio (H/M; either in relation to the estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses were performed to test the prognostic accuracy of clinical, neurological, and cardiovascular parameters. During a median follow-up of 5.5 years, 32 (22%) patients died. Five-year mortality rate was 42% for late H/M <1.60 and 7% for late H/M â‰¥1.60 (hazard ratio, 7.19; P<0.001). Late H/M was identified as an independent prognostic predictor. Fifty-three patients were submitted to liver transplantation. In comparison with neurophysiological score-matched controls, transplanted patients had lower long-term mortality (hazard ratio, 0.32; P=0.012). Patients with late H/M<1.60 were at higher risk of unfavorable outcome but seemed to have benefited from liver transplantation.Cardiac sympathetic denervation as assessed by MIBG imaging is a useful prognostic marker in transthyretin familial amyloid polyneuropathy.
The home environment and family asthma management among ethnically diverse urban youth with asthma. - Families, systems & health : the journal of collaborative family healthcare
Although the pediatric psychology literature underscores the importance of illness-related aspects of the home environment for optimal family asthma management, little is known about the contribution of more global aspects of the home environment (e.g., family routines/schedule, quality of stimulation provided to child) to asthma management in ethnic minority and urban families. The goals of this study were to (a) explore ethnic/racial group differences in global and specific dimensions of home environment quality among Latino, non-Latino White (NLW), and African American urban children with asthma; and (b) examine associations between the quality and quantity of support and stimulation within the home environment, as measured by the HOME Inventory, and family asthma management. Urban, low-income children (N = 131) between the ages of 6 and 13 with asthma and a primary caregiver participated in a multimodal assessment, including an in-home observation and semistructured interviews to assess aspects of home environment quality and family asthma management practices. While controlling for poverty, no ethnic group differences were found in the global home environment; however, there were significant differences in specific dimensions (e.g., Family Participation in Developmentally Stimulating Experiences, and Aspects of the Physical Environment) of home environment quality. Across the whole sample, home environment quality predicted family asthma management. When examining this association for specific ethnic groups, this finding did not hold for the Latino subsample. The results highlight the need to consider ethnic group differences in non-illness-specific aspects of the home environment when addressing families' asthma management strategies.PsycINFO Database Record (c) 2013 APA, all rights reserved.
Contextual and cultural risks and their association with family asthma management in urban children. - Journal of child health care : for professionals working with children in the hospital and community
This study examines the association between caregivers' perceptions of home and neighborhood safety on family asthma management in the context of cultural risk factors (e.g., discrimination and acculturative stress) in a sample of urban and ethnic minority families. Participants included 147 children (ages 6-13) and their primary caregiver from Latino, African American and Non-Latino White (NLW) backgrounds. When controlling for poverty, caregivers' perceptions of home and neighborhood safety predicted family asthma management for the overall sample and for the NLW families. Additionally, for caregivers who endorsed higher levels of perceived discrimination, home and neighborhood safety predicted family asthma management. This study demonstrates the utility of considering caregivers' perceptions of home and neighborhood safety when examining urban families' day-to-day engagement with asthma management tasks.
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