Browsing by Author "Chakraborty, Hrishikesh"
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Item Open Access Brain research to ameliorate impaired neurodevelopment--home-based intervention trial (BRAIN-HIT).(BMC pediatrics, 2010-04-30) Wallander, Jan L; McClure, Elizabeth; Biasini, Fred; Goudar, Shivaprasad S; Pasha, Omrana; Chomba, Elwyn; Shearer, Darlene; Wright, Linda; Thorsten, Vanessa; Chakraborty, Hrishikesh; Dhaded, Sangappa M; Mahantshetti, Niranjana S; Bellad, Roopa M; Abbasi, Zahid; Carlo, Waldemar; BRAIN-HIT InvestigatorsThis randomized controlled trial aims to evaluate the effects of an early developmental intervention program on the development of young children in low- and low-middle-income countries who are at risk for neurodevelopmental disability because of birth asphyxia. A group of children without perinatal complications are evaluated in the same protocol to compare the effects of early developmental intervention in healthy infants in the same communities. Birth asphyxia is the leading specific cause of neonatal mortality in low- and low-middle-income countries and is also the main cause of neonatal and long-term morbidity including mental retardation, cerebral palsy, and other neurodevelopmental disorders. Mortality and morbidity from birth asphyxia disproportionately affect more infants in low- and low-middle-income countries, particularly those from the lowest socioeconomic groups. There is evidence that relatively inexpensive programs of early developmental intervention, delivered during home visit by parent trainers, are capable of improving neurodevelopment in infants following brain insult due to birth asphyxia.This trial is a block-randomized controlled trial that has enrolled 174 children with birth asphyxia and 257 without perinatal complications, comparing early developmental intervention plus health and safety counseling to the control intervention receiving health and safety counseling only, in sites in India, Pakistan, and Zambia. The interventions are delivered in home visits every two weeks by parent trainers from 2 weeks after birth until age 36 months. The primary outcome of the trial is cognitive development, and secondary outcomes include social-emotional and motor development. Child, parent, and family characteristics and number of home visits completed are evaluated as moderating factors.The trial is supervised by a trial steering committee, and an independent data monitoring committee monitors the trial. Findings from this trial have the potential to inform about strategies for reducing neurodevelopmental disabilities in at-risk young children in low and middle income countries.Item Open Access Dose of early intervention treatment during children's first 36 months of life is associated with developmental outcomes: an observational cohort study in three low/low-middle income countries.(BMC pediatrics, 2014-10-25) Wallander, Jan L; Biasini, Fred J; Thorsten, Vanessa; Dhaded, Sangappa M; de Jong, Desiree M; Chomba, Elwyn; Pasha, Omrana; Goudar, Shivaprasad; Wallace, Dennis; Chakraborty, Hrishikesh; Wright, Linda L; McClure, Elizabeth; Carlo, Waldemar AThe positive effects of early developmental intervention (EDI) on early child development have been reported in numerous controlled trials in a variety of countries. An important aspect to determining the efficacy of EDI is the degree to which dosage is linked to outcomes. However, few studies of EDI have conducted such analyses. This observational cohort study examined the association between treatment dose and children's development when EDI was implemented in three low and low-middle income countries as well as demographic and child health factors associated with treatment dose.Infants (78 males, 67 females) born in rural communities in India, Pakistan, and Zambia received a parent-implemented EDI delivered through biweekly home visits by trainers during the first 36 months of life. Outcome was measured at age 36 months with the Mental (MDI) and Psychomotor (PDI) Development Indices of the Bayley Scales of Infant Development-II. Treatment dose was measured by number of home visits completed and parent-reported implementation of assigned developmental stimulation activities between visits. Sociodemographic, prenatal, perinatal, and child health variables were measures as correlates.Average home visits dose exceeded 91% and mothers engaged the children in activities on average 62.5% of days. Higher home visits dose was significantly associated with higher MDI (mean for dose quintiles 1-2 combined = 97.8, quintiles 3-5 combined = 103.4, p = 0.0017). Higher treatment dose was also generally associated with greater mean PDI, but the relationships were non-linear. Location, sociodemographic, and child health variables were associated with treatment dose.Receiving a higher dose of EDI during the first 36 months of life is generally associated with better developmental outcomes. The higher benefit appears when receiving ≥91% of biweekly home visits and program activities on ≥67% of days over 3 years. It is important to ensure that EDI is implemented with a sufficiently high dose to achieve desired effect. To this end groups at risk for receiving lower dose can be identified and may require special attention to ensure adequate effect.Item Open Access Establishing the value of genomics in medicine: the IGNITE Pragmatic Trials Network.(Genetics in medicine : official journal of the American College of Medical Genetics, 2021-03-29) Ginsburg, Geoffrey S; Cavallari, Larisa H; Chakraborty, Hrishikesh; Cooper-DeHoff, Rhonda M; Dexter, Paul R; Eadon, Michael T; Ferket, Bart S; Horowitz, Carol R; Johnson, Julie A; Kannry, Joseph; Kucher, Natalie; Madden, Ebony B; Orlando, Lori A; Parker, Wanda; Peterson, Josh; Pratt, Victoria M; Rakhra-Burris, Tejinder K; Ramos, Michelle A; Skaar, Todd C; Sperber, Nina; Steen-Burrell, Kady-Ann; Van Driest, Sara L; Voora, Deepak; Wiisanen, Kristin; Winterstein, Almut G; Volpi, Simona; IGNITE PTNPurpose
A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions.Methods
The Implementing Genomics in Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation.Results
Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression.Conclusion
IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.Item Open Access Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression.(Molecular autism, 2016-01) Casanova, Emily L; Sharp, Julia L; Chakraborty, Hrishikesh; Sumi, Nahid Sultana; Casanova, Manuel FBACKGROUND:Intellectual disability (ID), autism, and epilepsy share frequent yet variable comorbidities with one another. In order to better understand potential genetic divergence underlying this variable risk, we studied genes responsible for monogenic IDs, grouped according to their autism and epilepsy comorbidities. METHODS:Utilizing 465 different forms of ID with known molecular origins, we accessed available genetic databases in conjunction with gene ontology (GO) to determine whether the genetics underlying ID diverge according to its comorbidities with autism and epilepsy and if genes highly penetrant for autism or epilepsy share distinctive features that set them apart from genes that confer comparatively variable or no apparent risk. RESULTS:The genetics of ID with autism are relatively enriched in terms associated with nervous system-specific processes and structural morphogenesis. In contrast, we find that ID with highly comorbid epilepsy (HCE) is modestly associated with lipid metabolic processes while ID without autism or epilepsy comorbidity (ID only) is enriched at the Golgi membrane. Highly comorbid autism (HCA) genes, on the other hand, are strongly enriched within the nucleus, are typically involved in regulation of gene expression, and, along with IDs with more variable autism, share strong ties with a core protein-protein interaction (PPI) network integral to basic patterning of the CNS. CONCLUSIONS:According to GO terminology, autism-related gene products are integral to neural development. While it is difficult to draw firm conclusions regarding IDs unassociated with autism, it is clear that the majority of HCA genes are tightly linked with general dysregulation of gene expression, suggesting that disturbances to the chronology of neural maturation and patterning may be key in conferring susceptibility to autism spectrum conditions.Item Open Access High dosage folic acid supplementation, oral cleft recurrence and fetal growth.(International journal of environmental research and public health, 2013-02-04) Wehby, George L; Félix, Têmis Maria; Goco, Norman; Richieri-Costa, Antonio; Chakraborty, Hrishikesh; Souza, Josiane; Pereira, Rui; Padovani, Carla; Moretti-Ferreira, Danilo; Murray, Jeffrey CObjectives
To evaluate the effects of folic acid supplementation on isolated oral cleft recurrence and fetal growth.Patients and methods
The study included 2,508 women who were at-risk for oral cleft recurrence and randomized into two folic acid supplementation groups: 0.4 and 4 mg per day before pregnancy and throughout the first trimester. The infant outcome data were based on 234 live births. In addition to oral cleft recurrence, several secondary outcomes were compared between the two folic acid groups. Cleft recurrence rates were also compared to historic recurrence rates.Results
The oral cleft recurrence rates were 2.9% and 2.5% in the 0.4 and 4 mg groups, respectively. The recurrence rates in the two folic acid groups both separately and combined were significantly different from the 6.3% historic recurrence rate post the folic acid fortification program for this population (p = 0.0009 when combining the two folic acid groups). The rate of cleft lip with palate recurrence was 2.9% in the 0.4 mg group and 0.8% in the 4 mg group. There were no elevated fetal growth complications in the 4 mg group compared to the 0.4 mg group.Conclusions
The study is the first double-blinded randomized clinical trial (RCT) to study the effect of high dosage folic acid supplementation on isolated oral cleft recurrence. The recurrence rates were similar between the two folic acid groups. However, the results are suggestive of a decrease in oral cleft recurrence compared to the historic recurrence rate. A RCT is still needed to identify the effect of folic acid on oral cleft recurrence given these suggestive results and the supportive results from previous interventional and observational studies, and the study offers suggestions for such future studies. The results also suggest that high dosage folic acid does not compromise fetal growth.Item Open Access HPV prevalence at enrollment and baseline results from the Carolina Women's Care Study, a longitudinal study of HPV persistence in women of college age.(International journal of women's health, 2013-01) Banister, Carolyn E; Messersmith, Amy R; Chakraborty, Hrishikesh; Wang, Yinding; Spiryda, Lisa B; Glover, Saundra H; Pirisi, Lucia; Creek, Kim EBACKGROUND:Cervical cancer, a rare outcome of high-risk human papillomavirus (HPV) infection, disproportionately affects African American women, who are about twice more likely than European American women to die of the disease. Most cervical HPV infections clear in about one year. However, in some women HPV persists, posing a greater risk for cervical dysplasia and cancer. The Carolina Women's Care Study (CWCS) was conducted to explore the biological, genetic, and lifestyle determinants of persistent HPV infection in college-aged European American and African American women. This paper presents the initial results of the CWCS, based upon data obtained at enrollment. METHODS:Freshman female students attending the University of South Carolina were enrolled in the CWCS and followed until graduation with biannual visits, including two Papanicolaou tests, cervical mucus collection, and a questionnaire assessing lifestyle factors. We recruited 467 women, 293 of whom completed four or more visits for a total of 2274 visits. RESULTS AND CONCLUSION:CWCS participants were 70% European American, 24% African American, 3% Latina/Hispanic, and 3% Asian. At enrollment, 32% tested positive for any HPV. HPV16 infection was the most common (18% of infections). Together, HPV16, 66, 51, 52, and 18 accounted for 58% of all HPV infections. Sixty-four percent of all HPV-positive samples contained more than one HPV type, with an average of 2.2 HPV types per HPV-positive participant. We found differences between African American and European American women in the prevalence of HPV infection (38.1% African American, 30.7% European American) and abnormal Papanicolaou test results (9.8% African-American, 5.8% European American). While these differences did not reach statistical significance at enrollment, as the longitudinal data of this cohort are analyzed, the sample size will allow us to confirm these results and compare the natural history of HPV infection in college-aged African American and European American women.Item Open Access Modeling Occurrence of Dengue Cases in Malaysia.(Iranian journal of public health, 2016-11) Nurul Azam, Mohammad; Yeasmin, Mahbuba; Ahmed, Nasar U; Chakraborty, HrishikeshItem Open Access Optimizing Partner Notification Programs for Men Who Have Sex with Men: Factorial Survey Results from South China.(PloS one, 2016-01) Wang, Alberta L; Peng, Rui-Rui; Tucker, Joseph D; Chakraborty, Hrishikesh; Cohen, Myron S; Chen, Xiang-ShengBackground
Syphilis is prevalent among men who have sex with men (MSM) in China. Syphilis partner notification (PN) programs targeting MSM has been considered as one of effective strategies to prevention and control of the infection in the population. We examined willingness and preferences for PN among MSM to measure feasibility and optimize uptake.Methods
Participation in a syphilis PN program was measured using a factorial survey from both the perspective of the index patient and the partner. Respondents were recruited from April-July 2011 using convenience sampling at two sites-a MSM sexually transmitted disease (STD) clinic and a MSM community based organization (CBO). Respondents first evaluated three factorial survey vignettes to measure probability of participation and then an anonymous sociodemographic questionnaire. A two-level mixed linear model was fitted for the factorial survey analysis.Results
In 372 respondents with mean age (± SD) 28.5 (± 6.0) years, most were single (82.0%) and closeted gays (66.7%). The Internet was the most frequent place to search for sex. Few (31.2%) had legal names for casual partners, but most had instant messenger (86.5%) and mobile phone numbers (77.7%). The mean probability of participation in a syphilis PN program was 64.5% (± 32.4%) for index patients and 63.7% (± 32.6%) for partners. Referral of the partner to a private clinic or MSM CBO for follow-up decreased participation compared to the local Center for Disease Control and Prevention (CDC) or public STD clinic.Conclusions
Enhanced PN services may be feasible among MSM in South China. Internet and mobile phone PN may contact partners untraceable by traditional PN. Referral of partners to the local CDC or public STD clinic may maximize PN participation.Item Open Access Oral cleft prevention program (OCPP).(BMC pediatrics, 2012-11-26) Wehby, George L; Goco, Norman; Moretti-Ferreira, Danilo; Felix, Temis; Richieri-Costa, Antonio; Padovani, Carla; Queiros, Fernanda; Guimaraes, Camilla Vila Nova; Pereira, Rui; Litavecz, Steve; Hartwell, Tyler; Chakraborty, Hrishikesh; Javois, Lorette; Murray, Jeffrey COral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4 mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. CLINICALTRIALS.GOV IDENTIFIER: NCT00397917.Item Open Access Statewide Longitudinal Progression of the Whole-Patient Measure of Safety in South Carolina.(Journal for healthcare quality : official publication of the National Association for Healthcare Quality, 2018-09) Turley, Christine B; Brittingham, Jordan; Moonan, Aunyika; Davis, Dianne; Chakraborty, HrishikeshMeaningful improvement in patient safety encompasses a vast number of quality metrics, but a single measure to represent the overall level of safety is challenging to produce. Recently, Perla et al. established the Whole-Person Measure of Safety (WPMoS) to reflect the concept of global risk assessment at the patient level. We evaluated the WPMoS across an entire state to understand the impact of urban/rural setting, academic status, and hospital size on patient safety outcomes. The population included all South Carolina (SC) inpatient discharges from January 1, 2008, through to December 31, 2013, and was evaluated using established definitions of highly undesirable events (HUEs). Over the study period, the proportion of hospital discharges with at least one HUE significantly decreased from 9.7% to 8.8%, including significant reductions in nine of the 14 HUEs. Academic, large, and urban hospitals had a significantly lower proportion of hospital discharges with at least one HUE in 2008, but only urban hospitals remained significantly lower by 2013. Results indicate that there has been a decrease in harm events captured through administrative coded data over this 6-year period. A composite measure, such as the WPMoS, is necessary for hospitals to evaluate their progress toward reducing preventable harm.Item Open Access The effect of systematic pediatric care on neonatal mortality and hospitalizations of infants born with oral clefts.(BMC pediatrics, 2011-12-28) Wehby, George L; Castilla, Eduardo E; Goco, Norman; Rittler, Monica; Cosentino, Viviana; Javois, Lorette; Kindem, Mark; Chakraborty, Hrishikesh; Dutra, Graca; López-Camelo, Jorge S; Orioli, Iêda M; Murray, Jeffrey CCleft lip and/or palate (CL/P) increase mortality and morbidity risks for affected infants especially in less developed countries. This study aimed at assessing the effects of systematic pediatric care on neonatal mortality and hospitalizations of infants with cleft lip and/or palate (CL/P) in South America.The intervention group included live-born infants with isolated or associated CL/P in 47 hospitals between 2003 and 2005. The control group included live-born infants with CL/P between 2001 and 2002 in the same hospitals. The intervention group received systematic pediatric care between the 7th and 28th day of life. The primary outcomes were mortality between the 7th and 28th day of life and hospitalization days in this period among survivors adjusted for relevant baseline covariates.There were no significant mortality differences between the intervention and control groups. However, surviving infants with associated CL/P in the intervention group had fewer hospitalization days by about six days compared to the associated control group.Early systematic pediatric care may significantly reduce neonatal hospitalizations of infants with CL/P and additional birth defects in South America. Given the large healthcare and financial burden of CL/P on affected families and the relatively low cost of systematic pediatric care, improving access to such care may be a cost-effective public policy intervention.ClinicalTrials.gov: NCT00097149.Item Open Access Ultrafiltration in Acute Heart Failure: Implications of Ejection Fraction and Early Response to Treatment From CARRESS-HF.(Journal of the American Heart Association, 2020-12-08) Fudim, Marat; Brooksbank, Jeremy; Giczewska, Anna; Greene, Stephen J; Grodin, Justin L; Martens, Pieter; Ter Maaten, Jozine M; Sharma, Abhinav; Verbrugge, Frederik H; Chakraborty, Hrishikesh; Bart, Bradley A; Butler, Javed; Hernandez, Adrian F; Felker, G Michael; Mentz, Robert JBackground Ultrafiltration is not commonly used because of higher incidence of worsening renal function without improved decongestion. We examined differential outcomes of high versus low fluid removal and preserved versus reduced ejection fraction (EF) in CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure). Methods and Results Baseline characteristics in the ultrafiltration arm were compared according to 24-hour ultrafiltration-based fluid removal above versus below the median. Patients were stratified by EF (≤40% or >40%). We compared clinical parameters of clinical decongestion during the hospitalization based on initial (≤24 hours) response to ultrafiltration. Cox-proportional hazards models were used to identify associations between fluid removal <24 hours and composite of death, hospitalization, or unscheduled outpatient/emergency department visit during study follow-up. The intention-to-treat analysis included 93 patients. Within 24 hours, median fluid removal was 1.89 L (Q1, Q3: 1.22, 3.16). The high fluid removal group had a greater urine output (9.08 versus 6.23 L, P=0.027) after 96 hours. Creatinine change from baseline to 96 hours was similar in both groups (0.10 mg/dL increase, P=0.610). The EF >40% group demonstrated larger increases of change in creatinine (P=0.023) and aldosterone (P=0.038) from baseline to 96 hours. Among patients with EF >40%, those with above median fluid removal (n=17) when compared with below median (n=17) had an increased rate of the combined end point (87.5% versus 47.1%, P=0.014). Conclusions In patients with acute heart failure, higher initial fluid removal with ultrafiltration had no association with worsening renal function. In patients with EF >40%, ultrafiltration was associated with worsening renal function irrespective of fluid removal rate and higher initial fluid removal was associated with higher rates of adverse clinical outcomes, highlighting variable responses to decongestive therapy.