Last data update: Jul 01, 2024. (Total: 47134 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Chopra P [original query] |
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Development of a standards-based city-wide health information exchange for public health in response to COVID-19 (preprint)
Hota B , Casey P , McIntyre AF , Khan J , Rab S , Chopra A , Lateef O , Layden JE . medRxiv 2020 2020.08.12.20173559 Background Disease surveillance is a critical function of public health, provides essential information about disease burden, clinical and epidemiologic parameters of disease, and is an important element to effective and timely case and contact tracing. The COVID-19 pandemic has demonstrated the essential role these functions have to preserve public health. Syndromic surveillance, electronic laboratory reporting in the meaningful use program, and the growth of the National Healthcare Safety Network (NHSN) have created linkages between hospitals, commercial labs, and public health that can collect and organize data, often through EHR and order workflows, to improve the timeliness and completeness of reporting. In theory, the standard data formats and exchange methods provided by meaningful use should enable rapid healthcare data exchange in the setting of disruptive healthcare events like a pandemic. In reality, access to data remains challenging, and even if available, often lack conformity to regulated standards.Objective We sought to use regulated interoperability standards already in production to generate regional bed capacity awareness, enhance the capture of epidemiological risk factors and clinical variables among COVID-19 tested patients, and reduce the administrative burden of reporting for stakeholders in a manner that could be replicated by other public health agencies.Methods Following a public health order mandating data submission, we developed technical infrastructure to combine multiple data feeds from electronic health record systems. We measured the completeness of each feed, and the match rate between feeds.Results A cloud-based environment was created that received data from electronic lab reporting, consolidated clinical data architecture, and bed capacity data feeds from sites. Data governance was planned from the project beginning to aid in consensus and principles for data use. 88,906 total persons from CCDA data among 14 facilities, and 408,741 persons from ELR records among 88 facilities, were submitted. Fields routinely absent from ELR feeds included travel histories, clinical symptoms, and comorbidities. CCDA data provided an improvement in the quality of data available for surveillance and was highly complete with <5% for all records types with the exception of patient cell phone. 90.1% of records could be matched between CCDA and ELR feeds.Conclusions We describe the development of a city-wide public health data hub for the surveillance of COVID-19 infection. We were able to assess the completeness of existing ELR feeds, augment these feeds with CCDA documents, establish secure transfer methods for data exchange, develop cloud-based architecture to enable secure data storage and analytics, and produced meaningful dashboards for the monitoring of capacity and disease burden. We see this public health and clinical data registry as an informative example of the power of common standards across electronic records, and a potential template for future extension of the use of standards to improve public health surveillance.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received for this work.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:This work was conducted under a public health exemption through the Chicago Department of Public HealthAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectiv ly, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data used for this study was reported to the health department and is not publicly available at this time. |
Peripheral blood DNA methylation and autism spectrum disorder (preprint)
Andrews SV , Sheppard B , Windham GC , Schieve LA , Schendel DE , Croen LA , Chopra P , Alisch RS , Newschaffer CJ , Warren ST , Feinberg AP , Fallin MD , Ladd-Acosta C . bioRxiv 2018 320622 BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size, and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12×10−7. Seven CpGs showed differences at p < 1×10−5 and 48 at 1×10−4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpGs hits, which was consistent across EWAS and meQTL discovery p-value thresholds.ConclusionsWe report the largest case-control EWAS study of ASD to date. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the 7 sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. |
Development of a standards-based city-wide health information exchange for public health in response to COVID-19.
Hota B , Casey P , McIntyre AF , Khan J , Rab S , Chopra A , Lateef O , Layden JE . JMIR Public Health Surveill 2022 8 (9) e35973 BACKGROUND: Disease surveillance is a critical function of public health, provides essential information about disease burden, clinical and epidemiologic parameters of disease, and is an important element of effective and timely case and contact tracing. The COVID-19 pandemic demonstrates the essential role of disease surveillance in preserving public health. In theory, the standard data formats and exchange methods provided by EHR meaningful use should enable rapid healthcare data exchange in the setting of disruptive healthcare events like a pandemic. In reality, access to data remains challenging, and, even if available, often lacks conformity to regulated standards. As a result of the COVID-19 pandemic, we developed a regional data hub to enhance public health surveillance. OBJECTIVE: We sought to use regulated interoperability standards already in production to generate awareness of regional bed capacity and enhance the capture of epidemiological risk factors and clinical variables among patients tested for SARS-CoV-2. We describe the technical and operational components, governance model, and timelines required to implement the public health order which mandated electronic reporting of data from EHRs among hospitals in the Chicago jurisdiction. We also evaluate the data sources, infrastructure requirements and the completeness of data supplied to the platform and the capacity to link these sources. METHODS: Following a public health order mandating data submission by all acute care hospitals in Chicago, we developed the technical infrastructure to combine multiple data feeds from those EHR systems. We measured the completeness of each feed and the match rate between feeds. RESULTS: A cloud-based environment was created that received ELR, consolidated clinical data architecture, and bed capacity data feeds from sites. Data governance was planned from the project initiation to aid in consensus and principles for data use. Data from 88,906 persons from consolidated clinical data architecture (CCDA) records among 14 facilities, and 408,741 persons from ELR records among 88 facilities, were submitted. Most (90.1%) records could be matched between CCDA and ELR feeds. Data fields absent from ELR feeds included travel histories, clinical symptoms, and comorbidities. Less than 5% of CCDA data fields were empty. Merging CCDA with ELR data improved race, ethnicity, comorbidity, and hospitalization information data availability. CONCLUSIONS: We describe the development of a city-wide public health data hub for the surveillance of SARS-CoV-2 infection. We were able to assess the completeness of existing ELR feeds, augment these feeds with CCDA documents, establish secure transfer methods for data exchange, develop cloud-based architecture to enable secure data storage and analytics, and produce dashboards for monitoring of capacity and disease burden. We consider this public health and clinical data registry as an informative example of the power of common standards across EHR and a potential template for future use of standards to improve public health surveillance. |
The Michigan plan for appropriate tailored health care in pregnancy prenatal care recommendations
Peahl AF , Zahn CM , Turrentine M , Barfield W , Blackwell SD , Roberts SJ , Powell AR , Chopra V , Bernstein SJ . Obstet Gynecol 2021 138 (4) 593-602 OBJECTIVE: To describe MiPATH (the Michigan Plan for Appropriate Tailored Healthcare) in pregnancy panel process and key recommendations for prenatal care delivery. METHODS: We conducted an appropriateness study using the RAND Corporation and University of California Los Angeles Appropriateness Method, a modified e-Delphi process, to develop MiPATH recommendations using sequential steps: 1) definition and scope of key terms, 2) literature review and data synthesis, 3) case scenario development, 4) panel selection and scenario revisions, and 5) two rounds of panel appropriateness ratings with deliberation. Recommendations were developed for average-risk pregnant individuals (eg, individuals not requiring care by maternal-fetal medicine specialists). Because prenatal services (eg, laboratory tests, vaccinations) have robust evidence, panelists considered only how services are delivered (eg, visit frequency, telemedicine). RESULTS: The appropriateness of key aspects of prenatal care delivery across individuals with and without common medical and pregnancy complications, as well as social and structural determinants of health, was determined by the panel. Panelists agreed that a risk assessment for medical, social, and structural determinants of health should be completed as soon as individuals present for care. Additionally, the panel provided recommendations for: 1) prenatal visit schedules (care initiation, visit timing and frequency, routine pregnancy assessments), 2) integration of telemedicine (virtual visits and home devices), and 3) care individualization. Panelists recognized significant gaps in existing evidence and the need for policy changes to support equitable care with changing practices. CONCLUSION: The MiPATH recommendations offer more flexible prenatal care delivery for average-risk individuals. |
Molecular evaluation of fluoroquinolone resistance in serial Mycobacterium tuberculosis isolates from individuals diagnosed with multidrug-resistant tuberculosis.
Willby M , Chopra P , Lemmer D , Klein K , Dalton TL , Engelthaler DM , Cegielski P , Posey JE . Antimicrob Agents Chemother 2020 65 (1) ![]() ![]() Fluoroquinolones (FQ) are crucial components of multidrug-resistant tuberculosis (MDR TB) treatment. Varying levels of resistance are associated with specific mutations within the Quinolone Resistance Determining Region (QRDR) of gyrA We sequenced the QRDR from serial isolates of MDR TB patients in the Preserving Effective TB Treatment Study (PETTS) with baseline (FQ(R)) or acquired FQ resistance (FQ(ACQR)) using the IonTorrent™ Personal Genome Machine to a depth of 10,000x and reported single nucleotide polymorphisms in ≥1% of reads. FQ(R) isolates harbored 15 distinct alleles with 1.3 (max=6) on average per isolate. Eighteen alleles were identified in FQ(ACQR) isolates with an average of 1.6 (max=9) per isolate. Isolates from 78% of FQ(ACQR) individuals had mutant alleles identified within 6 months of treatment initiation. Asp94Gly followed by Ala90Val were the predominant alleles in initial FQ-resistant isolates. Seventy-seven percent (36/47) of FQ(ACQR) group patients had isolates with FQ resistance alleles prior to changes to the FQ component of their treatment. Unlike individuals treated initially with other FQs, none of the 21 individuals treated initially with levofloxacin developed genotypic or phenotypic FQ resistance, although, country of residence is likely a contributing factor since 69% of these individuals were from a single country. Initial detection of phenotypic and genotypic resistance occurred simultaneously for most; however, phenotypic resistance occurred earlier in isolates harboring mixtures of very low-abundance (<1% of reads) alleles while genotypic resistance often occurred earlier for low-level resistance-associated alleles. Understanding factors influencing acquisition and evolution of FQ resistance could reveal strategies for improved treatment success. |
Initial and Repeated Point Prevalence Surveys to Inform SARS-CoV-2 Infection Prevention in 26 Skilled Nursing Facilities - Detroit, Michigan, March-May 2020.
Sanchez GV , Biedron C , Fink LR , Hatfield KM , Polistico JMF , Meyer MP , Noe RS , Copen CE , Lyons AK , Gonzalez G , Kiama K , Lebednick M , Czander BK , Agbonze A , Surma AR , Sandhu A , Mika VH , Prentiss T , Zervos J , Dalal DA , Vasquez AM , Reddy SC , Jernigan J , Kilgore PE , Zervos MJ , Chopra T , Bezold CP , Rehman NK . MMWR Morb Mortal Wkly Rep 2020 69 (27) 882-886 Skilled nursing facilities (SNFs) are focal points of the coronavirus disease 2019 (COVID-19) pandemic, and asymptomatic infections with SARS-CoV-2, the virus that causes COVID-19, among SNF residents and health care personnel have been described (1-3). Repeated point prevalence surveys (serial testing of all residents and health care personnel at a health care facility irrespective of symptoms) have been used to identify asymptomatic infections and have reduced SARS-CoV-2 transmission during SNF outbreaks (1,3). During March 2020, the Detroit Health Department and area hospitals detected a sharp increase in COVID-19 diagnoses, hospitalizations, and associated deaths among SNF residents. The Detroit Health Department collaborated with local government, academic, and health care system partners and a CDC field team to rapidly expand SARS-CoV-2 testing and implement infection prevention and control (IPC) activities in all Detroit-area SNFs. During March 7-May 8, among 2,773 residents of 26 Detroit SNFs, 1,207 laboratory-confirmed cases of COVID-19 were identified during three periods: before (March 7-April 7) and after two point prevalence surveys (April 8-25 and April 30-May 8): the overall attack rate was 44%. Within 21 days of receiving their first positive test results, 446 (37%) of 1,207 COVID-19 patients were hospitalized, and 287 (24%) died. Among facilities participating in both surveys (n = 12), the percentage of positive test results declined from 35% to 18%. Repeated point prevalence surveys in SNFs identified asymptomatic COVID-19 cases, informed cohorting and IPC practices aimed at reducing transmission, and guided prioritization of health department resources for facilities experiencing high levels of SARS-CoV-2 transmission. With the increased availability of SARS-CoV-2 testing, repeated point prevalence surveys and enhanced and expanded IPC support should be standard tools for interrupting and preventing COVID-19 outbreaks in SNFs. |
Excess antibiotic treatment duration and adverse events in patients hospitalized with pneumonia: A multihospital cohort study
Vaughn VM , Flanders SA , Snyder A , Conlon A , Rogers MAM , Malani AN , McLaughlin E , Bloemers S , Srinivasan A , Nagel J , Kaatz S , Osterholzer D , Thyagarajan R , Hsaiky L , Chopra V , Gandhi TN . Ann Intern Med 2019 171 (3) 153-163 Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program. |
Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study
Dorman SE , Schumacher SG , Alland D , Nabeta P , Armstrong DT , King B , Hall SL , Chakravorty S , Cirillo DM , Tukvadze N , Bablishvili N , Stevens W , Scott L , Rodrigues C , Kazi MI , Joloba M , Nakiyingi L , Nicol MP , Ghebrekristos Y , Anyango I , Murithi W , Dietze R , Lyrio Peres R , Skrahina A , Auchynka V , Chopra KK , Hanif M , Liu X , Yuan X , Boehme CC , Ellner JJ , Denkinger CM , Study Team , Cain KP , Agaya J , McCarthy KD . Lancet Infect Dis 2018 18 (1) 76-84 BACKGROUND: The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. METHODS: In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. FINDINGS: Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (-2·7%, -3·9 to -1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. INTERPRETATION: For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. FUNDING: Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases. |
Developing a model to predict unfavourable treatment outcomes in patients with tuberculosis and human immunodeficiency virus co-infection in Delhi, India
Madan C , Chopra KK , Satyanarayana S , Surie D , Chadha V , Sachdeva KS , Khanna A , Deshmukh R , Dutta L , Namdeo A , Shukla A , Sagili K , Chauhan LS . PLoS One 2018 13 (10) e0204982 BACKGROUND: Tuberculosis (TB) patients with human immunodeficiency virus (HIV) co-infection have worse TB treatment outcomes compared to patients with TB alone. The distribution of unfavourable treatment outcomes differs by socio-demographic and clinical characteristics, allowing for early identification of patients at risk. OBJECTIVE: To develop a statistical model that can provide individual probabilities of unfavourable outcomes based on demographic and clinical characteristics of TB-HIV co-infected patients. METHODOLOGY: We used data from all TB patients with known HIV-positive test results (aged >/=15 years) registered for first-line anti-TB treatment (ATT) in 2015 under the Revised National TB Control Programme (RNTCP) in Delhi, India. We included variables on demographics and pre-treatment clinical characteristics routinely recorded and reported to RNTCP and the National AIDS Control Organization. Binomial logistic regression was used to develop a statistical model to estimate probabilities of unfavourable TB treatment outcomes (i.e., death, loss to follow-up, treatment failure, transfer out of program, and a switch to drug-resistant regimen). RESULTS: Of 55,260 TB patients registered for ATT in 2015 in Delhi, 928 (2%) had known HIV-positive test results. Of these, 816 (88%) had drug-sensitive TB and were >/=15 years. Among 816 TB-HIV patients included, 157 (19%) had unfavourable TB treatment outcomes. We developed a model for predicting unfavourable outcomes using age, sex, disease classification (pulmonary versus extra-pulmonary), TB treatment category (new or previously treated case), sputum smear grade, known HIV status at TB diagnosis, antiretroviral treatment at TB diagnosis, and CD4 cell count at ATT initiation. The chi-square p-value for model calibration assessed using the Hosmer-Lemeshow test was 0.15. The model discrimination, measured as the area under the receiver operator characteristic (ROC) curve, was 0.78. CONCLUSION: The model had good internal validity, but should be validated with an independent cohort of TB-HIV co-infected patients to assess its performance before clinical or programmatic use. |
Case-control meta-analysis of blood DNA methylation and autism spectrum disorder.
Andrews SV , Sheppard B , Windham GC , Schieve LA , Schendel DE , Croen LA , Chopra P , Alisch RS , Newschaffer CJ , Warren ST , Feinberg AP , Fallin MD , Ladd-Acosta C . Mol Autism 2018 9 40 ![]() Background: Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. Methods: DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. Findings: In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 x 10(- 7). Seven CpGs showed differences at p < 1 x 10(- 5) and 48 at 1 x 10(- 4). Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. Conclusions: No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD. |
Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease.
Shaw KA , Bertha M , Hofmekler T , Chopra P , Vatanen T , Srivatsa A , Prince J , Kumar A , Sauer C , Zwick ME , Satten GA , Kostic AD , Mulle JG , Xavier RJ , Kugathasan S . Genome Med 2016 8 (1) 75 ![]() ![]() BACKGROUND: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome. METHODS: We performed a prospective cohort study of 19 treatment-naive pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples. RESULTS: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status. CONCLUSIONS: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment. |
Missed opportunities along the prevention of mother-to-child transmission services cascade in South Africa: uptake, determinants, and attributable risk (the SAPMTCTE)
Woldesenbet S , Jackson D , Lombard C , Dinh TH , Puren A , Sherman G , Ramokolo V , Doherty T , Mogashoa M , Bhardwaj S , Chopra M , Shaffer N , Pillay Y , Goga A . PLoS One 2015 10 (7) e0132425 OBJECTIVES: We examined uptake of prevention of mother-to-child HIV transmission (PMTCT) services, predictors of missed opportunities, and infant HIV transmission attributable to missed opportunities along the PMTCT cascade across South Africa. METHODS: A cross-sectional survey was conducted among 4-8 week old infants receiving first immunisations in 580 nationally representative public health facilities in 2010. This included maternal interviews and testing infants' dried blood spots for HIV. A weighted analysis was performed to assess uptake of antenatal and perinatal PMTCT services along the PMTCT cascade (namely: maternal HIV testing, CD4 count test/result, and receiving maternal and infant antiretroviral treatment) and predictors of dropout. The population attributable fraction associated with dropouts at each service point are estimated. RESULTS: Of 9,803 mothers included, 31.7% were HIV-positive as identified by reactive infant antibody tests. Of these 80.4% received some form of maternal and infant antiretroviral treatment. More than a third (34.9%) of mothers dropped out from one or more steps in the PMTCT service cascade. In a multivariable analysis, the following characteristics were associated with increased dropout from the PMTCT cascade: adolescent (<20 years) mothers, low socioeconomic score, low education level, primiparous mothers, delayed first antenatal visit, homebirth, and non-disclosure of HIV status. Adolescent mothers were twice (adjusted odds ratio: 2.2, 95% confidence interval: 1.5-3.3) as likely to be unaware of their HIV-positive status and had a significantly higher rate (85.2%) of unplanned pregnancies compared to adults aged ≥20 years (55.5%, p = 0.0001). A third (33.8%) of infant HIV infections were attributable to dropout in one or more steps in the cascade. CONCLUSION: A third of transmissions attributable to missed opportunities of PMTCT services can be prevented by optimizing the uptake of PMTCT services. Identified risk factors for low PMTCT service uptake should be addressed through health facility and community-level interventions, including raising awareness, promoting women education, adolescent focused interventions, and strengthening linkages/referral-system between communities and health facilities. |
First population-level effectiveness evaluation of a national programme to prevent HIV transmission from mother to child, South Africa
Goga AE , Dinh TH , Jackson DJ , Lombard C , Delaney KP , Puren A , Sherman G , Woldesenbet S , Ramokolo V , Crowley S , Doherty T , Chopra M , Shaffer N , Pillay Y . J Epidemiol Community Health 2014 69 (3) 240-8 BACKGROUND: There is a paucity of data on the national population-level effectiveness of preventing mother-to-child transmission (PMTCT) programmes in high-HIV-prevalence, resource-limited settings. We assessed national PMTCT impact in South Africa (SA), 2010. METHODS: A facility-based survey was conducted using a stratified multistage, cluster sampling design. A nationally representative sample of 10 178 infants aged 4-8 weeks was recruited from 565 clinics. Data collection included caregiver interviews, record reviews and infant dried blood spots to identify HIV-exposed infants (HEI) and HIV-infected infants. During analysis, self-reported antiretroviral (ARV) use was categorised: 1a: triple ARV treatment; 1b: azidothymidine >10 weeks; 2a: azidothymidine ≤10 weeks; 2b: incomplete ARV prophylaxis; 3a: no antenatal ARV and 3b: missing ARV information. Findings were adjusted for non-response, survey design and weighted for live-birth distributions. RESULTS: Nationally, 32% of live infants were HEI; early mother-to-child transmission (MTCT) was 3.5% (95% CI 2.9% to 4.1%). In total 29.4% HEI were born to mothers on triple ARV treatment (category 1a) 55.6% on prophylaxis (1b, 2a, 2b), 9.5% received no antenatal ARV (3a) and 5.5% had missing ARV information (3b). Controlling for other factors groups, 1b and 2a had similar MTCT to 1a (Ref; adjusted OR (AOR) for 1b, 0.98, 0.52 to 1.83; and 2a, 1.31, 0.69 to 2.48). MTCT was higher in group 2b (AOR 3.68, 1.69 to 7.97). Within group 3a, early MTCT was highest among breastfeeding mothers 11.50% (4.67% to 18.33%) for exclusive breast feeding, 11.90% (7.45% to 16.35%) for mixed breast feeding, and 3.45% (0.53% to 6.35%) for no breast feeding). Antiretroviral therapy or >10 weeks prophylaxis negated this difference (MTCT 3.94%, 1.98% to 5.90%; 2.07%, 0.55% to 3.60% and 2.11%, 1.28% to 2.95%, respectively). CONCLUSIONS: SA, a high-HIV-prevalence middle income country achieved <5% MTCT by 4-8 weeks post partum. The long-term impact on PMTCT on HIV-free survival needs urgent assessment. |
Prevalence and risk factors associated with vancomycin-resistant Staphylococcus aureus precursor organism colonization among patients with chronic lower-extremity wounds in southeastern Michigan
Tosh PK , Agolory S , Strong BL , Verlee K , Finks J , Hayakawa K , Chopra T , Kaye KS , Gilpin N , Carpenter CF , Haque NZ , Lamarato LE , Zervos MJ , Albrecht VS , McAllister SK , Limbago B , MacCannell DR , McDougal LK , Kallen AJ , Guh AY . Infect Control Hosp Epidemiol 2013 34 (9) 954-60 ![]() BACKGROUND: Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Inc18-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer. OBJECTIVE: Identify the prevalence of VRSA precursor organisms. DESIGN: Prospective cohort with embedded case-control study. PARTICIPANTS: Southeastern Michigan adults with chronic lower-extremity wounds. METHODS: Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Inc18-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis). RESULTS: Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Inc18-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses. CONCLUSIONS: Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted. |
Age-associated DNA methylation in pediatric populations.
Alisch RS , Barwick BG , Chopra P , Myrick LK , Satten GA , Conneely KN , Warren ST . Genome Res 2012 22 (4) 623-32 ![]() DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis, monozygotic twins show indistinguishable childhood methylation, suggesting that DNAm is highly coordinated throughout early development. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from a cross-sectional study of 398 boys, aged 3-17 yr, and find significant age-associated changes in DNAm at 2078 loci. These findings correspond well with pyrosequencing data and replicate in a second pediatric population (N = 78). Moreover, we report a deficit of age-related loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. Meta-analysis (N = 1158) with two adult populations reveals that despite a significant overlap of age-associated loci, most methylation changes do not follow a lifelong linear pattern due to a threefold to fourfold higher rate of change in children compared with adults; consequently, the vast majority of changes are more accurately modeled as a function of logarithmic age. We therefore conclude that age-related DNAm changes in peripheral blood occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies should be matched closely for age. |
Setting research priorities to reduce global mortality from childhood pneumonia by 2015
Rudan I , El Arifeen S , Bhutta ZA , Black RE , Brooks A , Chan KY , Chopra M , Duke T , Marsh D , Pio A , Simoes EA , Tamburlini G , Theodoratou E , Weber MW , Whitney CG , Campbell H , Qazi SA . PLoS Med 2011 8 (9) e1001099 Igor Rudan and colleagues report the results of their consensus building exercise that identified health research priorities to help reduce child mortality from pneumonia. |
The associations of voluntary counseling and testing acceptance and the perceived likelihood of being HIV-infected among men with multiple sex partners in a South African township
Johnston L , O'Bra H , Chopra M , Mathews C , Townsend L , Sabin K , Tomlinson M , Kendall C . AIDS Behav 2010 14 (4) 922-31 This paper examines the socio-demographic factors and sexual risk behaviors (condom use, number of sexual partners, STI symptoms) associated with voluntary counselling and testing (VCT) acceptance and self-perceived risk of being HIV-infected among black men with multiple and younger sex partners in a South African township outside of Cape Town. Using respondent driven sampling, we interviewed 421 men, of whom 409 (97.3%) consented to provide a dried blood spot, 12.3% were HIVinfected (95% confidence intervals [CI.] 8.3, 16.9) and 47.2% (CI. 41.1, 53.6) accepted on site VCT. Twenty six percent (CI. 20.2, 30.7) reported having an HIV test in the past year. Few men perceived themselves as very likely to be infected with HIV (15.6%; CI. 10.4, 20.5). VCT acceptance was significantly associated with being older, married or living with a partner, having higher education, having four to six partners in the past three months and testing HIV positive. Self-perceived likelihood of being HIV infected was significantly associated with low condom use and having seven or more partners in the past three months, and testing HIV positive. These findings indicate that men correctly understand that engaging in certain HIV risk behaviors increases the likelihood of HIV-infection. However, those who perceive themselves at high risk of having HIV do not seek testing. Further investigation into the psychological and cultural barriers to reducing risky sexual behaviors and accessing VCT and other HIV services is recommended. |
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