This deliverable outlines the structure and tools planned to get incorporated in the ConcePTION e... more This deliverable outlines the structure and tools planned to get incorporated in the ConcePTION ecosystem to efficiently, robustly, and transparently generate evidence from a wide variety of data sources.
The goal of this deliverable is to describe the creation of the ConcePTION common data model (CDM... more The goal of this deliverable is to describe the creation of the ConcePTION common data model (CDM) for secondary re-use of electronic health care and surveillance data that will be used for demonstration studies in work package 1 (WP1). In addition, it will outline the current approaches and status for WP2.
IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV... more IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression whil...
This document contains the definition of <strong>Single Organ Cutaneous Vasculitis </str... more This document contains the definition of <strong>Single Organ Cutaneous Vasculitis </strong>and the operationalization to extract this event from different electronic health care databases in the EU, to calculate background rates of AESI The document contains the key definition, procedures and treatments, the diagnosis codes based on Codemapper output with changes/additions by data access providers, and when available published validation studies and background rates
Using existing data-sources for assessment of vaccine safety: a focus on methods Vaccines as a pu... more Using existing data-sources for assessment of vaccine safety: a focus on methods Vaccines as a public health intervention Vaccination is widely accepted as one of the foremost public health achievements of the last century, with the United States Centers for Disease Control reporting in 2014 that vaccines have prevented 322 million illnesses, 21 million hospitalizations, and 732,000 deaths over the lifespan of children born between 1984 and 2014 (1). Vaccines confer this degree of protection only when a large enough proportion of the population is vaccinated to produce herd immunity, or protection of the unvaccinated by the vaccinated (2). Because vaccines serve as a primary prevention measure, they are principally administered to healthy individuals. This means that public expectations for measurement of the safety and effectiveness of vaccines may be more stringent in terms of timeliness and accuracy than those for drugs which treat illness. The vaccine product life cycle Vaccines are rigorously tested for safety and effectiveness in clinical trials before receiving market authorization (3). Because clinical trials are limited in size and scope, however, adverse events and unexpected benefits may go undetected in trials and arise only when the vaccine is administered to large populations. Chen et al, in their paper describing the then newly-initiated Vaccine Adverse Events Reporting System (VAERS), displayed the cycle of vaccine confidence in an often-cited figure (figure 1). The figure displays how increasing vaccination coverage is paired with decreasing incidence of the vaccine-preventable disease but also potentially with increasing reports of vaccine-associated (either causally or temporally) adverse events. This increased reporting of adverse events following vaccination can lead to decreased confidence in the vaccine and associated decreases in coverage and effectiveness. The Vaccine Confidence Project, led by the London School of Hygiene and Tropical Health, has found that concern about vaccine safety is the primary cause of vaccine hesitancy in Europe (4). It is of utmost importance to public health that any adverse reactions or deficiencies in efficacy are detected and addressed quickly and accurately in order to maintain public confidence in vaccines(5). The phases of vaccine development, pharmacovigilance, and communication can be described using figure 1. Period one (Prevaccine) represents all phases of development and testing prior to market authorization of a vaccine while period two (Increasing Coverage) represents post-authorization vaccination of targeted populations. I focus in this thesis on time periods three (Loss of Confidence) and four (Resumption of Confidence) during which safety signals may be detected and verified, additional hypotheses regarding safety and efficacy may be tested, public health implications are assessed, and scientists, public health agencies, and healthcare providers communicate with the public about the benefits and risks of vaccines. Period five (Eradication), or complete elimination of the vaccine preventable disease, will not be addressed in this thesis.
The continued success of the global vaccination effort relies upon both the use of safe vaccines ... more The continued success of the global vaccination effort relies upon both the use of safe vaccines and public confidence in their benefit and safety In recent years, there have been examples of dramatic falls in the gains made in vaccine coverage and disease prevention in both the developed world and in low and middle-income countries, where scares have resulted in loss of public confidence While vaccine hesitancy and antivaccine communication has become global, the ability to respond to such concerns has remained largely fractured without coordination between countries Isolated collaborations that have included multiple countries for active surveillance using pooled data have generated information on measles-containing vaccines and aseptic meningitis and idiopathic thrombocytopenic purpura, rotavirus vaccines and intussusception as well as pandemic influenza vaccine and Guillain-Barre syndrome and narcolepsy Sustainable infrastructure and capacity building are needed for both timely hypothesis testing and to assess new vaccines such as Ebola, dengue, malaria and typhoid introduced particularly into LMICs A proposal to utilize this infrastructure to evaluate the association with GBS with vaccination including an evaluation of potential genetic risk factors has been submitted for funding to NIH In addition, in February 2020, the network has begun discussions as to how the network can address the need for a global comparative study of COVID-19 vaccines when these vaccines become available In conclusion, capacity currently exists globally to assess vaccine safety across a network of geographically diverse sites Developing this capacity further will be critical to the assessment of COVID-19 vaccines and other newly introduced vaccines in the future
Background HIV is associated with an increased risk of cardiovascular disease ( CVD ) in high‐inc... more Background HIV is associated with an increased risk of cardiovascular disease ( CVD ) in high‐income countries. Little is known about the CVD burden in sub‐Saharan Africa, where 70% of the world's HIV ‐positive population lives. This study aims to provide insight into the burden of CVD risk in a rural setting in sub‐Saharan Africa considering HIV infection and antiretroviral therapy ( ART ). Methods and Results A cross‐sectional analysis was conducted of the baseline of the Ndlovu Cohort study including HIV ‐negative and HIV ‐positive participants in rural South Africa between 2014 and 2017. Information was collected on demographics, socioeconomic status, and CVD risk factors. Carotid intima‐media thickness measurement was performed. The influence of HIV and ART on the burden of CVD was determined by comparing HIV ‐positive participants who were ART naive on first‐line or second‐line ART with HIV ‐negative participants. In total, 1927 participants were included, of whom 887 (46%...
Background: Recommendations on timing for introduction of allergenic foods in an infant diet have... more Background: Recommendations on timing for introduction of allergenic foods in an infant diet have changed twice during the past decade. How families with different demographic characteristics implement the change has not been studied in the United States. Objective: To compare the age of introduction of allergenic foods between an urban Medicaid-based population and a suburban private insuranceebased population in Cincinnati, Ohio. Methods: Two hundred parent surveys were distributed at well-child checkups between 4 and 36 months of age. Data were analyzed using distribution mapping to determine the difference in the age of introduction of infant formula, infant solids, whole cow's milk, eggs, peanut, and fish. Random forest analysis was used to determine the most important factors affecting the age of introduction for both populations. Results: There was no statistically significant difference in the age of infant solid introduction, but urban populations introduced allergenic foods earlier than suburban populations, with a statistically significant difference in the age of introduction of infant formula, whole cow's milk, eggs, peanut, and fish. The most important factor for the timing of all food introductions was the recommended age of introduction from health care professionals. Conclusions: There is a difference between urban and suburban populations in the timing of introduction of allergenic foods but not in other infant solid foods. The reliance on physician recommendation for both populations supports the need for education and guidance to health care professionals on up-to-date guidance and recommendations.
Objectives: Nephrotoxin exposure is a common cause of acute kidney injury (AKI) in hospitalized c... more Objectives: Nephrotoxin exposure is a common cause of acute kidney injury (AKI) in hospitalized children. AKI detection relies on regular serum creatinine (SCr) screening among exposed patients. We sought to determine how well administrative data identify hospitalized noncritically ill children with nephrotoxic medication-associated AKI in the contexts of incomplete and complete screening. Methods: We conducted a single-center retrospective cohort study among noncritically ill hospitalized children. We compared administrative data sensitivity to that among a separate cohort for whom adequate screening was defined as daily SCr measurement. For the original cohort, nephrotoxin exposure was defined as exposure to ≥3 nephrotoxins at once or ≥3 days of aminoglycoside therapy. AKI was defined by the change in SCr (pediatric-modified Risk Injury Failure Loss End-Stage Renal Disease [pRIFLE] criteria) or discharge code. Adequate SCr screening was defined as 2 measurements obtained ≤96 hours...
Children's diseases can negatively impact marital adjustment and contribute to poorer child healt... more Children's diseases can negatively impact marital adjustment and contribute to poorer child health outcomes. To cope with increased marital stress and childhood diseases severity, many people turn to spirituality. While most studies show a positive relationship between spirituality and marital adjustment, spirituality has typically been measured only in terms of individual behaviors. Using the Dyadic Adjustment Scale (DAS) and Daily Phone Diary data from a sample of 126 parents of children with cystic fibrosis as a context for increased marital stress, spiritual behavior of mother-father dyads and of whole families were used as predictors of marital adjustment. Frequency and duration of individual, dyadic and familial spiritual activities correlated positively with dyadic adjustment. Significant differences in spiritual activities existed between couples with marital adjustment scores above and below the cutoff for distress. The only significant factors in regressions of spiritual activities on marital adjustment scores were number of pulmonary exacerbations and parent age. Higher odds of maintaining a marital adjustment score greater than 100 were significantly associated with spending approximately twelve minutes per day in individual, but not conjugal or familial, spiritual activities. The Daily Phone
Paediatrics and international child health, Jan 21, 2014
Background: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood dea... more Background: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood deaths in most developing countries, including Nigeria. Vitamin D is associated with innate immunity and may play a role in the control of infections. Case-control studies, including a small study from Nigeria, show inconsistent results for the association between vitamin D status and risk of ALRTI. Aims: To examine the relationship between vitamin D status and hospitalization for ALRTI in Nigerian children. Methods: Fifty children aged 2-60 months hospitalised with ALRTI were studied prospectively. ALRTI was diagnosed on the basis of modified WHO criteria. Each patient was matched with controls for age and gender. The controls were enrolled either from children attending well-child clinics or general clinics without evidence of respiratory infection or admitted to the hospital for elective surgery. A structured questionnaire collected data on demography, health, diet, duration of exposure ...
Purpose The assumption that the occurrence of outcome event must not alter subsequent exposure pr... more Purpose The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated. Methods Using the 2009 H1N1 and seasonal influenza vaccines and Guillain-Barré syndrome as a model, we simulated a scenario in which an individual may encounter multiple unordered exposures and each exposure may be contraindicated by the occurrence of outcome event. The degree of contraindication was varied at 0%, 50%, and 100%. The first alternative approach used only cases occurring after exposure with follow-up time starting from exposure. The second used a pseudo-likelihood method. Results When the event-independent exposure assumption was satisfied, the standard SCCS approach produced nearly unbiased relative incidence estimates. When this assumption was partially or completely violated, two alternative SCCS approaches could be used. While the postexposure cases only approach could handle only one exposure, the pseudo-likelihood approach was able to correct bias for both exposures. Conclusions Violation of the event-independent exposure assumption leads to an overestimation of relative incidence which could be corrected by alternative SCCS approaches. In multiple exposure situations, the pseudo-likelihood approach is optimal; the post-exposure cases only approach is limited in handling a second exposure and may introduce additional bias, thus should be used with caution. Copyright
The Journal of Clinical Endocrinology & Metabolism, 2013
Background: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of v... more Background: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial. Objective: The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a randomized controlled trial in population in which vD deficiency is endemic. Design/Methods: Arab women were randomized at 12-16 weeks of gestation to 400, 2000, and 4000 IU/d vD3, which were continued to delivery. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during pregnancy and at delivery. The primary outcome was the maternal and cord blood 25(OH)D, and the secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL or greater (Ն80 nmol/L) at delivery. Setting: The locations were primary care and tertiary perinatal care centers. Results: Of 192 enrolled, 162 (84%) continued to delivery. Mean serum 25(OH)D of 8.2 ng/mL (20.5 nmol/L) at enrollment was low. Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group (P Ͻ .001) and was highest in the 4000 IU/d group. The percent who achieved 25(OH)D greater than 32 ng/mL and greater than 20 ng/mL concentrations in mothers and infants was highest in 4000 IU/d group. Safety measurements were similar by group and no adverse event related to vD supplementation. Conclusions: Vitamin D supplementation of 2000 and 4000 IU/d appeared safe in pregnancy, and 4000 IU/d was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants. These findings could apply to other populations in which vD deficiency is endemic.
RATIONALE: Without evidence to delay the introduction of allergenic foods for primary prevention ... more RATIONALE: Without evidence to delay the introduction of allergenic foods for primary prevention of atopic disease there have been no global recommendations for allergenic food introduction. We aimed to compare the age of introduction of allergenic foods in two populations: an urban Medicaid-based population and a suburban private insurance-based population in Cincinnati, Ohio. Our hypothesis was that the urban population introduces allergenic foods earlier than the suburban population. METHODS: Two hundred parent surveys were distributed at well child checks between 4-36 months of age. Data was analyzed using distribution mapping to determine the difference in the age of introduction of infant formula, infant solids, whole milk, eggs, peanut butter and fish between the two populations. Random forest analysis was used to determine the most important factors impacting the age of introduction for both populations. RESULTS: Urban populations introduce allergenic foods earlier than suburban populations with a statistically significant difference in the age of introduction of infant formula, whole milk, peanut butter and fish. There is no statistically significant difference in infant solid introduction which is widely accepted to be introduced between four and six months. The most important factor for all food introductions was the recommended age of introduction from health care providers. CONCLUSIONS: We conclude that urban populations introduce allergenic foods earlier than suburban populations with the exception of infant solid foods. Interestingly, the most important factor for age of introduction for both populations is physician recommendation, which without clear national guidelines has been left to individual physician discretion.
In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project-Building an ecos... more In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project-Building an ecosystem for better monitoring and communicating safety of medicines use in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation-with the vision that there is a societal obligation to rapidly reduce uncertainty about the safety of medication use in pregnancy and breastfeeding. The present paper introduces the set of concepts used to describe the European data sources involved in the ConcePTION project and illustrates the ConcePTION Common Data Model (CDM), which serves as the keystone of the federated ConcePTION network. Based on data availability and content analysis of 21 European data sources, the ConcePTION CDM has been structured with six tables designed to capture data from routine healthcare, three tables for data from public health surveillance activities, three curated tables for derived data on population (e.g., observation time and motherchild linkage), plus four metadata tables. By its first anniversary, the ConcePTION CDM has enabled 13 data sources to run common scripts to contribute to major European projects, demonstrating its capacity to facilitate effective and transparent deployment of distributed analytics, and its potential to address questions about utilization, effectiveness, and safety of medicines in special populations, including during pregnancy and breastfeeding, and, more broadly, in the general population.
Supplemental Digital Content is available in the text. Background: The Brighton Collaboration Glo... more Supplemental Digital Content is available in the text. Background: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. Methods: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. Results: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. Conclusions: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.
While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do ... more While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do not include enough subjects to detect rare adverse events, and they generally exclude special populations such as pregnant women. It is therefore necessary to conduct postmarketing vaccine safety assessments using observational data sources. The study of rare events has been enabled in through large linked databases and distributed data networks, in combination with development of case-centred methods. Distributed data networks necessitate common protocols, definitions, data models and analytics and the processes of developing and employing these tools are rapidly evolving. Assessment of vaccine safety in pregnancy is complicated by physiological changes, the challenges of mother-child linkage and the need for long-term infant follow-up. Potential sources of bias including differential access to and utilisation of antenatal care, immortal time bias, seasonal timing of pregnancy and unmea...
This deliverable outlines the structure and tools planned to get incorporated in the ConcePTION e... more This deliverable outlines the structure and tools planned to get incorporated in the ConcePTION ecosystem to efficiently, robustly, and transparently generate evidence from a wide variety of data sources.
The goal of this deliverable is to describe the creation of the ConcePTION common data model (CDM... more The goal of this deliverable is to describe the creation of the ConcePTION common data model (CDM) for secondary re-use of electronic health care and surveillance data that will be used for demonstration studies in work package 1 (WP1). In addition, it will outline the current approaches and status for WP2.
IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV... more IntroductionInsight into inflammation patterns is needed to understand the pathophysiology of HIV and related cardiovascular disease (CVD). We assessed patterns of inflammation related to HIV infection and CVD risk assessed with carotid intima media thickness (CIMT).MethodsA cross-sectional study was performed in Johannesburg, South Africa, including participants with HIV who were virally suppressed on anti-retroviral therapy (ART) as well as HIV-negative participants who were family members or friends to the HIV-positive participants. Information was collected on CVD risk factors and CIMT. Inflammation was measured with the Olink panel ‘inflammation’, allowing to simultaneously assess 92 inflammation markers. Differences in inflammation patterns between HIV-positive and HIV-negative participants were explored using a principal component analysis (PCA) and ANCOVA. The impact of differentiating immune markers, as identified by ANCOVA, on CIMT was assessed using linear regression whil...
This document contains the definition of <strong>Single Organ Cutaneous Vasculitis </str... more This document contains the definition of <strong>Single Organ Cutaneous Vasculitis </strong>and the operationalization to extract this event from different electronic health care databases in the EU, to calculate background rates of AESI The document contains the key definition, procedures and treatments, the diagnosis codes based on Codemapper output with changes/additions by data access providers, and when available published validation studies and background rates
Using existing data-sources for assessment of vaccine safety: a focus on methods Vaccines as a pu... more Using existing data-sources for assessment of vaccine safety: a focus on methods Vaccines as a public health intervention Vaccination is widely accepted as one of the foremost public health achievements of the last century, with the United States Centers for Disease Control reporting in 2014 that vaccines have prevented 322 million illnesses, 21 million hospitalizations, and 732,000 deaths over the lifespan of children born between 1984 and 2014 (1). Vaccines confer this degree of protection only when a large enough proportion of the population is vaccinated to produce herd immunity, or protection of the unvaccinated by the vaccinated (2). Because vaccines serve as a primary prevention measure, they are principally administered to healthy individuals. This means that public expectations for measurement of the safety and effectiveness of vaccines may be more stringent in terms of timeliness and accuracy than those for drugs which treat illness. The vaccine product life cycle Vaccines are rigorously tested for safety and effectiveness in clinical trials before receiving market authorization (3). Because clinical trials are limited in size and scope, however, adverse events and unexpected benefits may go undetected in trials and arise only when the vaccine is administered to large populations. Chen et al, in their paper describing the then newly-initiated Vaccine Adverse Events Reporting System (VAERS), displayed the cycle of vaccine confidence in an often-cited figure (figure 1). The figure displays how increasing vaccination coverage is paired with decreasing incidence of the vaccine-preventable disease but also potentially with increasing reports of vaccine-associated (either causally or temporally) adverse events. This increased reporting of adverse events following vaccination can lead to decreased confidence in the vaccine and associated decreases in coverage and effectiveness. The Vaccine Confidence Project, led by the London School of Hygiene and Tropical Health, has found that concern about vaccine safety is the primary cause of vaccine hesitancy in Europe (4). It is of utmost importance to public health that any adverse reactions or deficiencies in efficacy are detected and addressed quickly and accurately in order to maintain public confidence in vaccines(5). The phases of vaccine development, pharmacovigilance, and communication can be described using figure 1. Period one (Prevaccine) represents all phases of development and testing prior to market authorization of a vaccine while period two (Increasing Coverage) represents post-authorization vaccination of targeted populations. I focus in this thesis on time periods three (Loss of Confidence) and four (Resumption of Confidence) during which safety signals may be detected and verified, additional hypotheses regarding safety and efficacy may be tested, public health implications are assessed, and scientists, public health agencies, and healthcare providers communicate with the public about the benefits and risks of vaccines. Period five (Eradication), or complete elimination of the vaccine preventable disease, will not be addressed in this thesis.
The continued success of the global vaccination effort relies upon both the use of safe vaccines ... more The continued success of the global vaccination effort relies upon both the use of safe vaccines and public confidence in their benefit and safety In recent years, there have been examples of dramatic falls in the gains made in vaccine coverage and disease prevention in both the developed world and in low and middle-income countries, where scares have resulted in loss of public confidence While vaccine hesitancy and antivaccine communication has become global, the ability to respond to such concerns has remained largely fractured without coordination between countries Isolated collaborations that have included multiple countries for active surveillance using pooled data have generated information on measles-containing vaccines and aseptic meningitis and idiopathic thrombocytopenic purpura, rotavirus vaccines and intussusception as well as pandemic influenza vaccine and Guillain-Barre syndrome and narcolepsy Sustainable infrastructure and capacity building are needed for both timely hypothesis testing and to assess new vaccines such as Ebola, dengue, malaria and typhoid introduced particularly into LMICs A proposal to utilize this infrastructure to evaluate the association with GBS with vaccination including an evaluation of potential genetic risk factors has been submitted for funding to NIH In addition, in February 2020, the network has begun discussions as to how the network can address the need for a global comparative study of COVID-19 vaccines when these vaccines become available In conclusion, capacity currently exists globally to assess vaccine safety across a network of geographically diverse sites Developing this capacity further will be critical to the assessment of COVID-19 vaccines and other newly introduced vaccines in the future
Background HIV is associated with an increased risk of cardiovascular disease ( CVD ) in high‐inc... more Background HIV is associated with an increased risk of cardiovascular disease ( CVD ) in high‐income countries. Little is known about the CVD burden in sub‐Saharan Africa, where 70% of the world's HIV ‐positive population lives. This study aims to provide insight into the burden of CVD risk in a rural setting in sub‐Saharan Africa considering HIV infection and antiretroviral therapy ( ART ). Methods and Results A cross‐sectional analysis was conducted of the baseline of the Ndlovu Cohort study including HIV ‐negative and HIV ‐positive participants in rural South Africa between 2014 and 2017. Information was collected on demographics, socioeconomic status, and CVD risk factors. Carotid intima‐media thickness measurement was performed. The influence of HIV and ART on the burden of CVD was determined by comparing HIV ‐positive participants who were ART naive on first‐line or second‐line ART with HIV ‐negative participants. In total, 1927 participants were included, of whom 887 (46%...
Background: Recommendations on timing for introduction of allergenic foods in an infant diet have... more Background: Recommendations on timing for introduction of allergenic foods in an infant diet have changed twice during the past decade. How families with different demographic characteristics implement the change has not been studied in the United States. Objective: To compare the age of introduction of allergenic foods between an urban Medicaid-based population and a suburban private insuranceebased population in Cincinnati, Ohio. Methods: Two hundred parent surveys were distributed at well-child checkups between 4 and 36 months of age. Data were analyzed using distribution mapping to determine the difference in the age of introduction of infant formula, infant solids, whole cow's milk, eggs, peanut, and fish. Random forest analysis was used to determine the most important factors affecting the age of introduction for both populations. Results: There was no statistically significant difference in the age of infant solid introduction, but urban populations introduced allergenic foods earlier than suburban populations, with a statistically significant difference in the age of introduction of infant formula, whole cow's milk, eggs, peanut, and fish. The most important factor for the timing of all food introductions was the recommended age of introduction from health care professionals. Conclusions: There is a difference between urban and suburban populations in the timing of introduction of allergenic foods but not in other infant solid foods. The reliance on physician recommendation for both populations supports the need for education and guidance to health care professionals on up-to-date guidance and recommendations.
Objectives: Nephrotoxin exposure is a common cause of acute kidney injury (AKI) in hospitalized c... more Objectives: Nephrotoxin exposure is a common cause of acute kidney injury (AKI) in hospitalized children. AKI detection relies on regular serum creatinine (SCr) screening among exposed patients. We sought to determine how well administrative data identify hospitalized noncritically ill children with nephrotoxic medication-associated AKI in the contexts of incomplete and complete screening. Methods: We conducted a single-center retrospective cohort study among noncritically ill hospitalized children. We compared administrative data sensitivity to that among a separate cohort for whom adequate screening was defined as daily SCr measurement. For the original cohort, nephrotoxin exposure was defined as exposure to ≥3 nephrotoxins at once or ≥3 days of aminoglycoside therapy. AKI was defined by the change in SCr (pediatric-modified Risk Injury Failure Loss End-Stage Renal Disease [pRIFLE] criteria) or discharge code. Adequate SCr screening was defined as 2 measurements obtained ≤96 hours...
Children's diseases can negatively impact marital adjustment and contribute to poorer child healt... more Children's diseases can negatively impact marital adjustment and contribute to poorer child health outcomes. To cope with increased marital stress and childhood diseases severity, many people turn to spirituality. While most studies show a positive relationship between spirituality and marital adjustment, spirituality has typically been measured only in terms of individual behaviors. Using the Dyadic Adjustment Scale (DAS) and Daily Phone Diary data from a sample of 126 parents of children with cystic fibrosis as a context for increased marital stress, spiritual behavior of mother-father dyads and of whole families were used as predictors of marital adjustment. Frequency and duration of individual, dyadic and familial spiritual activities correlated positively with dyadic adjustment. Significant differences in spiritual activities existed between couples with marital adjustment scores above and below the cutoff for distress. The only significant factors in regressions of spiritual activities on marital adjustment scores were number of pulmonary exacerbations and parent age. Higher odds of maintaining a marital adjustment score greater than 100 were significantly associated with spending approximately twelve minutes per day in individual, but not conjugal or familial, spiritual activities. The Daily Phone
Paediatrics and international child health, Jan 21, 2014
Background: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood dea... more Background: Acute lower respiratory tract infection (ALRTI) is the leading cause of childhood deaths in most developing countries, including Nigeria. Vitamin D is associated with innate immunity and may play a role in the control of infections. Case-control studies, including a small study from Nigeria, show inconsistent results for the association between vitamin D status and risk of ALRTI. Aims: To examine the relationship between vitamin D status and hospitalization for ALRTI in Nigerian children. Methods: Fifty children aged 2-60 months hospitalised with ALRTI were studied prospectively. ALRTI was diagnosed on the basis of modified WHO criteria. Each patient was matched with controls for age and gender. The controls were enrolled either from children attending well-child clinics or general clinics without evidence of respiratory infection or admitted to the hospital for elective surgery. A structured questionnaire collected data on demography, health, diet, duration of exposure ...
Purpose The assumption that the occurrence of outcome event must not alter subsequent exposure pr... more Purpose The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated. Methods Using the 2009 H1N1 and seasonal influenza vaccines and Guillain-Barré syndrome as a model, we simulated a scenario in which an individual may encounter multiple unordered exposures and each exposure may be contraindicated by the occurrence of outcome event. The degree of contraindication was varied at 0%, 50%, and 100%. The first alternative approach used only cases occurring after exposure with follow-up time starting from exposure. The second used a pseudo-likelihood method. Results When the event-independent exposure assumption was satisfied, the standard SCCS approach produced nearly unbiased relative incidence estimates. When this assumption was partially or completely violated, two alternative SCCS approaches could be used. While the postexposure cases only approach could handle only one exposure, the pseudo-likelihood approach was able to correct bias for both exposures. Conclusions Violation of the event-independent exposure assumption leads to an overestimation of relative incidence which could be corrected by alternative SCCS approaches. In multiple exposure situations, the pseudo-likelihood approach is optimal; the post-exposure cases only approach is limited in handling a second exposure and may introduce additional bias, thus should be used with caution. Copyright
The Journal of Clinical Endocrinology & Metabolism, 2013
Background: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of v... more Background: Vitamin D (vD) deficiency in pregnancy is a global health problem and the amount of vD supplementation to prevent vD deficiency is controversial. Objective: The objective of the study was to determine effectiveness and safety of prenatal 2000 IU and 4000 IU/d compared with 400 IU/d vD3 supplementation in a randomized controlled trial in population in which vD deficiency is endemic. Design/Methods: Arab women were randomized at 12-16 weeks of gestation to 400, 2000, and 4000 IU/d vD3, which were continued to delivery. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured during pregnancy and at delivery. The primary outcome was the maternal and cord blood 25(OH)D, and the secondary outcomes were the achievement of sufficient serum 25(OH)D of 32 ng/mL or greater (Ն80 nmol/L) at delivery. Setting: The locations were primary care and tertiary perinatal care centers. Results: Of 192 enrolled, 162 (84%) continued to delivery. Mean serum 25(OH)D of 8.2 ng/mL (20.5 nmol/L) at enrollment was low. Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU than the 400 IU/d group (P Ͻ .001) and was highest in the 4000 IU/d group. The percent who achieved 25(OH)D greater than 32 ng/mL and greater than 20 ng/mL concentrations in mothers and infants was highest in 4000 IU/d group. Safety measurements were similar by group and no adverse event related to vD supplementation. Conclusions: Vitamin D supplementation of 2000 and 4000 IU/d appeared safe in pregnancy, and 4000 IU/d was most effective in optimizing serum 25(OH)D concentrations in mothers and their infants. These findings could apply to other populations in which vD deficiency is endemic.
RATIONALE: Without evidence to delay the introduction of allergenic foods for primary prevention ... more RATIONALE: Without evidence to delay the introduction of allergenic foods for primary prevention of atopic disease there have been no global recommendations for allergenic food introduction. We aimed to compare the age of introduction of allergenic foods in two populations: an urban Medicaid-based population and a suburban private insurance-based population in Cincinnati, Ohio. Our hypothesis was that the urban population introduces allergenic foods earlier than the suburban population. METHODS: Two hundred parent surveys were distributed at well child checks between 4-36 months of age. Data was analyzed using distribution mapping to determine the difference in the age of introduction of infant formula, infant solids, whole milk, eggs, peanut butter and fish between the two populations. Random forest analysis was used to determine the most important factors impacting the age of introduction for both populations. RESULTS: Urban populations introduce allergenic foods earlier than suburban populations with a statistically significant difference in the age of introduction of infant formula, whole milk, peanut butter and fish. There is no statistically significant difference in infant solid introduction which is widely accepted to be introduced between four and six months. The most important factor for all food introductions was the recommended age of introduction from health care providers. CONCLUSIONS: We conclude that urban populations introduce allergenic foods earlier than suburban populations with the exception of infant solid foods. Interestingly, the most important factor for age of introduction for both populations is physician recommendation, which without clear national guidelines has been left to individual physician discretion.
In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project-Building an ecos... more In 2019, the Innovative Medicines Initiative (IMI) funded the ConcePTION project-Building an ecosystem for better monitoring and communicating safety of medicines use in pregnancy and breastfeeding: validated and regulatory endorsed workflows for fast, optimised evidence generation-with the vision that there is a societal obligation to rapidly reduce uncertainty about the safety of medication use in pregnancy and breastfeeding. The present paper introduces the set of concepts used to describe the European data sources involved in the ConcePTION project and illustrates the ConcePTION Common Data Model (CDM), which serves as the keystone of the federated ConcePTION network. Based on data availability and content analysis of 21 European data sources, the ConcePTION CDM has been structured with six tables designed to capture data from routine healthcare, three tables for data from public health surveillance activities, three curated tables for derived data on population (e.g., observation time and motherchild linkage), plus four metadata tables. By its first anniversary, the ConcePTION CDM has enabled 13 data sources to run common scripts to contribute to major European projects, demonstrating its capacity to facilitate effective and transparent deployment of distributed analytics, and its potential to address questions about utilization, effectiveness, and safety of medicines in special populations, including during pregnancy and breastfeeding, and, more broadly, in the general population.
Supplemental Digital Content is available in the text. Background: The Brighton Collaboration Glo... more Supplemental Digital Content is available in the text. Background: The Brighton Collaboration Global Alignment of Immunization Safety in Pregnancy (GAIA) project developed case definitions for the assessment of adverse events in mothers and infants following maternal immunization. This study evaluated the applicability of these definitions to data collected in routine clinical care and research trial records across 7 sites in high-resource settings. Methods: Data collection forms were designed and used to retrospectively abstract the key elements of the GAIA definitions from records for 5 neonatal and 5 maternal outcomes, as well as gestational age. Level of diagnostic certainty was assessed by the data abstractor and an independent clinician, and then verified by Automated Brighton Case logic. The ability to assign a level of diagnostic certainty for each outcome and the positive predictive value (PPV) for their respective ICD-10 codes were evaluated. Results: Data from 1248 case records were abstracted: 624 neonatal and 622 maternal. Neonatal outcomes were most likely to be assessable and assigned by the level of diagnostic certainty. PPV for preterm birth, low birth weight, small for gestational age and respiratory distress were all above 75%. Maternal outcomes for preeclampsia and fetal growth restriction showed PPV over 80%. However, microcephaly (neonatal outcome) and dysfunctional labor (maternal outcome) were often nonassessable, with low PPVs. Conclusions: The applicability of GAIA case definitions to retrospectively ascertain and classify maternal and neonatal outcomes was variable among sites in high-resource settings. The implementation of the case definitions is largely dependent on the type and quality of documentation in clinical and research records in both high- and low-resource settings. While designed for use in the prospective evaluation of maternal vaccine safety, the GAIA case definitions would likely need to be specifically adapted for observational studies using alternative sources of data, linking various data sources and allowing flexibility in the ascertainment of the elements and levels of certainty of the case definition.
While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do ... more While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do not include enough subjects to detect rare adverse events, and they generally exclude special populations such as pregnant women. It is therefore necessary to conduct postmarketing vaccine safety assessments using observational data sources. The study of rare events has been enabled in through large linked databases and distributed data networks, in combination with development of case-centred methods. Distributed data networks necessitate common protocols, definitions, data models and analytics and the processes of developing and employing these tools are rapidly evolving. Assessment of vaccine safety in pregnancy is complicated by physiological changes, the challenges of mother-child linkage and the need for long-term infant follow-up. Potential sources of bias including differential access to and utilisation of antenatal care, immortal time bias, seasonal timing of pregnancy and unmea...
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Papers by Caitlin Dodd