Christophe Gerard Lambert

University of New Mexico | UNM · Center for Global Health

Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene ( CSF2 ) encodes granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor that mediates host immune responses. Since the eff...

Background Plasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb) < 5.0g/dL] is the most common clinical manifestation of severe malaria in such regions. Although innate immune response genes are known to influence the development of SMA,...

Birth defects are functional and structural abnormalities that impact 1 in 33 births in the United States. Birth defects have been attributed to genetic as well as other factors, but for most birth defects there are no known causes. Small molecule drugs, cosmetics, foods, and environmental pollutants may cause birth defects when the mother is expos...

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(S...

Epidemiological data across the United States show health disparities in COVID-19 infection, hospitalization, and mortality by race/ethnicity. While the association between elevated SARS-CoV-2 viral loads (VLs) (i.e. upper respiratory tract (URT) and peripheral blood (PB)) and increased COVID-19 severity has been reported, data remain largely unava...

Plasmodium falciparum (Pf) malaria is among the leading causes of childhood morbidity and mortality worldwide. During a natural infection, ingestion of the malarial parasite product, hemozoin (PfHz), by circulating phagocytic cells induces dysregulation in innate immunity and enhances malaria pathogenesis. Treatment of cultured peripheral blood mon...

Many patients with bipolar disorder (BD) are initially misdiagnosed with major depressive disorder (MDD) and are treated with antidepressants, whose potential iatrogenic effects are widely discussed. It is unknown whether MDD is a comorbidity of BD or its earlier stage, and no consensus exists on individual conversion predictors, delaying BD’s time...

Severe malarial anemia (SMA) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions. To gain enhanced understanding of predisposing factors for SMA, we explored the relationship between complement component 3 (C3) missense mutations [rs2230199 (2307C>G, Arg>Gly ¹⁰² ) and rs11569534 (34420G>...

Background: Malaria remains one of the leading global causes of childhood morbidity and mortality. In holoendemic Plasmodium falciparum transmission regions, such as western Kenya, severe malarial anemia [SMA, hemoglobin (Hb) < 6.0 g/dl] is the primary form of severe disease. Ubiquitination is essential for regulating intracellular processes involv...

Motivation: Genome wide association studies (GWAS) can reveal important genotype-phenotype associations, however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. Methods: Here, we describe rational ran...

Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been postulated to affect susceptibility to COVID-19. Observational studies so far have lacked rigorous ascertainment adjustment and international generalisability. We aimed to determine whether use of ACEIs or ARBs is associated with an increa...

Genome wide association studies (GWAS) can reveal important genotype–phenotype associations, however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. Here, we describe rational ranking, filtering and inte...

The LocalControl R package implements novel approaches to address biases and confounding when comparing treatments or exposures in observational studies of outcomes. While designed and appropriate for use in comparative safety and effectiveness research involving medicine and the life sciences, the package can be used in other situations involving...

Background: Incomplete suicidality coding in administrative claims data is a known obstacle for observational studies. With most of the negative outcomes missing from the data, it is challenging to assess the evidence on treatment strategies for the prevention of self-harm in bipolar disorder (BD), including pharmacotherapy and psychotherapy. Ther...

BACKGROUND Incomplete suicidality coding in administrative claims data is a known obstacle for observational studies. With most of the negative outcomes missing from the data, it is challenging to assess the evidence on treatment strategies for the prevention of self-harm in bipolar disorder (BD), including pharmacotherapy and psychotherapy. There...

BACKGROUND On March 11, 2020, the New Mexico (NM) Governor declared a Public Health Emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. The NM Medical Advisory Team (MAT) contacted faculty at the University of New Mexico (UNM) to form a team to assist in consolidating available information on severe acute respiratory syndrome...

Background: On March 11, 2020, the New Mexico (NM) Governor declared a Public Health Emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. The NM Medical Advisory Team (MAT) contacted University of New Mexico (UNM) faculty to form a team to consolidate growing information on severe acute respiratory syndrome coronavirus 2 (SAR...

Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the...

Alendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Out...

Introduction: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results. Methods: Using...

Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (...

Objective: We aimed to impute uncoded self-harm in administrative claims data of individuals with major mental illness (MMI), characterize self-harm incidence, and identify factors associated with coding bias. Materials and methods: The IBM MarketScan database (2003-2016) was used to analyze visit-level self-harm in 10 120 030 patients with ≥2 M...

Objective: To compare the largest set of bipolar disorder pharmacotherapies to date (102 drugs and drug combinations) for risk of diabetes mellitus (DM). Methods: The IBM MarketScan® database was used to retrospectively analyze data on 565,253 adults with bipolar disorder without prior glucose metabolism-related diagnoses. The pharmacotherapies...

Cyclooxygenase-2 [(COX-2) or prostaglandin endoperoxide H2 synthase-2 (PTGS-2)] induces the production of prostaglandins as part of the host-immune response to infections. Although a number of studies have demonstrated the effects of COX-2 promoter variants on autoimmune and inflammatory diseases, their role in malaria remains undefined. As such, w...

Background: Severe malarial anemia (SMA) is a leading cause of malaria-related morbidity and mortality in children. The genetic factors that influence development of SMA and inefficient erythropoiesis, a central pathogenic feature of SMA, are only partially understood. Methods: We performed a pilot Genome-wide Association Study (GWAS) on childre...

Background: Severe malarial anaemia (SMA) is a leading cause of childhood mortality in holoendemic Plasmodium falciparum regions. Methods: To gain an improved understanding of SMA pathogenesis, whole genome and transcriptome profiling was performed in Kenyan children (n=144, 3-36months) with discrete non-SMA and SMA phenotypes. Leukocyte associa...

Background: Leukocyte-associated immunoglobulin like receptor-1 (LAIR1) is a transmembrane inhibitory receptor that influences susceptibility to a myriad of inflammatory diseases. Our recent investigations of severe malarial anaemia (SMA) pathogenesis in Kenyan children discovered that novel LAIR1 genetic variants which were associated with decrea...

Background: This study compared the largest set of bipolar disorder pharmacotherapies to date (71 drugs and drug combinations) for risk of kidney disorders (KDs). Methods: This retrospective observational study used the IBM MarketScan® database to analyze data on 591,052 adults with bipolar disorder without prior nephropathy, for onset of KDs (o...

BACKGROUND Patient education has taken center stage in successfully shared decision-making between patients and health care providers; however, very little is known about how patients typically obtain information on their illness, especially as it relates to the treatment of bipolar disorder and what methods of information sharing are preferred. O...

Background: Patient education has taken center stage in successfully shared decision making between patients and health care providers. However, little is known about how patients with bipolar disorder typically obtain information on their illness and the treatment options available to them. Objective: This study aimed to obtain the perspectives...

Objectives This study compared 29 drugs for risk of psychiatric hospitalization in bipolar disorders, addressing the evidence gap on the >50 drugs used by US patients for treatment. Methods The Truven Health Analytics MarketScan® database was used to identify 190 894 individuals with bipolar or schizoaffective disorder who filled a prescription fo...

We present one of the largest reported retrospective observational study on drug-dependent risk of hospitalization in bipolar spectrum disorders, funded by the Patient-Centered Outcomes Research Institute (CER-1507-3160). The data were obtained from the Truven Health Analytics MarketScan® administrative claims database, transformed to the OMOP comm...

Patients suffering from bipolar disorder have an increased risk of attempting self-harm/suicide by numerous means. Although many suicidal patients are hospitalized for diagnosis and treatment, the vast majority of such visits are not documented with suicidality/selfharm diagnostic codes in administrative claims data, which makes studies related to...

Innovations to the R package LocalControl are presented. The package implements nonparametric approaches to address biases and confounding when comparing treatments or exposures inobservational studies. This work illustrates how LocalControl can address the problem of feature selection, and how it can provide bias corrected insight into what variab...

Objectives: As part of a series of Patient-Centered Outcomes Research Institute-funded large-scale retrospective observational studies on bipolar disorder (BD) treatments and outcomes, we sought the input of patients with BD and their family members to develop research questions. We aimed to identify systemic root causes of patient-reported challe...

Introduction Chromosomal microarray analysis (CMA) is recognized as the first-tier test in the genetic evaluation of children with developmental delays, intellectual disabilities, congenital anomalies and autism spectrum disorders of unknown etiology. Array Design To optimize detection of clinically relevant copy number variants associated with th...

Human Genome Informatics: Translating Genes into Health examines the most commonly used electronic tools for translating genomic information into clinically meaningful formats. By analyzing and comparing interpretation methods of whole genome data, the book discusses the possibilities of their application in genomic and translational medicine. Topi...

Introduction Chromosomal microarray analysis (CMA) is recognized as the first-tier test in the genetic evaluation of children with developmental delays, intellectual disabilities, congenital anomalies and autism spectrum disorders of unknown etiology. Array Design To optimize detection of clinically relevant copy number variants associated with th...

We announce the availability of a public OMOP Common Data Model v5 (CDMv5) dataset containing 2.33 million synthetic patients from the Centers for Medicare & Medicaid Services (CMS) Data Entrepreneurs’ Synthetic Public Use File (DE-SynPUF). We anticipate that this resource will be useful for researchers in developing OHDSI tools, as well as serve a...

Background: Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder...

Objectives Thyroid abnormalities in patients with bipolar disorder (BD) have been linked to lithium treatment for decades, yet other drugs have been less well studied. Our objective was to compare hypothyroidism risk for lithium versus the anticonvulsants and second‐generation antipsychotics commonly prescribed for BD. Methods Administrative claim...

Table S1. Significance of lithium vs. alternate therapies without bias correction. Table S2. Competing risk regression (CRR) model of risk of ending monotherapy after >0 months, >3 months, and >6 months of monotherapy. Fig. S1. Moving average of thyroid tests as a function of exposure time and treatment. Fig. S2. Cumulative incidence of hypothyr...

Background: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving variable size deletions of the 4p16.3 region. Seizures are frequently, but not always, associated with WHS. We hypothesised that the size and location of the deleted region may correlate with seizure presentation. Methods: Using chromosomal microarray ana...

It is well-known that claims coming from observational studies often fail to replicate when rigorously re-tested. The technical problems include multiple testing, multiple modeling and bias. Any or all of these problems can give rise to claims that will fail to replicate. There is a need for statistical methods that are easily applied, are easy to...

The entire drug safety enterprise has a need to search, retrieve, evaluate, and synthesize scientific evidence more efficiently. This discovery and synthesis process would be greatly accelerated through access to a common framework that brings all relevant information sources together within a standardized structure. This presents an opportunity to...

Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. We identified haplotypes shared among i...

Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD popul...

Supplemental data Tables S1–S4. Table S1. TaqMan assays used for CNV confirmation. Genomic coordinates and assay names for all TaqMan assays used for CNV confirmation. All coordinates are shown using hg19 coordinates. Table S2. CNVs identified in Utah ASD families. The chromosomal locations and copy number status of all CNVs identified in Utah ASD...

Supplemental methods and results. Supplemental methods. Details regarding sources of DNA samples used, methods for array processing, and sample quality control are described. Supplemental results. Analysis of population stratification using principal component analysis. The only samples used in CNV analyses were those demonstrated to be within the...

During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the stu...

Concordance of genotypes between technical replicates from genotyping experiment E2 by using Affy6 platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis and y-axis that are listed in Table 1. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E1 by using Affy6 platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis and y-axis that are listed in Table 1. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E3 by using Affy6 platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis and y-axis that are listed in Table 1. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E5 by using Illu1M platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis and y-axis that are listed in Table 1. (DOC)

Layout of samples on the plates and corresponding information. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E4 by using Illu1M platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis and y-axis that are listed in Table 1. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E1 and experiment E2 by using Affy6 platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis (genotyping experiment E2) and y-axis (genotyping experiment E1) that are listed in Table 1. (DOC)

Concordance of genotypes between technical replicates from genotyping experiment E4 and experiment E5 by using Illu1M platform. Each column and each row represent a technical replicate of a sample indicated by the sample codes at the x-axis (genotyping experiment E5) and y-axis (genotyping experiment E4) that are listed in Table 1. (DOC)