Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification.

AIMS: To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). METHODS: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008-2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012-2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15-<75 mL/min/1.73 m2 ; 90-730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories. RESULTS: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2 ; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390-1671) and 454 (192-850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. CONCLUSIONS: Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management.

Multiple TonB homologs are important for carbohydrate utilization by Bacteroides thetaiotaomicron.

IMPORTANCE: The human gut microbiota, including Bacteroides, is required for the degradation of otherwise undigestible polysaccharides. The gut microbiota uses polysaccharides as an energy source, and fermentation products such as short-chain fatty acids are beneficial to the human host. This use of polysaccharides is dependent on the proper pairing of a TonB protein with polysaccharide-specific TonB-dependent transporters; however, the formation of these protein complexes is poorly understood. In this study, we examine the role of 11 predicted TonB homologs in polysaccharide uptake. We show that two proteins, TonB4 and TonB6, may be functionally redundant. This may allow for the development of drugs targeting Bacteroides species containing only a TonB4 homolog with limited impact on species encoding the redundant TonB6.

Typhoid in India: An Age-old Problem With an Existing Solution.

Enteric fever continues to impact millions of people who lack adequate access to clean water and sanitation. The typhoid and paratyphoid fever burden in South Asia is broadly acknowledged, but current estimates of incidence, severity, and cost of illness from India are lacking. This supplement addresses this gap in our knowledge, presenting findings from two years of surveillance, conducted at multiple sites between October 2017 and February 2020, in the Surveillance for Enteric Fever in India (SEFI) network. Results provide contemporaneous evidence of high disease burden and cost of illness-the latter borne largely by patients in the absence of universal healthcare coverage in India. Against a backdrop of immediate priorities in the COVID-19 pandemic, these data are a reminder that typhoid, though often forgotten, remains a public health problem in India. Typhoid conjugate vaccines, produced by multiple Indian manufacturers, and recommended for use in high burden settings, ensure that the tools to tackle typhoid are an immediately available solution to this public health problem.

Typhoid Conjugate Vaccines and Enteric Fever Control: Where to Next?

After the unprecedented success and acceleration of the global agenda towards typhoid fever control with a strong World Health Organization recommendation and the approval of funding from Gavi, the Vaccine Alliance (Gavi), for the use of a new typhoid conjugate vaccine (TCV), we should turn our minds to the challenges that remain ahead. Despite the evidence showing the safety and clinical efficacy of TCV in endemic populations in developing countries, we should remain vigilant and explore hurdles for the full public health impact of TCV, including vaccine supply for the potential global demand, immunization strategies to optimize the effectiveness and long-term protection provided by the vaccines, potential use of TCV in outbreak settings, and scenarios for addressing chronic carriers. Finally, challenges face endemic countries with poor surveillance systems concerning awareness of the need for TCV and the extent of the issue across their populations, and how to target immunization strategies appropriately.

A 'Grantathon' model to mentor new investigators in mental health research.

BACKGROUND: There is a critical gap between needs and available resources for mental health treatment across the world, particularly in low- and middle-income countries (LMICs). In countries committed to increasing resources to address these needs it is important to conduct research, not only to assess the depth of mental health needs and the current provision of public and private mental health services, but also to examine implementation methods and evaluate mental health approaches to determine which methods are most effective in local contexts. However, research resources in many LMICs are inadequate, largely because conventional research training is time-consuming and expensive. Adapting a hackathon model may be a feasible method of increasing capacity for mental health services research in resource-poor countries. METHODS: To explore the feasibility of this approach, we developed a 'grantathon', i.e. a research training workshop, to build capacity among new investigators on implementation research of Indian government-funded mental health programmes, which was based on a need expressed by government agencies. The workshop was conducted in Delhi, India, and brought together junior faculty members working in mental health services settings throughout the country, experienced international behavioural health researchers and representatives of the Indian Council for Medical Research (ICMR), the prime Indian medical research funding agency. Pre- and post-assessments were used to capture changes in participants' perceived abilities to develop proposals, design research studies, evaluate outcomes and develop collaborations with ICMR and other researchers. Process measures were used to track the number of single-or multi-site proposals that were generated and funded. RESULTS: Participants (n = 24) generated 12 single- or multi-site research grant applications that will be funded by ICMR. CONCLUSION: The grantathon model described herein can be modified to build mental health services research capacity in other contexts. Given that this workshop not only was conceptualised and delivered but also returned results in less than 1 year, this model has the potential to quickly build research capacity and ultimately reduce the mental health treatment gap in resource-limited settings.

Is population structure sufficient to generate area-level inequalities in influenza rates? An examination using agent-based models.

BACKGROUND: In New Haven County, CT (NHC), influenza hospitalization rates have been shown to increase with census tract poverty in multiple influenza seasons. Though multiple factors have been hypothesized to cause these inequalities, including population structure, differential vaccine uptake, and differential access to healthcare, the impact of each in generating observed inequalities remains unknown. We can design interventions targeting factors with the greatest explanatory power if we quantify the proportion of observed inequalities that hypothesized factors are able to generate. Here, we ask if population structure is sufficient to generate the observed area-level inequalities in NHC. To our knowledge, this is the first use of simulation models to examine the causes of differential poverty-related influenza rates. METHODS: Using agent-based models with a census-informed, realistic representation of household size, age-structure, population density in NHC census tracts, and contact rates in workplaces, schools, households, and neighborhoods, we measured poverty-related differential influenza attack rates over the course of an epidemic with a 23 % overall clinical attack rate. We examined the role of asthma prevalence rates as well as individual contact rates and infection susceptibility in generating observed area-level influenza inequalities. RESULTS: Simulated attack rates (AR) among adults increased with census tract poverty level (F = 30.5; P < 0.001) in an epidemic caused by a virus similar to A (H1N1) pdm09. We detected a steeper, earlier influenza rate increase in high-poverty census tracts-a finding that we corroborate with a temporal analysis of NHC surveillance data during the 2009 H1N1 pandemic. The ratio of the simulated adult AR in the highest- to lowest-poverty tracts was 33 % of the ratio observed in surveillance data. Increasing individual contact rates in the neighborhood did not increase simulated area-level inequalities. When we modified individual susceptibility such that it was inversely proportional to household income, inequalities in AR between high- and low-poverty census tracts were comparable to those observed in reality. DISCUSSION: To our knowledge, this is the first study to use simulations to probe the causes of observed inequalities in influenza disease patterns. Knowledge of the causes and their relative explanatory power will allow us to design interventions that have the greatest impact on reducing inequalities. CONCLUSION: Differential exposure due to population structure in our realistic simulation model explains a third of the observed inequality. Differential susceptibility to disease due to prevailing chronic conditions, vaccine uptake, and smoking should be considered in future models in order to quantify the role of additional factors in generating influenza inequalities.

Seasonal variations in social contact patterns in a rural population in north India: Implications for pandemic control.

Social contact mixing patterns are critical to model the transmission of communicable diseases, and have been employed to model disease outbreaks including COVID-19. Nonetheless, there is a paucity of studies on contact mixing in low and middle-income countries such as India. Furthermore, mathematical models of disease outbreaks do not account for the temporal nature of social contacts. We conducted a longitudinal study of social contacts in rural north India across three seasons and analysed the temporal differences in contact patterns. A contact diary survey was performed across three seasons from October 2015-16, in which participants were queried on the number, duration, and characteristics of contacts that occurred on the previous day. A total of 8,421 responses from 3,052 respondents (49% females) recorded characteristics of 180,073 contacts. Respondents reported a significantly higher number and duration of contacts in the winter, followed by the summer and the monsoon season (Nemenyi post-hoc, p<0.001). Participants aged 0-9 years and 10-19 years of age reported the highest median number of contacts (16 (IQR 12-21), 17 (IQR 13-24) respectively) and were found to have the highest node centrality in the social network of the region (pageranks = 0.20, 0.17). A large proportion (>80%) of contacts that were reported in schools or on public transport involved physical contact. To the best of our knowledge, our study is the first from India to show that contact mixing patterns vary by the time of the year and provides useful implications for pandemic control. We compared the differences in the number, duration and location of contacts by age-group and gender, and studied the impact of the season, age-group, employment and day of the week on the number and duration of contacts using multivariate negative binomial regression. We created a social network to further understand the age and gender-specific contact patterns, and used the contact matrices in each season to parameterise a nine-compartment agent-based model for simulating a COVID-19 epidemic in each season. Our results can be used to parameterize more accurate mathematical models for prediction of epidemiological trends of infections in rural India.

Policies to reduce influenza in the workplace: impact assessments using an agent-based model.

OBJECTIVES: We examined the impact of access to paid sick days (PSDs) and stay-at-home behavior on the influenza attack rate in workplaces. METHODS: We used an agent-based model of Allegheny County, Pennsylvania, with PSD data from the US Bureau of Labor Statistics, standard influenza epidemic parameters, and the probability of staying home when ill. We compared the influenza attack rate among employees resulting from workplace transmission, focusing on the effects of presenteeism (going to work when ill). RESULTS: In a simulated influenza epidemic (R0 = 1.4), the attack rate among employees owing to workplace transmission was 11.54%. A large proportion (72.00%) of this attack rate resulted from exposure to employees engaging in presenteeism. Universal PSDs reduced workplace infections by 5.86%. Providing 1 or 2 "flu days"-allowing employees with influenza to stay home-reduced workplace infections by 25.33% and 39.22%, respectively. CONCLUSIONS: PSDs reduce influenza transmission owing to presenteeism and, hence, the burden of influenza illness in workplaces.

Adverse interactions between micro-RNAs and target genes from different species.

It is commonly assumed but not proven that microRNAs (miRNAs) and their targets coevolve. Under this assumption, miRNAs and targets from different species may interact adversely, resulting in reduced fitness. However, the strength of the adverse interactions may not be detectable because even outright deletions of miRNAs often manifest only subtle fitness effects. We tested and measured the strength of heterospecific interactions by carrying out transgenic experiments across Drosophila species by overexpressing the miR310s cluster of Drosophila melanogaster (Dm310s) and Drosophila pseudoobscura (Dp310s) in D. melanogaster. Flies overexpressing the heterospecific Dp310s are only one-third as viable as those overexpressing the conspecific Dm310s. The viability effect is easily detectable in comparison to the effect of the deletion of miR310s. The number of genes significantly misexpressed under the influence of Dp310s is 3-10 times greater than under Dm310s. Importantly, the numbers of predicted targets are similar between them. Expression analysis of the predicted target genes suggests that miRNAs may sometimes function to buffer fluctuations in the transcriptome output. After the buffering function has evolved, heterospecific combinations may cause adverse effects.

Efficiency of face mask ventilation before and after neuromuscular blockade: A randomised, double-blind controlled study.

Background and Aims: The traditional practice of administrating neuromuscular blocking drugs (NMBDs) after checking face mask ventilation is challenged repeatedly. This study compared the efficiency of face mask ventilation before and after administrating an NMBD in a patient with a normal airway. The secondary outcome measured was the grade of mask ventilation and tracheal intubating conditions. Methods: After ethical approval, patients (n = 120) in the age group of 18-65 years scheduled for elective surgery under general anaesthesia were randomly assigned into two groups. Group 1 received an NMBD before checking face mask ventilation. Group 2 received an NMBD after checking face mask ventilation. Lungs were ventilated for 180 s, during which expiratory tidal volume (Vte) was recorded as the primary outcome. Hans's grading for face mask ventilation was used to grade mask ventilation. The ease of intubation was assessed based on intubating conditions (ease of laryngoscopy, vocal cord movement, and limb movement). SPSS 20.0 software was used for statistical analysis. Results: For a total of 180 seconds of mask ventilation, the mean (standard deviation) Vte measured after apnoea was significantly higher in Group 1 versus Group 2 [471.9 (63.3) vs 434.8 (77.0) mL/breath, P = 0.004]. The intubating condition was either excellent or good in all patients. Conclusion: The administration of NMBDs resulted in a larger mask Vte and shorter intubation time.

Typhoid Control in an Era of Antimicrobial Resistance: Challenges and Opportunities.

Historically, typhoid control has been achieved with water and sanitation interventions. Today, in an era of rising antimicrobial resistance (AMR), two World Health Organization-prequalified vaccines are available to accelerate control in the shorter term. Meanwhile, water and sanitation interventions could be implemented in the longer term to sustainably prevent typhoid in low- and middle-income countries. This article first approaches typhoid control from a historical perspective, subsequently presents how vaccination could complement water and sanitation activities, and finally discusses the challenges and opportunities for impactful control of typhoid infection. It also addresses data blind spots and knowledge gaps to focus on for typhoid control and to ultimately progress towards elimination. This article presents a synthesis of discussions held in December 2021 during a roundtable session at the "12th International Conference on Typhoid and Other Invasive Salmonelloses".

Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and delays intestinal motility in mice.

Despite progress describing the effects of persistent organic pollutants (POPs) on the central nervous system, the effect of POPs on enteric nervous system (ENS) function remains underexplored. We studied the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a POP, and a potent aryl hydrocarbon receptor (AHR) ligand, on the ENS and intestinal motility in mice. C57Bl/6J mice treated with TCDD (2.4 µg/kg body weight) for 8 weeks (once per week) exhibited significant delay in intestinal motility as shown by reduced stool frequency, prolonged intestinal transit time, and a persistence of dye in the jejunum compared to control mice with maximal dye retention in the ileum. TCDD significantly increased Cyp1a1 expression, an AHR target gene, and reduced the total number of neurons and affected nitrergic neurons in cells isolated from WT mice, but not Ahr-/- mice. In immortalized fetal enteric neuronal cells, TCDD-induced nuclear translocation of AHR as well as increased Cyp1a1 expression. AHR activation did not affect neuronal proliferation. However, AHR activation resulted in enteric neuronal toxicity, specifically, nitrergic neurons. Our results demonstrate that TCDD adversely affects nitrergic neurons and thereby contributes to delayed intestinal motility. These findings suggest that AHR signaling in the ENS may play a role in modulating TCDD-induced gastrointestinal pathophysiology.

Background rate estimations for thrombosis with thrombocytopaenia: challenges in evaluating rare safety signals following vaccination in real time during a pandemic.

OBJECTIVES: During COVID-19 vaccination programmes, new safety signals have emerged for vaccines, including extremely rare cases of thrombosis with thrombocytopaenia syndrome (TTS). Background event rates before and during the pandemic are essential for contextualisation of such infrequent events. In the literature, most studies do not report an overall TTS event rate. Rather, background rates are mainly reported for subtypes of thrombotic/thromboembolic diagnoses included in the TTS clinical definition mostly by anatomical location, with reported rates for TTS subtypes varying widely. The objective of this study was to report prepandemic TTS background event rates in the general population. METHODS: Prepandemic background TTS rates were generated via secondary data analysis using a cohort design in the IBM Truven MarketScan (now Merative MarketScan) US health insurance claims database, from 1 January 2019 to 31 December 2019. Two algorithms were applied: thrombocytopaenia occurring±7 days (algorithm 1) or occurring 1 day prior to ≤14 days after the thrombotic/thromboembolic event (algorithm 2). RESULTS: The study population derived from the MarketScan database analysis included approximately 9.8 million adults (aged ≥18 years; mean age 45 years, 52% females). Using this study population, prepandemic background TTS incidence was estimated as 9.8-11.1 per 100 000 person-years. Event rates were higher in males and increased with age. Similar patterns were observed with both algorithms. CONCLUSIONS: This study presents an estimate of aggregate prepandemic background TTS event rates including by type of thrombosis/thromboembolism and age group. The background event rates are dependent on the precision of capturing underlying TTS events in variable data sources, and the ability of electronic health records or insurance claims databases to reflect the TTS clinical definition. Differences between reported event rates demonstrate that estimating background event rates for rare, unprecedented safety events is methodologically challenging.

Taking on Typhoid: Eliminating Typhoid Fever as a Global Health Problem.

Typhoid fever is a significant global health problem that impacts people living in areas without access to clean water and sanitation. However, collaborative international partnerships and new research have improved both knowledge of the burden in countries with endemic disease and the tools for improved surveillance, including environmental surveillance. Two typhoid conjugate vaccines (TCVs) have achieved World Health Organization prequalification, with several more in the development pipeline. Despite hurdles posed by the coronavirus disease 2019 pandemic, multiple TCV efficacy trials have been conducted in high-burden countries, and data indicate that TCVs provide a high degree of protection from typhoid fever, are safe to use in young children, provide lasting protection, and have the potential to combat typhoid antimicrobial resistance. Now is the time to double down on typhoid control and elimination by sustaining progress made through water, sanitation, and hygiene improvements and accelerating TCV introduction in high-burden locations.

Multiple TonB Homologs are Important for Carbohydrate Utilization by Bacteroides thetaiotaomicron.

The human gut microbiota is able to degrade otherwise undigestible polysaccharides, largely through the activity of the Bacteroides. Uptake of polysaccharides into Bacteroides is controlled by TonB-dependent transporters (TBDT) whose transport is energized by an inner membrane complex composed of the proteins TonB, ExbB, and ExbD. Bacteroides thetaiotaomicron (B. theta) encodes 11 TonB homologs which are predicted to be able to contact TBDTs to facilitate transport. However, it is not clear which TonBs are important for polysaccharide uptake. Using strains in which each of the 11 predicted tonB genes are deleted, we show that TonB4 (BT2059) is important but not essential for proper growth on starch. In the absence of TonB4, we observed an increase in abundance of TonB6 (BT2762) in the membrane of B. theta, suggesting functional redundancy of these TonB proteins. Growth of the single deletion strains on pectin galactan, chondroitin sulfate, arabinan, and levan suggests a similar functional redundancy of the TonB proteins. A search for highly homologous proteins across other Bacteroides species and recent work in B. fragilis suggests that TonB4 is widely conserved and may play a common role in polysaccharide uptake. However, proteins similar to TonB6 are found only in B. theta and closely related species suggesting that the functional redundancy of TonB4 and TonB6 may be limited across the Bacteroides. This study extends our understanding of the protein network required for polysaccharide utilization in B. theta and highlights differences in TonB complexes across Bacteroides species.

Observations of Oncologists on Treatment Selection With Interim Positron Emission Tomography-Adapted Approaches in Classic Hodgkin Lymphoma: The Real-World CONNECT Study.

PURPOSE: We surveyed oncologists who treat classic Hodgkin lymphoma (cHL) as part of the CONNECT study to understand the treatment decision-making process, including the impact of positron emission tomography/computed tomography (PET/CT) imaging. METHODS: US physicians self-identifying as oncologists, hematologists, or hematologists/oncologists with ≥2 years of practice experience who treated ≥1 adult with stage III/IV cHL in the frontline setting in the last year were surveyed (October 19-November 16, 2020). Physician demographics, guideline adherence, and PET/CT utilization, interpretation, and access barriers were assessed. RESULTS: In total, 301 physicians participated in the survey. Eighty-eight percent of physicians gave somewhat-to-significant consideration to NCCN guidelines. Most physicians (94%; n = 284) reported obtaining a PET/CT scan at diagnosis; of these physicians, 97% reported obtaining an interim PET/CT scan for stage III/IV cHL, with 65% typically obtaining an interim PET/CT scan after cycle 2. The Deauville 5-point scale (5PS) was the primary scoring system used to review PET/CT results by 62% of physicians, with a positive score defined as ≥3 by 44%, ≥4 by 37%, and ≥2 by 12% of physicians. Fifty-five percent of physicians reported difficulty in obtaining PET/CT scans. CONCLUSION: Although most physicians considered NCCN guidelines when treating patients with stage III/IV cHL, interim PET/CT scans after cycle 2 were not universally obtained. When PET/CT scans were obtained, Deauville 5PS scores were not always provided, and variability existed on what defined a positive score. These findings suggest that opportunities exist for education and improved PET-adapted treatment approaches.

The impact of workplace policies and other social factors on self-reported influenza-like illness incidence during the 2009 H1N1 pandemic.

OBJECTIVES: We assessed the impact of social determinants of potential exposure to H1N1--which are unequally distributed by race/ethnicity in the United States--on incidence of influenza-like illness (ILI) during the 2009 H1N1 pandemic. METHODS: In January 2010 we surveyed a nationally representative sample (n = 2079) of US adults from the Knowledge Networks online research panel, with Hispanic and African American oversamples. The completion rate was 56%. RESULTS: Path analysis examining ILI incidence, race, and social determinants of potential exposure to H1N1 demonstrated that higher ILI incidence was related to workplace policies, such as lack of access to sick leave, and structural factors, such as number of children in the household. Hispanic ethnicity was related to a greater risk of ILI attributable to these social determinants, even after we controlled for income and education. CONCLUSIONS: The absence of certain workplace policies, such as paid sick leave, confers a population-attributable risk of 5 million additional cases of ILI in the general population and 1.2 million cases among Hispanics. Federal mandates for sick leave could have significant health impacts by reducing morbidity from ILI, especially in Hispanics.

It's a long, long walk: accessibility to hospitals, maternity and integrated health centers in Niger.

BACKGROUND: Ease of access to health care is of great importance in any country but particularly in countries such as Niger where restricted access can put people at risk of mortality from diseases such as measles, meningitis, polio, pneumonia and malaria. This paper analyzes the physical access of populations to health facilities within Niger with an emphasis on the effect of seasonal conditions and the implications of these conditions in terms of availability of adequate health services, provision of drugs and vaccinations. The majority of the transport within Niger is pedestrian, thus the paper emphasizes access by those walking to facilities for care. Further analysis compared the change in accessibility for vehicular travel since public health workers do travel by vehicle when carrying out vaccination campaigns and related proactive health care activities. RESULTS: The majority of the roads in Niger are non-paved (90%). Six districts, mainly in the region of Tahoua lack medical facilities. Patient to health facility ratios were best in Agadez with 7000 people served per health facility. During the dry season 39% of the population was within 1-hours walk to a health center, with the percentage decreasing to 24% during the wet season. Further analyses revealed that vaccination rates were strongly correlated with distance. Children living in clusters within 1-hour of a health center had 1.88 times higher odds of complete vaccination by age 1-year compared to children living in clusters further from a health center (p < 0.05). Three key geographic areas were highlighted where access to health centers took greater than 4 h walk during the wet and dry season. Access for more than 730,000 people can be improved in these areas with the addition of 17 health facilities to the current total of 504 during the dry season (260,000 during the wet season). CONCLUSIONS: This study highlights critical areas in Niger where health services/facilities are lacking. A second finding is that population served by health facilities will be severely overestimated if assessments are solely conducted during the dry season. Mapped outputs can be used for future decision making processes and analysis.

Developing a common data model approach for DISCOVER CKD: A retrospective, global cohort of real-world patients with chronic kidney disease.

OBJECTIVES: To describe a flexible common data model (CDM) approach that can be efficiently tailored to study-specific needs to facilitate pooled patient-level analysis and aggregated/meta-analysis of routinely collected retrospective patient data from disparate data sources; and to detail the application of this CDM approach to the DISCOVER CKD retrospective cohort, a longitudinal database of routinely collected (secondary) patient data of individuals with chronic kidney disease (CKD). METHODS: The flexible CDM approach incorporated three independent, exchangeable components that preceded data mapping and data model implementation: (1) standardized code lists (unifying medical events from different coding systems); (2) laboratory unit harmonization tables; and (3) base cohort definitions. Events between different coding vocabularies were not mapped code-to-code; for each data source, code lists of labels were curated at the entity/event level. A study team of epidemiologists, clinicians, informaticists, and data scientists were included within the validation of each component. RESULTS: Applying the CDM to the DISCOVER CKD retrospective cohort, secondary data from 1,857,593 patients with CKD were harmonized from five data sources, across three countries, into a discrete database for rapid real-world evidence generation. CONCLUSIONS: This flexible CDM approach facilitates evidence generation from real-world data within the DISCOVER CKD retrospective cohort, providing novel insights into the epidemiology of CKD that may expedite improvements in diagnosis, prognosis, early intervention, and disease management. The adaptable architecture of this CDM approach ensures scalable, fast, and efficient application within other therapy areas to facilitate the combined analysis of different types of secondary data from multiple, heterogeneous sources.

Contemporary outcomes of anemia in US patients with chronic kidney disease.

BACKGROUND: Long-term clinical outcome data from patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD) are lacking. We characterized patients with NDD-CKD and anemia using real-world data from the USA. METHODS: This retrospective longitudinal observational study evaluated integrated Limited Claims and Electronic Health Record Data (IBM Health, Armonk, NY), including patients ≥18 years with two or more estimated glomerular filtration rate (eGFR) measures <60 mL/min/1.73 m2 ≥90 days apart. Anemia was defined as the first observed hemoglobin <10 g/dL within 6-month pre- and post-CKD index date. Data were analyzed from January 2012 to June 2018. Patients with documented iron-deficiency anemia at baseline were excluded. RESULTS: Comprising 22 720 patients (57.4% female, 63.9% CKD stage 3, median hemoglobin 12.5 g/dL), median (interquartile range) follow-up for patients with and without anemia were 2.9 (1.5-4.4) and 3.8 (2.2-4.8) years, respectively. The most prevalent comorbidities were dyslipidemia (57.6%), type 2 diabetes mellitus (38.8%) and uncontrolled hypertension (20.0%). Overall, 23.3% of patients had anemia, of whom 1.9% and <0.1% received erythropoiesis-stimulating agents (ESAs) or intravenous iron, respectively. Anemia prevalence increased with CKD stage from 18.2% (stage 3a) to 72.8% (stage 5). Patients with anemia had a higher incidence rate of hospitalizations for heart failure (1.6 versus 0.8 per 100 patient-years), CKD stage advancement (43.5 versus 27.5 per 100 patient-years), and a 40% eGFR decrease (18.1 versus 7.3 per 100 patient-years) versus those without anemia. CONCLUSIONS: Anemia, frequently observed in NDD-CKD and associated with adverse clinical outcomes, is rarely treated with ESAs and intravenous iron. These data suggest that opportunities exist for improved anemia management in patients with NDD-CKD.