One Health Risk and Disease (OHRAD): a tool to prioritise the risks for epidemic-prone diseases from One Health perspective.

BACKGROUND: The rise in epidemic-prone diseases daily poses a serious concern globally. Evidence suggests that many of these diseases are of animal origin and contribute to economic loss. Considering the limited time and other resources available for the animal and human health sectors, selecting the most urgent and significant risk factors and diseases is vital, even though all epidemic-prone diseases and associated risk factors should be addressed. The main aim of developing this tool is to provide a readily accessible instrument for prioritising risk factors and diseases that could lead to disease emergence, outbreak or epidemic. METHODS: This tool uses a quantitative and semi-quantitative multi-criteria decision analysis (MCDA) method that involves five steps: Identifying risk factors and diseases, Weighting the criteria, Risk and disease scoring, Calculating risk impact and disease burden score, and Ranking risks and diseases. It is intended to be implemented through a co-creation workshop and involves individual and group activities. The last two steps are automated in the MS Excel score sheet. RESULTS: This One Health Risk and Disease (OHRAD) prioritisation tool starts with an individual activity of identifying the risks and diseases from the more extensive list. This, then, leads to a group activity of weighing the criteria and providing scores for each risk and disease. Finally, the individual risk and disease scores with the rankings are generated in this tool. CONCLUSIONS: The outcome of this OHRAD prioritisation tool is that the top risks and diseases are prioritised for the particular context from One Health perspective. This prioritised list will help experts and officials decide which epidemic-prone diseases to focus on and for which to develop and design prevention and control measures.

Risk Assessment Tools from the One Health Perspective: A Narrative Review.

Background: 61% of the infections around the world that have emerged to date are zoonotic. Evidence warns that the threat posed by zoonoses is on the rise, and the risk of a new pandemic is higher now than ever. Early identification of risk, populations at risk, and risk of transmission are essential steps towards a prevention, preparation and response to outbreaks. This review aims to look at the tools available for identifying and estimating risks and threats from one health perspective and finally propose a list of indicators which could assess the risk of transmission of disease at the humans, animals and the environment intersection. Methods: The databases like PubMed, google scholar, Embase and Scopus were used to extract the relevant articles. A search was carried out using a keyword. A total of 1311 articles were listed initially after the search and reviewed. Out of 1311, only 26 tools which assessed the risk of diseases mainly infectious or were relevant to risk of transmission of any infectious diseases were included in the review. Results: The tools included in this review involve risk assessment at the environmental, animal and human dimensions. The tools are used to evaluate the contamination of the environment due to chemicals or toxins or the risk of transmission of infection due to environmental factors like air contamination, to identify the animal diseases like bovine respiratory disease and foot and mouth disease and to estimate the human health risk at the community or individual levels. Conclusion: Risk assessment tools are an essential part of the prevention of pandemics. These tools are helpful in assessing the risk of transmission of infections either from human to human, between human and animals, between animals and animals and so on. Thus this review gives us an insight into the existing risk assessment tools and the need for a One Health risk assessment tools to prevent outbreaks in future. It also provides a list of factors that can be included in a one health risk assessment tool.

Effects of Covid-19 Vaccination during Pregnancy on the Obstetric and Neonatal Outcomes in a Tertiary Health Care Center.

BACKGROUND: Pregnancy is an immuno-compromised state, and pregnant women with COVID-19 are at an increased risk for adverse pregnancy outcomes. Thus, the Center for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization (ACIP) have advocated for COVID-19 vaccination in pregnant women. COVAXIN and COVISHIELD were the vaccines being used in India in the first phase of vaccination, but limited data exist on pregnancy outcomes regarding SARS-CoV-2 vaccines and pregnancy and lactation. MATERIAL AND METHODS: A retrospective study was conducted which included only women who delivered after 24 weeks gestation. Women with an unknown vaccination status or with past or active COVID-19 infection were excluded. Demographic characteristics, maternal and obstetric outcomes, and fetal and neonatal outcomes were compared between the unvaccinated and vaccinated groups. Statistical analysis was done with Chi-square testing and the Fisher exact test using SPSS-26 software. RESULTS: Deliveries before a gestation of 37 weeks were significantly higher in the unvaccinated group compared to the vaccinated group. Rates of vaginal deliveries and preterm deliveries were found to be higher in the unvaccinated population. Women who had taken COVAXIN had a higher rate of adverse events compared to those who had taken COVISHIELD. CONCLUSION: There were no significant differences in adverse obstetric outcomes attributed to vaccine administration between the vaccinated and unvaccinated pregnant women. The beneficial effects of the vaccines in protecting against COVID-19 infection, particularly in pregnancy, outweigh the minor adverse events associated with vaccine administration.

Intraoperative Retinal Changes May Predict Surgical Outcomes After Epiretinal Membrane Peeling.

Purpose: To investigate whether intraoperative retinal changes during epiretinal membrane (ERM) peeling affect anatomic or functional outcomes after surgery. Methods: We measured retinal thickness using an intraoperative optical coherence tomography (iOCT) device in patients undergoing pars plana vitrectomy with membrane peeling for idiopathic ERM. Changes in intraoperative central macular thickness (iCMT) were compared with postoperative improvements in CMT and best-corrected visual acuity (VA). Results: Twenty-seven eyes from 27 patients (mean age 68 years) underwent iOCT-assisted ERM peeling surgery. Before surgery, mean VA was logMAR 0.50 ± 0.36 (Snellen 20/63), and mean baseline CMT was 489 ± 82 µm. Mean iCMT before peeling was 477 ± 87 µm, which correlated well with preoperative CMT (P < 0.001). Mean change in iCMT was -39.6 ± 37 µm (range -116 to +77 µm). After surgery, VA improved to logMAR 0.40 ± 0.38 (Snellen 20/50) at month 1 and logMAR 0.27 ± 0.23 (Snellen 20/37) at month 3, whereas CMT decreased to 397 ± 44 µm and 396 ± 51 µm at months 1 and 3. Eyes that underwent greater amount of iCMT change (absolute value of iCMT change) were associated with greater CMT reduction at month 1 (P < 0.001) and month 3 (P = 0.010), whereas those with greater intraoperative thinning (actual iCMT change) showed a trend toward better VA outcomes at months 1 (P = 0.054) and 3 (P = 0.036). Conclusions: Intraoperative changes in retinal thickness may predict anatomic and visual outcomes after idiopathic ERM peeling surgery. Translational Relevance: Our study suggests that intraoperative retinal tissue response to ERM peeling surgery measured by iOCT may be a prognostic indicator for restoration of retinal architecture and for visual acuity outcomes.

Clinical Outcomes of Warfarin Initiation in Advanced Chronic Kidney Disease Patients With Incident Atrial Fibrillation.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of warfarin initiation following the diagnosis of atrial fibrillation (AF) in patients with late-stage chronic kidney disease (CKD) who transitioned to dialysis. BACKGROUND: The clinical benefit of warfarin therapy for thromboprophylaxis after incident AF diagnosis in patients with late-stage CKD who are transitioning to dialysis is unknown. METHODS: In this retrospective cohort analysis, the study population was a national cohort of 22,771 U.S. veterans with incident end-stage renal disease who developed incident AF before initiating renal replacement therapy. This study examined the association of warfarin therapy following the diagnosis of incident AF with ischemic cerebrovascular accidents (CVAs) (ischemic stroke or transient ischemic attack), ischemic CVA-related hospitalization, major bleeding events (gastrointestinal or intracranial bleeding), bleeding event-related hospitalizations, and post-dialysis, all-cause mortality in multivariable adjusted Cox regression analyses that adjusted for demographic characteristics and comorbidities. RESULTS: The mean ± SD age of the cohort was 73.5 ± 8.8 years, 13% were African American, and the mean CHA2DS2-VASc score was 5.7 ± 2.1. Of the overall cohort, 6,682 (29.3%) patients were started on warfarin during the follow-up period. The hazard ratios (95% confidence intervals) for ischemic CVA, bleeding events, and death for those started on warfarin were 1.23 (1.16 to 1.30), 1.36 (1.29 to 1.44), and 0.94 (0.90 to 0.97), respectively, compared with those who received no anticoagulation. Warfarin exposure was associated with higher risk for ischemic CVA and bleeding event-related hospitalizations. CONCLUSIONS: In patients with late-stage CKD who transitioned to dialysis, warfarin use was associated with higher risk of ischemic and bleeding events but a lower risk of mortality. Future studies such as those comparing warfarin with newer oral anticoagulant agents are needed to granularly define the net clinical benefit of anticoagulation therapy in patients with advanced CKD with incident AF.

Cost-effectiveness and Outcomes with Early or Same-Day Discharge After Elective Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: Shorter hospital stay after percutaneous coronary intervention (PCI) can provide economic advantage. Same-day discharge (SDD) after transradial PCI is thought to reduce the cost of care while maintaining the quality and safety. This review summarizes the current knowledge of the benefits and safety of this concept. RECENT FINDINGS: Increase in rate of transradial PCI over the last two decades has resulted in recent growth in rate of acceptance of SDD after a successful procedure. SDD is shown to result in savings of $3500 to $5200 per procedure with comparable adverse event rate of traditional discharge processes. SDD after PCI is shown to be safe and results in cost advantage maintaining the safety profile. The acceptance rate of SDD is still not optimum, and further market penetration of SDD practice would be achieved only if the institutional and operator preference barriers are addressed.

Role of Frozen Section in Surgical Management of Ovarian Neoplasm.

OBJECTIVE: Cancers of the adnexae, including ovarian and fallopian tube, constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of ovarian cancer. Intraoperative frozen section diagnosis of ovarian tumors is widely used in making this distinction and to decide the course of surgery. Therefore, the accuracy of this technique is very important. The aim was to determine the overall accuracy, sensitivity, specificity, and predictive values of frozen section for ovarian tumors and to evaluate the role of frozen section in the surgical management of ovarian tumors. MATERIALS AND METHODS: This was a descriptive longitudinal study conducted in the gynecology department of a tertiary care hospital. During the 1 ½ year period of data collection, frozen section was performed among 60 cases of ovarian neoplasms. The overall accuracy, sensitivity, specificity and predictive values of frozen section for benign, borderline and malignant categories of ovarian tumors were studied. RESULTS: Out of the 60 patients of ovarian tumors, frozen section diagnosis showed that 43 (71.7%) tumors were benign, 11 (18.3%) were malignant and 6 (10%) were of borderline nature. Final histopathological diagnosis showed that 45 (75%) tumors were benign, 11 (18.3%) were malignant and 4 (6.7%) were borderline. Frozen section for benign tumors had 95% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 88% negative predictive value (NPV). Malignant tumors had 90% sensitivity, 97% specificity, 90% PPV and 97% NPV with frozen section. However, frozen section had low sensitivity (75%) and PPV (50%) for borderline tumors. Specificity was 94% and NPV 98% in this group of tumors. CONCLUSION: Frozen section was found to be an accurate and useful modality in the intraoperative evaluation of patients with ovarian neoplasm. The results can help to decide the type and extent of surgery.

Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results.

BACKGROUND/OBJECTIVE: To determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term. SUBJECT/METHODS: Thirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1-24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter. RESULTS: A total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant. CONCLUSIONS: Initial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.

Resolution of syphilis-related rapidly progressive glomerulonephritis with penicillin therapy: Case report
.

Renal manifestations of syphilis are variable, with membranous nephropathy being the most commonly described lesion. Rapidly progressive glomerulonephritis (RPGN) is rare and there is only one case report in the literature describing syphilis-associated crescentic glomerulonephritis. We report a rare case of RPGN secondary to latent syphilis, which resolved with penicillin treatment in the absence of immunosuppressive therapy. A 28-year-old Black male with a history of HIV was evaluated for severe acute kidney injury, nephrotic-range proteinuria, and active urine sediment. Serologies for glomerulonephritis were negative. Rapid plasma reagin and treponema pallidum particle agglutination assay were reactive, confirming syphilis diagnosis. Kidney biopsy revealed focal and segmental necrotizing and crescentic lesion. Patient received weekly benzathine penicillin (PCN) for 3 weeks, and renal function improved to baseline. This dramatic improvement happened with PCN alone, a finding which has not been previously reported. We recommend that syphilis be considered in the differential diagnosis of all patients with proteinuria or suspected glomerulonephritis.

Hyperlipidemia: Management with Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors.

Coronary artery disease is the leading cause of death in United States. Hyperlipidemia is an independent and potentially reversible risk factor for coronary artery disease. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, collectively known as statins, have been the mainstay of pharmacologic therapy. Their availability, ease of administration, low cost, and strong evidence behind safety and efficacy makes them one of the most widely prescribed lipid-lowering agents. However, some patients may be intolerant to statins, and few others suffer from very high serum levels of cholesterol in which statin therapy alone or in combination with other cholesterol-lowering agents is insufficient in reducing serum lipid levels to achieve desired levels. In 2015, the Food and Drug Administration approved a new family of lipid-lowering agents, collectively known as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.PCSK9 inhibitors are biologically active molecules that decrease serum low-density lipoprotein cholesterol compared with statin therapy alone. They serve as an alternative to statins for patients who are intolerant to statin or as supplemental therapy in those patients for whom lower levels in serum low-density lipoprotein cholesterol are not achieved by statins alone. This article discusses PCSK9 inhibitors, their mechanism of action, indications, efficacy, safety, costs and limitations.

Recurrent Pyroglutamic Acidosis Related to Therapeutic Acetaminophen.

Pyroglutamic acid, an intermediate in glutathione metabolism, can lead to elevated anion gap metabolic acidosis as rare complication of acetaminophen therapy in adults. Acquired pyroglutamic acidosis has been observed primarily in settings associated with glutathione deficiency. Risk factors for glutathione deficiency include critical illness, chronic liver or kidney disease, advanced age, female gender, alcohol abuse, malnutrition, pregnancy, antiepileptic drugs, and chronic acetaminophen use. Diagnosis of pyroglutamic acidosis requires both the exclusion of common etiologies of increased anion gap metabolic acidosis and a high index of suspicion. Treatment involves discontinuation of acetaminophen, supportive care, and addressing risk factors for glutathione deficiency. The current report describes an ambulatory patient with multiple risk factors for glutathione deficiency, who developed recurrent pyroglutamic acidosis due to acetaminophen use with therapeutic blood levels of acetaminophen.

Heart Failure Increases the Risk of Adverse Renal Outcomes in Patients With Normal Kidney Function.

BACKGROUND: Heart failure (HF) is associated with poor cardiac outcomes and mortality. It is not known whether HF leads to poor renal outcomes in patients with normal kidney function. We hypothesized that HF is associated with worse long-term renal outcomes. METHODS AND RESULTS: Among 3 570 865 US veterans with estimated glomerular filtration rate (eGFR) ≥60 mL min-1 1.73 m-2 during October 1, 2004 to September 30, 2006, we identified 156 743 with an International Classification of Diseases, Ninth Revision, diagnosis of HF. We examined the association of HF with incident chronic kidney disease (CKD), the composite of incident CKD or mortality, and rapid rate of eGFR decline (slopes steeper than -5 mL min-1 1.73 m-2 y-1) using Cox proportional hazard analyses and logistic regression. Adjustments were made for various confounders. The mean±standard deviation baseline age and eGFR of HF patients were 68±11 years and 78±14 mL min-1 1.73 m-2 and in patients without HF were 59±14 years and 84±16 mL min-1 1.73 m-2, respectively. HF patients had higher prevalence of hypertension, diabetes mellitus, cardiac, peripheral vascular and chronic lung diseases, stroke, and dementia. Incidence of CKD was 69.0/1000 patient-years in HF patients versus 14.5/1000 patient-years in patients without HF, and 22% of patients with HF had rapid decline in eGFR compared with 8.5% in patients without HF. HF patients had a 2.12-, 2.06-, and 2.13-fold higher multivariable-adjusted risk of incident CKD, composite of CKD or mortality, and rapid eGFR decline, respectively. CONCLUSIONS: HF is associated with significantly higher risk of incident CKD, incident CKD or mortality, and rapid eGFR decline. Early diagnosis and management of HF could help reduce the risk of long-term renal complications.

Application of Clinical Trial Results to Clinical Practice.

Two critical questions one must answer as one applies the results of a clinical trial to clinical practice are: (1) Regardless of whether the trial result is likely to be replicated or reproduced in a second large-scale trial, are the results likely to be reproduced in one's practice? (2) Regardless of whether the experimental treatment was better than the alternative on average for a population of patients, are the results clinically important for a given patient in one's practice? To determine if a study result is likely to be reproduced in one's clinical practice, it may be helpful to answer 5 questions: (1) Have steps been taken to minimize bias? (2) Is the result likely due to the treatment? (3) Is the result unlikely due to chance? (4) Is the study population representative of one's patients? (5) Is the totality of evidence consistent? If the answer to all 5 questions is "yes," then we posit that the trial result is likely to be reproduced in one's practice. If not, the likelihood of reproducibility is low. If the answer is yes to all questions except the last, then reproducibility in one's practice is not clear and depends on the strength of the prior versus the current evidence. If the prior evidence is strong, such as multiple pivotal randomized clinical trials, and if the current trial result is not consistent with the previous studies, then the current result may not be reproduced in one's practice. To determine if a study result is clinically important, a 3-step approach is suggested. Step 1. Decide, a priori, what a clinically meaningful difference between 2 treatments would be. This choice defines regions of beneficial, harmful, and trivial outcomes. Step 2. Identify the confidence intervals (CIs). Determine whether the 95% CI mostly includes the range of clinically beneficial outcomes and lies outside the range of clinically harmful outcomes. If these conditions are met, the result is probably clinically important, but the result may or may not be statistically significant. Put the CIs and the regions of benefit/harm together to make a decision about clinically important effects. Step 3. Assess the proportion of eyes with clinically meaningful changes in vision. The proportion of "responders" among patients receiving a given treatment reflects the likelihood of one's patient having a clinically meaningful response to the treatment. In summary, not all statistically significant results are reproduced, even those of carefully designed clinical trials. Determining if a study result is likely to be reproduced in one's practice is even more problematic. The 5-question test may help in this regard. The 5-question test attempts to assess whether steps have been taken to: minimize bias; avoid confounding; ensure adequate statistical power to support precision in the estimates of population parameters; insure external validity of the trial result; and determine whether there is a convergence of evidence consistent with the trial's major findings. To determine if a statistically significant result is likely to be clinically important, a 3-step approach may be useful, focusing on CIs and the proportion of eyes with clinically meaningful changes in vision. Application of clinical trial results to clinical practice requires critical analysis of the extant literature and good clinical judgment.

Posterior Segment Intraocular Foreign Bodies: A 10-Year Review.

PURPOSE: To describe the characteristics of open-globe injuries with posterior segment intraocular foreign bodies (IOFBs). DESIGN: Retrospective chart review study. PARTICIPANTS: Patients treated for posterior segment IOFB injuries. METHODS: Retrospective analysis of all patients with posterior segment IOFBs from 2003 to 2014 was conducted. Data including demographics, mechanism of injury, type of IOFB, method of diagnosis, presenting examination, medical and surgical treatment, visual outcomes, and complications were recorded. MAIN OUTCOME MEASURES: Visual acuity (VA); anatomically successful retinal reattachment; need for additional surgery; frequency of post-traumatic complications, such as sympathetic ophthalmia (SO), endophthalmitis, and enucleations; and accuracy of Ocular Trauma Score (OTS). RESULTS: Thirty-one patients (28 male; mean age, 36.6 years; 42% Hispanic) had posterior segment IOFB injuries, 23 (74%) of which were construction work related. Twenty-five IOFBs (81%) were metallic. Twenty-four IOFBs (77%) had Zone I entry. Computed tomography (CT) scan detected an IOFB in 21 of 22 eyes in which it was performed, with 1 scan highly suspicious for an IOFB. Average size of the IOFB was 10 mm3; size or initial VA did not have any correlation with final VA. The OTS had 60% accuracy in predicting final VA (n = 20). The majority of patients had traumatic cataract and vitreous hemorrhage (VH) on presentation (77% and 61%, respectively); 65% had a retinal tear or retinal detachment (RD), and these patients had worse final VA than those with no retinal pathology. Average time from injury to IOFB removal was 3 days because of the delay in presentation to our facility; 27 of 31 patients (87%) had IOFBs removed within 24 hours of presentation with pars plana vitrectomy (PPV) and either gas or silicone oil tamponade. Patients were admitted for an average of 4 days of intravenous antibiotics. The most common complication was recurrent RD in 11 patients (35%), which portended worse final VA. One patient (3%) developed SO. There were no cases of postoperative endophthalmitis or enucleation. CONCLUSIONS: Open-globe injuries with posterior segment IOFBs have a guarded visual prognosis, particularly when associated with RD. Increased awareness of the importance of eye protection can help minimize the occurrence of these injuries.

Localization and distribution of superoxide dismutase-1 in the neural tube morphogenesis of chick embryo.

Superoxide dismutase 1 (SOD- 1) is an antioxidant enzyme that regulates the levels of Reactive oxygen species (ROS) by catalyzing the conversion of superoxide radical into hydrogen peroxide (H2O2) and oxygen. ROS are known to play a significant role in various cellular processes, via redox modification of a variety of molecules that participate in signaling pathways involved in this processes. As the levels of ROS in cells are controlled by the levels of antioxidant enzymes, thus SOD-1 may be indirectly involved in regulating different cellular processes by maintaining the required levels of H2O2. Therefore, in the present study we have investigated the possible involvement of SOD- 1 in the neurulation during the development of chick embryo. During gastrulation, SOD- 1 immunoreactivity was observed throughout the ectoderm and cauda mesoderm areas, however, its presence during neurulation was restricted to certain areas of neural tube particularly in the dorsal neural tube where neural tube closure takes place. Assaying enzyme activity revealed a significant increase in the SOD activity during neurulation. Further, inhibition of SOD- 1 by Diethyldithiocarbamate (DDC) induced abnormalities in the development of the neural tube. SOD- 1 inhibition specifically affected the closure of neural tube in the anterior region. Thus, here we report the presence of SOD- 1 mainly in the ectoderm and tissues of ectodermal origin during gastrulation to neurulation which suggests that it may be involved in the regulating the cellular processes during neural tube morphogenesis.

Racial Differences in Association of Serum Calcium with Mortality and Incident Cardio- and Cerebrovascular Events.

CONTEXT: Abnormalities in calcium metabolism may potentially contribute to the development of vascular disease. Calcium metabolism may be different in African American (AA) vs white individuals, but the effect of race on the association of serum calcium with clinical outcomes remains unclear. OBJECTIVE: This study sought to examine race-specific associations of serum calcium levels with mortality and with major incident cardiovascular events. DESIGN AND SETTING: This was a historical cohort study in the U.S. Department of Veterans Affairs health care facilities. PARTICIPANTS: Participants included veterans (n = 1 967 622) with estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2. MAIN OUTCOME MEASURES: The association between serum calcium levels with all-cause mortality, incident coronary heart disease (CHD), and ischemic stroke incidence was examined in multivariable adjusted Cox proportional hazards models, including an interaction term for calcium and race. RESULTS: The association of calcium with all-cause mortality was U-shaped in both AA and white patients, but race modified the association of calcium with all-cause mortality. Compared with white patients, AA patients experienced lower risk of mortality when calcium was ≥ 8.8 mg/dL, with a statistically significant interaction (P < .001). Conversely, AA vs white race was associated with higher mortality when calcium was < 8.8 mg/dL. Calcium showed no significant association with ischemic stroke or CHD in both races; and race did not modify these associations (P = .37 and 0.11, respectively for interaction term). CONCLUSIONS: Race modified the U-shaped association between calcium and all-cause mortality. Serum calcium is not associated with incident stroke or CHD in either AA or white patients. The race-specific difference in the association of calcium levels with mortality warrants further examination.