Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 43 Records) |
Query Trace: Rhee S[original query] |
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Type 1 diabetes genetic risk in 109,954 veterans with adult-onset diabetes: The Million Veteran Program (MVP)
Yang PK , Jackson SL , Charest BR , Cheng YJ , Sun YV , Raghavan S , Litkowski EM , Legvold BT , Rhee MK , Oram RA , Kuklina EV , Vujkovic M , Reaven PD , Cho K , Leong A , Wilson PWF , Zhou J , Miller DR , Sharp SA , Staimez LR , North KE , Highland HM , Phillips LS . Diabetes Care 2024 OBJECTIVE: To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS: Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011-2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS: T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥ 90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and they resembled T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low risk group, the highest-risk group was more likely to have diabetic ketoacidosis (low 0.9% vs. highest GRS 3.7%), hypoglycemia prompting emergency visits (3.7% vs. 5.8%), outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%), a shorter median time to start insulin (3.5 vs. 1.4 years), use of a T1D diagnostic code (16.3% vs. 28.1%), low C-peptide levels if tested (1.8% vs. 32.4%), and glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001. CONCLUSIONS: Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk. However, the age and BMI of those participants resemble people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates. |
A modified Delphi approach to develop a trial protocol for antibiotic de-escalation in patients with suspected sepsis
Yarrington ME , Moehring RW , David MZ , Hamilton KW , Klompas M , Rhee C , Hsueh K , Ashley ED , Sinkowitz-Cochran RL , Ryan M , Anderson DJ . Antimicrob Steward Healthc Epidemiol 12/28/2021 1 (1) e44 BACKGROUND: Early administration of antibiotics in sepsis is associated with improved patient outcomes, but safe and generalizable approaches to de-escalate or discontinue antibiotics after suspected sepsis events are unknown. METHODS: We used a modified Delphi approach to identify safety criteria for an opt-out protocol to guide de-escalation or discontinuation of antibiotic therapy after 72 hours in non-ICU patients with suspected sepsis. An expert panel with expertise in antimicrobial stewardship and hospital epidemiology rated 48 unique criteria across 3 electronic survey rating tools. Criteria were rated primarily based on their impact on patient safety and feasibility for extraction from electronic health record review. The 48 unique criteria were rated by anonymous electronic survey tools, and the results were fed back to the expert panel participants. Consensus was achieved to either retain or remove each criterion. RESULTS: After 3 rounds, 22 unique criteria remained as part of the opt-out safety checklist. These criteria included high-risk comorbidities, signs of severe illness, lack of cultures during sepsis work-up or antibiotic use prior to blood cultures, or ongoing signs and symptoms of infection. CONCLUSIONS: The modified Delphi approach is a useful method to achieve expert-level consensus in the absence of evidence suifficient to provide validated guidance. The Delphi approach allowed for flexibility in development of an opt-out trial protocol for sepsis antibiotic de-escalation. The utility of this protocol should be evaluated in a randomized controlled trial. |
Neuroinvasive bacillus cereus infection in immunocompromised hosts: Epidemiologic investigation of 5 patients with acute myeloid leukemia
Little JS , Coughlin C , Hsieh C , Lanza M , Huang WY , Kumar A , Dandawate T , Tucker R , Gable P , Vazquez Deida AA , Moulton-Meissner H , Stevens V , McAllister G , Ewing T , Diaz M , Glowicz J , Winkler ML , Pecora N , Kubiak DW , Pearson JC , Luskin MR , Sherman AC , Woolley AE , Brandeburg C , Bolstorff B , McHale E , Fortes E , Doucette M , Smole S , Bunnell C , Gross A , Platt D , Desai S , Fiumara K , Issa NC , Baden LR , Rhee C , Klompas M , Baker MA . Open Forum Infect Dis 2024 11 (3) ofae048 BACKGROUND: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia. METHODS: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus, and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates. RESULTS: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year. CONCLUSIONS: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen. |
Serum concentrations of per- and polyfluoroalkyl substances and risk of renal cell carcinoma in the Multiethnic Cohort Study
Rhee J , Chang VC , Cheng I , Calafat AM , Botelho JC , Shearer JJ , Sampson JN , Setiawan VW , Wilkens LR , Silverman DT , Purdue MP , Hofmann JN . Environ Int 2023 180 108197 Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. We previously reported a positive association between serum perfluorooctanoate (PFOA) concentrations and risk of renal cell carcinoma (RCC) within the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, comprising predominantly White individuals enrolled in 1993-2001. To extend our investigations to a larger and more racially and ethnically diverse population, we conducted a nested case-control study of serum PFAS concentrations and RCC within the Multiethnic Cohort Study. We measured pre-diagnostic serum concentrations of nine PFAS among 428 RCC cases and 428 individually matched controls. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for risk of RCC in relation to each PFAS using conditional logistic regression, adjusting for RCC risk factors and other PFAS. PFOA was not associated with RCC risk overall [doubling in serum concentration, OR(continuous) = 0.89 (95 %CI = 0.67, 1.18)]. However, we observed suggestive positive associations among White participants [2.12 (0.87, 5.18)] and among participants who had blood drawn before 2002 [1.49 (0.77, 2.87)]. Furthermore, higher perfluorononanoate (PFNA) concentration was associated with increased risk of RCC overall [fourth vs. first quartile, OR = 1.84 (0.97, 3.50), P(trend) = 0.04; OR(continuous) = 1.29 (0.97, 1.71)], with the strongest association observed among African American participants [OR(continuous) = 3.69 (1.33, 10.25)], followed by Native Hawaiian [2.24 (0.70, 7.19)] and White [1.98 (0.92, 4.25)] participants. Most other PFAS were not associated with RCC. While PFOA was not associated with RCC risk overall in this racially and ethnically diverse population, the positive associations observed among White participants and those with sera collected before 2002 are consistent with previous PLCO findings. Our study also provided new evidence of a positive association between PFNA and RCC risk that was strongest in African American participants. These findings highlight the need for additional epidemiologic research investigating PFAS exposures and RCC in large racially and ethnically diverse populations. |
Healthcare-associated infections and conditions in the era of digital measurement
Classen DC , Rhee C , Dantes RB , Benin AL . Infect Control Hosp Epidemiol 2023 1-6 As the third edition of the Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals is released with the latest recommendations for the prevention and management of healthcare-associated infections (HAIs), a new approach to reporting HAIs is just beginning to unfold. This next generation of HAI reporting will be fully electronic and based largely on existing data in electronic health record (EHR) systems and other electronic data sources. It will be a significant change in how hospitals report HAIs and how the Centers for Disease Control and Prevention (CDC) and other agencies receive this information. This paper outlines what that future electronic reporting system will look like and how it will impact HAI reporting. |
Recommendations on data sharing in HIV drug resistance research
Inzaule SC , Siedner MJ , Little SJ , Avila-Rios S , Ayitewala A , Bosch RJ , Calvez V , Ceccherini-Silberstein F , Charpentier C , Descamps D , Eshleman SH , Fokam J , Frenkel LM , Gupta RK , Ioannidis JPA , Kaleebu P , Kantor R , Kassaye SG , Kosakovsky Pond SL , Kouamou V , Kouyos RD , Kuritzkes DR , Lessells R , Marcelin AG , Mbuagbaw L , Minalga B , Ndembi N , Neher RA , Paredes R , Pillay D , Raizes EG , Rhee SY , Richman DD , Ruxrungtham K , Sabeti PC , Schapiro JM , Sirivichayakul S , Steegen K , Sugiura W , van Zyl GU , Vandamme AM , Wensing AMJ , Wertheim JO , Gunthard HF , Jordan MR , Shafer RW . PLoS Med 2023 20 (9) e1004293 Author summary • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV. |
A nested case-control study of serum per- and polyfluoroalkyl substances and testicular germ cell tumors among U.S. Air Force servicemen
Purdue MP , Rhee J , Denic-Roberts H , McGlynn KA , Byrne C , Sampson J , Botelho JC , Calafat AM , Rusiecki J . Environ Health Perspect 2023 131 (7) 77007 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a component of firefighting foams used at military installations. Although high PFAS exposures have been related to cancer risks among civilian populations, the effects for military personnel are unclear. OBJECTIVES: We investigated associations between serum PFAS concentrations and testicular germ cell tumors (TGCT) among U.S. Air Force servicemen. METHODS: This nested case-control study involved active-duty Air Force servicemen with sera from the Department of Defense Serum Repository. We selected 530 cases and 530 controls individually matched on birth date, race and ethnicity, year entered the service, and year of sample collection, with prediagnostic serum samples collected between 1988 and 2017. A second prediagnostic sample, collected a median of 4 y after the first, was selected for 187 case-control pairs. Seven PFAS were quantified using isotope-dilution tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression adjusting for military grade, number of deployments, and, in some models, other PFAS, estimated associations between PFAS concentrations (categorized using quartiles among controls) and TGCT. RESULTS: Elevated concentrations of some PFAS were observed for military employment in firefighting [perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid] and service at a base with high PFAS concentrations in drinking water (PFHxS). Elevated PFOS concentrations in the second sample were positively associated with TGCT [OR for fourth vs. first quartile (ORQ4) = 2.6, 95% CI: 1.1, 6.4; ptrend = 0.02], including after adjustment for other PFAS (ORQ4 = 4.6, 95% CI: 1.4, 15.1; ptrend = 0.009). Associations with PFOS in the first/only samples were weak and not statistically significant. Elevated concentrations of perfluorononanoic acid were inversely associated with TGCT, whereas results were null for other PFAS. DISCUSSION: We identified service-related predictors of PFAS concentrations and increased TGCT relative risks with elevated PFOS concentrations among Air Force servicemen. These findings warrant further investigation in other populations and military service branches. 10.1289/EHP12603. |
Prevalence of HPV infection among Thai schoolgirls in the north-eastern provinces in 2018: implications for HPV immunization policy
Vongpunsawad S , Rhee C , Nilyanimit P , Poudyal N , Jiamsiri S , Ahn HS , Lee J , Seo HW , Klinsupa W , Park S , Premsri N , Namwat C , Silaporn P , Excler JL , Kim DR , Markowitz LE , Unger ER , Rerks-Ngarm S , Lynch J , Poovorawan Y . IJID Reg 2023 7 110-115 OBJECTIVE: The aim of this study was to determine the prevalence of high-risk (HR) and vaccine-type human papillomavirus (HPV) infection among Thai schoolgirls who were not included in the national HPV immunization program. METHODS: Cross-sectional surveys were conducted among grade 10 (15-16 years old) and grade 12 (17-18 years old) schoolgirls in two provinces of Thailand. Urine samples were collected using the Colli-Pee(Ⓡ) device from November 2018 to February 2019. The samples were initially tested using Cobas(Ⓡ) 4800. Subsequently, all Cobas-positive samples and 1:1 matched Cobas-negative samples were tested by Anyplex(Ⓡ) assay. Prevalences of any HPV, any HR HPV, vaccine-type HPV, and individual HR HPV types were estimated by school grade. RESULTS: Prevalences of any HPV and any HR HPV were 11.6% and 8.6% for grade 10, and 18.5% and 12.4% for grade 12 schoolgirls, respectively. Prevalences of bivalent vaccine-type HPV infection in grades 10 and 12 were 3.4% and 4.5%, respectively. Prevalences of quadrivalent and nonavalent vaccine-type HPV infections were 4.0%/6.6% and 6.4%/10.4% in grades 10 and 12, respectively. HPV16 was the most common type detected, followed by HPV58, 51, and 52. Circulating HR HPV types were similar between the school grades. CONCLUSION: A substantial burden of HR HPV infections was found among unvaccinated high school girls in Thailand. |
A prospective nested case-control study of serum concentrations of per- and polyfluoroalkyl substances and aggressive prostate cancer risk.
Rhee J , Barry KH , Huang WY , Sampson JN , Hofmann JN , Silverman DT , Calafat AM , Botelho JC , Kato K , Purdue MP , Berndt SI . Environ Res 2023 228 115718 Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent organic pollutants detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested an association between PFAS and prostate cancer, but evidence from population-based studies is limited. We investigated the association between pre-diagnostic serum PFAS concentrations and aggressive prostate cancer risk in a large prospective study. We measured pre-diagnostic serum concentrations of eight PFAS, including perfluorooctanoate (PFOA), for 750 aggressive prostate cancer cases and 750 individually matched controls within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We assessed the reproducibility of PFAS concentrations in serial samples collected up to six years apart among 60 controls using intraclass correlation coefficients (ICCs). Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with prostate cancer, adjusting for other PFAS and potential confounders. Concentrations of most PFAS were consistent (ICC>0.7) across the serial samples over time. We observed an inverse association between PFOA and aggressive prostate cancer (OR(continuous) = 0.79, 95% CI = 0.63, 0.99), but the association was limited to cases diagnosed ≤3 years after blood collection and became statistically non-significant for cases diagnosed with later follow-up (>3 years, OR(continuous) = 0.90, 95% CI = 0.79, 1.03). Other PFAS were not associated with aggressive prostate cancer risk. Although we cannot rule out an increased risk at higher levels, our findings from a population with PFAS serum concentrations comparable to the general population do not support an association with increased risk of aggressive prostate cancer. |
Prevalence of microcephaly and Zika virus infection in a pregnancy cohort in Kenya, 2017-2019
Osoro E , Inwani I , Mugo C , Hunsperger E , Verani JR , Omballa V , Wamalwa D , Rhee C , Nduati R , Kinuthia J , Jin H , Okutoyi L , Mwaengo D , Maugo B , Otieno NA , Mirieri H , Shabibi M , Munyua P , Njenga MK , Widdowson MA . BMC Med 2022 20 (1) 291 BACKGROUND: Zika virus (ZIKV), first discovered in Uganda in 1947, re-emerged globally in 2013 and was later associated with microcephaly and other birth defects. We determined the incidence of ZIKV infection and its association with adverse pregnancy and fetal outcomes in a pregnancy cohort in Kenya. METHODS: From October 2017 to July 2019, we recruited and followed up women aged ≥ 15 years and ≤ 28 weeks pregnant in three hospitals in coastal Mombasa. Monthly follow-up included risk factor questions and a blood sample collected for ZIKV serology. We collected anthropometric measures (including head circumference), cord blood, venous blood from newborns, and any evidence of birth defects. Microcephaly was defined as a head circumference (HC) < 2 standard deviations (SD) for sex and gestational age. Severe microcephaly was defined as HC < 3 SD for sex and age. We tested sera for anti-ZIKV IgM antibodies using capture enzyme-linked immunosorbent assay (ELISA) and confirmed positives using the plaque reduction neutralization test (PRNT(90)) for ZIKV and for dengue (DENV) on the samples that were ZIKV neutralizing antibody positive. We collected blood and urine from participants reporting fever or rash for ZIKV testing. RESULTS: Of 2889 pregnant women screened for eligibility, 2312 (80%) were enrolled. Of 1916 recorded deliveries, 1816 (94.6%) were live births and 100 (5.2%) were either stillbirths or spontaneous abortions (< 22 weeks of gestation). Among 1236 newborns with complete anthropometric measures, 11 (0.9%) had microcephaly and 3 (0.2%) had severe microcephaly. A total of 166 (7.2%) participants were positive for anti-ZIKV IgM, 136 of whom became seropositive during follow-up. Among the 166 anti-ZIKV IgM positive, 3 and 18 participants were further seropositive for ZIKV and DENV neutralizing antibodies, respectively. Of these 3 and 18 pregnant women, one and 13 (72.2%) seroconverted with antibodies to ZIKV and DENV, respectively. All 308 samples (serum and urine samples collected during sick visits and samples that were anti-ZIKV IgM positive) tested by RT-PCR were negative for ZIKV. No adverse pregnancy or neonatal outcomes were reported among the three participants with confirmed ZIKV exposure. Among newborns from pregnant women with DENV exposure, four (22.2%) were small for gestational age and one (5.6%) had microcephaly. CONCLUSIONS: The prevalence of severe microcephaly among newborns in coastal Kenya was high relative to published estimates from facility-based studies in Europe and Latin America, but little evidence of ZIKV transmission. There is a need for improved surveillance for microcephaly and other congenital malformations in Kenya. |
Potential misclassification of diabetes and prediabetes in the U.S.:Mismatched hba1c and glucose in NHANES 2005-2016
Staimez LR , Kipling LM , Nina Ham J , Legvold BT , Jackson SL , Wilson PWF , Rhee MK , Phillips LS . Diabetes Res Clin Pract 2022 189 109935 AIMS: To assess the prevalence and clinical implications of "mismatches" between HbA1c and glucose levels in the United States across the life course. METHODS: Participants ages 12-79 years from U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2016 without known diagnosis of diabetes and who had a 75g oral glucose tolerance test were included. Previously undiagnosed diabetes (DM), prediabetes, and normal glucose metabolism (NGM) were defined using American Diabetes Association cut-points. Mismatches were defined by the hemoglobin glycation index (HGI). RESULTS: In 10,361 participants, 5% and 41% had diabetes and prediabetes, respectively, by fasting or 2-hour glucose criteria. By HbA1c criteria, the high HGI tertile consisted of mostly abnormal classification (3% DM, 52% prediabetes) and the low HGI tertile contained mostly normal classification (78% NGM). Across all ages, 15% (weighted: 30 million individuals) had clinically significant mismatches of HGI magnitude ≥+0.5% (i.e., high mismatch) or ≤-0.5% (low mismatch). Mismatch was most common in older adults and non-Hispanic Black participants. CONCLUSIONS: Mismatches of clinically significant magnitude could lead to HbA1c-related misdiagnosis or inappropriate management in up to 30 million Americans. Older adults, non-Hispanic Black individuals, and others with high mismatches may benefit from complementing HbA1c with additional diagnostic and management strategies. |
A community intervention effectiveness study of single dose or two doses of bivalent HPV vaccine (CERVARIX) in female school students in Thailand
Jiamsiri S , Rhee C , Ahn HS , Poudyal N , Seo HW , Klinsupa W , Nilyanimit P , Premsri N , Namwat C , Vonpunsawad S , Chon Y , Park S , Kim DR , Unger ER , Markowitz L , Poovorawan Y , Rerks-Ngarm S , Excler JL , Lynch J . PLoS One 2022 17 (4) e0267294 Human papillomavirus (HPV) is a common infection principally spread through sexual activity. Most HPV infections are asymptomatic and resolve spontaneously. However, persistent infection may progress to cervical cancer. Highly efficacious HPV vaccines have been available since 2006, yet uptake into national programs has been slow in part due to cost. WHO guidelines call for a two-dose (0,6 month) schedule for girls 9-14 years of age. Post-hoc analyses of randomized trials have found high vaccine effectiveness following a single dose of vaccine. In order to provide additional data on the potential impact of single dose HPV vaccination in a real-world setting, we are conducting an effectiveness study among Thai schoolgirls. This is an observational study of a single dose (SD) or two doses (2D) of the bivalent HPV vaccine CERVARIX (GlaxoSmithKline plc.) administered in a school-based program to 8-9,000 Grade 8 female students in two provinces of Thailand beginning in 2018; one province is assigned the SD, and the other the standard 2D regimen. The reduction in HPV vaccine-type prevalence will be assessed in each province two and four years after vaccination by comparing HPV prevalence in urine samples obtained through cross-sectional surveys of the immunized grade cohort as they age and compared to a historical "baseline" HPV prevalence of same age students. |
Development and evaluation of a structured guide to assess the preventability of hospital-onset bacteremia and fungemia
Schrank GM , Sick-Samuels A , Bleasdale SC , Jacob JT , Dantes R , Gokhale RH , Mayer J , Mehrotra P , Mehta SA , MenaLora AJ , Ray SM , Rhee C , Salinas JL , Seo SK , Shane AL , Nadimpalli G , Milstone AM , Robinson G , Brown CH , Harris AD , Leekha S . Infect Control Hosp Epidemiol 2022 43 (10) 1-7 OBJECTIVE: To assess preventability of hospital-onset bacteremia and fungemia (HOB), we developed and evaluated a structured rating guide accounting for intrinsic patient and extrinsic healthcare-related risks. DESIGN: HOB preventability rating guide was compared against a reference standard expert panel. PARTICIPANTS: A 10-member panel of clinical experts was assembled as the standard of preventability assessment, and 2 physician reviewers applied the rating guide for comparison. METHODS: The expert panel independently rated 82 hypothetical HOB scenarios using a 6-point Likert scale collapsed into 3 categories: preventable, uncertain, or not preventable. Consensus was defined as concurrence on the same category among 70% experts. Scenarios without consensus were deliberated and followed by a second round of rating.Two reviewers independently applied the rating guide to adjudicate the same 82 scenarios in 2 rounds, with interim revisions. Interrater reliability was evaluated using the (kappa) statistic. RESULTS: Expert panel consensus criteria were met for 52 scenarios (63%) after 2 rounds.After 2 rounds, guide-based rating matched expert panel consensus in 40 of 52 (77%) and 39 of 52 (75%) cases for reviewers 1 and 2, respectively. Agreement rates between the 2 reviewers were 84% overall (, 0.76; 95% confidence interval [CI], 0.64-0.88]) and 87% (, 0.79; 95% CI, 0.65-0.94) for the 52 scenarios with expert consensus. CONCLUSIONS: Preventability ratings of HOB scenarios by 2 reviewers using a rating guide matched expert consensus in most cases with moderately high interreviewer reliability. Although diversity of expert opinions and uncertainty of preventability merit further exploration, this is a step toward standardized assessment of HOB preventability. |
Epidemiology, outcomes, and trends of patients with sepsis and opioid-related hospitalizations in U.S. hospitals
Alrawashdeh M , Klompas M , Kimmel S , Larochelle MR , Gokhale RH , Dantes RB , Hoots B , Hatfield KM , Reddy SC , Fiore AE , Septimus EJ , Kadri SS , Poland R , Sands K , Rhee C . Crit Care Med 2021 49 (12) 2102-2111 OBJECTIVES: Widespread use and misuse of prescription and illicit opioids have exposed millions to health risks including serious infectious complications. Little is known, however, about the association between opioid use and sepsis. DESIGN: Retrospective cohort study. SETTING: About 373 U.S. hospitals. PATIENTS: Adults hospitalized between January 2009 and September 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was identified by clinical indicators of concurrent infection and organ dysfunction. Opioid-related hospitalizations were identified by the International Classification of Diseases, 9th Revision, Clinical Modification codes and/or inpatient orders for buprenorphine. Clinical characteristics and outcomes were compared by sepsis and opioid-related hospitalization status. The association between opioid-related hospitalization and all-cause, in-hospital mortality in patients with sepsis was assessed using mixed-effects logistic models to adjust for baseline characteristics and severity of illness. The cohort included 6,715,286 hospitalizations; 375,479 (5.6%) had sepsis, 130,399 (1.9%) had opioid-related hospitalizations, and 8,764 (0.1%) had both. Compared with sepsis patients without opioid-related hospitalizations (n = 366,715), sepsis patients with opioid-related hospitalizations (n = 8,764) were younger (mean 52.3 vs 66.9 yr) and healthier (mean Elixhauser score 5.4 vs 10.5), had more bloodstream infections from Gram-positive and fungal pathogens (68.9% vs 47.0% and 10.6% vs 6.4%, respectively), and had lower in-hospital mortality rates (10.6% vs 16.2%; adjusted odds ratio, 0.73; 95% CI, 0.60-0.79; p < 0.001 for all comparisons). Of 1,803 patients with opioid-related hospitalizations who died in-hospital, 928 (51.5%) had sepsis. Opioid-related hospitalizations accounted for 1.5% of all sepsis-associated deaths, including 5.7% of sepsis deaths among patients less than 50 years old. From 2009 to 2015, the proportion of sepsis hospitalizations that were opioid-related increased by 77% (95% CI, 40.7-123.5%). CONCLUSIONS: Sepsis is an important cause of morbidity and mortality in patients with opioid-related hospitalizations, and opioid-related hospitalizations contribute disproportionately to sepsis-associated deaths among younger patients. In addition to ongoing efforts to combat the opioid crisis, public health agencies should focus on raising awareness about sepsis among patients who use opioids and their providers. |
Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.
Kadri SS , Sun J , Lawandi A , Strich JR , Busch LM , Keller M , Babiker A , Yek C , Malik S , Krack J , Dekker JP , Spaulding AB , Ricotta E , Powers Iii JH , Rhee C , Klompas M , Athale J , Boehmer TK , Gundlapalli AV , Bentley W , Datta SD , Danner RL , Demirkale CY , Warner S . Ann Intern Med 2021 174 (9) 1240-1251 BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute. |
Reading between the lines: A qualitative case study of national public health institute functions and attributes in the Joint External Evaluation
Clemente J , Rhee S , Miller B , Bronner E , Whitney E , Bratton S , Carnevale C . J Public Health Afr 2020 11 (1) 1329 National Public Health Institutes (NPHIs) are national-level institutions that can lead and coordinate a country's public health system. The Africa Centres for Disease Control and Prevention (Africa CDC) considers NPHI development critical to strengthening public health systems in Africa. This paper describes how Joint External Evaluation (JEE) reports demonstrate the role NPHIs can play in supporting the goals of IHR compliance and global health security. This study is a secondary document-based qualitative analysis of JEE reports from 11 countries in the WHO AFRO region (Botswana, Ethiopia, Liberia, Mozambique, Namibia, Nigeria, Rwanda, Sierra Leone, South Africa, Uganda, and Zambia). Researchers found three distinct thematic areas: i) core public health functions, ii) governance, and iii) coordination, collaboration, and communication. These themes and their interlinkages, both in pairs and all three, were of importance in displaying the roles that NPHIs could play in the strengthening of health systems. The data suggests that NPHIs, though not always explicitly mentioned in the data, may have a vital role in strengthening health systems across Africa and their governments' goals of achieving IHR compliance. |
Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals
Kadri SS , Lai YL , Warner S , Strich JR , Babiker A , Ricotta EE , Demirkale CY , Dekker JP , Palmore TN , Rhee C , Klompas M , Hooper DC , Powers JH3rd , Srinivasan A , Danner RL , Adjemian J . Lancet Infect Dis 2020 21 (2) 241-251 BACKGROUND: The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. METHODS: Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected-and subsequently confirmed-bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy-which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro-overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy. FINDINGS: 21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28-1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68-10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales. INTERPRETATION: Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes. FUNDING: US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality. |
Retinopathy develops at similar glucose levels but higher HbA 1c levels in people with black African ancestry compared to white European ancestry: evidence for the need to individualize HbA 1c interpretation.
Staimez LR , Rhee MK , Deng Y , Safo SE , Butler SM , Legvold BT , Jackson SL , Ford CN , Wilson PWF , Long Q , Phillips LS . Diabet Med 2020 37 (6) 1049-1057 AIMS: To examine the association of HbA(1c) and glucose levels with incident diabetic retinopathy according to black African or white European ancestry. METHODS: In this retrospective cohort study of 202 500 US Veterans with diabetes (2000-2014), measures included HbA(1c) , outpatient random serum/plasma glucose, and incident retinopathy [conversion from negative to ≥2 positive evaluations (ICD-9 codes), without a subsequent negative]. RESULTS: At baseline, the study population had a mean age of 59.3 years, their mean BMI was 31.9 kg/m(2) , HbA(1c) level was 57 mmol/mol (7.4%) and glucose level was 8.8 mmol/l, and 77% were of white European ancestry (white individuals) and 21% of black African ancestry (black individuals). HbA(1c) was 0.3% higher in black vs white individuals (P < 0.001), adjusting for baseline age, sex, BMI, estimated glomerular filtration rate (eGFR), haemoglobin, and average systolic blood pressure and glucose. Over 11 years, incident retinopathy occurred in 9% of black and 7% of white individuals, but black individuals had higher HbA(1c) , glucose, and systolic blood pressure (all P < 0.001); adjusted for these factors, incident retinopathy was reduced in black vs white individuals (P < 0.001). The population incidence of retinopathy (7%) was associated with higher mean baseline HbA(1c) in individuals with black vs white ancestry [63 mmol/mol (7.9%) vs 58 mmol/mol (7.5%); P < 0.001)], but with similar baseline glucose levels (9.0 vs 9.0 mmol/l; P = 0.660, all adjusted for baseline age, sex and BMI). CONCLUSIONS: Since retinopathy occurs at higher HbA(1c) levels in black people for a given level of average plasma glucose, strategies may be needed to individualize the interpretation of HbA(1c) measurements. |
Moderate-to-High Levels of Pretreatment HIV Drug Resistance in KwaZulu-Natal Province, South Africa.
Chimukangara B , Kharsany ABM , Lessells RJ , Naidoo K , Rhee SY , Manasa J , Graf T , Lewis L , Cawood C , Khanyile D , Diallo K , Ayalew KA , Shafer RW , Hunt G , Pillay D , Abdool SK , de Oliveira T . AIDS Res Hum Retroviruses 2019 35 (2) 129-138 There is evidence of increasing levels of pretreatment HIV drug resistance (PDR) in Southern Africa. We used data from two large population-based HIV surveillance studies to estimate prevalence of PDR in KwaZulu-Natal, the province with the highest HIV prevalence in South Africa. Sanger sequencing was performed on samples obtained from a longitudinal HIV surveillance program (study A, 2013-2014) and the HIV Incidence Provincial Surveillance System (study B, 2014-2015). Sequences were included for adult HIV positive participants (age >/=15 years for study A, age 15-49 years for study B) with no documented prior exposure to antiretroviral therapy (ART). Overall and drug class-specific PDR was estimated using the World Health Organization 2009 surveillance drug resistance mutation (SDRM) list, and phylogenetic analysis was performed to establish evidence of drug resistance transmission linkage. A total of 1,845 sequences were analyzed (611 study A; 1,234 study B). An overall PDR prevalence of 9.2% [95% confidence interval (CI) 7.0-11.7] was observed for study A and 11.0% (95% CI 8.9-13.2) for study B. In study B, the prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR exceeded 10% for sequences collected in 2014 (10.2%, 95% CI 7.5-12.9). The most prevalent SDRMs were K103NS (7.5%), M184VI (2.4%), and V106AM (1.4%). There was no evidence of large transmission chains of drug-resistant virus. High level NNRTI PDR (>10%) suggests a need to modify the standard first-line ART regimen and to focus attention on improving the quality of HIV prevention, treatment, and care. |
A national approach to pediatric sepsis surveillance
Hsu HE , Abanyie F , Agus MSD , Balamuth F , Brady PW , Brilli RJ , Carcillo JA , Dantes R , Epstein L , Fiore AE , Gerber JS , Gokhale RH , Joyner BL Jr , Kissoon N , Klompas M , Lee GM , Macias CG , Puopolo KM , Sulton CD , Weiss SL , Rhee C . Pediatrics 2019 144 (6) Pediatric sepsis is a major public health concern, and robust surveillance tools are needed to characterize its incidence, outcomes, and trends. The increasing use of electronic health records (EHRs) in the United States creates an opportunity to conduct reliable, pragmatic, and generalizable population-level surveillance using routinely collected clinical data rather than administrative claims or resource-intensive chart review. In 2015, the US Centers for Disease Control and Prevention recruited sepsis investigators and representatives of key professional societies to develop an approach to adult sepsis surveillance using clinical data recorded in EHRs. This led to the creation of the adult sepsis event definition, which was used to estimate the national burden of sepsis in adults and has been adapted into a tool kit to facilitate widespread implementation by hospitals. In July 2018, the Centers for Disease Control and Prevention convened a new multidisciplinary pediatric working group to tailor an EHR-based national sepsis surveillance approach to infants and children. Here, we describe the challenges specific to pediatric sepsis surveillance, including evolving clinical definitions of sepsis, accommodation of age-dependent physiologic differences, identifying appropriate EHR markers of infection and organ dysfunction among infants and children, and the need to account for children with medical complexity and the growing regionalization of pediatric care. We propose a preliminary pediatric sepsis event surveillance definition and outline next steps for refining and validating these criteria so that they may be used to estimate the national burden of pediatric sepsis and support site-specific surveillance to complement ongoing initiatives to improve sepsis prevention, recognition, and treatment. |
Global knowledge gaps in acute febrile illness etiologic investigations: A scoping review
Rhee C , Kharod GA , Schaad N , Furukawa NW , Vora NM , Blaney DD , Crump JA , Clarke KR . PLoS Negl Trop Dis 2019 13 (11) e0007792 BACKGROUND: Acute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations. METHODOLOGY/FINDINGS: Using pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38.0 degrees C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability. CONCLUSIONS: Wider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666. |
Racial differences in performance of HbA1c for the classification of diabetes and prediabetes among US adults of non-Hispanic black and white race
Ford CN , Leet RW , Kipling LM , Rhee MK , Jackson SL , Wilson PWF , Phillips LS , Staimez LR . Diabet Med 2019 36 (10) 1234-1242 AIM: To characterize differences between black and white people in optimal HbA1c thresholds for diagnoses of diabetes and prediabetes. METHODS: Data were included from the National Health and Nutrition Examination Survey, 2005-2014. Black and white adults (age 18-70 years) who underwent an oral glucose tolerance test and had available fasting plasma glucose, 2-h plasma glucose and HbA1c measurements were eligible for inclusion. Diabetes or prediabetes status was defined by fasting plasma glucose and 2-h plasma glucose using American Diabetes Association criteria. Classification of diabetes, prediabetes and dysglycaemia by HbA1c was evaluated for a range of HbA1c thresholds, with optimal thresholds defined as those values that maximized the sum of sensitivity and specificity (Youden's index). RESULTS: In 5324 black (32.3%) and white (67.7%) individuals, Youden's index (optimal) thresholds for HbA1c were >/=42 mmol/mol (6.0%) and >/=39 mmol/mol (5.7%) for discriminating diabetes vs non-diabetes, >/= 44 mmol/mol (6.2%) and >/=39 mmol/mol (5.7%) for discriminating diabetes vs prediabetes (excluding normoglycaemia), >/=39 mmol/mol (5.7%) and >/=37 mmol/mol (5.5%) for discriminating dysglycaemia vs normoglycaemia, and >/=39 mmol/mol (5.7%) and >/=37 mmol/mol (5.5%) for discriminating prediabetes vs normoglycaemia (excluding diabetes), in black and white people, respectively. CONCLUSIONS: Consistently higher optimal HbA1c thresholds in black people than in white people suggest a need to individualize HbA1c relative to glucose levels if HbA1c is used to diagnose diabetes and prediabetes. |
Strengths, pitfalls, and lessons learned in implementing electronic collection of childhood vaccination data in Zambia: The SmartCare experience
Clarke KEN , Phiri Chibawe C , Essiet-Gibson I , Dien Mwansa F , Jacenko S , Rhee C , Kwendakwape M , Kashoka A , MacNeil A . Int J Med Inform 2019 129 146-153 Background: Despite widespread interest in computerized vaccination information systems, evaluation of the data quality in these systems and their acceptability to frontline healthcare workers in low and middle-income countries aren't well addressed in the literature. Objective(s): Evaluation of vaccination data quality and facility-level staff perspectives on the strengths and challenges of a vaccination data module in a widely used electronic health record (EHR) system in Zambia. Method(s): After a desk review of data from two provinces, a cross-sectional mixed methods study was designed, including quantitative analysis of data quality and qualitative analysis of the module's acceptability to facility staff, using the Information System Success model as the framework for evaluation of system quality, service quality, and information quality. Data were collected from 10 purposively sampled health facilities. Result(s): There was low current use of the vaccination module by facilities in the study area (2%). Daily power outages presented a practical challenge. Staff who had used previous EHRs had concerns about sustainability. System quality: While the module was user-friendly, there were concerns about EHR compatibility with vaccination workflow and outreach settings, where vaccines are commonly administered to older children. Service quality: The module was viewed as dependable; perceptions were influenced by computer literacy. Information quality: The database contained incomplete and incongruous data. Staff perceived data as accurate but incomplete; easy access to data was a strength. Conclusion(s): Potential benefits of the vaccination module were frequently unrealized due to infrastructure, workflow, and data flow challenges that resulted in low module use and poor information quality. Elements to optimize vaccination information system implementation could include robust engagement of facility-level staff in system design, system suitability to the vaccination setting and workflow, and comprehensive planning for data flow, sustainability, data monitoring and feedback. Adaptability to the outreach setting might be increasingly important as vaccination schedules extend past infancy. |
Inappropriate use of antibiotics for childhood diarrhea case management - Kenya, 2009-2016
Rhee C , Aol G , Ouma A , Audi A , Muema S , Auko J , Omore R , Odongo G , Wiegand RE , Montgomery JM , Widdowson MA , O'Reilly CE , Bigogo G , Verani JR . BMC Public Health 2019 19 468 Background: Antibiotics are essential to treat for many childhood bacterial infections; however inappropriate antibiotic use contributes to antimicrobial resistance. For childhood diarrhea, empiric antibiotic use is recommended for dysentery (bloody diarrhea) for which first-line therapy is ciprofloxacin. We assessed inappropriate antibiotic prescription for childhood diarrhea in two primary healthcare facilities in Kenya. Methods: We analyzed data from the Kenya Population Based Infectious Disease Surveillance system in Asembo (rural, malaria-endemic) and Kibera (urban slum, non-malaria-endemic). We examined records of children aged 2-59 months with diarrhea (≥3 loose stools in 24 h) presenting for care from August 21, 2009 to May 3, 2016, excluding visits with non-diarrheal indications for antibiotics. We examined the frequency of antibiotic over-prescription (antibiotic prescription for non-dysentery), under-prescription (no antibiotic prescription for dysentery), and inappropriate antibiotic selection (non-recommended antibiotic). We examined factors associated with over-prescription and under-prescription using multivariate logistic regression with generalized estimating equations. Results: Of 2808 clinic visits with diarrhea in Asembo, 2685 (95.6%) were non-dysentery visits and antibiotic over-prescription occurred in 52.5%. Of 4697 clinic visits with diarrhea in Kibera, 4518 (96.2%) were non-dysentery and antibiotic over-prescription occurred in 20.0%. Antibiotic under-prescription was noted in 26.8 and 73.7% of dysentery cases in Asembo and Kibera, respectively. Ciprofloxacin was used for 11% of dysentery visits in Asembo and 0% in Kibera. Factors associated with over- and under-prescription varied by site. In Asembo a discharge diagnosis of gastroenteritis was associated with over-prescription (adjusted odds ratio [aOR]:8.23, 95% confidence interval [95%CI]: 3.68-18.4), while malaria diagnosis was negatively associated with antibiotic over-prescription (aOR 0.37, 95%CI: 0.25-0.54) but positively associated with antibiotic under-prescription (aOR: 1.82, 95%CI: 1.05-3.13). In Kibera, over-prescription was more common among visits with concurrent signs of respiratory infection (difficulty breathing; aOR: 3.97, 95%CI: 1.28-12.30, cough: aOR: 1.42, 95%CI: 1.06-1.90) and less common among children aged < 1 year (aOR: 0.82, 95%CI: 0.71-0.94). Conclusions: Inappropriate antibiotic prescription was common in childhood diarrhea management and efforts are needed to promote rational antibiotic use. Interventions to improve antibiotic use for diarrhea should consider the influence of malaria diagnosis on clinical decision-making and address both over-prescription, under-prescription, and inappropriate antibiotic selection. |
Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000-2016: A Pooled Sequence Analysis.
Chimukangara B , Lessells RJ , Rhee SY , Giandhari J , Kharsany ABM , Naidoo K , Lewis L , Cawood C , Khanyile D , Ayalew KA , Diallo K , Samuel R , Hunt G , Vandormael A , Stray-Pedersen B , Gordon M , Makadzange T , Kiepiela P , Ramjee G , Ledwaba J , Kalimashe M , Morris L , Parikh UM , Mellors JW , Shafer RW , Katzenstein D , Moodley P , Gupta RK , Pillay D , Abdool Karim SS , de Oliveira T . EClinicalMedicine 2019 9 26-34 Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC. |
Prevalence, underlying causes, and preventability of sepsis-associated mortality in US acute care hospitals
Rhee C , Jones TM , Hamad Y , Pande A , Varon J , O'Brien C , Anderson DJ , Warren DK , Dantes RB , Epstein L , Klompas M . JAMA Netw Open 2019 2 (2) e187571 Importance: Sepsis is present in many hospitalizations that culminate in death. The contribution of sepsis to these deaths, and the extent to which they are preventable, is unknown. Objective: To estimate the prevalence, underlying causes, and preventability of sepsis-associated mortality in acute care hospitals. Design, Setting, and Participants: Cohort study in which a retrospective medical record review was conducted of 568 randomly selected adults admitted to 6 US academic and community hospitals from January 1, 2014, to December 31, 2015, who died in the hospital or were discharged to hospice and not readmitted. Medical records were reviewed from January 1, 2017, to March 31, 2018. Main Outcomes and Measures: Clinicians reviewed cases for sepsis during hospitalization using Sepsis-3 criteria, hospice-qualifying criteria on admission, immediate and underlying causes of death, and suboptimal sepsis-related care such as inappropriate or delayed antibiotics, inadequate source control, or other medical errors. The preventability of each sepsis-associated death was rated on a 6-point Likert scale. Results: The study cohort included 568 patients (289 [50.9%] men; mean [SD] age, 70.5 [16.1] years) who died in the hospital or were discharged to hospice. Sepsis was present in 300 hospitalizations (52.8%; 95% CI, 48.6%-57.0%) and was the immediate cause of death in 198 cases (34.9%; 95% CI, 30.9%-38.9%). The next most common immediate causes of death were progressive cancer (92 [16.2%]) and heart failure (39 [6.9%]). The most common underlying causes of death in patients with sepsis were solid cancer (63 of 300 [21.0%]), chronic heart disease (46 of 300 [15.3%]), hematologic cancer (31 of 300 [10.3%]), dementia (29 of 300 [9.7%]), and chronic lung disease (27 of 300 [9.0%]). Hospice-qualifying conditions were present on admission in 121 of 300 sepsis-associated deaths (40.3%; 95% CI 34.7%-46.1%), most commonly end-stage cancer. Suboptimal care, most commonly delays in antibiotics, was identified in 68 of 300 sepsis-associated deaths (22.7%). However, only 11 sepsis-associated deaths (3.7%) were judged definitely or moderately likely preventable; another 25 sepsis-associated deaths (8.3%) were considered possibly preventable. Conclusions and Relevance: In this cohort from 6 US hospitals, sepsis was the most common immediate cause of death. However, most underlying causes of death were related to severe chronic comorbidities and most sepsis-associated deaths were unlikely to be preventable through better hospital-based care. Further innovations in the prevention and care of underlying conditions may be necessary before a major reduction in sepsis-associated deaths can be achieved. |
Sepsis surveillance using adult sepsis events simplified eSOFA criteria versus sepsis-3 sequential organ failure assessment criteria
Rhee C , Zhang Z , Kadri SS , Murphy DJ , Martin GS , Overton E , Seymour CW , Angus DC , Dantes R , Epstein L , Fram D , Schaaf R , Wang R , Klompas M . Crit Care Med 2019 47 (3) 307-314 OBJECTIVES: Sepsis-3 defines organ dysfunction as an increase in the Sequential Organ Failure Assessment score by greater than or equal to 2 points. However, some Sequential Organ Failure Assessment score components are not routinely recorded in all hospitals' electronic health record systems, limiting its utility for wide-scale sepsis surveillance. The Centers for Disease Control and Prevention recently released the Adult Sepsis Event surveillance definition that includes simplified organ dysfunction criteria optimized for electronic health records (eSOFA). We compared eSOFA versus Sequential Organ Failure Assessment with regard to sepsis prevalence, overlap, and outcomes. DESIGN: Retrospective cohort study. SETTING: One hundred eleven U.S. hospitals in the Cerner HealthFacts dataset. PATIENTS: Adults hospitalized in 2013-2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified clinical indicators of presumed infection (blood cultures and antibiotics) concurrent with either: 1) an increase in Sequential Organ Failure Assessment score by 2 or more points (Sepsis-3) or 2) 1 or more eSOFA criteria: vasopressor initiation, mechanical ventilation initiation, lactate greater than or equal to 2.0 mmol/L, doubling in creatinine, doubling in bilirubin to greater than or equal to 2.0 mg/dL, or greater than or equal to 50% decrease in platelet count to less than 100 cells/muL (Centers for Disease Control and Prevention Adult Sepsis Event). We compared area under the receiver operating characteristic curves for discriminating in-hospital mortality, adjusting for baseline characteristics. Of 942,360 patients in the cohort, 57,242 (6.1%) had sepsis by Sequential Organ Failure Assessment versus 41,618 (4.4%) by eSOFA. Agreement between sepsis by Sequential Organ Failure Assessment and eSOFA was good (Cronbach's alpha 0.81). Baseline characteristics and infectious diagnoses were similar, but mortality was higher with eSOFA (17.1%) versus Sequential Organ Failure Assessment (14.4%; p < 0.001) as was discrimination for mortality (area under the receiver operating characteristic curve, 0.774 vs 0.759; p < 0.001). Comparisons were consistent across subgroups of age, infectious diagnoses, and comorbidities. CONCLUSIONS: The Adult Sepsis Event's eSOFA organ dysfunction criteria identify a smaller, more severely ill sepsis cohort compared with the Sequential Organ Failure Assessment score, but with good overlap and similar clinical characteristics. Adult Sepsis Events may facilitate wide-scale automated sepsis surveillance that tracks closely with the more complex Sepsis-3 criteria. |
Variation in identifying sepsis and organ dysfunction using administrative versus electronic clinical data and impact on hospital outcome comparisons
Rhee C , Jentzsch MS , Kadri SS , Seymour CW , Angus DC , Murphy DJ , Martin GS , Dantes RB , Epstein L , Fiore AE , Jernigan JA , Danner RL , Warren DK , Septimus EJ , Hickok J , Poland RE , Jin R , Fram D , Schaaf R , Wang R , Klompas M . Crit Care Med 2018 47 (4) 493-500 OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to >/= 2.0 mg/dL, decrease in platelets to < 100 cells/microL, or lactate >/= 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals' claims data was low and variable: median 30% (range, 5-54%) for sepsis, 66% (range, 26-84%) for acute kidney injury, 39% (range, 16-60%) for thrombocytopenia, 36% (range, 29-44%) for hepatic injury, and 66% (range, 29-84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data. CONCLUSIONS: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals' sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons. |
Using objective clinical data to track progress on preventing and treating sepsis: CDC's new 'Adult Sepsis Event' surveillance strategy
Rhee C , Dantes RB , Epstein L , Klompas M . BMJ Qual Saf 2018 28 (4) 305-309 Sepsis is a leading cause of death and suffering, afflicting 1.7 million adults annually in the USA and contributing to over 250 000 deaths.1 The high burden of sepsis has catalysed numerous performance improvement and policy initiatives, including mandatory sepsis protocols in a growing number of US states, the Centers for Medicare and Medicaid Services’ (CMS) ‘SEP-1’ measure, and WHO’s resolution declaring sepsis a global health priority.2 Hospitals around the world are dedicating considerable resources to improving sepsis recognition and compliance with treatment bundles. |
Corneal infections associated with sleeping in contact lenses - six cases, United States, 2016-2018
Cope JR , Konne NM , Jacobs DS , Dhaliwal DK , Rhee MK , Yin J , Steinemann TL . MMWR Morb Mortal Wkly Rep 2018 67 (32) 877-881 Contact lenses, when worn and cared for properly, are a safe and effective form of vision correction used by an estimated 45 million Americans. However, contact lens wearers are at risk for contact lens-related eye infections, especially when wearers do not practice proper contact lens wear and care habits. These infections, affecting the cornea and known as microbial keratitis (Figure), can lead to serious adverse health outcomes. Because contact lenses are regulated by the Food and Drug Administration (FDA) as medical devices, contact lens-related corneal infections should be reported to FDA as an adverse event. To illustrate their serious health implications, six cases of contact lens-related corneal infection, in which sleeping in lenses was reported as the main risk factor, are presented. Consequences of infection reported among the identified cases included the need for frequent administration of antibiotic eye drops, multiple follow-up medical appointments, and permanent eye damage. Health education measures directed toward contact lens wearers should emphasize raising awareness of the risks of sleeping in contact lenses as well as adherence to all recommendations for the wear and care of contact lenses. Additional measures are needed to educate eye care professionals about the need to report contact lens-related corneal infections to MedWatch, the FDA Safety Information and Adverse Event Reporting program (https://www.fda.gov/MedWatch/). |
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