Variants of the APOL1 gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse.
We conducted a ...cross-sectional study investigating the association between APOL1 renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate eGFR of <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant). The secondary outcomes included renal impairment (eGFR <60 ml/min per 1.73 m2), albuminuria (albumin-to-creatinine ratio ACR >30 mg/mmol), and biopsy-proven HIV-associated nephropathy (HIVAN). Multivariable logistic regression was used to estimate the associations between APOL1 high-risk genotypes (G1/G1, G1/G2, G2/G2) and kidney disease outcomes.
A total of 2864 participants (mean age 48.1 SD 10.3, 57.3% female) were genotyped, of whom, 354 (12.4%) had APOL1 high-risk genotypes, and 99 (3.5%) had ESKD. After adjusting for demographic, HIV, and renal risk factors, individuals with APOL1 high-risk genotypes were at increased odds of ESKD (odds ratio OR 10.58, 95% CI 6.22–17.99), renal impairment (OR 5.50, 95% CI 3.81–7.95), albuminuria (OR 3.34, 95% CI 2.00–5.56), and HIVAN (OR 30.16, 95% CI 12.48–72.88). An estimated 49% of ESKD was attributable to APOL1 high-risk genotypes.
APOL1 high-risk genotypes were strongly associated with kidney disease in people of African ancestry with HIV and accounted for approximately half of ESKD cases in this cohort.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Sickle cell trait (SCT) has been associated with chronic kidney disease (CKD) in African Americans, although evidence for its impact in Africans and people with HIV is currently lacking. We conducted ...a cross-sectional study investigating the association between SCT and kidney disease in people of African ancestry with HIV in the UK.
The primary outcome was estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. Secondary outcomes were eGFR <90 ml/min per 1.73 m2, end-stage kidney disease (ESKD; eGFR <15 ml/min per 1.73 m2, chronic dialysis, or having received a kidney transplant), proteinuria (protein-to-creatinine ratio >50 mg/mmol), and albuminuria (albumin-to-creatinine ratio >3 mg/mmol). Multivariable logistic regression was used to estimate the associations between SCT and kidney disease outcomes.
A total of 2895 participants (mean age 48.1 SD 10.3, 57.2% female) were included, of whom 335 (11.6%) had SCT and 352 (12.2%) had eGFR <60 ml/min per 1.73 m2. After adjusting for demographic, HIV, and kidney risk factors including APOL1 high-risk genotype status, individuals with SCT were more likely to have eGFR <60 ml/min per 1.73 m2 (odds ratio 1.62 95% CI 1.14–2.32), eGFR <90 ml/min per 1.73 m2 (1.50 1.14–1.97), and albuminuria (1.50 1.09–2.05). Stratified by APOL1 status, significant associations between SCT and GFR <60 ml/min per 1.73 m2, eGFR <90 ml/min per 1.73 m2, proteinuria, and albuminuria were observed for those with APOL1 low-risk genotypes.
Our results extend previously reported associations between SCT and kidney disease to people with HIV. In people of African ancestry with HIV, these associations were largely restricted to those with APOL1 low-risk genotypes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nasca society emerged at the beginning of the Early Intermediate Period (AD1-750) and flourished along the arid south coast of Peru into the Middle Horizon (AD750-1000). In this study, long- and ...short-term residential mobility, palaeodiet and stress experiences for individuals from the ceremonial centre Cahuachi (n=41) and cemeteries in the Las Trancas river valley (n=13) are reconstructed. Emphasis is placed on understanding the synergy of movement, diet, stress, and the social and physical landscapes in producing the biochemical record archived in the human body. Through oxygen-isotope analysis of human tissues and modern environmental waters, it was demonstrated that, although most individuals buried at Cahuachi came from the Southern Nasca Region middle valleys, many spent a portion of their lives in other parts of the Rio Grande de Nasca drainage. Within-lifetime relocation was assessed using strontium- and oxygen-isotope analysis of bone and enamel pairs for a subset of individuals (n=20). These analyses revealed that half of the individuals analyzed moved between childhood and adulthood. Carbon- and nitrogen-isotope analyses of bone and hair showed dietary change consistent with (semi-) permanent relocation and with local mobility in the months/years before death. Together, these analyses suggest that movement, whether associated with burial at Cahuachi, relocation and/or local mobility, likely played an important role in the engagement of Nasca people with their physical and social landscapes. Long-term average diet consisted of a mixed C3/C4 plant base with greater reliance on maize and consumption of lower trophic level meat and plant-derived protein. Sequential isotopic analysis of hair demonstrated that some individuals had stable or seasonally shifting diets, and that others exploited multiple production zones. Dietary patterns are interpreted to represent flexibility in food acquisition as a means of minimizing risk associated with environmental and social instability. Biogenic patterns of cortisol production were observed in sequential analyses of hair, enabling direct reconstruction of stress experiences. Combined sequential isotopic and cortisol data provided insight into the metabolic and physiological causes of individual stress experiences associated with dietary change and residential mobility. Keywords: bioarchaeology, residential mobility, palaeodiet, stress, stable isotope analysis, cortisol, hair, Nasca, Cahuachi, Peru
Abstract
Background
Guidelines emphasize rapid antibiotic treatment for sepsis, but infection presence is often uncertain at initial presentation. We investigated the incidence and drivers of ...false-positive presumptive infection diagnosis among emergency department (ED) patients meeting Sepsis-3 criteria.
Methods
For a retrospective cohort of patients hospitalized after meeting Sepsis-3 criteria (acute organ failure and suspected infection including blood cultures drawn and intravenous antimicrobials administered) in 1 of 4 EDs from 2013 to 2017, trained reviewers first identified the ED-diagnosed source of infection and adjudicated the presence and source of infection on final assessment. Reviewers subsequently adjudicated final infection probability for a randomly selected 10% subset of subjects. Risk factors for false-positive infection diagnosis and its association with 30-day mortality were evaluated using multivariable regression.
Results
Of 8267 patients meeting Sepsis-3 criteria in the ED, 699 (8.5%) did not have an infection on final adjudication and 1488 (18.0%) patients with confirmed infections had a different source of infection diagnosed in the ED versus final adjudication (ie, initial/final source diagnosis discordance). Among the subset of patients whose final infection probability was adjudicated (n = 812), 79 (9.7%) had only “possible” infection and 77 (9.5%) were not infected. Factors associated with false-positive infection diagnosis included hypothermia, altered mental status, comorbidity burden, and an “unknown infection source” diagnosis in the ED (odds ratio: 6.39; 95% confidence interval: 5.14–7.94). False-positive infection diagnosis was not associated with 30-day mortality.
Conclusions
In this large multihospital study, <20% of ED patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication.
Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/concordance-between-initial-presumptive-versus-final-adjudicated-diagnoses-of-infection-among-patients-meeting-sepsis-3-criteria-in-the-emergency-department
In this large multihospital study, <20% of emergency department (ED) patients meeting Sepsis-3 criteria had no infection or only possible infection on retrospective adjudication and 18% of infected patients had a different source of infection diagnosed in the ED versus final adjudication.
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