BACKGROUND:Falls and fall risk factors are common among people living with HIV (PLWH). We sought to identify fall risk factors among men with and without HIV.
METHODS:Men aged 50–75 years with (n = ...279) and without HIV (n = 379) from the Bone Strength Substudy of the Multicenter AIDS Cohort Study were included. Multinomial logistic regression models identified risk factors associated with falling.
RESULTS:One hundred fourteen (41%) PLWH and 149 (39%) of uninfected men had ≥1 fall; 54 (20%) PLWH and 66 (17%) of uninfected men experienced ≥2 falls over 2 years. Five and 3% of PLWH and uninfected men, respectively, had a fall-related fracture (P = 0.34). In multivariate models, the odds of ≥2 falls were greater among men reporting illicit drug use, taking diabetes or depression medications, and with peripheral neuropathy; obesity was associated with a lower risk (all P < 0.05). In models restricted to PLWH, detectable plasma HIV-1 RNA, current use of efavirenz or diabetes medications, illicit drug use, and peripheral neuropathy were associated with greater odds of having ≥2 falls (P < 0.05). Current efavirenz use was associated with increased odds of an injurious fall; longer duration of antiretroviral therapy was protective (both P < 0.05). Greater physical activity was associated with lower risk of falls with fracture (P < 0.05).
CONCLUSIONS:Identified risk factors for recurrent falls or fall with fracture included low physical activity, detectable HIV-1 RNA, use of efavirenz, or use of medications to treat diabetes and depression. Fall risk reduction should prioritize interventions targeting modifiable risk factors including increased physical activity, antiretroviral therapy adherence, and transition off efavirenz.
Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, ...yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Most cognitive assessments have been developed in high‐income countries but are used in diverse contexts. Differences in culture and context may affect the performance of cognitive ...items.
Methods
We used the Harmonized Cognitive Assessment Protocol (HCAP) surveys in the United States, Mexico, India, England, and South Africa (combined N = 11,364) to quantify associations across countries between cognitive items and cognitive impairment status using age‐ and sex‐adjusted logistic regression.
Results
Associations were stronger in the United States (median odds ratio OR across items = 0.17) and England (median OR = 0.19), compared to South Africa (median OR = 0.23), India (median OR = 0.29), and Mexico (median OR = 0.28). Items assessing memory (e.g., delayed recall tasks) had the most consistent associations of the largest magnitudes across contexts.
Discussion
Transporting cognitive items among countries and cultures warrants caution. Our results can guide the design of future instruments by identifying items that performed well either in individual contexts or across the range of contexts considered.
HIGHLIGHTS
Little quantitative evidence exists to guide the design of cognitive assessments in cross‐national studies.
The performance of cognitive items for the measurement of dementia varied across countries.
Items with lower variation across countries (e.g., delayed word recall) should be used in future cross‐national assessments.
Across countries, there was variability in the performance of language assessments, with the exception of the animal naming task.
Results can be used to design future cross‐national or location‐specific cognitive assessments.
Background Among adults, lower socioeconomic status (SES) is a risk factor for chronic kidney disease (CKD), progression to end-stage renal disease, and poor health outcomes; but its impact on young ...people with CKD is not established. Study Design Prospective cohort study. Settings & Participants 572 children and adolescents aged 1-16 years with mild to moderate CKD residing in the United States and Canada who were enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Predictor Self-reported annual household income category as a proxy measure for SES: ≥$75,000 (high income), $30,000 to <$75,000 (middle income) and <$30,000 (low income). Outcomes & Measurements Clinical characteristics and CKD severity at baseline (glomerular filtration rate GFR and comorbid conditions related to disease severity and management) and longitudinally (GFR decline and changes in blood pressure z scores and height z scores per year). Results At baseline, low and middle household incomes, compared to high income, were associated with minority race (39% and 20% vs 7%), lower maternal education (28% and 5% vs 1%), abnormal birth history (34% and 32% vs 21%), and having at least one clinical comorbid condition (66% and 64% vs 55%). Baseline median GFRs were similar across income categories (43-45 mL/min/1.73 m2 ). After adjusting for baseline differences, average GFR declines per year for the low-, middle-, and high-income categories were −2.3%, −2.7%, and −1.9%, respectively, and were not statistically significantly different among groups. Blood pressure control tended to improve in all groups ( z score, −0.10 to −0.04) but higher income was associated with a faster improvement. Each group showed similar deficits in height at baseline. Height deficits diminished over time for participants from high-income families, but not among those from low-income families (z scores for height per year, 0.05 and −0.004, respectively; P = 0.03 for comparison of high and low income). Limitations Income is an imperfect measure for SES; CKiD participants are not representative of children and adolescents with CKD who are uninsured or not receiving care; statistical power to detect associations by income level is limited. Conclusions GFR decline was similar across income groups but better improvement in BP was observed among those with high income. Children and adolescents with CKD from lower income households are at higher risk of impaired growth.
Background
Chronic kidney disease (CKD) is associated with many comorbidities requiring complex management. We described treatment patterns for common modifiable CKD complications (high blood ...pressure, anemia, hyperphosphatemia, and acidosis) according to severity of CKD and examined factors associated with the absence of drug therapy, among participants with a persistent comorbidity, for 1 year in children enrolled in the CKiD study.
Methods
A total of 703 CKiD participants contributed 2849 person-visits over a median 3.5 years of follow-up. Using pairs of annual visits, we examined whether participants with abnormal biomarker levels at the first (index) visit persisted in the abnormal levels 1 year later according to CKD risk stage. Multivariate analyses identified demographic and clinical factors associated with the absence of drug therapy among those with persistent comorbid conditions for 1 year.
Results
The overall proportions of person-visits prescribing therapy at 1-year follow-up for treating anemia, acidosis, hyperphosphatemia, and high blood pressure were 54%, 45%, 29%, and 81%, respectively. The frequency of therapy increased with advanced CKD risk stage for all comorbidities; however, 19–23% of participants with acidosis, 24–27% with anemia, and 30–39% with hyperphosphatemia at high-risk stages (E and F) were not prescribed appropriate therapy despite the persistence of abnormal levels of these biomarkers for at least 1 year. The resolution of comorbidities at advanced CKD stages without treatment was unlikely.
Conclusions
Many children with CKD in the CKiD cohort did not receive pharmacological treatment for common and persistent modifiable comorbidities, even in severe CKD risk stages.
Graphical abstract
Introduction
The measurement of dementia in cross‐national contexts relies on the assessment of functional limitations. We aimed to evaluate the performance of survey items on functional limitations ...across culturally diverse geographic settings.
Methods
We used data from the Harmonized Cognitive Assessment Protocol Surveys (HCAP) in five countries (total N = 11,250) to quantify associations between items on functional limitations and cognitive impairment.
Results
Many items performed better in the United States and England compared to South Africa, India, and Mexico. Items on the Community Screening Instrument for Dementia (CSID) had the least variability across countries (SD = 0.73 vs. 0.92 Blessed and 0.98 Jorm IQCODE), but also the weakest associations with cognitive impairment (median odds ratio OR = 2.23 vs. 3.01 Blessed and 2.75 Jorm IQCODE).
Discussion
Differences in cultural norms for reporting functional limitations likely influences performance of items on functional limitations and may affect the interpretation of results from substantive studies.
Highlights
There was substantial cross‐country variation in item performance.
Items from the Community Screening Instrument for Dementia (CSID) had less cross‐country variability but lower performance.
There was more variability in performance of instrumental activities of daily living (IADL) compared to activities of daily living (ADL) items.
Variability in cultural expectations of older adults should be taken into account.
Results highlight the need for novel approaches to assessing functional limitations.
2 valid and reliable estimated glomerular filtration rate (GFR) equations for the pediatric population have been developed from directly measured GFR data in the Chronic Kidney Disease in Children ...(CKiD) cohort: the full CKiD and bedside CKiD equations. Although adult GFR estimating equations replicate relationships of measured GFR with biomarkers, it is unclear whether similar patterns exist among children and adolescents with chronic kidney disease (CKD).
Prospective cohort study in children and adolescents.
730 participants contributed 1,539 study visits.
Measured GFR by plasma iohexol disappearance (mGFR), estimated GFR by the full CKiD equation (eGFRCKiDfull; based on serum creatinine, cystatin C, serum urea nitrogen, height, and sex), and estimated GFR by the bedside CKiD equation (eGFRCKiDbed; calculated as 41.3 × height m/serum creatinine mg/dL) were predictors of CKD-related biomarkers. Deviations of mGFR from eGFRCKiDfull and deviations of eGFRCKiDfull from eGFRCKiDbed from linear regressions (ie, residuals) were included in bivariate analyses.
CKD-related biomarkers included values for urine protein-creatinine ratio, blood hemoglobin, serum phosphate, bicarbonate, potassium, systolic and diastolic blood pressure z scores, and height z scores.
The median age of 730 participants with CKD was 12.5 years, with median mGFR, eGFRCKiDfull, and eGFRCKiDbed of 51.8, 54.0, and 53.2mL/min/1.73m2, respectively. eGFRCKiDfull demonstrated as strong or stronger associations with CKD-related biomarkers than mGFR; eGFRCKiDbed associations were significantly attenuated (ie, closer to the null). Residual information in mGFR did not substantially increase explained variability. eGFRCKiDbed estimated faster GFR decline relative to mGFR and eGFRCKiDfull.
Simple linear summaries of biomarkers may not capture nonlinear associations.
eGFRCKiDfull closely approximated mGFR to describe relationships with CKD-severity indicators and progression in this pediatric CKD population. eGFRCKiDbed offered similar inferences, but associations were attenuated and rate of progression was overestimated. The eGFRCKiDfull equation from 2012 is preferred for pediatric research purposes.
Background
We investigated the putative associations of alcohol, cigarette, e-cigarette, and marijuana use with kidney function and proteinuria among adolescents and young adults (AYA) with ...pediatric-onset chronic kidney disease (CKD) enrolled in the Chronic Kidney Disease in Children (CKiD) study.
Methods
Participants responded to questions about past year and 30-day substance use. Associations between each substance and kidney function, proteinuria, nephrotic range proteinuria, and high blood pressure were separately estimated using repeated measures regression models, adjusting for sociodemographic characteristics. Models controlled for covariates at the present visit (contemporaneous) and additionally controlled for disease severity at the year prior to reporting substance use (lagged).
Results
A total of 441 participants ≥16 years contributed 1,245 person-visits with 39% reporting alcohol and 16%, 17%, and 15% reporting cigarette, e-cigarette, and marijuana use, respectively, over the previous year. In adjusted lagged models, past year and 30-day cigarette use were significantly associated with higher levels of proteinuria (+18.6%, 95%CI: +2.8%, +36.9%; and +20.0%, 95%CI: +0.7%, +43.1%, respectively). Inferences were similar when controlling for secondhand smoke exposure.
Conclusions
In a cohort of AYA with pediatric kidney diseases, substance use was non-trivial, and cigarette use was associated with higher proteinuria, although the prevalence of use was low. Occasional alcohol, e-cigarette, and marijuana use were not associated with proteinuria, disease progression, or elevated blood pressure. Pediatric nephrologists as specialty care providers are well-positioned to discuss substance use and should encourage tobacco prevention/treatment efforts among AYA at high risk for use in order to preserve kidney function and promote well-being.
Background
Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and ...the association between hormonal onset of puberty with changes in GFR.
Methods
Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI.
Results
Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (
p
< 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR.
Conclusions
LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Background
Recombinant growth hormone (rGH) is an efficacious therapy for growth failure in children with chronic kidney disease (CKD). We described rGH use and estimated its relationship with growth ...and kidney function in the Chronic Kidney Disease in Children (CKiD) cohort.
Methods
Participants included those with growth failure, prevalent rGH users, and rGH initiators who did not meet growth failure criteria. Among those with growth failure, height
z
scores and GFR were compared between rGH initiators and non-initiators across 42 months. Inverse probability weights accounted for differences in baseline variables in weighted linear regressions.
Results
Among 148 children with growth failure and no previous rGH therapy, 42 (28%) initiated rGH therapy. Of the initiators, average age was 8.9 years, height
z
score was 2.50 standard deviations (SDs) (0.6
th
percentile), and GFR was 44 ml/min/1.73m
2
. They were compared to 106 children with growth failure who never initiated therapy (8.8 years, −2.33 SDs, and 51 ml/min/1.73m
2
). At 30 and 42 months after rGH, height increased +0.26 (95%CI: −0.11, +0.62) and +0.35 (95%CI: −0.17, +0.87) SDs, respectively, relative to those who did not initiate rGH. rGH was not associated with GFR.
Conclusions
Participants with growth failure receiving rGH experienced significant growth, although this was attenuated relative to RCTs, and were more likely to have higher household income and lower GFR. A substantial number of participants, predominantly boys, without diagnosed growth failure received rGH and had the highest achieved height relative to mid-parental height. Since rGH was not associated with accelerated GFR decline, increasing rGH use in this population is warranted.
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