Elevated Serum Carboxymethyl-Lysine, an Advanced Glycation End Product, Predicts Severe Walking Disability in Older Women: The Women's Health and Aging Study I

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. Our aim was to characterize the relationship between serum carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking disability (inability to walk or walking speed $<0.4$ m/sec) over 30 months of followup in 394 moderately to severely disabled women, $\ge 65$ years, living in the community in Baltimore, Maryland (the Women's Health and Aging Study I). During followup, 154 (26.4%) women developed severe walking disability, and 23 women died. Women in the highest quartile of serum CML had increased risk of developing of severe walking disability in a multivariate Cox proportional hazards model, adjusting for age and other potential confounders. Women with elevated serum CML are at an increased risk of developing severe walking disability. AGEs are a potentially modifiable risk factor. Further work is needed to establish a causal relationship between AGEs and walking disability

On Dimensionality, Measurement Invariance, and Suitability of Sum Scores for the PHQ-9 and the GAD-7.

In psychiatry, severity of mental health conditions and their change over time are usually measured via sum scores of items on psychometric scales. However, inferences from such scores can be biased if psychometric properties such as unidimensionality and temporal measurement invariance for instruments are not met. Here, we aimed to evaluate these properties for common measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Assessment-7) in a large clinical sample (N = 22,362) undergoing psychotherapy. In addition, we tested consistency in dimensionality results across different methods (parallel analysis, factor analysis, explained common variance, the partial credit model, and the Mokken model). Results showed that while both Patient Health Questionnaire-9 and Generalized Anxiety Disorder Assessment-7 are multidimensional instruments with highly correlated factors, there is justification for sum scores as measures of severity. Temporal measurement invariance across 10 therapy sessions was evaluated. Strict temporal measurement invariance was established in both scales, allowing researchers to compare sum scores as severity measures across time.NIH

Older adults' beliefs about physician-estimated life expectancy: a cross-sectional survey

BACKGROUND: Estimates of life expectancy assist physicians and patients in medical decision-making. The time-delayed benefits for many medical treatments make an older adult's life expectancy estimate particularly important for physicians. The purpose of this study is to assess older adults' beliefs about physician-estimated life expectancy. METHODS: We performed a mixed qualitative-quantitative cross-sectional study in which 116 healthy adults aged 70+ were recruited from two local retirement communities. We interviewed them regarding their beliefs about physician-estimated life expectancy in the context of a larger study on cancer screening beliefs. Semi-structured interviews of 80 minutes average duration were performed in private locations convenient to participants. Demographic characteristics as well as cancer screening beliefs and beliefs about life expectancy were measured. Two independent researchers reviewed the open-ended responses and recorded the most common themes. The research team resolved disagreements by consensus. RESULTS: This article reports the life-expectancy results portion of the larger study. The study group (n = 116) was comprised of healthy, well-educated older adults, with almost a third over 85 years old, and none meeting criteria for dementia. Sixty-four percent (n = 73) felt that their physicians could not correctly estimate their life expectancy. Sixty-six percent (n = 75) wanted their physicians to talk with them about their life expectancy. The themes that emerged from our study indicate that discussions of life expectancy could help older adults plan for the future, maintain open communication with their physicians, and provide them knowledge about their medical conditions. CONCLUSION: The majority of the healthy older adults in this study were open to discussions about life expectancy in the context of discussing cancer screening tests, despite awareness that their physicians' estimates could be inaccurate. Since about a third of participants perceived these discussions as not useful or even harmful, physicians should first ascertain patients' preferences before discussing their life expectancies

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network

Elevated Serum Carboxymethyl-Lysine, an Advanced Glycation End Product, Predicts Severe Walking Disability in Older Women: The Women's Health and Aging Study I

Advanced glycation end products (AGEs) have been implicated in the pathogenesis of sarcopenia. Our aim was to characterize the relationship between serum carboxymethyl-lysine (CML), a major circulating AGE, and incident severe walking disability (inability to walk or walking speed < 0 . 4  m/sec) over 30 months of followup in 394 moderately to severely disabled women, ≥ 6 5 years, living in the community in Baltimore, Maryland (the Women’s Health and Aging Study I). During followup, 154 (26.4%) women developed severe walking disability, and 23 women died. Women in the highest quartile of serum CML had increased risk of developing of severe walking disability in a multivariate Cox proportional hazards model, adjusting for age and other potential confounders. Women with elevated serum CML are at an increased risk of developing severe walking disability. AGEs are a potentially modifiable risk factor. Further work is needed to establish a causal relationship between AGEs and walking disability