Publications

Chronic kidney disease (CKD) is highly prevalent in the United States and throughout the world,(1) with approximately 13% of adults affected.(2) In addition, according to recent estimates, almost half of patients with CKD stages 3 to 5 are 70 years of age and older.(2) In the United States, the number of prevalent end-stage renal disease cases continues to increase in patients older than age 65. In light of the demographic characteristics of patients with CKD and ESRD, there has been considerable focus on associations between CKD and cardiovascular outcomes.(3) Until recently, less attention had been paid to other consequences of CKD in general and among older individuals with CKD in particular, but there is now solid evidence linking CKD with impairments of physical function, cognitive function, and emotional function and quality of life. This review summarizes available literature on these topics, focusing specifically on physical functioning and frailty, cognitive function, emotional health, including depression and anxiety, and health-related quality of life.

Cas9-based RNA-guided nuclease (RGN) has emerged to be a versatile method for genome editing due to the ease of construction of RGN reagents to target specific genomic sequences. The ability to control the activity of Cas9 with a high temporal resolution will facilitate tight regulation of genome editing processes for studying the dynamics of transcriptional regulation or epigenetic modifications in complex biological systems. Here we show that fusing ligand-binding domains of nuclear receptors to split Cas9 protein fragments can provide chemical control over split Cas9 activity. The method has allowed us to control Cas9 activity in a tunable manner with no significant background, which has been challenging for other inducible Cas9 constructs. We anticipate that our design will provide opportunities through the use of different ligand-binding domains to enable multiplexed genome regulation of endogenous genes in distinct loci through simultaneous chemical regulation of orthogonal Cas9 variants.

BACKGROUND

The Morisky Medication Adherence scale (MMAS-8) is a widely used self-reported measure of adherence to antihypertensive medications that has not been validated in hypertensive patients in sub-Saharan Africa.

METHODS

We carried out a cross-sectional study to examine psychometric properties of a translated MMAS-8 (MMAS-U) in a tertiary care hypertension clinic in Uganda. We administered the MMAS-U to consecutively selected hypertensive adults and used principal factor analysis and Cronbach's alpha to determine its validity and internal consistency respectively. Then we randomly selected one-sixth of participants for a 2-week test-retest telephone interview. Lastly, we used ordinal logistic regression modeling to explore factors associated with levels of medication adherence.

RESULTS

Of the 329 participants, 228 (69%) were females, median age of 55 years [Interquartile range (IQR) (46-66)], and median duration of hypertension of 4 years [IQR (2-8)]. The adherence levels were low (MMAS-U score ≤ 5) in 85%, moderate (MMAS-U score 6-7) in 12% and high (MMAS-U score ≥8) in 3%. The factor analysis of construct validity was good (overall Kaiser's measure of sampling adequacy for residuals of 0.72) and identified unidimensionality of MMAS-U. The internal consistency of MMAS-U was moderate (Cronbach α = 0.65), and test-retest reliability was low (weighted kappa = 0.36; 95% CI -0.01, 0.73). Age of 40 years or greater was associated with low medication adherence (p = 0.02) whereas a family member buying medication for participants (p = 0.02) and purchasing medication from a private clinic (p = 0.02) were associated with high adherence.

CONCLUSION

The Ugandan version of the MMAS-8 (MMAS-U) is a valid and reliable measure of adherence to antihypertensive medication among Ugandan outpatients receiving care at a public tertiary facility. Though the limited supply of medication affected adherence, this easy to use tool can be adapted to assess medication adherence among adults with hypertension in Uganda.

A recurring conference theme was the essential place of social justice within family medicine, especially the need to focus on denominator populations, exalt the personal and caring qualities of doctoring, and address social determinants of health. Many expressed solidarity with "community," but it is not always easy to define community in our large and diverse nation. Exhortations for health advocacy were frequently voiced, but putting these into meaningful action agendas is a challenge. There was general agreement that medicine is in flux and that the many expressions of "commodity-centered consumerism" have altered organization and financing. The increasing demands by "consumers", who want low cost, instant availability, and shared decision-making, and yet change doctors when health plans alter coverage also differentially impact high-volume, low-margin specialties such as family medicine. Additional challenges were the electronic health record and calibrating an appropriate work/life balance. Five action steps are recommended: 1) speak out on the important social and moral issues; 2) be the experts on personal care; 3) make common cause with potential allies; 4) help institutions perceive the value of generalism; and 5) help find ways to enrich generalist disciplines to increase the joy of medicine and decrease the threat of burn out.

OBJECTIVE

Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis.

BACKGROUND

Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation.

DESIGN/METHODS

A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303).

RESULTS

We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency.

CONCLUSIONS

Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.