Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

Subgroup Variations in Bone Mineral Density Response to Zoledronic Acid After Hip Fracture

Minimizing post‐fracture bone loss is an important aspect of recovery from hip fracture, and determination of factors that affect bone mineral density (BMD) response to treatment after hip fracture may assist in the development of targeted therapeutic interventions. A post hoc analysis of the HORIZON Recurrent Fracture Trial was done to determine the effect of zoledronic acid (ZOL) on total hip (TH) and femoral neck (FN) BMD in subgroups with low‐trauma hip fracture. A total of 2127 patients were randomized (1:1) to yearly infusions of ZOL 5 mg (n = 1065) or placebo (n = 1062) within 90 days of operation for low‐trauma hip fracture. The 1486 patients with a baseline and at least one post‐baseline BMD assessment at TH or FN (ZOL = 745, placebo = 741) were included in the analyses. Percentage change from baseline in TH and FN BMD was assessed at months 12 and 24 and compared across subgroups of hip fracture patients. Percentage change from baseline in TH and FN BMD at months 12 and 24 was greater (p < 0.05) in ZOL‐treated patients compared with placebo in most subgroups. Treatment‐by‐subgroup interactions (p < 0.05) indicated that a greater effect on BMD was observed for TH BMD at month 12 in females, in patients in the lower tertile body mass index at baseline (≤22.6 kg/m²), and in patients with baseline FN BMD T‐score of ≤ –2.5; for FN BMD in patients who received ZOL for >6 weeks post‐surgery; and for TH and FN BMD in patients with a history of one or more prior fractures. All interactions were limited to the first 12 months after treatment with none observed for the 24‐month comparisons. (Clinical trial registration number NCT00046254.) © 2014 American Society for Bone and Mineral Research.     

Prevalence and Isotypic Complexity of the Anti-Chinese Hamster Ovary Host Cell Protein Antibodies in Normal Human Serum

Host cell-derived protein impurities may be present at low levels in biopharmaceutical products. Antibodies to host cell proteins are present in individuals with no known exposure to these products. In this study, antibodies to drug process-specific Chinese hamster ovary host cell-derived proteins (CHO-HCP) were measured in unexposed individuals using a validated enzyme-linked immunosorbent assay. Samples that tested positive for anti-CHO-HCP reactivity were further characterized to determine the isotypes and IgG subclasses expressed in each positive individual. The specificity of the detected anti-CHO-HCP antibody isotypes was confirmed by the competitive inhibition assay and the uncoated plate specificity testing. These antibody characterization experiments revealed that the prevalent anti-CHO-HCP antibody subclasses were predominantly IgG1 (present in 66.6% of individuals) and IgG2 (60%), with 33.3% positive for IgG3 while IgG4 was detected in low abundance. Forty percent (40%) of the individuals with IgG type reactivity were also identified as IgM-positive. Anti-CHO-HCP-specific IgE was not detected in the assays used in this study. Some individuals exhibited single isotype anti-CHO-HCP reactivity; others contained a combination of multiple antibody isotypes. Data presented in this study demonstrate the isotypic complexity and the high prevalence of anti-CHO-HCP antibodies in human serum with no known exposure to CHO cell-derived therapeutic biologics.     

Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria

Nanometer-sized gold, due to its beautiful and bountiful color and unique optical properties, is a versatile material for many industrial and societal applications. We have studied the effect of gold nanoparticles on Salmonella typhimurium strain TA 102. The gold nanoparticles in solution prepared using the citrate reduction method is found not to be toxic or mutagenic but photomutagenic to the bacteria; however, careful control experiments indicate that the photomutagenicity is due to the co-existing citrate and Au3? ions, not due to the gold nanoparticle itself. Au3? is also found to be photomutagenic to the bacteria at concentrations lower than 1 μM, but toxic at higher concentrations. The toxicity of Au3? is enhanced by light irradiation. The photomutagenicity of both citrate and Au3? is likely due to the formation of free radicals, as a result of light-induced citrate decarboxylation or Au3? oxidation of co-existing molecules. Both processes can generate free radicals that may cause DNA damage and mutation. Studies of the interaction of gold nanoparticles with the bacteria indicate that gold nanoparticles can be absorbed onto the bacteria surface but not able to penetrate the bacteria wall to enter the bacteria.     

Limited health literacy and adverse outcomes among kidney transplant candidates

More than one‐third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014‐November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0‐12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86‐4.43), frailty (aOR = 1.85, 95% CI:1.22‐2.80), comorbidity (Charlson comorbidity index [1‐point increase] aOR = 1.12, 95% CI: 1.04‐1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20‐5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54‐0.91) decreased likelihood of listing and a 2.42‐fold (95% CI: 1.16‐ to 5.05‐fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.     

Evaluation of Antioxidant and Antimicrobial Potential of Two Endangered Plant Species Atropa Belladonna and Matricaria Chamomilla

Background

Plants are the natural source of antioxidants as well as antimicrobial compounds that has great potentials in pharmaceutical industry. In the present study, two medicinal plants Atropa belladonna and Matricaria chamomilla were collected from Northern areas of Pakistan.

Materials and Methods

The extracts of the collected plants were obtained by microwave assisted extraction (MAE) with changing parameters, power level and time; methanol and ethanol were solvents used during extraction. The extracts of plants were tested against different bacterial strains.

Results

It was observed that ethanolic extracts of Atropa belladonna has more significant antimicrobial activity against S.aureus than E.coli. In parallel, methanolic extract of Matricaria chamomilla showed greater significant antibacterial activity against S.aureus when compared with E.coli. In comparison, ethanolic extracts of Matricaria chamomilla has shown more significant results against S. aureus than E.coli (p≤0.05). Both plants had no antibacterial activity against S.typhi. The free radical scavenging activity observed by DPPH assay, indicate that both plants have antioxidant activity at all levels of concentrations in solvent tested during the present work. However, methanolic extracts had greater antioxidant activity when compared with ethanolic extracts.

Conclusion

Present study is thus helpful in highlighting present potentials for antioxidant and antimicrobial properties in the selected plants.