Increase in blood pressure precedes distress behavior in nursing home residents with dementia.

BACKGROUND: Distress behaviors in dementia (DBD) likely increase sympathetic nervous system activity. The aim of this study was to examine the associations among DBD, blood pressure (BP), and intensity of antihypertensive treatment, in nursing home (NH) residents with dementia. METHODS: We identified long-stay Veterans Affairs NH residents with dementia in 2019-20 electronic health data. Each individual with a BP reading and a DBD incident according to a structured behavior note on a calendar day (DBD group) was compared with an individual with a BP reading but without a DBD incident on that same day (comparison group). In each group we calculated daily mean BP from 14 days before to 7 days after the DBD incident day. We then calculated the change in BP between the DBD incident day and, as baseline, the 7-day average of BP 1 week prior, and tested for differences between DBD and comparison groups in a generalized estimating equations multivariate model. RESULTS: The DBD and comparison groups consisted of 707 and 2328 individuals, respectively. The DBD group was older (74 vs. 72 y), was more likely to have severe cognitive impairment (13% vs. 8%), and had worse physical function scores (15 vs. 13 on 28-point scale). In the DBD group, mean systolic BP on the DBD incident day was 1.6 mmHg higher than baseline (p < .001), a change that was not observed in the comparison group. After adjusting for covariates, residents in the DBD group, but not the comparison group, had increased likelihood of having systolic BP > = 160 mmHg on DBD incident days (OR 1.02; 95%CI 1.00-1.03). Systolic BP in the DBD group began to rise 7 days before the DBD incident day and this rise persisted 1 week after. There were no significant changes in mean number of antihypertensive medications over this time period in either group. CONCLUSIONS: NH residents with dementia have higher BP when they experience DBD, and BP rises 7 days before the DBD incident. Clinicians should be aware of these findings when deciding intensity of BP treatment.

Comparison of Claims-Based Frailty Indices in U.S. Veterans 65 and Older for Prediction of Long-Term Institutionalization and Mortality.

BACKGROUND: Frailty is increasingly recognized as a useful measure of vulnerability in older adults. Multiple claims-based frailty indices (CFIs) can readily identify individuals with frailty, but whether 1 CFI improves prediction over another is unknown. We sought to assess the ability of 5 distinct CFIs to predict long-term institutionalization (LTI) and mortality in older Veterans. METHODS: Retrospective study conducted in U.S. Veterans ≥65 years without prior LTI or hospice use in 2014. Five CFIs were compared: Kim, Orkaby (Veteran Affairs Frailty Index [VAFI]), Segal, Figueroa, and the JEN-FI, grounded in different theories of frailty: Rockwood cumulative deficit (Kim and VAFI), Fried physical phenotype (Segal), or expert opinion (Figueroa and JFI). The prevalence of frailty according to each CFI was compared. CFI performance for the coprimary outcomes of any LTI or mortality from 2015 to 2017 was examined. Because Segal and Kim include age, sex, or prior utilization, these variables were added to regression models to compare all 5 CFIs. Logistic regression was used to calculate model discrimination and calibration for both outcomes. RESULTS: A total of 3 million Veterans were included (mean age 75, 98% male participants, 80% White, and 9% Black). Frailty was identified for between 6.8% and 25.7% of the cohort with 2.6% identified as frail by all 5 CFIs. There was no meaningful difference between CFIs in the area under the receiver operating characteristic curve for LTI (0.78-0.80) or mortality (0.77-0.79). CONCLUSIONS: Based on different frailty constructs, and identifying different subsets of the population, all 5 CFIs similarly predicted LTI or death, suggesting each could be used for prediction or analytics.

Comparative studies on in vitro antitumor activities and apoptosis-inducing effects of enantiomeric ruthenium(II) complexes.

On the basis of our previous comparative studies on the DNA binding of a pair of ruthenium(II) complex enantiomers, Δ-[Ru(bpy)2PBIP]2+ and Λ-[Ru(bpy)2PBIP]2+ {bpy = 2,2'-bipyridine, PBIP = 2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline}, in this study, their antitumor activities and mechanisms were further investigated comparatively. The cytotoxicity assay demonstrated that both the enantiomers exerted selective antiproliferative effects on cancer cell lines A2780 and PC3. Fluorescence localization experiments suggested that both the enantiomers effectively permeated the nucleus of HeLa cells and co-localized with DNA, resulting in their DNA damage and apoptosis. Flow cytometry experiments showed that the apoptosis was enhanced by increasing the concentration of each enantiomer. Western blotting analyses indicated that both extrinsic and intrinsic apoptosis pathways were activated by the two enantiomers. miRNA microarray analyses displayed that both the enantiomers up- and downregulated multiple miRNAs, some of which were predicted to be associated with carcinogenesis. The above experimental results also showed that the Δ-enantiomer exerted a more potent antitumor activity, a higher efficiency of entering cancer cells and a stronger apoptosis-inducing effect compared with the Λ-enantiomer. Combined with the previously published research results, experimental results from this study implied that the antitumor activity of a metal complex might have originated from the conformation change of DNA in tumor cells caused by the intercalation of the complex, that the antitumor mechanism of a metal complex could be related to its DNA-binding mode, and that the antitumor efficiency of a metal complex could result from its DNA-binding strength.

The impact and cost-effectiveness of user fee exemption by contracting out essential health package services in Malawi.

OBJECTIVES: To examine the impact and cost-effectiveness of user fee exemption by contracting out essential health package services to Christian Health Association of Malawi (CHAM) facilities through service-level agreements (SLAs) to inform policy-making in Malawi. METHODS: The analysis was conducted from the government perspective. Financial and service utilisation data were collected for January 2015 through December 2016. The impact of SLAs on utilisation of maternal and child health (MCH) services was examined using propensity score matching and random-effects models. Subsequently, the improved services were converted to quality-adjusted life years (QALYs) gained, using the Lives Saved Tool (LiST), and incremental cost-effectiveness ratios (ICERs) were generated. FINDINGS: Over the 2 years, a total of $1.5 million was disbursed to CHAM facilities through SLAs, equivalent to $1.24 per capita. SLAs were associated with a 13.8%, 13.1%, 19.2% and 9.6% increase in coverage of antenatal visits, postnatal visits, delivery by skilled birth attendants and BCG vaccinations, respectively. This was translated into 434 lives saved (95% CI 355 to 512) or 11 161 QALYs gained (95% CI 9125 to 13 174). The ICER of SLAs was estimated at $134.7/QALYs gained (95% CI $114.1 to $164.7). CONCLUSIONS: The cost per QALY gained for SLAs was estimated at $134.7, representing 0.37 of Malawi's per capita gross domestic product ($363). Thus, MCH services provided with Malawi's SLAs proved cost-effective. Future refinements of SLAs could introduce pay for performance, revising the price list, streamlining the reporting system and strengthening CHAM facilities' financial and monitoring management capacity.

Comparative studies on DNA-binding and in vitro antitumor activity of enantiomeric ruthenium(II) complexes.

A pair of ruthenium(II) complex enantiomers, Δ- and Λ-[Ru(bpy)2PBIP]2+ {bpy=2,2'-bipyridine, PBIP=2-(4-bromophenyl)imidazo[4,5-f]1,10-phenanthroline} have been synthesized and characterized. The systematic comparative studies between two enantiomers on their DNA binding-behaviors with calf thymus DNA (CT DNA) were carried out by viscosity measurements, spectrophotometric methods and molecular simulation technology. Additional assays were performed to explore the cytotoxicity of the ruthenium(II) enantiomers against tumor cell lines. DNA-binding studies show that both the enantiomers can bind to CT DNA via intercalative mode, and the Δ form binds to CT DNA more strongly than the Λ form does. Molecular simulation further shows that both the two enantiomers intercalate between base pairs of DNA in minor groove, and that the Δ form intercalates into DNA more deeply than the Λ form does. In addition, the cell proliferation assays show that the Δ form induces a greater cytotoxicity than the Λ form on human cervical cancer HeLa cells, which is positive correlated with the results in DNA binding studies and molecular docking, and implies that the DNA binding affinities of ruthenium(II) polypyridyl complexes might be constitute to the part of their anticancer mechanisms.

Study on interaction between curcumin and pepsin by spectroscopic and docking methods.

The interaction between curcumin and pepsin was investigated by fluorescence, synchronous fluorescence, UV-vis absorption, circular dichroism (CD), and molecular docking. Under physiological pH value in stomach, the fluorescence of pepsin can be quenched effectively by curcumin via a combined quenching process. Binding constant (Ka) and binding site number (n) of curcumin to pepsin were obtained. According to the theory of Förster's non-radiation energy transfer, the distance r between pepsin and curcumin was found to be 2.45 nm within the curcumin-pepsin complex, which implies that the energy transfer occurs between curcumin and pepsin, leading to the quenching of pepsin fluorescence. Fluorescence experiments also suggest that curcumin is located more closely to tryptophan residues than tyrosine residues. CD spectra together with UV-vis absorbance studies show that binding of curcumin to pepsin results in the extension of peptide strands of pepsin with loss of some ß-sheet structures. Thermodynamic parameters calculated from the binding constants at different temperatures reveal that hydrophobic force plays a major role in stabilizing the curcumin-pepsin complex. In addition, docking results support the above experimental findings and suggest the possible hydrogen bonds of curcumin with Thr-77, Thr-218, and Glu-287 of pepsin, which help further stabilize the curcumin-pepsin complex.