Quality of life among caregivers of people with end-stage kidney disease managed with dialysis or comprehensive conservative care

BACKGROUND: To measure health-related and care-related quality of life among informal caregivers of older people with end-stage kidney disease (ESKD), and to determine the association between caregiver quality of life and care recipient's treatment type. METHODS: A prospective cross-sectional study was conducted. Three renal units in the UK and Australia were included. Informal caregivers of people aged ≥75 years with ESKD managed with dialysis or comprehensive conservative non-dialytic care (estimated glomerular filtration (eGFR) ≤10 mL/min/1.73m2) participated. Health-related quality of life (HRQoL) was assessed using Short-Form six dimensions (SF-6D, 0-1 scale) and care-related quality of life was assessed using the Carer Experience Scale (CES, 0-100 scale). Linear regression assessed associations between care-recipient treatment type, caregiver characteristics and the SF-6D utility index and CES scores. RESULTS: Of 63 caregivers, 49 (78%) were from Australia, 26 (41%) cared for an older person managed with dialysis, and 37 (59%) cared for an older person managed with comprehensive conservative care. Overall, 73% were females, and the median age of the entire cohort was 76 years [IQR 68-81]. When adjusted for caregiver sociodemographic characteristics, caregivers reported significantly worse carer experience (CES score 15.73, 95% CI 5.78 to 25.68) for those managing an older person on dialysis compared with conservative care. However, no significant difference observed for carer HRQoL (SF-6D utility index - 0.08, 95% CI - 0.18 to 0.01) for those managing an older person on dialysis compared with conservative care. CONCLUSIONS: Our data suggest informal caregivers of older people on dialysis have significantly worse care-related quality of life (and therefore greater need for support) than those managed with comprehensive conservative care. It is important to consider the impact on caregivers' quality of life when considering treatment choices for their care recipients

Cost Efectiveness of Ambulatory Blood Pressure Monitoring Compared with Home or Clinic Blood Pressure Monitoring for Diagnosing Hypertension in Australia

Objectives The aim of this study was to evaluate the cost effectiveness of ambulatory blood pressure monitoring (ABPM) compared with home blood pressure monitoring (HBPM) and clinic blood pressure monitoring (CBPM) in diagnosing hypertension in Australia. Methods A cohort-based Markov model was built from the Payer’s perspective (Australian government) comparing lifetime costs and effectiveness of ABPM, HBPM and CBPM in people aged ≥ 35 years with suspected hypertension who have a CBPM between ≥ 140/90 mmHg and ≤ 180/110 mmHg using a sphygmomanometer and have not yet commenced antihypertensive treatment. The main outcome measures were incremental cost-effectiveness ratio (ICER) assessing cost per quality-adjusted life-year (QALY) and life-years (LYs) gained by ABPM versus HBPM and CBPM. Cost was measured in Australian dollars (A$). Results Over a lifetime model, ABPM had lower total costs (A$8,491) compared with HBPM (A$9,648) and CBPM (A$10,206) per person. ABPM was associated with a small but significant improvement in the quality and quantity of life for people with suspected hypertension with 12.872 QALYs and 17.449 LYs compared with 12.857 QALYs and 17.433 LYs with HBPM, and 12.850 QALYs and 17.425 LYs with CBPM. In the base-case analysis, ABPM dominated HBPM and CBPM. In scenario analyses, at 100% specificity of HBPM, ABPM no longer remained cost effective at a A$50,000/QALY threshold. However, in probabilistic sensitivity analysis, over 10,000 iterations, ABPM remained dominant. Conclusion ABPM was the dominant strategy for confirming the diagnosis of hypertension among Australian adults aged ≥ 35 years old with suspected hypertension. The findings of this study are important for reimbursement decision makers to support policy change and for clinicians to make practice changes consistent with ABPM recommendations in primary care

Health-related quality of life and well-being in people over 75 years of age with end-stage kidney disease managed with dialysis or comprehensive conservative care: A cross-sectional study in the UK and Australia

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To measure health-related quality of life (HRQoL) and well-being in older people with end-stage kidney disease (ESKD) and to determine the association between treatment type and sociodemographic characteristics on these outcome measures. In addition, to assess the convergent validity between the HRQoL and well-being measure and their feasibility and acceptability in this population. Design Prospective cross-sectional study. Setting Three renal units in the UK and Australia. Participants 129 patients with ESKD managed with dialysis or with an estimated glomerular filtration ≤10 mL/min/1.73 m 2 and managed with comprehensive conservative, non-dialytic care. Outcome measures HRQoL and well-being were assessed using Short-Form six dimensions (SF-6D, 0-1 scale); Kidney Disease Quality of Life (KDQOL-36) (0-100 scale) and Investigating Choice Experiments Capability Measure-Older people (ICECAP-O, 0-1 scale). Linear regression assessed associations between treatment, HRQoL and well-being. Pearson's correlation coefficient assessed convergent validity between instruments. Results Median age of 81 years (IQR 78-85), 65% males; 83 (64%) were managed with dialysis and 46 (36%) with conservative care. When adjusted for treatment type and sociodemographic variables, those managed on dialysis reported lower mean SF-6D utility (-0.05, 95% CI-0.12 to 0.01); lower KDQOL Physical Component Summary score (-3.17, 95% CI-7.61 to 1.27); lower Mental Component Summary score (-2.41, 95% CI-7.66 to 2.84); lower quality of life due to burden (-28.59, 95% CI-41.77 to-15.42); symptoms (-5.93, 95% CI-14.61 to 2.73) and effects of kidney disease (-16.49, 95% CI-25.98 to-6.99) and lower overall ICECAP-O well-being (-0.07, 95% CI-0.16 to 0.02) than those managed conservatively. Correlation between ICECAP-O well-being and SF-6D utility scores was strong overall, 0.65 (

The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract Background Rifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen. Methods 63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART. Results 97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases). Conclusions Good immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration

Bone Marrow Myeloid Cells Regulate Myeloid-Biased Hematopoietic Stem Cells via a Histamine-Dependent Feedback Loop

Myeloid-biased hematopoietic stem cells (MB-HSCs) play critical roles in recovery from injury, but little is known about how they are regulated within the bone marrow niche. Here we describe an auto-/paracrine physiologic circuit that controls quiescence of MB-HSCs and hematopoietic progenitors marked by histidine decarboxylase (Hdc). Committed Hdc+ myeloid cells lie in close anatomical proximity to MB-HSCs and produce histamine, which activates the H2 receptor on MB-HSCs to promote their quiescence and self-renewal. Depleting histamine-producing cells enforces cell cycle entry, induces loss of serial transplant capacity, and sensitizes animals to chemotherapeutic injury. Increasing demand for myeloid cells via lipopolysaccharide (LPS) treatment specifically recruits MB-HSCs and progenitors into the cell cycle; cycling MB-HSCs fail to revert into quiescence in the absence of histamine feedback, leading to their depletion, while an H2 agonist protects MB-HSCs from depletion after sepsis. Thus, histamine couples lineage-specific physiological demands to intrinsically primed MB-HSCs to enforce homeostasis. Chen et al. show that histidine decarboxylase (Hdc) marks quiescent myeloid-biased HSCs (MB-HSCs). Daughter myeloid cells form a spatial cluster with Hdc+ MB-HSCs and secrete histamine to enforce their quiescence and protect them from depletion, following activation by a variety of physiologic insults

Genome-wide expression profiling reveals transcriptomic variation and perturbed gene networks in androgen-dependent and androgen-independent prostate cancer cells.

Previously, we have developed a unique in vitro LNCaP cell model, which includes androgen-dependent (LNCaP-C33), androgen-independent (LNCaP-C81) and an intermediate phenotype (LNCaP-C51) cell lines resembling the stages of prostate cancer progression to hormone independence. This model is advantageous in overcoming the heterogeneity associated with the prostate cancer up to a certain extent. We characterized and compared the gene expression profiles in LNCaP-C33 (androgen-dependent) and LNCaP-C81 (androgen-independent) cells using Affymetrix GeneChip array analyses. Multiple genes were identified exhibiting differential expression during androgen-independent progression. Among the important genes upregulated in androgen-independent cells were PCDH7, TPTE, TSPY, EPHA3, HGF, MET, EGF, TEM8, etc., whereas many candidate tumor suppressor genes (HTATIP2, CDKN2A, CDKN2B, CDKN1C, TP53, TP73, ICAM1, SOCS1/2, SPRY2, PPP2CA, PPP3CA, etc.) were decreased. Pathway prediction analysis identified important gene networks associated with growth-promoting and apoptotic signaling that were perturbed during androgen-independent progression. Further investigation of one of the genes, PPP2CA, which encodes the catalytic subunit of a serine phosphatase PP2A, a potent tumor suppressor, revealed that its expression was decreased in prostate cancer compared to adjacent normal/benign tissue. Furthermore, the downregulated expression of PPP2CA was significantly correlated with tumor stage and Gleason grade. Future studies on the identified differentially expressed genes and signaling pathways may be helpful in understanding the biology of prostate cancer progression and prove useful in developing novel prognostic biomarkers and therapy for androgen-refractory prostate cancer

Development of Non-Natural Flavanones as Antimicrobial Agents

With growing concerns over multidrug resistance microorganisms, particularly strains of bacteria and fungi, evolving to become resistant to the antimicrobial agents used against them, the identification of new molecular targets becomes paramount for novel treatment options. Recently, the use of new treatments containing multiple active ingredients has been shown to increase the effectiveness of existing molecules for some infections, often with these added compounds enabling the transport of a toxic molecule into the infecting species. Flavonoids are among the most abundant plant secondary metabolites and have been shown to have natural abilities as microbial deterrents and anti-infection agents in plants. Combining these ideas we first sought to investigate the potency of natural flavonoids in the presence of efflux pump inhibitors to limit Escherichia coli growth. Then we used the natural flavonoid scaffold to synthesize non-natural flavanone molecules and further evaluate their antimicrobial efficacy on Escherichia coli, Bacillus subtilis and the fungal pathogens Cryptococcus neoformans and Aspergillus fumigatus. Of those screened, we identified the synthetic molecule 4-chloro-flavanone as the most potent antimicrobial compound with a MIC value of 70 µg/mL in E. coli when combined with the inhibitor Phe-Arg-ß-naphthylamide, and MICs of 30 µg/mL in S. cerevesiae and 30 µg/mL in C. neoformans when used alone. Through this study we have demonstrated that combinatorial synthesis of non-natural flavonones can identify novel antimicrobial agents with activity against bacteria and fungi but with minimal toxicity to human cells