Patient and Healthcare Provider Barriers to Hypertension Awareness,Treatment and Follow Up: A Systematic Review and Meta-Analysis of Qualitative and Quantitative Studies

Background

Although the importance of detecting, treating, and controlling hypertension has been recognized for decades, the majority of patients with hypertension remain uncontrolled. The path from evidence to practice contains many potential barriers, but their role has not been reviewed systematically. This review aimed to synthesize and identify important barriers to hypertension control as reported by patients and healthcare providers.

Methods

Electronic databases MEDLINE, EMBASE and Global Health were searched systematically up to February 2013. Two reviewers independently selected eligible studies. Two reviewers categorized barriers based on a theoretical framework of behavior change. The theoretical framework suggests that a change in behavior requires a strong commitment to change [intention], the necessary skills and abilities to adopt the behavior [capability], and an absence of health system and support constraints.

Findings

Twenty-five qualitative studies and 44 quantitative studies met the inclusion criteria. In qualitative studies, health system barriers were most commonly discussed in studies of patients and health care providers. Quantitative studies identified disagreement with clinical recommendations as the most common barrier among health care providers. Quantitative studies of patients yielded different results: lack of knowledge was the most common barrier to hypertension awareness. Stress, anxiety and depression were most commonly reported as barriers that hindered or delayed adoption of a healthier lifestyle. In terms of hypertension treatment adherence, patients mostly reported forgetting to take their medication. Finally, priority setting barriers were most commonly reported by patients in terms of following up with their health care providers.

Conclusions

This review identified a wide range of barriers facing patients and health care providers pursuing hypertension control, indicating the need for targeted multi-faceted interventions. More methodologically rigorous studies that encompass the range of barriers and that include low- and middle-income countries are required in order to inform policies to improve hypertension control.     

Effect of Ghrelin on Mortality and Cardiovascular Outcomes in Experimental Rat and Mice Models of Heart Failure: A Systematic Review and Meta-Analysis

BackgroundHeart failure (HF) continues to be a challenging condition in terms of prevention and management of the disease. Studies have demonstrated various cardio-protective effects of Ghrelin. The aim of the study is to determine the effect of Ghrelin on mortality and cardiac function in experimental rats/mice models of HF.MethodsData sources: PUBMED, Scopus. We searched the Digital Dissertations and conference proceedings on Web of Science. Search methods: We systematically searched for all controlled trials (upto November 2014) which assessed the effects of Ghrelin (irrespective of dose, form, frequency, duration and route of administration) on mortality and cardiac function in rats/ mice models of HF. Ghrelin administration irrespective of dose, form, frequency, duration and route of administration. Data collection and analysis: Two authors independently assessed each abstract for eligibility and extracted data on characteristics of the experimental model used, intervention and outcome measures. We assessed the methodological quality by SYRCLE’s risk of bias tool for all studies and the quality of evidence by GRADEpro. We performed meta-analysis using RevMan 5.3.ResultsA total of 325 animals (rats and mice) were analyzed across seven studies. The meta-analysis revealed that the mortality in Ghrelin group was 31.1% and in control group was 40% (RR 0.83, 95% CI 0.46 to 1.47) i.e Ghrelin group had 68 fewer deaths per 1000 (from 216 fewer to 188 more) as compared to the control group. The meta-analysis reveals that the heart rate in rats/mice on Ghrelin was higher (MD 13.11, 95% CI 1.14 to 25.08, P=0.66) while the mean arterial blood pressure (MD -1.38, 95% CI -5.16 to 2.41, P=0.48) and left ventricular end diastolic pressure (MD -2.45, 95% CI -4.46 to -0.43, P=0.02) were lower as compared to the those on placebo. There were insignificant changes in cardiac output (SMD 0.28, 95% CI -0.24 to 0.80, P=0.29) and left ventricular end systolic pressure (MD 1.48, 95% CI -3.86 to 6.82, P=0.59).ConclusionsThe existing data provides evidence to suggest that Ghrelin may lower the risk of mortality and improve cardiovascular outcomes. However; the quality of evidence as assessed by GRADEpro is low to very low. Clinical judgments to administer Ghrelin to patients with HF must be made on better designed animal studies.     

The direct profibrotic and indirect immune antifibrotic balance of blocking the cannabinoid 2 receptor

Cannabinoid 2 (CB2) receptors expressed on immune cells are considered to be antifibrogenic. Hepatic stellate cells (HSCs) directly interact with phagocytosis lymphocytes, but the nature of this interaction is obscure. We aimed to study the effects of CB2 receptors on hepatic fibrosis via their role in mediating immunity. Hepatic fibrosis was induced by carbon-tetrachloride (CCl(4)) administration in C57BL/6 wild-type (WT) and CB2 knockout (CB2(-/-)) mice. Irradiated animals were reconstituted with WT or CB2(-/-) lymphocytes. Lymphocytes from na?ve/fibrotic WT animals and healthy/cirrhotic hepatitis C virus were preincubated in vitro with or without CB2 antagonist, evaluated for proliferation and apoptosis, and then cocultured with primary mouse HSCs or a human HSC line (LX2), respectively. Lymphocyte phagocytosis was then evaluated. Following CCl(4)-administration, CB2(-/-) mice developed significant hepatic fibrosis but less necroinflammation. WT mice harbored decreased liver CD4(+) and NK(+) cells but increased CD8(+) subsets. Na?ve CB2(-/-) mice had significantly decreased T cell subsets. Adoptive transfer of CB2(-/-) lymphocytes led to decreased fibrosis in the irradiated WT recipient compared with animals receiving WT lymphocytes. Moreover, necroinflammation also tended to decrease. In vitro, a CB2-antagonist directly increased human HSC activation and increased apoptosis and decreased proliferation of mice/human T cells (healthy/fibrotic) and their phagocytosis. We concluded that CB2(-/-) lymphocytes exert an antifibrotic activity, whereas lack of CB2 receptor in HSCs promotes fibrosis. These findings broaden our understanding of cannabinoid signaling in hepatic fibrosis beyond their activity solely in HSCs.     

Genome-wide association study identifies candidate markers for bull fertility in Holstein dairy cattle

The decline in the reproductive efficiency of dairy cattle has become a challenging problem worldwide. Female fertility is now taken into account in breeding goals while generally less attention is given to male fertility. The objective of this study was to perform a genome-wide association study in Holstein bulls to identify genetic variants significantly related to sire conception rate (SCR), a new phenotypic evaluation of bull fertility. The analysis included 1755 sires with SCR data and 38,650 single nucleotide polymorphisms (SNPs) spanning the entire bovine genome. Associations between SNPs and SCR were analyzed using a mixed linear model that included a random polygenic effect and SNP genotype either as a linear covariate or as a categorical variable. A multiple testing correction approach was used to account for the correlation between SNPs because of linkage disequilibrium. After genome-wide correction, eight SNPs showed significant association with SCR. Some of these SNPs are located close to or in the middle of genes with functions related to male fertility, such as the sperm acrosome reaction, chromatin remodeling during the spermatogenesis, and the meiotic process during male germ cell maturation. Some SNPs showed marked dominance effects, which provide more evidence for the relevance of non-additive effects in traits closely related to fitness such as fertility. The results could contribute to the identification of genes and pathways associated with male fertility in dairy cattle.     

Whole-genome scan for quantitative trait loci associated with birth weight, gestation length and passive immune transfer in a Holstein × Jersey crossbred population

We herein report results from a daughter design genome-scan study aiming to identify quantitative trait loci (QTL) associated with birth weight, direct gestation length and passive immune transfer in a backcross (Holstein × Jersey) × Holstein population. Two-hundred and seventy-six calves, offspring of seven crossbred sires, were genotyped for 161 microsatellite markers distributed along the 29 bovine autosomes. The genome scan was performed through interval mapping using an animal model in order to identify QTL accounting for phenotypic differences between individual animals. Based on significant chi-squared values, we identified putative QTL on BTA7 and BTA14 for gestation length, on BTA2, BTA6 and BTA14 for birth weight and on BTA20 for passive immune transfer. In total, these QTL accounted for 12%, 18% and 1% of the phenotypic variance in gestation length, birth weight and passive immune transfer respectively. We also report results from a supplementary and independent influential grand-daughter Holstein family. In this family, findings on BTA7 and BTA14 for direct gestation length were in agreement with results in the crossbred population. Two other regions on BTA6 and BTA21 putatively underlying QTL for direct gestation length variability were discovered with this analysis.     

Granulocyte-macrophage colony stimulating factor is anabolic and interleukin-1β is catabolic for rat articular chondrocytes

Objective: To study the effects of GM-CSF and IL-1β, both implicated in tissue damage in arthritis, on articular chondrocyte proliferation and metabolism, and to explore their agonist/antagonist effects. Methods: Chondrocytes were obtained from 1-month-old rats. First-passage monolayers were incubated for 24 h with or without GM-CSF and/or IL-1β, and labeled with ³H-thymidine, ³⁵S–SO₄ and ¹⁴C-proline. Proteoglycan and collagen synthesis were analyzed by liquid chromatography and SDS–PAGE. Gene expression was measured by RT-PCR. Results: IL-1β exerts potent, and GM-CSF weak, inhibitory effects on DNA synthesis. GM-CSF strongly stimulates, and IL-1β inhibits, proteoglycan and collagen synthesis. IL-1β suppresses the effect of GM-CSF, and increases the release of radioactive molecules from pre-labeled cartilage fragments; GM-CSF decreases the IL-1β-induced effect. Interestingly, both cytokines induce the expression of each other’s gene. Conclusions: IL-1β appears to be a catabolic and anti-anabolic agent for chondrocytes, whereas GM-CSF is mainly anabolic, and blocks the IL-1β-induced catabolic effect. It is postulated that both agents are implicated in inflammation: IL-1β promotes tissue catabolism and destruction, whereas GM-CSF enhances tissue reconstruction.     

Application of BATMAN and BAYESIL for quantitative <Superscript>1</Superscript>H-NMR based metabolomics of urine: discriminant analysis of lean,obese, and obese-diabetic rats

Introduction

BATMAN and BAYESIL are software tools, which can provide a solution for automated metabolite quantifications based on the proton nuclear magnetic resonance (¹H-NMR) spectral data of bio-fluids. However, their specific application for the quantitative ¹H-NMR based metabolomics of urine has not been investigated.

Objectives

The aim of this study is to evaluate the performance of BATMAN and BAYESIL in the quantitative metabolite analysis of urine based on its ¹H-NMR spectra.

Methods

BATMAN and BAYESIL were used for automated metabolite quantification based on the ¹H-NMR spectra of the urine from the lean, obese and obese-diabetic rat groups. PLS-DA model was used to discriminate the three different groups based on the results from the quantifications.

Results

BATMAN was found to be superior to BAYESIL in identifying and quantifying the metabolites in the urine samples, owing to its flexibility that allows users to define and adjust the relevant signals of the pure standard metabolites in the database in order to fit the signals in the samples, a necessary step since variations and peak shift are natural in most ¹H-NMR spectra. The results of BATMAN also agreed well with that of the manual deconvolution method, which indicated the higher accuracy in metabolite quantification, despite the need of pre-processing and longer processing time than BAYESIL. However, in the case where the problems in baseline correction and peak shift of ¹H-NMR spectra are absent, the use of BAYESIL is more advantageous. Application of quantitative ¹H-NMR based metabolomics of the urine showed that PLS-DA model derived from BATMAN could satisfactorily discriminate the lean, obese, and obese-diabetic rat groups.

Conclusion

Both BATMAN and BAYESIL are useful for the quantitative automation of urine metabolites based on its ¹H-NMR spectra. The results from BATMAN method is superior to BAYESIL but require expertise in spectroscopy and longer computer time. Both methods help in simplifying the interpretation of metabolite status in the VIP analysis.