Strategies for Effective Stakeholder Engagement in Strengthening Referral Networks for Management of Hypertension Across Health Systems in Kenya

BackgroundIneffective referral networks in low- and middle-income countries hinders access to evidence-based therapies by hypertensive patients, leading to high cardiovascular mortality and morbidity. The STRENGTHS (Strengthening Referral Networks for Management of Hypertension Across Health Systems) study evaluates strategies to improve referral processes utilizing the International Association of Public Participation framework to engage stakeholders.ObjectivesThis study sought to identify and engage key stakeholders involved in referral of patients in the Ministry of Health, western Kenya.MethodsKey stakeholders involved in policy formulation, provision, or consumption of public health care service were mapped out and contacted by phone, letters, and emissaries to schedule meetings, explain research objectives, and obtain feedback.ResultsKey stakeholders identified were the Ministry of Health, the Academic Model Providing Access to Healthcare, health professionals, communities and their leadership, and patients. Engaging them resulted in permission to contact research in their areas of jurisdiction and enabled collaboration in updating care protocols with emphasis on timely and appropriate referrals.ConclusionsEarly stakeholder identification and engagement using the International Association of Public Participation model eased explanation of research objectives, building consensus, and shaping the interventions to improve the referral process.     

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.     

Myocardial strain rate is a superior method for evaluation of left ventricular subendocardial function compared with tissue Doppler imaging

OBJECTIVES: This study was performed to evaluate subendocardial function using strain rate imaging (SRI). BACKGROUND: The subendocardium and mid-wall of the left ventricle (LV) play important roles in ventricular function. Previous methods used for evaluating this function are either invasive or cumbersome. Strain rate imaging by ultrasound is a newly developed echocardiographic modality based on tissue Doppler imaging (TDI) that allows quantitative assessment of regional myocardial wall motion. METHODS: We examined eight sheep using TDI in apical four-chamber views to evaluate the LV free wall. Peak strain rates (SRs) during isovolumic relaxation (IR), isovolumic contraction (IC), and myocardial strain were measured in the endocardial (End), mid-myocardial (Mid), and epicardial (Epi) layers. For four hemodynamic conditions (created after baseline by blood, dobutamine, and metoprolol infusion), we compared differences in SR of End, Mid, and Epi layers to peak positive and negative first derivative of LV pressure (dP/dt). RESULTS: Strain rate during IC showed a good correlation with +dP/dt (r = 0.74, p < 0.001) and during IR with -dP/dt (r = 0.67, p = 0.0003). There was a significant difference in SR between the myocardial layers during both IC and IR (End: -3.4 +/- 2.2 s(-1), Mid: -1.8 +/- 1.5 s(-1), Epi: -0.63 +/- 1.0 s(-1), p < 0.0001 during IC; End: 2.2 +/- 1.5 s(-1), Mid: 1.0 +/- 0.8 s(-1), Epi: 0.47 +/- 0.64 s(-1), p < 0.0001 during IR). Also, SRs of the End and Mid layers during IC were significantly altered by different hemodynamic conditions (End at baseline: 1.7 +/- 0.7 s(-1); blood: 2.0 +/- 1.1 s(-1); dobutamine: 3.4 +/- 2.3 s(-1); metoprolol: 1.0 +/- 0.4 s(-1); p < 0.05). Myocardial strain showed differences in each layer (End: -34.3 +/- 12.6%; Mid: -22.6 +/- 12.1%; Epi: -11.4 +/- 7.9%; p < 0.0001) and changed significantly in different hemodynamic conditions (p < 0.0001). CONCLUSIONS: Strain and SR appear useful and sensitive for evaluating myocardial function, especially for the subendocardial region.     

Do routinely measured delivery variables predict anal sphincter outcome?

PURPOSE: Trauma to the anal sphincter is a recognized complication of primiparous childbirth. This damage may be compounded during subsequent deliveries leading to symptoms. Earlier work is inconclusive as to which delivery variables are associated with such damage and may prove useful in predicting its occurrence, thereby allowing the potential for intervention in these later deliveries to protect the traumatized anal sphincter. The purpose of the present study was to determine whether routinely recorded obstetric variables can be correlated to anal sphincter damage in a consecutive series of females. METHODS: A prospective study was undertaken in a single maternity unit. Patients delivering were assessed before discharge using a symptom questionnaire and endoanal ultrasound. Delivery data were collected prospectively and analyzed statistically to see if a significant difference existed in the presence of an anal sphincter defect. RESULTS: A total of 159 patients were assessed. Endosonography revealed sphincter injuries in 8.7 percent of the normal vaginal delivery group and 83 percent of the forceps delivery group. No correlation was found between head circumference, baby weight, maternal body mass index, epidurals, episiotomy, length of each stage of labor, and duration of active pushing. Forceps delivery was the only factor to be significantly associated with sphincter trauma. CONCLUSION: Besides forceps delivery, commonly measured delivery variables are not useful predictors of anal sphincter trauma. Normal vaginal deliveries do not warrant routine postnatal anorectal assessment. but this should be routine for all instrument deliveries.Supported by the British Medical Association (Katherine Bishop Harman Award, 1996).Read at the meeting of The American Society of Colon and Rectal Surgeons, San Antonio, Texas, May 2 to 7, 1998.     

Inhibition of MTOR disrupts autophagic flux in podocytes

Inhibitors of the mammalian target of rapamycin (MTOR) belong to a family of drugs with potent immunosuppressive, antiangiogenic, and antiproliferative properties. De novo or worsening proteinuria can occur during treatment with these agents, but the mechanism by which this occurs is unknown. We generated and characterized mice carrying a podocyte-selective knockout of the Mtor gene. Although Mtor was dispensable in developing podocytes, these mice developed proteinuria at 3 weeks and end stage renal failure by 5 weeks after birth. Podocytes from these mice exhibited an accumulation of the autophagosome marker LC3 (rat microtubule-associated protein 1 light chain 3), autophagosomes, autophagolysosomal vesicles, and damaged mitochondria. Similarly, human podocytes treated with the MTOR inhibitor rapamycin accumulated autophagosomes and autophagolysosomes. Taken together, these results suggest that disruption of the autophagic pathway may play a role in the pathogenesis of proteinuria in patients treated with MTOR inhibitors.     

What is the Best Criterion for the Interpretation of Adrenal Vein Sample Results in Patients with Primary Hyperaldosteronism?

Background

In patients with primary hyperaldosteronism, adrenal vein sampling (AVS) has emerged as a gold standard for distinguishing between unilateral and bilateral disease, but multiple criteria have been used and no consensus exists as to the most accurate criterion. The objective of this study was to determine which AVS criteria most accurately identify patients with unilateral surgical disease and are associated with significant clinical improvement after adrenalectomy.

Methods

This is a retrospective analysis of AVS results in 108 patients with primary hyperaldosteronism treated at a single institution. Literature review of AVS criteria was used to distinguish between unilateral and bilateral disease.

Results

Of the 10 AVS criteria identified in the literature, one criterion (ACTH stimulation, positioning: cortisol [adrenal]/cortisol [periphery] [Ca/Cp]?>?5.0 and lateralization: aldosterone/cortisol [A/C] [dominant {D}]: A/C [nondominant {ND}]?>?4:1) was the most accurate in identifying and correctly predicting lateralization of disease (P value range:??1.1 and lateralization: A/C (D): A/C (ND)?>?2:1. For this criterion, the overall true positive was 85%. However, we found no significant difference in clinical outcome based on individual criteria fulfillment.

Conclusions

Of the multiple criteria used for AVS evaluation, one criterion has the best accuracy. With the increasing use of AVS, there should be a consensus by which these results are evaluated and surgeons recommend adrenalectomy.     

Emerging strategies for the transdermal delivery of peptide and protein drugs

Transdermal delivery has been at the forefront of research addressing the development of non-invasive methods for the systemic administration of peptide and protein therapeutics generated by the biotechnology revolution. Numerous approaches have been suggested for overcoming the skin's formidable barrier function; whereas certain strategies simply act on the drug formulation or transiently increase the skin permeability, others are designed to bypass or even remove the outermost skin layer. This article reviews the technologies currently under investigation, ranging from those in their early-stage of development, such as laser-assisted delivery to others, where feasibility has already been demonstrated, such as microneedle systems, and finally more mature techniques that have already led to commercialisation (e.g., velocity-based technologies). The principles, mechanisms involved, potential applications, limitations and safety considerations are discussed for each approach, and the most advanced devices in each field are described.