Lay advisor interventions for hypertension outcomes: A Systematic Review, Meta-analysis and a RE-AIM evaluation.

Introduction: Lay advisor interventions improve hypertension outcomes; however, the added benefits and relevant factors for their widespread implementation into health systems are unknown. We performed a systematic review to: (1) summarize the benefits of adding lay advisors to interventions on hypertension outcomes, and (2) summarize factors associated with successful implementation in health systems using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. Methods: We systematically searched several databases, including Ovid MEDLINE, CINAHL, PsycINFO from January 1981 to May 2023. All study designs of interventions delivered solely by lay advisors for adults with hypertension were eligible. If both arms received the lay advisor intervention, the study arm with lower intensity was assigned as the low-intensity intervention. Results: We included 41 articles, of which 22 were RCTs, from 7,267 screened citations. Studies predominantly included socially disadvantaged populations. Meta-analysis (9 RCTs; n = 4,220) of eligible lay advisor interventions reporting outcomes showed improved systolic blood pressure (BP) [-3.72 mm Hg (CI -6.1 to -1.3; I2 88%)], and diastolic BP [-1.7 mm Hg (CI -1 to -0.9; I2 7%)] compared to control group. Pooled effect from six RCTs (n = 3,277) comparing high-intensity with low-intensity lay advisor interventions showed improved systolic BP of -3.6 mm Hg (CI -6.7 to -0.5; I2 82.7%) and improved diastolic BP of -2.1 mm Hg (CI -3.7 to -0.4; I2 70.9%) with high-intensity interventions. No significant difference in pooled odds of hypertension control was noted between lay advisor intervention and control groups, or between high-intensity and low-intensity intervention groups. Most studies used multicomponent interventions with no stepped care elements or reporting of efficacious components. Indicators of external validity (adoption, implementation, maintenance) were infrequently reported. Discussion: Lay advisor interventions improve hypertension outcomes, with high intensity interventions having a greater impact. Further studies need to identify successful intervention and implementation factors of multicomponent interventions for stepped upscaling within healthcare system settings as well as factors used to help sustain interventions.

Partnering With Patients With Sarcoidosis to Implement a Community Advisory Board.

BACKGROUND: Community advisory boards (CABs) are increasingly recognized as a means of incorporating patient experience into clinical practice and research. The power of CABs is derived from engaging with community members as equals throughout the research process. Despite this, little is known of community member experience and views on best practices for running a CAB in a rare pulmonary disease. RESEARCH QUESTION: What are CAB members' views on the best practices for CAB formation and maintenance in a rare pulmonary disease? STUDY DESIGN AND METHODS: In August 2021, we formed the Cleveland Clinic Sarcoidosis Health Partners (CC-HP) as a CAB to direct research and clinic improvement initiatives at a quaternary sarcoidosis center. We collaboratively evaluated our process for formation and maintenance of the CC-HP with the patient members of the group. Through the series of reflection/debriefing discussions, CAB patient members developed a consensus account of salient obstacles and facilitators of forming and maintaining a CAB in a rare pulmonary disease. RESULTS: Clinician and community members of the CC-HP found published guidelines to be an effective tool for structuring formation of a CAB in a rare pulmonary disease. Facilitators included a dedicated coordinator, collaborative development of projects, and a focus on improving clinical care. Obstacles to CAB functioning were formal structure, focus on projects with academic merit but no immediate impact to patients, and overreliance on digital resources. INTERPRETATION: By centering our evaluation of our CAB on community member experience, we were able to both identify facilitators and impediments to CAB as well as improve our own processes.

IL-6/STAT3 axis dictates the PNPLA3-mediated susceptibility to non-alcoholic fatty liver disease.

BACKGROUND & AIMS: A number of genetic polymorphisms have been associated with susceptibility to or protection against non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain unknown. Here, we focused on the rs738409 C>G single nucleotide polymorphism (SNP), which produces the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and is strongly associated with NAFLD. METHODS: To enable mechanistic dissection, we developed a human pluripotent stem cell (hPSC)-derived multicellular liver culture by incorporating hPSC-derived hepatocytes, hepatic stellate cells, and macrophages. We first applied this liver culture to model NAFLD by utilising a lipotoxic milieu reflecting the circulating levels of disease risk factors in affected individuals. We then created an isogenic pair of liver cultures differing only at rs738049 and compared NAFLD phenotype development. RESULTS: Our hPSC-derived liver culture recapitulated many key characteristics of NAFLD development and progression including lipid accumulation and oxidative stress, inflammatory response, and stellate cell activation. Under the lipotoxic conditions, the I148M variant caused the enhanced development of NAFLD phenotypes. These differences were associated with elevated IL-6/signal transducer and activator of transcription 3 (STAT3) activity in liver cultures, consistent with transcriptomic data of liver biopsies from individuals carrying the rs738409 SNP. Dampening IL-6/STAT3 activity alleviated the I148M-mediated susceptibility to NAFLD, whereas boosting it in wild-type liver cultures enhanced NAFLD development. Finally, we attributed this elevated IL-6/STAT3 activity in liver cultures carrying the rs738409 SNP to increased NF-κB activity. CONCLUSIONS: Our study thus reveals a potential causal link between elevated IL-6/STAT3 activity and 148M-mediated susceptibility to NAFLD. IMPACT AND IMPLICATIONS: An increasing number of genetic variants manifest in non-alcoholic fatty liver disease (NAFLD) development and progression; however, the underlying mechanisms remain elusive. To study these variants in human-relevant systems, we developed an induced pluripotent stem cell-derived multicellular liver culture and focused on a common genetic variant (i.e. rs738409 in PNPLA3). Our findings not only provide mechanistic insight, but also a potential therapeutic strategy for NAFLD driven by this genetic variant in PNPLA3. Our liver culture is therefore a useful platform for exploring genetic variants in NAFLD development.

Generation of Human Pluripotent Stem Cell-Derived Polarized Hepatocytes.

Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) are valuable tools to study liver biology. HLCs, however, lack certain key in vivo characteristics relevant to their physiological function. One such characteristic is cellular polarity, which is critical to hepatocyte counter-current flow systems involving canalicular bile secretion and sinusoidal secretion of large quantities of serum proteins into blood. Model systems using non-polarized hepatocytes, therefore, cannot recapitulate this physiological function of hepatocytes. Here, we describe a stepwise protocol to generate hPSC-derived polarized HLCs (pol-HLCs), which feature clearly defined basolateral and apical membranes separated by tight junctions. Pol-HLCs not only display many hepatic functions but are also capable of directional cargo secretion, mimicking the counter-current flow systems. We describe protocols for stem cell culture maintenance and for differentiating hPSCs into pol-HLCs. In addition, we describe protocols to assay the pol-HLCs for basic hepatic functions and polarized hepatic characteristics. Once successfully differentiated, these pol-HLCs can be used as an in vitro model system to study hepatocyte biology, disease mechanisms, genetic variation, and drug metabolism. The establishment of hepatic polarity from non-polarized hPSCs also provides a useful tool to study the development and maintenance of hepatic polarity. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Maintenance of hPSCs Basic Protocol 2: Differentiation of hPSCs to pol-HLCs Basic Protocol 3: Assaying pol-HLCs for basic hepatic functions Support Protocol 1: Assessment of pol-HLC monolayer tightness Support Protocol 2: Assessment of pol-HLC polarity.