Methods for living guidelines: early guidance based on practical experience. Paper 2: consumer engagement in living guidelines.

OBJECTIVES: To describe and reflect on the consumer engagement approaches used in five living guidelines from the perspectives of consumers (i.e., patients, carers, the public, and their representatives) and guideline developers. STUDY DESIGN AND SETTING: In a descriptive report, we used a template to capture engagement approaches and the experiences of consumers and guideline developers in living guidelines in Australia and the United Kingdom. Responses were summarized using descriptive synthesis. RESULTS: One guideline used a Consumer Panel, three included two to three consumers in the guideline development group, and one did both. Much of our experience was common to all guidelines (e.g., consumers felt welcomed but that their role initially lacked clarity). We identified six challenges and opportunities specific to living guidelines: managing the flow of work; managing engagement in online environments; managing membership of the panel; facilitating more flexibility, variety and depth in engagement; recruiting for specific skills-although these can be built over time; developing living processes to improve; and adapting consumer engagement together. CONCLUSION: Consumer engagement in living guidelines should follow established principles of consumer engagement in guidelines. Conceiving the engagement as living, underpinned by a living process evaluation, allows the approach to be developed with consumers over time.

Shortness of breath due to portopulmonary hypertension and hepatopulmonary syndrome: diagnostic challenges and complex management approach in frail patients.

A 60-year-old woman with a background of frailty, non-alcoholic fatty liver disease (NAFLD), cirrhosis and type 2 diabetes mellitus (T2DM), presented with worsening shortness of breath and a drop in oxygen saturation on sitting and standing up. Her chest X-ray demonstrated evidence of upper lobe venous diversion. Given the hypoxia, she had a computed tomography pulmonary angiography (CTPA) to rule out a pulmonary embolism. The only finding from the CTPA was pulmonary hypertension in the absence of any clots in the lungs. An ultrasound of the abdomen confirmed portal hypertension with splenomegaly and a cirrhotic liver, therefore, an initial diagnosis of portopulmonary hypertension and hepatopulmonary syndrome was made.The patient declined an agitated saline contrast echocardiography. Based on frailty she was not deemed to be a suitable candidate for a liver transplant and was discharged with a package of care alongside home oxygen therapy with periodic review in the gastroenterology clinic. She was assessed as stable with no new concerns while on home oxygen and diuretics.This case highlights challenges in diagnosing and managing patients with cirrhosis, portopulmonary hypertension and hepatopulmonary syndrome with a background of complex comorbidities and frailty.

Divergent effects of HIV reverse transcriptase inhibitors on pancreatic beta-cell function and survival: Potential role of oxidative stress and mitochondrial dysfunction.

Antiretroviral therapy (ART), a life-saving treatment strategy in HIV/AIDS, has been implicated in increasing the risk of type 2 diabetes mellitus (T2DM). Direct damaging effects on beta-cell function and survival by either non-nucleoside reverse transcriptase inhibitors (NNRTIs) or nucleoside/tide reverse transcriptase inhibitors (NRTIs) may predispose individuals to developing T2DM or if already type 2 diabetic, to insulin dependency. The aim of this study was to investigate the effects of the NNRTIs efavirenz, rilpivirine and doravirine, and the NRTIs tenofovir disoproxil fumarate and emtricitabine, on beta-cell function and survival while suggesting potential cellular and molecular mechanism(s). Our results show contrasting effects within the NNRTI class as doravirine did not cause damaging effects in the rat insulinoma INS-1E cells while efavirenz and rilpivirine reduced insulin release and cell viability, and induced apoptosis in INS-1E cells. Additionally, efavirenz and rilpivirine increased ROS generation, disrupted Δψm and upregulated the mRNA and protein expression of CHOP and GRP78, key markers of endoplasmic reticulum stress. In silico docking studies predict a possible inhibition of the mitochondrial ATP synthase by rilpivirine. On the contrary, both the NRTIs tenofovir disoproxil fumarate and emtricitabine did not affect GSIS, cell viability and apoptosis/necrosis levels in INS-1E cells. The deleterious effects observed in beta-cells exposed to efavirenz or rilpivirine may be, at least partially, mediated by oxidative stress and mitochondrial toxicity. These findings provide potential mechanism(s) by which efavirenz and rilpivirine may contribute to the pathogenesis of T2DM and the progression of T2DM to insulin dependency in HIV-infected type 2 diabetics.