Insulin resistance and non-alcoholic fatty liver disease: a review of the pathophysiology and the potential targets for drug actions

Insulin resistance refers to the reduced physiological effects of insulin on various tissues. Insulin resistance has been implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), which is a spectrum of diseases ranging from hepatic steatosis on one end to steatohepatitis, liver cirrhosis and hepatocellular carcinoma on the other end. In most parts of the developed world, it is now the most commoncause of chronic liver disease and the most commonindication for liver transplantation. A similar findingis emerging in the developing world due to the rising prevalence of obesity and widespread adoption of Western lifestyles. Despite these epidemiological data, there are no universally approved medications for the treatment of NAFLD. The pathophysiological mechanisms of NAFLD essentially include adipose tissue insulin resistance, hepatic insulin resistance, inflammation and fibrosis. At the subcellular level, mitochondrial dysfunction, oxidative changes and endoplasmic reticulum dysfunction have been documented. Several drugs have been tested in vitro and in animal studies to target these pathophysiological mechanisms. Some are presently going through clinical trials, while others have already gone through clinical trials with variable results. Other potential target sites of drug development for the treatment of NAFLD are based on the complex pathophysiology of the disease. Insulin resistance plays an important role in the development of NAFLD. There are potential targets in the pathophysiology of NAFLD that can be explored in the development of medications for the disease

Quality of stroke guidelines in low- and middle-income countries: a systematic review.

OBJECTIVE: To identify gaps in national stroke guidelines that could be bridged to enhance the quality of stroke care services in low- and middle-income countries. METHODS: We systematically searched medical databases and websites of medical societies and contacted international organizations. Country-specific guidelines on care and control of stroke in any language published from 2010 to 2020 were eligible for inclusion. We reviewed each included guideline for coverage of four key components of stroke services (surveillance, prevention, acute care and rehabilitation). We also assessed compliance with the eight Institute of Medicine standards for clinical practice guidelines, the ease of implementation of guidelines and plans for dissemination to target audiences. FINDINGS: We reviewed 108 eligible guidelines from 47 countries, including four low-income, 24 middle-income and 19 high-income countries. Globally, fewer of the guidelines covered primary stroke prevention compared with other components of care, with none recommending surveillance. Guidelines on stroke in low- and middle-income countries fell short of the required standards for guideline development; breadth of target audience; coverage of the four components of stroke services; and adaptation to socioeconomic context. Fewer low- and middle-income country guidelines demonstrated transparency than those from high-income countries. Less than a quarter of guidelines encompassed detailed implementation plans and socioeconomic considerations. CONCLUSION: Guidelines on stroke in low- and middle-income countries need to be developed in conjunction with a wider category of health-care providers and stakeholders, with a full spectrum of translatable, context-appropriate interventions

Primary stroke prevention worldwide: translating evidence into action

Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course