The effects of intermittent hypoxia on hepatic expression of fatty acid translocase CD36 in lean and diet-induced obese mice.

BACKGROUND: Both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are prevalent within obese individuals. We aimed to investigate the effects of intermittent hypoxia (IH), a clinical feature of OSA, on hepatic expression of fatty acid translocase (CD36) in relation to liver injury in lean and diet-induced obese mice. METHODS: Four-week-old male C57BL/6J mice were randomized to standard diet (SD) or high fat (HF) diet groups. At 13-week-old, all mice were exposed to either air or IH (IH30; thirty hypoxic episodes per hour) for four weeks. We assessed liver injury through lipid profile, oxidative and inflammatory stress, histological scoring and hepatic CD36 expression. RESULTS: In lean mice, IH elevated serum and hepatic triglyceride and free fatty acid (FFA) levels, in line with upregulation of hepatic CD36 expression and myeloperoxidase (MPO)-positive cells in support of inflammatory infiltrates along with increase in serum malondialdehyde (MDA), C-X-C motif chemokine ligand 1(CXCL-1) and monocyte chemoattractant protein-1 (MCP-1). In diet-induced obese mice, an increase in hepatic alanine transaminase (ALT) activity, serum and hepatic levels of lipid parameters and inflammatory markers, serum MDA level, hepatic expressions of CD36 and α-smooth muscle actin (α-SMA), and MPO-positive cells was observed. IH potentiated hepatic ALT activity, serum CXCL-1 and hepatic interleukin-6 (IL-6), in line with inflammatory infiltrates, but paradoxically, reduced hepatic FFA level and hepatic CD36 expression, compared to obese mice without IH exposure. However, IH further augmented diet-induced liver steatosis and fibrosis as shown by histological scores. CONCLUSION: This study contributes to support that IH featuring OSA may lead to liver injury via differential regulation of hepatic CD36 expression in lean and diet-induced obese mice.

Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice.

BACKGROUND: Assessing pain in infants, children and young people with life-limiting conditions remains a challenge due to diverse patient conditions, types of pain and often a reduced ability or inability of patients to communicate verbally. AIM: To systematically identify pain assessment tools that are currently used in paediatric palliative care and examine their psychometric properties and feasibility and make recommendations for clinical practice. DESIGN: A systematic literature review and evaluation of psychometric properties of pain assessment tools of original peer-reviewed research published from inception of data sources to April 2021. DATA SOURCES: PsycINFO via ProQuest, Web of Science Core, Medline via Ovid, EMBASE, BIOSIS and CINAHL were searched from inception to April 2021. Hand searches of reference lists of included studies and relevant reviews were performed. RESULTS: From 1168 articles identified, 201 papers were selected for full-text assessment. Thirty-four articles met the eligibility criteria and we examined the psychometric properties of 22 pain assessment tools. Overall, the Faces Pain Scale-Revised (FPS-R) had high cross-cultural validity, construct validity (hypothesis testing) and responsiveness; while the Faces, Legs, Activity, Cry and Consolability (FLACC) scale and Paediatric Pain Profile (PPP) had high internal consistency, criterion validity, reliability and responsiveness. The number of studies per psychometric property of each pain assessment tool was limited and the methodological quality of included studies was low. CONCLUSION: Balancing aspects of feasibility and psychometric properties, the FPS-R is recommended for self-assessment, and the FLACC scale/FLACC Revised and PPP are the recommended observational tools in their respective age groups.

Access and Unmet Needs of Orphan Drugs in 194 Countries and 6 Areas: A Global Policy Review With Content Analysis.

OBJECTIVES: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. METHODS: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. RESULTS: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). CONCLUSIONS: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.

Prevalence, Safety and Long-Term Retention Rates of Biologics in Hong Kong from 2001 to 2015.

BACKGROUND: Biologic agents were initially introduced as treatment for rheumatoid arthritis (RA) but have since been used for other medical conditions. As new biologics become increasingly widespread in treatment regimens, it is important to understand their safety and utilization in the post-marketing context. PURPOSE: The aim of this study was to investigate long-term prescribing patterns and the safety of biologics in real clinical settings in Hong Kong. METHODS: This was a population-based drug utilization study in Hong Kong using a territory-wide electronic medical database Clinical Data Analysis and Reporting System (CDARS). Patients who received biologic treatments from 2001 to 2015 were identified and their corresponding demographic and clinical details retrieved from CDARS. The annual prevalence of biologic prescriptions, the long-term retention rates and incidence rates of infections associated with biologic treatments were evaluated. RESULTS: A total of 30,298 patients (male: 44%) prescribed biologic treatments were identified from CDARS from 2001 to 2015. The annual prevalence of biologic prescriptions increased from 0.1 to 16.1 per 100 persons for both sexes. Infliximab had the highest first-year retention rate of 95.6% among all biologics and continuously attained the highest retention rate from second to fifth year. The overall incidence rate of serious infections was less than five per 100 person-years. Specifically, the incidence rates of tuberculosis, upper and lower respiratory infections and herpes zoster were 0.52, 3.24, 4.99 and 1.01 per 100 person-years, respectively. CONCLUSION: This population-based study revealed an increasing prevalence of biologic prescribing. Results from the study described the long-term retention rates and incidence rates of serious infections of biologic treatments for all indications, and confirmed the safety of biologic treatments. Since this study provides an overview of all biologic utilization, further studies on cost effectiveness, safety and compliance of treatment in different patient groups are still warranted.