Towards a transparent, credible, evidence-based decision-making process of new drug listing on the Hong Kong Hospital Authority Drug Formulary: challenges and suggestions

The aim of this article is to describe the process, evaluation criteria, and possible outcomes of decision-making for new drugs listed in the Hong Kong Hospital Authority Drug Formulary in comparison to the health technology assessment (HTA) policy overseas. Details of decision-making processes including the new drug listing submission, Drug Advisory Committee (DAC) meeting, and procedures prior to and following the meeting, were extracted from the official Hong Kong Hospital Authority drug formulary management website and manual. Publicly-available information related to the new drug decision-making process for five HTA agencies [the National Institute of Health and Care Excellence (NICE), the Scottish Medicines Consortium (SMC), the Australia Pharmaceutical Benefits Advisory Committee (PBAC), the Canadian Agency for Drugs and Technologies in Health (CADTH), and the New Zealand Pharmaceutical Management Agency (PHARMAC)] were reviewed and retrieved from official documents from public domains. The DAC is in charge of systemically and critically appraising new drugs before they are listed on the formulary, reviewing submitted applications, and making the decision to list the drug based on scientific evidence to which safety, efficacy, and cost-effectiveness are the primary considerations. When compared with other HTA agencies, transparency of the decision-making process of the DAC, the relevance of clinical and health economic evidence, and the lack of health economic and methodological input of submissions are the major challenges to the new-drug listing policy in Hong Kong. Despite these challenges, this review provides suggestions for the establishment of a more transparent, credible, and evidence-based decision-making process in the Hong Kong Hospital Authority Drug Formulary. Proposals for improvement in the listing of new drugs in the formulary should be a priority of healthcare reforms

Urotensin II and the Circulatory System

Urotensin II (UII), first isolated from the spinal cord of teleost fish, is the most potent vasoconstrictor known. It is more potent than endothelin-1 and acts through UT-II, a seven-transmembrane-domain, G-protein-coupled receptor. Human UII is an 11-amino-acid cyclic peptide that is expressed in various tissues, including the central nervous system, heart, kidney, and blood vessels. It circulates in human plasma, and its plasma level is elevated in renal failure, congestive heart failure, diabetes, and portal hypertension. In the kidney, UII has vasodilatory and natriuretic effects, mediated through nitric oxide. The development of UII-receptor antagonists may provide a useful research tool, and a novel treatment for cardiorenal diseases

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias:a systematic review and meta-analysis

Following publication of the original article [1], the authors noticed an error in the second author’s name. The name of the second author, "Gregory Y. H. Lip", was incorrectly written as "Gregory-Y H Lip". This has been corrected with this erratum. The original article [1] has been corrected

Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia

Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Pneumonia and Septic Shock

CONTEXT: Individuals with type 2 diabetes mellitus (DM) have an increased risk of pneumonia and septic shock. Traditional glucose-lowering drugs have recently been found to be associated with a higher risk of infections. It remains unclear whether sodium-glucose cotransporter 2 inhibitors (SGLT2is), which have pleiotropic/anti-inflammatory effects, may reduce the risk of pneumonia and septic shock in DM. METHODS: MEDLINE, Embase, and ClinicalTrials.gov were searched from inception up to May 19, 2022, for randomized, placebo-controlled trials of SGLT2i that included patients with DM and reported outcomes of interest (pneumonia and/or septic shock). Study selection, data extraction, and quality assessment (using the Cochrane Risk of Bias Assessment Tool) were conducted by independent authors. A fixed-effects model was used to pool the relative risk (RRs) and 95% CI across trials. RESULTS: Out of 4568 citations, 26 trials with a total of 59 264 patients (1.9% developed pneumonia and 0.2% developed septic shock) were included. Compared with placebo, SGLT2is significantly reduced the risk of pneumonia (pooled RR 0.87, 95% CI 0.78-0.98) and septic shock (pooled RR 0.65, 95% CI 0.44-0.95). There was no significant heterogeneity of effect size among trials. Subgroup analyses according to the type of SGLT2i used, baseline comorbidities, glycemic control, duration of DM, and trial follow-up showed consistent results without evidence of significant treatment-by-subgroup heterogeneity (all P(heterogeneity) > .10). CONCLUSION: Among DM patients, SGLT2is reduced the risk of pneumonia and septic shock compared with placebo. Our findings should be viewed as hypothesis generating, with concepts requiring validation in future studies

Association between serum alkaline phosphatase and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005–2006

Background: Alkaline phosphatase (ALP) is a widely used marker for skeletal and hepatobiliary disorders, but its activity is also increased in atherosclerosis and peripheral vascular disease. It is an inflammatory marker like C-reactive protein (CRP). We therefore analyzed its relationship with CRP in the United States National Health and Nutrition Examination Survey (NHANES) 2005–2006. Methods: The analysis included 4155 men and non-pregnant women over the age of 20 years. The relationship between log-transformed ALP and plasma CRP was analyzed using univariate and multivariate models. Results: ALP activity was significantly correlated with age, waist circumference, body mass index, blood pressure, exercise, alcohol, triglycerides, and other liver enzymes after adjusting for age, gender and ethnicity (p<0.001). ALP was significantly associated with a higher frequency of cardiovascular disease (p=0.02), hypertension (p=0.01) hypercholesterolemia (p=0.04), and diabetes (p=0.02). Compared to the lowest quartile of ALP, the adjusted odds ratio (OR) associated with the highest quartile were 1.9 [95% confidence intervals (CI) 1.1–3.5], 1.6 (95% CI 1.0–2.5), 1.5 (95% CI 1.1–2.1) and 1.7 (95% CI 1.0–2.4) for cardiovascular disease, hypertension, hypercholesterolemia, and diabetes, respectively. In multivariate analysis, log ALP was an independent predictor of log CRP (p=1.0×10−6). A multivariate model that included log ALP, ethnicity, glycohemoglobin, waist circumference, albumin, apolipoprotein B, γ-glutamyltransferase and uric acid explained 40% of the variance in log CRP. Conclusions: ALP is a marker of cardiometabolic risk, but it needs to be tested as part of a multivariate model in prospective studies. Clin Chem Lab Med 2010;48:167–73.Peer Reviewe

Evaluation of GDF15 as a therapeutic target of cardiometabolic diseases in human: A Mendelian randomization studyResearch in context

Background: Growth differentiation factor 15 (GDF15) is a key regulator of body weight in animals by regulating food intake. Its receptor, glial cell-derived neurotrophic factor receptor alpha-like (GFRAL), was identified recently. Pre-clinical studies showed that it is a promising therapeutic target for cardiometabolic diseases and anorexia/cachexia. Although many pharmaceutical companies are developing drugs targeting GFRAL, whether the findings from animal studies can be extrapolated to man is unknown. Mendelian randomization (MR) is useful in investigating the relationship between risk factors and disease outcomes. We aimed to use a two-sample MR approach to evaluate the clinical usefulness of targeting GDF15 for cardiometabolic diseases. Methods: Genetic instruments and summary statistics for MR analyses were obtained from a large genome-wide association study (GWAS) of GDF15 and cardiometabolic outcomes (n = 27,394 to 644,875), including body mass index, waist-hip ratio, waist circumference, whole-body lean mass, fat percentage, Type 2 Diabetes, fasting glucose, glycated haemoglobin, fasting insulin, LDL-cholesterol, HDL-cholesterol, total cholesterol, triglycerides, coronary artery disease, and estimated BMD (eBMD). Conventional inverse variance weighted (IVW) method was adopted to obtain the causal estimates of GDF-15 with different outcomes; weighted median and MR-egger were used for sensitivity analyses. Findings: There was null association between GDF15 levels and anthropometric outcomes. One SD increase in genetically-determined GDF15 was significantly associated with reduced HDL-C (beta: -0.048SD; SE: 0.014; P = .001) but the result was not significant in sensitivity analyses. A consistent significant causal association was observed between GDF15 and eBMD in IVW (beta: 0.026 SD; SE: 0.005; P < .001) and subsequent sensitivity analyses. Interpretation: This study sheds lights on the potential of drugs targeting the GDF15/GFRAL axis. It suggested that the effect of targeting GDF15/GFRAL axis for weight control in human may be different from the effects observed in animal studies. GDF15 treatment may improve BMD in humans. Fund: No specific funding was received for this study