The Hong Kong Society of Rheumatology consensus recommendations for the management of gout.

Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains suboptimal. Like other countries, the treatment goal in Hong Kong usually focuses on relieving symptoms of gout but not treating the serum urate level to target. As a result, patients with gout continue to suffer from the debilitating arthritis, as well as the renal, metabolic, and cardiovascular complications associated with gout. The Hong Kong Society of Rheumatology spearheaded the development of these consensus recommendations through a Delphi exercise that involved rheumatologists, primary care physicians, and other specialists in Hong Kong. Recommendations on acute gout management, gout prophylaxis, treatment of hyperuricemia and its precautions, co-administration of non-gout medications with urate-lowering therapy, and lifestyle advice have been included. This paper serves as a reference guide to all healthcare providers who see patients who are at risk and are known to have this chronic but treatable condition.

Five-year cardiovascular event risk in early rheumatoid arthritis patients who received treat-to-target management: a case-control study.

OBJECTIVES: This study explored whether the excess cardiovascular (CV) disease (CVD) risk in RA could be ameliorated by suppression of inflammation using a treat-to-target (T2T) approach. We compared the CV event (CVE) incidence among ERA patients managed by a T2T strategy with a CV risk factor-matched non-RA population and a historical RA cohort (HRA). METHODS: This was an observational study using the city-wide hospital data and the ERA registry. ERA patients received T2T management while HRA patients received routine care. Each ERA/HRA patient was matched to three non-RA controls according to age, gender and CV risk factors. Patients on antiplatelet/anticoagulant agents, with pre-existing CVD, chronic kidney disease or other autoimmune diseases were excluded. All subjects were followed for up to 5 years. The primary end point was the first occurrence of a CVE. RESULTS: The incidence of CVE in the ERA cohort (n = 261) and ERA controls were similar with a hazard ratio of 0.53 (95% CI 0.15, 1.79). In contrast, the incidence of CVE in the HRA cohort (n = 268) was significantly higher than that of the HRA controls with a hazard ratio of 1.9 (95% CI 1.16, 3.13). The incidence of CVE in the ERA cohort was significantly lower than that of the HRA cohort and the difference became insignificant after adjusting for inflammation, the use of methotrexate and traditional CV risk factors. CONCLUSION: ERA patients managed by a T2T strategy did not develop excess CVE compared with CV risk factor-matched controls over 5 years.

Prevalence of Childhood Obesity in the United States in 1999-2018: A 20-Year Analysis.

INTRODUCTION: Obesity is a public health crisis in the USA. This study aimed to estimate the prevalence of obesity and severe obesity in US children and adolescents and identify novel targetable risk factors associated with childhood obesity. METHODS: From the US National Health and Nutrition Examination Survey from 1999 to 2018, 35,907 children aged 2-19 with body mass index (BMI) data were included. Obesity and severe obesity were defined as BMI ≥95th percentile and ≥120% of 95th percentile of US Centers for Disease Control and Prevention growth charts, respectively. Trends in the prevalence of obesity and subgroup analyses according to socioeconomic factors and language used in the interview were analyzed. RESULTS: The prevalence of obesity and severe obesity increased from 14.7 [95% confidence interval: 12.9-17.0]% to 19.2 [17.2-21.0]% and 3.9 [2.9-5.0]% to 6.1 [4.8-8.0]% in 1999-2018, respectively (p = 0.001 and p = 0.014, respectively). In 2017-2018, the prevalence of obesity among children from Spanish-speaking households was 24.4 [22.4-27.0]%, higher than children from English-speaking households (p = 0.027). CONCLUSION: The prevalence of childhood obesity kept increasing in 1999-2018. The problem is worse in children from Spanish-speaking households. Novel and targeted public health intervention strategies are urgently warranted to effectively halt the rising epidemic of childhood obesity.

Nurse-Led Consultation for Patients With Rheumatoid Arthritis at Low Disease Activity: A Randomized Noninferiority Trial.

OBJECTIVE: To determine the effectiveness of nurse-led consultations in patients with stable rheumatoid arthritis (RA) in Hong Kong. METHODS: The present work was a single-center, randomized, open-label, noninferiority trial. Patients who had rheumatoid arthritis (RA) with low disease activity (LDA) were randomized at a 1:1 ratio to attend a nurse-led consultation or rheumatologist follow-up visit for 2 years. The primary end point was the proportion of patients whose RA remained at LDA. Secondary end points included the proportion of patients with RA in disease remission and the scores recorded on the Leeds Satisfaction Questionnaire at 2 years, changes from baseline on the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), modified Sharp/van der Heijde score (SHS), Health Assessment Questionnaire disability index (HAQ DI), Short Form 36 (SF-36) physical component score, and 19-item Compliance Questionnaire for Rheumatology (CQR-19) score. RESULTS: Among 280 patients who were randomized equally to either attend nurse-led consultations or rheumatologist follow-up visits, 267 patients completed the study. In the nurse-led consultation and rheumatologist follow-up groups, 92.1% and 91.4% patients, respectively, remained at LDA at 2 years. The 95% confidence intervals (95% CIs) of the adjusted treatment difference were within the predefined noninferiority margin in both the intention-to-treat analysis (95% CI 5.75, 7.15) and the per-protocol analysis (95% CI 1.67, 7.47). Although the changes in DAS28-CRP score over 2 years were significantly different between the 2 treatment groups (P < 0.001), there were no significant changes from baseline in SHS, HAQ DI, SF-36 physical component scores, and CQR-19 scores. At the end of the study, more patients expressed satisfaction with nurse-led consultations. CONCLUSION: Nurse-led consultations were not inferior to rheumatologist follow-up visits in patients with stable RA.

Association of Alendronate and Risk of Cardiovascular Events in Patients With Hip Fracture.

The risk of cardiovascular events (CVEs) with alendronate use in real-world hip fracture patients is unknown. This study aimed to investigate the risk of CVE with and without use of alendronate in patients with hip fracture. We conducted a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with hip fracture from 2005 through 2013 were followed until November 6, 2016. Alendronate and other antiosteoporosis medications use during the study period were examined. We matched treated and nontreated patients based on time-dependent propensity score. The risks of cardiovascular mortality, myocardial infarction, and stroke between treatment groups were evaluated using conditional Cox regression stratified by match pairs. To examine the associations over time, outcomes were assessed at 1 year, 3 years, 5 years, and 10 years. Among 34,991 patients with newly diagnosed hip fracture, 4602 (13.2%) received antiosteoporosis treatment during follow-up. Physical functioning or survival prospect was not significantly different between treated and nontreated patients. A total of 4594 treated patients were matched with 13,568 nontreated patients. Results of Cox regression analysis revealed that alendronate was associated with a significantly lower risk of 1-year cardiovascular mortality (HR 0.33; 95% CI, 0.17 to 0.65) and incident myocardial infarction (HR 0.55; 95% CI, 0.34 to 0.89), whereas marginally significant reduction in risk of stroke was observed at 5 years and 10 years (HR at 5 years: 0.82; 95% CI, 0.67 to 1.00; p = 0.049; HR at 10 years: 0.83; 95% CI, 0.69 to 1.01; p = 0.065). The strength of the association declined over time but remained significant. Similar results were observed when all nitrogen-containing bisphosphonates (N-BPs) were analyzed together. These findings were robust in multiple sensitivity analyses. Additional studies in other population samples and randomized clinical trials may be warranted to further understand the relationship between use of various antiosteoporosis medication and risk of CVE in patients with hip fracture. © 2018 American Society for Bone and Mineral Research.

Pharmacokinetics of the BCL-2 Inhibitor Venetoclax in Healthy Chinese Subjects.

Venetoclax has been approved in the United States, Europe, Canada, and Australia for appropriate patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The objective of this phase 1 study was to evaluate the pharmacokinetics of venetoclax in Chinese subjects to inform the dose selection of venetoclax in a phase 2 study of patients with relapsed/refractory (R/R) CLL in China. Twelve healthy first-generation Han Chinese subjects received a single 100-mg dose of venetoclax following a low-fat breakfast. Pharmacokinetic parameters were estimated using noncompartmental methods. After a single dose of venetoclax in healthy Chinese subjects, the median time to peak concentration was 6 hours (range, 4 to 6 hours), and the mean ± SD Cmax , AUCinf , and terminal half-life were 1.0 ± 0.32 µg/mL, 12.6 ± 5.4 µg·h/mL, and 18.4 ± 2.97 hours, respectively. On average, venetoclax Cmax and AUCinf values were 94% and 66% higher, respectively, in Chinese subjects compared with those observed historically for non-Asian subjects receiving the same dose. Based on these pharmacokinetic results and the established exposure-response relationship of venetoclax in non-Asian CLL subjects, a 400-mg once-daily dosage regimen was selected for evaluating the venetoclax pharmacokinetics, efficacy, and safety in the venetoclax phase 2 open-label study in Chinese subjects with R/R CLL.

The effectiveness of a 'Do Not Use' list and perceptions of healthcare professionals on error-prone abbreviations.

BACKGROUND: The use of error-prone abbreviations has led to medication errors. Many safety organisations have introduced 'Do Not Use' lists (lists of error-prone abbreviations that should be avoided by prescribers), but the effectiveness of these lists have not been studied. OBJECTIVE: We assessed the effectiveness of the 'Do Not Use' list introduced to the study hospital, and sought the attitudes of healthcare professionals on other potentially dangerous abbreviations (not included in the 'Do Not Use' list) used in prescriptions. SETTING: The study was conducted in a university affiliated tertiary hospital in Hong Kong. METHODS: An uncontrolled observational study was conducted. In-patient prescriptions were reviewed to assess the use of error-prone abbreviations included in the 'Do Not Use' list before, after its introduction, and following the first reinforcement. An on-line survey was also conducted among prescribers, pharmacists and nurses. MAIN OUTCOME MEASURE: Rate of using error-prone abbreviations and other unapproved abbreviations among reviewed prescriptions. RESULTS: 3,238 prescriptions (23,398 drug items) were reviewed. The use of abbreviations in the 'Do Not Use' list decreased from 7.8 to 3.3 % after its introduction (P < 0.001) and to 1.3 % after the first reinforcement (P < 0.001). However, unapproved abbreviations were used to denote prescribing instructions in 19.2 % of the drugs prescribed. 49 different types of unapproved abbreviations were used for drug names. CONCLUSIONS: A 'Do Not Use' list is effective in reducing error-prone abbreviations. Reinforcements of the 'Do Not Use' list further improves prescriber adherence. However, many other unapproved abbreviations (not included in current 'Do Not Use' lists) are used when prescribing. Periodic reminders on error-prone abbreviations and education of prescribers on associated risks may help to reduce the use of error-prone abbreviations in hospitals.

Hay fever and hypertension in the US adult population.

PURPOSE: Hypertension is associated with inflammation. Whether the inflammation caused by allergic diseases such as allergic rhinitis can predispose to hypertension is controversial. Therefore, we studied the association between hay fever and hypertension in the United States National Health and Nutrition Examination Survey (NHANES). METHODS: We analyzed data on 1883 men and 2029 women in NHANES 2005-2006. We included participants aged 20 years or older who had valid data on hay fever and hypertension. RESULTS: 13.5% of the participants had a previous diagnosis of hay fever and 36.2% of them had hypertension. There were ethnic differences in the prevalence of previous hay fever diagnosis (p < 0.001) and hypertension (p < 0.001). There was no significant association between previous hay fever diagnosis and hypertension in men in any age group. The association between previous hay fever diagnosis and hypertension in women was significant in those aged 20-39 years (OR = 2.59, 95%CI = 1.26-5.30, p = 0.013). The association between previous hay fever diagnosis and hypertension in women aged form 20 to 39 years remained significant after adjustment for age, race and body mass index (OR = 2.74, 95%CI = 1.48-5.06, p = 0.003). After further adjustment for physical activity, alcohol consumption and smoking, the association was not attenuated (OR = 2.68, 95%CI = 1.38-5.18, p = 0.006). Further adjustment for liver enzymes, C-reactive protein and immunoglobulin E level attenuated the association slightly (OR = 2.72, 95%CI = 1.19-6.22, p = 0.021). CONCLUSIONS: In this nationally representative population-based survey, previous hay fever diagnosis is not significantly associated with hypertension in adults overall. There is an association in subgroup of young women aged 20-39. Further work is needed to confirm that this is a true association.

Plasma level of adrenomedullin is influenced by a single nucleotide polymorphism in the adiponectin gene.

OBJECTIVE: Adrenomedullin (ADM) and adiponectin are both involved in inflammation and cardiovascular diseases. The plasma levels of these peptides are influenced by single nucleotide polymorphisms (SNPs) in the ADM and ADIPOQ genes respectively. There is some evidence that ADM may regulate adiponectin gene expression, but whether adiponectin can regulate ADM expression is unclear, and was therefore investigated. METHODS: Plasma ADM level was measured in 476 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS2). We genotyped them for 2 ADIPOQ SNPs that are known to be associated with plasma adiponectin level. RESULTS: The minor allele frequencies of ADIPOQ SNPs rs182052 and rs12495941 were 40.6% and 42.2% respectively. Plasma ADM level was significantly associated with rs182052 after adjusting for age and sex (ß=0.104, P=0.023) but not with rs12495941 (ß=0.071, P=0.120). In multivariate analysis, plasma ADM level increased with the number of minor alleles of rs182052 (P=0.013). Compared to subjects with GG genotype, subjects with AA genotype had 17.7% higher plasma ADM level (95% CI: 3.6%-33.7%). Subgroup analysis revealed that the association was significant in diabetic patients (ß=0.344, P=0.001) but not in non-diabetic subjects. CONCLUSION: Plasma ADM level is related to SNP rs182052 in the ADIPOQ gene. Our findings provide new evidence of the interplay between these two important peptides in cardiovascular disease and diabetes. Knowing the genotype may help to refine the interpretation of these biomarkers.

Reduced serum beta-trace protein is associated with metabolic syndrome.

OBJECTIVES: ß-trace protein (BTP), also known as lipocalin-type prostaglandin D2 synthase, has shown to regulate glucose and lipid metabolism in vivo. We sought to study the relationship of serum BTP with diabetes and metabolic syndrome (MetS). METHODS: Data on 3136 participants aged ≥20 years of the National Health and Nutrition Examination Survey III were examined. Logistic regression was used to assess the association of BTP with diabetes and MetS. RESULTS: Reduced levels of BTP were associated with diabetes and MetS in age, sex, and race/ethnicity adjusted models. After further multivariable adjustment, BTP levels in quartile 1 remained significantly associated with MetS (odds ratio 2.04 [95% CI 1.14-3.70], Ptrend = 0.003) when compared with quartile 4. Among the five components of MetS, BTP was associated with hypertriglyceridemia (Ptrend < 0.001) but not diabetes (Ptrend = 0.099). CONCLUSION: MetS is associated with a reduced serum level of BTP.

High ferritin and low transferrin saturation are associated with pre-diabetes among a national representative sample of U.S. adults.

BACKGROUND & AIMS: Iron overload is known to cause diabetes. However, the underlying mechanism is poorly understood. We therefore studied the association of different markers of iron metabolism, namely ferritin, erythrocyte protoporphyrin and transferrin saturation (TSAT, as defined by a percentage of transferrin that is saturated with iron) with pre-diabetes (preDM) in US adults without chronic kidney disease, anemia, and iron deficiency. METHODS: Data on 2575 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2002 who were free of diabetes, chronic kidney disease, iron deficiency, and anemia were analyzed. Data on 3876 participants of the NHANES III (1988-1994) were used as replication. Homeostasis model assessment of insulin resistance (HOMA-IR), blood glycosylated hemoglobin level (HbA1C), fasting glucose, insulin, and preDM (defined as a fasting plasma glucose 100-125 mg/dl or an HBA1C value 5.7-6.4%) were measured as the outcomes. RESULTS: Logistic regression analyses indicated independent associations of high ferritin (Ptrend = 0.028) and low TSAT (P(trend) = 0.029) with preDM after adjusting for sociodemographics, physical activity (active/sedementary), metabolic and inflammatory markers (triglycerides, total cholesterol, HDL cholesterol, mean arterial pressure, CRP, white cell count, and albumin), and liver enzymes (GGT, Alk phos, AST, and ALT). The NHANES III data showed similar associations. Combining the results showed a more significant association for high ferritin (P(meta) = 0.016) and low TSAT (P(meta) = 0.002). Moreover, TSAT was associated with HbA1C, fasting glucose, insulin, and HOMA-IR (P(meta) ≤ 0.001). CONCLUSIONS: Higher ferritin and lower TSAT are associated with higher risk of preDM in a general population without confounding diseases. Further research is needed to examine the underlying mechanism of these two indices, especially TSAT, in the pathophysiology of preDM.