Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial.

BACKGROUND: Diabetes leads to chronic kidney disease (CKD) and kidney failure, requiring dialysis or transplantation. Astragalus, a common herbal medicine and US pharmacopeia-registered food ingredient, is shown kidney protective by retrospective and preclinical data but with limited long-term prospective clinical evidence. This trial aimed to assess the effectiveness of astragalus on kidney function decline in macroalbuminuric diabetic CKD patients. METHODS: This randomized, assessor-blind, standard care-controlled, multi-center clinical trial randomly assigned 118 patients with estimated glomerular filtration rate (eGFR) of 30-90 ml/min/1.73m2 and urinary albumin-to-creatinine ratio (UACR) of 300-5000 mg/g from 7 public outpatient clinics and the community in Hong Kong between July 2018 and April 2022 to add-on oral astragalus granules (15 gs of raw herbs daily equivalent) or to continue standard care alone as control for 48 weeks. Primary outcomes were the slope of change of eGFR (used for sample size calculation) and UACR of the intention-to-treat population. Secondary outcomes included endpoint blood pressures, biochemistry, biomarkers, concomitant drug change and adverse events. (ClinicalTrials.gov: NCT03535935) RESULTS: During the 48-week period, the estimated difference in the slope of eGFR decline was 4.6 ml/min/1.73m2 per year (95 %CI: 1.5 to 7.6, p = 0.003) slower with astragalus. For UACR, the estimated inter-group proportional difference in the slope of change was insignificant (1.14, 95 %CI: 0.85 to 1.52, p = 0.392). 117 adverse events from 31 astragalus-treated patients and 41 standard care-controlled patients were documented. The 48-week endpoint systolic blood pressure was 7.9 mmHg lower (95 %CI: -12.9 to -2.8, p = 0.003) in the astragalus-treated patients. 113 (96 %) and 107 (91 %) patients had post-randomization and endpoint primary outcome measures, respectively. CONCLUSION: In patients with type 2 diabetes, stage 2 to 3 CKD and macroalbuminuria, add-on astragalus for 48 weeks further stabilized kidney function on top of standard care.

Add-on Rehmannia-6-Based Chinese Medicine in Type 2 Diabetes and CKD: A Multicenter Randomized Controlled Trial.

BACKGROUND: Diabetes is the leading cause of CKD and kidney failure. We assessed the real-world effectiveness of Rehmannia-6-based Chinese medicine treatment, the most used Chinese medicine formulation, on the change in eGFR and albuminuria in patients with diabetes and CKD with severely increased albuminuria. METHODS: In this randomized, assessor-blind, standard care-controlled, parallel, multicenter trial, 148 adult patients from outpatient clinics with type 2 diabetes, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g were randomized 1:1 to a 48-week add-on protocolized Chinese medicine treatment program (using Rehmannia-6-based formulations in the granule form taken orally) or standard care alone. Primary outcomes were the slope of change in eGFR and UACR between baseline and end point (48 weeks after randomization) in the intention-to-treat population. Secondary outcomes included safety and the change in biochemistry, biomarkers, and concomitant drug use. RESULTS: The mean age, eGFR, and UACR were 65 years, 56.7 ml/min per 1.73 m 2 , and 753 mg/g, respectively. Ninety-five percent ( n =141) of end point primary outcome measures were retrievable. For eGFR, the estimated slope of change was -2.0 (95% confidence interval [CI], -0.1 to -3.9) and -4.7 (95% CI, -2.9 to -6.5) ml/min per 1.73 m 2 in participants treated with add-on Chinese medicine or standard care alone, resulting in a 2.7 ml/min per 1.73 m 2 per year (95% CI, 0.1 to 5.3; P = 0.04) less decline with Chinese medicine. For UACR, the estimated proportion in the slope of change was 0.88 (95% CI, 0.75 to 1.02) and 0.99 (95% CI, 0.85 to 1.14) in participants treated with add-on Chinese medicine or standard care alone, respectively. The intergroup proportional difference (0.89, 11% slower increment in add-on Chinese medicine, 95% CI, 0.72 to 1.10; P = 0.28) did not reach statistical significance. Eighty-five adverse events were recorded from 50 participants (add-on Chinese medicine versus control: 22 [31%] versus 28 [36%]). CONCLUSIONS: Rehmannia-6-based Chinese medicine treatment stabilized eGFR on top of standard care alone after 48 weeks in patients with type 2 diabetes, stage 2-3 CKD, and severely increased albuminuria. CLINICAL TRIAL REGISTRY: Semi-individualized Chinese Medicine Treatment as an Adjuvant Management for Diabetic Nephropathy (SCHEMATIC), NCT02488252 .

Screening for diabetic retinopathy with different levels of financial incentive in a randomized controlled trial.

AIMS/INTRODUCTION: To examine the impact of different levels of financial incentive in terms of fee subsidization on diabetic retinopathy screening in the private primary care setting in Hong Kong. MATERIALS AND METHODS: All general practitioners working in the private sector and registered in two electronic public databases were invited to participate. Consecutive patients with diabetes mellitus were then recruited by the participating practitioners. The recruited participants were randomly allocated to one of three screening groups with different fee levels (HK$0, HK$150 [US$19], HK$300 [US$39]) in a randomized controlled trial. Screening uptake and severity of diabetic retinopathy detected were compared. RESULTS: Out of 1,688 eligible practitioners, 105 participated and invited 402 patients, with 239 initially agreeing to participate (59.5%). After randomization, 78, 75 and 76 participants in the HK$0, HK$150 and HK$300 fee groups, respectively, reconfirmed their participation and were offered screening at the relevant fee. The uptake of screening was 79.5% (62/78), 81.3% (61/75) and 63.2% (48/76), in the HK$0, HK$150 and HK$300 groups, respectively (P < 0.018). Being in the HK$150 fee group was associated with higher uptake of screening than being in the HK$300 fee group (odds ratio 2.31, P = 0.039). No significant difference was found in the prevalence of any diabetic retinopathy (33.9%, 27.9% and 37.5%, P = 0.378) or sight-threatening diabetic retinopathy (4.8%, 8.2% and 16.7%; P = 0.092) among the groups. CONCLUSION: A screening fee of HK$150, representing approximately a half subsidy, appears to be as effective in maximizing uptake as a full subsidy (HK$0) and without deterring those at high risk of diabetic retinopathy from screening.

Efficacy, safety and response predictors of adjuvant astragalus for diabetic kidney disease (READY): study protocol of an add-on, assessor-blind, parallel, pragmatic randomised controlled trial.

INTRODUCTION: Diabetic kidney disease (DKD) is a prevalent and costly complication of diabetes with limited therapeutic options, being the leading cause of end-stage kidney disease in most developed regions. Recent big data studies showed that add-on Chinese medicine (CM) led to a reduced risk of end-stage kidney disease and mortality among patients with chronic kidney disease (CKD) and diabetes. Astragalus, commonly known as huang-qi, is the most prescribed CM or used dietary herb in China for diabetes and DKD. In vivo and in vitro studies showed that astragalus ameliorated podocyte apoptosis, foot process effacement, mesangial expansion, glomerulosclerosis and interstitial fibrosis. Nevertheless, the clinical effect of astragalus remains uncharacterised. This pragmatic clinical trial aims to evaluate the effectiveness of add-on astragalus in patients with type 2 diabetes, stage 2-3 CKD and macroalbuminuria, and to identify related response predictors. METHODS AND ANALYSIS: This is an add-on, assessor-blind, parallel, pragmatic randomised controlled clinical trial. 118 patients diagnosed with DKD will be recruited and randomised 1:1 to receive 48 weeks of add-on astragalus or standard medical care. Primary endpoints are the changes in estimated glomerular filtration rate and urine albumin-to-creatinine ratio between baseline and treatment endpoint. Secondary endpoints include adverse events, fasting blood glucose, glycated haemoglobin, lipids and other biomarkers. Adverse events are monitored through self-complete questionnaire and clinical visits. Outcomes will be analysed by regression models. Subgroup and sensitivity analyses will be conducted for different epidemiological subgroups and statistical analyses. Enrolment started in July 2018. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West/East/Kowloon Central clusters (UW 16-553/HKEC-2019-026/REC (KC/KE)-19-0049/ER-4). We will report the findings in medical journals and conferences. The dataset will be available on reasonable request. TRIAL REGISTRATION NUMBER: NCT03535935.

Distinct profiles of cognitive impairment associated with different silent cerebrovascular lesions in hypertensive elderly Chinese.

BACKGROUND/OBJECTIVES: Silent cerebrovascular lesions (SCLs) and their underlying pathology are now recognized as important causes of cognitive impairment in the elderly. However, the distinct profile of cognitive deficits associated with each type of SCLs remains unclear. METHODS: Of 497 otherwise healthy hypertensive elderly Chinese, 398 participants (mean age 72.0, ranging from 65 to 99, SD = 5.1) successfully completed a battery of structured neuropsychological tests and a multi-sequence 3 T MRI scanning. SCLs were rated independently. Correlations between each MRI marker and cognitive function were assessed using a series of linear regression models. RESULTS: Strictly lobar cerebral microbleeds were linked to impaired language function (B = -0.231, p < 0.05). Silent lacunes were associated with poor executive function, but the association disappeared after additional adjustment for white matter hyperintensities. White matter hyperintensities (especially periventricular hyperintensities) were associated with poor executive function (B = -0.126, p < 0.05) and slower information processing speed (B = -0.149, p < 0.05). CONCLUSION: Different SCLs were associated with different patterns of cognitive deficits, indicating that different SCLs may have distinct impacts on cognitive performance.

Immune Responses to Twice-Annual Influenza Vaccination in Older Adults in Hong Kong.

Background: Many health authorities recommend influenza vaccination of older adults to reduce disease burden. We hypothesized that in tropical and subtropical areas with more prolonged influenza seasons, twice-annual influenza vaccination might provide older adults with improved immunity against influenza. Methods: In 2014-2015, Hong Kong experienced a substantial A(H3N2) winter epidemic with a mismatched vaccine. Local authorities procured and administered to older adults the 2015 southern hemisphere influenza vaccine, which included an updated and matching A/Switzerland/9715293/2013(H3N2) strain. We compared immune parameters in pre- and postvaccination sera from older adults ≥75 years of age who received 1 vs 2 influenza vaccines per year. Results: We enrolled 978 older adults with 470 vaccinations for summer 2015 and 827 vaccinations for winter 2015-2016. Recipients of southern hemisphere vaccination had higher geometric mean titers (GMTs) by the hemagglutination inhibition assay against all 3 vaccine strains. When receiving influenza vaccination for the subsequent winter, the southern hemisphere vaccine recipients had higher prevaccination GMTs but lower postvaccination GMTs, compared to those who had not received the southern hemisphere vaccine. Furthermore, cellular immunity was impacted by biannual vaccination, with reduced influenza-specific CD4 T-cell responses in the second season of vaccination. Conclusions: We observed some reductions in immune responses in the twice-annual vaccination group compared with the once-annual vaccination group, in the context of unchanging vaccine strains, while protection was likely to have been improved during the summer and autumn for the twice-annual vaccination group due to the continued circulation of the A/Switzerland/9715293/2013(H3N2) virus.

Semi-individualised Chinese medicine treatment as an adjuvant management for diabetic nephropathy: a pilot add-on, randomised, controlled, multicentre, open-label pragmatic clinical trial.

INTRODUCTION: Diabetes mellitus and diabetic nephropathy (DN) are prevalent and costly to manage. DN is the leading cause of end-stage kidney disease. Conventional therapy blocking the renin-angiotensin system has only achieved limited effect in preserving renal function. Recent observational data show that the use of Chinese medicine (CM), a major form of traditional medicine used extensively in Asia, could reduce the risk of end-stage kidney disease. However, existing clinical practice guidelines are weakly evidence-based and the effect of CM remains unclear. This trial explores the effect of an existing integrative Chinese-Western medicine protocol for the management of DN. OBJECTIVE: To optimise parameters and assess the feasibility for a subsequent phase III randomised controlled trial through preliminary evaluation on the effect of an adjuvant semi-individualised CM treatment protocol on patients with type 2 diabetes with stages 2-3 chronic kidney disease and macroalbuminuria. METHODS AND ANALYSIS: This is an assessor-blind, add-on, randomised, controlled, parallel, multicentre, open-label pilot pragmatic clinical trial. 148 patients diagnosed with DN will be recruited and randomised 1:1 to a 48-week additional semi-individualised CM treatment programme or standard medical care. Primary end points are the changes in estimated glomerular filtration rate and spot urine albumin-to-creatinine ratio between baseline and treatment end point. Secondary end points include fasting blood glucose, glycated haemoglobin, brain natriuretic peptide, fasting insulin, C peptide, fibroblast growth factor 23, urinary monocyte chemotactic protein-1, cystatin C, nephrin, transforming growth factor-ß1 and vascular endothelial growth factor. Adverse events are monitored through self-completed questionnaire and clinical visits. Outcomes will be analysed by regression models. Enrolment started in July 2015. ETHICS AND REGISTRATION: This protocol is approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (reference number UW 14-301). TRIAL REGISTRATION NUMBER: NCT02488252.

The Correlation of Retinal Nerve Fiber Layer Thickness With Blood Pressure in a Chinese Hypertensive Population.

To investigate the association between retinal nerve fiber layer (RNFL) thickness and blood pressure (BP) in subjects with systemic hypertension. Subjects with systemic hypertension on anti-hypertensive medications were screened by fundus photography and referred for glaucoma work-up if there was enlarged vertical cup-to-disc (VCDR) ratio ≥0.6, VCDR asymmetry ≥0.2, or optic disc hemorrhage. Workup included a complete ophthalmological examination, Humphrey visual field test, and RNFL thickness measurement by optical coherence tomography. The intraocular pressure (IOP) and RNFL thicknesses (global and quadrant) were averaged from both eyes and the means were correlated with: the systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) using Pearson correlation. Among 4000 screened hypertensive subjects, 133 were referred for glaucoma workup and 110 completed the workup. Of the 4000 screened subjects, 1.3% had glaucoma (0.9% had normal tension glaucoma [NTG], 0.2% had primary open angle glaucoma, and 0.2% had primary angle closure glaucoma), whereas 0.3% were NTG suspects. The SBP was negatively correlated with the mean superior RNFL thickness (P = 0.01). The DBP was negatively correlated with the mean global (P = 0.03), superior (P = 0.02), and nasal (P = 0.003) RNFL thickness. The MAP was negatively correlated with the mean global (P = 0.01), superior (P = 0.002), and nasal (P = 0.004) RNFL thickness while positively correlated with the mean IOP (P = 0.02). In medically treated hypertensive subjects, glaucoma was present in 1.3%, with NTG being most prevalent. MAP control may help with IOP lowering and RNFL preservation, although future prospective studies will be needed.

Absence of detectable influenza RNA transmitted via aerosol during various human respiratory activities--experiments from Singapore and Hong Kong.

Two independent studies by two separate research teams (from Hong Kong and Singapore) failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin's mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR) assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing), talk (counting in English/second language), cough (from 1 m/0.1 m away) and laugh, onto a thermal, breathing manikin. The manikin's face was swabbed at specific points (around both eyes, the nostrils and the mouth) before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team's in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B) infection with high viral loads, ranging from 10(5)-10(8) copies/mL (Hong Kong volunteers/assay) and 10(4)-10(7) copies/mL influenza viral RNA (Singapore volunteers/assay). These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within these exposure time-frames. Various reasons are discussed in an attempt to explain these findings.

Erectile dysfunction and lower urinary tract symptoms: prevalence and risk factors in a Hong Kong primary care setting.

OBJECTIVES: To study the prevalence and associated risk factors of erectile dysfunction and lower urinary tract symptoms in a primary care population in Hong Kong. DESIGN: Questionnaire study. SETTING: Sai Ying Pun Jockey Club General Outpatient Clinic, Hong Kong. PARTICIPANTS: Male patients (n=950) seen between November 2010 and February 2011. MAIN OUTCOME MEASURES: International Prostate Symptom Score, and the five-item version of the International Index of Erectile Function. RESULTS: The point prevalence of any degree of erectile dysfunction in our sample was 68% (mild 13%, mild-to-moderate 14%, moderate 16%, and severe 24%). Univariate analysis showed that age, education, working status, marital status, and smoking were associated factors. Further multiple logistic regression analysis identified age and smoking as significantly associated. The point prevalence of moderate and severe lower urinary tract symptoms was 36% and 32%, respectively. For the predictors of such symptoms, univariate analysis identified five factors (age, education, working status, marital status, and smoking) and only working status was not significantly associated with these symptoms in the multiple logistic regression analysis. The Pearson coefficient test showed a significant negative relation (r= -0.525; P<0.0001) between the two outcome measures (International Prostate Symptom Score and the five-item version of the International Index of Erectile Function). CONCLUSIONS: We showed that erectile dysfunction and lower urinary tract symptoms are common health problems in Chinese males seen in primary care. The correlation between the two outcome measures was statistically significant. Primary care physicians should increase awareness on erectile dysfunction and lower urinary tract symptoms so as to provide early screening and detection, as well as comprehensive treatment.

Detection of glaucoma in a cohort of chinese subjects with systemic hypertension.

Purpose. To determine the presence and type of glaucoma in a cohort of adult Chinese subjects with systemic hypertension. Methods. This prospective cohort study included 200 hypertensive Chinese adults aged >40 years old who underwent screening via frequency doubling technology (FDT) perimetry and intraocular pressure (IOP) measurement by noncontact tonometry (NCT) in a general outpatient clinic. Those with IOP > 21 mmHg and/or visual field (VF) defects on FDT were referred for complete ophthalmological examination. The diagnosis of glaucoma was based on an abnormal VF on Humphrey Field Analyzer (HFA) by Hodapp-Parrish-Anderson's criteria and an increased vertical cup-disc ratio (VCDR). Results. The mean age of the subjects was 64.66 ± 9.47 years, and the male:female ratio was 92 : 108. All patients were hypertensive with a mean blood pressure (BP) of 131.1 ± 15.1/76.6 ± 11.1 mmHg whilst on systemic antihypertensive medication. Of the 111 patients that had an abnormal initial screening, 14 (7.9%) were confirmed to have glaucoma with the highest prevalence of normal tension glaucoma (NTG) (6.2%), followed by primary angle closure glaucoma (PACG) (1.1%) and primary open angle glaucoma (POAG) (0.5%). The positive predictive value of FDT perimetry was 71%. Conclusion. Nearly 8% of the adults with systemic hypertension had glaucoma, and NTG was the most prevalent type.

Comparative epidemiology of pandemic and seasonal influenza A in households.

BACKGROUND: There are few data on the comparative epidemiology and virology of the pandemic 2009 influenza A (H1N1) virus and cocirculating seasonal influenza A viruses in community settings. METHODS: We recruited 348 index patients with acute respiratory illness from 14 outpatient clinics in Hong Kong in July and August 2009. We then prospectively followed household members of 99 patients who tested positive for influenza A virus on rapid diagnostic testing. We collected nasal and throat swabs from all household members at three home visits within 7 days for testing by means of quantitative reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay and viral culture. Using hemagglutination-inhibition and viral-neutralization assays, we tested baseline and convalescent serum samples from a subgroup of patients for antibody responses to the pandemic and seasonal influenza A viruses. RESULTS: Secondary attack rates (as confirmed on RT-PCR assay) among household contacts of index patients were similar for the pandemic influenza virus (8%; 95% confidence interval [CI], 3 to 14) and seasonal influenza viruses (9%; 95% CI, 5 to 15). The patterns of viral shedding and the course of illness among index patients were also similar for the pandemic and seasonal influenza viruses. In a subgroup of patients for whom baseline and convalescent serum samples were available, 36% of household contacts who had serologic evidence of pandemic influenza virus infection did not shed detectable virus or report illness. CONCLUSIONS: Pandemic 2009 H1N1 virus has characteristics that are broadly similar to those of seasonal influenza A viruses in terms of rates of viral shedding, clinical illness, and transmissibility in the household setting.