The effectiveness of dietary approaches to stop hypertension (DASH) counselling on estimated 10-year cardiovascular risk among patients with newly diagnosed grade 1 hypertension : a randomised clinical trial

The Dietary Approaches to Stop Hypertension (DASH) has been shown to lower blood pressure in the West. However, the real-life impact of DASH on reducing cardiovascular (CV) risk in routine clinical setting has not been studied. Methods A parallel-group, open-labelled, physician-blinded, randomised controlled trial was conducted in January–June 2013 and followed up for 6- and 12-months in primary care settings in Hong Kong. Patients newly diagnosed with grade 1 hypertension (aged 40–70 years) who had no concomitant medical conditions requiring dietary modifications were consecutively recruited. Subjects were randomised to standard education (usual care) (n = 275), or usual care plus dietitian-delivered DASH-based dietary counselling in a single one-to-one session (intervention) (n = 281). Primary outcomes were the changes in estimated 10-year CV risk. Results Outcome data were available for 504 (90.6%) and 485 (87.2%) patients at 6 and 12 months, respectively. There was no difference in the reduction of 10-year CV risk between the two groups at 6 months (−0.13%, 95% confidence interval [95% CI] −0.50% to 0.23%, p = 0.477) and 12 months (−0.08%, 95% CI −0.33% to 0.18%, p = 0.568). Multivariate regression analyses showed that male subjects, younger patients, current smokers, subjects with lower educational level, and those who dined out for main meals for ≥4 times in a typical week were significantly associated with no improvements in CV risk. Conclusions The findings may not support automatic referral of newly diagnosed grade 1 hypertensive patients for further one-to-one dietitian counselling on top of primary care physician's usual care. Patients with those risk factors identified should receive more clinical attention to reduce their CV risk

Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review

The prevalence of diabetes mellitus is rising globally, and it induces a substantial public health burden to the healthcare systems. Its optimal control is one of the most significant challenges faced by physicians and policy-makers. Whereas some of the established oral hypoglycaemic drug classes like biguanide, sulphonylureas, thiazolidinediones have been extensively used, the newer agents like dipeptidyl peptidase-4 (DPP-4) inhibitors and the human glucagon-like peptide-1 (GLP-1) analogues have recently emerged as suitable options due to their similar efficacy and favorable side effect profiles. These agents are widely recognized alternatives to the traditional oral hypoglycaemic agents or insulin, especially in conditions where they are contraindicated or unacceptable to patients. Many studies which evaluated their clinical effects, either alone or as add-on agents, were conducted in Western countries. There exist few reviews on their effectiveness in the Asia-Pacific region. The purpose of this systematic review is to address the comparative effectiveness of these new classes of medications as add-on therapies to sulphonylurea drugs among diabetic patients in the Asia-Pacific countries. We conducted a thorough literature search of the MEDLINE and EMBASE from the inception of these databases to August 2013, supplemented by an additional manual search using reference lists from research studies, meta-analyses and review articles as retrieved by the electronic databases. A total of nine randomized controlled trials were identified and described in this article. It was found that DPP-4 inhibitors and GLP-1 analogues were in general effective as add-on therapies to existing sulphonylurea therapies, achieving HbA1c reductions by a magnitude of 0.59–0.90% and 0.77–1.62%, respectively. Few adverse events including hypoglycaemic attacks were reported. Therefore, these two new drug classes represent novel therapies with great potential to be major therapeutic options. Future larger-scale research should be conducted among other Asia-Pacific region to evaluate their efficacy in other ethnic groups

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Experiences of community-dwelling older adults with chronic low back pain in Hong Kong and Switzerland ::a qualitative study

Introduction: The prevalence of chronic low back pain (LBP) increases with age and older adults are more vulnerable to develop chronic LBP. A recent Swiss study has shown that 78% of community-dwelling older adults aged ≥65 years experienced chronic LBP. Similarly, a study in Hong Kong found that approximately 30% of people aged above 60 years experienced chronic LBP. The aim of this collaborative research project was to illuminate older adults’ experiences of living with chronic LBP and its implication on older adults’ daily life in Western and Eastern cultures. Methods: Twenty-five older people experiencing chronic LBP living in Switzerland or Hong Kong were recruited through health professionals or community centres. Using semi-structured interviews, participants shared their experiences regarding chronic LBP and its implications on their daily life. The interviews were recorded and transcribed “ad verbatim” in the original language. An inductive thematic analysis was used, using a qualitative data analysis software program (NVivo) and a shared code book in English. The Swiss and Hong Kong research teams engaged in collaborative analysis until a consensus was established, taking into consideration of cultural specificities. Ethical approval was obtained from the local ethic committees in both regions. Results: Themes were related to negative perceptions/experiences: (1) interferences of daily function; (2) pessimistic attitudes toward their conditions/prognosis; and (3) self-perceived burden related to families. Conversely, four themes revealed attributes to social roles: (1) maintaining their roles in families; (2) experiencing supports from family and friends; (3) being content despite LBP; and (4) enjoying social activities. Cultural differences between Switzerland and Hong Kong were related to social circles and offers from the healthcare system, influencing individual experiences and perceptions. Discussion: Although chronic LBP may negatively impact older adults, individual approaches as well as social and health system supports influence older adults’ attitude toward their pain and self-management strategies

Cardiovascular mortality in hypertensive patients newly prescribed perindopril vs. lisinopril: a 5-year cohort study of 15,622 Chinese subjects

Background: Perindopril and lisinopril are two common ACE inhibitors prescribed for management of hypertension. Few studies have evaluated their comparative effectiveness to reduce mortality. This study compared the all-cause and cardiovascular related mortality among patients newly prescribed ACE inhibitors. Methods: All adult patients newly prescribed perindopril or lisinopril from 2001 to 2005 in all public clinics or hospitals in Hong Kong were retrospectively evaluated, and followed up until 2010. Patients prescribed the ACE inhibitors for less than a month were excluded. The all-cause mortality and cardiovascular-specific (i.e. coronary heart disease, heart failure and stroke) mortality were compared. Cox proportional hazard regression model was used to assess the mortality, controlling for age, sex, socioeconomic status, patient types, the presence of comorbidities, and medication adherence as measured by the proportion of days covered. An additional model using propensity scores was performed to minimize indication bias. Results: A total of 15,622 patients were included in this study, in which 6910 were perindopril users and 8712 lisinopril users. The all-cause mortality (22.2% vs. 20.0%, p < 0.005) and cardiovascular mortality (6.5% vs. 5.6%, p < 0.005) were higher among lisinopril users than perindopril users. From regression analyses, lisinopril users were 1.09-fold (95% C.I. 1.01–1.16) and 1.18-fold (95% C.I. 1.02–1.35) more likely to die from any-cause and cardiovascular diseases, respectively. Age-stratified analysis showed that this significant difference was observed only among patients aged > 70 years. The additional models controlled for propensity scores yielded comparable results. Conclusions: The long-term all-cause and cardiovascular related mortality rates of lisinopril users was significantly different from those of perindopril users. These findings showed that intra-class variation on mortality exists among ACE inhibitors among those aged 70 years or older. Future studies should consider a longer, large-scale randomized controlled trial to compare the effectiveness between different medications in the ACEI class, especially among the elderly

Search Strategy.

<p>Search Strategy.</p

Studies included in the present review.

a<p>SU =  sulphonylurea.</p>b<p>A-GI =  α-glucosidase inhibitors.</p>c<p>NS =  Non-significant.</p

Flowchart of study selection.

<p>Flowchart of study selection.</p

Ultra-Rare Genetic Variation in the Epilepsies: A Whole-Exome Sequencing Study of 17,606 Individuals

Sequencing-based studies have identified novel risk genes associated with severe epilepsies and revealed an excess of rare deleterious variation in less-severe forms of epilepsy. To identify the shared and distinct ultra-rare genetic risk factors for different types of epilepsies, we performed a whole-exome sequencing (WES) analysis of 9,170 epilepsy-affected individuals and 8,436 controls of European ancestry. We focused on three phenotypic groups: severe developmental and epileptic encephalopathies (DEEs), genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We observed that compared to controls, individuals with any type of epilepsy carried an excess of ultra-rare, deleterious variants in constrained genes and in genes previously associated with epilepsy; we saw the strongest enrichment in individuals with DEEs and the least strong in individuals with NAFE. Moreover, we found that inhibitory GABAA receptor genes were enriched for missense variants across all three classes of epilepsy, whereas no enrichment was seen in excitatory receptor genes. The larger gene groups for the GABAergic pathway or cation channels also showed a significant mutational burden in DEEs and GGE. Although no single gene surpassed exome-wide significance among individuals with GGE or NAFE, highly constrained genes and genes encoding ion channels were among the lead associations; such genes included CACNA1G, EEF1A2, and GABRG2 for GGE and LGI1, TRIM3, and GABRG2 for NAFE. Our study, the largest epilepsy WES study to date, confirms a convergence in the genetics of severe and less-severe epilepsies associated with ultra-rare coding variation, and it highlights a ubiquitous role for GABAergic inhibition in epilepsy etiology