Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Biomechanical Ambulatory Assessment of 3D Knee Angle Using Novel Inertial Sensor-Based Technique

Three-dimensional (3D) knee angle measurement is one of the key measures in human gait analysis. Inertial sensor capable of measuring joint motion under unconstrained conditions is a practical tool for clinical evaluation and rehabilitation. An inertial measurement unit (IMU) consisting of accelerometer and gyroscope allows orientation measurement in 3D with an additional sensor (i.e., magnetometer). However, ferromagnetic interference negatively affects the performance of magnetometer and thus reduces measurement accuracy. In this study, a technique based on nonlinear autoregressive neural network with exogenous inputs (NARX) is presented to measure 3D segmental orientation during gait without the use of magnetometer. With IMUs attached to the thigh and shank, 3D knee angles in long-distance treadmill walking were computed and validated against an optical motion analysis system as the gold standard. Pseudo-integrator (PI) was also compared to the reference system for benchmarking. The learning capability of NARX was further assessed with the comparison of complementary filter (CF) to the reference system. The proposed NARX model was shown to outperform PI with biases between -3.5 degrees and -0.2 degrees, and root mean square errors between 4.5 degrees and 2.5 degrees. Results demonstrated the capability of NARX in providing accurate estimates of 3D knee joint angle while avoiding interference as encountered in systems incorporating magnetometer, suggesting that NARX is feasible to computing long-term ambulatory measurements of body segment orientation and 3D joint angles

Domestic Help

Domestic Help is a short film produced by four final year students of the Wee Kim Wee School of Communication and Information, as their Final Year Project (FYP). It touches on the social issue of foreign domestic helpers and their plight in Singapore. The project took about nine months to complete, under the supervision of Associate Professor Adam Knee and Mr Kym Campbell. This FYP report aims to document the process of this 15-minute short film, from conceptualization to the post-production stages of producing the film. It will also document our personal reflections on this challenging journey in filmmaking and the lessons we took away from this project.Bachelor of Communication Studie

Influence of age on patellar tendon reflex response.

BackgroundA clinical parameter commonly used to assess the neurological status of an individual is the tendon reflex response. However, the clinical method of evaluation often leads to subjective conclusions that may differ between examiners. Moreover, attempts to quantify the reflex response, especially in older age groups, have produced inconsistent results. This study aims to examine the influence of age on the magnitude of the patellar tendon reflex response.Methodology/principal findingsThis study was conducted using the motion analysis technique with the reflex responses measured in terms of knee angles. Forty healthy subjects were selected and categorized into three different age groups. Patellar reflexes were elicited from both the left and right patellar tendons of each subject at three different tapping angles and using the Jendrassik maneuver. The findings suggested that age has a significant effect on the magnitude of the reflex response. An angle of 45° may be the ideal tapping angle at which the reflex can be elicited to detect age-related differences in reflex response. The reflex responses were also not influenced by gender and were observed to be fairly symmetrical.Conclusions/significanceNeurologically normal individuals will experience an age-dependent decline in patellar reflex response

Reflex amplitude of random groups in mean (± standard error) according to tapping angle.

<p>Reflex amplitude of random groups in mean (± standard error) according to tapping angle.</p

Representative knee angle of a patellar tendon reflex test.

<p>Time 0 is the time the reflex hammer struck the patellar tendon. Reflex amplitude is measured as the offset of knee angle from the original position.</p

Comparison of mean values of experimental and theoretical maximum tapping velocities (±SD).

a<p><i>P</i><0.001 when compared to the maximum velocity of other tapping angles.</p>b<p>Comparison between experimental and theoretical maximum velocities.</p

Representative relationship between the tapping angle and the experimental maximum tapping velocity.

<p>Representative relationship between the tapping angle and the experimental maximum tapping velocity.</p

Mean values of patellar tendon reflex amplitudes according to tapping angle (± standard error).

<p>The reflex amplitude increased gradually with the increment of tapping angle. ^* denotes statistical significance difference compared to tapping angle of 15°. ^# denotes statistical significance difference compared to tapping angle of 30°. ^$ denotes statistical significance difference compared to tapping angle of 45°. ^¤ denotes statistical significance difference compared to tapping angle of 60°. ^¢ denotes statistical significance difference compared to tapping angle of 75°. ^¥ denotes statistical significance difference compared to tapping angle of 90°. Symbols (^¤, ^¥) in bold indicates statistical significance difference at <i>P</i><0.01, symbols not in bold indicates statistical significance difference at <i>P</i><0.001.</p

Comparison of reflex response among the three age groups at different tapping angles.

<p>Comparison of reflex response among the three age groups at different tapping angles.</p