Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

An assessment of pharmacy students’ empathy levels in Malaysia

This study examined the validity and reliability of the student version of Jefferson Scale of Empathy-Health Profession (JSE-HPS) in a sample of pharmacy students and to subsequently use JSE-HPS to assess empathy levels in first to fourth (final) year pharmacy students in public and private universities in Malaysia. The JSE-HPS was administered to 719 first to fourth (final) year pharmacy students; 313 were enrolled at a public university and 406 at a private university in Malaysia. Both descriptive and inferential statistics were performed using SPSS® version 18. The JSE-HPS demonstrated good internal consistency (Cronbach’s � = 0.70). A three-factor solution emerged and included ‘perspective taking’, ‘compassionate care’ and ‘standing in patient’s shoes’ factors, accounting for 16.4%, 16%, and 7.6% of the variance, respectively. The total mean empathy score was 83.02±8.23, the actual score ranged between 46.05 and 113.25. Overall, males and students of Malay origin were more empathic than females and students of other ethnic origins. Junior students (year one and two) were more empathic than senior students (year three and four), and public university students had significantly higher mean empathy score compared to those enrolled at a private university (83.89 versus 82.34, p=0.012). This study confirms the construct validity and internal consistency of the JSE-HPS for measuring empathy in pharmacy students. Empathy scores among students vary depending on type of university and year of study

Reasons of using complementary and alternative medicines (CAM) among elderly Malaysians of Kuala Lumpur and Selangor states: an exploratory study

Background: This study is aimed to explore the types of CAM and reasons of using CAM among elderly Malaysians. Method: This cross-sectional study was conducted on a sample of 256 conveniently selected elderly Malaysians who were residing in the states of Selangor and Kuala Lumpur. A pre-validated interviewadministered questionnaire was used to gather information. Data was entered into PASW version 18 and analyzed. Results: A total of 256 questionnaires were included in the study. A response rate of 64% was achieved. Out of 256 respondents, 92 (35.9%) were male while 164 (64.1%) were female. More than half of the respondents (n ¼ 141; 55.1%) agreed that CAM is more effective than allopathic medicine. Chinese respondents showed strong belief in the effectiveness of CAM. In terms of safety of CAM, close to three quarters of respondents (n ¼ 178; 69.5%) believed that CAM is safer than allopathic medicine. A large majority of respondents agreed that CAM has less side effects compared to allopathic medicine (n ¼ 201; 78.5%) and also agreed that CAM is good to maintain overall health and wellbeing (n ¼ 212; 82.8%). A majority of the respondents expressed that they use CAM because allopathic medicine is less effective (n ¼ 113; 44.1%). Conclusion: The current study reflects the reasons of using CAM among lay public from different ethnicities. There are no reports of adverse effects related to CAM use. Future approaches should be intended for awareness campaigns for consumers, highlighting safety profile of CAM and as well as forbidding their use without the consultation of healthcare professional

Use and perceived benefits of mouthwash among Malaysian adults: An exploratory insight

Objectives: The purpose of the current research is to comprehend the use as well as the perception of mouthwash benefits among Malaysian adults in Selangor state, Malaysia. Materials and Methods: Questionnaires were distributed following convenience sampling to 400 respondents in public places around Selangor over a period of 3 months. The questions were divided into 4 main categories which were demographics, behavior, knowledge, and perceived benefits. The data collected were entered into PASW version 20 and analyzed. Descriptive and inferential statistics were applied. Chi-square was used to compute the association between the variables. Results: The majority of the respondents (n = 178, 44.5%) were between the ages of 18-25 years. Female respondents outnumbered males with 243 (60.8%) and 157 (39.3%), respectively. There was a high level of awareness among the respondents regarding the use of mouthwash where more than 57% answered the knowledge questions correctly. When asked for the reason for using a particular brand, respondents stated that their selection depends on it being "a family brand", affordability and taste. Respondents had a good perception on the use of mouthwash and its benefits. Conclusion: The public needs to be educated on the role of mouthwash. Knowledge gaps on mouthwash need to be bridged to ascertain the beneficial nature of mouthwash. A mixed method research is recommended to gather more information on oral hygiene practices among Malaysian general population, particularly focusing on the use of mouthwash

Use of oral cleaning devices and their perceived benefits among Malaysians in Kuala Lumpur and Johor Bahru: An exploratory structured approach

Background and Objectives: Various devices have been used to maintain oral hygiene. These include toothbrush and toothpaste, mouthwash, dental floss, miswak, and toothpick. This study attempts to investigate the use of various oral cleaning devices and their perceived benefits among Malaysians. Methods: A quantitative cross-sectional study conducted in two different cities of Malaysia. A convenience sampling approach was adopted. A total of 787 participants agreed to participate in the current research. A validated questionnaire translated into national language was used for data collection. Statistical Analysis Used: Data analysis was performed using Statistical Package for Social Sciences version 20. Results: About 302 respondents were in the age range of 18 – 25 years old (38.4%). There were marginally more females (55.7%) than males (44.3%). Although 99.9% of the participants used a toothbrush, a significant majority (n = 590, 75%) used more than a single device to maintain their oral hygiene. Only 311 respondents knew that toothpicks were inappropriate to use to remove food between teeth and gums, while a majority (n = 592, 75.2%) did not realize that some mouthwashes can stain the teeth. Less than half (42.1%) knew that improper use of miswak might harm the teeth. Conclusions: Although their oral hygiene behaviors are relatively at a higher level, their perceived oral health benefits did not compare well

Use and perceived benefits of mouthwash among Malaysian adults: an exploratory insight

This study aimed to explore the use and perceived benefits of mouthwash among Malaysian adults. Method: This is a cross-sectional study which was conducted in public places around the states of Selangor and Penang, Malaysia. It is a questionnaire-based study which was conducted as face-to-face interview. A convenience sample of 792 mouthwash users was recruited in 2013 in an ethically approved study (International Medical University). The study instrument was formulated on the basis of literature search and subjected to 20 experts for validation purpose. A pilot study was conducted to compute Cronbach Alpha (0.78). Data was entered into PASW version 20. Descriptive and inferential statistics were applied. Results: A response rate of 99% was achieved. More than two third of the respondents are female, suggesting women are more likely to use mouthwash (n ¼486; 61.8 %). The major reason to use mouthwash were to mask halitosis (n¼287; 36.5%) and to prevent oral diseases (n¼243; 30.9%). Majority knew that fluoride helps in reducing plaque (n¼599; 76.1%) and tooth decay (n¼631; 80.2%). Respondents were not clear that only tooth brushing alone is insufficient to prevent gum disease (n¼553; 70.3%). More than two thirds perceived that mouthwash is useful in reducing plaque (n¼567; 72.0%) as well as periodontal disease (n¼580; 73.7%). Respondents perceived that mouthwash is more effective in eliminating halitosis (n¼714; 90.7%) and preventing caries (n¼630; 80.1%). The frequency of mouthwash use was statistically significant with age, gender, race and monthly income (p¼0.018. 0.091, 0.010, 0.030) . Conclusion: This study indicates that Malaysian adults have good knowledge on the use and perceived benefits of mouthwash. A nationwide study is advocated to gather more information from general population, targeting the use of mouthwash in a large scale to minimize oral health problems

Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study

Background Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51–19.97) than planned admissions (OR: 2.32, 95% CI: 1.43–3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8–51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies

Safety of Nonsteroidal Anti-inflammatory Drugs in Major Gastrointestinal Surgery: A Prospective, Multicenter Cohort Study

Background Significant safety concerns remain surrounding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) following gastrointestinal surgery, leading to wide variation in their use. This study aimed to determine the safety profile of NSAIDs after major gastrointestinal surgery. Methods Consecutive patients undergoing elective or emergency abdominal surgery with a minimum one-night stay during a 3-month study period were eligible for inclusion. The administration of any NSAID within 3 days following surgery was the main independent variable. The primary outcome measure was the 30-day postoperative major complication rate, as defined by the Clavien–Dindo classification (Clavien–Dindo III–V). Propensity matching with multivariable logistic regression was used to produce odds ratios (OR) and 95 % confidence intervals. Results From 9264 patients, 23.9 % (n = 2212) received postoperative NSAIDs. The overall major complication rate was 11.5 % (n = 1067). Following propensity matching and adjustment, use of NSAIDs were not significantly associated with any increase in major complications (OR 0.90, 0.60–1.34, p = 0.560). Conclusions Early use of postoperative NSAIDs was not associated with an increase in major complications following gastrointestinal surgery

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien\u2013Dindo Grades III\u2013V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49\u20132.96, P &lt; 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46\u20130.75, P &lt; 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease