Left ventricular mass regression, all-cause and cardiovascular mortality in chronic kidney disease: a meta-analysis

Background Cardiovascular disease is an important driver of the increased mortality associated with chronic kidney disease (CKD). Higher left ventricular mass (LVM) predicts increased risk of adverse cardiovascular outcomes and total mortality, but previous reviews have shown no clear association between intervention-induced LVM change and all-cause or cardiovascular mortality in CKD. Methods The primary objective of this meta-analysis was to investigate whether treatment-induced reductions in LVM over periods ≥12 months were associated with all-cause mortality in patients with CKD. Cardiovascular mortality was investigated as a secondary outcome. Measures of association in the form of relative risks (RRs) with associated variability and precision (95% confidence intervals [CIs]) were extracted directly from each study, when reported, or were calculated based on the published data, if possible, and pooled RR estimates were determined. Results The meta-analysis included 42 trials with duration ≥12 months: 6 of erythropoietin stimulating agents treating to higher vs. lower hemoglobin targets, 10 of renin-angiotensin-aldosterone system inhibitors vs. placebo or another blood pressure lowering agent, 14 of modified hemodialysis regimens, and 12 of other types of interventions. All-cause mortality was reported in 121/2584 (4.86%) subjects in intervention groups and 168/2606 (6.45%) subjects in control groups. The pooled RR estimate of the 27 trials ≥12 months with ≥1 event in ≥1 group was 0.72 (95% CI 0.57 to 0.90, p = 0.005), with little heterogeneity across studies. Directionalities of the associations in intervention subgroups were the same. Sensitivity analyses of ≥6 months (34 trials), ≥9 months (29 trials), and >12 months (10 trials), and including studies with no events in either group, demonstrated similar risk reductions to the primary analysis. The point estimate for cardiovascular mortality was similar to all-cause mortality, but not statistically significant: RR 0.67, 95% CI 0.39 to 1.16. Conclusions These results suggest that LVM regression may be a useful surrogate marker for benefits of interventions intended to reduce mortality risk in patients with CKD.

Strategies for discontinuation of proton pump inhibitors (PPIs) in patients with long-term PPI administration: a randomized controlled trial

Background Proton pump inhibitors (PPIs), including potassium ion-competitive acid blocker, are widely used worldwide and are often used for long periods of time. However, in recent years, potential side effects associated with long-term PPI use have been reported. Many patients take PPI for a long period of time, even though it is unnecessary, and it is necessary to discontinue PPI administration in such patients. However, sudden discontinuation may cause symptoms to recur and discontinuation may be unsuccessful. A strategy for safe and secure PPI discontinuation has not yet been established. The purpose of this study is to determine whether PPI can be safely discontinued by tapering the PPI dose or by abrupt discontinuation of PPI, and to establish a strategy for safe and secure PPI discontinuation. Methods The evaluation will be conducted as a multicenter, randomized, parallel-group clinical trial with five assessment points at the start of the study and 2 weeks, 4 weeks, 6 months, and 12 months after the start of the study. One intervention group is the group in which PPI administration is abruptly discontinued (Group A), and the second group is the group in which the PPI dose is gradually tapered and then PPI administration is discontinued (Group B). The primary outcome and secondary outcome are the proportion of patients who successfully discontinued the PPI at 6 months and at 12 months after the start of the study in groups A and B, respectively. Discussion We predict that the proportion of patients who successfully discontinue PPI will be higher in the group in which PPI administration was gradually tapered than in the group in which PPI administration was abruptly discontinued. On the other hand, we expect that many participants will succeed in discontinuing PPI regardless of the discontinuation strategy due to the explanation that discontinuation is necessary. Trial registration Japan Registry of Clinical Trials, jRCT1031180383. Registered 20 March 2019, https://jrct.niph.go.jp/latest-detail/jRCT1031180383.

Severe Primary Open-Angle Glaucoma and Agricultural Profession: A Retrospective Cohort Study

While exposure to pesticides is a known risk factor for neurodegenerative brain diseases, little is known about the influence of environment on glaucoma neuropathy. We aimed to determine whether farmers are at higher risk of developing severe primary open-angle glaucoma (POAG). This retrospective cohort study (tertiary referral center, Reims University Hospital, France) included patients diagnosed with POAG in the last two years. Univariate analysis and adjusted multivariate logistic regression were performed to evaluate the association between agricultural profession and all recorded data. Glaucoma severity (primary outcome) and the number of patients who underwent filtering surgery (secondary outcome) were analyzed. In total, 2065 records were screened, and 772 patients were included (66 in the farmer group and 706 in the nonfarmer group). The risk of severe glaucoma was higher in the farmer group (adjusted odds ratio (aOR) 1.87, p = 0.03). More patients underwent filtering surgery in the farmer group in univariate analysis (p = 0.02) but with no statistical significance after adjustment (p = 0.08). These results suggest pesticide exposure may be a factor accelerating the neurodegeneration in POAG, although a direct link between the agricultural profession and the disease requires further extended studies to be demonstrated.

The Effects of Diabetes Self-Management Education on Quality of Life for Persons With Type 1 Diabetes: A Systematic Review of Randomized Controlled Trials

Purpose: It is well documented that chronic conditions, such as diabetes, impact quality of life (QoL). QoL assessment is essential when developing and evaluating diabetes self-management education support interventions. The aim of this systematic review was to evaluate the evidence and gaps in the research and the impact of diabetes self-management education (DSME) on QoL outcomes in persons with type 1 diabetes mellitus (T1DM). Methods A systematic review of English language studies published between January 1, 2007, and March 31, 2020, was conducted using a modified Cochrane review method. Studies were included if they were randomized controlled trials (RCTs), participants had T1DM with or without caregivers, a DSME intervention alone or a component(s) of the ADCES7™ Self-Care Behaviors was described, and QoL was a primary or secondary outcome. A 3-tiered review process was utilized for selecting articles. Retained articles were assessed for risk of bias. Results: Nineteen articles, reporting on 17 RCTs, met inclusion criteria, of which 7 studies reported QoL as the primary outcome and 10 as a secondary outcome. Seven studies detected significant impact of DMSE on QoL outcomes in either the participants or family caregivers, which varied in participant populations, selection of QoL tools (generic vs diabetes-specific), intervention type, intervention length, and type of interventionist. Conclusion: DSME has the potential to influence QoL outcomes in people with T1DM. Research using more standardized methods are needed to delineate impact on a broader range of factors that influence QoL for those living with T1DM across the life span and their caregivers.

Evaluation of the Clinical Impact of Thromboprophylaxis in Patients With COVID-19 Following Hospital Discharge

Background: Data are limited regarding the incidence of thromboembolism post-hospital discharge among COVID-19 patients. Guidelines addressing the role of extended thromboprophylaxis for COVID-19 patients are limited and conflicting. Objective: The purpose of this study was to evaluate the incidence of post-discharge thromboembolic and bleeding events and the role of thromboprophylaxis among COVID-19 patients. Methods: A retrospective analysis was conducted of hospitalized patients with symptomatic COVID-19 infection who were discharged from a University of Colorado Health (UCHealth) hospital between March 1, 2020, and October 31, 2020. The primary outcome was objectively confirmed thromboembolism within 35 days post-discharge. The main secondary outcome was the incidence of bleeding events within 35 days post-discharge. Outcomes were compared between those who received extended prophylaxis and those who did not. Results: A total of 1171 patients met the study criteria. A total of 13 (1.1%) of patients had a documented thromboembolic event and 10 (0.9%) patients had a documented bleeding event within 35 days post-discharge. None of the 132 patients who received extended prophylaxis had a thromboembolic event compared to 13 of 1039 who did not receive extended prophylaxis (0 and 1.3%, respectively; P = .383). The incidence of bleeding was higher among patients who received extended prophylaxis compared to those who did not (3.0% vs 0.6%, P = .019). Conclusions and Relevance: These results suggest that post-discharge extended prophylaxis may be beneficial for select COVID-19 patients, while carefully weighing the risk of bleeding. Application of our findings may assist institutions in development of thromboprophylaxis protocols for discharged COVID-19 patients.

The Role of Acupuncture in Hormonal Shock-Induced Cognitive-Related Symptoms in Perimenopausal Depression: A Randomized Clinical Controlled Trial

Introduction: Perimenopausal depression is predominantly caused by hormone shock, but the underlying physical and psychological factors are still unclear.Objectives: To explore the constituent components of perimenopausal depression by dynamically depicting its influencing factors and interactive pathways from the perspective of embodied cognition.Methods: This is a randomized clinical controlled trial. In this study, electroacupuncture was compared with escitalopram. A total of 242 participants with mild to moderate perimenopausal depression were enrolled from 6 hospitals in China. Each participant had a 12-week intervention and a 12-week follow-up period. The primary outcome of this study is the Hamilton Depression Rating Scale (HAMD-17), and the secondary outcome is the menopause-specific quality of life scale (MENQOL), serum Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estrogen (E2) levels.Results: The structural equation model suggested that hormone levels were not directly associated with HAMD-17 (P = 0.852), while MENQOL was statistically correlated with HAMD-17 as an intermediary variable (P < 0.001). Electroacupuncture gradually showed positive impacts on MENQOL and HAMD-17 during the follow-up period (P < 0.05). Cognitive impairment is the dominant dimension of perimenopausal depression.Conclusions: Hormonal shock may affect clinical symptoms and poor quality of life to induce cognitive impairment leading perimenopausal depression, and this impact on cognition is embodied. Electroacupuncture has positive effect on perimenopausal depression and quality of life.

Proactive Management of Intraoperative Hypotension Reduces Biomarkers of Organ Injury and Oxidative Stress during Elective Non-Cardiac Surgery: A Pilot Randomized Controlled Trial

Background: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. Methods: We randomly assigned patients undergoing major general surgery to early warning system (EWS) and hemodynamic algorithm (intervention group, n = 20) or standard care (n = 20). The primary outcome was the difference in hypotension (defined as mean arterial pressure < 65 mmHg) and as secondary outcome surrogate markers of organ injury and oxidative stress. Results: The median number of hypotensive episodes was lower in the intervention group (−5.0 (95% CI: −9.0, −0.5); p < 0.001), with lower time spent in hypotension (−12.8 min (95% CI: −38.0, −2.3 min); p = 0.048), correspondent to −4.8% of total surgery time (95% CI: −12.7, 0.01%; p = 0.048).The median time-weighted average of hypotension was 0.12 mmHg (0.35) in the intervention group and 0.37 mmHg (1.11) in the control group, with a median difference of −0.25 mmHg (95% CI: −0.85, −0.01; p = 0.025). Neutrophil Gelatinase-Associated Lipocalin (NGAL) correlated with time-weighted average of hypotension (R = 0.32; p = 0.038) and S100B with number of hypotensive episodes, absolute time of hypotension, relative time of hypotension and time-weighted average of hypotension (p < 0.001 for all). The intervention group showed lower Neuronal Specific Enolase (NSE) and higher reduced glutathione when compared to the control group. Conclusions: The use of an EWS coupled with a hemodynamic algorithm resulted in reduced intraoperative hypotension, reduced NSE and oxidative stress.

Epigenetic Signatures in Antidepressant Treatment Response: a Methylome-wide Association Study in the EMC Trial

Although the currently available antidepressants are well established in the treatment of major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N=40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients’ response before treatment.

Efficacy of repetitive transcranial magnetic stimulation (rTMS) for reducing consumption in patients with alcohol use disorders (ALCOSTIM): study protocol for a randomized controlled trial

Background The number of people with an alcohol use disorder (AUD) was recently estimated to be 63.5 million worldwide. The global burden of disease and injury attributable to alcohol is considerable: about 3 million deaths, namely one in 20, were caused by alcohol in 2015. At the same time, AUD remains seriously undertreated. In this context, alternative or adjunctive therapies such as brain stimulation could play an important role. The early results of studies using repetitive transcranial magnetic stimulation (rTMS) suggest that stimulations delivered to the dorsolateral prefrontal cortex significantly reduce cravings and improve decision-making processes in various addictive disorders. We therefore hypothesize that rTMS could lead to a decrease in alcohol consumption in patients with AUD. Methods/design We report the protocol of a randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy of rTMS on alcohol reduction in individuals diagnosed with AUD. The study will be conducted in 2 centers in France. Altogether, 144 subjects older than 18 years and diagnosed with AUD will be randomized to receive 5 consecutive twice-daily sessions of either active or sham rTMS (10 Hz over the right DLPFC, 2000 pulses per day). The main outcomes of the study will be changes in alcohol consumption within the 4 weeks after the rTMS sessions. Secondary outcome measures will include changes in alcohol consumption within the 24 weeks, alcohol cravings, clinical and biological improvements, effects on mood and quality of life, and cognitive and safety assessments, and, for smokers, an assessment of the effects of rTMS on tobacco consumption. Discussion Several studies have observed a beneficial effect of rTMS on substance use disorders by reducing craving, impulsivity, and risk-taking behavior and suggest that rTMS may be a promising treatment in addiction. However, to date, no studies have included sufficiently large samples and sufficient follow-up to confirm this hypothesis. The results from this large randomized controlled trial will give a better overview of the therapeutic potential of rTMS in AUD. Trial registration ClinicalTrials.gov NCT04773691. Registered on 26 February 2021 https://clinicaltrials.gov/ct2/show/NCT04773691?term=trojak&draw=2&rank=5.

Hypokalemia Measurement and Management in Patients With Status Asthmaticus on Continuous Albuterol

OBJECTIVE: Status asthmaticus is commonly treated in pediatric patients by using continuous albuterol, which can cause hypokalemia. The primary aim of this study was to determine if serial potassium monitoring is necessary by examining treatment frequency of hypokalemia. METHODS: This retrospective analysis was performed in 185 pediatric patients admitted with status asthmaticus requiring continuous albuterol between 2017 and 2019. All patients were placed on intravenous fluids containing potassium. The primary outcome measure was the treatment of hypokalemia in relation to the number of laboratory draws for potassium levels. The secondary outcome measure was hypokalemia frequency and relation to the duration and initial dose of continuous albuterol. RESULTS: Included were 156 patients with 420 laboratory draws (average, 2.7 per patient) for potassium levels. The median lowest potassium level was 3.40 mmol/L (interquartile range, 3.2–3.7). No correlation was found between initial albuterol dose and lowest potassium level (P = .52). Patients with hypokalemia had a mean albuterol time of 12.32 (SD, 15.76) hours, whereas patients without hypokalemia had a mean albuterol time of 11.50 (SD, 12.53) hours (P = .29). Potassium levels were treated 13 separate times. CONCLUSIONS: The number of laboratory draws for potassium levels was high in our cohort, with few patients receiving treatment for hypokalemia beyond the potassium routinely added to maintenance fluids. Length of time on albuterol and dose of albuterol were not shown to increase the risk of hypokalemia. Serial laboratory measurements may be decreased to potentially reduce health care costs, pain, and anxiety surrounding needlesticks.