Electrolyte Disorder

The global elderly population is rapidly increasing, with the 65-and-over age group being the fastest growing. Currently, about 9% of the world's population is over 65, and this proportion is projected to reach 16% by 2050. The silvering of China's population continues its steady march. By the end of 2023, the population aged 60 and above is 296.97 million, accounting for 21.1% of the national population, of which 216.76 million are aged 65 and above, accounting for 15.4% of the national population. As China's population continues to age, the silver tsunami shows no signs of abating. By 2030, it is estimated that the number of elderly individuals aged 65 and above will have surged to approximately 240 million. And by 2050, the ranks of octogenarians and above are projected to reach a staggering 100 million. The overall health status of China's elderly population is a cause for concern. More than 80% of individuals aged 65 and above suffer from at least one chronic disease, and by the age of 75, this number increases to at least three. Approximately 44 million elderly citizens are either partially or fully disabled, casting a long shadow over their own lives, placing a significant burden on their families, and society. The health of China's elderly has become a pressing public health issue that demands the attention of the entire nation. Frailty is a geriatric syndrome characterized by an increased vulnerability to stressors. It is a state of diminished physiological reserve and impaired function across multiple organ systems, leading to increased dependency and mortality. Epidemiological data suggest that the prevalence of frailty in the elderly population ranges from approximately 4.9% to 27.3%. Among community-dwelling elderly individuals, the prevalence is estimated to be between 6.9% and 14.9%. The incidence of frailty increases with advancing age, with over 25% of individuals aged 85 and older experiencing this debilitating condition. Research has painted a sobering picture of the consequences of persistent frailty in the elderly population. It has been shown to increase the risk of a cascade of negative events, including falls, disability, delirium, hospitalization, and even premature mortality. The risk of morbidity and mortality escalates significantly, with a 68% increase in all-cause mortality for every 0.1-unit increase in the frailty index (HR=1.68, 95% CI: 1.66-1.71). Frailty also places a heavy burden on caregivers and healthcare systems, straining resources and exacerbating the challenges of caring for an aging population. Furthermore, frail elderly individuals are particularly vulnerable to precipitous declines in health, even from minor stressors such as infections, new medications, falls, constipation, or urinary retention. These events can trigger a downward spiral, leading to hospitalization, disability, and even death, severely compromising the quality of life for elderly individuals and placing a greater demand on healthcare services. In the global tapestry of frailty research, interventions have largely focused on isolated threads, such as exercise regimens, nutritional counseling, risk factor modification, and comprehensive care. However, the intricate web of frailty demands a more holistic approach, one that weaves together these diverse strands. There is a notable lack of research investigating comprehensive intervention measures. It is of utmost importance to conduct community-based research to explore a comprehensive nutritional intervention model for frailty that is tailored to the unique characteristics of the Chinese population, scientifically sound, and sustainable.

This study group has developed a new method for diagnosing methanol poisoning using a single drop of blood with a point-of-care (POC) device, eliminating the need for laboratory equipment. The device measures formate, present only in cases of methanol poisoning. The research comprises two studies. The initial observational study (Study 1a) will assess the sensitivity and specificity of the POC formate assay compared to the laboratory formate assay (the gold standard). If the sensitivity is greater than 0.80, a feasibility three-arm cluster randomized controlled trial (RCT) (Study 1b) will follow to determine the feasibility of recruiting hospitals to a cluster RCT of formate diagnostic approaches. This design will be used in the second study to test the clinical- and cost-effectiveness of incorporating the formate POC assay into routine clinical use. Primary Objectives: Study 1a: Determine the sensitivity and specificity of the POC formate assay compared to the laboratory formate assay. Study 1b: Assess the feasibility of recruiting hospitals for a cluster RCT of formate diagnostic approaches. Secondary Objectives: Study 1a: Evaluate the use of the POC formate assay to identify methanol poisoning across diverse healthcare systems. Study 1b: Compare clinical and resource use when introducing the POC formate assay into routine clinical practice. Primary Endpoints: Study 1a: Sensitivity and specificity of the POC formate test for diagnosing methanol poisoning. Study 1b: Number of hospitals successfully recruited to the study. Secondary Endpoints for Study 1a: Time from patient arrival at the emergency department to sample collection. Time from sample collection to result display by the POC assay and the laboratory assay. Delay between result displays by the POC and the laboratory assay. Time from sample collection until the clinician is informed of the results. Time to initiation of antidote treatment and stopping unnecessary therapy in patients without methanol poisoning. Secondary Endpoints for Study 1b: Time to stopping unnecessary therapy in patients without methanol poisoning. Proportion of patients with management changes based on the laboratory formate assay. Clinical outcomes such as deaths, intubations, and dialysis needs. Cost comparison between the POC formate assay, the laboratory assay, and no assay. The study will include patients suspected of methanol poisoning or unexplained metabolic acidosis at large referral hospitals in Bangladesh and India. The study aims to determine whether the POC formate test can speed up the initiation of appropriate treatment, reduce unnecessary treatment costs, and improve clinical outcomes. Study Population: Patients presenting with suspected methanol poisoning or unexplained metabolic acidosis. Number of Participants: Study 1a: 1,620 participants. Study 1b: 4,500 participants. Inclusion Criteria: Patients with suspected methanol poisoning or metabolic acidosis of unknown cause, including children aged 16-17 (with assent), adults (with consent), and those with relatives who can provide consent. Exclusion Criteria: Individuals unwilling to provide assent or consent. Unaccompanied unconscious patients or those without a relative to provide consent. Previously recruited individuals. These studies aim to raise awareness of the methanol poisoning crisis, improve early detection and treatment, and establish high-quality protocols for patient care. They also aim to encourage junior doctors to pursue academic careers and practice good clinical habits. Raising awareness will help warn the public about dangerous alcohol and prevent further poisonings.

This is a Phase III, multicentre, randomised, double-blind, placebo-controlled, parallel-group study to evaluate the safety, tolerability, and efficacy of baxdrostat versus placebo, on the reduction of Seated Blood Pressure (SBP) and achieving normalization of the Renin Angiotensin Aldosterone System (RAAS) in approximately 180 participants ≥ 18 years of age with Primary Aldosteronism (PA), with or without prior treatment with Mineralocorticoid Receptor Antagonists (MRAs) or potassium-sparing diuretics. Baxdrostat (or placebo) will be administered once daily, up-titrated after 2 weeks based on clinical response and tolerability. The study is planned to be conducted globally in approximately 90 study centres and 12 countries.

The purpose of this 26 week study is is to evaluate the efficacy and safety of veverimer in treating adults with moderate-to-severe chronic kidney disease (CKD) and metabolic acidosis.

Eligible participants with hyperkalemia will first be randomized in a 5:1 ratio to receive oral WS016 (12g) or placebo three times daily, for a total of six doses over 48 hours. After the 48-hour corrective treatment, participants whose serum potassium is within the normal range will be re-randomized in a 1:1:1:1 ratio to receive oral WS016 (6g, 12g, or 18g) or placebo once daily for 28 consecutive days. Participants who complete the 28-day maintenance phase or prematurely discontinue from it due to hyperkalemia or hypokalemia, and who meet the eligibility criteria, will be eligible to enter Part B. In Part B, participants will receive WS016 for 11 months, starting at 12g once daily, with subsequent dose adjustments based on serum potassium levels.

Acutelines is a prospective biobank including patients with a broad spectrum of acute conditions. Its aim is to facilitate interdisciplinary research on the etiology and development of acute diseases with the aid of systematically collected biomaterials and medical data over various timepoints, both during the course of the patient's disease and after recovery. Clinical data, imaging data and biomaterial (i.e. blood, urine, feces, hair) are collected for patients presenting to the Emergency Department (ED) with a broad range of acute disease presentations. A deferred consent procedure (by proxy), is in place to allow collecting data and biomaterials prior to obtaining written consent. The digital infrastructure in place and the software used ensures automated capturing of all bed-side monitoring data (i.e. electrophysiological waveforms, vital parameters), and the secure importation of data from other sources, such as the electronic health records of the hospital, ambulance and general practitioner, municipal registration, health insurance companies and pharmacy. Follow up data are collected for all included patients during the first 72-hours of their hospitalization and 3-months, 1-year, 2-years and 5 years after their ED visit. Data and materials to be collected includes: * Demographic and health data (i.e. \[experiences\] health, quality of life, functional status) * Medical history (i.e. co-morbidity, intoxications, medication use) * Admission reason to emergency department * Physical examination and vital parameters * Clinical diagnostic data (i.e. \[point-of-care\] ultrasound, X-ray, CT-scan, laboratory results) * Electrophysiological waveforms (i.e. electrocardiogram \[ECG\], plethysmography) * Biomaterials * Treatment (i.e. medication use, non-pharmacological treatment, treatment decisions, length-of-stay in hospital, admission to intensive care unit \[ICU\])

Post-operative pain from breast surgery can be controlled by regular pain medications such as paracetamol, non-steroidal anti-inflammatory (NSAIDs), and narcotics. Nerve blocks are commonly used as multimodal approaches for acute post-operative pain relief. Pectoral and stellate ganglion blocks are regional anesthesia techniques that target the thoracic nerves and sympathetic nerve ganglia to provide analgesia for the upper extremity and chest regions. When combined, these blocks have shown promising results in alleviating perioperative pain for patients undergoing modified radical mastectomy. Magnesium sulfate, a well-known adjuvant, has been studied extensively for its analgesic properties and anti-inflammatory effects.

Ure-Na 15 gram tablets would be used to add to the dialysis fluid How much urea to add would be a simple calculation based on the 45X dialysis system and the patients serum urea concentration. The dialysate fluid urea concentration would be made to be about 15-40 mg/dL lower than the serum concentration. The patients labs/vitals and symptoms would be closely monitored throughout the dialysis treatment.

Protocol Subjects will first come into the lab for a screening visit (approximately 1 hour). In this visit, they will learn more about the study, provide written informed consent (if they choose to participate), fill out a medical history form, have their weight, height, and body composition measured, and have a finger stick blood test to measure glycosylated hemoglobin (HbA1c). Those with A1c values \>7% at screening will not be included in the study. We will provide them with information about HbA1c levels that meet the diagnostic criterion for diabetes immediately. Those with A1c values from 6.5 to ≤7% will be provided with information about HbA1c levels that meet the diagnostic criterion for diabetes at the end of the trial. We will suggest they share this information with their doctor. We will answer any questions they may have. Two groups of 72 volunteers each will be grouped as having normal weight or obesity based on their BMI. The subjects who enroll in the study will undergo an 8-week cross-ver study with two separate arms based on BMI category. Subjects in each BMI category will be evaluated weekly as described below and depicted in Figure 1: Week 1: Baseline. During this week, the subjects will maintain their habitual fluid intake without any intervention. Weeks 2-4 \& Weeks 6-8: All subjects will follow 3 weeks of consuming only plain water and a 3-week of non-sugar sweetened beverages, in a random order. Weeks 2 and 6: The subject will consume very-low fluid intake, of 1.2 and 1.5 L/day for females and males, respectively. Week 3 \& week 7: Subjects will consume low fluid intake, of 1.6 and 2.0 L/day for females and males, respectively. Week 4 \& week 8: Subjects will consume adequate fluid intake according to the US dietary guidelines (2.2 and 3.0 L/day L/day for females and males, respectively). Week 5: Wash-out period, where subjects can return to their habitual fluid and dietary intake. Fluid intake: Fluid intake will be controlled by providing drinks and programmable smart water bottles to record fluid intake and provide periodic reminders. Plain Water: During the 3 weeks, subjects will be instructed to consume fluids only in the form of plain water (tap, bottle, sparkling), coffee up to 1 cup a day, and alcohol, up to 2 servings per week only during week 5 but not anywhere else during the study. Non-Sugar-Sweetened beverages: During the 3-week period, of the NSSB portion of the study 1.0 L of fluids per day will be coming from non-sugar-sweetened beverages, with the rest coming from water. Procedures: During this study, beverages will be provided for participants. Programmable smart water bottles will be used to record fluid intake and provide periodic reminders. Participants will be instructed to keep their diet as usual, without making any changes during the study. The ASA24 will be administered at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. The volunteers will be asked to fill out 24-hour recalls (ASA24) three times each one of the weeks 1, 2 and 3. We will collect 2 weekdays and 1 weekend day. ASA24 is an online nutritional assessment tool developed by the NCI. 1 Week before data collection begins: Subjects will visit the lab to place the CGM for baseline data collection, distribute frozen meals, watches, urine containers, and water bottles. Day Before each Testing: During the 24 hours prior to each testing day, subjects will be provided with verbal and written instructions on the 24-h urine collection protocol and two 3L urine collection containers, which will include the preservative. They will be asked to collect all their urine beginning with the second void of the day. The first morning urine sample will not be collected; the second void on the day before testing will begin the 24-hour collection. The last urine sample to be collected will be the first morning urine sample of the testing day in a separate container. To measure compliance with the 24-h urine collection protocol, subjects will be asked to complete a 24-h urine collection log. They will record the time when they collect the urine samples, and if they missed any voids. Urine will be analyzed for hydration measures, urine creatinine, and non-nutritive sweeteners. Also participants will have to consume the same dinner before each one of the 8 lab visits, that will be provided in the form of frozen meal from the research team. TESTING DAYS Each subject will visit the lab once a week for 8 consecutive weeks after at least 10 h of fasting. Upon arrival in the lab, subjects will provide a urine sample measured for hydration biomarkers and their body weight and body composition will be assessed on a bioelectrical impedance scale. We will acess seated blood pressure. Next, participants will fill out cognitive and perceptual questionaires. After this we will access resting metabolic rate, endothelial function by flow mediated dilation (FMD). After the completion of the FMD test, we will proceed to the oral glucose tolerance test (OGTT). Glycemic Test: Three separate glycemic tests will be performed depending on the stage of the protocol: 1. Insulin Resistance on Matthews's homeostatic model assessment of insulin resistance (HOMA-IR) is based on fasting glucose and insulin. 2. Oral Glucose Tolerance Test (OGTT). This 120-minute test consists of a fasted blood sample followed by 75 grams of glucose solution ingestion. Four more blood samples will be collected 30, 60, 90, and 120 minutes after the ingestion. 3. Ambulatory 24-hour glucose responses will be assessed via continuous glucose monitor (CGM) during the 7-week intervention. Each CGM lasts for 14 days, thus 4 monitors will be used for each volunteer. The Abbott libre pro will be used to asses interstitial blood glucose every 15 min. Blood Analysis: Fasting blood samples will analyzed for : * Glucose and insulin to assess insulin resistance based on Matthews's homeostatic model assessment of insulin resistance (HOMA-IR). * Osmolality, sodium, and copeptin for hydration assessment. * Glucagon and cortisol, since both are stimulated by vasopressin, and impacting glucose regulation. Blood Samples during the Oral Glucose Tolerance Test (OGTT) will be analyzed: \- Glucose, insulin, glucagon, and cortisol. The primary outcome of the OGTT will be the area under the curve for glucose, insulin, glucagon, and cortisol during the 120-minute test. Cognitive Data: A neuropsychological test measuring such aspects of cognition as attention, executive function and memory will be administered to each subject. We will ask participants to complete a cognitive task designed to examine mostly their Executive function (inhibition) abilities, named the Flanker's test. The task will be administered on a laptop computer, lasts 5 minutes and will be given at each visit. Perceptual Data: Perceptual data on hunger, cravings, thirst, and mouth dryness will be collected in a pen and paper format. Mood Assessment: Mood will be assessed by the validated thirty-five-question Adult Short Profile of Mood States (POMS) questionnaire (POMS 2®-A Short, Multi-Health Systems Inc.). It will be administed on a laptop computer and it lasts 5 min Sleep Quality Assessment: This will be assessed via the Pittsburgh Sleep Quality Index. This is a short questionnaire that takes about 2-3 minutes to fill out. The sleep quality assessment will be completed on paper. Resting Blood pressure: After the cognitive/ perceptual test, a resting blood pressure in seated position will be taken with and automated blood pressure cuff in duplicate. Resting Metabolic Rate: Resting metabolic rate via indirect calorimetry for 30 minutes. This will take place while subjects are resting prior to the flow mediated dilation test. Flow Mediated Dilation Test: Endothelium-dependent, FMD of the brachial artery is assessed at baseline (pre-condition) and at the end of each visit (post-condition), at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. Measurement procedures are done in accordance with established guidelines and performed by a registered sonographer using B-mode ultrasound (Philips Epic Elite™,Bothell WA). FMD analyses are conducted in a dim, quiet, temperature-controlled environment (22-25 oC) with the participants lying down on an ultrasound bed. Participants will be sized for appropriate blood pressure cuff (Hokanson Instruments, Bellevue, WA) and cuff will be placed around the right arm, 2-3 cm below the elbow/forearm area. Simultaneous ultrasound images (B-mode) and doppler waveforms of the brachial artery are captured for baseline before the blood pressure cuff is inflated to a suprasystolic pressure of 250 mmHg for 5 minutes. After 5 minutes, the cuff will be rapidly deflated, and arterial images will be obtained for 6 minutes post-inflation. Subjects may experience mild discomfort as the cuff is inflated on the upper arm. The images are obtained and analyzed by a trained, blinded researcher using an automated, previously validated FMD software. Oral Glucose Tolerance Test (OGTT): Before this test, an indwelling catheter will be placed in an antecubital vein by a trained and experienced phlebotomist using sterile techniques. After a couple of minutes of rest, a baseline blood sample will be taken and the subject will ingest a drink containing 75 g glucose. Four more blocatheterd samples will be taken at 30, 60, 90, and 120 minutes after the drink ingestion. Blood samples will be analyzed for glucose, insulin, glucagon, cortisol, and copeptin. Extra plasma and serum aliquots will be stoford in the deep freezer to -nalysis of other health related biomarkers. The first blood sample will be 15 mL and the remaining four samples will be 10 mL. The total volume for each test will be 55 mL.The total blood volume for all samples during the eight testing sessions will be 440 mL, which is equivalent to a blood donation. Continuous Glucose Monitor (CGM): Ambulatory glucose measurements will be obtained using CGM sensors during the entire 8-week period. Since the sensors work for 14 days, a new sensor will be used every two weeks and placed on an alternate arm. The Abbot FreeStyle Libre Pro sensor will be used and it will be applied at the back of the upper arm. A protective round band-aid will also be used to ensure the sensor will not fall off. Physical Activity: Physical activity will be assessed via the validated International Physical Activity Questionnaire (IPAQ). This questionnaire will take approximately 2 minutes to complete. Participants will take the questionnaire on paper. The questionnaire will be administered at the end of weeks 1, 2, 3, 4, 5, 6, 7, and 8. IPAQ data will be expressed as a continuous variable of MET-min per week and a three-level categorical variable of physical activity level. Also, participants will wear a Garmin smart watch that provides heart rate, sleep quality, and time spent on different levels of physical activity. Participants will wear this watch for the entire duration of the intervention. Researchers will provide the watch, and participants will be required to return the watch upon completion of the study.

The AK+ Guard™ application is an investigational Software as a Medical Device (SaMD) developed by AccurKardia, Inc. (New York, USA). It is designed to aid in the diagnosis of moderate to severe hyperkalemia (serum potassium ≥ 6.5 mmol/L) in adults using artificial intelligence analysis of Lead I electrocardiogram (ECG) data. The software is intended as a clinical decision support tool for adults at risk of hyperkalemia, including but not limited to those with end-stage renal disease (ESRD), chronic kidney disease (CKD) on renin-angiotensin-aldosterone system inhibitors, heart failure, adrenal disorders, and patients taking aldosterone synthase inhibitors. The AK+ Guard™ application analyzes only Lead I ECG signals, which may be obtained from standard 12-lead ECGs, clinical-grade ECG devices with Lead I capability, or consumer wearable devices (e.g., Apple Watch). This pilot study is designed to generate preliminary real-world evidence on both the diagnostic performance of the application and its usability in daily life. The study includes two arms: Arm 2A - Outpatient Diagnostic Accuracy: * Estimate sensitivity, specificity, PPV, and NPV of AK+ Guard™ in ambulatory CKD stages III-IV * Evaluate interoperability across selected Lead I ECG capture devices (Apple Watch, HeartBeam, and 12 lead reference) * Characterize system reliability metrics (upload success, algorithm runtime) in the outpatient setting Arm 2B - Remote Patient Monitoring * Quantify participant compliance, data completeness, and attrition during four week remote monitoring * Evaluate user experience using System Usability Scale (SUS) score, Net Promoter Score (NPS), and semi structured feedback * Capture technical performance metrics in a real world, unsupervised context