Laboratory Values Research Articles

The use of N-acetylcysteine to prevent further progression of preeclampsia

HIGHLIGHTS 1. The generation of free radicals in the placenta leads to endothelial dysfunction, which contributes greatly in preeclampsia.2. N-acetylcysteine have a role in the oxidative stress pathway, helping in glutathione synthesis and as a free radical scavenger.3. N-Acetylcysteine supplementation in women with preexisting preeclampsia had positive effects on oxidative stress biomarkers, laboratory values, and blood pressure. ABSTRACT Objectives: Preeclampsia is a prevalent disorder among pregnant women, characterized by hypertension and proteinuria, leading to serious complications. However, the precise pathophysiology of preeclampsia remains debated. Oxidative stress is believed to play a significant role in its development, and N-acetylcysteine (NAC) is known to influence this pathway. NAC aids in glutathione synthesis, a critical antioxidant, and acts as a free radical scavenger. This study aimed to examine the role of NAC in women with preeclampsia, focusing on its potential therapeutic benefits. Materials and Methods: A comprehensive literature search was conducted using PubMed and ScienceDirect databases, yielding 17 articles from PubMed and 395 articles from ScienceDirect. Reviews were excluded, resulting in 12 articles from PubMed and 89 articles from ScienceDirect. After further screening, 5 articles were selected for review, including 2 human studies and 3 animal studies, to understand the impact of NAC on preeclampsia. Results: Human studies indicated that NAC supplementation reduced the rate of preeclampsia among women at increased risk. Animal studies supported these findings, showing improvements in oxidative stress biomarkers, laboratory values, and blood pressure in models treated with NAC. NAC supplementation was associated with positive outcomes in managing oxidative stress, a key factor in the pathogenesis of preeclampsia. Conclusion: NAC supplementation in women with preexisting preeclampsia has beneficial effects on oxidative stress biomarkers, laboratory values, and blood pressure. These highlight the potential of NAC as a therapeutic intervention for preeclampsia, particularly in women at high risk. However, no significant differences were observed in maternal complication rate between the NAC-treated group and the control group. Further research is needed to fully understand the clinical implications of NAC supplementation and its long-term safety and efficacy in managing preeclampsia.

Manifestation and Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease in a Predominately African American Population at a Multi-Specialty Healthcare Organization.

African Americans (AA) have a high incidence of risk factors associated with MASLD (metabolic dysfunction-associated steatotic liver disease); the AA population has a lower incidence of MASLD and MASH (metabolic-associated steatotic hepatitis) than Caucasian and Hispanic Americans (non-AA). We investigated if underlying risk factor variation between AA and non-AA individuals could provide a rationale for the racial diversity seen in MASLD/MASH. Using ICD-10 codes, patients from 2017 to 2020 with MASLD/MASH were identified and confirmed to have either MASLD or MASH. Despite the large (>80%) AA population in our clinics, only 54% of the MASLD/MASH patients were African American. When the non-invasive NAFLD Fibrosis Scores (NFS) evaluated at early diagnosis were compared to the most recent values, the only increase in fibrosis score by NFS over time was in non-AA MASH patients. The increase in fibrosis only in non-AA MASLD patients is consistent with racial disparity in the disease progression in non-AA as compared to AA patients. Even with the large proportion of AA patients in our study, there was no significant racial disparity in the earliest assessment of either risk factors, laboratory values, or fibrosis scores that would account for racial disparity in the development and progression of MASLD.

Sex-stratified analyses of comorbidities associated with an inpatient delirium diagnosis using real world data.

Delirium is a detrimental mental condition often seen in older, hospitalized patients and is currently hard to predict. In this study, we leverage electronic health records (EHR) to identify 7,492 UCSF patients and 19,417 UC health system patients with an inpatient delirium diagnosis and the same number of control patients without delirium. We found significant associations between comorbidities or laboratory values and an inpatient delirium diagnosis, including metabolic abnormalities and psychiatric diagnoses. Some associations were sex-specific, including dementia subtypes and infections. We further explored the associations with anemia and bipolar disorder by conducting longitudinal analyses from the time of first diagnosis to development of delirium, demonstrating a significant relationship across time. Finally, we show that an inpatient delirium diagnosis leads to increased risk of mortality. These results demonstrate the powerful application of the EHR to shed insights into prior diagnoses and laboratory values that could help predict development of inpatient delirium and the importance of sex when making these assessments.

Uncovering Harmonization Potential in Health Care Data Through Iterative Refinement of Fast Healthcare Interoperability Resources Profiles Based on Retrospective Discrepancy Analysis: Case Study.

Cross-institutional interoperability between health care providers remains a recurring challenge worldwide. The German Medical Informatics Initiative, a collaboration of 37 university hospitals in Germany, aims to enable interoperability between partner sites by defining Fast Healthcare Interoperability Resources (FHIR) profiles for the cross-institutional exchange of health care data, the Core Data Set (CDS). The current CDS and its extension modules define elements representing patients' health care records. All university hospitals in Germany have made significant progress in providing routine data in a standardized format based on the CDS. In addition, the central research platform for health, the German Portal for Medical Research Data feasibility tool, allows medical researchers to query the available CDS data items across many participating hospitals. In this study, we aimed to evaluate a novel approach of combining the current top-down generated FHIR profiles with the bottom-up generated knowledge gained by the analysis of respective instance data. This allowed us to derive options for iteratively refining FHIR profiles using the information obtained from a discrepancy analysis. We developed an FHIR validation pipeline and opted to derive more restrictive profiles from the original CDS profiles. This decision was driven by the need to align more closely with the specific assumptions and requirements of the central feasibility platform's search ontology. While the original CDS profiles offer a generic framework adaptable for a broad spectrum of medical informatics use cases, they lack the specificity to model the nuanced criteria essential for medical researchers. A key example of this is the necessity to represent specific laboratory codings and values interdependencies accurately. The validation results allow us to identify discrepancies between the instance data at the clinical sites and the profiles specified by the feasibility platform and addressed in the future. A total of 20 university hospitals participated in this study. Historical factors, lack of harmonization, a wide range of source systems, and case sensitivity of coding are some of the causes for the discrepancies identified. While in our case study, Conditions, Procedures, and Medications have a high degree of uniformity in the coding of instance data due to legislative requirements for billing in Germany, we found that laboratory values pose a significant data harmonization challenge due to their interdependency between coding and value. While the CDS achieves interoperability, different challenges for federated data access arise, requiring more specificity in the profiles to make assumptions on the instance data. We further argue that further harmonization of the instance data can significantly lower required retrospective harmonization efforts. We recognize that discrepancies cannot be resolved solely at the clinical site; therefore, our findings have a wide range of implications and will require action on multiple levels and by various stakeholders.

Leveraging real-world data to predict cancer cachexia stage, quality of life, and survival in a racially and ethnically diverse multi-institutional cohort of treatment-naïve patients with pancreatic ductal adenocarcinoma.

Cancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management. The main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS). A population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations. CC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS. Using clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

Application and comparison of point-of-care devices for field evaluation of underlying health status of Guatemalan sugarcane workers.

With chronic disease prevalence on the rise globally, surveillance and monitoring are critical to improving health outcomes. Point-of-care (POC) testing can facilitate epidemiological research and enhance surveillance systems in limited resource settings, but previous research has identified bias between POC devices and laboratory testing. We compared the performance of two POC blood analyzers, the iSTAT handheld (Abbott, Princeton, NJ, USA) and the StatSensor Creatinine (Nova Biomedical, Waltham, MA, USA) to concurrent blood samples analyzed at a local laboratory that were collected from 89 agricultural workers in Guatemala. We measured creatinine and other measures of underlying health status with the POC and the lab blood samples. Pearson correlation coefficients, Bland-Altman plots, no intercept linear regression models and two-sample t-tests were used to evaluate the agreement between the POC and lab values collected across three study days and to assess differences by study day in a field setting. On average there was no observed difference between the iSTAT and lab creatinine measurements (p = 0.91), regardless of study day. Using lab creatinine as the gold standard, iSTAT creatinine results were more accurate compared to the Statsensor, which showed some bias, especially at higher values. The iSTAT had good agreement with the lab for sodium and blood urea nitrogen (BUN), but showed differences for potassium, anion gap, bicarbonate (TCO2), glucose, and hematocrit. In this tropical field setting, the research team devised a protocol to prevent the devices from overheating. In limited resource settings, POC devices carry advantages compared to traditional lab analyses, providing timely results to patients, researchers, and healthcare systems to better evaluate chronic health conditions. Technical challenges due to use of POC devices in high heat and humidity environments can be addressed using a standard protocol for transporting and operating the devices.

Exploring The Prevalence And Underlying Causes Of Anemia In Hemodialysis Patients. A Cross-Sectional Study

Background: Anemia is a common complication among patients with chronic kidney disease (CKD), especially those who are on hemodialysis. It also has a marked effect on their Quality of Life and with it, the morbidity-morbility. This research aimed to evaluate the frequency and incidence of anemia in hemodialysis patients at MMC. Objectives: to find out the incidence and etiological factors responsible for anemia in hemodialysis patients at MMC. Study design: a cross-sectional study Duration and place of study. From June 2023 to Aug 2023 department of nephrology mmc mardan Methods This study was designed as a cross-sectional analysis on 200 hemodialysis patients of MMC. Demographics, clinical parameters and laboratory values were collected. Anemia was characterized by an hemoglobin <13 g/dL in men and <12 g/dL for women. Statistical Analysis: Descriptive statistics, including mean and standard deviation assisted by the p-value for determining significance. Results Out of 200 Patients had a mean age of 58.4 years (SD =12.6). 85% of patients had anemia, with a mean hemoglobin 10.2 g/dL (SD 1.4) in anaemic patient's. The main causes of anemia were iron deficiency (60%), inflammatory states (40%) and erythropoietin resistance(alone or in combinations) for 25%, respectively. Anemia prevalence was significantly associated with all the comorbidities and with increased duration of hemodialysis. Conclusion Anemia is highly prevalent among hemodialysis patients at MMC, most often attributed to iron deficiency and inflammation. Treatments are effective as long the condition can be caught early and so, regular monitoring is vital for a more positive prognosis. Additional investigation is necessary to improve anemia care in this population. Keywords: Anemia, Hemodialysis, Prevalence, Causes

Long-term outcomes of patients with IgA nephropathy in the German CKD cohort.

The importance of albuminuria as opposed to proteinuria in predicting kidney outcomes in primary immunoglobulin A nephropathy (IgAN) is not well established. From 2010 to 2012, 421 patients with biopsy-proven IgAN have been enrolled into the German Chronic Kidney Disease (GCKD) cohort, a prospective observational cohort study (N=5217). Adjudicated endpoints include a composite kidney endpoint (CKE) consisting of eGFR decline >40%, eGFR <15ml/min/1.73m2 and initiation of kidney replacement therapy; the individual components of the CKE; and combined major adverse cardiac events (MACE), including non-fatal myocardial infarction, non-fatal stroke and all-cause mortality. The associations between the incidence of CKE and baseline factors, including demographics, laboratory values and comorbidities were analysed using the Cox proportional hazards regression model. The mean age of IgAN patients at baseline was 51.6years (±13.6) and 67% were male. The patient-reported duration of disease at baseline was 5.9±8.1years. Baseline median urine albumin:creatinine ratio (UACR) was 0.4g/g [interquartile range (IQR) 0.1-0.8] and mean eGFR was 52.5±22.4ml/min/1.73m2. Over a follow-up of 6.5years, 64 (15.2%) patients experienced a >40% eGFR decline, 3 (0.7%) reached eGFR <15ml/min/1.73m2, 53 (12.6%) initiated kidney replacement therapy and 28% of the patients experienced the CKE. Albuminuria, with reference to <0.1g/g, was most associated with CKE. Hazard ratios (HRs) at UACRs of 0.1-0.6g/g, 0.6-1.4g/g, 1.4-2.2g/g and >2.2g/g were 2.03 [95% confidence interval (CI) 1.02-4.05], 3.8 (95% CI 1.92-7.5), 5.64 (95% CI 2.58-12.33) and 5.02 (95% CI 2.29-11-03), respectively. Regarding MACE, the presence of diabetes [HR 2.53 (95% CI 1.11-5.78)] was the most strongly associated factor, whereas UACR and eGFR did not show significant associations. In the GCKD IgAN subcohort, more than every fourth patient experienced a CKE event within 6.5years. Our findings support the use of albuminuria as a surrogate to assess the risk of poor kidney outcomes.

Development of a Machine Learning-Based Model for Accurate Detection and Classification of Polycystic Ovary Syndrome on Pelvic Ultrasound.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that disrupts reproductive function and hormonal balance. It primarily affects reproductive-aged women and leads to physical, metabolic, and emotional challenges affecting the quality of life.In this study, we develop a machine learning-based model to accurately identify PCOS pelvic ultrasound images from normal pelvic ultrasound images. By leveraging 1,932 pelvic ultrasound images from the Kaggle online platform (Google LLC, Mountain View, CA), we were able to create a model that accurately detected multiple small follicles in the ovaries and an increase in ovarian volume for PCOS pelvic ultrasound images from normal pelvic ultrasound images. Our developed model demonstrated a promising performance, achieving a precision value of82.6% and a recall value of 100%, including a sensitivity and specificity of 100% each. The value of the overall accuracy proved to be 100% and the F1 score was calculated to be 0.905. As the results garnered from our study are promising, further validation studies are necessary to generalize the model's capabilities and incorporate other diagnostic factors of PCOS such as physical exams and lab values.

A Propensity-Matched Cohort Study of Intravenous Iron versus Red Cell Transfusions for Preoperative Iron-Deficiency Anemia.

While preoperative anemia is associated with adverse perioperative outcomes, the benefits of treatment with iron replacement versus red blood cell (RBC) transfusion remain uncertain. We used a national database to establish trends in preoperative iron-deficiency anemia (IDA) treatment and to test the hypothesis that treatment with preoperative iron may be superior to RBC transfusion. This study is a propensity-matched retrospective cohort analysis from 2003 to 2023 using TriNetX Research Network, which included surgical patients diagnosed with IDA within 3 months preoperatively. After matching for surgery type and comorbidities, we compared a cohort of patients with preoperative IDA who were treated with preoperative intravenous (IV) iron but not RBCs (n = 77,179), with a cohort receiving preoperative RBCs but not IV iron (n = 77,179). Propensity-score matching was performed for age, ethnicity, race, sex, overweight and obesity, type 2 diabetes, hyperlipidemia, essential hypertension, heart failure, chronic ischemic heart disease, neoplasms, hypothyroidism, chronic kidney disease, nicotine dependence, surgery type, and lab values from the day of surgery including ferritin, transferrin, and hemoglobin split into low (<7 g/dL), medium (7-<12 g/dL), and high (≥12 g/dL) to account for anemia severity. The primary outcome was 30-day postoperative mortality with the secondary outcomes being 30-day morbidity, postoperative hemoglobin level, and 30-day postoperative RBC transfusion. Compared with RBC transfusion, preoperative IV iron was associated with lower risk of postoperative mortality (n = 2550/77,179 [3.3%] vs n = 4042/77,179 [5.2%]; relative risk [RR], 0.63, 95% confidence interval [CI], 0.60-0.66), and a lower risk of postoperative composite morbidity (n = 14,174/77,179 [18.4%] vs n = 18,632/77,179 [24.1%]; RR, 0.76, 95% CI, 0.75-0.78) (both P = .001 after Bonferroni adjustment). Compared with RBC transfusion, IV iron was also associated with a higher hemoglobin in the 30-day postoperative period (10.1 ± 1.8 g/dL vs 9.4 ± 1.7 g/dL, P = .001 after Bonferroni adjustment) and a reduced incidence of postoperative RBC transfusion (n = 3773/77,179 [4.9%] vs n = 12,629/77,179 [16.4%]; RR, 0.30, 95% CI, 0.29-0.31). In a risk-adjusted analysis, preoperative IDA treatment with IV iron compared to RBC transfusion was associated with a reduction in 30-day postoperative mortality and morbidity, a higher 30-day postoperative hemoglobin level, and reduced postoperative RBC transfusion. This evidence represents a promising opportunity to improve patient outcomes and reduce blood transfusions and their associated risk and costs.

Dealing with an uncertain future: a survey study on what patients with chronic kidney disease actually want to know.

Prognostic uncertainty is a recurring theme among patients with chronic kidney disease (CKD). We developed a survey to explore whether CKD patients want to know more about their future, and if so, which topics they prioritize. In addition, we explored differences between several subgroups. A survey was constructed and tested in collaboration with the Dutch Kidney Patients Association. The survey consisted of three parts: (i) demographics, (ii) considerations about the future, and (iii) prognostic information. The survey was distributed among CKD patients (all stages) through patient associations and via healthcare professionals in two Dutch hospitals. Descriptive statistics were used to summarize the results. All results were stratified by population, sex, and age. A total of 163 patients (45 CKD, 26 dialysis, and 92 kidney transplantation) participated in the survey. The mean age was 63.9 (SD 12.0) and 48.5% was male. Most patients think about their future with CKD occasionally (56.4%) or often (35.0%). Nearly half of the patients (49.7%) discuss the future with their nephrologist, some (19.6%) do not but would like to, and 20 (15.3%) prefer not to. Most patients (73.6%) want more prognostic information, regardless of it being positive or negative. Key topics to receive prognostic information about were laboratory values, symptoms, and physical well-being. Dialysis patients prioritized mental over physical well-being. CKD patients without kidney replacement therapy (KRT) indicated thinking about, and discussing their future more regularly than KRT patients. Patients with CKD contemplate their future regularly and express interest in receiving prognostic information on a variety of topics. One in five patients currently do not discuss their future with CKD with their nephrologist, despite wanting to do so. These findings underline the need to tailor prognostic information provision to patients' preferences, advocating more attention to this subject both in research and clinical practice.

Development and Validation of a Machine Learning COVID-19 Veteran (COVet) Deterioration Risk Score.

To develop the COVid Veteran (COVet) score for clinical deterioration in Veterans hospitalized with COVID-19 and further validate this model in both Veteran and non-Veteran samples. No such score has been derived and validated while incorporating a Veteran sample. Adults (age ≥ 18 yr) hospitalized outside the ICU with a diagnosis of COVID-19 for model development to the Veterans Health Administration (VHA) (n = 80 hospitals). External validation occurred in a VHA cohort of 34 hospitals, as well as six non-Veteran health systems for further external validation (n = 21 hospitals) between 2020 and 2023. eXtreme Gradient Boosting machine learning methods were used, and performance was assessed using the area under the receiver operating characteristic curve and compared with the National Early Warning Score (NEWS). The primary outcome was transfer to the ICU or death within 24 hours of each new variable observation. Model predictor variables included demographics, vital signs, structured flowsheet data, and laboratory values. A total of 96,908 admissions occurred during the study period, of which 59,897 were in the Veteran sample and 37,011 were in the non-Veteran sample. During external validation in the Veteran sample, the model demonstrated excellent discrimination, with an area under the receiver operating characteristic curve of 0.88. This was significantly higher than NEWS (0.79; p < 0.01). In the non-Veteran sample, the model also demonstrated excellent discrimination (0.86 vs. 0.79 for NEWS; p < 0.01). The top three variables of importance were eosinophil percentage, mean oxygen saturation in the prior 24-hour period, and worst mental status in the prior 24-hour period. We used machine learning methods to develop and validate a highly accurate early warning score in both Veterans and non-Veterans hospitalized with COVID-19. The model could lead to earlier identification and therapy, which may improve outcomes.

Risk factors for readmission after sepsis and its association with mortality

BackgroundSepsis is associated with an approximately 20 % 30-day readmission rate and with subsequent mortality. ObjectivesTo determine the demographics, comorbidities that had been documented prior to sepsis onset, processes of care, commonly administered laboratory tests measured near discharge, and post-sepsis infections that may be associated with readmission and, secondarily, whether readmission is an independent risk factor for 90-day mortality. MethodsUsing a database of patients who met Sepsis-3 criteria divided into Construction and Validation groups, we used logistic regression to estimate the factors independently associated with readmission within 30 days after discharge and proportional hazard regression to estimate the factors independently associated with 90-day mortality. ResultsOf the 30,798 patients ≥ 18 years at our combined referral and community hospital and were discharged alive who met Sepsis-3 criteria between July 10, 2009 and September 7, 2019, 5943 (19 %) were readmitted within 30 days. Thirteen thousand, four hundred forty-four (44 %) of the patients were female, 25,293 (82 %) White, 3523 (11 %) Black, and the mean age was 59 ± 17 years. Among the readmitted patients, 894 (15 %) died within 90 days from the original discharge compared to 11 % (p < 0.001) who had not been readmitted. Seven comorbidities, five processes of care (presepsis platelet transfusion, postsepsis platelet transfusion, operation, ICU length of stay, and hospital length of stay), five culture results, two discharge laboratory values, and discharge location were associated with readmission. The model had good discrimination, 0.770 ± 0.004 (Construction Group) and 0.748 ± 0.006 (Validation Group) and good relevancy (area under the precision recall curve), 0.390 ± 0.004 (Construction group) and 0.476 ± 0.005 (Validation group). Readmission within 30 days was independently associated with a 56 % higher risk of death (HR=1.562, 95 % CI=1.434, 1.703, p < 0.001) within 90 days from discharge. ConclusionsComorbidities, abnormal laboratory values, processes of care, and post-sepsis onset culture results, but not demographic characteristics, were associated with 30-day readmission. Readmission was associated with 90-day mortality.

Diagnostic value of systemic immune inflammation index in acute appendicitis and complicated appendicitis in pregnant patients.

Acute pain in the right lower quadrant during pregnancy is difficult to approach and acute appendicitis must be excluded. The complication rate in pregnant acute appendicitis increases as a result of delayed diagnosis due to physiological and anatomic changes. The systemic immune inflammatory index (SII), which includes several inflammatory tests, is considered to be a good indicator of acute inflammation. The aim of the present study was to investigate the diagnostic value of SII in the diagnosis of acute appendicitis and complicated appendicitis in pregnant women. This was designed as a retrospective, single-center case-control study. This study was performed in pregnant women over 12 weeks of gestation who were diagnosed with acute appendicitis as indicated by pathology report and met the inclusion criteria. Vital parameters, demographic characteristics, laboratory values, presence of complicated appendicitis, and pathology reports were taken into analysis. The present study was performed with 76 pregnant women, including 38 pregnant women with acute appendicitis and 38 pregnant women with healthy controls. SII had a sensitivity of 82.0% and specificity of 66.7% with a cut-off value of 840.13 in pregnant acute appendicitis cases (AUC: 0.790; 95% CI: 0.686-0.984; p < 0.001) and SII level was significantly higher in complicated appendicitis cases with a sensitivity and specificity of 66.7% and 91.3%, respectively, with a cut-off value of 2301.66 (AUC: 0.812; 95% CI: 0.665-0.958; p = 0.001). SII is a cost-effective, rapid, easily calculated, and powerful marker that can be used for the diagnosis of both acute and complicated appendicitis in pregnant patients.

Plant-based diet in hyperkalemic chronic kidney disease patients receiving sodium zirconium cyclosilicate: a feasibility clinical trial

BackgroundPlant-based diets (PBD) may induce hyperkalemia in chronic kidney disease (CKD) patients. ObjectivesWe explored the safety and feasibility of PBD in hyperkalemic CKD patients receiving the potassium binder sodium zirconium cyclosilicate (SZC). MethodsIn the current 6-wk trial, 26 hyperkalemic patients with CKD stage 4–5 not on dialysis received a low-protein low-potassium diet plus SZC for 3 wk and then a PBD with high potassium content delivered as a weekly food basket while continuing SZC for subsequent 3 wk. Plasma potassium was monitored weekly and SZC was titrated to achieve normokalemia. The 24-h urine excretion of potassium and sodium, 24-h food records, dietary quality, nutritional status, Bristol stool scale, Quality of life (QoL), and renal treatment satisfaction were assessed at baseline (week 0), week 3, and week 6. ResultsMean plasma potassium decreased from 5.5 to 4.4 mEq/L within 48–72 h after baseline, then rose to 4.7–5.0 mEq/L throughout the remaining study period following dose adjustments of SZC that matched the increased potassium intake of PBD from week 3 to week 6. Over the study period, 24-h urinary potassium excretion decreased from week 0 to week 3 and increased from week 3 to week 6. During the study, 58% of patients had fasting plasma potassium between 3.5 and 5.0 mEq/L and there was no episode of plasma potassium >6.5 mEq/L or <3.0 mEq/L during the study. P-carbon dioxide increased from baseline until week 6 (21 ± 2 to 23 ± 2 mEq/L; P = 0.002; mean ± SD), whereas remaining laboratory values remained unchanged. Fiber intake, dietary quality, the domain physical functioning from QoL, and 1 question of renal treatment satisfaction improved, whereas stool type and frequency did not change after starting PBD. ConclusionsPBD in hyperkalemia-prone CKD patients receiving SZC improved dietary quality and increased the intake of healthy foods, whereas plasma potassium concentration remained stable within normal values for most patients. Trial registration numberThis trial was registered at the https://clinicaltrials.gov/study/NCT04207203 as NCT04207203.

A Randomized Controlled Trial Testing the Effects of a Social Needs Navigation Intervention on Health Outcomes and Healthcare Utilization among Medicaid Members with Type 2 Diabetes.

Health systems are increasingly assessing and addressing social needs with referrals to community resources. The objective of this randomized controlled trial was to randomize adult Medicaid members with type 2 diabetes to receive usual care (n = 239) or social needs navigation (n = 234) for 6 months and compare HbA1c (primary outcome), quality of life (secondary outcome), and other exploratory outcomes with t-tests and mixed-effects regression. Eligible participants had an HbA1c test in claims in the past 120 days and reported 1+ social needs. Data were collected from November 2019 to July 2023. Surveys were completed at baseline and at 3-, 6-, and 12-month follow-up. Health plan data included care management records and medical and pharmacy claims. The sample was from Louisiana, USA, M = 51.6 (SD = 9.5) years old, 76.1% female, 66.5% Black, 29.4% White, and 3.0% Hispanic. By design, more navigation (91.5%) vs. usual care (6.7%) participants had a care plan. Social needs persisted for both groups. No group differences in HbA1c tests and values were observed, though the large amount of missing HbA1c lab values reduced statistical power. No group differences were observed for other outcomes. Proactively eliciting and attempting to provide referrals and resources for social needs did not demonstrate significant health benefits or decrease healthcare utilization in this sample.

Population pharmacokinetics and exposure-response analyses of SAF-189s in Chinese patients with ALK+/ROS1+ non-small cell lung cancer.

SAF-189s is a potent ALK/ROS1 inhibitor that is currently in clinical development for treating advanced ALK+/ROS1+ non-small cell lung cancer (NSCLC). Comprehensive population pharmacokinetics (PopPK) and exposure-response models were developed to evaluate the efficacy and safety of SAF-189s by integrating data from two clinical studies. The PopPK model was developed using plasma concentration data collected from patients with ALK+/ROS1+ advanced NSCLC (n = 299) and healthy subjects (n = 24). The covariates (demographics, laboratory values, subject types, and concomitant medications) were evaluated to determine their potential influence on the between-patient variability in the pharmacokinetics of SAF-189s. Individual exposure values were then used to investigate the relationships with the efficacy endpoints (overall response rate (ORR), progression-free survival (PFS), and duration of response (DOR)) and key safety endpoints (adverse events of interest). The final PopPK model of SAF-189s was described by a one-compartment model with delayed first-order absorption and time-dependent elimination by allowing the clearance to decrease stepwise over time. Age was included as a covariate for apparent clearance (CL/F), while prior anti-cancer therapy in ALK+ patients (ALKPOT) was included for apparent volume of distribution (V/F). There were no apparent exposure-response relationships for any of the efficacy endpoints at doses of 80-210mg. The relationship between exposure and safety suggested that a higher steady-state exposure was associated with more frequent incidences of hyperglycemia and proteinuria; the 210-mg dose group was also less tolerated than the other low-dose groups. PopPK and exposure-response models were developed for SAF-189s, and their results demonstrate that SAF-189s exposures are at the plateau of exposure-response for efficacy. The 210-mg dose group had a significantly higher safety risk, while the 160-mg dose group was well-tolerated. Thus, 160mg of SAF-189s once daily was selected as the recommended phase III dose for the ALK+/ROS1+ or ROS1+ NSCLC patients.

Population Pharmacokinetic Analysis of Dolutegravir in Treatment-Experienced Adults Living with HIV-1.

The World Health Organization has recommended the use of dolutegravir (DTG) for both first and second-line antiretroviral treatment in both adults and children down to 4 weeks of age. We developed a population pharmacokinetic(PopPK) model following oral administration of DTG 50 mg QD and 50 mg BID in HIV-infected treatment-experienced adults (607) based on pooled data from four phase 2/3 trials. DTG population pharmacokinetics are described by a one-compartment model with first-order absorption, absorption lag-time, and first-order elimination. The PopPK parameter estimates were apparent oral clearance (CL/F) = 1.00 L/h, apparent volume of distribution (V/F) = 18.9 L, absorption rate constant (Ka) = 1.99 per hour, and absorption lag time = 0.333 h, respectively. The final model included inter-individual and inter-occasion variability on apparent clearance (CL/F). Weight, smoking status, use of metabolic inducers as part of background antiretroviral therapy (ART) classified by their level of induction, use of atazanavir or atazanavir-ritonavir as part of background ART, and albumin level were predictors of CL/F; weight and albumin level were predictors of V/F; and sex and concomitant use of metal cation-containing vitamin/mineral supplements were predictors of relative bioavailability (F). The current model-based analysis suggests that the DTG dose adjustment is not required based on the demographics, laboratory values, smoking status, concomitant use of mild metabolic inducers or inhibitors in the background therapy, or use of metal cation-containing vitamin/mineral supplements because these covariate effects are not predicted to have a clinically relevant impact on safety and efficacy.

Clinical relevance of positively determined myositis antibodies in rheumatology: a retrospective monocentric analysis

BackgroundThe increased availability of myositis autoantibodies represents new possibilities and challenges in clinical practice (Lundberg IE, Tjärnlund A, Bottai M, Werth VP, Pilkington C, de Visser M, et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis. 2017;76:1955–64. https://doi.org/10.1136/annrheumdis-2017-211468.). The aim of this study was to perform a retrospective data analysis of patient cases with positive myositis autoantibodies to analyse their significance in routine rheumatology practice.MethodsA monocentric analysis of all the orders used to determine myositis autoantibodies from July 2019 to May 2022 in the Department of Rheumatology, Krankenhaus Porz am Rhein, Cologne, Germany, was carried out.ResultsIn the defined time interval, a total of 71,597 laboratory values for the antibodies mentioned above were obtained. A total of 238 different positive autoantibodies ​​were detected in 209 patients. Idiopathic inflammatory myopathy was diagnosed in 37 patients (18%), and inflammatory rheumatic diseases other than idiopathic inflammatory myopathy were diagnosed in 90 patients (43%). No inflammatory rheumatic disease was diagnosed in 82 patients (39%). General clusters of clinical manifestations were observed.ConclusionsIn our cohort, we were able to show that a relevant proportion of patients with positive myositis antibodies did not have idiopathic inflammatory myopathies or inflammatory rheumatic diseases. This finding indicates the importance of myositis autoantibodies in this group of patients. However, further studies on the course of symptoms and examination results in patients without inflammatory rheumatic diseases and with positive myositis antibodies are necessary.

Factors associated with lower quarter performance-based balance and strength tests: a cross-sectional analysis from the project baseline health study.

Physical performance tests are predictive of mortality and may screen for certain health conditions (e.g., sarcopenia); however, their diagnostic and/or prognostic value has primarily been studied in age-limited or disease-specific cohorts. Our objective was to identify the most salient characteristics associated with three lower quarter balance and strength tests in a cohort of community-dwelling adults. We applied a stacked elastic net approach on detailed data on sociodemographic, health and health-related behaviors, and biomarker data from the first visit of the Project Baseline Health Study (N = 2,502) to determine which variables were most associated with three physical performance measures: single-legged balance test (SLBT), sitting-rising test (SRT), and 30-second chair-stand test (30CST). Analyses were stratified by age (<65 and ≥65). Female sex, Black or African American race, lower educational attainment, and health conditions such as non-alcoholic fatty liver disease and cardiovascular conditions (e.g., hypertension) were consistently associated with worse performance across all three tests. Several other health conditions were associated with either better or worse test performance, depending on age group and test. C-reactive protein was the only laboratory value associated with performance across age and test groups with some consistency. Our results highlighted previously identified and several novel salient factors associated with performance on the SLBT, SRT, and 30CST. These tests could represent affordable, noninvasive biomarkers of prevalent and/or future disease in adult individuals; future research should validate these findings. ClinicalTrials.gov, identifier NCT03154346, registered on May 15, 2017.