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Updates in chronic kidney disease management: A systematic review
No full textChronic kidney disease (CKD) is a significant global health challenge that impacts both patients and the health care system. This systematic review aims to evaluate the efficacy and safety of emerging therapeutic strategies for CKD management, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), finerenone, sacubitril/valsartan, and potassium binders. We conducted searches in databases including PubMed, Scopus, CINAHL Complete, and Web of Science Core Collection to identify experimental and observational studies pertaining to each of these agents. Included studies were those that enrolled adult patients with CKD who evaluated SGLT2i, GLP-1RA, finerenone, sacubitril/valsartan, and potassium binders compared to other medications or placebo and evaluated renal-related outcomes as a primary or secondary outcome. Methodological quality and risk of bias were assessed using the Cochrane Risk of Bias (version 2) tool for experimental studies and ROBINS-I for observational studies. After screening 2135 unique studies, 138 studies were eligible for this review. These studies describe a substantial and growing body of evidence focused on improving the management of CKD beyond renin-angiotensin system inhibitors (RASi), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). Currently, SGLT2i have demonstrated consistent benefits with large effect sizes in preventing the progression of CKD, solidifying this class as a first-line treatment along with RASi. Subsequent consideration for GLP-1RA, finerenone, and sacubitril/valsartan should be dependent on patient-specific comorbidities, while potassium binders may allow for longer use of RASi
A prospective study of a whole blood metal mixture and depressive symptoms among Black women from Detroit, Michigan
No full textExposure to metals has been previously associated with depressive symptoms, but few studies have considered potential effects of metal mixtures. In addition, few previous studies have been conducted among Black women, who are disproportionately at risk for exposure to some metals and greater depression incidence and severity. We analyzed data from the Study of Environment, Lifestyle, and Fibroids (SELF), a prospective cohort study of reproductive-aged Black women from Detroit, to examine associations between a mixture of metals, metalloids, and trace elements ( metals ) and depressive symptoms (n = 1450). SELF participants self-identified as Black or African American and were 23-34 years of age at enrollment. We collected covariate information on structured questionnaires and whole blood samples at baseline. We quantified 17 metals in whole blood using inductively coupled plasma mass spectrometer triple quadruple or Direct Mercury Analyzer-80. Participants reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D) at the 20-month follow-up visit, where higher CES-D scores reflected greater depressive symptoms. We used quantile-based g-computation to estimate the cumulative association of the metal mixture with CES-D scores, adjusting for age, household income, educational attainment, body mass index, smoking status, alcohol intake, and parity. We estimated beta coefficients (with 95 % confidence intervals [CI]) as the percent difference in CES-D scores per quartile increase in all metals. A one-quartile increase in the metal mixture was associated with 14.8 % lower (95 % CI=-26.7 %, -1.1 %) CES-D scores, reflecting lower depressive symptoms. The mixture association was driven by nickel, copper, cesium, molybdenum, and lead. Other neurotoxic metals (cadmium, arsenic, mercury, chromium) were associated with greater depressive symptoms. Findings from this study suggest that exposure to a mixture of metals may affect depressive symptoms in Black women, with individual metals acting in opposing directions
Child Opportunity Index at birth and asthma with recurrent exacerbations in the US ECHO program
No full textBACKGROUND: Environmental exposures and social determinants likely influence specific childhood asthma phenotypes.
OBJECTIVE: We hypothesized that the Child Opportunity Index (COI) at birth, measuring multiple neighborhood opportunities, influences incidence rates (IRs) for asthma with recurrent exacerbations (ARE).
METHODS: We tested for COI associations with ARE IRs in 15,877 children born between 1990 and 2018 in the ECHO (Environmental Influences on Child Health Outcomes) program. Parent-reported race and ethnicity and other demographics were assessed as effect modifiers.
RESULTS: The IRs of ARE for children born in very low COI neighborhoods was higher (IR = 10.98; 95% CI: 9.71, 12.25) than for other COI categories. Rates for non-Hispanic Black (NHB) children were significantly higher than non-Hispanic White children in every COI category. The ARE IRs for children born in very low COI neighborhoods were several-fold higher for NHB and Hispanic Black children (IR = 15.30; 95% CI: 13.10, 17.49; and IR = 18.48; 95% CI: 8.80, 28.15, respectively) when compared to White children. Adjusting for individual-level characteristics, children born in very low COI neighborhoods demonstrated an ARE IR ratio of 1.26 (95% CI: 0.99, 1.59) with a higher incidence of cases among children ages 2 to 4 years and with a parental history of asthma.
CONCLUSIONS: Rates of ARE were higher among children born in under-resourced communities, and this relationship is strongest for young minoritized children with a parental history of asthma. Higher rates for NHB even in the highest COI categories suggest that risk associated with race persists regardless of social disadvantage
Efficacy of Once-Nightly Sodium Oxybate in Patients with Narcolepsy: Post Hoc Analyses of Sensitivity, Effect Size, and Numbers Needed to Treat from the Phase 3 REST-ON Trial
No full textBACKGROUND: Once-nightly sodium oxybate (ON-SXB; LUMRYZ™; FT218) treatment significantly improved the coprimary endpoints of mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression of Improvement (CGI-I) rating, and number of weekly cataplexy episodes versus placebo in a randomized, placebo-controlled trial (REST-ON). The objective of these post hoc sensitivity analyses was to evaluate the robustness of treatment with ON-SXB, while accounting for missing participant data. Number needed to treat (NNT) and effect size analyses were conducted to quantify the treatment benefits.
METHODS: Participants ≥ 16 years of age with narcolepsy type 1 or 2 were randomized 1:1 to receive ON-SXB (4.5 g [week 1]; 6 g [weeks 2-3]; 7.5 g [weeks 4-8]; or 9 g [weeks 9-13]) or placebo. Sensitivity analyses included completer population, placebo-based multiple imputation (MI) with a missing-not-at-random assumption, analysis of covariance (ANCOVA), and tipping-point-based MI of worsening values until P \u3e 0.05. Mean differences and P-values were calculated for the MWT and number of cataplexy episodes. For CGI-I, odds ratios and P-values were calculated for completers; mean differences (1-7 points; lower values indicate greater improvement) and P-values were calculated using ANCOVA. Effect sizes were calculated using Cohen\u27s d; NNTs were calculated as the inverse of the absolute risk reduction.
RESULTS: In the completer population (ON-SXB, n = 69; placebo, n = 79), all ON-SXB doses demonstrated significant improvements versus placebo for all coprimary endpoints (P \u3c 0.001). All ON-SXB doses demonstrated significant improvements (P \u3c 0.001) versus placebo for all coprimary endpoints when missing values in both treatment arms were imputed from observed values in the placebo arm (i.e., missing data were replaced with placebo data) and when analyzed using ANCOVA. Tipping-point-based analysis on the change from baseline in mean sleep latency on the MWT demonstrated that implausible or nearly implausible baseline MWT assumptions were needed to render the differences between ON-SXB and placebo no longer statistically significant. All doses of ON-SXB had NNTs of three and effect sizes of 0.7-0.9 for MWT response. For the response in terms of number of cataplexy episodes, NNT was six for the 6 g dose and three for the 7.5 g and 9 g doses; the effect sizes were between -0.7 and -0.8. For the Epworth Sleepiness Scale (ESS) response, NNTs ranged from three to six, with a dose-response effect. Effect sizes were between -0.5 and -0.7 for all doses.
CONCLUSIONS: These post hoc results demonstrate the robustness of the REST-ON clinical trial efficacy data.
CLINICAL TRIAL ID: NCT02720744
Ankle Peak Systolic Velocity Correlates with Toe Pressure in Patients with Peripheral Artery Disease
No full textBACKGROUND: Conventional screening of Peripheral Artery Disease (PAD) with Ankle Brachial Index may be limited in diabetic patients due to arterial calcification. Alternatively, ankle peak systolic velocity (APSV) may be a more accurate measure of limb perfusion in those patients. This study aims to assess the correlation between APSV and toe pressure (TP) in patients evaluated for PAD.
METHODS: This is a single-center retrospective study examining the correlation between APSV and TP in patients evaluated for PAD at a tertiary medical center between January 2019 and August 2020. Spearman Correlation and multivariate linear regression were used to assess the association between APSV and TP. The optimal cutoffs for APSV corresponding to TP of 30 mm Hg and 50 mm Hg were generated using the Youden index.
RESULTS: A total of 224 patients with median age of 72 years were included in this study. 61% of patients were females and 54% were diabetic. The mean APSV of the overall population was 62 cm/s. APSV was significantly correlated with TP (R = 0.6, P \u3c 0.001) in both diabetic and nondiabetic patients. On multivariate analysis, TP was significantly associated with APSV (estimate B 0.41, 95% confidence interval 0.29-0.53, P \u3c 0.001). The optimal cutoffs of APSV to detect a TP ≤ 30 mm Hg and TP ≥ 50 mm Hg were 35 cm/s and 44 cm/s, respectively.
CONCLUSION: APSV is a reliable measure for evaluating perfusion in PAD patients. Its adoption in the clinical setting can significantly improve the accuracy of PAD diagnosis, allowing earlier detection and treatment
Controversies in Allergy: Should I Combine an ICS With a SABA or With Formoterol for Reliever Therapy?
No full textMultiple approaches with inhaler therapies can be utilized when treating asthma. Inhaled corticosteroids (ICS) reduce airway inflammation while bronchodilators relax airway smooth muscle. Anti-inflammatory reliever (AIR) therapy combines an ICS with quick-onset bronchodilators for use as a rescue therapy. Several AIR strategies have demonstrated efficacy in reducing asthma exacerbations. There are currently two inhalers that combine an ICS with a quick onset bronchodilator into a single inhaler: one which combines an ICS with short-acting beta(2)-agonist (ICS-SABA) and one which combines an ICS with the long-acting beta(2)-agonist formoterol (ICS-formoterol). Alternatively, AIR therapy can be provided with the ICS and the SABA in two separate inhalers. The provider may come across challenges when choosing a specific therapy best suited for each patient, including insurance and regulatory issues. This article reviews the literature on AIR therapy in adult and pediatric populations with asthma along with implementation considerations when choosing a specific AIR strategy
Development and validation of a prognostic model for postoperative hypotension in patients receiving epidural analgesia.
No full textBACKGROUND AND AIMS: Postoperative hypotension is common in adults receiving epidural analgesia. Although risk factors have been reported in the literature, prognostic models have not been developed or validated. We aimed to develop and validate a multivariable, prognostic model for postoperative hypotension in patients receiving epidural analgesia.
MATERIAL AND METHODS: We retrieved retrospective cohort data of adults undergoing abdominal or thoracic surgery at five hospitals between 2014 and 2023 who received epidural analgesia for at least 24 hours after surgery. A systematic literature search helped define a priori candidate exposures. The primary outcome was postoperative hypotension during the first 72 hours after surgery. Multiple logistic regression was performed to evaluate a multivariable model. Exposures identified as statistically significant were used for logistic regression, linear discriminant analysis, and decision-tree model of random forest. Classification error was used to compare models, and variable importance was used for random forest analysis.
RESULTS: In total, 829 participants were included. The incidence of postoperative hypotension was 38.8%. Multivariable analysis identified the following independent prognostic factors: male sex, white race, body mass index, intraoperative hypotension, use of arterial line, bupivacaine concentration of 0.125% (vs. lower concentrations), and anesthesia duration. The error misclassification rate was 67% for multiple logistic regression, 27% for linear discriminant analysis, and 33.4% for random forest model.
CONCLUSION: Using retrospective cohort data, a prognostic model of hypotension produced the best performance results using linear discriminant analysis, with an error misclassification rate of 27%. Further studies are required to perform model optimization for future clinical use
Association between pre-existing Pulmonary Hypertension and COVID-19 related outcomes in inpatient and ambulatory care settings
No full textBACKGROUND: Afflicting up to 1% of population, pulmonary hypertension (PH) is commonly associated with cardiopulmonary and metabolic diseases, but the effect of COVID-19 in patients with pre-existing PH remains unclear.
METHODS: We conducted a retrospective cohort study in patients who had undergone right-heart-catheterization within the VA Healthcare system and had a subsequent hospital admission with COVID-19 (inpatient cohort, n=1204) or had COVID-19 positivity but not admitted (outpatient cohort, n=6576). Inpatient findings were confirmed in a non-VA validation cohort (n=656) who had undergone echocardiography with subsequent admission. PH was defined invasively as mean pulmonary artery pressure (mPAP) \u3e20 mmHg and non-invasively as estimated right ventricular systolic pressure (RVSP) \u3e30 mmHg. In-hospital outcomes (inpatient cohort) and 1-year mortality (outpatient cohort) were assessed using multivariable logistic or Cox regression adjusting for confounders.
RESULTS: Pre-existing PH was independently associated with greater in-hospital mortality (PH using mPAP: adjusted odds ratio [aOR] 1.60, 95%CI: 1.04-2.46; PH using RVSP: aOR 2.12, 95% CI 1.18-3.82). Among outpatients, those with COVID-19 had \u3e8-fold higher 90-day and 2.8 fold higher 91-365 day adjusted hazard of mortality irrespective of PH status. Hazards of 90-day hospitalization were similarly driven by COVID-19. The findings were comparable for patient subgroup with normal pulmonary capillary wedge pressures.
CONCLUSION: Pre-existing PH is independently associated with higher in-hospital COVID-19 mortality. In outpatients, COVID-19 positivity was associated with increased mortality over 1 year irrespective of PH status, with highest risk within the first 90 days
Teens train your brain! A mixed-methods feasibility trial of a working memory training program for adolescents from an economically disadvantaged community
No full textExposure to early socioeconomic disadvantage impacts the development of working memory, a component of executive functions underlying engagement in risky behaviors including substance misuse. Given that working memory develops across adolescence, coinciding with increases in the onset and rapid escalation of substance use and other risky behaviors, interventions designed to improve working memory may have promise for supporting behavioral health for youth from low-resource areas. However most working memory programs have been developed for adults from higher-resource contexts and may not be feasible for youth from socioeconomically distressed communities. The current study (n = 23) uses a mixed methods approach to evaluate the implementation potential and preliminary effectiveness of a computer-based working memory training program among youth ages 12 to 16 from a very low-resource community. Participants (48% female; 100% Black) were administered tests of working memory before and after completing a working memory program or a control computer program. Results suggest youth in the active condition found the intervention to be acceptable, appropriate and enjoyable and evidenced statistically significant increases in working memory. No improvement was seen among youth in the comparison condition. Findings suggest preliminary support for implementation of this program in an impoverished urban setting
Management of Challenging Psoriasis Clinical Scenarios
No full textPsoriasis, a chronic inflammatory skin condition, can have a significant impact on patients\u27 quality of life. Adoption of novel and emerging treatments has significantly improved psoriasis care in clinical practice, but challenges remain. The \u27Bridging the Gaps in Challenging Psoriasis\u27 meeting was held in October 2024 to discuss relevant evidence, knowledge gaps, and best practices pertaining to challenging presentations of psoriasis. This report captures important insights and practice impacting guidance gathered from the panel discussion on five topics. The meeting commenced with an in-depth discussion on managing psoriasis in high-impact areas (e.g., scalp, intertriginous regions, nails, and the palms and soles) followed by a discussion on the importance of identifying and addressing common comorbidities associated with psoriasis. The panel explored key considerations and unique challenges when treating psoriasis in patients with darker skin tones (\u27skin of color\u27) and highlighted the need for tailored therapeutic approaches. A comprehensive dialogue ensued on strategies for managing primary and secondary treatment failures. The session concluded with a concise discussion on the future of psoriasis treatments and pharmacologic therapies currently being developed to manage psoriasis. While discussing various challenging psoriasis scenarios, the dermatology experts emphasized the need to approach psoriasis as a systemic disease and advocated for comprehensive management that addresses both the skin and the broader health of the patient