Effects of long-term lithium therapy on kidney functioning in mood disorders: A population-based historical cohort study.

AIMS: Lithium is Food and Drug Administration-approved for bipolar disorder (BD) and is also used in depressive disorders but is underutilized due to concerns about chronic kidney disease (CKD). We explored clinical and demographic profiles of patients on long-term lithium therapy (LTLT) and assessed kidney function. Our aims were to identify the predictors for CKD stage ≥3 and the impact of lithium discontinuation post-CKD diagnosis. METHODS: We conducted a population-based historical cohort study of adult patients with mood disorders on LTLT at the Marshfield Clinical Health System from 1990 to 2019. Data on lithium therapy and kidney-related information (estimated glomerular filtration rate and CKD) were extracted from electronic medical records. RESULTS: Among 1603 patients with mood disorders (mean age 42.1 years, 60% females), 15.3% (n = 246) developed CKD stage ≥3. Patients without CKD were on lithium for 4.5 years, compared to 6.6 years for those with CKD. Hypertension, age, and BD were significant CKD risk factors. Kidney function declined linearly with lithium duration, returning to pre-treatment trajectory in patients without CKD but showed no improvement in those with CKD after lithium discontinuation. CONCLUSION: The findings suggest that CKD occurs in 15% of patients with mood disorder receiving LTLT, with its progression potentially influenced by existing comorbidities rather than lithium alone. These results underscore the importance of monitoring kidney function in patients on LTLT and considering individual risk factors for CKD development. In patients who developed CKD, Li discontinuation did not impact change in kidney function.

Risk factors for treatment of asymptomatic bacteriuria in a rural health system.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Asymptomatic bacteriuria is often inappropriately treated, leading to antimicrobial-related adverse events and contributing to antimicrobial resistance. This study examined the asymptomatic bacteriuria treatment rate at a rural Wisconsin health system and the patient-specific factors that may be influencing clinicians' decisions to treat. METHODS: This is a retrospective descriptive report of patients admitted from January to May 2022 at 7 rural Wisconsin hospitals. Patients were included if they were a hospitalized adult with asymptomatic bacteriuria. Patients were excluded if they had a urinary tract abnormality, active infection, symptoms of a urinary tract infection, a planned urological surgery, or treatment or prophylaxis for a urinary tract infection within 72 hours of admission, were immunocompromised, or were transferred from an outside facility. Electronic and manual chart abstraction were used for data collection. RESULTS: Of 429 patients with a positive urine culture, 137 patients with asymptomatic bacteriuria were included in the study. The median age was 75 years, and most patients were female (80.3%). The treatment rate of asymptomatic bacteriuria was 78.1%, amounting to 393 days of unnecessary antimicrobial therapy. Symptoms of fatigue (P = 0.014) and altered mentation (P < 0.006) and urinalysis results of nitrite positivity (P = 0.026) and pyuria (P < 0.001) were each independently associated with antimicrobial treatment. CONCLUSION: Despite guideline recommendations to avoid treatment of asymptomatic bacteriuria, treatment rates in rural hospitalized patients remain high. Nonspecific signs and symptoms of altered mentation and fatigue as well as laboratory findings of nitrite positivity and pyuria were factors associated with a decision to treat. Future stewardship efforts should speak to the poor specificity of these factors.

A National Survey of Neonatologists' Perspectives on Probiotics Use in Neonatal Intensive Care Units in the U.S.A.

Introduction: Most recent clinical reports from the American Academy of Pediatrics (AAP) concluded current evidence does not support routine universal administration of probiotics to preterm infants, particularly those with birth weight <1000 grams. Despite this, the use of probiotics is increasing in US neonatal intensive care units (NICU).Objectives: Collaborating with the Perinatal Neonatal Medicine of AAP, we conducted a national survey to obtain neonatologist opinion on probiotics use.Methods: Survey questionnaires were sent to 3000 neonatologists via email.Results: Of 3000 potential respondents, 249 (8.3 %) completed the survey. Seventy-five (30%) neonatologists working in 23 different NICUs reported using probiotics in their practice, while 168 (70%) neonatologists working in 54 different NICUs reported not using probiotics. Of those not currently use probiotics, 49% indicated they would consider using probiotics in the future vs. 12% indicating they would not use probiotics. The most common indication for probiotics use was average gestational age < 32 weeks and mean birth weight < 1500 grams. Probiotics were discontinued at mean gestational age of 35 weeks. Respondents who prescribe probiotics were more likely to work in a setting without fellowship or residency training (48% vs 20%). Probiotics users were more often from the West (29 % vs 7%) and less often from Northeast (5% vs 34%) compared to non-users. The proportion of those using probiotics did not significantly differ by NICU size, NICU level, or years working in a NICU. Similac Tri-Blend, Evivo, and Culturelle were the top three probiotics used in the respondent's NICU.Conclusion: Though a majority of respondents are not currently using probiotics in their NICU, a large number of nonusers are interested in using probiotics in the future. Differences continue to exist in the brand of probiotics used in US NICUs.

Novel predictors of permanent pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: Conduction and rhythm abnormalities requiring permanent pacemakers (PPM) are short-term complications following transcatheter aortic valve replacement (TAVR), and their clinical outcomes remain conflicting. Potential novel predictors of post-TAVR PPM, like QRS duration, QTc prolongation, and supraventricular arrhythmias, have been poorly studied. AIM: To evaluate the effects of baseline nonspecific interventricular conduction delay and supraventricular arrhythmia on post-TAVR PPM requirement and determine the impact of PPM implantation on clinical outcomes. METHODS: A retrospective cohort study that identified patients with TAVR between January 1, 2012 to December 31, 2019. The group was dichotomized into those with post-TAVR PPM and those without PPM. Both groups were followed for one year. RESULTS: Out of the 357 patients that met inclusion criteria, the mean age was 80 years, 188 (52.7%) were male, and 57 (16%) had a PPM implantation. Baseline demographics, valve type, and cardiovascular risk factors were similar except for type II diabetes mellitus (DM), which was more prevalent in the PPM cohort (59.6% vs 40.7%; P = 0.009). The PPM cohort had a significantly higher rate of pre-procedure right bundle branch block, prolonged QRS > 120 ms, prolonged QTc > 470 ms, and supraventricular arrhythmias. There was a consistently significant increase in the odds ratio (OR) of PPM implantation for every 20 ms increase in the QRS duration above 100 ms: QRS 101-120 [OR: 2.44; confidence intervals (CI): 1.14-5.25; P = 0.022], QRS 121-140 (OR: 3.25; CI: 1.32-7.98; P = 0.010), QRS 141-160 (OR: 6.98; CI: 3.10-15.61; P < 0.001). After model adjustment for baseline risk factors, the OR remained significant for type II DM (aOR: 2.16; CI: 1.18-3.94; P = 0.012), QRS > 120 (aOR: 2.18; CI: 1.02-4.66; P = 0.045) and marginally significant for supraventricular arrhythmias (aOR: 1.82; CI: 0.97-3.42; P = 0.062). The PPM cohort had a higher adjusted OR of heart failure (HF) hospitalization (aOR: 2.2; CI: 1.1-4.3; P = 0.022) and nonfatal myocardial infarction (MI) (aOR: 3.9; CI: 1.1-14; P = 0.031) without any difference in mortality (aOR: 1.1; CI: 0.5-2.7; P = 0.796) at one year. CONCLUSION: Pre-TAVR type II DM and QRS duration > 120, regardless of the presence of bundle branch blocks, are predictors of post-TAVR PPM. At 1-year post-TAVR, patients with PPM have higher odds of HF hospitalization and MI.

Changes in Pediatric Intensive Care Admissions in Wisconsin During the 2020 COVID-19 Pandemic.

BACKGROUND: We perceived changes in the frequency of and reasons for admissions to Wisconsin pediatric intensive care units (PICU) during the advent of the COVID-19 pandemic, and we hypothesized that the rates of total, scheduled, and respiratory viral admissions were lower during the first calendar year of the pandemic than would have been predicted by historical admission data. Such findings would reflect important changes in PICU utilization paradigms during the pandemic. There are no descriptions of PICU admission changes in a single American state during the pandemic. METHODS: We compared all Wisconsin PICU admissions during the COVID-19 pandemic in 2020 (the study epoch) to admissions in seasonally matched, growth-adjusted "no-COVID-19" projections generated by time series analysis of all Wisconsin PICU admissions in the previous 5 years (the control epoch). RESULTS: We identified 27,425 PICU admissions with 294,577 associated diagnoses in the study and control epochs. Total admissions were 60 ± 9 week-1 in the study epoch versus 103 ± 4 projected (RR 0.63; 95% CI, 0.59-0.68; P < 0.001). Scheduled admissions were 17 ± 6 week-1 in the study epoch versus 28 ± 3 projected (RR 0.61; 95% CI, 0.55-0.67; P < 0.001). Respiratory viral admissions were 8 ± 5 week-1 in the study epoch versus 19 ± 9 projected (RR 0.40; 95% CI, 0.33-0.48; P < 0.001). Some admission categories experienced dramatic declines (c, respiratory/ear, nose, throat), while others experienced less decline (eg, injury/poisoning/adverse effects) or no significant change (eg, diabetic ketoacidosis). Except cases of COVID-19, no category had significantly increased weekly admissions. There were 104 admissions associated with COVID-19 diagnoses in 2020, 4.3% of the study epoch admissions. CONCLUSIONS: We describe PICU admission changes in the first calendar year of COVID-19, informing health care staffing and service planning, as well as decisions regarding strategies to combat the evolving pandemic.

Dental manifestations in adult hypophosphatasia and their correlation with biomarkers.

Hypophosphatasia (HPP) is a genetic condition with broad clinical manifestations caused by alkaline phosphatase (ALP) deficiency. Adults with HPP exhibit a wide spectrum of signs and symptoms. Dental manifestations including premature tooth loss are common. Much of the published literature reporting dental manifestations consists of case reports and series of symptomatic patients, likely biased towards more severe dental manifestations. The objective of this study was to systematically explore the dental manifestations among adults with HPP by conducting a comprehensive dental evaluation. To minimize bias, the study explored dental manifestations in an unselected cohort of adults with HPP. Participants were identified searching electronic health record (EHR) data from a rural health system to discover adults with persistent ALP deficiency. Heterozygotes with pathogenic (P), likely pathogenic (LP), or uncertain variants (VUS) in ALPL and at least one elevated ALP substrate were defined as adults with HPP and underwent genetic, dental, oral radiographic, and biomarker evaluation. Twenty-seven participants completed the study. Premature tooth loss was present in 63% (17/27); 19% (5/27) were missing eight or more teeth. Statistically significant associations were found between premature permanent tooth loss and HPP biomarkers ALP (p = 0.049) and bone-specific ALP (p = 0.006). Serum ALP (ρ = -0.43, p = 0.037) and bone-specific ALP (ρ = -0.57, p = 0.004) were negatively correlated with number of teeth lost prematurely. As noted with tooth loss, periodontal breakdown was associated with bone-specific ALP. An inverse association between periodontal breakdown and bone-specific ALP was observed (p = 0.014). These findings suggest a role for ALP in maintenance of dentition.

Pancreaticoduodenectomy is safe in appropriately resourced rural hospitals.

BACKGROUND: Research shows improved safety and treatment outcomes for patients undergoing pancreaticoduodenectomy at high-volume centers. Regionalization of pancreaticoduodenectomy to high-volume urban centers can result in unintended negative consequences for rural patients and communities. This report examines outcomes after pancreaticoduodenectomy performed at a rural hospital and compares them with national standards. METHODS: A prospectively maintained database of pancreatic operations performed at a rural tertiary hospital was queried. Demographic and clinical information for patients undergoing pancreaticoduodenectomy (2007-2019) was analyzed. Primary outcomes were the rates of patient mortality and morbidity. Secondary outcomes were readmission rates, indications, and associations with clinical variables. RESULTS: We included 118 patients in our study. There were 41 postoperative complications (34.7%), including 1 death (0.9%). The 90-day readmission rate was 24.6%. The most common indication for readmission was deep space infection (n = 7, 24.1%). Patients requiring an intraoperative transfusion were more likely to need hospital readmission (41.4% vs 9.0% of patients without transfusion, P = .016). Patients with postoperative complications required readmission more frequently (51.7% vs 29.2%, P = .093). These findings are similar to data from urban hospitals. CONCLUSION: Patient safety and surgical outcomes after pancreaticoduodenectomy performed in appropriately resourced rural hospitals can be comparable with national standards. Safely treating rural patients near their home benefits patients and their communities.

Oligotrophic wetland sediments susceptible to shifts in microbiomes and mercury cycling with dissolved organic matter addition.

Recent advances have allowed for greater investigation into microbial regulation of mercury toxicity in the environment. In wetlands in particular, dissolved organic matter (DOM) may influence methylmercury (MeHg) production both through chemical interactions and through substrate effects on microbiomes. We conducted microcosm experiments in two disparate wetland environments (oligotrophic unvegetated and high-C vegetated sediments) to examine the impacts of plant leachate and inorganic mercury loadings (20 mg/L HgCl2) on microbiomes and MeHg production in the St. Louis River Estuary. Our research reveals the greater relative capacity for mercury methylation in vegetated over unvegetated sediments. Further, our work shows how mercury cycling in oligotrophic unvegetated sediments may be susceptible to DOM inputs in the St. Louis River Estuary: unvegetated microcosms receiving leachate produced substantially more MeHg than unamended microcosms. We also demonstrate (1) changes in microbiome structure towards Clostridia, (2) metagenomic shifts toward fermentation, and (3) degradation of complex DOM; all of which coincide with elevated net MeHg production in unvegetated microcosms receiving leachate. Together, our work shows the influence of wetland vegetation in controlling MeHg production in the Great Lakes region and provides evidence that this may be due to both enhanced microbial activity as well as differences in microbiome composition.

Persistent Urban Influence on Surface Water Quality via Impacted Groundwater.

Growing urban environments stress hydrologic systems and impact downstream water quality. We examined a third-order catchment that transitions from an undisturbed mountain environment into urban Salt Lake City, Utah. We performed synoptic surveys during a range of seasonal baseflow conditions and utilized multiple lines of evidence to identify mechanisms by which urbanization impacts water quality. Surface water chemistry did not change appreciably until several kilometers into the urban environment, where concentrations of solutes such as chloride and nitrate increase quickly in a gaining reach. Groundwater springs discharging in this gaining system demonstrate the role of contaminated baseflow from an aquifer in driving stream chemistry. Hydrometric and hydrochemical observations were used to estimate that the aquifer contains approximately 18% water sourced from the urban area. The carbon and nitrogen dynamics indicated the urban aquifer also serves as a biogeochemical reactor. The evidence of surface water-groundwater exchange on a spatial scale of kilometers and time scale of months to years suggests a need to evolve the hydrologic model of anthropogenic impacts to urban water quality to include exchange with the subsurface. This has implications on the space and time scales of water quality mitigation efforts.

Influence of leaching solution and catchment location on the fluorescence of water-soluble organic matter.

Organic matter (OM) plays a significant role in biogeochemical processes in soil and water systems. Water-soluble organic matter (WSOM) leached from soil samples is often analyzed as representative of potentially mobile OM. However, there are many WSOM extraction methods in the literature with no clear guidelines for method selection. In this study, four common leaching solutions (0.5 M K2SO4, 0.01 M CaCl2, 2 M KCl, and H2O) were used to extract WSOM from various locations within a forested catchment. Fluorescence spectroscopy was used to analyze the impact of extraction method on WSOM chemistry. While all four methods consistently identified chemical differences between WSOM from a north-facing slope, south-facing slope, and riparian zone, there were clear differences in fluorescence signals between the leaching methods. All three salt solutions contained WSOM with a higher fluorescence index and humification index than WSOM leached with H2O, suggesting the presence of salts releases different fractions of the soil organic matter. A parallel factor analysis (PARAFAC) model developed from the leachates identified a distinctive soil humic fluorophore observed in all samples and fluorescent artifacts present in H2O-leached samples.

A preliminary assessment of water partitioning and ecohydrological coupling in northern headwaters using stable isotopes and conceptual runoff models.

We combined a conceptual rainfall-runoff model and input-output relationships of stable isotopes to understand ecohydrological influences on hydrological partitioning in snow-influenced northern catchments. Six sites in Sweden (Krycklan), Canada (Wolf Creek; Baker Creek; Dorset), Scotland (Girnock) and the USA (Dry Creek) span moisture and energy gradients found at high latitudes. A meta-analysis was carried out using the Hydrologiska Byråns Vattenbalansavdelning (HBV) model to estimate the main storage changes characterizing annual water balances. Annual snowpack storage importance was ranked as Wolf Creek > Krycklan > Dorset > Baker Creek > Dry Creek > Girnock. The subsequent rate and longevity of melt were reflected in calibrated parameters that determine partitioning of waters between more rapid and slower flowpaths and associated variations in soil and groundwater storage. Variability of stream water isotopic composition depends on the following: (i) rate and duration of spring snowmelt; (ii) significance of summer/autumn rainfall; and (iii) relative importance of near-surface and deeper flowpaths in routing water to the stream. Flowpath partitioning also regulates influences of summer evaporation on drainage waters. Deviations of isotope data from the Global Meteoric Water Line showed subtle effects of internal catchment processes on isotopic fractionation most likely through evaporation. Such effects are highly variable among sites and with seasonal differences at some sites. After accounting for climate, evaporative fractionation is strongest at sites where lakes and near-surface runoff processes in wet riparian soils can mobilize isotopically enriched water during summer and autumn. Given close soil-vegetation coupling, this may result in spatial variability in soil water isotope pools available for plant uptake. We argue that stable isotope studies are crucial in addressing the many open questions on hydrological functioning of northern environments. © 2015 The Authors. Hydrological Processes published by John Wiley & Sons Ltd.

Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat.

The effects of raloxifene on acquisition of a delayed matching to position (DMP) T-maze task and on hippocampal acetylcholine release were evaluated and compared with estradiol, to determine whether raloxifene has estrogenic effects on cognitive performance and hippocampal cholinergic activity. Ovariectomized rats received continuous treatment with raloxifene (one of two doses), estradiol, or vehicle for 30 days, followed by behavioral training, and then in vivo microdialysis assessment of basal and potassium-stimulated acetylcholine release. The data show that estradiol significantly enhanced DMP acquisition, whereas raloxifene did not. In contrast, both estradiol and the higher dose of raloxifene significantly increased potassium-stimulated acetylcholine release in the hippocampus. These data suggest that, despite increasing evidence for estrogenic effects of raloxifene in brain, raloxifene does not mimic the effects of estrogen on cognitive performance as assessed by acquisition of a simple spatial memory task in ovariectomized rats.

Estrogen and cognition: applying preclinical findings to clinical perspectives.

The effects of hormone replacement therapy on brain aging and cognition are an important public health issue, which, despite much research and debate, has not yet been resolved. In this Mini-Review, we describe how much of the clinical literature takes on new meaning when interpreted in light of recent preclinical data. We predict, based on these data, that hormone replacement therapy will in fact provide substantial benefit with respect to age-related cognitive decline, provided that therapy is administered in an appropriate regimen and is initiated within a window of time following the loss of ovarian function. The application of these data to recent clinical findings is discussed.

Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus.

Short-term estrogen replacement has been shown to enhance basal forebrain cholinergic function. Whether or not long-term estrogen replacement can enhance basal forebrain cholinergic function has been questioned in light of recent studies showing that several cholinergic measures which are increased following short-term treatment are not increased following longer-term (>30 days) treatment. In the present study, in vivo microdialysis was used to assess the effects of continuous estradiol replacement on basal forebrain cholinergic function. Our data show that 6-7 weeks of continuous estradiol replacement significantly enhanced potassium-stimulated acetylcholine release in the hippocampus of ovariectomized rats, and that this effect was reversed following discontinuation of the estrogen treatment. These data are consistent with the hypothesis that estrogen-mediated effects on cholinergic neurons can contribute to the effects of long-term estrogen replacement on cognitive performance recently described.