Increased Health Care Costs Research Articles

The Double-Edged Sword of Extremely High Prices for Gene Therapies in Sickle Cell Disease

This Viewpoint discusses the high cost of new gene therapies for sickle cell disease, the challenges these costs pose for health care access, and new policy approaches to ensure fair reimbursement for payers and manufacturers without further increasing health care costs or barriers to access for underserved populations.

Ageism Harms Older People's Health, Cognition, and Well-Being: A Selective Review and Policy Recommendations

Ageism refers to stereotypes, prejudice, and discrimination directed towards individuals based on their age, such as perceptions that someone is “too old” for certain activities. Ageism directed at older people is prevalent; over 90% of older people in the United States report that they regularly experience ageism, such as when others assume they are forgetful or need assistance because of their age. Experiencing ageism is associated with poorer health outcomes, reduced cognitive performance, and increased healthcare costs. Reducing ageism requires a multifaceted approach, including strengthening anti-ageism laws and reframing societal narratives about what it means to grow older. Growing older should not be presented as a problem but as a fundamental part of the human journey. Ageism can also be reduced through positive intergenerational interactions and educational initiatives. Reducing ageism can promote healthier aging trajectories.

The ReInvigorate Study—phrenic nerve-to-diaphragm stimulation for weaning from mechanical ventilation: a protocol for a randomized pivotal clinical trial

BackgroundIn the United States in 2017, there were an estimated 903,745 hospitalizations involving mechanical ventilation (MV). Complications from ventilation can result in longer hospital stays, increased risk of disability, and increased healthcare costs. It has been hypothesized that electrically pacing the diaphragm by phrenic nerve stimulation during mechanical ventilation may minimize or reverse diaphragm dysfunction, resulting in faster weaning.MethodsThe ReInvigorate Trial is a prospective, multicenter, randomized, controlled clinical trial evaluating the safety and efficacy of Stimdia’s pdSTIM System for facilitating weaning from MV. The pdSTIM system employs percutaneously placed multipolar electrodes to stimulate the cervical phrenic nerves and activate contraction of the diaphragm bilaterally. Patients who were on mechanical ventilation for at least 96 h and who failed at least one weaning attempt were considered for enrollment in the study. The primary efficacy endpoint was the time to successful liberation from mechanical ventilation (treatment vs. control). Secondary endpoints will include the rapid shallow breathing index and other physiological and system characteristics. Safety will be summarized for both primary and additional analyses. All endpoints will be evaluated at 30 days or at the time of removal of mechanical ventilation, whichever is first.DiscussionThis pivotal study is being conducted under an investigational device exception with the U.S. Food and Drug Administration. The technology being studied could provide a first-of-kind therapy for difficult-to-wean patients on mechanical ventilation in an intensive care unit setting.Trial registrationClinicaltrials.gov, NCT05998018, registered August 2023.

Microbial Diversity of Periprosthetic Joint Infections in Diabetic and Nondiabetic Patients Following Hip Arthroplasty

BackgroundPeriprosthetic joint infection (PJI) is a major complication following hip arthroplasty, leading to prolonged hospital stays, increased health care costs, and major morbidity. Diabetes mellitus is a prevalent comorbidity among hip arthroplasty patients, contributing to an increased risk of surgical complications, including infections. However, limited evidence exists regarding the microbial profiles of PJIs in diabetic patients compared to nondiabetic counterparts. MethodsWe conducted a retrospective cohort study to investigate the microbial diversity of PJIs in diabetic and nondiabetic patients following hip arthroplasty. Medical records of patients who underwent hip arthroplasty procedures between 1996 and 2021 were reviewed. Patients diagnosed with PJI, based on the international consensus meeting, were included in the study. Microbiological data, including culture results, and risk factors were collected and analyzed. A total of 4,261 culture-positive patients diagnosed with PJI following hip arthroplasty were included in the analysis. ResultsMicrobiological analysis revealed a diverse spectrum of microbial pathogens, with Staphylococcus species being the most commonly isolated pathogen. Comparison between diabetic and nondiabetic patients revealed differences in the microbial profiles of PJIs, with diabetic patients more likely to be infected with specific pathogens, including Candida albicans (P = 0.01 odds ratio (OR) 2.8, confidence interval (CI) 1.2 to 6.2), Klebsiella pneumoniae (P = 0.03 OR 2.4, CI 1.0 to 5.6), Staphylococcus aureus (P = 0.04 OR 1.3, CI 1.0 to 1.8), Staphylococcus epidermidis (P < 0.001 (R 1.7, CI 1.4 to 2.2), Polymicrobial infections (P < 0.001 OR 1.5, CI 1.2 to 1.8), and Clostridium perfringens (P = 0.04 OR 5.9, CI 1.0 to 33.1). ConclusionsOur study provides valuable insights into the microbial diversity of PJIs in diabetic and nondiabetic patients following hip arthroplasty. The identification of a tendency to different microbial profiles in diabetic patients underscores the need for tailored approaches to infection prevention and management in this high-risk population. Further research is needed to elucidate the underlying mechanisms and develop targeted interventions to improve patient outcomes.

Estimating the economic impact of comorbidities in patients with MASH and defining high-cost burden in patients with noncirrhotic MASH.

Metabolic dysfunction-associated steatohepatitis (MASH) is associated with high health care costs. This US study investigated the economic burden of MASH, particularly in patients without cirrhosis, and the impact of comorbidities on health care costs. This retrospective, observational study used data from patients diagnosed with MASH aged ≥18 years from October 2015 to March 2022 (IQVIA Ambulatory electronic medical record-US). Patients were stratified by the absence or presence of cirrhosis. Primary outcomes included baseline characteristics and annualized total health care cost after MASH diagnosis during follow-up. In addition, this study defined high costs for the MASH population and identified patient characteristics associated with increased health care costs among those without cirrhosis. Overall, 16,919 patients (14,885 without cirrhosis and 2034 with cirrhosis) were included in the analysis. The prevalence of comorbidities was high in both groups; annual total health care costs were higher in patients with cirrhosis. Patients with a high-cost burden (threshold defined using the United States national estimated annual health care expenditure of $13,555) had a higher prevalence of comorbidities and were prescribed more cardiovascular medications. MASH diagnosis was associated with an increase in cost, largely driven by inpatient costs. In patients without cirrhosis, an increase in cost following MASH diagnosis was associated with the presence and burden of comorbidities and cardiovascular medication utilization. Comorbidities, such as cardiovascular disease and type 2 diabetes, are associated with a higher cost burden and may be aggravated by MASH. Prioritization and active management may benefit patients without cirrhosis with these comorbidities. Clinical care should focus on preventing progression to cirrhosis and managing high-burden comorbidities.

The effect of intravenous ondansetron on QT interval in the emergency department

ObjectiveOndansetron, a 5HT3 receptor antagonist, is commonly used in emergency departments to treat nausea and vomiting. In 2011, the Food and Drug Administration (FDA) issued a warning that this medicine may cause QT prolongation, potentially leading to deadly arrhythmias. The objective of this study was to characterize the QT interval prolongation associated with ondansetron use in the Emergency Department. MethodsThis was a prospective, observational cohort study of adult patients who presented to the emergency department during a one-year period and were treated with intravenous ondansetron. We investigated the QT prolongation associated with dosages. ECGs were obtained before the medication and 5, 15, and 30 minutes after IV drug administration. Every QT measurement was recorded and compared to the zero point. The severity of drug-induced QT prolongation was determined according to the recommendations of the International Conference on Compliance (ICH). QTc prolongation was categorized as ‘negligible’ (<5 ms), ‘significant’ (>20 ms), ‘potential concern’ (>30 ms), or ‘definitely worrying’ (>60 ms). ResultsOf the 435 patients enrolled in the study, 60% (261 patients) were female and the mean age was 39 (±18). The QT prolongation peaked at the fifth minute and remained consistent at the fifteenth and thirty-first minutes. The maximum prolongation of the mean QT duration occured at the fifth minute (7.9 ± 18.1 ms). No patient revealed any problems with cardiac conduction. The prolonged QT interval was not related to the dose of ondansetron, but QT measurements were higher in the 30th minute in patients treated with 8 mg of ondansetron. The effect of ondansetron administration on QT prolongation was found to be above the ‘negligible’ but below the ‘significant’ value, according to the ICH recommendations. DiscussionIn this study, QT prolongation due to ondansetron administration was below the ‘important’ value according to the recommendations of the ICH. No cases of cardiac arrhythmia were reported in any of the partients. Thus, routine ECG monitoring in patients given ondansetron due to the risk of QTc prolongation does not seem cost-effective when evaluated together with additional factors such as its negative impact on emergency patient flow, waste of personnel and time, and increase in healthcare costs. In the absence of a known risk of cardiac arrhythmia, IV administration of 4 mg and 8 mg of ondansetron doses no risk of QT prolongation in the emergency population.

For whom the bell tolls: assessing the incremental costs associated with failure to rescue after elective colorectal surgery

BackgroundFailure to rescue after elective surgery is associated with increased healthcare costs. These costs are poorly understood and have not been reported for colorectal surgery. This study aimed to assess the incremental costs of failure to rescue after elective colorectal surgery. MethodsThis was a retrospective study of adult patients identified in the National Inpatient Sample from 2016 to 2019 who underwent an elective colectomy or proctectomy. Patients were stratified into 4 groups: uneventful recovery, successfully rescued, failure to rescue, and died without rescue attempts. “Rescue” was defined as admissions with ≥1 procedure code ≥1 day after the initial procedure. The primary outcome was total admission costs. ResultsOf 451,490 admissions for elective colorectal resection, 94.6% had an uneventful recovery, 4.8% were successfully rescued, 0.4% were failure to rescue, and 0.3% died without rescue attempts. The median total hospital cost for the uneventful recovery cohort was $16,751 (IQR, $12,611-$23,116), for the successfully rescued cohort was $42,295 (IQR, $27,959-$67,077), for the failure-to-rescue cohort was $53,182 (IQR, $30,852-$95,615), and for the died without attempted rescue cohort was $29,296 (IQR, $19,812-$45,919). When comparing cost quantiles by regression analysis, failure-to-rescue patients had significantly higher costs than the successfully rescued patients for the last 3 quantiles (fifth quantile [90th percentile], $163,963 vs $106,521; P < .001). ConclusionAcross a nationally representative cohort, the median total hospital costs for patients who failed to be rescued were $10,887 more than for those who were successfully rescued. These findings emphasize the importance of shared decision making and medical futility and highlight opportunities for resource optimization after postoperative complications.

Comparative Analysis of Decellularization Methods on Bovine Pericardium Scaffolds for Cardiac Tissue Engineering

Background: Congenital heart disease (CHD) involves structural heart abnormalities present since fetal development. Corrective surgery is often the ideal treatment, utilizing implants or scaffolds for tissue repair. However, repeated surgeries may be required due to declining function of grafts, leading to increased healthcare costs. Bovine pericardium is a promising scaffold material for tissue engineering due to its composition of collagen, glycosaminoglycans (GAGs), and proteoglycans. This study aimed to compare the effectiveness of bovine pericardium scaffolds using different decellularization methods: sodium dodecyl sulfate (SDS) and hydrogen peroxide (H2O2). Methods: An experimental study was conducted with bovine pericardium scaffolds divided into control and treatment groups. The treatment groups used decellularization with SDS (0.5%, 1%) and H2O2 (3%). Scaffolds were evaluated for tensile strength, strain, Young's modulus, and histological properties, including nuclear density, collagen density, and GAG content. Data were analyzed using statistical methods to compare the effectiveness of each decellularization technique. Results: Histological analysis revealed that all decellularized samples showed no nuclear density, while control samples displayed light nuclear density. Collagen density was light in scaffolds treated with SDS 0.5% and H2O2, while SDS 1% resulted in no collagen presence. GAG density was absent in SDS-treated samples and minimal in H2O2-treated samples. Tensile strength was highest in H2O2-treated scaffolds (24.01 N) and lowest in SDS 0.5%. SDS 1% showed the greatest tensile strain, while H2O2-treated scaffolds had the highest stiffness. Conclusion: The decellularization methods effectively removed cellular components from the bovine pericardium scaffolds, with varying impacts on the extracellular matrix. SDS 1% provided the most elastic scaffold, while H2O2 preserved tensile strength and stiffness. These findings suggest that the choice of decellularization method can be optimized based on the desired mechanical properties of the scaffold for cardiac tissue engineering applications. Further research is needed to evaluate the long-term performance of these scaffolds in clinical settings.

Health economic evaluation of an electronic mindfulness-based intervention (eMBI) to improve maternal mental health during pregnancy – a randomized controlled trial (RCT)

BackgroundAnxiety and depression are the most prevalent psychiatric diseases in the peripartum period. They can lead to relevant health consequences for mother and child as well as increased health care resource utilization (HCRU) and related costs. Due to the promising results of mindfulness-based interventions (MBI) and digital health applications in mental health, an electronic MBI on maternal mental health during pregnancy was implemented and assessed in terms of transferability to standard care in Germany. The present study focused the health economic outcomes of the randomized controlled trial (RCT).MethodsThe analysis, adopting a payer’s and a societal perspective, included women of increased emotional distress at < 29 weeks of gestation. We applied inferential statistics (α = 0.05 significance level) to compare the intervention group (IG) and control group (CG) in terms of HCRU and costs. The analysis was primarily based on statutory health insurance claims data which covered the individual observational period of 40 weeks.ResultsOverall, 258 women (IG: 117, CG: 141) were included in the health economic analysis. The results on total health care costs from a payer’s perspective indicated higher costs for the IGi compared to the CG (Exp(ß) = 1.096, 95% CI: 1.006–1.194, p = 0.037). However, the estimation was not significant after Bonferroni correction (p < 0.006). Even the analysis from a societal perspective as well as sensitivity analyses did not show significant results.ConclusionsIn the present study, the eMBI did neither reduced nor significantly increased health care costs. Further research is needed to generate robust evidence on eMBIs for women suffering from peripartum depression and anxiety.Trial registrationGerman Clinical Trials Register: DRKS00017210. Registered on 13 January 2020. Retrospectively registered.

Dutch municipalities tackling climate change adaptation to heat stress through mainstreaming across sectors

As climate change accelerates, adapting to heat stress means preventing excess deaths, increased healthcare costs, reduced productivity, and damaged infrastructure and buildings. In cities, the urban heat island effect exacerbates these impacts. Adapting to heat stress requires action by a multitude of actors in different domains, including infrastructure and building owners, health care and social workers, and vulnerable inhabitants. While there is research on heat stress adaptation by single sectors, there is a significant knowledge gap regarding heat adaptation across sectors. To contribute to bridging this knowledge gap, we answer the following research question: To what extent and how are municipalities in the Dutch Province of Overijssel mainstreaming heat stress as part of their adaptation efforts? To answer this question, we combine action-oriented research employing the Institutional Analysis and Development Framework in a Dutch municipality, with a survey conducted among 15 municipalities located in the same province. Our research identifies two major challenges. First, the implementation of heat adaptation remains limited. Second, we identified two challenges regarding mainstreaming, namely a mismatch between the responsibility of heat adaptation in the built environment vis-à-vis the health care sector, and a lack of information on vulnerable groups that makes cross-sectoral collaboration more difficult. Thus, the extent to which heat adaptation is being mainstreamed as part of municipalities’ efforts to adapt the built environment is still quite limited and heat stress management at the intersection with the health care sector remains mostly absent, leaving vulnerable groups exposed.

Study protocol of the HessenKohorte2042: a prospective, longitudinal cohort study characterising quality of life in people with Parkinson’s disease and their caregivers using a bio-psycho-social approach

IntroductionQuality of life (QoL) is of paramount importance as an outcome to monitor and guide therapies for people with Parkinson’s disease (PwPD). In particular, due to the heterogeneous symptoms that...

Bone Tissue Changes in Individuals Living with HIV/AIDS: The Importance of a Hierarchical Approach in Investigating Bone Fragility.

Skeletal alterations and their complications can significantly impact the quality of life and overall prognosis of patients living with HIV (PLWHIV). Considering skeletal alterations are often asymptomatic and unapparent during routine clinical evaluation, these conditions are frequently overlooked in the clinical management of PLWHIV. However, since the use of combined antiretroviral therapy (cART) has increased life expectancy in PLWHIV effectively, osteopenia, osteoporosis, and bone fragility are now considered to have a major health impact, with a substantial increase in healthcare costs. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to bone changes in PLWHIV, focusing on the importance of taking a multi-scale approach in the assessment of bone hierarchical organization. Even though a low bone mineral density is frequently reported in PLWHIV, numerous ambiguities still remain to be solved. Recent data suggest that assessment of other bone properties (on various levels of the bone structure) could contribute to our understanding of bone fragility determinants in these individuals. Special attention is needed for women living with HIV/AIDS since a postmenopausal status was described as an important factor that contributes to skeletal alterations in this population. Further research on complex etiopathogenetic mechanisms underlying bone alterations in PLWHIV may lead to the development of new therapeutic approaches specifically designed to reduce the health burden associated with skeletal disorders in this population. A major challenge in the clinical management of PLWHIV lies in the adverse skeletal effects of some frequently prescribed cART regimens (e.g., regimens containing tenofovir disoproxil fumarate), which may require a switch to other pharmacological approaches for maintained HIV infection (e.g., regimens containing tenofovir alafenamide). Taken together, the findings are indicative that the HIV/AIDS status should be taken into consideration when designing new guidelines and strategies for individualized prevention, diagnosis, and treatment of increased bone fragility.

Machine learning-enabled prediction of prolonged length of stay in hospital after surgery for tuberculosis spondylitis patients with unbalanced data: a novel approach using explainable artificial intelligence (XAI)

BackgroundTuberculosis spondylitis (TS), commonly known as Pott’s disease, is a severe type of skeletal tuberculosis that typically requires surgical treatment. However, this treatment option has led to an increase in healthcare costs due to prolonged hospital stays (PLOS). Therefore, identifying risk factors associated with extended PLOS is necessary. In this research, we intended to develop an interpretable machine learning model that could predict extended PLOS, which can provide valuable insights for treatments and a web-based application was implemented.MethodsWe obtained patient data from the spine surgery department at our hospital. Extended postoperative length of stay (PLOS) refers to a hospitalization duration equal to or exceeding the 75th percentile following spine surgery. To identify relevant variables, we employed several approaches, such as the least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE) based on support vector machine classification (SVC), correlation analysis, and permutation importance value. Several models using implemented and some of them are ensembled using soft voting techniques. Models were constructed using grid search with nested cross-validation. The performance of each algorithm was assessed through various metrics, including the AUC value (area under the curve of receiver operating characteristics) and the Brier Score. Model interpretation involved utilizing methods such as Shapley additive explanations (SHAP), the Gini Impurity Index, permutation importance, and local interpretable model-agnostic explanations (LIME). Furthermore, to facilitate the practical application of the model, a web-based interface was developed and deployed.ResultsThe study included a cohort of 580 patients and 11 features include (CRP, transfusions, infusion volume, blood loss, X-ray bone bridge, X-ray osteophyte, CT-vertebral destruction, CT-paravertebral abscess, MRI-paravertebral abscess, MRI-epidural abscess, postoperative drainage) were selected. Most of the classifiers showed better performance, where the XGBoost model has a higher AUC value (0.86) and lower Brier Score (0.126). The XGBoost model was chosen as the optimal model. The results obtained from the calibration and decision curve analysis (DCA) plots demonstrate that XGBoost has achieved promising performance. After conducting tenfold cross-validation, the XGBoost model demonstrated a mean AUC of 0.85 ± 0.09. SHAP and LIME were used to display the variables’ contributions to the predicted value. The stacked bar plots indicated that infusion volume was the primary contributor, as determined by Gini, permutation importance (PFI), and the LIME algorithm.ConclusionsOur methods not only effectively predicted extended PLOS but also identified risk factors that can be utilized for future treatments. The XGBoost model developed in this study is easily accessible through the deployed web application and can aid in clinical research.

Predictive analytics for early detection of hospital-acquired complications: An artificial intelligence approach.

Hospital-acquired complications (HACs) have an adverse impact on patient recovery by impeding their path to full recovery and increasing healthcare costs. The aim of this study was to create a HAC risk prediction machine learning (ML) framework using hospital administrative data collections within North Metropolitan Health Service (NMHS), Western Australia. A retrospective cohort study was performed among 64,315 patients between July 2020 to June 2022 to develop an automated ML framework by inputting HAC and the healthcare site to obtain site-specific predictive algorithms for patients admitted to the hospital in NMHS. Univariate analysis was used for initial feature screening for 270 variables. Of these, 77 variables had significant relationship with any HAC. After excluding non-contemporaneous data, 37 variables were included in developing the ML framework based on logistic regression (LR), decision tree (DT) and random forest (RF) models to predict occurrence of four specific HACs: delirium, aspiration pneumonia, pneumonia and urinary tract infection. All models exhibited similar performance with area under the curve scores around 0.90 for both training and testing datasets. For sensitivity, DT and RF exceeded LR performance while on average, false positives were lowest for LR-based models. Patient's length of stay, Charlson Index, operation length and intensive care unit stay were common predictors. Integrating ML-based risk detection systems into clinical workflows can potentially enhance patient safety and optimise resource allocation. LR-based models exhibited best performance. We have successfully developed a "real-time" risk prediction model, where patient risk scores are calculated and reviewed daily.

Health Care Expenditure in United States Adults With Heart Failure With and Without Diabetes

The health costs for heart failure (HF) among individuals with and without diabetes can help understand the conjoint burden of diabetes and HF. Using the 2008–2019 US national Medical Expenditure Panel Survey data including 2,019 adults with HF and a 2-part adjusted model, we estimated mean and adjusted incremental direct medical expenditures related to diabetes. The total direct expenditures for individuals with HF increased by 27%: $24,725 (95% confidence interval [CI]: $20,457-$28,993) in 2008-2009 to $31,426 (95% CI: $25,705-$37,147) in 2018-2019. The expenditures rose by 34% among those with diabetes. Inpatient costs represented the highest fraction of costs ∼ 43.3 % and were 8% higher among those with diabetes vs. those without diabetes. The drug costs accounted for 24% of all costs, increased by 44%, and were 86% higher among HF patients with diabetes vs. those without diabetes. The adjusted excess costs among individuals with HF and diabetes vs. HF without diabetes was $6,818 (95% CI: 2,241-11,395); the corresponding excess costs for drugs and medical costs other than drugs were $3,297 (95% CI: 2,168-4,426) and $3,554 (95% CI: -777-7,886). Among US adults with HF, the estimated adjusted total direct excess costs were $5.2 billion per year higher among individuals with diabetes vs. those without diabetes. In conclusion, diabetes is associated with substantially increased health care costs among patients with HF, suggesting the need for an integrated management of diabetes and HF.

Predicting return of lung function after a pulmonary exacerbation using the cystic fibrosis respiratory symptom diary-chronic respiratory infection symptom scale

BackgroundPulmonary exacerbations (PExs) in people with cystic fibrosis (PwCF) are associated with increased healthcare costs, decreased quality of life and the risk for permanent decline in lung function. Symptom burden, the continuous physiological and emotional symptoms on an individual related to their disease, may be a useful tool for monitoring PwCF during a PEx, and identifying individuals at high risk for permanent decline in lung function. The purpose of this study was to investigate if the degree of symptom burden severity, measured by the Cystic Fibrosis Respiratory Symptom Diary (CFRSD)- Chronic Respiratory Infection Symptom Scale (CRISS), at the onset of a PEx can predict failure to return to baseline lung function by the end of treatment.MethodsA secondary analysis of a longitudinal, observational study (N = 56) was conducted. Data was collected at four time points: year-prior-to-enrollment annual appointment, termed “baseline”, day 1 of PEx diagnosis, termed “Visit 1”, day 10–21 of PEx diagnosis, termed “Visit 2” and two-weeks post-hospitalization, termed “Visit 3”. A linear regression model was performed to analyze the research question.ResultsA regression model predicted that recovery of lung function decreased by 0.2 points for every increase in CRISS points, indicating that participants with a CRISS score greater than 48.3 were at 14% greater risk of not recovering to baseline lung function by Visit 2, than people with lower scores.ConclusionMonitoring CRISS scores in PwCF is an efficient, reliable, non-invasive way to determine a person’s status at the beginning of a PEx. The results presented in this paper support the usefulness of studying symptoms in the context of PEx in PwCF.

Postoperative Hyponatremia After Endoscopic Endonasal Resection of Pituitary Adenomas: Historical Complication Rates and Risk Factors

Hyponatremia is a common complication following endoscopic endonasal resection (EER) of pituitary adenomas. We report a single-center, multisurgeon study detailing baseline clinical data, outcomes, and factors associated with postoperative hyponatremia. This was a retrospective cohort study of patients undergoing EER for pituitary adenoma at Tufts Medical Center. Most procedures were performed by the senior author (C.B.H.). Cases were included if at least 1 postoperative sodium value was available and pathology confirmed pituitary adenoma. Hyponatremia was defined as a postoperative sodium level <135 mEq/L. A total of 272 patients underwent 310 EER procedures that met the study inclusion criteria. The mean patient age was 53.3 years, and mean tumor size was 18.8 mm. Postoperative hyponatremia occurred in 12.6% of cases, with 3.6% developing hyponatremia prior to discharge. Lower preoperative sodium level was associated with an increased risk of developing any postoperative hyponatremia. Older age, prolactinoma pathology, and use of selective serotonin reuptake inhibitors were associated with moderate to severe hyponatremia (≤129 mEq/L), and lower preoperative sodium was associated with mild hyponatremia (130-134 mEq/L). Hyponatremia-related readmissions within 30 days occurred in 3.9% of patients. Both African-American race and postoperative hyponatremia were associated with an increased risk of 30-day readmission. The mean nadir sodium for hyponatremic patients was 129.9 mEq/L. Growth hormone-secreting pathology was associated with lower postoperative nadir sodium, whereas higher preoperative sodium was associated with higher postoperative nadir sodium. Hyponatremia is a common postoperative complication of EER for pituitary lesions that can cause significant morbidity, increased readmissions, and increased healthcare costs.

Developmental dyslexia genes are selectively targeted by diverse environmental pollutants

BackgroundDevelopmental dyslexia, a complex neurodevelopmental disorder, not only affects children’s academic performance but is also associated with increased healthcare costs, lower employment rates, and reduced productivity. The pathogenesis of dyslexia remains unclear and it is generally considered to be caused by the overlap of genetic and environmental factors. Systematically exploring the close relationship between exposure to environmental compounds and susceptibility genes in the development of dyslexia is currently lacking but high necessary.MethodsIn this study, we systematically compiled 131 publicly reported susceptibility genes for dyslexia sourced from DisGeNET, OMIM, and GeneCards databases. Comparative Toxicogenomics Database database was used to explore the overlap between susceptibility genes and 95 environmental compounds, including metals, persistent organic pollutants, polycyclic aromatic hydrocarbons, and pesticides. Chemical bias towards the dyslexia risk genes was taken into account in the observation/expectation ratios > 1 and the corresponding P value obtained by hypergeometric probability test.ResultsOur study found that the number of dyslexia risk genes targeted by each chemical varied from 1 to 109. A total of 35 chemicals were involved in chemical reactions with dyslexia-associated genes, with significant enrichment values (observed/expected dyslexia risk genes) ranging from 1.147 (Atrazine) to 66.901 (Dibenzo(a, h)pyrene).ConclusionThe results indicated that dyslexia-associated genes were implicated in certain chemical reactions. However, these findings are exploratory, and further research involving animal or cellular experiments is needed.

Delirium in Neurocritical Care: Uncovering Undisclosed Psychotropic Substance and Medication Use and Stress Exposure by Hair Analysis.

In intensive care, delirium is frequent, prolongs the stay, increases health care costs, and worsens patient outcome. Several substances and medications as well as stress can impact the risk of delirium; however, assessment of previous exposure to psychotropic agents and stress by self-reports or third-party information is not always reliable. Hair analysis can be used to objectively assess medication and substance use (including chronic alcohol consumption), and allows for the determination of stress-related long-term changes in steroid hormones and endocannabinoids. Consecutive adult patients with acute brain injury admitted to the neurocritical care unit were included. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit. Liquid chromatography coupled with tandem mass spectrometry was used to investigate psychoactive substances and medications, ethyl glucuronide, steroid hormones, and endocannabinoids in hair samples. Univariable and multivariable analyses were used to reveal any associations with the occurrence of delirium. Of 50 consecutive patients, 21 (42%) were diagnosed with delirium. Detection of antipsychotics or antidepressants in hair was more frequent in patients with delirium (antidepressants: 43% vs. 14%, p = 0.040; antipsychotics: 29% vs. 0%, p = 0.021). These patients also displayed higher ethyl glucuronide levels (p = 0.049). Anandamide (AEA) concentrations were higher in patients with delirium (p = 0.005), whereas oleoylethanolamide (p = 0.045) and palmitoylethanolamide (PEA) (p = 0.017) concentrations were lower in patients with delirium. Backward stepwise logistic regression analysis revealed antidepressants and AEA/PEA to be independent relevant predictors of delirium. Hair analysis provides crucial and otherwise unattainable information regarding chronic stress and the use of psychotropic substances and medications. Undisclosed antidepressant/antipsychotic use or intense chronic alcohol consumption is susceptible to treatment (continuation of medication or provision of low-dose benzodiazepines in case of alcohol). Chronic stress can be evaluated using stress markers and endocannabinoids in hair, potentially allowing for personalized delirium risk stratification and preventive measures.

Highlighting the South Asian Heart Failure Epidemic.

Heart failure (HF) remains a progressive syndrome with high morbidity and mortality, and accounts for many hospitalisations globally with a downstream impact of increasing healthcare costs. South Asian individuals account for most of the global burden of non-communicable diseases. In this systematic review, a literature search was performed for all studies focusing on South Asians and HF using PubMed as the primary research tool and citations were included from relevant MEDLINE-indexed journals. Upon identification of relevant studies, pertinent data points were extracted systematically from each eligible study. South Asians have an earlier age of onset of many non-communicable diseases compared to other ethnic groups worldwide, including cardiovascular disease (CVD). Given the large number of South Asians impacted by CVD and both traditional and non-traditional risk factors for CVD, HF has the potential to become an epidemic among South Asians across the world. Individuals of South Asian origin are at elevated risk for CVD compared to many other populations and should be followed closely for the potential development of HF. This review describes what is unique to South Asian individuals at risk for and with established HF, as well as management and prognostic considerations. Future directions and potential policy changes are highlighted that can reduce the HF burden among South Asians globally.