High-risk Conditions Research Articles

Incidence of Staphylococcus aureus Bacteremia in Patients Following Implantation of Cardiac Implantable Electronic Devices: A Danish Nationwide Cohort Study.

Staphylococcus aureus bacteremia (SAB) is a high-risk condition associated with high morbidity and mortality. In the presence of cardiac implantable electronic devices (CIEDs), SAB may cause or clinically indicate device infection. We aimed to estimate the 10-year absolute risk of SAB in adult Danish first-time CIED carriers. Secondary aims included identification of risk factors associated with SAB. A registry-based study utilizing Danish nationwide registers and including consecutive Danish patients undergoing first CIED implantation between 2000 and 2020 was conducted. The primary outcome was first-time SAB after CIED implantation. A total of 87 257 patients with first CIED implantation in the study period were identified (median age, 75 years; 62.6% were male; median follow-up, 3.8 years). Patients with pacemakers (PMs) were older and with more noncardiovascular comorbidities compared to patients with implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy devices with or without defibrillator capacity (CRTs). In total, 1366 patients (1.6%) developed SAB. The 10-year absolute risk (95% confidence interval) of SAB was 2.0% (1.9%-2.1%) for PM, 2.6% (2.2%-3.1%) for ICD, and 3.7% (3.0%-4.5%) for CRT. A multivariable Cox analysis identified hemodialysis (hazard ratio [HR], 8.51), SAB before CIED (HR, 2.76), liver disease (HR, 2.35), and carrying a CRT device (HR, 1.68) among the covariates associated with increased risk of SAB. The absolute risk of SAB in Danish CIED carriers increased with more advanced CIED systems. The risk was highest within the first 3 months after CIED implantation and increased with the presence of certain covariates including renal dialysis, SAB before CIED, male sex, and advancing age.

Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients

PurposeClinicians consider polypharmacy, comorbidities, and other factors including the potential for drug-drug interactions (DDIs) when evaluating therapeutic options for specific clinical diagnoses. Contemporary treatment for coronavirus disease 2019 (COVID-19) includes direct-acting antivirals (DAAs). We sought to characterize patients’ characteristics, comorbidities, and medications received during their hospitalization for COVID-19 and quantify potential DDIs that clinicians consider in selecting appropriate DAAs. MethodsPatients hospitalized with a primary diagnosis of COVID-19 between May 2020 and December 2022 from the PINC AI Healthcare Database were identified. Medications administered during the hospitalization with the potential to cause DDIs with nirmatrelvir/ritonavir, remdesivir, or molnupiravir (per the Emergency Use Authorization factsheet or package insert) were assessed. For DDIs with nirmatrelvir/ritonavir, medications are categorized as “Contraindicated,” “Avoid Concomitant Use,” or “Other DDIs” (includes recommendation for dose modification or clinical and laboratory monitoring). For remdesivir, coadministration with chloroquine phosphate and hydroxychloroquine sulfate was not recommended. For molnupiravir, no drugs are listed as having potential DDIs. In a subset of patients, a multivariable logistic regression model was used to examine the association between documented patient/hospital characteristics and the likelihood of being “Contraindicated” to receive nirmatrelvir/ritonavir. FindingsOf the 788,238 patients hospitalized for COVID-19 in 920 hospitals, 53% were ≥ 65 years old, and 31% had Charlson Comorbidity Index (CCI) ≥ 3. During the study period, about half of the patients received medications categorized as “Contraindicated” (11%) and/or “Avoid Concomitant Use” (41%) with nirmatrelvir/ritonavir. The frequency of administered drugs was higher in those aged ≥ 65 years (68%), CCI ≥ 3 (78%), with high-risk underlying conditions (55%). About 1% of patients received medications that were not recommended to be coadmistered with remdesivir. Among a subset of patients hospitalized for COVID-19 in 2022, those who were older, had higher CCI, high-risk underlying conditions, severe hepatic impairment, Medicare insurance, and hospitalized in larger hospitals were significantly more likely to be categorized as “Contraindicated” when considering nirmatrelvir/ritonavir as a therapeutic option to manage COVID-19. ImplicationsA significant proportion of patients hospitalized for COVID-19 receive medications for other conditions that have the potential to result in DDIs with DAAs; most predominantly with nirmatrelvir/ritonavir, a strong CYP3A enzyme inhibitor, fewer with remdesivir, and none with molnupiravir. Higher age and comorbidity burden were significantly associated with a higher likelihood of receiving medications that are “Contraindicated” with nirmatrelvir/ritonavir. In the evolving COVID-19 era, these findings provide insights into patients hospitalized for COVID-19, and the polypharmacy evaluations that clinicians may encounter when selecting among DAAs to manage COVID-19.

Returning Incidental Research Findings From 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography to Participants: A Survey of Investigators From a Clinical Trial of Rheumatoid Arthritis.

There are limited data on researchers' attitudes and beliefs on returning and managing incidental research findings from whole body 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG PET/CT) imaging. Site principal investigators (PIs) who enrolled participants for the Treatments Against Rheumatoid Arthritis and Effect on FDG PET/CT (TARGET) trial were surveyed. Of the 28 TARGET site PIs eligible for the study, 18 consented to participate (response rate: 64%). Many site PIs returned incidental findings to participants (61%), and the most common finding that was returned was serious (but not life-threatening) and treatable (54.5%). More than half of the investigators believed that adequacy of clinical follow up (58.8%) and legal liability if incidental findings are not disclosed (55.6%) were extremely important factors in returning incidental research findings from whole body FDG PET/CT. All investigators felt very obligated to return incidental research findings if scans revealed a treatable, high-risk medical condition. Most investigators felt very obligated to disclose incidental findings with important health implications (94.4%), for which proven preventive or therapeutic interventions exist (77.8%), that provide early detection of a health problem (72.2%), if participants ask for their incidental findings (72.2%), and if scans have established validity for a particular medical condition (61.1%). Although it is recommended that researchers report and manage incidental research findings, our data show differing views and uncertainties on what and how to return, and the extent of follow up needed to manage, incidental findings from whole body FDG PET/CT; this highlights the need for more specific and standardized guidance.

Aldo-Keto reductase 1C3 reduces myocardial cell damage after acute myocardial infarction by activating the Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-antioxidant response element pathway to inhibit ferroptosis.

Acute myocardial infarction (AMI) is a high-risk cardiovascular condition associated with increased cellular damage and oxidative stress. Aldo-Keto Reductase 1C3 (AKR1C3) is a stress-regulating gene. Nevertheless, its specific role and mechanisms regarding AMI remain unclear. We assessed cardiac function through echocardiography; tissue damage was evaluated using Hematoxylin and Eosin (HE) and Masson trichrome staining. AKR1C3 expression levels were measured through Reverse transcription-quantitative polymerase chain reaction and western blot. Assessed cell viability using Cell Counting Kit-8 and lactate dehydrogenase (LDH) assays. The extent of ferroptosis was determined by measuring the levels of Fe2+, boron-dipyrromethane (BODIPY) and malondialdehyde (MDA), the glutathione/glutathione disulfide (GSH/GSSG) ratio, and the expression of Glutathione Peroxidase 4 (GPX4) and Solute carrier 7A11 (SLC7A11). Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2-Antioxidant response element (Keap1-Nrf2-ARE) pathway activation was analyzed through western blotting. Nrf2 was inhibited with ML385 and activated with (R)-Sulforaphane to investigate the Keap1-Nrf2-ARE pathway. The rats in the AMI group displayed reduced heart function, more tissue damage, and lower AKR1C3 expression compared to the Sham group. Similarly, hypoxia-treated H9C2 cells showed reduced viability, and decreased AKR1C3 expression. Overexpressing AKR1C3 in H9C2 cells enhanced viability. Knocking down AKR1C3 exhibited the opposite effect. Of the inhibitors tested, Ferrostatin-1 most effectively restored cell viability in hypoxia-treated H9C2 cells. Moreover, H9C2 cells subjected to hypoxia suggested Keap1-Nrf2-ARE pathway inhibition. Overexpressing AKR1C3 reduced ferroptosis and activated the Keap1-Nrf2-ARE pathway in hypoxia-treated cells, knocking down AKR1C3 exhibited the opposite effect. Further experiments using ML385 in hypoxia-treated H9C2 cells with overexpressed AKR1C3 showed decreased viability and increased ferroptosis compared to the control. Using (R)-Sulforaphane in hypoxia-treated H9C2 cells with knocked-down AKR1C3 exhibited the opposite effect. This study's findings indicate that AKR1C3 plays a role in regulating ferroptosis in myocardial cells, with the Keap1-Nrf2-ARE pathway likely being a key mechanism behind it.

Proportion of Patients in the United States Who Fill Their Nirmatrelvir/Ritonavir Prescriptions.

Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking. This retrospective cohort study included individuals aged ≥ 12years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates. A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions. Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5days.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

The Morphometric Analysis of the Ethmoid Roof for Endoscopic Sinus Surgery With Multidetector Computed Tomography.

Most potential major complications in endoscopic sinus surgery are related to the ethmoid bone. To prevent complications, it is necessary to define the concept of a "dangerous ethmoid." The coronal multidetector computed tomography (MDCT) scans of a total of 271 patients, including 101 patients under 18 years old and 170 patients over 18 years old, were examined. For each patient, the depth of the olfactory fossa (DOF), the width of the olfactory fossa (WOF), the angle between the lateral lamella and the cribriform plate (LLCPA), the length of the lateral lamella (LLL), the distance between the nasal floor and the ethmoid roof (NFERL), and the width of the olfactory cleft (WOC) were recorded. The Keros and Gera types were determined. NFERL was found to be significantly higher in males across all age groups. WOC was significantly higher in males only under 18 years old. Only LLCPA was found to be significantly higher on the right side in both sexes. It was determined that NFERL increased with age, while WOC increased with age until 18. Keros type III and Gera type C, which are called dangerous types, were detected in 28 and 24 cases in total, respectively. The data obtained from significant anatomical landmarks in pediatric and adult cases provide useful information about the region in preoperative planning. The analysis results of the prevalence of Keros and Gera classifications allow the identification of high-risk anatomical conditions within the ethmoid.

MYC translocation is a valuable marker for the development and relapse of extramedullary disease in multiple myeloma.

To study the cytogenetic characteristics of extramedullary disease (EMD) in patients with multiple myeloma (MM) and their impact on prognosis. Patients with newly diagnosed MM (NDMM) at Peking Union Medical College Hospital (Beijing, China) between June 2007 and December 2019 were recruited for this study. Demographic information, clinical data, fluorescence in situ hybridization (FISH) results of marrow and tissue samples, and survival outcome data were collected. A total of 439 patients with NDMM were divided into those without EMD (non-EMD, n = 339), those with EMD with primary paraosseous plasmacytoma (pEMD-B, n = 48), those with primary EMD with soft-tissue involvement (pEMD-S, n = 33), and those with secondary EMD (sEMD, n = 19). The incidence of EMD was 18.5% (81/439) at diagnosis and 22.8% (100/439) throughout the disease course. Comparison of FISH results showed a higher proportion of RB1 deletion (n = 20; 60.0% vs. 20.0%, p = .013) and MYC translocation (n = 12; 44.4% vs. 12.5%, p = .041) in the extramedullary tissues than in the paired bone marrow samples. At diagnosis, the percentage of MYC translocations in the sEMD group was notably higher than that in the non-EMD group (55.6% vs. 15.5%, p = .012). The median overall survival (OS) of patients with pEMD-S (32 months) and sEMD (17 months) was significantly shorter (both p = .001) than that of non-EMD patients (60 months). Soft-tissue EMD can be considered a high-risk condition, even in the era of novel agents. MYC translocation can serve as a valuable marker that correlates with extramedullary spread and relapse in patients with MM and should be considered for inclusion in routine FISH panels in clinical practice.

Temporal-spatial-fusion-based risk assessment on the adjacent building during deep excavation

Foundation pit excavation will inevitably cause uneven ground settlement to pose potential risks to adjacent structures and infrastructures. To better perceive the risk status of adjacent buildings using multi-source information, a temporal-spatial-fusion-based risk assessment (TSFRA) model under the consideration of uncertainty and causality is developed by integrating FAHP (Fuzzy Analytic Hierarchy Process), DGDT (DAG-GNN, DEMATEL method, and topological analysis), and CM (cloud model). More specifically, FAHP handles temporal weights of excavation conditions based on expert knowledge. DGDT determines spatial weights for monitoring points, with DAG-GNN constructing causal graphs in a data-driven manner, DEMATEL handling global interactions, and topological analysis calculating node importance. CM can finally fuse the temporal (excavation conditions) and spatial (monitoring points) weights with settlement monitoring data, resulting in qualitative assessments of the overall risk status of adjacent buildings in uncertain environments. The proposed TSFRA is verified in the case of a Shanghai metro station construction project. Results indicate that the perceived risk of the project is at a relatively low level, consistent with the actual condition. High-risk excavation conditions and locations can be easily identified. There is a trend toward higher risk during the excavation of soft soil layers, and thus some risk control measures can be formulated to avoid potential risk events. In short, the weight determination and fusion method in TSFRA contribute to handling uncertainties in expert judgments and causalities in collected data, which can practically provide more reliable decision-making in excavation-induced risk assessment and control for ensuring the safety of adjacent buildings.

Recommendations for Prevention and Control of Influenza in Children, 2024-2025: Policy Statement.

This statement updates the recommendations of the American Academy of Pediatrics for the routine use of influenza vaccines and antiviral medications in the prevention and treatment of influenza in children during the 2024-2025 influenza season. A detailed review of the evidence supporting these recommendations is published in the accompanying technical report (www.pediatrics.org/cgi/doi/10.1542/peds.2024-068508). The American Academy of Pediatrics recommends annual influenza vaccination of all children without medical contraindications starting at 6 months of age. Children are at risk for hospitalization and death from influenza. Influenza vaccination is an important strategy for protecting children and the broader community as well as reducing the overall burden of respiratory illnesses when other viruses are cocirculating. Any licensed influenza vaccine appropriate for age and health status can be administered, ideally as soon as possible in the season, without preference for one product or formulation over another. All licensed influenza vaccines for use in the United States are trivalent for the 2024-2025 influenza season. Antiviral treatment of influenza is recommended for children with suspected (eg, influenza-like illness [fever with either cough or sore throat]) or confirmed influenza who are hospitalized or have severe or progressive disease or have underlying conditions that increase their risk of complications of influenza, regardless of duration of illness. Antiviral treatment should be initiated as soon as possible. Antiviral treatment may be considered in the outpatient setting for symptomatic children who are not at high risk for influenza complications with suspected or confirmed influenza disease, if treatment can be initiated within 48 hours of illness onset. Antiviral treatment may also be considered for children with suspected or confirmed influenza disease whose siblings or household contacts either are younger than 6 months or have a high-risk condition that predisposes them to complications of influenza. Antiviral chemoprophylaxis is recommended for the prevention of influenza virus infection as an adjunct to vaccination in certain individuals, especially exposed children who are asymptomatic and are at high risk for influenza complications but have not yet been immunized or those who are not expected to mount an effective immune response.

Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: Risk Management and Surveillance Strategies.

Background and aims: Hereditary colorectal cancer syndromes (HCCS), including familial adenomatous polyposis (FAP) and Lynch syndrome (LS), are the two most important high-risk conditions for colorectal cancer (CRC). Inflammatory bowel disease (IBD) increases the risk by two to six times compared with that in the general population. The intersection of these two conditions has rarely been documented in literature. We aimed to summarize the prevalence, pathogenesis, and current evidence-based management of IBD and HCCS and the underlying molecular mechanisms of accelerated carcinogenesis due to combined inflammation and genetic predisposition. Methods: PubMed and Scopus were searched until June 2024 to identify relevant studies investigating the epidemiology, pathogenesis, and management of IBD and coexisting hereditary CRC syndromes. Results: Co-occurrence of IBD and hereditary CRC syndromes is exceptionally uncommon. Individuals with LS and IBD tend to develop CRC at a younger age than those without IBD, with patients with ulcerative colitis facing particularly elevated risks. The interaction between mismatch deficiency and chronic inflammation requires further investigation.

The use of reduced DOAC doses in atrial fibrillation patients does not always lead to good anticoagulation levels and avoid adverse events

BackgroundThe MAS study (Blood Advances 2024) showed that a high proportion of Italian AF patients treated with direct oral anticoagulants (DOACs) receive reduced doses. This sub-analysis of MAS data aimed to analyze the effects of reduced (appropriate or not)- or standard-dose use on DOAC activity assessed at baseline and the occurrence of thrombotic or bleeding complications during follow-up. MethodsThe MAS study design, the methods for DOAC measurement, the results, and the adverse events during follow-up, are described in detail elsewhere. ResultsSeven hundred AF patients (42 % of the total 1657) received a reduced dose (considered inappropriate in 140 [20 %]). They were older, more frequently women, with lower body mass index (BMI), hemoglobin levels, and creatinine clearance. They more often had cerebral or cardiovascular diseases, were taking more medications, with higher scores for thrombotic or bleeding risk. Despite the use of low doses, 133 (19.0 %) patients had high standardized C-trough DOAC levels and experienced a high proportion of bleeding events (8.3 % per year). Conversely, some patients (4.7 %) had very low levels, resulting in a high incidence of thrombotic events (6.7 % per year). No difference was detected if the reduced dose was appropriate or not. ConclusionThe unpredictable, highly variable inter-individual anticoagulant effect of DOACs may lead to either too low or too high anticoagulant levels, increasing the risk of thrombotic or bleeding events. This is particularly relevant for patients with high-risk conditions, such as those chosen for reduced-dose treatment. Further studies are needed to investigate this important clinical issue.

Efficacy of systemic Chemotherapy on high-risk stage II and III Mucnious colon cancer. CHEMUCCA study part I

BackgroundLocally advanced colon cancer is a high-risk condition for tumour recurrence with poor survival. The current treatment is surgery followed by adjuvant chemotherapy based on fluoropyrimidines and oxaliplatin. This approach has improved the oncological outcomes on this population, however the mucinous condition has not been studied in depth and although the evidence is weak, it is thought to have a worse response to systemic chemotherapy. The CHEMUCCA study aims to answer this question. ObjectiveTo evaluate the effectiveness of adjuvant systemic chemotherapy using the disease-free survival for stage II and III mucinous colon cancer who underwent surgical resection plus systemic adjuvant chemotherapy vs. surgery alone. Patients and methodsRetrospective analytical study including patients diagnosed with high-risk stage II and stage III colon cancer, treated between 2010 and 2021, with a minimum follow-up of 3 years. Demographic variables and tumour features were analysed. The primary endpoint was disease-free survival. Log rank test and Cox regression were used. ResultsOf 1134 patients with high-risk stage II and III colon cancer disease, 206 (18,17 %) had mucinous histology and 928 (81,83 %) had non-mucinous histology. 708 patients who received adjuvant chemotherapy, 129 (62,62 %) in mucinous group and 579 (62,39 %) in the non-mucinous group. Adjuvant systemic chemotherapy in stage II and III mucinous colon cancer improved the DFS (HR = 0.58 [95 % CI 0.37−0.91]; p = 0,017). However, in a stratified analysis, patients with high-risk stage II mucinous colon cancer showed no benefit with this approach (HR = 0.4541 [95 % CI 0.19−1.03]; p = 0.06). ConclusionAdjuvant chemotherapy has demonstrated to be effective in locally advanced mucinous colorectal cancer improving the oncological outcomes. However, this benefit could be diminished in high-risk stage II mucinous colon cancer patients. The administration of adjuvant chemotherapy on this patient's sub-group must be balanced according to risk versus benefits.

2023 International Evidence-Based Polycystic Ovary Syndrome Guideline Update: Insights From a Systematic Review and Meta-Analysis on Elevated Clinical Cardiovascular Disease in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta-analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence-Based PCOS Guideline. A systematic review and meta-analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26-2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07-2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43-4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20-2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53-2.69]; I2 = 0%). Meta-analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity. This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence-Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high-risk condition.

Severe hyperlactatemia in the emergency department: clinical characteristics, etiology and mortality

BackgroundSevere hyperlactatemia (lactate level ≥ 10 mmol/L) is associated with high mortality rates in critically ill patients. However, there is limited data on emergency department (ED) patients. We aimed to investigate the clinical characteristics, etiology and outcomes of patients with severe hyperlactatemia in the ED setting.MethodsA retrospective cohort study was conducted at a tertiary care hospital in Thailand. We included adult patients with a venous lactate sample taken in the ED within one hour. We excluded patients after out-of-hospital cardiac arrest, transferred to/from another hospital or those with missing clinical data. Mortality rates were evaluated among patients with increasing degrees of lactate elevation and among patients with severe hyperlactatemia, stratified by causative etiology.ResultsWe analyzed venous lactate levels in 40,047 patients, with 26,680 included in the analysis. Among these, 1.7% had severe hyperlactatemia (lactate ≥ 10 mmol/L), 10.5% moderate (4–9.99 mmol/L), 28.8% mild (2—3.99 mmol/L), and 59.0% normal levels (< 2 mmol/L). Severe hyperlactatemia was associated with high mortality rates of 29%, 37%, and 38% at 7, 28, and 60 days respectively, significant ICU admissions and mechanical ventilation rates. Patients with severe hyperlactatemia were stratified into high (> 50% mortality), moderate (21–50%), and low (< 20%) 28-day mortality risk groups. High-risk conditions included non-septic shock, traumatic injuries/burns, and neurological issues, with mortality rates of 51.1%, 61.8%, and 57.1%, respectively. In the moderate risk group, namely infection without shock showed a high prevalence, with a mortality rate of 36%. In the low-risk group, seizures and fainting were associated with lower mortality, exhibiting mortality rates of 0%.ConclusionsSevere hyperlactatemia is associated with higher rates of ICU admission and mortality compared to other degrees of lactate elevation in a general ED population. However, mortality rates can vary considerably, depending on the underlying etiology associated with different primary diagnoses.

Radiomic study of antenatal prediction of severe placenta accreta spectrum from MRI.

We previously demonstrated the potential of radiomics for the prediction of severe histological placenta accreta spectrum (PAS) subtypes using T2-weighted MRI. We aim to validate our model using an additional dataset. Secondly, we explore whether the performance is improved using a new approach to develop a new multivariate radiomics model. Multi-centre retrospective analysis was conducted between 2018 and 2023. Inclusion criteria: MRI performed for suspicion of PAS from ultrasound, clinical findings of PAS at laparotomy and/or histopathological confirmation. Radiomic features were extracted from T2-weighted MRI. The previous multivariate model was validated. Secondly, a 5-radiomic feature random forest classifier was selected from a randomized feature selection scheme to predict invasive placenta increta PAS cases. Prediction performance was assessed based on several metrics including area under the curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity, and specificity. We present 100 women [mean age 34.6 (±3.9) with PAS], 64 of whom had placenta increta. Firstly, we validated the previous multivariate model and found that a support vector machine classifier had a sensitivity of 0.620 (95% CI: 0.068; 1.0), specificity of 0.619 (95% CI: 0.059; 1.0), an AUC of 0.671 (95% CI: 0.440; 0.922), and accuracy of 0.602 (95% CI: 0.353; 0.817) for predicting placenta increta. From the new multivariate model, the best 5-feature subset was selected via the random subset feature selection scheme comprised of 4 radiomic features and 1 clinical variable (number of previous caesareans). This clinical-radiomic model achieved an AUC of 0.713 (95% CI: 0.551; 0.854), accuracy of 0.695 (95% CI 0.563; 0.793), sensitivity of 0.843 (95% CI 0.682; 0.990), and specificity of 0.447 (95% CI 0.167; 0.667). We validated our previous model and present a new multivariate radiomic model for the prediction of severe placenta increta from a well-defined, cohort of PAS cases. Radiomic features demonstrate good predictive potential for identifying placenta increta. This suggests radiomics may be a useful adjunct to clinicians caring for women with this high-risk pregnancy condition.

Myasthenia gravis in pregnancy: Successful outcome with multidisciplinary management

Myasthenia gravis (MG) is a rare autoimmune disorder characterized by nicotinic acetylcholine receptor autoantibodies, affecting the neuromuscular transmission leading to progressive weakness. MG during pregnancy is a high-risk condition that may affect both the mother and the fetus leading to adverse perinatal outcomes. We are presenting clinical course of two pregnant women, one of them was already diagnosed case of MG and second was diagnosed during postpartum period while waiting for discharge of baby. Literature review of the previously published cases and their management is also presented.

Home and Community-Based Services: A Systematic Review and Evidence Map.

Many adults aged 60years or older have functional limitations and require home and community-based services (HCBS) to support their independence and delay the transition to an institutionalized setting. This systematic review provides an evidence map of the existing literature on HCBS identifying evidence gaps for policy and research. A comprehensive literature search of multiple databases including Medline, Embase, and Scopus was conducted through December 7, 2023. Interviews with various stakeholders were conducted to solicit additional perspectives. Narrative and thematic synthesis was conducted to evaluate HCBS in terms of populations, interventions, outcomes, person-centeredness, and relevant quality measures. We identified 27 primary studies and 29 quality measures. Populations of HCBS studies can be categorized as those with functional disability, cognitive impairment, high-risk/frail conditions, and disease-specific conditions (Parkinson's disease, Alzheimer's disease, and post-stroke). HCBS interventions targeted optimization of person-centered planning, nonpharmacological approaches for dementia care, physical rehabilitation, self-directed home care, geriatric resources for practical support at home, and interdisciplinary care coordination for high-risk conditions. Person-centered planning and self-direction of HCBS services were not explicitly described in many studies and very few studies focused on addressing health-related social needs, whereas the majority reported primary clinical outcomes. Numerous quality measures exist for HCBS, some of which were validated, addressed multiple person-centered domains, and may apply across various conditions and populations. Key challenges in the literature on HCBS include limited numberof randomized trials, inadequate descriptions of interventions to determine person-centeredness, limited information on facilitators and barriers, and limited information on workforce challenges in recruiting, retaining, and training personnel delivering HCBS. This evidence map describes the current state of HCBS and identifies evidence gaps for future research and policy decisions.

Seasonal Patterns of Injury Characteristics Among Farmers and Ranchers in the U.S. Central States

ABSTRACT Objective In high-risk agricultural environments, tasks, weather, and work conditions vary throughout the year. Also, injuries peak during certain periods. The primary objective of this study was to examine operator- and farm-level characteristics as risk factors for injuries within each of the four seasons. The secondary objective was to examine seasonal differences in the incident location and primary cause of these injuries. Method We analyzed data from the 2018 and 2020 Farm and Ranch Health and Safety Surveys (FRHSS), conducted in seven U.S. states by the Central States Center for Agricultural Safety and Health (CS-CASH), which were collected using a stratified random sampling approach to ensure representativeness. The survey data were merged with operation-level data from the Farm Market iD database. We employed Generalized Estimating Equations (GEE) to examine the association of seasonal injuries with individual and operation-level characteristics. The chi-square test of independence was used to assess the association between injury incident location and season, as well as injury cause and season. Pairwise Z-tests of proportions were conducted to evaluate the differences in the proportions of injuries due to specific combinations of injury location and cause across each pair of seasons. Results Surveys conducted in 2018 and 2020 yielded a combined response rate of 15.9%, with 5,428 responses and 7,915 unique operators. Of these, 903 operators reported at least one injury during the past 12 months. Seasonally, most injuries occurred in spring (34.2%), followed by summer (24.7%). Male operators had higher injury odds in the spring (adjusted OR = 1.42) and summer (aOR = 2.41). Those managing both a farm and a ranch reported increased injury risks in winter (aOR = 1.73) and spring (aOR = 1.48). Operators in cow-calf operations faced higher springtime injury risks (aOR = 1.45). High stress and exhaustion were consistent risk factors across all seasons. The highest proportion of injury incidents occurred in the farmyard (43.6%), and livestock were the most common cause of injury (24.9%). Conclusion Results highlight the need for season-specific prevention and intervention strategies, considering farmers’ and ranchers’ risk characteristics, injury locations, and causes. These findings can inform targeted measures for high-risk populations at optimal times and locations.