Navigating High-Risk and Ultrahigh-Risk Multiple Myeloma: Challenges and Emerging Strategies.

Despite significant improvement in the outcomes of patients with newly diagnosed multiple myeloma (NDMM) with novel therapies, there is still an underserved high-risk (HR) population that experiences early disease progression and death. With the median survival crossing 10 years, we defined ultrahigh-risk (uHR)MM as MM leading to death within 24-36 months of diagnosis and HRMM as MM leading to death within 36-60 months. Several features have emerged as markers of uHRMM: the co-occurrence of two or more high-risk cytogenetic abnormalities, extramedullary disease, plasma cell leukemia and a high-risk gene expression profiling signature. The heterogeneous risk definition across trials, the few trials available designed for HR patients, and the small HR subgroups in all-comers trials make it difficult to generate recommendations with high levels of evidence. Nevertheless, regardless of treatment administered, several studies consistently showed that achieving and maintaining measurable residual disease negativity is now considered the main factor able to mitigate the adverse prognosis related to baseline features. For fit patients with HR transplant-eligible (TE) NDMM, quadruplet induction/consolidation treatment with anti-CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors and dexamethasone, and autologous stem-cell transplant and maintenance with, if available, at least a doublet combination could be considered the option of choice. For non-TE NDMM, considering the recent data generated and carefully reviewing those upcoming, quadruplet treatment consisting of anti-CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors, and dexamethasone should also be considered. Future trials integrating BCMA-directed novel generation immunotherapies hold great potential for further advancing the treatment landscape in all NDMM patients with HR disease.

A method for determining groups in cumulative incidence curves in competing risk data.

The cumulative incidence function is the standard method for estimating the marginal probability of a given event in the presence of competing risks. One basic but important goal in the analysis of competing risk data is the comparison of these curves, for which limited literature exists. We proposed a new procedure that lets us not only test the equality of these curves but also group them if they are not equal. The proposed method allows determining the composition of the groups as well as an automatic selection of their number. Simulation studies show the good numerical behavior of the proposed methods for finite sample size. The applicability of the proposed method is illustrated using real data.

The association between alcohol consumption and pulmonary function: a scoping review.

INTRODUCTION: The health effects of alcohol are well established but the influence on pulmonary function remains debated. Studies indicate that small amounts of alcohol are beneficial and heavy consumption is harmful, suggesting a U-shaped association. Our objective is to determine whether there is an association between alcohol intake and changes in pulmonary function parameters, exploring the potential protective effect of moderate alcohol consumption and the harm caused by heavy drinking. METHODS: A comprehensive search from PubMed, Embase, Cochrane and CINAHL was carried out, and studies were evaluated using the JBI methodological framework for scoping reviews. Two independent reviewers conducted parallel screening and data extraction. A data extraction form was utilised to organise key themes, with qualitative analysis and visual representation of the results. RESULTS: Among 4427 screened abstracts, 179 underwent full-text review, resulting in 30 eligible studies. Of these, 10 showed a negative effect, nine reported no impact, nine exhibited a positive effect and two indicated a nonlinear U-shaped association between alcohol consumption and pulmonary function parameters. CONCLUSION: While the U-shaped curve hypothesis remains unconfirmed by the current literature, there are notable associations. Heavy alcohol consumption appears to negatively affect pulmonary function, while low to moderate intake shows a positive influence in included studies. However, the diversity in study quality, the nonstandardised alcohol intake quantification and the confounding role of smoking challenge definitive conclusions. The need for consistent, long-term international studies is evident to further explore this relationship while addressing the complex interplay between alcohol and smoking.

Evaluation of urban flood susceptibility through integrated Bivariate statistics and Geospatial technology.

Flood disasters are frequent natural disasters that occur annually during the monsoon season and significantly impact urban areas. This area is characterized by impermeable concrete surfaces, which increase runoff and are particularly susceptible to flooding. Therefore, this study aims to adopt Bi-variate statistical methods such as frequency ratio (FR) and weight of evidence (WOE) to map flood susceptibility in an urbanized watershed. The study area encompasses an urbanized watershed surrounding the Chennai Metropolitan area in southern India. The essential parameters considered for flood susceptibility zonation include geomorphology, soil, land use/land cover (LU/LC), rainfall, drainage, slope, aspect, Topographic Wetness Index (TWI), and Normalized Difference Vegetation Index (NDVI). The flood susceptibility map was derived using 70% of randomly selected flood areas from the flood inventory database, and the other 30% was used for validation using the area under curve (AUC) method. The AUC method produced a frequency ratio of 0.806 and a weight of evidence value of 0.865 contributing to the zonation of the three classes. The study further investigates the impact of urbanization on flood susceptibility and is further classified into high, moderate, and low flood risk zones. With the abrupt change in climatic scenarios, there is an increase in the risk of flash floods. The results of this study can be used by policymakers and planners in developing a preparedness system to mitigate economic, human, and property losses due to floods in any urbanized watershed.

Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

How to Define and Manage Low-Risk Drug Allergy Labels.

Risk stratification in drug allergy implies that specific risk categories (eg, low, moderate, and high) classify historical drug hypersensitivity reactions. These risk categories can be based on reaction phenotypic characteristics, the timing of the reaction and evaluation, the required reaction management, and individual characteristics. Although a multitude of frameworks have been described in the literature, particularly for penicillin allergy labels, there has yet to be a global consensus, and approaches continue to vary between allergy centers. Immune-mediated drug allergies can sometimes be confirmed using skin testing, but a negative drug challenge is required to demonstrate tolerance and remove the allergy from the electronic health record ("delabel" the allergy). Even for quintessential IgE-mediated drug allergy, penicillin allergy, recent data reveal that a direct oral challenge, without prior skin testing, is an appropriate diagnostic strategy in those who are considered low-risk. Drug allergy pathogenesis and clinical manifestations may vary depending on the culprit drug, and as such, the optimal approach should be based on risk stratification that considers individual patient and reaction characteristics, the likely hypersensitivity reaction phenotype, the drug class, and the patient's clinical needs. This article will describe low-risk drug allergy labels, focusing on ß-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs, iodinated contrast media, and common chemotherapeutics. This review will also address practical management approaches using currently available risk stratification and clinical decision tools.

Human exposure to formaldehyde and health risk assessment: a 46-year systematic literature review.

After confirming that formaldehyde (FA) is carcinogenic, many studies were conducted in different countries to investigate this finding. Therefore, according to the dispersion of related studies, a bibliometric review of the current literature was performed with the aim of better understanding the exposure to FA and the resulting health risk, for the first time, using the Scopus database and the two open-source software packages, Bibliometrix R package. After screening the documents in Excel, the data was analyzed based on three aspects including performance analysis, conceptual structure, and intellectual structure, and the results were presented in tables and diagrams. A total of 468 documents were analyzed over period 1977-2023, in which 1956 authors from 56 countries participated. The number of scientific publications has grown significantly from 1977 (n = 1) to 2022 (n = 19). Zhang Y., from the Yale School of Public Health (USA), was identified as the most impactful author in this field. The Science of the Total Environment journal was identified as the main source of articles related to exposure to formaldehyde by publishing 25 studies. The United States and China were the most active countries with the most international collaboration. The main topics investigated during these 46 years included "formaldehyde" and "health risk assessment", which have taken new directions in recent years with the emergence of the keyword "asthma". The present study provides a comprehensive view of the growth and evolution of studies related to formaldehyde and the resulting health risks, which can provide a better understanding of existing research gaps and new and emerging issues.

Risk of Head and Neck Cancer in Patients with Psoriasis: A Nationwide Population-based Study.

An association between psoriasis and cancer risk has been suggested in prior studies, but few have focused on head and neck cancers. Using the Korean National Health Insurance Service database, the relevance between psoriasis and head and neck cancer risks was investigated in a cross-sectional study of 3,869,264 individuals over 20 years of age, who received general health examination in 2009 and were followed until 2020. Head and neck cancer incidence rates were compared between individuals with and without psoriasis, and contributing factors were analysed. The head and neck cancer risk was significantly increased in the psoriasis group compared with the non-psoriasis group (hazard ratio [HR] 1.36; 95% confidence interval [CI] 1.07-1.74; p = 0.01) after adjusting for age, sex, body mass index, income, smoking, alcohol, exercise, diabetes mellitus, hypertension and dyslipidaemia. The risk was especially elevated for nasopharyngeal (HR 2.04; 95% CI 1.12-3.70; p = 0.02) and salivary gland cancer (HR 1.96; 95% CI 1.08-3.56; p = 0.03). Alcohol consumption significantly influenced the risk, particularly for oropharyngeal and oral cavity cancer. Our study provides insights into the potential risks of head and neck cancer in patients with psoriasis, which could aid in refining patient management strategies.

Association between pulse pressure and carotid plaques in old adults with uncontrolled hypertension: results from a community-based screening in Hangzhou, China.

BACKGROUND: There is a broad pulse pressure (PP) and a high prevalence of carotid plaques in old adults. Previous studies have indicated that PP is strongly associated with carotid plaque formation. This study aimed to explore this association in old adults with uncontrolled hypertension. METHODS: 1371 hypertensive patients aged ≥ 60 years with uncontrolled hypertension were enrolled in a community-based screening in Hangzhou, China. Carotid plaques were assessed using ultrasonography. Logistic regression models were used to estimate the association between PP and carotid plaques by odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Carotid plaques were detected in 639 (46.6%) of subjects. Multiple plaques were found in 408 (63.8%) and soft plaques in 218 (34.1%). Elevated PP was associated with a high prevalence of carotid plaques. After adjusting for traditional risk factors, compared to patients within the lowest tertile of PP, those within the highest tertiles had an increased risk of carotid plaques (OR 2.061, CI 1.547-2.745). For each 1-SD increase, the risk increased by 40.1% (OR 1.401, CI 1.237-1.587). There was a nonlinear association between PP and carotid plaques (P nonlinearity = 0.039). The risk increased rapidly after the predicted PP level reached around 60 mmHg. The associations were stronger among participants with multiple and soft plaques. CONCLUSIONS: Our findings suggested that PP was independently associated with carotid plaques in old adults with uncontrolled hypertension who have an increased risk of atherosclerosis.

Predicting Pulmonary Embolism in Total Joint Arthroplasty Patients A Pilot Study.

Postoperative venous thromboembolism (VTE) is a common and costly complication following total joint arthroplasty (TJA). Development of a refined thrombophilic screening panel will better equip clinicians to identify patients at high-est risk for developing VTEs. In this pilot study, 62 high-risk TJA recipients who had developed pulmonary emboli (PE) within 90-days of surgery were eligible to participate. Of these patients, 14 were enrolled and subsequently adminis-tered a pre-determined panel of 18 hematologic tests with the aim of identifying markers that are consistently elevated or deficient in patients developing PE. A separate cohort of seven high-risk TJA recipients who did not report a symp-tomatic VTE within 90-days of surgery were then enrolled and Factor VIII and lipoprotein(a) levels were assessed. The most common aberrance was noted in 10 patients (71.4%) who had elevated levels of Factor VIII followed by five patients (35.7%) who had elevated levels of lipoprotein(a). Factor VIII was significantly prevalent (p < 0.001) while lipoprotein(a) failed to achieve statistical significance (p = 0.0708). Of the patients who were within normal limits of Factor VIII, three-fourths were "high-normal" with Fac-tor VIII levels within 5% of the upper limit of normal. This study demonstrates the potential utility of this hematologic panel as part of a perioperative screening protocol aimed at identifying patients at risk for developing VTEs. However, future larger scale studies assessing the capabilities and limitations of our findings are warranted.

Verbal Probability Terms for Communicating Clinical Risk - a Systematic Review.

Verbal probability expressions such as 'likely' and 'possible' are commonly used to communicate uncertainty in diagnosis, treatment effectiveness as well as the risk of adverse events. Probability terms that are interpreted consistently can be used to standardize risk communication. A systematic review was conducted. Research studies that evaluated numeric meanings of probability terms were reviewed. Terms with consistent numeric interpretation across studies were selected and were used to construct a Visual Risk Scale. Five probability terms showed reliable interpretation by laypersons and healthcare professionals in empirical studies. 'Very Likely' was interpreted as 90% chance (range 80 to 95%); 'Likely/Probable,' 70% (60 to 80%); 'Possible,' 40% (30 to 60%); 'Unlikely,' 20% (10 to 30%); and 'Very Unlikely' with 10% chance (5% to 15%). The corresponding frequency terms were: Very Frequently, Frequently, Often, Infrequently, and Rarely, respectively. Probability terms should be presented with their corresponding numeric ranges during discussions with patients. Numeric values should be presented as X-in-100 natural frequency statements, even for low values; and not as percentages, X-in-1000, X-in-Y, odds, fractions, 1-in-X, or as number needed to treat (NNT). A Visual Risk Scale was developed for use in clinical shared decision making.

Medicare Advantage Health Risk Assessments Contribute Up To $12 Billion Per Year To Risk-Adjusted Payments.

With Medicare Advantage (MA) enrollment surpassing 50 percent of Medicare beneficiaries, accurate risk-adjusted plan payment rates are essential. However, artificially exaggerated coding intensity, where plans seek to enhance measured health risk through the addition or inflation of diagnoses, may threaten payment rate integrity. One factor that may play a role in escalating coding intensity is health risk assessments (HRAs)-typically in-home reviews of enrollees' health status-that enable plans to capture information about their enrollees. In this study, we evaluated the impact of HRAs on Hierarchical Condition Categories (HCC) risk scores, variation in this impact across contracts, and the aggregate payment impact of HRAs, using 2019 MA encounter data. We found that 44.4 percent of MA beneficiaries had at least one HRA. Among those with at least one HRA, HCC scores increased by 12.8 percent, on average, as a result of HRAs. More than one in five enrollees had at least one additional HRA-captured diagnosis, which raised their HCC score. Potential scenarios restricting the risk-score impact of HRAs correspond with $4.5-$12.3 billion in reduced Medicare spending in 2020. Addressing increased coding intensity due to HRAs will improve the value of Medicare spending and ensure appropriate payment in the MA program.

Pollution, spatial distribution, and health risks assessment of nutrient concentration in surface water resources of Maroon-Jarahi Basin in southwestern Iran.

Nowadays, the introduction of nutrients caused by human activities is considered an environmental issue and a significant problem in river basins and coastal ecosystems. In this study, the concentration of nutrients ( NO 3 - and PO 4 3 - ) in the surface water sources of the Maroon-Jarahi watershed in the southwest of Iran was determined, and the pollution status and health risk assessment were done. The average concentration of nitrate and phosphate in Ludab, Maroon, Zard, Allah, Jarahi rivers, and Shadegan wetland were obtained at 2.25-0.59, 4.59-1.84, 4.07-2.02, 5.40-2.81, 11.51-4.67, 21.63 and 6.20 (mg/l), respectively. A comparison of the results with the World Health Organization (WHO) limit showed that nitrate was lower than in all stations, but phosphate was higher than the limit in some stations of the Maroon, Allah, Jarahi rivers, and Shadegan wetland. Calculation of linear regression analysis showed significant positive relationships between nitrate and phosphate in all surface water sources (except Ludab) and based on the N/P ratio, nitrogen was estimated as the limiting factor in phytoplankton growth (N/P < 16). The evaluation of the status of the Nutrient pollution index (NPI) was observed as: Shadegan > Jarahi > Allah > Maroon > Zard > Ludab that the Jarahi River and Shadegan wetland were in the medium pollution class (1 < NPI ≤ 3) and other waterbodies were in the non-polluted to low pollution state (NPI < 1). Calculation of the chronic daily intake (CDI) showed that water body nutrients cause more non-carcinogenic health risks through the oral route than dermal exposure, and according to HI, children's health is more at risk than adults. Findings showed that surface water resources especially downstream of the Maroon-Jarahi watershed are at eutrophication risk, and to control the nearby human activities and as a result increase the nutrients in these water resources, measures should be taken.

Framework development for the physical vulnerability assessment index of hand-dug Wells in Are-Ekiti, Southwestern Nigeria.

The article presents a comprehensive framework for assessing the physical vulnerability of hand-dug wells within the Are Community, Southwestern Nigeria. The study spans from March to April 2023 and meticulously examines 90 wells, focusing on critical parameters such as well collar, well cover, and well lining information. The analysis reveals significant variations in well collar construction materials and dimensions, emphasizing the community's adaptive strategies. The Well Collar Height Index (WCi), Well Cover Index (WCOi), Well Lining Index (WLi), and the derived Vulnerability Index categorize wells into vulnerability classes, offering a nuanced understanding of susceptibility levels. Notably, the study identifies wells with Very High vulnerability that demand urgent attention, as well as wells with effective protective measures categorized as Very Low vulnerability. The article emphasizes the need for a nuanced understanding of local practices and materials, highlighting the variability in well collar construction. It discusses the implications of well cover conditions and the critical role of well linings in assessing groundwater vulnerability. The Vulnerability Index combines these parameters, guiding targeted interventions based on risk severity. The study lays the groundwork for future interventions to enhance the safety and sustainability of water sources within the Are Community. It recommends immediate comprehensive measures for highly vulnerable wells, ongoing monitoring, community engagement, and knowledge sharing. The future scope includes incorporating geochemical analysis, targeted interventions, regular maintenance, community training, and exploring alternative water sources for sustainable improvements.

Pediatric psychoSocial Risk Index: Factor Analysis and Item Reduction Study.

OBJECTIVES: The Pediatric psychoSocial Risk Index (PSRI) is psychosocial risk screening instrument for health practitioners. The objective of this study was to confirm validity evidence of a truncated version of PSRI. METHODS: PSRI was completed initially by 100 parents of children aged 0 to 18 years admitted to a tertiary hospital; 50 parents repeated the PSRI 3 days later. Analysis includes principal component analysis (PCA) to include the least number of items that explain the most variance in a shortened version of PSRI as well as confirming test-retest reliability and internal consistency of the shortened instrument. RESULTS: PSRI originally had 86 items, 85 close-ended items were analyzed. Three items were excluded because of missing test-retest data. Item reduction resulted in truncation of 16 items; 66 items remained. A Kaiser-Mayer-Orkin test of sampling adequacy resulted in reduction of 14 items; 52 items remained. Initial PCA led to reduction of 26 items. The PCA was rerun on remaining items, resulting in reduction of 6 further items; 18 items remained. Two items with >10% missingness were removed leaving 16 items in the final PSRI. Test-retest reliability was 0.98 and mean within-person across-item reliability was 0.95. Cronbach α was 0.9. Remaining items represented 9 social risk themes: food insecurity, medical complexity, home environment, behavioral issues, financial insecurity, parenting confidence, parental mental health, social support, and unmet medical needs. CONCLUSIONS: PSRI was reduced from 86 to 16 items with high internal consistency and reliability. PSRI demonstrates adequate validity supporting practitioners to screen families about their psychosocial risk.

Atmospheric gaseous mercury and associated health risk assessment in the economic capital of India.

Mercury cycling in coastal metropolitan areas on the west coast of India becomes complex due to the combined effects of both intensive domestic anthropogenic emissions and marine air masses. The present study is based on yearlong data of continuous measurements of gaseous elemental mercury (GEM) concentration concurrent with meteorological parameters and some air pollutants at a coastal urban site in Mumbai, on the west coast of India, for the first time. The concentration of GEM was found in a range between 2.2 and 12.3 ng/m3, with a mean of 3.1 ± 1.1 ng/m3, which was significantly higher than the continental background values in the Northern Hemisphere (~ 1.5 ng/m3). Unlike particulates, GEM starts increasing post-winter to peak during the monsoon and decrease towards winter. July had the highest concentration of GEM followed by October, and a minimum in January. GEM exhibited a distinct diurnal cycle, mainly with a broad peak in the early morning, a narrow one by nightfall, and a minimum in the afternoon. The peaks and their timing suggest the origin of urban mobility and the start of local activities. A positive correlation between SO2, PM2.5, temperature, relative humidity, and GEM indicates that emissions from local industrial plants in the Mumbai coastal area. Principal component analysis (PCA) and cluster analysis (CA) confirm this fact. Monthly back trajectory analysis showed that air mass flows are predominantly from the Arabian Sea and local human activities. Assessment of human health risks by USEPA model reveals that the hazardous quotient, HQ < 1, implies negligible carcinogenic risk. GEM observations in Mumbai during the study period are below the World Health Organization's (WHO) safe limit (200 ng/m3) for long-term inhalation.

Emergency department risk model: timely identification of patients for outpatient care coordination.

OBJECTIVE: Major depressive disorder (MDD) is linked to a 61% increased risk of emergency department (ED) visits and frequent ED usage. Collaborative care management (CoCM) models target MDD treatment in primary care, but how best to prioritize patients for CoCM to prevent frequent ED utilization remains unclear. This study aimed to develop and validate a risk identification model to proactively detect patients with MDD in CoCM at high risk of frequent (≥ 3) ED visits. STUDY DESIGN: This retrospective cohort study utilized electronic health records from Mayo Clinic's primary care system to develop and validate a machine learning-based risk identification model. The model predicts the likelihood of frequent ED visits among patients with MDD within a 12-month period. METHODS: Data were collected from Mayo Clinic's primary care system between May 1, 2006, and December 19, 2018. Risk identification models were developed and validated using machine learning classifiers to estimate frequent ED visit risks over 12 months. The Shapley Additive Explanations model identified variables driving frequent ED visits. RESULTS: The patient population had a mean (SD) age of 39.78 (16.66) years, with 30.3% being male and 6.1% experiencing frequent ED visits. The best-performing algorithm (elastic-net logistic regression) achieved an area under the curve of 0.79 (95% CI, 0.74-0.84), a sensitivity of 0.71 (95% CI, 0.57-0.82), and a specificity of 0.76 (95% CI, 0.64-0.85) in the development data set. In the validation data set, the best-performing algorithm (random forest) achieved an area under the curve of 0.79, a sensitivity of 0.83, and a specificity of 0.61. Significant variables included male gender, prior frequent ED visits, high Patient Health Questionnaire-9 score, low education level, unemployment, and use of multiple medications. CONCLUSIONS: The risk identification model has potential for clinical application in triaging primary care patients with MDD in CoCM, aiming to reduce future ED utilization.