Multiple Morbidities Research Articles

Traditional Chinese Medicine: An Important Coping Strategy with Challenges of Radiation Injury

People turn nervous when mention is made of radiation injuries, which cause multiple organ morbidities and are difficult to manage. However, the discovery of antiradiation drugs remains challenging. Traditional Chinese medicine (TCM) may be an effective treatment strategy because of its overall regulation. Herein, we systematically review TCM formulae, herbs, and natural products as potential antiradiation candidates. At the same time, we categorize them by their effective characteristics and target organs. In addition, TCM formulae, herbs, and ingredients used to block the absorption and accelerate the excretion of radionuclides are considered in this review. To better manage radiation injuries, the scientific basis of TCM for radioprotection requires further in-depth research.

Medication adherence and quality of life among geriatric patients: Insights from a hospital-based cross-sectional study in India.

Understanding the factors that influence medication adherence and the multidimensional aspects of quality of life in the elderly is of paramount importance in enhancing their overall well-being. Since geriatric patients usually suffer from multiple morbidities due to their declining age, the adherence towards their medications plays a very crucial role in their quality of life. This cross-sectional study explores the intricate relationship between medication adherence and quality of life among 310 elderly patients at a single medical college and hospital. Participants completed the Morisky Medication Adherence Scale (MMAS-8) to assess medication adherence and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire, which comprises four domains (physical health, psychological health, social relationships, and environment) to evaluate quality of life. Statistical analyses, including correlations, paired t-tests, ANOVA, and Backward Multiple Linear Regression, were employed to examine the relationships and differences among variables. The findings indicate varying levels of medication adherence among participants, with a significant proportion exhibiting medium adherence (47.1%) and highlighting the need for interventions to address challenges in medication adherence among the elderly population. Notably, gender emerged as a significant factor influencing quality of life, with males reporting higher satisfaction across all domains compared to females. Medication adherence exhibited a significant correlation with the social relationships domain (DOM3) of the WHOQOL-BREF, underlining the importance of adherence in fostering positive social interactions. Our study revealed a significant association between medication adherence (MMAS- 8) and the quality of life (WHOQOL-BREF) among elderly patients. We also observed noteworthy gender differences in quality-of-life perceptions. It emphasizes the need for tailored interventions that consider medication adherence issues to enhance the overall quality of life among this vulnerable population.

Classification of long-term disease patterns in inflammatory bowel disease and analysis of their associations with adverse health events.

With existing researches identifying an increased rate of long-term conditions (LTCs) among Inflammatory Bowel Disease (IBD) patients, yet there is a lack of exploration into the patterns of comorbidity and prognostic rates for IBD patients with multiple morbidities. The study included 8,305 participants who self-reported having IBD, comprising ulcerative colitis (UC) and Crohn's disease (CD). Latent class analysis (LCA) was utilized to create optimal categories of LTC combinations for UC and CD patients with additional long-term conditions. Using Cox proportional hazards models, we compared the all-cause mortality rates over a 16-year follow-up among UC and CD patients within different LTC categories, both without LTCs and with the addition of one LTC, the probability of major adverse cardiovascular events (MACE), and the rates of IBD-related surgeries. A total of 5,617 participants reported having two or more LTCs, with the LCA method identifying three prevalence categories among CD patients, and four prevalence categories among UC patients. The highest mortality rate among CD patients was found in category 3: (HR 1.789, 95% CI (1.439-2.224)), and the highest rates of MACE were also in category 3: (HR 11.432, 95% CI (9.332-14.005)), with hypertension being the distinguishing characteristic of this category, and the highest rates of IBD-related surgeries being associated with pain in category 1: (HR 1.217, 95% CI (0.983-1.506)). Among UC patients, the highest mortality rate was in category 3: (HR 2.221, 95% CI (1.837-2.684)), with the highest MACE rates found in category 3: (HR 6.422, 95% CI (5.659-7.288)), and the highest rates of IBD-related surgeries being associated with pain, also in category 3: (HR 1.218, 95% CI (1.041-1.425)). The rates of adverse health outcomes in IBD patients is closely associated with multimorbidity patterns, underscoring the need to fully consider multimorbidity patterns in the assessment, management, and treatment strategies for IBD.

Socio-Economic Determinants of the Physical Activity Intensity in Russia

The study examines the socioeconomic, demographic and health determinants of physical activity intensity in Russia. Using RLMS-HSE (the Russia Longitudinal Monitoring Survey – Higher School of Economics) data for 2021 and indicators of six levels of physical activity intensity, the authors built ordered probit models and calculated average marginal effects for a set of covariates. The independent variables were selected based on the SLOTH microeconomic model describing individual preferences towards physical activity.The ordered probit regression provided empirical support for Meltzer and Jena's theoretical framework, stating that as income increases, with the pronounced substitution effect, the time spent on physical activity decreases, and the intensity of physical activity rises. In our study, the thesis about an increase in intensity with rising income was confirmed for a subsample of men but not women. For women, the intensity was determined by factors such as multiple morbidity and residing outside of Moscow or Saint Petersburg, which were not significant in the regressions for men.The study resulted in several important conclusions. The intensity analysis showed that physician recommendations regarding the type of physical activity should consider patients' workload. For individuals with a busy schedule, recommended types of exercise that require a long time (for example, walking) are not suitable. At the same time, intense workouts (such as tennis or gym classes) can be built into the schedule. There is a need to develop sports infrastructure at workplaces, allowing individuals to allocate time for classes without bearing additional time and monetary costs associated with travel to the location of workouts. As income increases, exercising near the workplace allows an individual to increase the intensity of physical activity without incurring additional time costs

Right ventricular failure following left ventricular assist device implantation

Abstract Background Left ventricular assist device (LVAD) therapy is a lifesaving option for patients with medical therapy-refractory advanced heart failure.(1) Right ventricular failure (RVF) is a cause of major morbidity and mortality after LVAD implantation.(2,3) Our objective was to get the outcomes and predictors of RVF in adult patients undergoing LVAD implantation. Methods This retrospective study enrolled 73 adult patients with LVAD (Heart Mate III) implantation, of them 24(32.9%) patients had RVF after LVAD implantation. Results The patients with RVF had statistically significant more frequencies of acute kidney injyry (p<0.001), new need for dialysis(p<0.001), RVAD insertion (p<0.001), total mortality (p=0.012) and on-VAD mortality(p=0.018) with prolonged ICU stay (p<0.001) compared to the non-RVF group respectively. The pre-LVAD pulmonary vascular resistance(PVR) ≥3 WU (OR:2.4, 95%CI: 1.52-7.38, p=0.04) and diastolic pulmonary gradient(DPG) ≥ 7 mmHg (OR:6.4,95%CI: 5.49-18.6, p<0.001) were the independent predictors of RVF after LVAD implantation. Cox proportional regression analysis revealed that RVF was associated with increased risk of death (HR:3.12,95%CI:1.42-6.85, p=0.005). Conclusion Early RVF post-LVAD carries significant risks of mortality and multiple morbidities. Concomitant BiVAD implantation needs to be considered in patients with elevated DPG and PVR to avoid post-LVAD RVF.The significant variables of patients.Kaplan-Meier curves of the 2 groups.

Clinico-demographic profile of burns in the Middle-East and North-Africa (MENA) region: a systematic review and meta-analysis

Burn injuries remain a public health issue with risk of mortality and multiple post-burn morbidities. This article aims to systematically review and meta-analyse data about burns in the Middle-East and North-Africa (MENA) region. Methods Pubmed, Web of Science, Scopus, Global Index Medicus, Cochrane Library and Google scholar data were searched from their dates of inception till April 2024. Results One hundred and one studies were included in this review, representing data from twelve countries in the region. Data was sub-grouped into two groups: pediatric group and emergency room (ER) group. The pooled random-effect estimates were male gender 58.6% [95% CI 56.9–60.2%], accidental injury 91.1% [95% CI 85.9–94.5%], scald burn 50% [95% CI 46.7–53.4%], at home injury 79.9% [95% CI 76.7–82.8%], upper limbs involvement 51.7% [95% CI 46.8–56.6%], mean body surface area burned (BSAB) 17.2% [95% CI 14.69–19.84%], second-degree burns 56.5% [95% CI 49–63.8%], length of stay 11.18 days [95% CI 9.68–12.68%] and mortality rate 9.1% [95% CI 7.5–11%]. All included studies were of good quality. Conclusion This review shows scarcity of studies from many countries in the MENA region. These data will inform policy makers and burn specialists about the extent of this public issue in the region.

Assessing causality in deprescribing studies: A focus on adverse drug events and adverse drug withdrawal events.

Generating real-world evidence about the effect of medication discontinuation or dose reduction on outcomes, such as reduction of adverse drug effects (ADE; intended benefit) and occurrence of adverse drug withdrawal events (ADWE; unintended harm), is crucial to informing deprescribing decisions. Determining the causal effects of deprescribing is difficult for many reasons, including lack of randomization in real-world study designs and other design and measurement issues that pose threats to internal validity. The inherent challenge is how to identify the effects, both intended benefits and unintended harms, of a new medication stoppage or reduction when implemented in patients with many potential clinical and social risks that may influence the likelihood of deprescribing as well as outcomes. We discuss methodological issues of estimating the effect of medication discontinuation or reduction on risk of ADEs and ADWEs considering: (1) sampling study populations of sufficient size with the potential to demonstrate clinically meaningful and quantifiable outcomes, (2) accurate and appropriately timed measurement of covariates, outcomes, and discontinuation, and (3) statistical approaches to managing confounding and other biases inherent in long-term medication use by individuals with multiple morbidities. Designing rigorous deprescribing studies that address internal validity threats will support evidence generation by improving the ability to assess benefits and harms when the exposure of interest is the absence of a medication. Iterative learnings about data quality, variable definition, variable measurement, and exposure-outcome associations will inform strategies to improve the causal inferences possible in real-world deprescribing studies.

Real-World Clinical and Healthcare Resource Burden Among Burosumab-Naïve Patients With Familial Hypophosphatemia.

To examine the real-world clinical and healthcare resource burden of familial hypophosphatemia (FH). In a retrospective, observational cohort study using MarketScan claims data from 2017 to 2021, clinical characteristics and healthcare resource utilization (HCRU) and costs were compared between burosumab-naïve pediatric and adult patients with ≥ 1 FH diagnosis code and matched controls without FH. Patient characteristics were evaluated at baseline, and disease characteristics, HCRU, and costs were evaluated over a 12-month follow-up period. Outcomes were analyzed descriptively. Costs were additionally analyzed using multivariate regression models. Overall, 570 patients with FH and 1710 non-FH matched controls were included. Approximately 10% of study participants were aged < 18 years. Patients with FH had 7.8-fold higher mean baseline comorbidity (Charlson Comorbidity Index). The prevalence of morbidities over the 12-month follow-up period was higher in patients with FH than controls, including renal disease (33% vs 3%), arthralgia (25% vs 10%), osteoarthritis (17% vs 6%), and delayed growth/walking difficulty (16% vs 2%; all P < .001). All-cause HCRU was significantly greater for patients with FH than controls over follow-up, including the proportion of patients with at least one inpatient admission (60% vs 4%), outpatient emergency room visit (52% vs 16%), and outpatient pharmacy prescription (96% vs 71%; all P < .001). The mean annual total healthcare cost per patient was also 22.6-fold higher for patients with FH than controls (adjusted cost difference = $129 643; P < .001). Differences were apparent across all age groups. Compared with non-FH matched controls, burosumab-naïve patients with FH experienced multiple morbidities and had substantially higher HCRU and costs.

Research progress on community health management model for older adults with chronic diseases and multiple morbidities.

With the rapid ageing of the population, the number of older adults with two or more chronic diseases is increasing. There are individual differences in health assessment, diagnosis, treatment, health management, and medication safety for older adults with chronic conditions and multiple morbidities. Managing these conditions poses increasingly complex challenges for the healthcare system. Developing effective community health management models specifically designed for older adults with multiple chronic diseases is crucial for improving their overall health. This study provides a comprehensive review of the progress in research on community health management models for older adults with multiple chronic diseases, aiming to offer valuable insights for health management in this population.

Characteristics and real-world medication persistence of people living with HIV treated with DTG/3TC or BIC/FTC/TAF: a hospital claims database study in Japan.

As the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH) has improved, chronic disease burden and polypharmacy have increased in PLWH. Simplification of the antiretroviral therapy (ART) regimen for PLWH has become crucial. The real-world treatment patterns and medication persistence of the 2-drug single-tablet regimen (STR), dolutegravir/lamivudine (DTG/3TC), compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) prescribed were investigated. This retrospective, database study extracted data from a hospital-based medical claims database in Japan. The changes in ART distributions by year during the identification period between January 1, 2018 and December 31, 2021 were observed. Patients with disease record of HIV-1 infection and prescribed DTG/3TC or BIC/FTC/TAF as the first prescription of STR during the identification period were divided into two cohorts; DTG/3TC cohort and BIC/FTC/TAF cohort, respectively. Patient without medication records more than 3 months and no future data more than 6 months were excluded. Patients' characteristics were compared between the DTG/3TC cohort and the BIC/FTC/TAF cohort by Mantel-Haenszel test to adjust for age. Medication persistence was compared between the two cohorts by evaluating the continuation rates using Kaplan-Meier methods, using the log-rank test to assess the difference between the Kaplan-Meier curves. The median time-to-first prescription was compared between the two cohorts by Kaplan-Meier methods. Prescriptions of DTG/3TC and BIC/FTC/TAF increased steadily from 2019 to 2021 after the release year of each STR. There was no significant difference in the time-to-first prescription (p = 0.3). A total of 959 patients were included, with 120 patients and 839 patients on DTG/3TC and BIC/FTC/TAF, respectively. The proportion of dyslipidemia at baseline was significantly higher in the DTG/3TC cohort than in the BIC/FTC/TAF cohort after adjusting for mean age (p = 0.002). There was no significant difference in medication persistence between the two cohorts (p = 0.91). This study showed that DTG/3TC was likely to be selected for elderly patients and those with chronic disease in real-world clinical practice, which seems in accordance with the treatment strategy recommended by guidelines. Comparable medication persistence was observed with both regimens, aligning with findings from other countries. The 2-drug single-tablet regimen DTG/3TC may be an important ART regimen for PLWH with multiple morbidities and polypharmacy in an aging society. Due to the limitations of the database, further research to assess viral loads, emergence of resistance and adverse events will be encouraged.

External validation and comparative analysis of the HOSPITAL score and LACE index for predicting readmissions among patients hospitalised with community-acquired pneumonia in Australia.

ObjectiveCommunity-acquired pneumonia (CAP) is a leading cause of emergency hospitalisations globally and is associated with high readmission rates. Specific score systems developed for all medical conditions such as the HOSPITAL score and the LACE index can also usefully predict CAP readmissions. However, there is limited evidence regarding their performance in the Australian healthcare settings.MethodsThis multicentre retrospective study analysed adult CAP discharges from two metropolitan hospitals in South Australia between 1 January 2018 and 31 December 2023. Data for determining the HOSPITAL score and the LACE index were derived from electronic medical records. Demographic characteristics of patients readmitted within 30 days were compared with those who were not readmitted. The scores were evaluated for overall performance, discriminatory power and calibration, with discriminatory power assessed using the concordance statistic (C-statistic).ResultsOver 6years, 7245 CAP discharges were recorded, with 1329 (18.3%) readmissions within 30days. The mean (s.d.) age of the cohort was 74.4 (17.8) years. Readmitted patients were more likely to have multiple morbidities and frailty than those not readmitted (P<0.05). They also had a higher mean number of emergency department presentations and hospital admissions in the previous year and a longer initial hospital stay (P<0.05). Overall, the mean (s.d.) HOSPITAL score and LACE index were 3.4 (2.1) and 9.3 (3.6), respectively. Among readmissions, 28.4% occurred in patients with a HOSPITAL score >4 (intermediate and high-risk group), while 25.8% occurred in patients in the high-risk LACE category (LACE index>10). The C-statistic for the HOSPITAL score and LACE index was 0.62 (95% CI 0.61-0.64) and 0.63 (95% CI 0.61-0.65), respectively, with no significant difference in the area under the receiver operating characteristic curves (P>0.05).ConclusionsThe predictive abilities of the HOSPITAL score and the LACE index for CAP readmissions are modest and comparable in an Australian setting.

Patient and Physician Communication in the Allogeneic Transplantation Setting: Challenges and Potential Solutions

Allogeneic hematopoietic cell transplantation is a challenging treatment characterized by multiple morbidities, the need for long-term care, and a significant mortality risk. Consequently, close patient and physician communication throughout treatment is crucial. We aimed to review the literature examining patient and physician communication around critical aspects experienced by allogeneic survivors over the transplantation trajectory, such as the informed consent process, transplantation-related morbidity (eg, psychosocial distress, cognitive dysfunction, sexuality), adherence to treatment, and the use of complementary and alternative medicine, as well as interventions and strategies to improve patient and physician communication. We found a paucity of studies examining communication on these topics. Nevertheless, there is evidence of significant communication gaps around morbidities often experienced by allogeneic survivors, such as psychosocial distress, fatigue, and sexual functioning, due to both patient and physician barriers. Similarly, there is a concern that gaps also exist when addressing the informed consent process, cognitive dysfunction, adherence to treatment, and use of complementary and alternative medicine. The use and discussion of patient-reported outcome measures as part of clinical care is associated with patient and physician satisfaction with communication and better detection and management of symptoms. Although other strategies, such as decision aids, question prompt lists, and communication skills training, have improved communication in oncology, they have not been tested in the allogeneic setting. Future research is clearly needed to examine patient and physician communication in the allogeneic transplantation setting and test strategies to improve communication during this challenging treatment.

Polypharmacy and potentially inappropriate medications in older adults who use long-term care services: a cross-sectional study

BackgroundOlder adults requiring care often have multiple morbidities that lead to polypharmacy, including the use of potentially inappropriate medications (PIMs), leading to increased medical costs and adverse drug effects. We conducted a cross-sectional study to clarify the actual state of drug prescriptions and the background of polypharmacy and PIMs.MethodsUsing long-term care (LTC) and medical insurance claims data in the Ibaraki Prefecture from April 2018 to March 2019, we included individuals aged ≥ 65 who used LTC services. The number of drugs prescribed for ≥ 14 days and the number of PIMs were counted. A generalized linear model was used to analyze the association between the backgrounds of individuals and the number of drugs; logistic regression analysis was used for the presence of PIMs. PIMs were defined by STOPP-J and Beers Criteria.ResultsHerein, 67,531 older adults who received LTC services were included. The median number of total prescribed medications and PIMs was 7(IQR 5–9) and 1(IQR 0–1), respectively. The main PIMs were loop diuretics/aldosterone antagonists (STOPP-J), long-term use of proton pump inhibitors (Beers Criteria), benzodiazepines/similar hypnotics (STOPP-J and Beers Criteria), and nonsteroidal anti-inflammatory drugs (STOPP-J and Beers Criteria). Multivariate analysis revealed that the number of medications and presence of PIMs were significantly higher in patients with comorbidities and in those visiting multiple medical institutions. However, patients requiring care level ≥1, nursing home residents, users of short-stay service, and senior daycare were negatively associated with polypharmacy and PIMs.ConclusionsPolypharmacy and PIMs are frequently observed in older adults who require LTC. This was prominent among individuals with comorbidities and at multiple consulting institutions. Utilization of nursing care facilities may contribute to reducing polypharmacy and PIMs.Graphical

Using clustering of genetic variants in Mendelian randomization to interrogate the causal pathways underlying multimorbidity from a common risk factor.

Mendelian randomization (MR) is an epidemiological approach that utilizes genetic variants as instrumental variables to estimate the causal effect of an exposure on a health outcome. This paper investigates an MR scenario in which genetic variants aggregate into clusters that identify heterogeneous causal effects. Such variant clusters are likely to emerge if they affect the exposure and outcome via distinct biological pathways. In the multi-outcome MR framework, where a shared exposure causally impacts several disease outcomes simultaneously, these variant clusters can provide insights into the common disease-causing mechanisms underpinning the co-occurrence of multiple long-term conditions, a phenomenon known as multimorbidity. To identify such variant clusters, we adapt the general method of agglomerative hierarchical clustering to multi-sample summary-data MR setup, enabling cluster detection based on variant-specific ratio estimates. Particularly, we tailor the method for multi-outcome MR to aid in elucidating the causal pathways through which a common risk factor contributes to multiple morbidities. We show in simulations that our "MR-AHC" method detects clusters with high accuracy, outperforming the existing methods. We apply the method to investigate the causal effects of high body fat percentage on type 2 diabetes and osteoarthritis, uncovering interconnected cellular processes underlying this multimorbid disease pair.

Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases

Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by physical frailty and the frailty index, categorizing participants as non-frail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: hazard ratio [HR] 1.66, 95% CI 1.40-1.97; frailty index: HR 2.01, 95% CI 1.67-2.42) and frailty (physical frailty: HR 3.32, 95% CI 2.54-4.34; frailty index: HR 4.54, 95% CI 3.65-5.66) than in those with non-frailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as MRI-derived liver proton density fat fraction >5%, than the non-frail group (physical frailty: odds ratio 1.64, 95% CI 1.32-2.04; frailty index: odds ratio 1.48, 95% CI 1.30-1.68). Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. While frailty is common and associated with a poor prognosis in people with MASLD (metabolic dysfunction-associated steatotic liver disease) and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Postnatally acquired cytomegalovirus infection among preterm infants.

Although there are multiple benefits of mother's own milk feeding for very-low birth weight, low gestation infants, those born to cytomegalovirus (CMV)-seropositive mothers are at risk for acquiring postnatal CMV infection. This review will describe the risk and consequences of postnatal CMV infection among very preterm infants. Postnatal CMV may manifest as clinically silent infection or as mild to severe and occasionally fatal disease. The risk of disease is balanced by the health benefits of human milk feeding to preterm infants. Postnatal CMV infection has been associated with increased risks of multiple preterm morbidities such as bronchopulmonary dysplasia, necrotizing enterocolitis and neurodevelopmental impairment, but current evidence is limited by the selection bias inherent to reporting in case series and retrospective cohort studies. Knowledge gaps exist regarding the risk-benefit balance of pasteurization to inactivate CMV in fresh breast milk, as well as the optimal dosing, duration and efficacy of treating infected infants with antiviral medications. Multicenter, prospective studies are urgently needed to accurately determine the true burden that postnatal CMV infection presents to very preterm infants. Such studies will inform the need for preventive strategies and treatment guidance.

Predictive Modeling of Future Trends in US Healthcare Data and Outcomes

Predictive modeling has great potential to help guide healthcare policymaking and planning through forecasting future trends in domains such as disease prevalence, resource utilization, and costs. However, past research in this area has been limited by mostly examining small, narrow datasets that only captured specific illnesses or geographic regions. This study aimed to leverage more sophisticated predictive analytics to generate informed estimations of the most consequential healthcare trends anticipated in the United States throughout the next decade. The analysis drew upon an extensive collection of over 50 million longitudinal electronic health records spanning a 5-year timeframe, comprehensive national public health statistics from the same period, and Medicare claims encompassing 72 million beneficiaries. Advanced machine learning techniques, including neural networks and Bayesian additive regression trees, were applied to identify nonlinear relationships and temporal patterns across 500 variables related to patient demographics, medical diagnoses, therapeutic procedures, reimbursement amounts, and clinical outcomes. Models were trained using data from 2010 to 2015 then utilized to project trends and forecasts for the years 2020 to 2025. Five-fold cross-validation testing was conducted to evaluate the accuracy and generalizability of the predictive models. The model projections indicate that chronic disease prevalence nationwide will rise by approximately 40% by the conclusion of 2025, primarily fueled by growing epidemics of obesity and an increasingly aging American population. Additionally, heart disease and stroke are estimated to maintain their positioning as leading causes of death, but cases of dementia and Alzheimer's disease specifically are projected to climb even more sharply at over a 50% increase. Healthcare costs on the whole are anticipated to rise on average between 4-6% annually, and costs may potentially double for elderly patients presenting with multiple morbidities. As outpatient and home-based care options expand further, inpatient hospital facility utilization may drop marginally between 10-15%. Improved management of chronic medical conditions within local community settings could reduce preventable hospital readmissions from 25-30%. Primary care, nursing, and mental healthcare roles are likely to face looming staffing shortages as well. Telehealth adoption is forecasted to surge by approximately 45% as virtual visit formats help address access obstacles. By 2025, biologics and gene therapies could account for over 25% of total drug spending pertaining to oncology and rare disease treatment. Larger Medicaid, Medicare, and ACA commercial coverage markets may motivate higher rates of health insurance enrollment over the next few years.

P-745 effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from UK HFEA registry

Abstract Study question How does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) compared to double embryo transfer (DET)? Summary answer 2xSET may provide greater or comparable live birth rates with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET. What is known already Elective single embryo transfer (SET) in IVF/ICSI is widely encouraged over DET to minimise the risk of multiple birth and associated morbidities. Despite this, UK multiple birth rates following IVF remain higher than spontaneous conception, with 5% of IVF pregnancies resulting in multiple birth compared to 0.4%-1.2% multiple gestation rates following spontaneous conception. Owing to advancements in cryopreservation techniques, live birth and ongoing pregnancy rates are now comparable between fresh and frozen embryo transfer. Consequently, 2xSET has been suggested as an alternate technique to achieve comparable live birth rates with fewer multiple gestation pregnancies compared to DET. Study design, size, duration This retrospective cohort study was conducted using Human Fertilisation and Embryology Authority (HFEA) register data, which encompasses national data from all IVF clinics in the UK. Within this analysis, all women who underwent their first oocyte collection and IVF or ICSI treatment cycle with subsequent SET, DET or 2xSET between 2010 and 2019 using either blastocyst or cleavage stage embryos were included (N = 125,149). Participants/materials, setting, methods This national retrospective cohort study utilised UK HFEA register data from 2010-2019, including all women who underwent their first oocyte collection and subsequent embryo transfer (N = 125,149). The rate of live birth, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using either blastocyst or cleavage stage embryos, and was stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05. Main results and the role of chance 2xSET pregnancies following blastocyst-stage transfer achieved a greater live birth occurrence rate of 0.47 (0.13) (median (interquartile range)) than SET, 0.41 (0.13), and DET, 0.38 (0.13) (P &amp;lt; 0.05). When using SET as a reference standard, 2xSET achieved a lower multiple birth rate, odds ratio (OR) of 6.87 (95%CI 6.14-7.68), than DET, OR 28.20 (95%CI 25.20-31.57), and lower preterm birth rate; OR 1.11 (95%CI 1.06-1.15) in 2xSET, and OR 2.80 (95%CI 2.67-2.94) in DET. Pregnancy loss or neonatal death rate was also lower in 2xSET, OR 1.14 (95%CI 1.08-1.21), compared to DET, OR 2.11 (95%CI 1.98-2.24). Conversely, in cleavage-stage embryo transfer pregnancies, no significant difference in live birth occurrence rate was observed, achieving rates of 0.27 (0.21) for SET, 0.26 (0.13) for DET, and 0.29 (0.18) for 2xSET. 2xSET was less likely to result in multiple birth than DET, OR 0.14 (95%CI 0.11-0.19). Moreover, when using SET as a reference standard, 2xSET was less likely to result in preterm birth than DET, OR 1.02 (95%CI 0.87-1.23) and 2.48 (95%CI 2.17-2.82) respectively, as well as pregnancy loss or neonatal death, OR 1.07 (95%CI 0.85-1.35) and 2.03 (95%CI 1.70-2.42) respectively. Limitations, reasons for caution Certain confounders are not recorded within HFEA registry data, including patient body mass index (BMI), evaluation of embryo quality, and endometrial thickness at embryo transfer. Consequently, while our analysis identifies broad trends in embryo transfer success and morbidity, results may differ within certain patient populations. Wider implications of the findings 2xSET may provide greater or comparable live birth rates with lower multiple birth and morbidity than DET. Promotion of 2xSET where appropriate for maternal age and embryo quality should be implemented to enhance reproductive outcomes and reduce the risk of morbidity in IVF/ICSI pregnancies. Trial registration number Not Applicable

Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.

Preclinical evidence demonstrates that senescent cells accumulate with aging and that senolytics delay multiple age-related morbidities, including bone loss. Thus, we conducted a phase 2 randomized controlled trial of intermittent administration of the senolytic combination dasatinib plus quercetin (D + Q) in postmenopausal women (n = 60 participants). The primary endpoint, percentage changes at 20 weeks in the bone resorption marker C-terminal telopeptide of type 1 collagen (CTx), did not differ between groups (median (interquartile range), D + Q -4.1% (-13.2, 2.6), control -7.7% (-20.1, 14.3); P = 0.611). The secondary endpoint, percentage changes in the bone formation marker procollagen type 1 N-terminal propeptide (P1NP), increased significantly (relative to control) in the D + Q group at both 2 weeks (+16%, P = 0.020) and 4 weeks (+16%, P = 0.024), but was not different from control at 20 weeks (-9%, P = 0.149). No serious adverse events were observed. In exploratory analyses, the skeletal response to D + Q was driven principally by women with a high senescent cell burden (highest tertile for T cell p16 (also known as CDKN2A) mRNA levels) in which D + Q concomitantly increased P1NP (+34%, P = 0.035) and reduced CTx (-11%, P = 0.049) at 2 weeks, and increased radius bone mineral density (+2.7%, P = 0.004) at 20 weeks. Thus, intermittent D + Q treatment did not reduce bone resorption in the overall group of postmenopausal women. However, our exploratory analyses indicate that further studies are needed testing the hypothesis that the underlying senescent cell burden may dictate the clinical response to senolytics. ClinicalTrials.gov identifier: NCT04313634 .

An Umbrella Review and Updated Meta-Analysis of Imaging Modalities in Occult Scaphoid and Hip and Femoral Fractures.

Background: Occult fractures may cause multiple morbidities. If occult fractures were detected earlier, complications may be preventable. This umbrella review and updated meta-analysis will aim to evaluate the use of imaging modalities in detecting occult scaphoid and hip fractures. Methods: The protocol for this study is available in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42024525388). The literature search started and ended on 17 March 2024. We searched seven academic databases: MEDLINE, Cochrane Library, Pubmed, Science Direct, Google Scholar, WHO International Clinical Trials Registry Platform, and The Joanna Briggs Institute (JBI) database. The meta-analysis was conducted with the STATA program using the "midas" command. Results: There are four systematic reviews evaluating occult hip and femoral fractures with 6174 patients and two reviews evaluating occult scaphoid fractures with 1355 patients. The prevalence of occult scaphoid fracture and occult hip and femoral fractures is 23.87% (95% CI 18.25-29.49) and 44.8% (95% CI 39.38-51.4), respectively. Magnetic resonance imaging (MRI) had the best posterior probability of positive likelihood ratio (LR+) with 95% and 96% and negative likelihood ratio (LR-) with 0.15% and 1% for both occult scaphoid and hip fractures, respectively, assuming a 25% baseline. MRI could both confirm and exclude occult hip fractures while it can only confirm occult scaphoid fractures. Bone scans are inappropriate for either type of occult fractures The level of evidence for occult scaphoid fracture is weak while it is suggestive for occult hip fractures. Conclusion: The findings strengthen the use of MRI after an initially negative radiograph fracture for occult hip and femoral fractures, with a CT scan as a viable second option.