Causal mediation analyses for the natural course of hepatitis C: a prospective cohort study.

BackgroundHepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.MethodsA community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants' serum samples. The cohort data were linked to Taiwan's National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases.ResultsIn 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose-response relationship of HCV viral load was further demonstrated for the mediation effect.ConclusionBoth intrahepatic and extrahepatic manifestations mediated approximately a half of HCV-induced mortality. The mediation mechanisms are supported by a dose-response relationship of HCV viral load.

Patient Experience with Chronic Refractory Gout and Its Impact on Health-Related Quality of Life: Literature Review and Qualitative Analysis.

INTRODUCTION: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL). METHODS: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population. RESULTS: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants. CONCLUSIONS: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.

The global burden, trends and cross-country inequalities of female breast and gynaecologic cancers: A population based study.

OBJECTIVE: To analyse the global burden, trends and cross-country inequalities of female breast and gynaecologic cancers (FeBGCs). DESIGN: Population-Based Study. SETTING: Data sourced from the Global Burden of Disease Study 2019. POPULATION: Individuals diagnosed with FeBGCs. METHODS: Age-standardised mortality rates (ASMRs), age-standardised Disability-Adjusted Life Years (DALYs) rates (ASDRs) and their 95% uncertainty interval (UI) described the burden. Estimated annual percentage changes (EAPCs) and their confidence interval (CI) of age-standardised rates (ASRs) illustrated trends. Social inequalities were quantified using the Slope Index of Inequality (SII) and Concentration Index. MAIN OUTCOME MEASURES: The main outcome measures were the burden of FeBGCs and the trends in its inequalities over time. RESULTS: In 2019, the ASDRs per 100 000 females were as follows: breast cancer: 473.83 (95% UI: 437.30-510.51), cervical cancer: 210.64 (95% UI: 177.67-234.85), ovarian cancer: 124.68 (95% UI: 109.13-138.67) and uterine cancer: 210.64 (95% UI: 177.67-234.85). The trends per year from 1990 to 2019 were expressed as EAPCs of ASDRs and these: for Breast cancer: -0.51 (95% CI: -0.57 to -0.45); Cervical cancer: -0.95 (95% CI: -0.99 to -0.89); Ovarian cancer: -0.08 (95% CI: -0.12 to -0.04); and Uterine cancer: -0.84 (95% CI: -0.93 to -0.75). In the Social Inequalities Analysis (1990-2019) the SII changed from 689.26 to 607.08 for Breast, from -226.66 to -239.92 for cervical, from 222.45 to 228.83 for ovarian and from 74.61 to 103.58 for uterine cancer. The concentration index values ranged from 0.2 to 0.4. CONCLUSIONS: The burden of FeBGCs worldwide showed a downward trend from 1990 to 2019. Countries or regions with higher Socio-demographic Index (SDI) bear a higher DALYs burden of breast, ovarian and uterine cancers, while those with lower SDI bear a heavier burden of cervical cancer. These inequalities increased over time.

Publicly available surveillance data on tick-borne encephalitis in Europe, 2023.

The European Centre for Disease Prevention and Control (ECDC) defines a case of tick-borne encephalitis (TBE) as an infection by the TBE virus (TBEV) with clinical manifestations of central nervous system inflammation (e.g., meningitis, encephalitis). To better understand the TBE surveillance landscape, online searches were conducted to determine if cases of TBE, TBEV infection, acute meningitis or encephalitis, or viral meningitis or encephalitis were subject to statutory reporting in European countries in 2023. In countries with statutory reporting, notification responsibility and available information on surveillance-reported cases were determined. The number of TBE cases reported to ECDC were compared with the number of cases recorded in national surveillance reports. Of 44 countries of the Europe Region of the United Nations, 37 (84 %) mandated statutory reporting of cases of TBE, TBEV infection, or acute/viral meningitis/encephalitis. Twenty-six (87 %) of 30 countries with identified surveillance reports recorded TBE cases in 2020-2023. Of these countries, 17 (65 %) required TBE reporting by clinicians and laboratories, 5 (19 %) by clinicians only, and 4 (15 %) by laboratories only. Twenty-four countries reported on TBE cases to ECDC in 2020; however, surveillance for TBE in Europe is heterogeneous. Standardization of TBE surveillance would enhance the understanding of TBE disease burden in Europe.

Demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases: a retrospective cross-sectional study.

BACKGROUND: This study aimed to explore the demographic characteristics, diagnostic challenges, treatment patterns, and caregiver burden of mitochondrial diseases. METHODS: This retrospective cross-sectional study enrolled patients diagnosed with mitochondrial diseases from the Department of Neurology at Peking University First Hospital between January 2010 and December 2021. A questionnaire covering demographic characteristics, diagnostic dilemma, treatment, economic aspects, and caregiver stress was administered, and disability was assessed using the modified Rankin Scale (mRS). RESULTS: A total of 183 patients (mean age: 16 (IQR: 12-25), 49.72% males) were enrolled, including 124 pediatric patients and 59 adult patients. MELAS (106. 57.92%) and Leigh syndrome (37, 20.22%) were predominant among the mitochondrial disease subtypes. Among them, 132 (72.13%) patients were initially misdiagnosed with other diseases, 58 (31.69%) patients visited 2 hospitals before confirmed as mitochondrial disease, and 39 (21.31%) patients visited 3 hospitals before confirmed as mitochondrial disease. Metabolic modifiers were the most common type of drugs used, including several dietary supplements such as L-carnitine (117, 63.93%), Coenzyme Q10 (102, 55.74%), idebenone (82, 44.81%), and vitamins (99, 54.10%) for proper mitochondrial function. Mothers are the primary caregivers for both children (36.29%) and adults (38.98%). The mRS score ranged from 0 to 5, 92.35% of the patients had different degrees of disability due to mitochondrial disease. The average monthly treatment cost was 3000 RMB for children and 3100 RMB for adults. CONCLUSIONS: This study provided valuable insights into the characteristics and challenges of mitochondrial diseases, which underscores the need for improved awareness, diagnostic efficiency, and comprehensive support for patients and caregivers.

Patient-reported symptoms and burden of eosinophilic esophagitis: evidence from real-world clinical practice.

BACKGROUND: Eosinophilic esophagitis is a chronic inflammatory disorder of the esophagus. This real-world study used patient and physician surveys to describe the clinical characteristics and disease burden of eosinophilic esophagitis-overall and in a subgroup of patients with dysphagia despite treatment. METHODS: Data analyzed in this study were collected in 2020 from US and EU patients with eosinophilic esophagitis. Eligible patients were aged ≥ 12 years with a diagnosis of eosinophilic esophagitis, had an esophageal count of ≥ 15 eosinophils/high-power field at diagnosis, and were currently prescribed treatment for eosinophilic esophagitis. RESULTS: Overall, 1001 patients were included, of whom 356 (36%) had dysphagia despite treatment. Demographics and clinical characteristics were similar in both populations. The severity of eosinophilic esophagitis was mild in more patients overall (69%) versus those with dysphagia despite treatment (48%). Patient disease history was similar in both populations, with some exceptions: common patient-reported symptoms were dysphagia (70% and 86%) and heartburn/acid reflux (55% and 49%), and common physician-reported symptoms were dysphagia (75% and 91%) and food impaction (46% and 52%). Treatment history was similar in both populations; overall, the most common treatments were proton pump inhibitors (83%) and topical corticosteroids (51%). Patients reported slightly more days with symptoms, higher impacts on activities of daily living, and slightly higher anxiety or depression in the dysphagia-despite-treatment population versus the overall population. CONCLUSIONS: Eosinophilic esophagitis presents severe symptoms and comorbidities that substantially impact patients' well-being and quality of life. Greater awareness of and novel treatments for eosinophilic esophagitis are needed.

Treatment burden and the perspectives of patients with psoriasis using topical treatments: results from a national survey of adults with psoriasis in the United States.

BACKGROUND: Topical treatments are the foundation for patients with psoriasis; however, adherence can be limited by patient preferences and treatment burden. METHODS: The Harris Poll conducted an online survey of US patients with psoriasis who use prescription topical therapy to examine their preferences and perspectives on topical treatments. RESULTS: Among patients with psoriasis who use topical treatment (n = 507), most participants described their psoriasis symptoms as mild (31%) or moderate (59%). The body areas most often reported to be affected by psoriasis were the scalp, elbows, legs, intertriginous areas, arms, and knees. Participants reported psoriasis affecting the scalp (39%), elbows (20%), and legs (excluding knees; 19%) caused the greatest impact on quality of life. Most participants (76%) preferred topical therapies to treat their psoriasis, while 20% preferred pills, and 4% preferred injections. The most common product attributes that participants wanted in a topical psoriasis treatment and that would help them to continue to use the treatment were: improvement in plaques (68%), itch relief (68%), and easy to apply (63%). CONCLUSION: The respondents to this survey reported that they prefer topical treatments to pills or injections (76%) and most (89%) reported they are interested in trying a new topical treatment.

The Burden of Inpatient Hospitalizations with Cardiac and Cerebrovascular Diseases in Patients with Type 1 Diabetes: Insights from the National Inpatient Sample in the US.

BACKGROUND: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). METHODS: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 and 2019. The in-hospital mortality rates, length of stay (LoS), and healthcare costs were determined. RESULTS: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p < 0.001). The estimated total care cost for all patients with T1DM with CCD was approximately USD 326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77), and stroke (OR 1.47, 95%CI 1.04-2.09). CONCLUSIONS: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Global burden of fracture of sternum and/or ribs: An analysis of 204 countries and territories between 1990 and 2019.

BACKGROUND: Sternum and rib fractures represent a significant global health concern, contributing to morbidity and disability on a worldwide scale. However, there is a notable lack of recent epidemiological data detailing the global and regional burden of these fractures. METHODS: We undertook a systematic analysis of the prevalence of sternum and rib fractures at the global, regional, and national levels in 2019, while also examining time trends spanning from 1990 to 2019. To achieve this, we extracted data from the Global Burden of Disease Study 2019, enabling us to determine incidence, prevalence, years lived with disability (YLDs), and their corresponding age-standardized rates. RESULTS: In 2019, there were 4.1 million incident cases and 2 million prevalent cases of sternum and rib fractures worldwide. These figures represent increases of 43.7 % and 64.1 %, respectively, since 1990. YLDs also exhibited a notable increase, rising by 62.4 % to reach 190,834 cases. However, since 1990, their equivalent age-standardized rates, which ranged from 5.5 % to 7.1 %, have decreased. Notably, China had the greatest incidence (1.2 million cases), prevalence (573,000 cases), and number of YLDs (55,400 cases), all in 2019. The greatest age-standardized incidence rate (143/100,000) and age-standardized prevalence rate (65/100,000) were both recorded in Greenland in the same year. It's critical to emphasize that men experience these fractures at considerably higher rates than women. Around 70 % of incident instances included unintentional injuries worldwide and across all regions. High-socioeconomic regions had the highest rates of incidence, prevalence, and YLDs, albeit these rates have declined by 6.4 % to 7.1 % since 1990, whereas low-middle and low-income areas have had rises. CONCLUSIONS: This study, which spans the years 1990 to 2019, provides a thorough and current assessment of the global burden attributed to sternum and rib fractures. In terms of nations, regions, sociodemographic index (SDI) levels, age groups, genders, and reasons, it reveals significant variances and trends. The knowledge obtained from this study can be extremely useful in formulating health policy, allocating resources, and developing methods to prevent these injuries.

Systematic literature review of the somatic comorbidities experienced by adults with phenylketonuria.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism that, if untreated, causes Phe accumulation in the brain leading to neurophysiologic alterations and poor outcomes. Lifelong management centers on dietary Phe restriction, yet long-term complete metabolic control is unachievable for many adults. High blood Phe levels or chronic Phe and intact protein restriction in the diet may lead to somatic comorbidities. A systematic literature review was conducted to evaluate somatic comorbidities experienced by adults with PKU. METHODS: Clinical and observational studies reporting somatic comorbidities experienced by individuals with PKU aged ≥ 16 years (or classified as adults) evaluating a Phe-restricted diet with or without pharmacologic therapy versus no therapeutic intervention (including healthy controls), or pharmacologic therapy versus a Phe-restricted diet alone, were identified. PubMed® was searched (February 1, 2022 and updated November 1, 2023), using a pre-defined search strategy, followed by two-stage screening and data extraction. Included studies were grouped by PKU population comparison. RESULTS: 1185 records were screened; 51 studies across 12,602 individuals were extracted. Bone-related abnormalities were the most reported outcome (n = 21); several outcome measures were used. Original study groupings included: Phe-restricted diet versus healthy controls or reference values (n = 40); treatment-adherent versus those non-adherent (n = 12). Additional groups added as part of a protocol amendment included: different Phe-restricted diets (n = 4); severe versus less severe disease (n = 5). Vote counting indicated a higher burden of ≥ 1 comorbidity (or outcome measure) for the Phe-restricted diet group by 37 of 38 studies included in the analysis of Phe-restricted diet versus healthy controls; higher burden in healthy controls was reported in 12 studies. Vote counting was similar between those treatment adherent (n = 7) versus non-adherent (n = 10). CONCLUSIONS: Adults with PKU have a higher comorbidity burden than a non-PKU population. More robust studies are needed to better understand the relationship between effective metabolic control and comorbidity burden, using consistent outcome measures. This SLR was supported by BioMarin Pharmaceutical Inc., Novato, CA, and is registered with the Research Registry (reviewregistry1476).

Balancing the benefits and risks of China's national salt iodization policy over 30 years using disability-adjusted life years (DALYs): a systematic review and meta-analysis.

Both insufficient and excessive iodine intake can lead to thyroid-related disorders. Although China has made progress in eliminating iodine deficiency over the past few decades, the incidence of thyroid cancer is increasing. Currently, there is a lack of relevant research on the tradeoff between the benefits and risks of salt iodization in China. In this study, we developed a method that combines the total probability algorithm and disease burden to evaluate the appropriate amount of salt iodization. Following the principle of minimizing the comprehensive disease burden and using the metabolic model of human iodine nutrition. Based on the average national iodine level in water, the optimal iodine content in Chinese salt is determined to be 17 mg/kg. However, iodine content in water is not evenly distributed in China. Approximately 3.23% of administrative villages have water iodine concentrations exceeding 80 ug/L, eliminating the need for iodine fortification in salt. Approximately 83.51% of administrative villages need to continue implementing the salt iodization policy, with the optimal iodine content in salt ranging from 15 to 18 mg/kg. In 13.16% of administrative villages, the iodine content in salt is determined based on the local water iodine concentration, ranging from 0 to 15 mg/kg. Our study cracks open a window of insight suggesting that the optimal iodine content for salt is lower than the existing benchmark dictated by the prevailing policy in China. Hence, there is an urgent need to refine and advance the iodine supplementation strategy in salt to pave the way for precision medicine and health-centric iodine supplementation strategies.

Secular trends in incidence and mortality of non-Hodgkin's lymphoma in China, 1990-2019, and predictions to 2030: Outlook for the future burden of disease.

BACKGROUND: The aim of this study was to analyze the trend of non-Hodgkin's lymphoma incidence and mortality in China from 1990 to 2019, along with assessing the effects of age, period, and cohort, as well as to predict future trends. MATERIAL AND METHODS: Using data from the Global Burden of Disease Study 2019 we calculated the estimated annual percentage changes in the incidence and mortality of non-Hodgkin's lymphoma. Age-period-cohort analysis was used to assess the independent effects of these elements. Incidence and mortality until 2030 were predicted using a Bayesian age-period-cohort approach. RESULTS: During 1990-2019, there was a significant increase in the age-standardized incidence and mortality rate in non-Hodgkin's lymphoma. Strong effects of birth cohort and period on non-Hodgkin's lymphoma incidence and mortality were observed. In terms of prediction, future non-Hodgkin's lymphoma incidence and mortality in China will continue to increase, while the mortality rate will decrease; for women, both the rates are projected to rise, but they will remain lower than men. CONCLUSIONS: Currently, the non-Hodgkin's lymphoma burden is high in China, and it is expected to continue increasing in the future. Policymakers need to prioritize addressing the factors contributing to sex differences in disease burden, including variations in environmental exposures and lifestyles among men and women.

Assessing Participants' Experiences with Vitiligo from Patient Interviews.

INTRODUCTION: Vitiligo is an autoimmune disease, causing skin depigmentation. Individuals with vitiligo incur substantial psychosocial burden and have expressed frustration with their treatments. Here, we describe the burden of vitiligo and opinions on what constitutes meaningful change among participants of two qualitative interview studies. METHODS: Qualitative interviews were conducted with a subgroup of adolescent and adult participants with vitiligo from two pivotal phase 3 clinical trials of ruxolitinib cream (Study 1) and a real-world panel (Study 2). Participants were asked about their disease burden, treatment goals, importance of facial/body improvement (treatment satisfaction: scale range 0-10), and meaningfulness of change (yes/no). RESULTS: A total of 36 participants from Study 1 and 23 from Study 2 were interviewed. In Study 1, the highest degree of impact was on reduced self-esteem (facial lesions, 62.5%; body lesions, 55.6%), social inhibition (facial lesions, 65.6%; body lesions, 61.1%), and sun sensitivity (facial lesions, 31.3%; body lesions, 55.6%). Most participants (83.3%) reported that facial improvement was equally (36.1%) or more important (47.2%) than body improvement, with mean treatment satisfaction of 8.1 and 6.9, respectively. Meaningful change was reported by 83.3% and 92.9% of participants with 50-74% and ≥ 75% improvement per the facial Vitiligo Area Scoring Index, respectively, and by 82.6% of participants with ≥ 25% improvement per the total Vitiligo Area Scoring Index per Study 1 outcomes at Week 24. In Study 2, most (82.6%) participants felt that the noticeability of their vitiligo affected their behavior. Nearly all (87.0%) said that an ideal treatment would repigment or return natural color to their facial skin; 56.5% considered ≥ 50% facial repigmentation to be the smallest meaningful improvement. CONCLUSIONS: Participants from both qualitative interviews expressed substantial psychosocial burden. Repigmentation in both facial and body vitiligo were important, with meaningful change determined to be ≥ 50% facial repigmentation and ≥ 25% body repigmentation.

Vitiligo is an autoimmune disease that causes white patches to appear on the skin, affecting about 2% of people worldwide. People with vitiligo often have poor quality of life due to their disease and frequently do not believe that treatments work. We explored how people with vitiligo felt about their disease, and asked what hopes they had for treatment. Individual telephone interviews were conducted with 36 adolescents and adults with vitiligo from two clinical studies (Study 1) and 23 adolescents and adults with vitiligo from a real-world panel (Study 2) in the USA and Canada. Those from Study 1 said that their vitiligo caused them to have low self-esteem and to feel lonely. Most said that it was as important or more important to restore color to white patches on their face (i.e., repigmentation) than the body. Most achieving repigmentation of more than 50% on the face or more than 25% on the body were pleased with their treatment. In Study 2, most people said that their disease affected their behavior, and nearly all said that completely restoring color to their facial skin (i.e., 100% repigmentation) was important. Over half said that the smallest change they thought was important was more than 50% facial repigmentation. In short, people with vitiligo in two interview studies said that their vitiligo affected their quality of life. Most people with vitiligo in these studies reported that it was important to repigment more than 50% on the face and more than 25% on the body.

Disease burden of esophageal cancer attributable to low fruit intake in China and globally from 1990 to 2019.

OBJECTIVE: To understand the disease burden of esophageal cancer (EC) attributable to inadequate fruit intake in China and global from 1990 to 2019 stratified by age and sex. METHODS: Global Burden of Disease Study (GBD 2019) were pooled to calculate the number of deaths, standardized mortality rate, disability-adjusted life years (DALY) and DALY rate of EC attributed to low fruit intake in China and globally by age and sex from 1990 to 2019. The population attributable fractions (PAF) were applied to estimate the proportion of EC caused by low fruit intake. Joinpoint was used to estimate average annual percentage of change (AAPC) to reflect the time change trend of the EC burden attributable to inadequate fruit intake in China and globally. RESULTS: In the Chinese population in 2019, the attributable DALY of EC in males was 356,000 person-years, while it was 80,600 person-years in females. The attributable standardized mortality and DALY rates for different age groups in China increased with age, peaking in the group aged 70 years and above. From 1990 to 2019 in China, the number of deaths, standardized mortality rates, DALY and standardized DALY rates of EC attributable to inadequate fruit intake showed a decreasing trend (AAPCs: -1.62%, -4.54%, -2.10% and -4.88%, respectively), with statistical significance (P<0.001). CONCLUSION: The overall burden of EC attributed to inadequate fruit intake in China has demonstrated a downward trend. However, due to the aging population, the disease burden in China remains higher than the global average. Hence, prevention and health education efforts should focus on the population with low fruit intake.

Unbiased identification of risk factors for invasive Escherichia coli disease using machine learning.

BACKGROUND: Invasive Escherichia coli disease (IED), also known as invasive extraintestinal pathogenic E. coli disease, is a leading cause of sepsis and bacteremia in older adults that can result in hospitalization and sometimes death and is frequently associated with antimicrobial resistance. Moreover, certain patient characteristics may increase the risk of developing IED. This study aimed to validate a machine learning approach for the unbiased identification of potential risk factors that correlate with an increased risk for IED. METHODS: Using electronic health records from 6.5 million people, an XGBoost model was trained to predict IED from 663 distinct patient features, and the most predictive features were identified as potential risk factors. Using Shapley Additive predictive values, the specific relationships between features and the outcome of developing IED were characterized. RESULTS: The model independently predicted that older age, a known risk factor for IED, increased the chance of developing IED. The model also predicted that a history of ≥ 1 urinary tract infection, as well as more frequent and/or more recent urinary tract infections, and ≥ 1 emergency department or inpatient visit increased the risk for IED. Outcomes were used to calculate risk ratios in selected subpopulations, demonstrating the impact of individual or combinations of features on the incidence of IED. CONCLUSION: This study illustrates the viability and validity of using large electronic health records datasets and machine learning to identify correlating features and potential risk factors for infectious diseases, including IED. The next step is the independent validation of potential risk factors using conventional methods.

Global burden and management of women with epilepsy in pregnancy: A modeling study.

BACKGROUND: Most pregnant women with epilepsy do not receive proper medical care, which creates a special burden worldwide. We aimed to qualify this special global burden and assess the impact of different clinical management strategies to reduce it. METHODS: The data used in this study were extracted from articles published between 2005 and 2022. We calculated the economic costs associated with major burdens experienced by pregnant women with epilepsy. We developed a microsimulation model to estimate the different effects of various interventions and their combinations as integrated strategies for pregnant women with epilepsy and related burden reduction. We also compared the regional differences in disease burden and interventions. FINDINGS: The total economic burden for pregnant women with epilepsy is estimated to reach $1.8 billion globally annually, which is more than three times the burden for epilepsy alone. Folic acid supplementation is projected to be the most effective intervention, with a 9.1% reduction in major congenital malformations, a 14.9% reduction in autism spectrum disorder, and a 10.8% reduction in offspring-related economic burden globally annually. Integrated strategies are associated with a reduced economic burden of up to $37.7 million annually globally. Folic acid supplementation is the most effective intervention in high- and upper-middle-income countries, whereas changes in antiseizure medication prescriptions are more effective in lower-middle- and low-income countries. CONCLUSION: This study highlights the huge burden for pregnant women with epilepsy and actions that must be taken to improve their quality of life. FUNDING: This work was supported by the Sichuan Science and Technology Program (2023YFS0047).

Quality of Life Evaluation in Patients with Follicular Cell Lymphoma: A Real-World Study in Europe and the United States.

INTRODUCTION: Follicular lymphoma (FL) is an indolent subtype of non-Hodgkin's lymphoma (NHL), characterized by a long natural course of remissions/relapses. We aimed to evaluate real-world quality of life (QoL) in patients with FL, by line of therapy (LOT), and across countries. METHODS: Data were drawn from the Adelphi FL Disease Specific Programme™, a cross-sectional survey of physicians and their patients in Europe [France, Germany, Italy, Spain, the United Kingdom (UK)], and the United States (US) from June 2021 to January 2022. Patients provided demographics and patient-reported outcomes via the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30). Bivariate analysis assessed QoL versus NHL, across LOT [first line (1L), second line (2L), third line or later (3L+)] and country. RESULTS: Patients (n = 401) had a mean [standard deviation (SD)] age of 66.0 (9.24) years, 58.1% were male, and 41.9%/22.9% were Ann Arbor stage III/IV. Patients with FL mean EORTC global health status (GHS)/QoL, nausea/vomiting, pain, dyspnea, appetite loss, and diarrhea scores were statistically significantly worse (p < 0.05) versus the NHL reference values. Mean (SD) GHS/QoL worsened from 1L [56.5 (22.21)] to 3L+ [50.4 (20.11)]. Physical and role functioning, fatigue, pain, dyspnea, and diarrhea scores also significantly worsened across later LOTs (p < 0.05). Across all functional domains, mean scores were significantly lower (p < 0.05) and almost all symptom scores (excluding diarrhea) were significantly higher (p < 0.05) for European versus US patients. CONCLUSIONS: Patients with FL at later LOTs had significantly worse scores in most QoL aspects than earlier LOTs. European patients had significantly lower functioning and higher symptom burden than in the US. These real-world findings highlight the need for novel FL therapies that alleviate patient burden, positively impacting QoL.

There is little information about the effects of follicular lymphoma and treatments on quality of life as assessed by patients. We surveyed doctors and their patients with follicular lymphoma across France, Germany, Italy, Spain, the United Kingdom, and the United States (US), and asked patients to complete a form reporting their quality of life. A total of 401 patients were included.In general, patients with follicular lymphoma treated across all lines of treatment had worse quality of life and symptoms of nausea and vomiting, pain, shortness of breath, appetite loss, and diarrhea compared to a reference group of patients with non-Hodgkin's lymphoma (NHL). Overall quality of life and physical, role, and social functioning of patients with follicular lymphoma worsened from the first to the third line of treatment. Fatigue, pain, dyspnea, and diarrhea symptom scores also worsened across the lines of therapies. European patients had worse quality of life, functioning, and symptoms compared to US patients. Better treatments are needed to improve symptoms, functions, and quality of life for patients with follicular lymphoma.

Relationship between burden of cerebral small vessel disease on imaging and cognitive impairment of COPD patients.

OBJECTIVE: This study aims to explore the relationship between the burden of cerebral small vessel disease (CSVD) on imaging and cognitive impairment (CI) in patients with chronic obstructive pulmonary disease (COPD). METHODS: The study included 118 COPD patients admitted to Changxing People's Hospital between July 2020 and July 2023. All patients received a 1.5 T MRI of the brain and pulmonary function tests. A cognitive function assessment was conducted via the Montreal Cognitive Assessment (MoCA) scale, and patients were divided into two groups. The relationship between the MoCA and CSVD burden score was analyzed by Pearson correlation, and to identify risk factors, multiple logistic regression analysis was performed. RESULTS: The study showed a negative correlation between the MoCA and CSVD burden score in COPD patients (r=-0.479, P<0.001). Multiple logistic regression analysis found that age (OR=2.264, 95 % CI: 1.426-3.596, P<0.001), COPD grade (OR=3.139, 95 % CI: 2.012-4.898, P<0.001), as well as CSVD burden score (OR=5.336, 95 % CI: 1.191-23.900, P<0.001) were the independent risk factors for CI in COPD patients (P<0.05). CONCLUSION: When screening for cognitive impairment in COPD patients, the CSVD burden score can be used in conjunction with cognitive assessment scales to make judgments.

Comparative analysis of atherosclerotic cardiovascular disease burden between ages 20-54 and over 55 years: insights from the Global Burden of Disease Study 2019.

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.