High Disease Burden Research Articles

Effects of depression and stress on oral self-care among perinatal women in Appalachia: A longitudinal study.

Oral health during the perinatal period and beyond affects the health and well-being of women and their offspring. Oral self-care behaviours can maintain or improve oral health; depression or stress during the perinatal period may compromise these behaviours. The aim of the study was to investigate the independent and combined effects of depression and stress on oral self-care behaviours of perinatal women in Appalachia, given the high burden of oral disease in this region. A total of 1172 women in the first or second trimester of pregnancy were enrolled in the Center for Oral Health Research in Appalachia, cohort 2 (COHRA2) in West Virginia or Pittsburgh, Pennsylvania. Participants completed the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale-10, and self-report items about oral self-care behaviours (i.e. toothbrushing and flossing) during pregnancy and five times in the 2+ years following birth. A Generalized Estimating Equation approach was used to analyse the longitudinal data. Maternal depression and stress were independently negatively related to toothbrushing and flossing frequency. These findings for toothbrushing were more pronounced in those with high levels of depression and high levels of stress, so there were both independent and combined effects. Frequency of toothbrushing and flossing stayed constant over time, so time was not associated with outcomes. About three-fourths of the sample reported toothbrushing levels that are consistent with established guidelines (i.e. two times daily), but almost half of the participants had very low levels of flossing (i.e. once or less a week). Interventions targeting stress and depression throughout the perinatal period might be helpful in improving oral self-care behaviours and oral health among women in Appalachia, in addition to the benefit of decreasing emotional distress.

Cancer mortality and geographic inequalities: a detailed descriptive and spatial analysis of social determinants across US counties, 2018–2021

ObjectiveIn the United States, cancer mortality rates continue to decline, yet geographic and racial disparities persist and are particularly evident in the Delta region, characterized by high economic distress and disease burden. We examined cancer mortality patterns by demographic groups across geographic region (Delta vs non-Delta) and investigated the influence of macro-level social determinants of health (SDoH) in cancer death. Study design and methodsThis observational study included cancer death records of individuals aged ≥20 years from 2018 to 2021 in the United States. County-level characteristics were ascertained through the linkage of multiple national administrative and community surveys. We estimated age-standardized mortality rates (ASR) and rate ratios. We calculated the adjusted relative risks by county-level SDoH (geographic region, rurality, household income, income inequality, health insurance, and education) and other factors using age-adjusted multivariate quasi-Poisson regression. ResultsIn 2018–2021, approximately 2.4 million cancer deaths occurred in the United States. We observed important declines in the Black-White disparities, from 16.6% in 2018 (ASR = 289.9 vs 248.6 per 100,000) to 12.1% in 2021 (281.1 vs 250.8) in the Delta region and from 15.9% (254.9 vs 219.9) to 10.7% (240.6 vs 217.3) in the non-Delta region, though Black men in the Delta region remained the highest rate (ASR2021 = 346.9 per 100,000). County-level analyses provided strong evidence of geographic inequality and the role of SDoH, particularly education and income inequality. ConclusionsUnfavorable SDoH are associated with increased cancer death risk. Region-specific health policies and interventions in the Delta region are essential to advance cancer health equity.

Patient profiles in randomised controlled trials versus a real-world study, in psoriatic arthritis: scoping review and meta-analysis.

Patients with psoriatic arthritis (PsA) in randomised controlled trials (RCTs) may not reflect patients in clinical practice. The objective was to perform a meta-analysis of PsA patients' characteristics in RCTs of biologic disease-modifying antirheumatic drugs (bDMARDs), and to compare them to patient profiles in a real-world study. Data sources: (a) Scoping literature review of phase III RCTs of bDMARDs in PsA published 2015-2020; (b) International observational study of PsA patients starting a bDMARD enrolled in 2015-2018 (PsABio: NCT02627768). Data collected at baseline included swollen and tender joint counts (SJC/TJC), enthesitis, skin involvement (body surface area -BSA-), C-reactive protein (CRP), physician global assessment (PhGA) and patient-reported outcomes (HAQ, pain). Univariate random-effects meta-analysis was conducted to calculate pooled means and proportions. Overall, 5654 patients from 10 RCTs were compared to 930 PsABio patients. Demographic data were similar. SJC/TJC were higher in RCTs than in PsABio (pooled means, 11.8/21.5 vs 5.7/11.9 respectively); enthesitis was more frequent in RCTs (64.7% vs 48.2%); as were patients with a BSA≥3% (62.2% vs 54.0%). PhGA was higher in RCTs (59.7mm vs 54.1mm). In contrast, patient-reported outcomes were similar, while CRP was significantly higher in PsABio (1.1 vs 1.4mg/dl). PsA patients starting a bDMARD in RCTs had highly active disease and a high patient-reported disease burden. In contrast, PsABio real-world patients starting a bDMARD had lower joint counts, skin disease and PhGA, but presented with similar patient-reported disease burden. The extrapolation of RCT data in clinical practice should take these elements into account.

HPB SO77 - Effects of Patient and Operative Variables on Isolation of Primary Human Hepatocytes

Abstract Background Isolation of human primary hepatocytes from tissue samples derived from therapeutic hepatectomy offers an important resource for a range of pharmacological and toxicology based experimental platforms, whilst simultaneously providing an opportunity to reduce the use of animal models. This study analysed the impact of a range of patient and operative derived variables on the yield and viability of isolated human primary hepatocytes. Method Excess hepatic tissue from resected liver parenchyma was sampled from consented patients undergoing major and minor hepatectomy for a range of oncological and non-oncological indications. Tissue dissociation and hepatocyte isolation was performed using a two-step collagenase perfusion procedure. Hepatocyte viability was calculated using the Trypan blue exclusion test while hepatocyte yield was calculated by the number of cells isolated divided by the tissue mass isolated from. Patient and operative variables were collected retrospectively from 25 patients in a prospectively maintained database. Results Samples from normal liver parenchyma achieved high hepatocyte viability and yields in all patients. Improved hepatoctye viability was associated with female sex, with a 2.9% increase in viability in samples from women (P<0.05). Patient age, BMI, operative indication, neo-adjuvant chemotherapy, as well as prolonged intra-operative Pringle time and blood loss did not significantly affect hepatocyte yield or viability, allowing use of primary human hepatocytes from a wide range of patients in a plethora of translational research experiments. Conclusion High levels of hepatocyte viability and yield are achievable across a broad range of patients, even in instances patients with high burdens of disease, prolonged Pringle time or higher levels of intra-operative blood loss. Tissue samples from consenting patients undergoing therapeutic liver resection provide an invaluable resource for various translational experimental platforms, including primary human hepatocytes. To date, more than 400 patients have donated tissue used in a range of basic science techniques, significantly reducing reliance on animal models.

Clinical patterns of metabolic syndrome in young, clinically stable, olanzapine-exposed patients with schizophrenia.

Schizophrenia (SCZ) is a chronic, disabling mental illness with a high disease burden and is often comorbid with metabolic syndrome (MetS). The aim of this study was to determine the prevalence of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and to explore predictive factors affecting the development and severity of MetS. A total of 274 patients with SCZ who met the inclusion criteria were enrolled in this study, and their demographic data and general clinical information were collected. Concurrently, patients were assessed for psychopathology, illness severity, and antipsychotic drug-related adverse effects. The prevalence of MetS in the target population was 35.77%, and the MetS subtype of abdominal obesity + high triglycerides + low level of high-density lipoprotein cholesterol accounted for the majority of patients in the MetS subgroup. Binary logistic regression showed that body mass index (BMI), uric acid (UA), thyroid-stimulating hormone, and QT-c interval could significantly and positively predict the development of MetS. Multiple linear regression showed that olanzapine concentration, BMI, and UA could significantly and positively predict higher MetS scores. This study reports the clinical patterns of MetS in young, clinically stable, olanzapine-exposed patients with SCZ and identifies the correlations influencing the development and severity of MetS. These findings could potentially be applied toward the prevention of and intervention in MetS.

Real-world use of androgen-deprivation therapy intensification for metastatic hormone-sensitive prostate cancer: a systematic review.

To conduct a systematic literature review of real-world data (RWD) studies to summarise treatment patterns among men with metastatic hormone-sensitive prostate cancer (mHSPC).While androgen-deprivation therapy (ADT) is a primary treatment strategy for mHSPC, ADT intensification with androgen receptor pathway inhibitors (ARPIs) and/or chemotherapy is recommended by current guidelines and has improved clinical outcomes in the last decade. We searched electronic databases (PubMed; Excerpta Medica dataBASE [EMBASE]) for eligible studies (retrospective or prospective observational RWD studies examining mHSPC treatment patterns) between database inception and July 2023, and manually screened the past 2 years of relevant conference proceedings. Of 2336 retrieved citations, 29 studies met the inclusion criteria, covering North America (United States, n = 21; Canada, n = 2), Europe (n = 8), and Asia (n = 6). Most studies utilised retrospective cohorts (n = 26) and included men with a median age of ≥70 years (n = 20). ADT monotherapy was predominantly used across geographies, followed by ADT + ARPI and ADT + docetaxel in the United States and Europe but not in Asia, where use of each combination remained low. Studies with recent electronic medical record data from cancer centres/registries showed >40% use of ADT + ARPI in the United States and Europe. Abiraterone was the most frequently used ARPI, followed by enzalutamide. Quantitative factors associated with ADT intensification were high disease burden, younger age, Eastern Cooperative Oncology Group performance status score of 0 to 1, fewer comorbidities, and oncologist physician specialty; qualitative factors were patient preference, unsatisfactory response to ADT, ability to tolerate adverse events, and absence of cost barriers. While there was an increasing trend in ADT intensification for mHSPC over the study period across geographies, use remained suboptimal considering the high proportion of patients who were still receiving ADT monotherapy only. These findings highlight the need for interventions to further optimise current mHSPC therapies with high guideline concordance.

Abstract 4140116: Adherence to Lipid Lowering Therapy among US Veterans with Atherosclerotic Cardiovascular Disease

Introduction/Background: US Veterans experience a high burden of cardiovascular disease (CVD). Improved adherence to lipid-lowering therapy (LLT) is strongly associated with reducing low-density lipoprotein cholesterol (LDL-C), which has the potential to reduce morbidity and mortality among Veterans with atherosclerotic cardiovascular disease (ASCVD). Goals/Aims: To describe adherence to statin and non-statin LLT among US Veterans with ASCVD. Methods/Approach: Using Veterans’ Health Administration (VHA) electronic health records from January 1, 2003, to December 31, 2019, we identified regular users of the VHA who were on at least one LLT within 12-months after ASCVD diagnosis. ASCVD diagnosis was identified using ICD9/10 and Current Procedural Terminology codes. Medication possession ratio (MPR) was calculated as the sum of days’ supply for all fills of a given LLT during 12-, 24-, and 36-month follow-up, divided by the number of days in the follow-up period. Medication adherence was defined as MPR ≥ 0.80. Results/Data (descriptive and inferential statistics): The total number of Veterans on an LLT within 12-months after ASCVD diagnosis was 2,194,684 [mean (SD) age=68 (10) years, 98% male, and 75% white race]. Overall proportion of patients who were adherent to LLT was 68%, 64%, and 62%, at 12-, 24-, and 36-months post ASCVD diagnosis, respectively (Table). Conclusion(s): Suboptimal adherence to LLT was observed in one third of US Veterans with ASCVD. Adherence rates were highest in the first 12 months post ASCVD diagnosis. Future studies are needed to understand factors contributing to low and declining LLT adherence over time among Veterans.

Abstract 4119868: Statin and PCSK9 Inhibitor Utilization and Spending in Medicaid between 2018 to 2022: A National Analysis

Introduction: Low-income working-aged adults in the Medicaid program have a high burden of cardiovascular risk factors and disease, but often face barriers accessing necessary therapies. Little is known about contemporary patterns of utilization and spending on lipid-lowering therapies in Medicaid programs. Goal: To evaluate national trends in utilization and spending on statins and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in Medicaid. Methods: We performed a serial cross-sectional study using the Medicaid Spending by Drug Database, which contains national-level Medicaid spending data for medications partially or fully reimbursed by Medicaid for the approximately 84 million beneficiaries. We evaluated annual trends in utilization (prescription fills) and total spending for statins and PCSK9i from 2018 to 2022, both overall and by individual drug formulation. Spending was adjusted for inflation and reported in 2022 US dollars. Results: Medicaid beneficiaries filled 20.4 million statin prescriptions in 2018 compared to 20.3 million in 2022, representing a 0.4% decrease. However, Medicaid spending on statins decreased by 7.1%, from $246.2 million to $226.8 million over the same period. Prescription fills for generic Rosuvastatin increased the most (0.79 million to 2.6 million, +224.2%), while fills for brand-name Crestor decreased the most (0.065 million to 0.003 million, -95.2%). Medicaid beneficiaries filled 121,737 prescriptions for PCSK9 inhibitors in 2022 compared to 7,617 in 2018 (+1498%), coinciding with a 640% increase in total spending ($8.9 million to $65.7 million). Repatha Sureclick was the most filled PCSK9i in Medicaid with 80,503 fills in 2022, representing $43.9 million in total Medicaid spending. Conclusions: Despite almost no change in statin utilization between 2018 and 2022, Medicaid spending on statins fell by approximately $20 million, driven by a shift from brand-name to generic formulations. In contrast, spending on PCSK9 inhibitors increased by $57 million as these medications became more widely used. Understanding these trends is critical as Medicaid programs work to ensure access to effective cardiovascular therapies while also identifying opportunities for cost efficiencies nationwide.

Abstract 4136781: Stethoscopes to Sequencers: How Next Generation Sequencing Aids Pediatric Cardiac Intensive Care Diagnosis

Background: Despite a high burden of rare genetic diseases among children admitted to cardiac intensive care units (CICUs), comprehensive guidelines for genetic testing in children with heart disease, particularly those that are critically ill, are lacking. Traditional testing methods, such as karyotype, chromosomal microarray (CMA) and candidate gene panels, are often employed based on suspected diagnoses. Rapid advancements in next-generation sequencing (NGS) technologies allow for more comprehensive genetic evaluation which is already recommended for patients with ventricular dysfunction, primary arrhythmias, and pulmonary hypertension (PH). Broad application of NGS in intensive care settings for pediatric heart disease has not been extensively investigated. Aims: Evaluate diagnostic efficacy of NGS in critically ill pediatric patients with cardiac disease. Methods: Retrospective cohort of patients who underwent exome or genome sequencing in a pediatric CICU between January 2020 and August 2023. Results: Exome or genome sequencing was performed on 49 patients with median testing age of 46 days (IQR 7-609). Primary cardiac phenotypes included congenital heart disease, ventricular dysfunction, arrhythmia, and PH. Forty-two pathogenic or likely pathogenic variants were identified and 23 (46.9%) resulted in a genetic diagnosis, of those, 16 (69.6%) were associated with a cardiac phenotype. Positivity rate did not differ between primary cardiac phenotypes but was significantly higher when the patient had associated multiple congenital anomalies (Fig. 1). Genome sequencing trended towards a higher positivity rate (54.5%) than exome (31.3%), though did not meet statistical significance (Fig. 1). Notably, 84.6% and 38.5% of the identified pathogenic variants would have remained undetectable by CMA and many commercially available gene panels, respectively. Conclusion: Exome and genome sequencing demonstrate high diagnostic yield across isolated and non-isolated cardiac disease and various cardiac phenotypes with diagnostic efficacy surpassing CMA and many commercial gene panels. As NGS technologies evolve, they promise to streamline diagnoses and enhance therapeutic decision-making for this patient population.

Abstract 4136978: Six-month Changes in Lipid Management in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program

Background: US Veterans have a high burden of cardiovascular disease (CVD). While cholesterol management is one of the most effective approaches for reducing CVD burden, over two-thirds of Veterans with atherosclerotic cardiovascular disease (ASCVD) are not optimally managed. Aims: To evaluate LDL-C monitoring, lipid lowering therapy (LLT) use, and LDL-C levels at baseline and six-months for Veterans in the Veterans Affairs Lipid Optimization Reimagined Quality Improvement (VALOR-QI) Program. Methods: VALOR-QI is a national quality improvement collaboration between the US Department of Veterans Affairs and the American Heart Association (AHA) with the goal of improving lipid management among Veterans with ASCVD. To assess and address barriers to achieving optimal lipid levels, Clinical Champions, Health Care Coaches, and participating providers from 50 VA sites work with AHA QI Consultants. Eligible Veterans (those with an ASCVD diagnosis at two outpatient or one inpatient visit or one ASCVD procedure) were considered engaged in VALOR-QI if they had a qualifying appointment with a participating provider during the program. We examined rates of LDL-C monitoring and LLT use at baseline (start of site monitoring) and 6 months after. Among Veterans who were in the program ≥6 months and had >1 LDL-C measure, we investigated percent meeting an LDL-C goal of <70 mg/dL at their first LDL-C (closest to their first visit with priority given to labs within 365 days before their first visit) and follow-up LDL-C (closest to 6 months after entering the program) and mean LDL-C change (paired t-test). Results: Six months after starting VALOR-QI, sites had a 41% increase in LDL-C monitoring and a 6% increase in LLT use. Among 29,610 Veterans engaged in the program ≥6 months with at least two lipid labs [mean (SD) age 71.0 (9.3) years, 95% men, 72% white race], the proportion who met the LDL-C goal <70 mg/dL increased from 44% at their first measure to 51% at 6-month follow-up. Among these Veterans, we observed a mean LDL-C decrease of 5.1 mg/dL (95% CI: -5.50, -4.78). Conclusion: We observed an increase in lipid monitoring and LLT use and improved LDL-C at 6-month follow-up among US Veterans engaged in VALOR-QI.

Crowdsourcing Adverse Events Associated With Monoclonal Antibodies Targeting Calcitonin Gene-Related Peptide Signaling for Migraine Prevention: Natural Language Processing Analysis of Social Media.

Clinical trials demonstrate the efficacy and tolerability of medications targeting calcitonin gene-related peptide (CGRP) signaling for migraine prevention. However, these trials may not accurately reflect the real-world experiences of more diverse and heterogeneous patient populations, who often have higher disease burden and more comorbidities. Therefore, postmarketing safety surveillance is warranted. Regulatory organizations encourage marketing authorization holders to screen digital media for suspected adverse reactions, applying the same requirements as for spontaneous reports. Real-world data from social media platforms constitute a potential venue to capture diverse patient experiences and help detect treatment-related adverse events. However, while social media holds promise for this purpose, its use in pharmacovigilance is still in its early stages. Computational linguistics, which involves the automatic manipulation and quantitative analysis of oral or written language, offers a potential method for exploring this content. This study aims to characterize adverse events related to monoclonal antibodies targeting CGRP signaling on Reddit, a large online social media forum, by using computational linguistics. We examined differences in word frequencies from medication-related posts on the Reddit subforum r/Migraine over a 10-year period (2010-2020) using computational linguistics. The study had 2 phases: a validation phase and an application phase. In the validation phase, we compared posts about propranolol and topiramate, as well as posts about each medication against randomly selected posts, to identify known and expected adverse events. In the application phase, we analyzed posts discussing 2 monoclonal antibodies targeting CGRP signaling-erenumab and fremanezumab-to identify potential adverse events for these medications. From 22,467 Reddit r/Migraine posts, we extracted 402 (2%) propranolol posts, 1423 (6.33%) topiramate posts, 468 (2.08%) erenumab posts, and 73 (0.32%) fremanezumab posts. Comparing topiramate against propranolol identified several expected adverse events, for example, "appetite," "weight," "taste," "foggy," "forgetful," and "dizziness." Comparing erenumab against a random selection of terms identified "constipation" as a recurring keyword. Comparing erenumab against fremanezumab identified "constipation," "depression," "vomiting," and "muscle" as keywords. No adverse events were identified for fremanezumab. The validation phase of our study accurately identified common adverse events for oral migraine preventive medications. For example, typical adverse events such as "appetite" and "dizziness" were mentioned in posts about topiramate. When we applied this methodology to monoclonal antibodies targeting CGRP or its receptor-fremanezumab and erenumab, respectively-we found no definite adverse events for fremanezumab. However, notable flagged words for erenumab included "constipation," "depression," and "vomiting." In conclusion, computational linguistics applied to social media may help identify potential adverse events for novel therapeutics. While social media data show promise for pharmacovigilance, further work is needed to improve its reliability and usability.

The journey to diagnosis of wild-type transthyretin-mediated (ATTRwt) amyloidosis: a path with multisystem involvement

BackgroundWild-type and hereditary transthyretin-mediated amyloidosis (ATTRwt and ATTRv amyloidosis, respectively) are progressive, fatal diseases with a broad range of clinical presentations and multisystem effects. Despite having a higher prevalence, ATTRwt amyloidosis is less well characterized due to its non-hereditary nature, and its relatively poorer disease awareness delays diagnosis. Understanding of its natural history has evolved in recent years, but this is largely based on physician-collected data rather than patients’ reports of their own experiences. A mixed methods approach was used to evaluate how the healthcare journeys of patients with ATTRv and ATTRwt amyloidosis compare.MethodsA quantitative survey was administered to US-patients diagnosed with both ATTRwt amyloidosis and ATTRv amyloidosis identified through a patient support group. Subsequent in-depth interviews with participants with ATTRwt amyloidosis were conducted. Quantitative data with related qualitative quotes from patients were produced to characterize their paths to diagnosis and the disease burden experienced.ResultsA total of 47 respondents completed the survey (ATTRv, n = 20 and ATTRwt, n = 27) and a total of 14 survey respondents with ATTRwt amyloidosis were interviewed. Survey results reported a high disease burden for patients with both conditions, with patients with ATTRwt amyloidosis reporting more diagnoses and procedures prior to their final diagnosis. Interviews with participants with ATTRwt amyloidosis revealed that patients face a high symptomatic burden of disease. Diagnosis was often delayed due to three key factors: (1) early signs of ATTRwt amyloidosis were often assumed to be related to old age; (2) many medical specialists working in silos were involved in participants’ diagnostic; and (3) there was a general lack of disease awareness. Early indicators such as carpal tunnel syndrome were often overlooked. Participants were typically diagnosed after the disease had progressed to include severe cardiac symptoms such as atrial fibrillation and severe shortness of breath. Sleep apnoea was also reported by a number of participants, with a considerable impact on quality of life.ConclusionsOur study provides insight into the overall impact of the patient journey on their quality of life and demonstrates how increased awareness of ATTRwt amyloidosis and more coordinated engagement with physicians could reduce the time to diagnosis.

Global burden and cross-country inequalities in diseases associated with high body mass index from 1990 to 2019: Result from the Global Burden of Disease Study 2019.

High body mass index (BMI) has gradually become an increased risk factor for the global burden of diseases (GBD). As the disease burden and the number of elders globally increase, it is crucial for policymakers to realise the associations between high BMI and disease burden worldwide in a timely manner and to develop effective interventions for different countries and ages. We used the GBD 2019 database to analyse the deaths and disability-adjusted life-years (DALYs) in the disease burden associated with high BMI and indicated the health inequality at the global, regional, and national levels. We applied the slope index of inequality and concentration index, two standard metrics of absolute and relative gradient inequality recommended by the World Health Organization (WHO), to quantify the distributive inequalities in the burden of diseases associated with high BMI. These rates were reported per 100 000 population as crude incidence rates, death rates, and DALYs rates. All the estimates were generated with a 95% uncertainty interval (UIs). Globally, we revealed that an estimated age-standardised mortality rate associated with high BMI is 6.26 million (95% UIs = 3.99, 8.91). The age-standardised DALYs rate is 19.32 million (95% UIs = 12.77, 26.40), and the global population attributable fraction was 9% (95% UIs = 5, 12) in 2019. The largest number of high-BMI-related deaths in women mainly concentrated in the age group of 65-79 years, whereas the largest number in men was in the age group of 60-69 years. The age-standardised DALYs rate of diseases associated with high BMI was larger in the high-middle and middle socio-demographic index (SDI) (population attributable fraction (PAF) = 11 and PAF = 9) regions than those with high SDI (PAF = 1) and low SDI (PAF = 5) regions. In this study, our results showed that the disease burden of global deaths and DALYs associated with high BMI has substantially increased between 1990-2019. Furthermore, we demonstrated that countries with higher SDI development levels shoulders higher burden of diseases associated with high BMI. Future policies to prevent and reduce the burden should be developed and implemented based on country-specific development status.

Determination of the Level of von Willebrand Factor, ADAMTS13, and Ratio of ADAMTS13:von Willebrand Factor in Sickle Cell Disease Patients.

Sickle cell anemia (SCA) is a hypercoagulable state characterized by a significant alteration in hemostatic parameters which may predispose an increased risk of vaso-occlusive crisis (VOC). Sickle cell disease (SCD) is the most common genetic disorder in sub-Saharan Africa. Nigeria bears a high disease burden with an estimated prevalence of 1%-3% of its population being affected by the disease. The study seeks to determine the role of von Willebrand factor (VWF), ADAMTS13, and the ratio of ADAMTS13:VWF antigen in the pathogenesis of VOC. The objective of this study is to evaluate the level of VWF, ADAMTS13, and their ratio in SCD subjects in Calabar and to determine their role in the pathogenesis of VOC. This is a comparative study carried out at the University of Calabar Teaching Hospital (UCTH), Calabar. Sixty SCA patients were evaluated in VOC and steady states as well as five parented healthy controls. VWF: Ag and ADAMTS13:Ag were evaluated using Assaypro enzyme-linked immunosorbent assay kits with Lot nos. 01751728 and 04222167R, respectively. Data were analyzed by IBM SPSS Chicago software version 21. The study was approved by the UCTH Institution Ethical Review Board. The mean ages of the SCA subjects and controls were 23.5 ± 7.2 years and 26.5 ± 5.6 years, respectively (P = 0.706). There were 23 (38.3%) males in the SCA group and 21 (42.0%) females in the controls. There was no significant difference in their sex distribution (P = 0.063). The mean (standard deviation [SD]) of VWF in VOC, steady state, and controls were 2.52 ± 0.34, 1.34 ± 0.23, and 1.41 ± 0.23 IU/mL, respectively. The differences in mean were significantly higher in VOC state (P = 0.003). The mean ± SD of ADAMTS13 in VOC, steady state, and controls were 0.61 ± 0.10, 0.44 ± 0.06, and 0.62 ± 0.10 μg/L, respectively. ADAMTS13 levels did not differ significantly across the groups (P = 0.270). Similarly, there was no significant difference between ADAMTS13:VWF ratios across the groups (P = 0.318). VWF level is elevated in VOC state and thus may be implicated in the pathogenesis of VOC. ADAMTS13 and the ratio of ADAMTS13:VWF are not significantly affected in VOC.

Recurrent Hospitalizations for Fluid Overload in Diabetes with Kidney Failure Treated with Dialysis.

Background & Aims Diabetes Mellitus is the most common cause of end-stage kidney disease (ESKD) in Singapore. ESKD patients have high disease burden and are at increased risk of recurrent hospitalizations, including fluid overload. This study aimed to characterize the risk factors associated with readmissions for fluid overload that will identify high-risk hospitalizations for interventions to reduce readmissions. Methods Retrospective cohort study of all hospitalizations for fluid overload in adults with diabetes and ESKD on dialysis in SingHealth hospitals between 2018 and 2021. Fluid overload was defined by discharge codes for fluid overload, heart failure, pulmonary edema, and generalized edema until 30th December 2022. Multivariable Cox regression analysis using the Prentice, Williams and Peterson Total Time (PWP-TT) model was performed for the outcomes of readmissions for fluid overload within 30 days and 90 days of discharge. Results Among 3234 hospitalizations for fluid overload, readmission for fluid overload within 30-day and 90-day occurred in 585 (18.1%) and 967 (29.9%) hospitalizations, respectively. Ischemic heart disease, peripheral vascular disease and lower hemoglobin level were independently associated with readmissions for fluid overload within 30 and 90 days. Additionally, heart failure, hemodialysis (compared to peritoneal dialysis) and lack of statin at discharge were associated with increased 90-day readmission risk. Conclusion Modifiable (hemoglobin level, statin use) and non-modifiable factors (ischemic heart disease, peripheral vascular disease and heart failure) influenced the risk of readmission for fluid overload. These results may guide risk stratification and inform targeted interventions to reduce avoidable, unplanned readmissions for recurrent fluid overload among individuals with diabetes and ESKD.

Clinical outcomes of pediatric patients with congenital toxoplasmosis in a fourthlevel center Introduction. Congenital

Congenital toxoplasmosis is a highly prevalent parasitic disease worldwide, with a high burden of disease and neurodevelopmental involvement in pediatric patients. To describe the clinical sequelae and neurodevelopmental state of pediatric patients with congenital toxoplasmosis at the Hospital Militar Central during 2013 to 2020. We conducted an observational, descriptive, cross-sectional study with an analytical component, including pediatric patients diagnosed with congenital toxoplasmosis. Patients consulted the Hospital Militar Central from January 2013 to December 2020. The Ages and Stages Questionnaires 3 neurodevelopmental scale was applied to children under six years old. Forty-five patients with confirmed congenital toxoplasmosis were included, with a mean age of 5.9 years; 60% were male; 11.2 % were symptomatic at birth, and 33% presented chorioretinitis. During the follow-up, 73% presented ophthalmologic sequelae, 64% cerebral calcifications, 4.4% hydrocephalus, 11.2% cerebral palsy, and 13.4% focal epilepsy. In children under six years old, 58% presented neurodevelopmental compromise, and in those over six years old, 62% had cognitive deficits. In this cohort, 68% of the patients received posnatal treatment, with a statistically significant association between not receiving treatment and ophthalmological sequelae (OR = 5.2; p < 0.001). Congenital toxoplasmosis is associated with important long-term sequelae similar to those described in several Latin American series. These findings highlight the importance of early diagnosis, evaluation, treatment, and timely interdisciplinary follow-up of patients in our country to improve their prognosis.

Treatment satisfaction in patients with hidradenitis suppurativa: A real-world survey from the EU5 and US.

Introduction Hidradenitis suppurativa (HS) is a debilitating, inflammatory skin disorder. Treatment strategies in patients with HS are challenging; real-world evidence in a HS population is warranted for greater disease understanding. The objective of this analysis was to describe real-world treatment patterns and treatment satisfaction in patients with HS. Methods This was a cross-sectional market research survey with retrospective data collection in patients with HS from the United States and five European countries (France, Germany, Italy, Spain, United Kingdom) between November 2020 and April 2021, using physician- and patient-reported surveys. Eligible physicians were general dermatologists actively managing patients with HS; dermatologists were required to have consulted with ≥2 patients with HS in the previous 12 months. Adult (≥18 years) and adolescent (10‒17 years) HS patients visiting a participating dermatologist were included. Outcomes included treatment patterns, flare status, treatments prescribed in response to flares, previous surgeries, barriers to biologics, and patient- and physician-reported satisfaction with the disease control provided by treatment. Results Survey data from 1787 patients were collected from 312 dermatologists. The most frequently prescribed treatments were topicals, oral antibiotics, and antiseptic washes/creams at diagnosis and sampling. At sampling, biologics were more frequently prescribed in patients with more severe disease (prescribed in 26.6%, 31.0% and 52.4% of patients with mild, moderate, and severe disease, respectively); oral antibiotics (48.8%), topicals (37.4%), and biologics (34.3%) were the most frequently prescribed treatment classes in response to a flare. Of patients currently not receiving a biologic, dermatologists reported that 18.9% of patients' condition warranted their use. Approximately one quarter of dermatologists (24.5%) and patients (27.4%) were not satisfied with current treatment; of patients who were dissatisfied, 12.8% reported they would never raise their dissatisfaction with their doctor. Conclusion These real-world data suggest a high disease burden and potential undertreatment in patients with HS. Patients received multiple treatments, and a notable proportion underwent surgery. Robustly integrating the patient voice in HS treatment decisions may lead to better outcomes and improved treatment satisfaction.

A bibliometric analysis of studies conducted over the last 10 years on cardiovascular disease risk identification and prevention in primary care

Objective: This bibliometric analysis was conducted to determine the trends of studies on cardiovascular disease risk identification and prevention in primary care from 2013 to 2024 and visualize the latest developments. Methods: The data were collected in February-March 2024 from the database “Web of Science Core Collection,” the analysis was carried out using the VOSviewer program. The change in the number of publications of the published articles by year, author, country, and institution citation analyses, country, institution, and author collaboration analyses, journal and author co-citation analyses, and keyword analyses were evaluated. Results: Five hundred and ninety-two authors from 64 countries and 377 institutions contributed to 443 studies published in 80 journals between 2013 and 2024 on determining and preventing cardiovascular disease risk in primary care. "BMC Family Practice" was the journal in which most articles were published, and "Circulation" was the most cited. The first three countries that support published articles most are the United States, England, and Australia. Focusing on the topics "blood-pressure control", "coronary-artery calcium", "physician-pharmacist collaboration", "low-density lipoprotein cholesterol", "health-risk assessment", "pollution", "primary care", "coronary heart disease", "prevention", "cardiovascular disease" and "mortality" will help fill the gap in the field. Conclusions: This bibliometric analysis has shown increasing interest in studies related to cardiovascular disease risk and prevention in primary care. Primary prevention guidelines are important resources in addressing risk factors. Global collaborations and long-term studies are necessary in this field, led by developed countries with a high disease burden.

Peripheral Endothelial Dysfunction Is Associated With Incident Major Depressive Disorder.

A subset of individuals with major depressive disorder (MDD) have a high burden of cardiovascular risk factors and cerebral small-vessel disease, implicating vascular disease in the development of depression. Cross-sectional studies demonstrate a link between endothelial dysfunction and MDD, but the prospective association between peripheral endothelial dysfunction (PED) and an incident diagnosis of MDD is unknown. Patients undergoing a baseline assessment of cardiovascular risk were evaluated for PED using reactive hyperemia-peripheral arterial tonometry (≤1.8 consistent with PED). Patient medical records were reviewed to identify those who underwent a formal clinical evaluation of MDD after the index PED evaluation. The frequency of PED was compared in those with and without MDD. Logistic regression analyses were performed to assess the association between baseline PED and incident MDD. Between January 2006 and December 2020, 1614 patients underwent testing for PED. Four hundred eighty-four (30.1%) patients underwent a formal evaluation for MDD after (0-15 years) the index procedure (mean±SD age, 52.8±13.8 years; 65.2% women). Of these, 157 (32.4%) had PED and 108 (31.0%) were diagnosed with MDD. Individuals with MDD had a higher frequency of PED (40.2% versus 30.2%; P=0.034) compared with those without MDD. In multivariable analyses, PED was significantly associated with MDD (odds ratio, 2.3 [95% CI, 1.4-3.8]; P<0.001). PED is significantly associated with incident MDD. Thus, PED may be a useful marker to identify individuals at increased risk of depression who may benefit from more frequent and earlier management strategies.

Effectiveness of transitional care in Inflammatory Bowel Disease; Development, Validation, and Initial outcomes of a Transition Success Score.

The effectiveness of transition programs from paediatric to adult healthcare in adolescents with inflammatory bowel disease is not clear, as prospective studies using validated outcome measures for transition are lacking. This study aimed to develop and validate a quantitative Transition Success Score, and to apply it in a multicenter setting to assess the effectiveness of transitional care. The Top 10 outcome items related to successful transition, identified through an international Delphi study with IBD stakeholders, were integrated into a generic questionnaire, the Transition Success Score. In a prospective, multicenter study, Transition Success Score was scored by adult healthcare providers, young adult patients and caregivers, 9-15 months after transfer of care. In seven Dutch hospitals, 160 patients completed the Transition Success Score. The mean score was 25 (range 17-27), 25.6% of patients achieving maximum score. Hypothesis testing for construct validity revealed significant associations with characteristics related to transitional care, such as knowledge, independence, and quality of life (p <0.005). Structural validation indicated the score was most effective at discerning lower levels of transition success. Internal consistency was acceptable (0.64). High disease burden, exacerbation during or after transfer, and certain personality profiles were associated with lower scores. The Transition Success Score serves as a quantitative tool to evaluate the effectiveness of transitional care interventions and to identify inflammatory bowel disease patients at risk of encountering challenges during the transition to adult healthcare.