Registry Data Research Articles

Bacterial contamination of autologous blood salvaged during deceased donor liver transplantation: a prospective observational study.

Decompensated cirrhotic patients experience severely increased intestinal permeability and bacterial translocation. Thus, autologous blood salvaged during deceased donor liver transplantation (DDLT) may be contaminated with enteric bacteria. We aimed to evaluate bacterial contamination of autologous blood salvaged during DDLT and its association with post-transplant bacteremia. In 30 patients undergoing DDLT, bacterial culture was performed in salvaged autologous blood samples: one before graft reperfusion (non-leukoreduced) and two after graft reperfusion (non-leukoreduced and leukoreduced). The primary outcome was bacterial contamination of salvaged autologous blood. Seven of 30 patients (23.3%) were positive for bacteria (3 enteric/4 non-enteric) before graft reperfusion while 11 patients (36.7%) were positive (5 enteric/6 non-enteric) after graft reperfusion. Six of 7 patients who were positive for bacteria before graft reperfusion were positive after graft reperfusion with the same bacteria. Only 4 of 11 contaminated blood samples were converted to negative after leukoreduction. Post-transplant bacteremia risk was insignificantly greater in patients who received autologous blood with bacteria than in patients without bacteria (30.0% vs. 5.0%, P = 0.06). We found contamination of salvaged autologous blood with enteric bacteria throughout DDLT and incomplete performance of leukoreduction, indicating high bacterial load. The potential association between contaminated autotransfusion and post-transplant bacteremia warrants further validation in a larger prospective study.Clinical trial notation: This study was registered at the Clinical Research Information Service (CRiS; https://cris.nih.go.kr ; No. KCT0007223; principal registration investigator: Sangbin Han, date of registration: April 25, 2022).

Effect of weighted blankets on sleep quality among adults with insomnia: a pilot randomized controlled trial.

Weighted blanket is an emerging non-pharmacotherapy for sleep disorders, but its effect on sleep among relatively healthy adults with insomnia remains uncertain. This study aimed to evaluate whether weighted blankets could better improve sleep quality and sleep-related symptoms among adults with insomnia. In a prospective, pilot randomized controlled trial conducted in three tertiary hospitals in China, participants with clinical insomnia were randomized (1:1) to receive weighted blanket intervention or normal blanket intervention for 1 month by random-number tables. The primary outcomes were sleep quality assessed with Pittsburgh Sleep Quality Index (PSQI) and insomnia severity assessed with Insomnia Severity Index. Subjective outcomes were measured at baseline, 1 week, and 1-month post-intervention. Sleep was also objectively monitored by actigraphy. We did analysis by intention to treat. A total of 102 participants were randomly assigned to receive weighted blanket intervention (n = 52) or normal blanket intervention (n = 50). 95 (93.1%) participants completed the follow-up, and 7 (6.9%) participants dropped out of the study. The weighted blanket group had significant improvements in sleep quality compared to the normal blanket group after 1 month of intervention (changes in the mean [SD] of PSQI score: -4.1 [4.1] vs. -2.0 [3.2], P = 0.006). Similar results were observed for daytime sleepiness, stress, anxiety, fatigue, and bodily pain (all P < 0.05). Recordings from actigraphy showed a decrease in the mean (SD) of the number of awakenings in weighted blanket group (-1.4 [9.5]) and an increase in normal blanket group (+ 1.0 [7.9]) (P = 0.280). No severe adverse events occurred. Weighted blanket might be an effective, safe and promising non-pharmacotherapy tool for improving sleep-related symptoms among adults with insomnia, although validation with a larger sample size is needed. Chinese Clinical Trial Registry: ChiCTR2300078011, date of registration: 11/27/2023, retrospectively registered.

Effectiveness of a multi-component sleep-mood group intervention on improving insomnia in university students - a pilot randomized controlled trial.

Sleep and mental health problems are very common in university students. The objective of this study was to assess the effectiveness of a multi-component sleep-mood intervention on improving sleep and mental health in university students with clinically significant insomnia symptoms, and to investigate possible mediators. Thirty-five participants were randomized to the Sleep Mood Intervention: Live Effectively (SMILE) intervention (n = 23), or wait-list group (n = 12). SMILE is a multi-component group therapy and includes elements of cognitive behavioral therapy for insomnia (CBT-I), mindfulness, and lifestyle modifications, in four weekly two-hour sessions. The primary outcome was insomnia severity. Secondary outcomes were severity of depression and anxiety, and quality of life (QoL). Dysfunctional beliefs and attitudes about sleep and pre-sleep arousal were assessed as mediators. Intention-to-treat analysis showed significant time x treatment interaction on insomnia symptoms p = .02, partial η²=0.15, d = 0.84 [95% CI: 0.63 to 1.14], with significantly lower insomnia severity for SMILE compared to waitlist at post-test. No significant effects were found on depression d = 0.02 [95% CI: -0.35 to 0.37], anxiety d = 0.15 [95% CI: -0.16 to 0.53], and QoL d = 0.09 [95% CI: -0.25 to 0.42]. Dysfunctional beliefs mediated the effect on insomnia severity, but pre-sleep arousal did not. This integrated group intervention is associated with reductions in insomnia symptoms in university students. Since no significant effects were detected on mood and QoL, future studies with larger sample size may explore the effects of this intervention on these outcomes. Registry: Overzicht van Medisch-wetenschappelijk Onderzoek. NL-OMON46359. Date of registration: September 18th, 2018.

Long-Term Cancer Outcomes Following Bariatric Surgery: A Comparative Analysis of Surgical Procedures

Background/Objectives: Metabolic and bariatric surgery (MBS) is known to reduce cancer risk. However, the association between specific bariatric procedures and cancer incidence is not well-studied. This study examined the association between four different MBS procedures and cancer incidence. Methods: Bariatric surgery registry data were linked with statewide cancer registry data from 1979 to 2018. The study included 27,092 adult subjects (aged ≥ 18 years old at surgery) who underwent MBS (BMI ≥ 30 kg/m2 at surgery) from 1979 to 2017. Cancer records were linked to MBS patient records, resulting in 1547 cancer cases. Cox proportional hazards regression was used to examine the association between MBS procedure types and cancer incidence. Results: Of all patients, 75% underwent Roux-en-Y gastric bypass (RYGB), 9% adjustable gastric banding (AGB), 10% sleeve gastrectomy (SG), and 6% duodenal switch (BPD-DS). The overall cancer incidence during the follow-up period was 6.4% for RYGB, 4.6% for AGB, 1.6% for SG, and 5.9% for BPD-DS. The mean follow-up duration from surgery to cancer incidence or censoring was 167 months (standard deviation = 121 months). Compared to RYGB, patients who underwent AGB (Hazard Ratio [HR] = 1.26, p = 0.03) and BPD-DS (HR = 1.91, p &lt; 0.01) had a significantly higher hazard of developing cancer, while SG (HR = 1.17, p = 0.33) showed no significant difference. Conclusions: These findings suggest that AGB and BPD-DS may be associated with higher cancer risks compared to RYGB. Additional large population studies are needed to better understand the long-term cancer risks and mechanisms associated with different MBS types.

Adapting COVID-19 research infrastructure to capture influenza and respiratory syncytial virus alongside SARS-CoV-2 in UK healthcare workers winter 2022/23 and beyond: protocol for a pragmatic sub-study

Introduction During the COVID-19 pandemic, extensive research was conducted on SARS-CoV-2; however, important questions about other respiratory pathogens remain unanswered. A severe influenza season in 2022–2023 with simultaneous circulation of SARS-CoV2 and respiratory syncytial virus is anticipated. This sub-study aims to determine the incidence and impact of these respiratory viruses on healthcare workers, the symptoms they experienced, the effectiveness of both COVID-19 and influenza vaccination and the burden of these infections on the National Health Service (NHS) workforce. Methods and analysis This is a longitudinal prospective cohort sub-study, utilising the population and infrastructure of the SARS-CoV-2 Immunity &amp; Reinfection Evaluation (SIREN) study, which focuses on hospital staff in the UK. Participants undergo fortnightly nucleic acid amplification testing on a multiplex assay including SARS-CoV-2, influenza A and B and RSV, regardless of symptoms. Questionnaires are completed every two weeks, capturing symptoms, sick days, exposures, and vaccination records. Serum samples are collected monthly or quarterly from participants associated with a SIREN site. This sub-study commenced on 28/11/22 to align with the predicted influenza season and participants’ influenza vaccine status. The SIREN Participant Involvement Panel shaped the aims and methods for the study, highlighting its acceptability. UK devolved administrations were supported to develop local protocols. Analysis plans include incidence of asymptomatic and symptomatic infection, comparisons of vaccination coverage, assessment of sick day burden, and effectiveness of seasonal influenza against infection and time off work. Data are also integrated into UKHSA nosocomial modelling. Ethics and dissemination The protocol was approved by the Berkshire Research Ethics Committee (IRAS ID 284460, REC Reference 20SC0230) on 14/11/2022. Participants were informed in advance. As the frequency and method of sampling remained the same, implied consent processes were approved by the committee. Participants returning to the study give informed consent. Regular reports to advisory groups and peer-reviewed publications are planned to disseminate findings and inform decision making. Clinical trial registration number: ISRCTN11041050; registration date: 12 January 2021. Sub study included in protocol version: v8.0, and amended in v9.0

The effectiveness of a problem-solving intervention with workplace involvement on self-reported sick leave, psychological symptoms and work ability: a cluster randomised clinical trial.

Problem-solving interventions with workplace involvement (PSI-WPI) have been shown to reduce sick leave and increase return to work in an occupational health services context. However, many employees struggle with reduced work functioning, anxiety-, and depressive symptoms up to 12months after a sick leave episode, and it is unclear if the intervention affects outcomes other than sick leave. The aim of this study is to investigate if a PSI-WPI added to care as usual (CAU) is superior to CAU with respect to self-reported sick leave, psychological symptoms, work ability, work performance, and health after RTW when provided in primary care. Employed individuals aged 18-59years on sick leave (2 to 12weeks) diagnosed by a physician at a primary care center with mild to moderate depression, anxiety, or adjustment disorder were enrolled in a two-armed cluster-randomised trial evaluating the effectiveness of a PSI-WPI. Multiple outcomes were recorded at baseline, six months, 12months, and every fourth week during the study period. Outcomes were categorised into psychological symptoms, health, work ability, work performance, and self-reported sick leave. Data were analysed using MANOVA, GEE (Generalized Estimating Equations), and cox regression. One hundred ninety-nine individuals responded to the invitation to participate; one participant withdrew, one was excluded as the employment ended, nine did not answer the baseline survey, and three were removed from the analysis due to missing data. The analysis included 81 subjects who received the intervention and 104 subjects who received the control. Baseline characteristics were similar across both groups. No differences between the groups were found among either variables except one. There was a significant difference between the groups in self-rated health (EQ5D) in favour of the CAU group from baseline to six-month follow-up, with a mean difference of -8.44 (-14.84, -2.04). A problem-solving intervention with workplace involvement added to CAU did not result in statistically significant reductions in outcomes. Further research is needed to understand why problem-solving interventions appear to have an effect on sick leave in an occupational health services context and not in a primary care context. NCT3346395, registration date 2017-11-17.

Simplification of a registry-based algorithm for ejection fraction prediction in heart failure patients: Applicability in cardiology centres of the Netherlands.

Left ventricular ejection fraction (EF) is used to categorize heart failure (HF) into phenotypes but this information is often missing in electronic health records or non-HF registries. We tested the applicability of a simplified version of a multivariable algorithm, that was developed on data of the Swedish Heart Failure Registry to predict EF in patients with HF. We used data from 4,868 patients with HF from the Cardiology Centers of the Netherlands database, an organization of 13 cardiac outpatient clinics that operate between the general practitioner and the hospital cardiologist. The algorithm included 17 demographical and clinical variables. We tested model discrimination, model performance and calculated model sensitivity, specificity, positive and negative predictive values for EF ≥ vs. <50% and EF ≥ vs. <40%. We additionally performed a multivariable multinomial analysis for all three separate HF phenotypes (with reduced, mildly reduced and preserved EF) HFrEF vs. HFmrEF vs. HFpEF. Finally, we internally validated the model by using temporal validation. Mean age was 66 ±12 years, 44% of patients were women, 68% had HFpEF, 17% had HFrEF, and 15% had HFmrEF. The C-statistic was of 0.71 for EF ≥/< 50% (95% CI: 0.69-0.72) and of 0.74 (95% CI: 0.73-0.75) for EF ≥/< 40%. The model had the highest sensitivities for EF ≥50% (0.72, 95% CI: 0.63-0.75) and for EF ≥40% (0.70, 95% CI: 0.65-0.71). Similar results were achieved by the multinomial model, but the C-statistics for predicting HFpEF vs HFrEF was lower (0.61, 95% CI 0.58-0.63). The internal validation confirmed good discriminative ability. A simple algorithm based on routine clinical characteristics can help discern HF phenotypes in non-cardiology datasets and research settings such as research on primary care data, where measurements of EF is often not available.

Home Mechanical Ventilation and Risk of Hospitalization in Obesity Hypoventilation Syndrome - The Population-based DISCOVERY Study.

Patients with obesity hypoventilation syndrome (OHS) have high risk of hospitalization, which might be decreased by home mechanical ventilation (HMV). To evaluate annualized hospitalization rate (AHR) and change in AHR in patients with OHS starting home mechanical ventilation (HMV), and explore if there were any difference in AHR by starting HMV acutely or electively. Population-based longitudinal study of patients with OHS starting HMV in the Swedish DISCOVERY cohort between 1996 and 2018, cross-linked with the National Patient Registry for national data on hospital admissions. AHR was calculated for each patient for three years before (Year -3, -2, -1) and three years after (Year 1, 2, 3) the year of starting HMV (Year 0; start date ± 6 months). Differences in AHR were analyzed using Wilcoxon signed-rank test (between years) and Mann-Whitney U test (between acute/elective). Proportion of patients hospitalized in each year was analyzed and comparison between years was done with McNemar´s test. Factors associated with change in AHR were identified using multivariate linear regression models. In total, 2,445 patients were included: 47% females, mean age 62.3 ± 12.2 years, and 1,418 (58%) started HMV electively. Overall, AHR decreased with 0.88 (95%CI 0.74-1.02) hospitalization/year after start of HMV and starting treatment acutely was associated with greater decrease in AHR. There was no statistically significant difference in AHR in Year 1 between acute and elective start (P=0.199). The year after start of HMV, proportion of patients hospitalized decreased from 84% to 54% (P<0.05). Initiation of HMV was associated with reduced hospitalization rate in patients with OHS, irrespective of acute or elective start. Majority of patients with OHS are hospitalized in the year of HMV initiation.

Non-adherence to antidementia medications and associated factors: a study of Spanish population-based registry data

IntroductionWith an increasing prevalence, dementia is one of the most disabling diseases among the elderly. Impaired cognitive function and behavioral and psychological symptoms predispose patients to medication non-adherence, resulting in increased morbidity, mortality, and healthcare costs. The aim of this study was to estimate the prevalence of non-adherence to antidementia medications and to identify the main predictors.MethodsA population-based registry study was conducted in 2022 in Castile and Leon, Spain. A total of 17,563 patients with dementia were included. The medication possession ratio (MPR) was used as an indirect method to measure adherence. The cut-off point for determining that a patient was nonadherent was 80% of MPR. Multivariate logistic regression was used to identify predictors of nonadherence based on sociodemographic and health-related variables.ResultsIn 2022, 6.2% of the population over 80 years old used antidementia medications. Of these patients, 70% were women, 28.15% were institutionalized, and over 90% were polymedicated and had multiple prescribers. The most used medicines were donepezil (43.49%), rivastigmine (36.84%), and memantine (30.7%). The combined use of an acetylcholinesterase inhibitor plus memantine was relevant (13.33%). Men were less adherent than women, and the prevalence of non-adherence decreased with age. The medication associated with the highest prevalence of non-adherence was rivastigmine (19%), followed by donepezil (17%) and memantine (13.23%). Institutionalized patients (13%) and patients on combination therapy (13.29%) had the lowest prevalence of non-adherence. Protective factors against non-adherence include institutionalization, polymedication, use of memantine or combination therapy, and comorbid mental illness.ConclusionsIn Castile and Leon, one in six patients were non-adherent to antidementia medications. Younger male patients with cardiometabolic disease are more likely to be non-adherent to antidementia medications. On the other hand, institutionalization is a protective factor against non-adherence, but still 10% of nursing home patients are non-adherent to antidementia medications.

Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundInflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties.MethodsThis is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB).DiscussionModulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints.Trial registrationRegistered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.

Expected benefits and concerns regarding virtual reality in caring for terminally ill cancer patients – a qualitative interview study

BackgroundMany palliative cancer patients require inpatient hospital treatment for medical reasons, which contrasts their frequent desire to be at home. Virtual reality (VR) could be a way of bringing the home environment closer to them. First observations have shown benefits from VR for inpatients in palliative care. The aim of this qualitative, descriptive study was to explore the expectations of in-patients suffering from incurable cancer and their relatives about VR, in particular individualized VR images of the patients’ own home.MethodsSemi-structured interviews with inpatients suffering from incurable cancers and their relatives in three medical settings (palliative care, hematology, radiotherapy) of a German university hospital. Qualitative content analysis about expected benefits and concerns regarding VR-videos showing their private home; defining the main topics deductively and the subcategories inductively. We also assessed the patients’ subjective perspective on their remaining time to live to estimate the impact of double awareness on the results. The Patient Advisory Board informed the study protocol and conduct.ResultsWe interviewed 15 patients (8 men; age M = 63.4, SD = 11.34; range 39–82) under palliative care, and four relatives. We organized the interview content in 6 themes (general interest, desired content, non-desired content, expected benefits, concerns, and irregularities) and 26 sub-themes. Most patients and relatives were interested in using VR during hospital treatment. They often preferred viewing nature or tourist sites over seeing their home or family. Reasons could be linked to privacy concerns and the general desire for distraction from the current situation that they specified with their expectation of well-being, a break from the patient-experience, the pursue of curiosity, and the VR evoking fond memories.ConclusionVR seems to be of interest for palliative cancer patients, especially as distraction and relief from their illness. The desired content can be very different, so a choice from a selection of VR-content should be made available. If patients want to see videos of their own home, recordings by relatives instead of study or hospital staff seem to meet the need for privacy.Trial registrationRegistered at Deutsches Register Klinischer Studien; registration number: DRKS00032172; registration date: 11/07/2023. https://drks.de/search/de/trial/DRKS00032172.

ACVECC-Veterinary Committee on Trauma registry report 2020-2021.

To report summative data from the American College of Veterinary Emergency and Critical Care (ACVECC)-Veterinary Committee on Trauma (VetCOT) registry, with further individual evaluation of university and private practices and level I and II Veterinary Trauma Centers (VTCs). Multi-institutional registry data report, January 1, 2020, to December 31, 2021. VTCs identified and verified by ACVECC-VetCOT. Dogs and cats with evidence of trauma. Data were input to a web-based data capture system (REDCap) by data entry personnel trained in registry software use and operational definitions of data variables. Patient data on demographics, trauma type, preadmission care, trauma severity assessment at presentation (modified Glasgow Coma Score and Animal Trauma Triage score), key laboratory parameters, interventions, and outcome were collected. Summary descriptive data for each species are reported. Twenty-two VTCs contributed data to the VetCOT registry during a 24-month period, culminating in a total of 9758 complete trauma case records for dogs and 11734 for cats. Head trauma in dogs and cats was seen at a higher percentage in both university-only VTCs (encompassing both level I and II) (20.1% and 24.1%, respectively) and level I-only VTCs (24.3% and 24.1%, respectively), in comparison to private-only VTCs (encompassing both level I and II) (13.5% and 16.2%, respectively) and individual level II VTCs (14.1% and 18.9%, respectively). Canine and feline surgical procedures were performed at a higher percentage at university VTCs (50% and 40.5%, respectively) compared to private VTCs (39.2% and 28.6%, respectively). Overall survival to discharge for dogs and cats remains high at 93.1% and 83.6%, respectively. The VetCOT registry has continued to show powerful potential in collating a large, multifaceted, international dataset in trauma for both dogs and cats. As published in previous VetCOT registry reports, survival to discharge has remained static across both university and private practice veterinary hospitals; however, further breakdown has identified university and level I VTCs admitting and managing a higher number of head traumas, as well as university VTCs performing a higher proportion of surgical procedures. Data from this registry will continue to aid in the design of clinical trials, prospective observational studies, and translational research, which will improve the understanding and outcome of trauma patients.

Association of Homelessness and Unstable Housing With Cardiovascular Care Utilization Among Veterans.

Veterans are disproportionately more likely to experience homelessness and unstable housing (HUH) compared with the general population. Cardiovascular disease is the leading cause of death among Veterans experiencing HUH. We aimed to understand whether HUH status among Veterans with preexisting cardiovascular disease was associated with disparities in cardiovascular care access and utilization. Retrospective study of all Veterans with preexisting cardiovascular disease between 2017 and 2019 using Veterans Affairs Corporate Data Warehouse and Homeless registry data. Primary outcomes were annual outpatient visits for cardiovascular disease management and visits with cardiovascular disease-related specialists. Secondary outcomes included cardiovascular disease-related procedures and emergency department visits and hospitalizations. HUH status was determined based on response to a screener, diagnostic codes, or use of homelessness services, and outcomes were assessed in the first year HUH status was determined. After applying inverse probability of treatment weighting, negative binomial and logistic regression models were fit to estimate the association between experiencing HUH and the outcomes of interest. Among 1 357 973 Veterans (mean age, 71.6 [SD=10.6] years; 2.5% female) with preexisting cardiovascular disease, 56 093 were identified as experiencing HUH during the study period. Veterans experiencing HUH had fewer outpatient visits for cardiovascular disease management or with cardiovascular disease-related specialists (4.3% [95% CI, 2.5%-6.1%] and 14.1% [95% CI, 12.5%-15.8%], respectively) compared with housed Veterans. HUH status was associated with lower rates of receiving certain procedures including coronary artery bypass graft, lower extremity revascularization, and carotid artery stenosis interventions and higher rates of all-cause and cardiovascular emergency department visits and hospitalizations. Veterans with chronic cardiovascular conditions experiencing HUH had lower rates of outpatient visits for cardiovascular disease management and higher rates of emergency department visits and hospitalizations. Given the disproportionate burden of cardiovascular disease in this population, interventions to improve access to cardiovascular care are needed.

Evaluating machine learning model bias and racial disparities in non-small cell lung cancer using SEER registry data.

Despite decades of pursuing health equity, racial and ethnic disparities persist in healthcare in America. For cancer specifically, one of the leading observed disparities is worse mortality among non-Hispanic Black patients compared to non-Hispanic White patients across the cancer care continuum. These real-world disparities are reflected in the data used to inform the decisions made to alleviate such inequities. Failing to account for inherently biased data underlying these observations could intensify racial cancer disparities and lead to misguided efforts that fail to appropriately address the real causes of health inequity. Estimate the racial/ethnic bias of machine learning models in predicting two-year survival and surgery treatment recommendation for non-small cell lung cancer (NSCLC) patients. A Cox survival model, and a LOGIT model as well as three other machine learning models for predicting surgery recommendation were trained using SEER data from NSCLC patients diagnosed from 2000-2018. Models were trained with a 70/30 train/test split (both including and excluding race/ethnicity) and evaluated using performance and fairness metrics. The effects of oversampling the training data were also evaluated. The survival models show disparate impact towards non-Hispanic Black patients regardless of whether race/ethnicity is used as a predictor. The models including race/ethnicity amplified the disparities observed in the data. The exclusion of race/ethnicity as a predictor in the survival and surgery recommendation models improved fairness metrics without degrading model performance. Stratified oversampling strategies reduced disparate impact while reducing the accuracy of the model. NSCLC disparities are complex and multifaceted. Yet, even when accounting for age and stage at diagnosis, non-Hispanic Black patients with NSCLC are less often recommended to have surgery than non-Hispanic White patients. Machine learning models amplified the racial/ethnic disparities across the cancer care continuum (which are reflected in the data used to make model decisions). Excluding race/ethnicity lowered the bias of the models but did not affect disparate impact. Developing analytical strategies to improve fairness would in turn improve the utility of machine learning approaches analyzing population-based cancer data.

Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study.

Childhood cancer treatments predispose to late health problems and premature death. Our aim was to use national registry data to study associations between cancer therapy exposures and late health outcomes in aging male childhood cancer survivors (CCS). The study comprised 200 male CCS (survival ≥5 years) treated with conventional cancer therapy at a single institution in 1964-2000 and 1000 matched population controls. Analyses involved registry-based data on prescription drug purchases, reimbursements for chronic conditions, hospital admissions, and deaths that occurred ≥5 years after the cancer diagnosis. Mean age of CCS was 45.4 years. Compared to population controls, CCS had a higher risk for hospital admissions due to cardiovascular diseases and late mortality, both of which increased after age 40 years. CCS also had a higher risk for purchases of antihypertensives and lipid-lowering drugs within the last year of the study. Heart radiation ≥10 Gy was associated with hospitalizations due to cardiovascular diseases (HR 4.14, 95%CI 1.81-9.48), purchases of antihypertensives (OR 3.05, 95%CI 1.32-7.36), and purchases of lipid-lowering drugs (OR 2.93, 95%CI 1.08-7.73). Testosterone deficiency developed typically during pediatric follow-up, and it was associated with testicular radiation ≥20 Gy (HR 41.2, 95%CI 15.4-110) but not with alkylating agents. Of patients treated with testicular radiation ≥20 Gy, 91% had purchased testosterone within the last year. Reassuringly, CCS had no excess risk for purchases of opioids, anxiolytics, antiepileptics, or antidepressants. These findings emphasize the need for risk-based follow-up. Middle-aged male CCS are at an increased risk of premature cardiovascular morbidity and excess mortality.

Circulating microRNAs associated with bronchodilator response in childhood asthma

BackgroundBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

Analyses of gingival papilla blood flow via color doppler flow imaging and micro-flow imaging in patients with advanced periodontitis: a clinical pilot study

BackgroundResearch investigating the potential link between gingival microvascular blood flow and inflammatory status is scarce. This study aims to assess color doppler flow imaging (CDFI) and micro-flow imaging (MFI) as tools for the assessment of gingival papilla blood flow (GPBF) and to examine their diagnostic utility as a noninvasive means of detecting gingival bleeding.MethodsCDFI and MFI were used to assess the GPBF grade (0–4) of 140 anterior gingival papilla sites in advanced periodontitis patients. Correlations between GPBF grades and periodontal characteristics were examined, and diagnostic performance as a means of predicting bleeding on probing (BOP) was examined using receiver operating characteristic curves.ResultsGPBF grades 0 and 1 assessed by the MFI were 14.29% and 15.71% respectively, lower than the 28.57% and 24.29% assessed by the CDFI. In contrast, MFI detected a higher frequency of GPBF grade 2 sites (40.71%) relative to CDFI (22.14%). The CDFI and MFI provided consistent results in 62.14% of the sites, while the MFI demonstrated higher ratings in rest 37.86% of the sites. A significant positive correlation was detected between GPBF grade and the modified gingival index (MGI), bleeding index (BI), BOP, and probing depth (PD). It showed high accuracy for CDFI or MFI to diagnosing BOP with a sensitivity of 80.51% and 96.43% and a specificity of 77.27% and 57.14%, respectively. Area under the receiver operator characteristic curve values when predicting BOP based on the GPBF grade determined using CDFI and MFI approaches 0.887 (95% CI 0.833–0.942) and 0.917 (95% CI 0.862–0.972), respectively, and there were no significant differences between these values (Z = − 1.502, p = 0.133).ConclusionsBoth MFI and CDFI can be employed for the evaluation of GPBF, and MFI is better suited to detecting mild inflammation.Trial registration ChiCTR2200066021 (Date of registration: 22/11/2022).

Performance of expert fuzzy systems for prediction of rabbit feed intake after weaning.

The postweaning phase is stressful for rabbits due to maternal separation and the introduction of solid feed. Stress can be aggravated when animals are subjected to thermal discomfort. Therefore, thermal variables, such as air temperature, which influence the productive and physiological performance of animals, require greater control in this phase of life of rabbits to ensure their well-being and productive efficiency. Thus, the objective of the present study was to develop and compare fuzzy inference systems (FISs) with different configurations to predict the feed intake (FI) of New Zealand White (NZW) rabbits subjected to different thermal conditions after weaning. The experiment lasted 14 days, and twelve rabbits between 30 and 43 days old were used. The animals were housed in air-conditioned wind tunnels and subjected to air temperatures of 20, 24, 28 and 32°C. For the FIS configurations, Mamdani inference with five defuzzification methods (center of gravity (COG), bisector of area (BOA), largest of maximum (LOM), mean of maximum (MOM) and smallest of maximum (SOM)) and Sugeno inference with two defuzzification methods (weighted average (WA) and weighted sum (WS)), were evaluated. In both inference methods, the input variables (air temperature and time after weaning) were represented by triangular, Gaussian or trapezoidal functions. In turn, the output variable (FI, g) was represented by triangular, Gaussian or trapezoidal functions in the Mamdani FIS and by singleton functions in the Sugeno FIS. Thus, all developed FISs were validated, and their results were compared to the experimental data using statistical indices. As a result, adequate FI prediction performances were obtained for rabbits using both inference methods, regardless of the configurations used in their development. However, the smallest simulation errors were obtained using the Sugeno FIS with Gaussian inputs and WA defuzzification and is therefore a system with greater generalization capacity for unknown scenarios. Thus, the developed models can be used as a support system for decisions on the management of rabbits, aiding the efficient production and welfare of the animals, as well as the maintenance of thermal variables through the activation of installed climate systems inside the rabbit production environment.Trial registration number: 085/17. Date of registration: 14/12/2017.

Exploring the impact of BRCA1 and BRCA2 mutation type and location on Olaparib maintenance therapy in platinum-sensitive relapsed ovarian Cancer patients: A single center report

ObjectiveIn patients with platinum-sensitive relapsed ovarian cancer (PSROC) harboring pathogenic/likely pathogenic variants (PV) in BRCA1 and BRCA2 genes, olaparib maintenance monotherapy (OMT) is a viable option. Our study aimed to evaluate the impact of different BRCA1/2 PV in survival outcomes and safety of OMT in BRCA1/2-mutated PSROC patients, focusing on the type and location of PV. MethodsWe assessed the outcomes of 100 BRCA1/2-mutated PSROC patients treated at our institute, analyzing progression-free survival (PFS) and overall survival (OS). Germline and tumor BRCA1/2 genotyping was conducted using Illumina's next-generation sequencing (NGS). ResultsPFS and OS were significantly shorter in PSROC patients with PV in BRCA1 compared to those with PV in BRCA2 (PFS:14.0 vs. 38.8 months, p = 0.007, OS: 21.8 vs. 62.0 months, p = 0.011). Notably, there was a significant difference in PFS based on the intragenic location of BRCA1 PV, with shorter PFS in patients with 1st/2nd relapse, harboring PV in BRCA1 RING domain compared to those with PV in the DNA binding domain (DBD) and BRCT domains (12.4 vs. 23.0 months, p = 0.046). No differences in PFS and OS were observed between patients with germline versus somatic BRCA1/2 PV (PFS:14.9 vs.19.3, p = 0.316, OS: not reached vs. 25.8 months; p = 0.224). However, there were significant differences in the reasons for OMT discontinuation between patients with germline and somatic BRCA1/2 PV, primarily due to adverse side effects. ConclusionsIn summary, the type and location of BRCA1 and BRCA2 PV provide additional insight into the expected survival outcomes of olaparib MT in PSROC patients.Trial registration number: ISRCTN42408038, Name of registry: ISRCTN registry, Date of registration: 24/11/2015.

Comparative effectiveness of monovalent XBB.1.5 containing covid-19 mRNA vaccines in Denmark, Finland, and Sweden: target trial emulation based on registry data

ObjectiveTo estimate the effectiveness of vaccination with a monovalent covid-19 mRNA vaccine containing the omicron XBB.1.5 subvariant against severe covid-19 disease in Denmark, Finland, and Sweden.DesignTarget trial emulation based on registry data.SettingDenmark, Finland, and Sweden, 1 October 2023 to 21 April 2024.ParticipantsSource population of 3 898 264 individuals eligible for vaccination with the XBB.1.5 containing covid-19 mRNA vaccine at the start of the study on 1 October 2023. Study cohort comprised 1 876 282 recipients of an XBB.1.5 containing vaccine during the study period matched with 1 876 282 non-recipients. Individuals were aged ≥65 years (mean age 75.4 years, standard deviation 7.4 years) and had received at least four doses of a previous covid-19 vaccine.Main outcome measuresCumulative incidences of hospital admissions and deaths related to covid-19 in a follow-up period of 24 weeks after immunisation (defined as one week after vaccination) in recipients of an XBB.1.5 containing covid-19 mRNA vaccine and matched non-recipients. Cumulative incidences were used to calculate comparative vaccine effectiveness (1−risk ratio) and risk differences.ResultsThe associated comparative vaccine effectiveness was 57.9% (95% confidence interval (CI) 49.9% to 65.8%) against hospital admission for covid-19 (1085 v2635 events) and 75.2% (70.6% to 79.9%) against deaths related to covid-19 disease (348 v1458 events) after 24 weeks of follow-up. This result corresponded to 154.7 (95% CI 78.3 to 231.0) hospital admissions for covid-19 and 120.3 (110.5 to 130.2) deaths prevented per 100 000 individuals who were vaccinated with an XBB.1.5 containing vaccine. The associated comparative vaccine effectiveness was similar irrespective of sex, age group (65-74v≥75 years), number of doses of previous covid-19 vaccines, subgroup of co-administered seasonal influenza vaccines, and period of when either the omicron XBB or BA.2.86 sublineage was predominant. Although the observed reduction in risk was highest during the first weeks after vaccination, comparative vaccine effectiveness was well maintained after 24 weeks of follow-up.ConclusionsIn this study, in adults aged ≥65 years, vaccination with a monovalent XBB.1.5 containing covid-19 mRNA vaccine was associated with reduced rates of hospital admissions for covid-19 and deaths related to covid-19, during the autumn and winter of 2023-24 in Denmark, Finland, and Sweden.