Case-cohort Study Research Articles

Elevated stress-responsive biomarkers are associated with HIV acquisition in young women in rural South Africa: A HPTN 068 case cohort study.

Biological markers of stress have been associated with HIV progression and pathogenesis but not with HIV incidence. We sought to determine if elevated stress-responsive biomarkers would be associated with incident HIV among adolescent girls and young women (AGYW). We conducted a case-cohort study within the HIV Prevention Trials Network (HPTN) 068 study among 949 AGYW in South Africa. Cases were AGYW who tested HIV-positive during the eight-year follow-up. Unmatched controls were randomly selected from the HIV-negative population at enrollment. Dried blood spots from cases and controls were tested from enrollment (2011-2012) for C-reactive protein (CRP), herpes simplex virus type-1 (HSV-1) antibody titers, and cytomegalovirus (CMV) antibody titers. Cox proportional hazards models estimated the association between each biomarker and time to incident HIV. Compared to AGYW with the lowest CRP levels, those with medium and high CRP levels had a higher hazard ratio (HR) of incident HIV (HR: 1.45, 95% CI: 0.95, 2.21; HR: 1.50, 95% CI: 0.98,2.30, respectively), although not statistically significant. The relative hazard of incident HIV was also higher among AGYW who were CMV seropositive vs. seronegative (low antibodies HR: 2.18, 95% CI: 1.2,3.87; medium HR: 2.25, 95% CI: 1.28,3.95; high HR: 1.78, 95% CI: 0.99,3.21). Those with the highest HSV-1 antibody levels experienced an increased hazard of HIV compared to those who were HSV-1 seronegative (HR: 1.58, 95% CI: 1.03,2.44). Biological stress may increase AGYW's susceptibility to HIV acquisition through changes in immune function, viral infection, and increased biological vulnerability to disease.

Plasma sphingolipids mediate the association between gut microbiome composition and type 2 diabetes risk in the HELIUS cohort: a case-cohort study

IntroductionThe association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether...

Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study.

Background: Diet is known to impact cardiovascular disease (CVD) risk, but evidence for the essential minerals of magnesium (Mg), calcium (Ca), and potassium (K) is inconsistent. Methods: We conducted a case-cohort study within a non-smoking subgroup of the Danish Diet, Cancer and Health cohort, a prospective study of 50-64-year-olds recruited between 1993-1997. We identified incident heart failure (HF), acute myocardial infarction (AMI) and stroke cases through 2015 with an 1135-member subcohort. We measured the dietary intake of minerals, also known as elements, and calculated a combined dietary intake (CDI) score based on joint Ca, Mg and K intakes (mg/d) from Food Frequency Questionnaires. We estimated adjusted hazard ratios (HRs) with Cox proportional hazard models. Results: Most HRs examining associations between CDI score and CVD were null. However, the third quartile of CDI was associated with a lower risk for heart failure (HR: 0.89; 95% CI: 0.67, 1.17), AMI (HR: 0.79; 95% CI: 0.60, 1.04), and stroke (HR: 0.63; 95% CI: 0.44, 0.88). Conclusions: We did not find consistent evidence to suggest that higher levels of essential minerals are associated with incident HF, AMI, and stroke, though results suggest a potential U-shaped relationship between select minerals and CVD outcomes.

Value of foetal umbilical vein standardised blood flow volume in predicting weight gain in the third trimester: a prospective case-cohort study.

This study aims to establish a prediction model of foetal umbilical vein standardised blood flow volume (sQuv) on estimated foetal weight (EFW) in the third trimester. A case-cohort study involving 200 eligible normal foetuses was conducted at the Ultrasound Department of Longquanyi District of Maternity and Child Healthcare Hospital between June 1, 2020 and December 31, 2021. Ultrasound measurements were taken at two separate intervals to assess EFW and the rate of EFW (rEFW) [first: between 28 w and 33 w6d of gestational age (GA); second: after 4-6 weeks]. Umbilical vein blood flow volume (Quv) and sQuv (normalised with EFW) were calculated only during the initial measurement. Using general linear regression, a prediction model for EFW based on GA and sQuv was developed, with the gestational week employed as a calibration scalar and validated using linear regression cross-validation. In the third trimester, EFW exhibited significant correlations with GA, abdominal circumference (AC), head circumference (HC) and Quv (all ρ > 0.6, P < 0.001). Furthermore, the rEFW showed significant correlations with Quv and sQuv (all ρ > 0.6, P < 0.001). A linear regression equation was established using a general linear regression model: rEFW = 0.32689 × sQuv. Additionally, a foetal weight prediction model (EFW = -2,554.6770 + 0.9655 × sQuv + 129.6916 × GA) was established using sQuv. The above two formulas were cross-validated by intra-group linear regression and proved to be of good efficacy. In the third trimester, EFW displayed significant correlations with GA, AC, HC and Quv. Additionally, the rEFW exhibited significant correlations with Quv and sQuv. The sQuv during the third trimester has predictive value for foetal weight, serving as an early warning indicator.

Progressive multifocal leukoencephalopathy and spectrum of predisposing conditions: a 20-year retrospective cohort study in a tertiary center in São Paulo, Brazil.

Epidemiological studies on predisposing conditions and outcomes of progressive multifocal leukoencephalopathy (PML) cases have been carried out exclusively in high-income countries. We aim to report and compare the main characteristics and outcomes of patients with PML and several underlying diseases in a referral center in a middle-income country. We performed a retrospective cohort study of PML cases admitted to a tertiary care hospital in São Paulo, Brazil during 2000-2022. Demographic and PML-specific variables were recorded. One-year case-fatality rate and factors associated with death were identified using a multivariate Cox proportional hazards regression model. Ninety-nine patients with PML were included. HIV infection (84.8%) and malignancy (14.1%) were the most prevalent underlying conditions. Other predisposing diseases were autoimmune/inflammatory diseases (5.1%) and solid organ transplantation (1.0%). One (1.0%) patient had liver cirrhosis and another (1.0%) patient was previously healthy. Focal motor deficits (64.2%) and gait instability (55.1%) were the most common signs. The one-year case-fatality rate was 52.5% (95% CI 42.2-62.7). The one-year case-fatality rate (95% CI) in patients with or without malignancy (85.7%, 95% CI 57.2-98.2% and 47.1%, 95% CI 36.1-58.2%, respectively) were statistically different (P = 0.009). Crude and adjusted Cox regression models identified malignancy as independently associated with death (adjusted HR = 3.92, 95% CI 1.76-8.73, P = 0.001). HIV/AIDS was the predisposing condition in 84.8% of PML cases. The one-year case-fatality rate was 52.5% and having a malignancy was independently associated with death. This study reports emerging data on the epidemiology and outcome of PML in a middle-income country.

Case-cohort design as an efficient approach to evaluating COVID-19 vaccine effectiveness, waning, heterologous immune effect and optimal dosing interval

Though widely applied in other epidemiological fields, the case-cohort study design has seen little application in the field of vaccinology. Case-cohort studies use probabilistic sampling and reweighting to draw inferences about effects (in this case vaccine efficacy) at the population level in an efficient manner. The SARS-CoV-2 pandemic was met with high vaccine uptake, and high rates of population testing prior to the emergence of Omicron variants of concern, in Ontario, Canada, providing an ideal environment for application of case-cohort methodology. We combined a population-based case line list and vaccination database for the province of Ontario between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2 % sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68 %, 95 % CI 67 %–69 %; second dose efficacy 88 %, 95 % CI 87–88 %). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95 % CI 0.61–0.67) at 6–8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4–6 months after the second vaccine dose, but rose markedly thereafter. We conclude that a case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination in real time, and also served to quantify the timing and magnitude of infection breakthrough risk in the same cohort. Heterologous vaccination and extended dosing intervals improved the durability of immune response.

Rigid Sternal Fixation and Enhanced Recovery for Opioid-Free Analgesia After Cardiac Surgery

BackgroundWe evaluated the individual contributions of rigid-plate fixation (RPF) and an enhanced recovery protocol (ERP) on postoperative pain, opioid use, and other outcomes after median sternotomy as they were sequentially adopted into practice. MethodsThis single-center, retrospective, case-cohort study compared outcomes between median sternotomy patients (all comers) who underwent operation before implementation of RPF or ERP (“controls”), patients closed with RPF before ERP implementation (“RPF-only”), and patients managed with RPF and ERP during early “RPF+ERP-2020” and late “RPF+ERP-2022” implementation. ResultsThe analysis included 608 median sternotomy patients (mean age, 65.7 ± 10.8 years; 29.6% women). Of those, 59.2% were isolated coronary artery bypass grafting, 7.7% were isolated valve procedures, and the rest were mixed/concomitant procedures. Median in-hospital, postoperative opioid administration was 172.5 morphine milligram equivalents (MMEs) in the control cohort vs 0 MMEs for RPF+ERP-2022 (P < .0001), despite similar or slightly reduced patient-reported pain scores. The proportion of patients discharged directly to home was 66.2% for controls, 79.6% for RPF-only (P = .010), and 93.5% for RPF+ERP-2022 (P < .0001). Median opioids prescribed at discharge were 600 MMEs for controls and 0 for RPF+ERP-2020 and RPF+ERP-2022 (P < .0001). At discharge, 86.7% of RPF-only patients received prescription opioids vs 5% in RPF+ERP-2020 and 4.3% RPF+ERP-2022 (P < .0001). These outcomes occurred without increased readmissions. ConclusionsSystematic implementation of RPF and ERP was associated with a significant and clinically meaningful decrease in opioid use in this large, real-world patient population.

Healthcare resource utilization and costs associated with psychiatric comorbidities in pediatric patients with attention-deficit/hyperactivity disorder: a claims-based case-cohort study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) has been shown to pose considerable clinical and economic burden; however, research quantifying the excess burden attributable to common psychiatric comorbidities of ADHD among pediatric patients is scarce. This study assessed the impact of anxiety and depression on healthcare resource utilization (HRU) and healthcare costs in pediatric patients with ADHD in the United States.MethodsPatients with ADHD aged 6–17 years were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was the date of initiation of a randomly selected ADHD treatment. Patients with ≥ 1 diagnosis for anxiety and/or depression during both the baseline (6 months pre-index) and study period (12 months post-index) were classified in the ADHD+anxiety/depression cohort; those without diagnoses for anxiety nor depression during both periods were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts. All-cause HRU and healthcare costs during the study period were compared using regression analyses. Cost analyses were also performed in subgroups by comorbid conditions.ResultsThe reweighted ADHD-only cohort (N = 204,723) and ADHD+anxiety/depression cohort (N = 66,231) had similar characteristics (mean age: 11.9 years; 72.8% male; 56.2% had combined inattentive and hyperactive ADHD type). The ADHD+anxiety/depression cohort had higher HRU than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 10.3; emergency room visits: 1.6; outpatient visits: 2.3; specialist visits: 5.3; and psychotherapy visits: 6.1; all p < 0.001). The higher HRU translated to greater all-cause healthcare costs; the mean per-patient-per-year (PPPY) costs in the ADHD-only cohort vs. ADHD+anxiety/depression cohort was $3,988 vs. $8,682 (p < 0.001). All-cause healthcare costs were highest when both comorbidities were present; among patients with ADHD who had only anxiety, only depression, and both anxiety and depression, the mean all-cause healthcare costs were $7,309, $9,901, and $13,785 PPPY, respectively (all p < 0.001).ConclusionsComorbid anxiety and depression was associated with significantly increased risk of HRU and higher healthcare costs among pediatric patients with ADHD; the presence of both comorbid conditions resulted in 3.5 times higher costs relative to ADHD alone. These findings underscore the need to co-manage ADHD and psychiatric comorbidities to help mitigate the substantial burden borne by patients and the healthcare system.

A case-cohort study of per- and polyfluoroalkyl substance concentrations and incident prostate cancer in the cancer prevention Study-II LifeLink cohort study

IntroductionPer- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics. MethodsWe conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998–2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline–June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption). ResultsProstate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88–1.59)] and PFOS [HR (95% CI): 1.18 (0.89–1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02–2.31) and PFOS 1.62 (1.08–2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage. ConclusionsOur findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

68 The Emerging Role of Stem Cell Enriched Fat Grafts for Breast Reconstruction: A Systematic Review and Meta-Analysis

Abstract Aim Recent trials involving adipose derived stem cell (ADSC) enriched fat grafts have shown promising results when compared to routine autologous fat transfer (AFT) in breast reconstruction surgeries. The current systematic review and meta-analysis aimed to compare outcomes of ADSC-enriched fat grafts versus routine AFT for breast reconstruction purposes. Method A search of electronic information was conducted identifying all case control and cohort studies comparing the outcomes of ADSC-enriched fat grafts versus routine AFT for breast reconstruction. Primary outcomes included volume retention, fat necrosis and cancer recurrence. Secondary outcome measures were patient satisfaction post-surgery, cyst development, redness and swelling, infection and operation time. Fixed and random effects modelling were used for the analysis. Six studies enrolling 381 subjects were selected. Results There was a significant difference between the ADSC-enriched fat grafts and routine AFT groups in terms of mean volume retention (standardised mean difference [MD]= 2.52, P= 0.05). There were no significant differences between the two groups in terms of fat necrosis (Odds Ratio [OR]= 3.81, P =0.13) and cancer recurrence (OR= 1.39, P= 0.58). For secondary outcomes, the intervention group had similar results compared with the control group in terms of patient satisfaction, redness and swelling as well as infection and cyst development. Operation time was shorter for the latter group. Conclusions ADSC-enriched fat grafting is a superior option compared to the routine AFT for breast reconstruction surgery as it improves the mean volume retention and does not worsen patient satisfaction and surgical complications.

Exposure to fibres and risk of pleural mesothelioma in the Norwegian Offshore Petroleum Workers cohort

ObjectivesPleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure...

Serum mature and furin-cleaved proprotein convertase subtilisin/kexin type 9 levels and their association with cardiovascular events in statin-treated patients with cardiovascular disease

Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9. This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort). From 1,478 patients in sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ration [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 [95% CI, 0.645-1.392] (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE. In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD.

Clostridioides difficile infection following COVID-19: A nationwide analysis using routine surveillance data in Wales

CDI incidence has increased in Wales from summer 2020 and has remained elevated. There is evidence of poorer outcomes from concurrent CDI and COVID-19 infections, but it is not clear if infection with COVID-19 directly impacts likelihood of CDI infection. We investigated the relationship between CDI and COVID-19 and the impact of secondary infections. We conducted two analytical studies using routine surveillance data: i) population level ecological case control study comparing CDI cases in the Welsh population by SARS-COV-2 exposure in the previous 90 days, ii) cohort study of COVID-19 cases by secondary infection presence, investigating CDI development within 90 days. Case control: 12% (196/1645) of CDI cases had prior COVID-19 and were twice as likely to have had COVID-19 compared to general population controls, when controlling for other infection history (OR 2.1, CI 1.8-2.5, p<0.0001). CDI cases were 8 times more likely to have had other infections, independent of COVID-19 history (OR 8.0, CI 7.0-9.0, p<0.001). 2% (2,255/137,620)) of the COVID-19 cohort developed >1 secondary infection, and <1% (185/137620) developed CDI within 90 days. CDI risk was four times higher in those with secondary infections, after age and sex adjustment (RR 4.6, CI 3.1 - 6.1, p<0.001). CDI risk increased with age and did not differ by sex. Findings suggest a relationship between COVID-19 and CDI. However, incidence of CDI following COVID-19 was a rare outcome generally, suggesting other factors are likely contributing to the increased rates of CDI observed since 2020.

Incident traumatic spinal cord injury and risk of Alzheimer's disease and related dementia: longitudinal case and control cohort study.

Retrospective case/control longitudinal cohort study OBJECTIVES: Prevalent traumatic spinal cord injury (TSCI) is associated with Alzheimer's disease and related dementia (ADRD). We examined the hazard ratio for ADRD after incident TSCI and hypothesized that ADRD hazard is greater among adults with incident TSCI compared with their matched control of adults without TSCI. Using 2010-2020 U.S. national private administrative claims data, we identified adults aged 45 years and older with probable (likely and highly likely) incident TSCI (n = 657). Our controls included one-to-ten matched cohort of people without TSCI (n = 6553). We applied Cox survival models and adjusted them for age, sex, years of living with certain chronic conditions, exposure to six classes of prescribed medications, and neighborhood characteristics of place of residence. Hazard ratios were used to compare the results within a 4-year follow-up. Our fully adjusted model without any interaction showed that incident TSCI increased the risk for ADRD (HR = 1.30; 95% CI, 1.01-1.67). People aged 45-64 with incident TSCI were at high risk for ADRD (HR = 5.14; 95% CI, 2.27-11.67) and no significant risk after age 65 (HR = 1.20; 95% CI, .92-1.55). Our sensitivity analyses confirmed a higher hazard ratio for ADRD after incident TSCI at 45-64 years of age compared with the matched controls. TSCI is associated with a higher hazard of ADRD. This study informs the need to update clinical guidelines for cognitive screening after TSCI to address the heightened risk of cognitive decline and to shed light on the causality between TSCI and ADRD.

Comparison of the diagnostic value of various microRNAs in blood for colorectal cancer: a systematic review and network meta-analysis

BackgroundDespite the existence of numerous studies investigating the diagnostic potential of blood microRNAs for colorectal cancer, the microRNAs under consideration vary widely, and comparative analysis of their diagnostic value is lacking. Consequently, this systematic review aims to identify the most effective microRNA blood tumor markers to enhance clinical decision-making in colorectal cancer screening.MethodA comprehensive search of databases, including PubMed, Embase, Web of Science, Scopus, and Cochrane, was conducted to identify case‒control or cohort studies that examined the diagnostic value of peripheral blood microRNAs in colorectal cancer. Studies were included if they provided sensitivity and specificity data, were published in English and were available between January 1, 2000, and February 10, 2023. The Critical Appraisal Skills Programme (CASP) checklist was employed for quality assessment. A Bayesian network meta-analysis was performed to estimate combined risk ratios (RRs) and 95% confidence intervals (CIs), with results presented via rankograms. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202,380,092.ResultsFrom an initial pool of 2254 records, 79 met the inclusion criteria, encompassing a total of 90 microRNAs. The seven most frequently studied microRNAs (43 records) were selected for inclusion, all of which demonstrated moderate to high quality. miR-23, miR-92, and miR-21 exhibited the highest sensitivity and accuracy, outperforming traditional tumor markers CA19-9 and CEA in terms of RR values and 95% CI for both sensitivity and accuracy. With the exception of miR-17, no significant difference was observed between each microRNA and CA19-9 and CEA in terms of specificity.ConclusionsAmong the most extensively researched blood microRNAs, miR-23, miR-92, and miR-21 demonstrated superior diagnostic value for colorectal cancer due to their exceptional sensitivity and accuracy. This systematic review and network meta-analysis may serve as a valuable reference for the clinical selection of microRNAs as tumor biomarkers.

Liver involvement in dengue: A systematic review.

Liver involvement is an unusual yet frequently overlooked dengue complication. Pivotal for an efficient clinical management, the early diagnosis of dengue-associated liver involvement relies on an accurate description of its clinical and biological characteristics, its prognosis factors, its association with severe dengue and its clinical management. We conducted a systematic review by searching PubMed and Web of Science databases for original case reports, cohort and cross-sectional studies reporting the clinical and/or biological features of dengue-associated liver involvement. The study was registered in PROSPERO (CRD42021262657). Of the 2552 articles identified, 167 were included. Dengue-associated liver involvement was characterised by clinical features including abdominal pain, hepatomegaly, jaundice, nausea/vomiting, and an echogenic liver exhibiting hepatocellular necrosis and minimal inflammation. Elevated Aspartate Aminotransferase and Alanine Aminotransferase but also elevated bilirubin, Alkaline Phosphatase, gamma-glutamyl transferase, increased International Normalised Ratio, creatinine and creatine kinase, lower albumin and prolonged prothrombin and activated partial thromboplastin time were prevalent in dengue-associated liver involvement. Cardiovascular and haematological systems were frequently affected, translating in a strong association with severe dengue. Liver involvement was more common in males and older adults. It was associated with dengue virus serotype-2 and secondary infections. Early paracetamol intake increased the risk of liver involvement, which clinical management was mostly conservative. In conclusion, this systematic review demonstrates that early monitoring of transaminases, clinical assessment, and ultrasound examination allow an efficient diagnosis of dengue-associated liver involvement, enabling the early identification and management of severe dengue.

Hysterectomy—a possible risk factor for operative intervention in female patients for degenerative lumbar spine conditions: a case control and cohort study

Researchers have recently linked hysterectomy, which alters sex hormone levels, to diseases like osteoporosis, lumbar spondylolisthesis, hypertension and diabetes etc. However, the association between hysterectomy and lumbar disc herniation (LDH)/lumbar spinal stenosis (LSS) remains unclarified. To determine whether there is a correlation between hysterectomy and surgical intervention for LDH/LSS in women, further substantiated through imaging and clinical research. A case control and cohort study. The study group comprised 1202 female patients aged 45 and older who had undergone operative treatment due to LDH/LSS (825 for LDH and 377 for LSS), and the comparison group comprised 1168 females without lumbar diseases who visited health examination clinic during the same period. One hundred and 2 hysterectomized patients were further selected (Hysterectomy cohort) and matched approximately with the control cohort at a 1:2 ratio from the study group with a minimum follow-up of 2 years. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) were calculated to assess the association between hysterectomy and surgical intervention for LDH/LSS in women after adjusted by confounding factors. Patients from both the hysterectomy and control cohorts underwent a comprehensive assessment. This assessment included the evaluation of several parameters: the functional cross-sectional area, fat infiltration rate, relative functional cross-sectional area of the lumbar paravertebral muscles, facet joint degeneration grade, cartilage endplate damage, Modic changes for the L3/4-L5/S1 segments, Pfirrmann grade of lumbar disc degeneration, and disc height index for the L1/2-L5/S1 segments. Additionally, the Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) scores were recorded preoperatively and at the last follow-up. Associations between hysterectomy and patients treated surgically for LDH or LSS were analyzed using multivariate binomial logistic regression analysis. Lumbar X-ray, computed tomography (CT) and magnetic resonance imaging (MRI) were used to evaluate the imaging variables. Imaging and clinical variables were compared. Hysterectomized women were associated with requiring surgery due to LDH/LSS, with ORs of 2.613 (p<.001) and 2.084 (p=.006), respectively. The imaging evaluation further revealed that the hysterectomy cohort had more severe degeneration of the paraspinal muscles, facet joints, endplates, and intervertebral discs, Modic changes at L3/4-L5/S1 segments, and intervertebral height reduction at L1/2-L5/S1 segments when compared to the control cohort (p<.01). Compared to the control cohort, the hysterectomy cohort exhibited higher preoperative and last follow-up VAS scores for low back pain, and last follow-up JOA scores (p<.01). Based on the findings of this study, it seems that women who have had a hysterectomy are correlated with requiring surgical intervention due to LDH/LSS. Imaging and clinical studies also indicate that hysterectomized patients exhibited more severe lumbar degeneration and back pain.

Treatment of positive catheter tip culture without bloodstream infections in critically ill patients. A case-cohort study from the OUTCOMEREA network

PurposeThis study aimed to evaluate the impact on subsequent infections and mortality of an adequate antimicrobial therapy within 48 h after catheter removal in intensive care unit (ICU) patients with positive catheter tip culture.MethodsWe performed a retrospective analysis of prospectively collected data from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS) for adequate antimicrobial treatment, based on expert opinion of 45 attending physicians. We conducted a 1:1 case-cohort study matched on the PS score of being adequately treated. A PS-matched subdistribution hazard model was used for detecting subsequent infections and a PS-matched Cox model was used to evaluate the impact of antibiotic therapy on mortality.ResultsWe included 427 patients with a catheter tip culture positive with potentially pathogenic microorganisms. We matched 150 patients with an adequate antimicrobial therapy with 150 controls. In the matched population, 30 (10%) subsequent infections were observed and 62 patients died within 30 days. Using subdistribution hazard models, the daily risk to develop subsequent infection up to Day-30 was similar between treated and non-treated groups (subdistribution hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62–1.89, p = 0.78). Using Cox proportional hazard models, the 30-day mortality risk was similar between treated and non-treated groups (HR 0.89, 95% CI 0.45–1.74, p = 0.73).ConclusionsAntimicrobial therapy was not associated with decreased risk of subsequent infection or death in short-term catheter tip colonization in critically ill patients. Antibiotics may be unnecessary for positive catheter tip cultures.

Volatile organic compounds and mortality from ischemic heart disease: A case-cohort study

BackgroundVolatile organic compounds (VOCs) are major components of air pollution and tobacco smoke, two known risk factors for cardiovascular diseases. VOCs are ubiquitous in the environment and originate from a wide range of sources, including the burning of biomass, fossil fuels, and consumer products. Direct evidence for associations between specific VOCs and ischemic heart disease (IHD) mortality in the general population is scarce. MethodsIn a case-cohort study (stratified by age groups, sex, residence, and tobacco smoking), nested within the population-based Golestan cohort study (n = 50,045, 40–75 years, 58% women, enrollment: 2004–2008) in northeastern Iran, we measured urinary concentrations of 20 smoking-related VOC biomarkers using ultra high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. We calculated hazard ratio (HR) and 95% confidence interval (CI) for their associations with IHD mortality during follow-up to 2018, using Cox regression models adjusted for age, ethnicity, education, marital status, body mass index, physical activity, wealth, and urinary cotinine. ResultsThere were 575 non-cases from random subcohort and 601 participants who died from IHD, mean (standard deviation) age, 58.2 (9.3) years, with a median of 8.4 years follow-up. Significant associations [3rd vs. 1st tertile, HR (95% CI), P for trend] were observed between biomarkers of acrylamide [1.68(1.05,2.69), 0.025], acrylonitrile [2.06(1.14,3.72), 0.058], acrolein [1.98(1.30,3.01), 0.003 and 2.44(1.43,4.18), 0.002], styrene/ethylbenzene [1.83(1.19,2.84), 0.007 and 1.44(1.01,2.07), 0.046], dimethylformamide/methylisocyanate [2.15(1.33,3.50), 0.001], and 1,3butadiene [2.35(1.52,3.63),<0.001] and IHD mortality. These associations were independent of tobacco smoking, and they were only present in the non-smoking subgroup. ConclusionOur findings provide direct evidence for associations between exposure to several VOCs with widespread household and commercial use and IHD mortality many years after these exposures. These results highlight the importance of VOC exposure in the general population as a risk factor for cardiovascular diseases and underline the importance of bio-monitoring non-tobacco VOC exposure.

Hazard of Failed Nonoperative Management for Symptomatic Accessory Navicular in Children and Adolescents: A Population-Based Case-Cohort Study.

The accessory navicular (AN) is an idiopathic condition of the foot present in 4% to 21% of the population. Most ANs remain asymptomatic, but children and adolescents who develop symptoms can have remarkably reduced quality of life. Although many respond to conservative measures, surgery is occasionally needed. Our purpose was to determine factors associated with the failure of nonoperative management. This single-institution retrospective case-cohort study included patients up to age 19 years presenting between 2000 and 2021 with symptomatic AN and treated with standard-of-care. All 298 surgical cases, indicating failed nonoperative treatment, were included. For the subcohort, 299 patients were randomly sampled from all eligible patients, regardless of treatment. Baseline characteristics were summarized for the surgical cases and subcohort. Proportional hazards assumptions were checked and stratification implemented when necessary. Marginal structural proportional hazard modeling was used to estimate hazard ratios with 95% confidence intervals via inverse probability and LinYing weighting methods. The 298 surgical cases failed nonoperative management at a median of 5.2 months (IQR, 2.0-11.6 mo). In the subcohort, 86 failures of nonoperative management and 213 nonfailures constituted a 28.8% surgery rate. In both cohorts, nearly all patients played sports. Univariate proportional hazard modeling found older age ( P =0.02) and activity limitation ( P <0.001) at presentation, female sex ( P =0.002), higher BMI ( P =0.01), AN on the right ( P <0.001), and bone marrow edema of the AN ( P <0.001) and navicular body ( P <0.001) on MRI were associated with increased hazard of nonoperative failure. Nearly all of the surgical cohort reported improvement in pain (278/296, 94%) and returned to their primary sport (236/253, 93%) after surgery. Most also experienced full resolution of symptoms (187/281, 67%). Symptomatic AN predominantly affects female athletes, leading to surgery in 28.8% of our subcohort. Conservative treatment may be less successful-and therefore surgery could be more strongly considered-in older age, activity limitation at presentation, female sex, higher BMI, right-sided AN, and bone marrow edema on MRI. Surgery is effective for symptomatic and functional improvement. Case-cohort-Level III.