Multivariable Conditional Logistic Regression Models Research Articles

Association between coronary artery stenosis and myocardial injury in patients with acute pulmonary embolism: A case-control study.

The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE. In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation. The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P=0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243-5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056-5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792-30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467-8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288-36.484) were independently associated with elevated hs-cTnI. CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa. A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05. In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF. This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression.

Intracranial arterial calcification in patients with unruptured and ruptured intracranial aneurysms.

Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.

Factors associated with keratoconus in Israel-A cross-sectional population-based study.

To identify potential factors associated with keratoconus. This cross-sectional study included data from Israel's largest healthcare provider for the years 2005-2020. Keratoconus patients and age-matched controls were identified. Demographic factors and comorbid conditions, including smoking, diabetes mellitus, asthma, myalgia, mental retardation, Down syndrome, atopic dermatitis and allergy/allergic rhinitis, were compared between the two cohorts. The independent risk factors associated with keratoconus were determined using a multivariable conditional logistic regression model. Overall, 145 508 subjects were reviewed of which 13 228 were keratoconus patients. A ten-fold group (n = 132 280) of age-matched control subjects served as controls for comparisons. In multivariable analysis, several factors were found to be significantly associated with keratoconus. Male gender (OR = 1.27, p < 0.001), Arab ethnicity (OR = 1.50, p < 0.001), diabetes (OR = 1.19, p < 0.001), asthma (OR = 1.50, p < 0.001), myalgia (OR = 1.09, p = 0.02), mental retardation (OR = 2.63, p < 0.001), atopic dermatitis (OR = 1.35, p < 0.001) and allergic rhinitis (OR = 1.21, p < 0.001) were significantly associated with keratoconus. Smoking was significantly protective of keratoconus (OR = 0.66, p < 0.001). This population-based study reports male gender, Arab ethnicity, diabetes, asthma, myalgia, mental retardation/Down syndrome, atopic dermatitis and allergic rhinitis as factors associated with keratoconus while smoking demonstrates a protective effect. The results of this study could guide enhanced screening strategies and early interventions, particularly for high-risk groups.

Subacute Thyroiditis Following COVID-19 and COVID-19 Vaccination

ObjectiveCOVID-19 infection and immunizations have been implicated in developing a range of thyroid diseases, including subacute thyroiditis (SAT). This study aimed to evaluate the association between COVID-19 infection and/or COVID-19 vaccination with SAT. MethodsA population of 3 million adults insured by Clalit Health Services was evaluated from March 2020 to September 2022. Patients with a new diagnosis of SAT were identified and matched in a 1:10 ratio to a control group. Each control was assigned an index date that was identical to that of their matched case, defined as the date of SAT diagnosis. Multivariate conditional logistic regression models were used to evaluate the association between COVID-19 infection, vaccine, and thyroiditis. ResultsA total of 3221 patients with SAT were matched with 32 210 controls. Rates of COVID-19 vaccination (first, second, or third dose) and COVID-19 infection were evaluated prior to the date of SAT diagnosis (disease group) or index date (control group) to detect a possible association. No difference was detected between the groups in relation to vaccinations at the 30 days, 60 days, and 90 days of time points (P = .880/0.335/0.174, respectively). No difference was found between groups in relation to COVID-19 infection at these time points (P = .735/0.362/0.956, respectively). There was higher use of medications for the treatment of thyroiditis, including nonsteroidal anti-inflammatory drugs (28.6% vs 7.9%, P < .01), steroids (10.3% vs 1.8%, P < .01), and beta-blockers (18.3% vs 5.4%, P < .01). ConclusionBased on this large population study, no association was found between COVID-19 infection and/or the COVID-19 vaccine and SAT.

Childhood maltreatment, parenting style and anxiety in Chinese youths: A case-control study

BackgroundAlthough evidence in supporting the associations between childhood maltreatment (CM), parenting style and anxiety in children and adolescents exists, few high-quality analytical epidemiological studies which focusing on clinically diagnosed anxiety disorders (AD) had been published. ObjectiveThe aim of this study was to further corroborate the associations between CM, parenting style, and AD in a large representative sample of Chinese children and adolescents. Participants and settingStudy subjects were derived from the Mental Health Survey for Children and Adolescents in Yunnan (MHSCAY), a population-based cross-sectional program. MethodsIndividually matched case-control study design was adopted. Univariate and multivariate conditional binary logistic regression models were used to estimate the associations between CM, parenting style and AD. Dose-response trends were estimated using the Cochran-Armitage Chi-square test. A series of stratified analyses were conducted to explore effect modification on exposure-outcome association by some important features. ResultsTotally we screened out 202 cases and 404 matched controls, with an age mean of 14.43 years. Conditional logistic regression models revealed that EA and a higher level of parental over-protection were significantly associated with increased risk of AD, with adjusted ORs of 3.39 (95 % CI: 2.07–5.56) and 1.93 (95 % CI: 1.28–2.90). Stratified analysis identified noticeable effect modification by sex, age, and whether the only child in the family. ConclusionsMajor findings of this study suggested that children and adolescents who had experienced EA or raised up by over-protective parents are at increased risk of AD. Targeted intervention measures should be developed and implemented for these high-risk youths.

Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status

PurposeRisk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score.MethodsAll cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden’s statistic.ResultsWe analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95.ConclusionPredicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Keeping university open did not increase the risk of SARS-CoV-2 acquisition: A test negative case-control study among students.

During the SARS-CoV-2 testing program offered through the RT-PCR test by Sapienza University of Rome, we conducted a test-negative case-control study to identify risk factors for acquiring SARS-CoV-2 infection among university students. Each SARS-CoV-2-positive case detected was matched to two controls randomly selected from students who tested negative on the same day. 122 positive students and 244 negative students were enrolled in the study. Multivariable conditional logistic regression models were built. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. A second model was limited to students who had attended campus. Out of 8223 tests for SARS-CoV-2, 173 students tested positive (2.1%), of whom 122 (71.5%) were included in the case-control study. In the first analysis, being a non-Italian student (aOR: 8.93, 95% CI: 2.71-29.41), having received only the primary vaccination course (aOR: 2.94, 95% CI: 1.24-6.96) compared to the booster dose, known exposure to a COVID-19 case or someone with signs/symptoms suggestive of COVID-19 (aOR: 6.51, 95% CI: 3.48-12.18), and visiting discos (aOR: 4.07, 95% CI: 1.52-10.90) in the two weeks before testing increased the likelihood of SARS-CoV-2 infection. Conversely, students attending in-person lectures on campus seemed less likely to become infected (aOR: 0.34, 95% CI: 0.15-0.77). No association was found with other variables. The results of the second model were comparable to the first analysis. This study indicates that if universities adopt strict prevention measures, it is safe for students to attend, even in the case of an infectious disease epidemic.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study

BackgroundAging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. MethodsA case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. ResultsThe study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). ConclusionsNSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

Association between amino acids and recent osteoporotic fracture: a matched incident case-control study.

Osteoporotic fracture is a major public health issue globally. Human research on the association between amino acids (AAs) and fracture is still lacking. To examine the association between AAs and recent osteoporotic fractures. This age and sex matched incident case-control study identified 44 recent x-ray confirmed fracture cases in the Second Hospital of Jilin University and 88 community-based healthy controls aged 50+ years. Plasma AAs were measured by high performance liquid chromatography coupled with mass spectrometry. After adjusting for covariates (i.e., body mass index, milk intake >1 time/week, falls and physical activity), we conducted conditional logistical regression models to test the association between AAs and fracture. Among cases there were 23 (52.3%) hip fractures and 21 (47.7%) non-hip fractures. Total, essential, and non-essential AAs were significantly lower in cases than in controls. In the multivariable conditional logistic regression models, after adjusting for covariates, each standard deviation increase in the total (odds ratio [OR]: 0.304; 95% confidence interval [CI]: 0.117-0.794), essential (OR: 0.408; 95% CI: 0.181-0.923) and non-essential AAs (OR: 0.290; 95%CI: 0.107-0.782) was negatively associated with recent fracture. These inverse associations were mainly found for hip fracture, rather than non-hip fractures. Among these AAs, lysine, alanine, arginine, glutamine, histidine and piperamide showed the significantly negative associations with fracture. There was a negative relationship between AAs and recent osteoporotic fracture; such relationship appeared to be more obvious for hip fracture.

Prospective findings from the Dongfeng-Tongji cohort: Exposure to various metals, the expression of microRNA-4286, and the incidence of acute coronary syndrome

Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: −13.36% [-22.74%, −2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

To study the association of pro-inflammatory markers with incident diabetes in India. We did a nested case-control study within the CARRS (Centre for ArdiometabolicRiskReduction inSouth Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI:1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI:1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI:0.06, 0.55]). Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

Relation of body surface area-to-mass ratio to risk of exertional heat stroke in healthy men and women.

Risk of exertional heat stroke (EHS) is an ongoing challenge for United States military personnel, for athletes and for individuals with occupational stressors that involve prolonged activity in hot environments. Higher body mass index (BMI) is significantly associated with increased risk for EHS in activity duty U.S. Soldiers. During exercise, heat is generated primarily by contracting skeletal muscle (and other metabolically active body mass) and dissipated based on body surface area (BSA). Thus, in compensable environments, a higher BSA·mass-1 may be a benefit to heat dissipation and decrease the risk of EHS. The purpose of the present analysis was to test the hypothesis that BSA·mass-1 ratio is an important biophysical characteristic contributing to the risk of EHS. We employed a matched case-control approach, where each individual with a diagnosis of EHS was matched to five controls who were never diagnosed with EHS but were in the same unit and had the same job title. We used a multivariate conditional logistic regression model including variables of BSA·mass-1, sex, age, military rank, and race. BSA·mass-1 significantly predicted EHS risk (P = 0.006), such that people with higher BSA·mass-1 were at lower risk of developing EHS when controlling for other potential factors such as age and race. This relationship persisted after adjustment for other anthropometric measures of body size including weight, BMI, and BSA. These data suggest that biophysical factors play an important role in EHS risk, particularly in a healthy military-aged cohort of men and women.NEW & NOTEWORTHY With the impacts of climate change yielding higher average ambient temperatures over time, the incidence of EHS for individuals participating in outdoor activities may consequently increase. With the larger sample size in this study compared with prior research in this field, we were able to use various methods that had not been applied before. For example, we were able to mutually adjust for different measurements of body size to understand which metric had the highest association with EHS risk. Understanding factors that may be modifiable may be important for developing interventions to counteract the increased risk of EHS associated with climate change.

The Risk of Herpes Zoster Events in Patients with Spondyloarthritis and the Effect of BNT162b2 mRNA COVID-19 Vaccine.

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case-control studies, identifying all new HZ cases diagnosed from 1 January-31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19-2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15-12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68-3.14).

Maternal factors in the origin of cleft lip/cleft palate: A population-based case-control study.

Orofacial clefts are among the most common birth defects, with an estimated worldwide incidence of around 1.5-1.7 per 1000 live-born babies. The most frequent form of orofacial clefts is cleft lip with or without cleft palate (CL ± CP). The role of environmental factors in the development of clefts is unclear in most patients, thus the aim of this study was to estimate possible maternal risk factors in the origin of CL ± CP. 1648 CL ± CP cases, 2654 matched controls and 57 231 population controls were evaluated from The Hungarian Case-Control Surveillance of Congenital Abnormalities. Maternal factors during the critical period in cases and controls were compared. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated in a multivariable conditional logistic regression model. Among socio-demographic data, we have found significant differences between maternal employment. The proportion of unskilled mothers (6.5%) were higher in the CL ± CP group than in controls (3.5%). Medically recorded maternal anaemia, excessive vomiting and threatened abortion were associated with a higher risk of CL ± CP. An elevated risk was also found in various acute illnesses such as influenza (OR: 2.4, 95% CI: 3.0-5.8), acute bronchitis (OR: 4.5, 95% CI: 1.6-12.6) and urinary tract infections (OR: 3.5, 95% CI: 2.0-6.0). Maternal migraine and essential hypertension occurred more frequently in the mothers of cases than in controls. The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of CL ± CP.

Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case-Control Study from Korea.

Background: Few risk factors for the development of intracranial aneurysms (IAs) are known. We investigated the potential role of thyroid diseases in IA development using nationwide real-world data. Methods: A nested case-control study within the National Health Insurance Service-National Sample Cohort data from 2002 to 2019 was performed. A total of 5335 patients with unruptured IA were matched by age and sex with 80,025 controls at a ratio of 1:15. We estimated the odds ratios (ORs) and corresponding confidence intervals [CIs] between thyroid diseases and unruptured IA using a multivariable conditional logistic regression model. Results: Tobacco smoking, use of antihypertensive medication, and hypothyroidism were significantly associated with an elevated risk for unruptured IA in univariate analysis. In multivariable analysis, a history of hypothyroidism was associated with unruptured IA (adjusted OR: 1.46 [CI: 1.26-1.69]). Among patients with hypothyroidism, long-term use of thyroid hormone for >5 years was associated with a reduced risk for unruptured IA (adjusted OR: 0.69 [CI: 0.48-0.99]). A history of hyperthyroidism was associated with a reduced risk for unruptured IAs (adjusted OR: 0.71 [CI: 0.54-0.93]). In secondary analyses of the data according to sex, the respective observed associations between hypothyroidism and hyperthyroidism and the risk of IAs were found to be statistically significant in females but not in males. Conclusions: Hypothyroidism is associated with an increased risk of unruptured IAs, whereas hyperthyroidism is associated with a reduced risk. Overall, the findings suggest that thyroid hormones may play a protective role in the development of unruptured IAs. Further studies are needed to clarify potential direct causality and the biologic mechanisms relating thyroid dysfunction and unruptured IA.

Antiemetic prophylaxis with droperidol in morphine-based intravenous patient-controlled analgesia: a propensity score matched cohort study

BackgroundThere are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA.MethodsPatients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs).ResultsAfter matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35–0.67, p < 0.0001). The antiemetic effect of droperidol was significant within 36 h after surgery and attenuated thereafter. Droperidol was significantly associated with a lower risk of antiemetic uses (aOR: 0.58, 95% CI: 0.41–0.80, p = 0.0011). The rate of unintentional sedation was comparable between the patients with (9.1%) and without (7.8%; p = 0.4481) the addition of droperidol. Postoperative opioid consumption and numeric rating scale acute pain scores were similar between groups.ConclusionsThe addition of droperidol to IV-PCA reduced the risk of PONV without increasing opiate consumption or influencing the level of sedation. However, additional prophylactic therapies are needed to prevent late-onset PONV.

Association Between Guillain-Barré Syndrome and COVID-19 Infection and Vaccination: A Population-Based Nested Case-Control Study.

Existing data regarding occurrence of Guillain-Barré syndrome (GBS) after coronavirus disease 2019 (COVID-19) infection and vaccination are inconclusive. We aimed to assess the association between GBS and both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 vaccine. We conducted a nested case-control study in a cohort of 3,193,951 patients aged 16 years or older, without a diagnosis of prior GBS, from the largest health care provider in Israel. Participants were followed from January 1, 2021, until June 30, 2022, for the occurrence of GBS. Ten randomly selected controls were matched to each case of GBS on age and sex. We assessed both SARS-CoV-2 infection and COVID-19 vaccine administration in the prior 6 weeks in cases and controls. Overall, 76 patients were diagnosed with GBS during follow-up and were matched to 760 controls. A positive test for SARS-CoV-2 was detected in 9 (11.8%) cases and 18 (2.4%) controls. An administration of COVID-19 vaccine was detected in 8 (10.5%) cases (all Pfizer-BioNTech [BNT162b2] vaccine) and 136 (17.9%) controls (134 Pfizer-BioNTech vaccine). Multivariable conditional logistic regression models showed that the odds ratio for GBS associated with SARS-CoV-2 infection and COVID-19 vaccine administration was 6.30 (95% CI 2.55-15.56) and 0.41 (95% CI 0.17-0.96), respectively. The results were similar when exposure to SARS-CoV-2 infection or COVID-19 vaccine administration was ascertained in the prior 4 and 8 weeks, although did not reach statistical significance for COVID-19 vaccine at 4 weeks. Our study suggests that SARS-CoV-2 infection is associated with increased risk of GBS, whereas Pfizer-BioNTech COVID-19 vaccine is associated with decreased risk of GBS.

Effectiveness of the booster dose of inactivated COVID-19 vaccine against Omicron BA.5 infection: a matched cohort study of adult close contacts

BackgroundAlthough COVID-19 vaccines and their booster regimens protect against symptomatic infections and severe outcomes, there is limited evidence about their protection against asymptomatic and symptomatic infections in real-world settings, particularly when considering that the majority of SARS-CoV-2 Omicron infections were asymptomatic. We aimed to assess the effectiveness of the booster dose of inactivated vaccines in mainland China, i.e., Sinopharm (BBIBP-CorV) and Sinovac (CoronaVac), against Omicron infection in an Omicron BA.5 seeded epidemic.MethodsBased on an infection-naive but highly vaccinated population in Urumqi, China, the study cohort comprised all 37,628 adults who had a contact history with individuals having SARS-CoV-2 infections, i.e., close contacts, between August 1 and September 7, 2022. To actively detect SARS-CoV-2 infections, RT-PCR tests were performed by local authorities on a daily basis for all close contacts, and a testing-positive status was considered a laboratory-confirmed outcome. The cohort of close contacts was matched at a ratio of 1:5 with the fully vaccinated (i.e., 2 doses) and booster vaccinated groups (i.e., 3 doses) according to sex, age strata, calendar date, and contact settings. Multivariate conditional logistic regression models were adopted to estimate the marginal effectiveness of the booster dose against Omicron BA.5 infection after adjusting for confounding variables. Subgroup analyses were performed to assess vaccine effectiveness (VE) in different strata of sex, age, the time lag from the last vaccine dose to exposure, and the vaccination status of the source case. Kaplan–Meier curves were employed to visualize the follow-up process and testing outcomes among different subgroups of the matched cohort.FindingsBefore matching, 37,099 adult close contacts were eligible for cohort enrolment. After matching, the 2-dose and 3-dose groups included 3317 and 16,051 contacts, and the proportions with Omicron infections were 1.03% and 0.62% among contacts in the 2-dose and 3-dose groups, respectively. We estimated that the adjusted effectiveness of the inactivated booster vaccine versus 2 doses against Omicron infection was 35.5% (95% CI 2.0, 57.5). The booster dose provided a higher level of protection, with an effectiveness of 60.2% (95% CI 22.8, 79.5) for 15–180 days after vaccination, but this VE decreased to 35.0% (95% CI 2.8, 56.5) after 180 days. Evidence for the protection of the booster dose was detected among young adults aged 18–39 years, but was not detected for those aged 40 years or older.InterpretationThe receipt of the inactivated vaccine booster dose was associated with a significantly lower Omicron infection risk, and our findings confirmed the vaccine effectiveness (VE) of booster doses against Omicron BA.5 variants. Given the rapid evolution of SARS-CoV-2, we highlight the importance of continuously monitoring the protective performance of vaccines against the genetic variants of SARS-CoV-2, regardless of existing vaccine coverage.

Association of plasma iron with the risk of incident cancer in Chinese adults with hypertension: a nested case-control study.

Iron is an essential element for organismal health but excessive iron is potentially toxic. However, few observational studies link plasma iron (PI) concentrations and cancer risk, and the results are inconsistent. This study aimed to explore the associations of PI concentrations with cancer risk in Chinese adults with hypertension. We conducted a nested, case-control study, including 223 pairs of incident cancer cases and matched controls from the China Stroke Primary Prevention Trial. The median time between blood sample collection and subsequent cancer event occurrence was 2.13 years. The odds ratio (OR) and 95% confidence interval (CI) for the risk of cancer by PI were estimated from multivariable conditional logistic regression models. There was a nonlinear association between PI concentrations and total cancer risk. When compared with participants in tertile 2 of PI, the ORs of total cancer were 2.17 (95%CI: 1.25-3.85) and 1.29 (95%CI: 0.77-2.19) in participants in PI tertiles 3 and 1, respectively. Furthermore, higher PI was associated with increased digestive system cancer risk (OR=3.25, 95%CI:1.29-8.90), while lower PI was associated with increased risk of non-digestive system cancer (OR=3.32, 95%CI: 1.39-8.71). In a sensitivity analysis, the increases in total cancer risk or digestive system cancer risk were still observed with higher PI after excluding cancer cases occurring within the first year. Our results showed an increased risk of cancer related to higher PI or lower PI in Chinese adults with hypertension. Higher iron levels were linked to an increased risk of digestive system cancers, whereas lower iron levels were linked to an increased risk of non-digestive system cancers.