Multivariable Fractional Polynomial Research Articles

Distribution of Normative Percentiles of Liver Stiffness Measurement Using Ultrasound Shear Wave Elastography in an Adult Asian Indian Population

Abstract Objective The aim of this study was to determine the normative percentiles for liver stiffness measurement (LSM) using shear wave elastography in an adult Asian Indian population as part of the preventive radiology initiative of the Indian Radiological and Imaging Association (IRIA). Methods LSMs were ascertained by two-dimensional (2D) shear wave elastography using the Mindray Resona series of ultrasound machines. The image quality was assessed using the motion stability index (M-STB) and reliability (RLB) map. Ten acquisitions were documented, and an interquartile range-to-median (IQR/M) ratio ≤30% kilopascal (kPa) units was considered a good-quality measurement. A subgroup of the study population without comorbidities was chosen to derive the normative percentile distribution of LSM using a generalized least squares multivariable fractional polynomial regression model that adjusted for sex and body mass index (BMI). The effectiveness of the estimated percentiles was assessed on the entire study population using the greater than 90th percentile value of the LSM as the cutoff for abnormality. Results The study included 852 people who underwent shear wave elastography from June 2022 to July 2023. The magnitude of compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH) was 6.81% (95% confidence interval [CI]: 5.30–8.7) and 4.91% (95% CI: 3.67–6.60), respectively. The normative percentiles were estimated from 282 persons without associated comorbidity and risk factors. The mean age (standard deviation [SD]) of the normal individuals was 40.90 ± 12.92 years, and 210 (71.47%) were males. The mean age (SD) of the 570 persons excluded from the normative percentiles analysis was 47.94 (12.49) years and 72.11% were males. The sex- and BMI-adjusted age-specific 90th percentiles of LSM were 8.76, 8.78, 8.96, 8.97, 9.25, and 9.45 kPa for 18 to 20, 21 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years, respectively. Conclusion The sex- and BMI-adjusted age-specific 90th percentiles for LSM using shear wave elastography in Asian Indian adults are almost similar to the greater than 9 kPa cutoff proposed by the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement guidelines to discriminate cACLD and CSPH from normal individuals.

Predictive Model of Recovery to Prefracture Activities-of-Daily-Living Status One Year after Fragility Hip Fracture.

Background and Objectives: Achieving prefracture functional status is a critical objective following a hip fracture, yet fewer than half of patients reach this milestone. The adoption of tools for assessing functional outcomes is increasingly recognized as essential for evaluating recovery following treatment for fragility hip fractures. We developed multivariable clinical prediction criteria to estimate the likelihood of patients regaining their prefracture activities-of-daily-living (ADL) status one year after sustaining a fragility hip fracture. Materials and Methods: A retrospective cohort of patients treated for fragility hip fractures at a university-affiliated tertiary care center between February 2017 and April 2019 served as the basis for developing and internally validating the clinical prediction criteria. We applied a multivariable fractional polynomial method to integrate several continuous predictors into a binary logistic regression model. Results: The study included 421 patients, 324 (77%) of whom reported regaining their prefracture activities-of-daily-living level one year after experiencing fragility hip fractures. Significant predictors, such as the prefracture Barthel index, EQ-VAS score, and treatment modality, were incorporated into the predictive model. The model demonstrated excellent discriminative power (AuROC of 0.86 [95% CI 0.82-0.91]) and satisfactory calibration. Conclusions: The predictive model has significant discriminative ability with good calibration and provides clinicians with a means to forecast the recovery trajectories of individual patients one year after a fragility hip fracture, which could be useful because prompt clinical decision-making is aided by this information. Patients and caregivers can also be counseled and encouraged to follow up with the medical activities and interventions deemed essential by doctors who used the prediction tool. Access to the model is provided through a web application. External validation is warranted in order to prove its applicability and generalizability.

A lack of association between BMI and chemoimmunotherapy efficacy in advanced non-small cell lung cancer: Secondary analysis of the IMpower150 and IMpower130 clinical trials

BackgroundMultiple studies have indicated that patients with high body mass index (BMI) may have favourable survival outcomes following treatment with an immune checkpoint inhibitor (ICI). However, this evidence is limited by several factors, notably the minimal evidence from randomised controlled trials (RCTs), the use of categorised BMI with inconsistent cut point definitions, and minimal investigation of contemporary combination ICI therapy. Moreover, whether overweight and obese patients gain a larger benefit from contemporary frontline chemoimmunotherapy in non-small cell lung cancer (NSCLC) is unclear.MethodsThis secondary analysis pooled individual patient data from the intention-to-treat population of the IMpower130 and IMpower150 RCTs comparing chemoimmunotherapy versus chemotherapy. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS). The potentially non-linear relationship between BMI and chemoimmunotherapy treatment effect was evaluated using Multivariable Fractional Polynomial Interaction (MFPI). As a sensitivity analysis, chemoimmunotherapy treatment effect (chemoimmunotherapy versus chemotherapy) on survival was also estimated for each BMI subgroup defined by World Health Organisation classification. Exploratory analyses in the respective chemoimmunotherapy and chemotherapy cohort were undertaken to examine the survival outcomes among BMI subgroups.ResultsA total of 1282 patients were included. From the MFPI analysis, BMI was not significantly associated with chemoimmunotherapy treatment effect with respect to either OS (p = 0.71) or PFS (p = 0.35). This was supported by the sensitivity analyses that demonstrated no significant treatment effect improvement in OS/PFS among overweight or obese patients compared to normal weight patients (OS: normal BMI HR = 0.74 95% CI 0.59–0.93, overweight HR = 0.78 95% CI 0.61–1.01, obese HR = 0.84 95% CI 0.59–1.20). Exploratory analyses further highlighted that survival outcomes were not significantly different across BMI subgroups in either the chemoimmunotherapy therapy cohort (Median OS: normal BMI 19.9 months, overweight 17.9 months, and obese 19.5 months, p = 0.7) or the chemotherapy cohort (Median OS: normal 14.1 months, overweight 15.9 months, and obese 16.7 months, p = 0.7).ConclusionThere was no association between high BMI (overweight or obese individuals) and enhanced chemoimmunotherapy treatment benefit in front-line treatment of advanced non-squamous NSCLC. This contrasts with previous publications that showed a superior treatment benefit in overweight and obese patients treated with immunotherapy given without chemotherapy.

Early Sepsis-Associated Acute Kidney Injury and Obesity.

The prevalence of obesity is increasing in the intensive care unit (ICU). Although obesity is a known risk factor for chronic kidney disease, its association with early sepsis-associated acute kidney injury (SA-AKI) and their combined association with patient outcomes warrant further investigation. To explore the association between obesity, early SA-AKI incidence, and clinical outcomes in patients with sepsis. This nationwide, prospective cohort study analyzed patients aged 19 years or older who had sepsis and were admitted to 20 tertiary hospital ICUs in Korea between September 1, 2019, and December 31, 2021. Patients with preexisting stage 3A to 5 chronic kidney disease and those with missing body mass index (BMI) values were excluded. Sepsis and hospitalization in the ICU. The primary outcome was SA-AKI incidence within 48 hours of ICU admission, and secondary outcomes were mortality and clinical recovery (survival to discharge within 30 days). Patients were categorized by BMI (calculated as weight in kilograms divided by height in meters squared), and data were analyzed by logistic regression adjusted for key characteristics and clinical factors. Multivariable fractional polynomial regression models and restricted cubic spline models were used to analyze the clinical outcomes with BMI as a continuous variable. Of the 4041 patients (median age, 73 years [IQR, 63-81 years]; 2349 [58.1%] male) included in the study, 1367 (33.8%) developed early SA-AKI. Obesity was associated with a higher incidence of SA-AKI compared with normal weight (adjusted odds ratio [AOR], 1.40; 95% CI, 1.15-1.70), as was every increase in BMI of 10 (OR, 1.75; 95% CI, 1.47-2.08). While obesity was associated with lower in-hospital mortality in patients without SA-AKI compared with their counterparts without obesity (ie, underweight, normal weight, overweight) (AOR, 0.72; 95% CI, 0.54-0.94), no difference in mortality was observed in those with SA-AKI (AOR, 0.85; 95% CI, 0.65-1.12). Although patients with obesity without SA-AKI had a greater likelihood of clinical recovery than their counterparts without obesity, clinical recovery was less likely among those with both obesity and SA-AKI. In this cohort study of patients with sepsis, obesity was associated with a higher risk of early SA-AKI and the presence of SA-AKI modified the association of obesity with clinical outcomes.

A nomogram model for predicting 5-year risk of prediabetes in Chinese adults

Early identification is crucial to effectively intervene in individuals at high risk of developing pre-diabetes. This study aimed to create a personalized nomogram to determine the 5-year risk of pre-diabetes among Chinese adults. This retrospective cohort study included 184,188 participants without prediabetes at baseline. Training cohorts (92,177) and validation cohorts (92,011) were randomly assigned (92,011). We compared five prediction models on the training cohorts: full cox proportional hazards model, stepwise cox proportional hazards model, multivariable fractional polynomials (MFP), machine learning, and least absolute shrinkage and selection operator (LASSO) models. At the same time, we validated the above five models on the validation set. And we chose the LASSO model as the final risk prediction model for prediabetes. We presented the model with a nomogram. The model's performance was evaluated in terms of its discriminative ability, clinical utility, and calibration using the area under the receiver operating characteristic (ROC) curve, decision curve analysis, and calibration analysis on the training cohorts. Simultaneously, we also evaluated the above nomogram on the validation set. The 5-year incidence of prediabetes was 10.70% and 10.69% in the training and validation cohort, respectively. We developed a simple nomogram that predicted the risk of prediabetes by using the parameters of age, body mass index (BMI), fasting plasma glucose (FBG), triglycerides (TG), systolic blood pressure (SBP), and serum creatinine (Scr). The nomogram's area under the receiver operating characteristic curve (AUC) was 0.7341 (95% CI 0.7290–0.7392) for the training cohort and 0.7336 (95% CI 0.7285–0.7387) for the validation cohort, indicating good discriminative ability. The calibration curve showed a perfect fit between the predicted prediabetes risk and the observed prediabetes risk. An analysis of the decision curve presented the clinical application of the nomogram, with alternative threshold probability spectrums being presented as well. A personalized prediabetes prediction nomogram was developed and validated among Chinese adults, identifying high-risk individuals. Doctors and others can easily and efficiently use our prediabetes prediction model when assessing prediabetes risk.

A Correlation Study of Plasma and Breast Milk Retinol Concentrations in Breastfeeding Women in China.

Retinol in breast milk is related to plasma concentration among breastfeeding women, but the linear or curvilinear relationships between the two remains unclear. We conducted a cross-sectional study in 403 Chinese breastfeeding women at 42 ± 7 days postpartum. Plasma and breast milk samples were assayed using high performance liquid chromatography to determine the concentration of retinol. Partial Spearman correlation and multivariable fractional polynomial regression were used to examine the relationships between the two retinol concentrations and between plasma retinol concentration and milk-to-plasma (M/P) retinol. The median (interquartile range, IQR) of the retinol concentration in the plasma was 1.39 (1.21, 1.63) μmol/L and 1.15 (0.83, 1.49) μmol/L in the breast milk, respectively. The partial correlation coefficient between them was 0.17 (p < 0.01). A linear relationship was observed with an adjusted regression coefficient of 0.34 (95% CI: 0.19, 0.49). The relationship between the plasma retinol and M/P ratio was nonlinear and segmented at 1.00 μmol/L of plasma retinol. The regression coefficients, below and above the segmented point, were -1.69 (95% CI: -2.75, -0.62) and -0.29 (95% CI: -0.42, -0.16), respectively. Plasma and breast milk retinol were positively correlated, whereas women with a low concentration of plasma retinol showed a stronger capacity of transferring retinol to breast milk.

Prediction of childhood overweight and obesity at age 10–11: findings from the Studying Lifecourse Obesity PrEdictors and the Born in Bradford cohorts

BackgroundIn England, 41% of children aged 10–11 years live with overweight or obesity. Identifying children at risk of developing overweight or obesity may help target early prevention interventions. We aimed to develop and externally validate prediction models of childhood overweight and obesity at age 10–11 years using routinely collected weight and height measurements at age 4–5 years and maternal and early-life health data.MethodsWe used an anonymised linked cohort of maternal pregnancy and birth health records in Hampshire, UK between 2003 and 2008 and child health records. Childhood body mass index (BMI), adjusted for age and sex, at 10–11 years was used to define the outcome of overweight and obesity (BMI ≥ 91st centile) in the models. Logistic regression models and multivariable fractional polynomials were used to select model predictors and to identify transformations of continuous predictors that best predict the outcome. Models were externally validated using data from the Born in Bradford birth cohort. Model performance was assessed using discrimination and calibration.ResultsChildhood BMI was available for 6566 children at 4–5 (14.6% overweight) and 10–11 years (26.1% overweight) with 10.8% overweight at both timepoints. The area under the curve (AUC) was 0.82 at development and 0.83 on external validation for the model only incorporating two predictors: BMI at 4–5 years and child sex. AUC increased to 0.84 on development and 0.85 on external validation on additionally incorporating maternal predictors in early pregnancy (BMI, smoking, age, educational attainment, ethnicity, parity, employment status). Models were well calibrated.ConclusionsThis prediction modelling can be applied at 4–5 years to identify the risk for childhood overweight at 10–11 years, with slightly improved prediction with the inclusion of maternal data. These prediction models demonstrate that routinely collected data can be used to target early preventive interventions to reduce the prevalence of childhood obesity.

Does the one-leg rise test reflect quadriceps strength in individuals following anterior cruciate ligament reconstruction?

ObjectiveTo explore if one-leg rise test performance is associated with quadriceps strength following anterior cruciate ligament reconstruction (ACLR). DesignCross-sectional. Participants100 individuals (50 females, 50 males) aged 18–40 years, 9–36 months post-ACLR with ongoing knee symptoms (KOOS4 <80/100). Main outcome measuresNumber of one-leg rise repetitions (using an adjustable-height plinth) and isometric quadriceps strength using isokinetic dynamometry (60° flexion, normalised to body mass). Multivariable fractional polynomial regression models adjusted for sex explored relationships between one-leg rise performance (repetitions) and quadriceps strength (Nm/kg) for each limb. ResultsA non-linear, increasing association between one-leg rise performance and quadriceps strength was observed, with the rate of increase attenuating at higher values of one-leg rise performance. Similar relationships were observed in the ACLR (β = 0.15, 95%CI 0.10 to 0.20; adjusted r2 = 0.51) and contralateral limb (β = 0.14, 95%CI 0.08 to 0.19; r2 = 0.42). ConclusionThe one-leg rise test can be an indicator of quadriceps strength in individuals after ACLR, enabling clinicians to easily monitor quadriceps strength recovery without specialised equipment. With the relationship between one-leg rise performance and quadriceps strength attenuating with a larger number of one-leg rises achieved, other factors (e.g., motivation, endurance) likely contribute to one-leg rise performance at higher values.

Biomarker analysis of the phase II JO25567 study comparing erlotinib with or without bevacizumab in first-line advanced EGFR+non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), such as erlotinib, are standard-of-care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC), but most patients progress within 1 year. Previously, we demonstrated that erlotinib plus bevacizumab (EB) improved progression-free survival (PFS) in patients with EGFR-positive non-squamous NSCLC in the randomized JO25567 study. To understand this effect, we conducted comprehensive exploratory biomarker analyses. Using blood and tissue specimens from patients enrolled in the JO25567 study, angiogenesis-related serum factors, plasma vascular endothelial growth factor-A (pVEGFA), angiogenesis-related gene polymorphisms, and messenger RNAs (mRNAs) in tumor tissue were analyzed. Interactions between potential predictors and treatment effect on PFS were analyzed in a Cox model. Continuous variable predictors were evaluated by multivariate fractional polynomial interaction methodology and subpopulation treatment effect pattern plotting (STEPP). Overall, 152 patients treated with EB or erlotinib alone (E) were included in the analysis. Among 26 factors analyzed in 134 baseline serum samples, high follistatin and low leptin were identified as potential biomarkers for worse and better outcomes with EB, with interaction P values of 0.0168 and 0.0049, respectively. Serum concentrations of 12 angiogenic factors were significantly higher in patients with high follistatin. Low pVEGFA levels related to better outcomes with EB, interaction P=0.033. VEGF-A165a was the only predictive tissue mRNA, showing a similar trend to pVEGFA. No valid results were obtained in 13 polymorphisms of eight genes. EB treatment showed better treatment outcomes in patients with low pVEGFA and serum leptin, and limited efficacy in patients with high serum follistatin.

Association between serum iron markers, iron supplementation and cardiovascular morbidity in pre-dialysis chronic kidney disease.

The optimal range of serum iron markers and usefulness of iron supplementation are uncertain in patients with pre-dialysis chronic kidney disease (CKD). We investigated the association between serum iron indices and risk of cardiovascular disease (CVD) events and the effectiveness of iron supplementation using Chronic Kidney Disease Japan Cohort data. We included 1416 patients ages 20-75years with pre-dialysis CKD. The tested exposures were serum transferrin saturation and serum ferritin levels and the outcome measures were any cardiovascular event. Fine-Gray subdistribution hazard models were used to examine the association between serum iron indices and time to events. The multivariable fractional polynomial interaction approach was used to evaluate whether serum iron indices were effect modifiers of the association between iron supplementation and cardiovascular events. The overall incidence rate of CVD events for a median of 4.12years was 26.7 events/1000 person-years. Patients with serum transferrin saturation <20% demonstrated an increased risk of CVD [subdistribution hazard ratio (HR) 2.13] and congestive heart failure (subdistribution HR 2.42). The magnitude of reduction in CVD risk with iron supplementation was greater in patients with lower transferrin saturations (P=.042). Maintaining transferrin saturation >20% and adequate iron supplementation may effectively reduce the risk of CVD events in patients with pre-dialysis CKD.

Humoral response after a BNT162b2 heterologous third dose of COVID-19 vaccine following two doses of BBIBP-CorV among healthcare personnel in Peru

BackgroundThe inactivated virus vaccine, BBIBP-CorV, was principally distributed across low- and middle-income countries as primary vaccination strategy to prevent poor COVID-19 outcomes. Limited information is available regarding its effect on heterologous boosting. We aim to evaluate the immunogenicity and reactogenicity of a third booster dose of BNT162b2 following a double BBIBP-CorV regime. MethodsWe conducted a cross-sectional study among healthcare providers from several healthcare facilities of the Seguro Social de Salud del Perú - ESSALUD. We included participants two-dose BBIBP-CorV vaccinated who presented a three-dose vaccination card at least 21 days passed since the vaccinees received their third dose and were willing to provide written informed consent. Antibodies were determined using LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin Inc., Stillwater, USA). Factors potentially associated with immunogenicity, and adverse events, were considered. We used a multivariable fractional polynomial modeling approach to estimate the association between anti-SARS-CoV-2 IgG antibodies’ geometric mean (GM) ratios and related predictors. ResultsWe included 595 subjects receiving a third dose with a median (IQR) age of 46 [37,54], from which 40% reported previous SARS-CoV-2 infection. The overall geometric mean (IQR) of anti-SARS-CoV-2 IgG antibodies was 8,410 (5,115 – 13,000) BAU/mL. Prior SARS-CoV-2 history and full/part-time in-person working modality were significantly associated with greater GM. Conversely, time from boosting to IgG measure was associated with lower GM levels. We found 81% of reactogenicity in the study population; younger age and being a nurse were associated with a lower incidence of adverse events. ConclusionsAmong healthcare providers, a booster dose of BNT162b2 following a full BBIBP-CorV regime provided high humoral immune protection. Thus, SARS-CoV-2 previous exposure and working in person displayed as determinants that increase anti-SARS-CoV-2 IgG antibodies.

Effects of influential points and sample size on the selection and replicability of multivariable fractional polynomial models

BackgroundThe multivariable fractional polynomial (MFP) approach combines variable selection using backward elimination with a function selection procedure (FSP) for fractional polynomial (FP) functions. It is a relatively simple approach which can be easily understood without advanced training in statistical modeling. For continuous variables, a closed test procedure is used to decide between no effect, linear, FP1, or FP2 functions. Influential points (IPs) and small sample sizes can both have a strong impact on a selected function and MFP model.MethodsWe used simulated data with six continuous and four categorical predictors to illustrate approaches which can help to identify IPs with an influence on function selection and the MFP model. Approaches use leave-one or two-out and two related techniques for a multivariable assessment. In eight subsamples, we also investigated the effects of sample size and model replicability, the latter by using three non-overlapping subsamples with the same sample size. For better illustration, a structured profile was used to provide an overview of all analyses conducted.ResultsThe results showed that one or more IPs can drive the functions and models selected. In addition, with a small sample size, MFP was not able to detect some non-linear functions and the selected model differed substantially from the true underlying model. However, when the sample size was relatively large and regression diagnostics were carefully conducted, MFP selected functions or models that were similar to the underlying true model.ConclusionsFor smaller sample size, IPs and low power are important reasons that the MFP approach may not be able to identify underlying functional relationships for continuous variables and selected models might differ substantially from the true model. However, for larger sample sizes, a carefully conducted MFP analysis is often a suitable way to select a multivariable regression model which includes continuous variables. In such a case, MFP can be the preferred approach to derive a multivariable descriptive model.

P785 A retrospective cohort study on vedolizumab trough levels in Crohn’s disease patients

Abstract Background Background: Vedolizumab (VDZ), an α47-integrin inhibitor, is approved for the treatment of moderate to severe Crohn’s disease (CD). Exposure-response relationship for VDZ is less evident in CD. Here, we are exploring associations between serum VDZ serum concentrations and clinical/biomarker-defined endpoints from a single center, real-world cohort. Methods Methods: Electronic health data records of CD patients during their first year of treatment with VDZ from January 2014 – July 2022 at our tertiary care center were obtained. Serum drug levels (TDL) and their correlation with outcomes were assessed at specified timepoints – weeks 12 (± 2), 26 (± 4) and 52 (± 6). Clinical remission was assessed by patient reported outcomes as suggested in STRIDE II guidelines (stool frequency ≤ 3 and abdominal pain ≤ 1). Fecal calprotectin (fCP) values ≤ 150 µg/g marked biomarker remission. Vedolizumab drug levels were measured with IDKmonitor Vedolizumab drug level ELISA kit (Immundiagnostik AG, Germany), In case of missing data patients were categorized as non-responders. For association modelling, multivariable fractional polynomials and generalised additive models were used (R statistical software, v4.1.2; R Core Team). Results Results: In total, 58 patients (females = 55.2%) with at least two available data points were included (Table 1). Sixteen individuals (16/58, 27.6%) were naive for biologics therapies. 98.3% (57/58) reached week 12 (± 2). Both at weeks 26 and 52 91.4% (53/58) subjects still were on drug. Clinical remission was achieved in 51.7% (30/58), 49.1% (26/53) and 45.2% (24/53) cases at weeks 12, 26 and 52, respectively, with biomarker remission rates of 24.1% (14/58), 35.8% (19/53) and 27.6% (16/53) patients reached biomarker remission. TDLs differed only between clinical remitters and non-remitters at week 26 (Mann-Whitney-U-test, p = 0.04). Also, there was no significant association between clinical and biomarker remission at defined timepoints and corresponding TDLs (for all p &amp;gt; 0.05). TDLs at week 2 and 6 were correlated with fCP values at the same time (rho: -0.327, p = 0.03 at week 2 and rho: -0.356, p = 0.02 at week 6). When TDLs at week 2 and week 6 were taken into consideration and associated separately with therapy outcomes in a univariate regression, only association between serum levels at week 6 and biomarker remission at weeks 26 and 52 was found (p = 0.02 and p = 0.03, respectively). Conclusion Conclusion: The only association between serum drug levels and remission was found between TDLs at week 6 and biomarker remission at weeks 26 and 52 suggesting a complex exposure-response relation for vedolizumab in CD patients.

Predictive model for prolonged length of hospital stay in patients with osteoporotic femoral neck fracture: A 5-year retrospective study.

Prolonged length of stay (LOS) in osteoporotic femoral neck fracture patients increased the hospital care cost and demonstrated in-hospital complications. This study aimed to develop an ease-of use predictive model of prolonged LOS in osteoporotic femoral neck fracture patients. In this 5-year retrospective study, the medical charts of 255 patients admitted to hospital with an osteoporotic femoral neck fracture resulting from a simple fall from January 2014 to December 2018 were reviewed. Multivariable fractional polynomials (MFP) algorithms was applied to develop the predictive model from candidate predictors of prolonged LOS. The discrimination performance of predictive model was evaluated using the receiver operating characteristic curve (ROC). Internal validity was assessed using bootstrapping. From 289 patients who were hospitalized with an osteoporotic fracture of femoral neck throughout this study, 255 (88%) fulfilled the inclusion criteria. There was 54.90% (140 of 255 patients) of patients who had prolonged LOS. The predictors of the predictive model were age, BMI, ASA score class 3 or 4, arthroplasty and time from injury to surgery. The area under ROC curve of the model was 0.83 (95% confidence interval 0.77-0.88). Internal validation with bootstrap re-sampling revealed an optimism of -0.002 (range -0.300-0.296) with an estimated shrinkage factor of 0.907 for the predictive model. The current predictive model developed from preoperative predictors which had a good discriminative ability to differentiate between length of hospitalization less than 14 days and prolonged LOS in osteoporotic femoral neck patients. This model can be applied as ease-of use calculator application to help patients, their families and clinicians make appropriate decisions in terms of treatment planning, postoperative care program, and cost-effectiveness before patients receiving the definitive treatments.

Association between Alcohol Consumption and Health-Related Quality of Life among Hospital and Ambulatory Care Patients with Past Year Depressive Symptoms.

Little is known about how substance use affects health-related quality of life (HRQOL) in depressed individuals. Here, associations between alcohol consumption and HRQOL in hospital and ambulatory care patients with past-year depressive symptoms are analyzed. The sample consisted of 590 participants (26.8% non-drinkers) recruited via consecutive screenings. Individuals with alcohol use disorders were excluded. HRQOL was assessed with the Veterans Rand 12-item health survey (VR-12). Multivariable fractional polynomials (MFP) regression analyses were conducted (1) to test for non-linear associations between average daily consumption and HRQOL and (2) to analyze associations between alcohol consumption and the physical and mental health component summaries of the VR-12 and their subdomains. Alcohol consumption was positively associated with the physical health component summary of the VR-12 (p = 0.001) and its subdomains general health (p = 0.006), physical functioning (p < 0.001), and bodily pain (p = 0.017), but not with the mental health component summary (p = 0.941) or any of its subdomains. Average daily alcohol consumption was not associated with HRQOL. Alcohol consumption was associated with better physical HRQOL. Findings do not justify ascribing alcohol positive effects on HRQOL. Data indicate that non-drinkers may suffer from serious health disorders. The results of this study can inform the development of future alcohol- and depression-related interventions.

Association of Time to Rapid Response Team Activation With Patient Outcomes Using a Range of Physiologic Deterioration Thresholds.

Retrospective multicenter cohort study. Three academic hospitals in Pennsylvania. We included the RRT activation of a hospitalization for non-ICU inpatients greater than or equal to 18 years old. None. The primary exposure was time to RRT activation after physiologic deterioration. We selected four Cardiac Arrest Risk Triage (CART) score thresholds a priori from which to measure time to RRT activation (CART score ≥ 12, ≥ 16, ≥ 20, and ≥ 24). The primary outcome was 7-day mortality-death or discharge to hospice care within 7 days of RRT activation. For each CART threshold, we modeled the association of time to RRT activation duration with 7-day mortality using multivariable fractional polynomial regression. Increased time from clinical decompensation to RRT activation was associated with higher risk of 7-day mortality. This relationship was nonlinear, with odds of mortality increasing rapidly as time to RRT activation increased from 0 to 4 hours and then plateauing. This pattern was observed across several thresholds of physiologic derangement. Increasing time to RRT activation was associated in a nonlinear fashion with increased 7-day mortality. This relationship appeared most marked when using a CART score greater than 20 threshold from which to measure time to RRT activation. We suggest that these empirical findings could be used to inform RRT delay definitions in further studies to determine the clinical impact of interventions focused on timely RRT activation.

Air quality and the risk of out-of-hospital cardiac arrest in Singapore (PAROS): a time series analysis

Previous studies have reported positive associations between out-of-hospital cardiac arrest (OHCA) and air pollutant concentrations, but there are inconsistencies across studies. We aimed to investigate the association between pollutant concentrations and the risk of OHCA in Singapore. We did a time series analysis of all cases of OHCA in Singapore reported between July 1, 2010, and Dec 31, 2018, to the Pan-Asian Resuscitation Outcomes Study (PAROS), a prospective, population-based registry. Using multivariable fractional polynomial modelling, we investigated the immediate (day 0) and lagged (up to 5 days after exposure) association between 10 μg/m³ increases in concentrations of particulate matter with a diameter of 2·5 μm or smaller (PM_2·5), particulate matter with a diameter of 10 μm or smaller (PM₁₀), ozone (O₃), nitrogen dioxide (NO₂), and sulphur dioxide (SO₂) and 1 mg/m³ increase in carbon monoxide (CO) and relative risk (RR) of OHCA. We extracted data for 18 131 cases of OHCA. The median age of this cohort of cases was 65 years (IQR 56-80), 6484 (35·8%) were female, 11 647 (64·2%) were male, 12 270 (67·7%) were Chinese, 2873 (15·8%) were Malay, and 2010 (11·1%) were Indian. Every 10 μg/m³ increase in PM_2·5 was associated with increased risk of OHCA (RR 1·022 [95% 1·002-1·043]) over the next 2 days, which decreased over the subsequent 3 days (3-5 days after exposure; 0·976 [0·955-0·998]). For PM₁₀, O₃, NO₂, and SO₂, we did not observe any associations between increased concentration and risk of OHCA on day 0 or cumulative risk over time (ie, at 0-1 days, 0-2 days, 0-3 days, 0-4 days, 0-5 days, and 3-5 days after exposure). For CO, we observed a cumulative decreased risk of OHCA across 0-5 days after exposure (0·876 [0·770-0·997]) and at days 3-5 after exposure (0·810 [0·690-0·949]). We observed effect modification of the association between increasing PM_2·5 concentration and OHCA 0-2 days after exposure by cardiac arrest rhythm (non-shockable 1·027 [1·004-1·050] vs shockable 1·002 [0·956-1·051]) and location of OHCA (at home: 1·033 [1·008-1·057] vs not at home 0·955 [0·957-1·035]). In hypothetical modelling, the number of OHCA events associated with PM_2·5 could be reduced by 8% with a 1 μg/m³ decrease in PM_2·5 concentrations and by 30% with a 3 μg/m³ decrease in PM_2·5 concentrations. Increases in PM_2·5 concentration were associated with an initial increased risk of OHCA and a subsequent reduced risk from 3-5 days after exposure, suggesting a short-term harvesting effect. A decrease in PM_2·5 concentrations could reduce population demand for emergency health services. National Medical Research Council, Singapore, under the Clinician Scientist Award, Singapore and the Singapore Translational Research Investigator Award (MOH-000982-01).

Impact of Flow Reversal Duration on Neurological Outcomes of Transcarotid Artery Revascularization (TCAR)

Flow reversal is a key component of transcarotid artery revascularization (TCAR). However, the impact of flow reversal duration on neurological outcomes and the duration of flow reversal which optimizes TCAR's outcomes is not known. We evaluated the association of flow reversal time with the intraoperative and postoperative neurological outcomes of TCAR. We studied all patients undergoing TCAR from September 2016 to October 2021. The exposure of interest was the duration of flow reversal. Multivariable logistic and fractional polynomial models were used to study the impact of flow reversal duration on in-hospital stroke, intraoperative neurological change/intolerance and stroke/death following TCAR and to identify the flow reversal time above which significant perioperative neurological events occur. The study included 19,462 patients with mean age of 73.4years who were mostly Caucasian (91%) and male (63%). The mean flow reversal time was 10.7minutes, and the overall stroke rate was 1.4%. The odds of intraoperative neurological change increased by 3.6% per minute increase in flow reversal time (odds ratio (OR), 1.04; 95%, 1.01-1.06; P<0.002). Flow reversal duration >10minutes was associated with 78% increased odds of neurological changes compared to flow reversal duration <10minutes. There was no significant association between flow reversal duration and stroke, and stroke/death in the first 5minutes after initiation of flow reversal. The odds of stroke increased by 2.7% per minute increase in flow reversal time >5minutes (OR, 1.03; 95%, 1.01-1.04; P<0.001), with flow reversal duration >10minutes associated with 38% increased odds of stroke compared to flow reversal duration ≤10minutes (OR, 1.37, 95% confidence interval (CI), 1.09-1.73, P=0.006). The odds of stroke/death increased by 2.5% per minute increase in flow reversal time >5minutes (OR, 1.03; 95%, 1.01-1.04; P<0.001). Flow reversal duration >10minutes was associated with 25% increased odds of stroke/death compared to flow reversal duration <10minutes (OR, 1.25, 95% CI, 1.01-1.53, P=0.038). Symptomatic status did not modify outcomes. Our findings suggest that outcomes following TCAR are optimal if the duration of flow reversal is minimized. A clinical cutoff time of 10minutes is suggested by this study and recommended as a guide. Further studies targeted at the flow reversal component of TCAR are needed to solidify the evidence regarding the clinical effects of temporarily induced retrograde cerebral blood flow during TCAR.

The influence of air quality and meteorological variations on influenza A and B virus infections in a paediatric population in Singapore

IntroductionInfluenza is an important cause of paediatric illness across the globe. However, information about the relationships between air pollution, meteorological variability and paediatric influenza A and B infections in tropical settings is limited. MethodsWe analysed all daily reports of influenza A and B infections in children <5 years old obtained from the largest specialist women and children's hospital in Singapore. In separate negative binomial regression models, we assessed the dependence of paediatric influenza A and B infections on air quality and meteorological variability, using multivariable fractional polynomial modelling and adjusting for time-varying confounders. ResultsApproximately 80% of 7329 laboratory-confirmed reports were caused by influenza A. We observed positive associations between sulphur dioxide (SO2) exposure and the subsequent risk of infection with both influenza types. We observed evidence of a harvesting effect of SO2 on Influenza A but not Influenza B. Ambient temperature was associated with a decline in influenza A reports (Relative Risk at lag 5 [RRlag5]: 0.949, 95% CI: 0.916–0.983). Rainfall was positively associated with a subsequent increase in influenza A reports (RRlag3: 1.044, 95% CI: 1.017–1.071). Nitrogen dioxide (NO2) concentration was positively associated with influenza B reports (RRlag5: 1.015, 95% CI: 1.005–1.025). There was a non-linear association between CO and influenza B reports. Absolute humidity increased the ensuing risk of influenza B (RRlag5: 4.799, 95% CI: 2.277–10.118). Influenza A and B infections displayed dissimilar but predictable within-year seasonal patterns. ConclusionsWe observed different independent associations between air quality and meteorological variability with paediatric influenza A and B infections. Anticipated seasonal infection peaks and variations in air quality and meteorological parameters can inform the timing of community measures aimed at reducing influenza infection risk.

Interbirth interval and maternal anaemia in 21 sub-Saharan African countries: A fractional-polynomial analysis.

BackgroundMaternal anaemia is a global public health problem contributing to adverse maternal and perinatal outcomes. In addition to other risk factors, interbirth interval has been identified as a potentially modifiable risk factor of maternal anaemia. However, the current evidence for the association between interbirth interval and maternal anaemia remains inconclusive. Hence, this study examined the association between the interbirth interval and maternal anaemia in sub-Saharan Africa.MethodsWe conducted a multinational cross-sectional study of interbirth interval (time between two singleton live births) and maternal anaemia (haemoglobin levels < 12 g/dl for non-pregnant women, < 11 g/dl for pregnant women) for 21 sub-Saharan African countries using the most recent nationally representative Demographic and Health Surveys, 2010–2017. A weighted multivariable fractional polynomial function was used to estimate the non-linear relationship between interbirth interval and maternal anaemia, considering interbirth interval as a continuous variable and adjusting for potential confounders. Analyses were stratified by reproductive classification (non-pregnant and pregnant women).ResultsThere were 81,693 women included in the study (89.2% non-pregnant, 10.8% pregnant). Of all women, 32.2% were in their postpartum period. Overall, 36.9% of women had anaemia (36.0% of non-pregnant and 44.3% of pregnant women). Of the participants, 15% had a short interbirth interval (<24 months), and 16% had a long interbirth interval (≥ 60 months). We found that both short and longer interbirth intervals were associated with an increased risk of maternal anaemia in a dose-response fashion. Relatively a lower risk of maternal anaemia was observed between 24 and 40 months of interbirth intervals.ConclusionsOur findings suggest that both short and longer interbirth intervals were associated with an increased risk of maternal anaemia in sub-Saharan Africa.