Cox's Hazards Regression Model Research Articles

Factors impeding switching from clozapine to paliperidone among patients with chronic schizophrenia—A retrospective cohort study.

Clozapine is an old antipsychotic that is effective for schizophrenia, however undesirable side effects affect drug adherence. The present study aimed to investigate the predictors for failed switching from clozapine to paliperidone (FSCP) among patients with chronic schizophrenia. This 9-year (January 2010-December 2018) retrospective study included 78 individuals with schizophrenia who wished to switch from clozapine to paliperidone and resided in a nursing home in Taiwan. The univariate Cox proportional hazards regression model (Cox model) was applied to estimate the potential factors for subsequent FSCP, followed by a multivariate Cox model to determine significant predictors of FSCP after adjusting for other covariates. Thirty eight of the 78 participants (48.7%) failed to switch from clozapine to paliperidone. After forward selection in the Cox hazard regression model, a higher number of total admission days during 1 year before switching, longer duration of clozapine use before switching, and higher average daily dose of clozapine during 1 year before switching were significantly associated with FSCP. It is suggested that clinicians should discuss with their patients about the risk factors if they intend to switch from clozapine to paliperidone. Further studies are warranted to verify our findings and extend the applicability. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Low baseline vitamin D levels correlate with adverse pathological features and clinical outcomes among patients with breast cancer.

552 Background: Serum vitamin D levels have been linked to breast cancer development; however, the impact on breast cancer features and outcomes remains unclear. The present study aimed at investigating the prognostic value of baseline vitamin D level among non-metastatic breast cancer patients. Methods: In this study; we prospectively assessed female patients presenting to our department with non-metastatic breast cancer during the period from October 2018 to December 2019 for their baseline serum vitamin D levels measured by ELISA test before starting systemic therapy, in addition to other clinicopathological factors. Low Vit-D was defined as Vit-D level less than 30 ng /l. Chi-square test (Fisher’s exact test) was used to examine the relation between qualitative variables. Survival analysis was done using Kaplan-Meier method and comparison between two survival curves was done using log-rank test. Multivariate analysis was done using Cox-regression hazard model for the significant factors affecting survival on univariate analysis. Results: We enrolled 221 patients with non-metastatic breast cancer as they matched our eligibility criteria. Median age at diagnosis was (50.7± 10.9). About two thirds of the patients (64.7%) were post menopause. Median vitamin D level was (23.1 ng/l) with a range of (4-62.46 ng/liter). Around half of the patients (56.5%) had vitamin D level lower than 30 ng/liter, with higher numbers of low vitamin D levels among HER2 positive and triple negative (TNBC) patients compared to hormonal receptor positive (HR+ve) patients (P=<0.001). There was a significant negative correlation between vitamin D levels and tumor size, lymph node positivity and stage at diagnosis (the lower the vitamin D level, the larger the tumor size, and the higher the number of positive lymph nodes and the stage; r= -0.414, r= -0.586, r= -0.674; respectively; p<0.001). On follow up, the number of local recurrences, bone metastases and liver metastases were significantly higher among the low vitamin D level group, however; there was no significant difference between the two groups in terms of development of brain and lung metastases. Disease free survival (DFS) and overall survival (OS) was significantly worse among the low vitamin D level group (p<0.001). Conclusions: Low serum vitamin D in breast cancer patients negatively correlates with tumor size, lymph node positivity and stage at diagnosis. It is linked to HER-2 positive and TNBC, and is significantly associated with worse DFS and OS.

MO993: Incidence of Ptld and Its Relationship with Cmv-Serostatus Positivity Among Childhood and Adulthood Population: A Registry Data Study

Abstract BACKGROUND AND AIMS It is unknown how the epidemiology of post-transplant lymphoproliferative disease (PTLD) and its relationship with CMV infection differ between adult and pediatric kidney transplant recipients. In addition, with current advancements in immunosuppressive therapy, the incidence of PTLD has changed dramatically. The aim of our study is to elucidate the relationship between PTLD and CMV infection. Moerover, to assess the incidence of PTLD among Adult and pediatric renal transplant patients in the current era. METHOD All renal transplant patients registered in the Organ Procurement and Transplantation Network between 2005 and 2019 were retrospectively reviewed. Patient were followed up till December 2020. Patients who had multiple organ transplant or those with previous renal transplants were excluded from the study. Data about recipient factors (age, sex ethnicity, diabetes, CMV serostatus, and EBV serostatus), donor factors (living or deceased), transplant factors (PRA, Cold ischemia time, HLA mismatches, induction and immunosuppressive therapy) were reviewed. Incidence rate of PTLD at one year and five years post-transplant were calculated among the Adult and Pediatric population. Univariate and Multivariate cox-hazard regression models were performed to assess the relationship between CMV serostatus and occurrence of PTLD. RESULTS About 10 947 pediatric renal transplant patients were included. About 315 pediatric patients developed PTLD during the follow-up time (2.88%). About 50.55% of PTLD occurred within the first-year post-transplant. 60% occurred within two-year post-transplant, while 80.63% of them occurred within five years post-transplant. CMV recipient infection was not associated with PTLD occurrence in the pediatric population (HR = 0.88, Pvalue = 0.81, 95% confidence interval ranged between 0.66 and 1.18). Proportional hazard assumption was not violated with P = 0.55. Among the adult population, 1990/277 955 developed PTLD (0.77%). About 25.77% of PTLD among the adult population occurred within the first-year post-transplant. About 39.39% of PTLD in the adult occurred within two-year post-transplant. About 66.55% of PTLD in the adult occurred within five-years post-transplant. CMV recipient positive serostatus was associated with a protective effect against occurrence of PTLD (HR = 0.82, Pvalue <0.01, 95% confidence interval ranged between 0.73 and 0.94). The most common type of PTLD among the pediatric and adult population was monomorphic PTLD ( 40% and 34%, respectively). CONCLUSION PTLD is a rare complication of renal transplantation in the current era. The risk of development of PTLD is highest during the first-year post-transplant. CMV recipient positive serostatus has a protective effect against development of PTLD.

Efficacy of Cryoballoon Ablation for Atrial Fibrillation and Recurrence Predictors in an Asian Cohort.

Background: Cryoballoon ablation (CBA) for atrial fibrillation (AF) is a rhythm control procedure used in clinical trials, mostly in Western countries. Its efficacy and the predictors of AF recurrence after CBA remain unclear for Asian populations. We aimed to investigate the efficacy of CBA and the predictors of AF recurrence after CBA in Asian AF patients. Methods: We included consecutive AF patients undergoing CBA for rhythm control between 2014 and 2020. The baseline characteristics, including AF types, symptom severity, and left atrial diameter (LAD), were analyzed. Holter’s monitoring and 12-lead ECG were performed to document AF recurrence. A multivariate Cox hazards regression model was used to evaluate the risk of AF recurrence. Results: A total of 120 AF patients (aged 61.9 ± 9.3 years) were included. The percentage of patients free from AF in the year following CBA was 74.2%. Among the three independent predictors of AF recurrence within one year were the presence of persistent AF (p = 0.025), an LAD ≥ 4.75 cm (p = 0.016), and pre-procedural cardioversion (p = 0.025). All patients survived and none had a stroke after CBA. Conclusion: CBA for AF is an effective and safe procedure in Asian populations. The presence of persistent AF, an LAD ≥ 4.75 cm, and severe symptoms are predictors of AF recurrence in the year following CBA.

Time spent in outdoor light is associated with the risk of dementia: a prospective cohort study of 362094 participants

BackgroundData on the association between free-living daytime sunlight exposure and incident dementia are scarce. The objective is to evaluate whether the time spent in outdoor light is related to the dementia risk and to investigate whether the optimal duration varies with clinical parameters.MethodsData were from a prospective cohort of 362,094 UK Biobank participants. A questionnaire survey was conducted to investigate how many hours the participants spent outdoors on typical summer and winter days. A restricted cubic spline (RCS) was performed to explore the potential nonlinear relationship between sunlight exposure and the risk of dementia. We used multivariate Cox proportional hazard regression models to estimate the hazard ratios (HRs) for the associations between sunlight exposure and dementia outcomes, with the change points as a reference.ResultsAfter a median follow-up of 9.0 years, 4149 (1.15%) individuals were diagnosed with dementia. RCS showed a J-shaped relationship between time spent in outdoor light and the dementia risk, with the lowest risk at three change points (1.5 h/day on average, 2 h/day in summer, and 1 h/day in winter). Cox hazard regression models showed a marked increase in risk at low exposure (HR=1.287, 95%CI 1.094–1.515) but a relatively slow increase at higher exposure (HR=1.070, 95%CI 1.031–1.10). Results are more pronounced among participants over 60 years old, females, and those with exactly 7 h of sleep every night.ConclusionsSunlight exposure had a J-shaped association with dementia risk. Giving detailed guidance on sunlight exposure can effectively prevent dementia.

Outcomes and prognostic factors after surgery for bone metastases in the extremities and pelvis: A retrospective analysis of 140 patients

BackgroundSurgical therapy of bone metastases is becoming increasingly important due to prolonged life expectancy and improved oncological treatment options. In a mostly palliative approach, it is necessary to identify those patients who might benefit from surgery. The shorter the remaining lifetime, the more restricted the indication and the less radical the intervention should be. The aim of this study was to evaluate the postoperative outcomes and prognostic factors for survival of patients with surgically treated bone metastases. MethodsWe retrospectively included 140 patients who underwent surgery for 151 bone metastases in the extremities and pelvis at our hospital between 2010 and 2020. We examined patient demographics, surgical procedures, 30-day complications, local tumour progression, and reoperations. Survival was calculated using Kaplan-Meier analysis. Prognostic factors were investigated by univariate analysis using the log-rank test and multivariate analysis using the Cox regression hazard model. ResultsIn 138 patients, the median survival time was 12.3 months. The overall survival rates at one, two, three and five years were 52.3%, 37.6%, 28.0%, and 18.0%, respectively. In univariate analysis, lung cancer, renal cell carcinoma, pathological fracture, visceral metastasis and multiple bone metastases were significantly associated with prognosis. No significant influence was determined for gender, age, location of bone metastasis, type of surgical procedure and time between diagnosis of primary tumour and surgery for bone metastasis. Multivariate analysis confirmed that pathological fracture, visceral metastasis and lung cancer were negative prognostic variables in terms of survival. Within 30 days, the incidence of complications was 25.0% and mortality was 9.3%. The most common complications were urinary tract infections (5.0%), pneumonia (4.3%), and delirium (2.9%). Local tumour progression occurred in 12 patients (8.7%) and five reoperations (3.6%) were performed. There were no significant differences between patients treated with endoprosthetic replacement (n = 47) and those treated with internal fixation (n = 91) in terms of 30-day complications and mortality as well as local tumour progression. ConclusionsSurvival of patients after surgery for bone metastases in the extremities or pelvis is very limited. The presence of a pathological fracture, visceral metastasis and lung cancer were independent prognostic factors for poor survival. Both internal fixation and endoprosthetic replacement achieved similar outcomes.

Rhythm Control Better Prevents Dementia than Rate Control Strategies in Patients with Atrial Fibrillation-A Nationwide Cohort Study.

Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm control group had a lower rate of dementia than the rate control group (adjust HR: 0.75, p = 0.031). The rhythm control strategy reduced the risk of dementia particularly in those receiving aspirin (p = 0.03). Conclusions: In patients with AF, pharmacological rhythm control was associated with a lower risk of dementia than rate control over a long-term follow-up period, particularly in patients receiving aspirin treatment.

Expression of Membranous CD155 Is Associated with Aggressive Phenotypes and a Poor Prognosis in Patients with Bladder Cancer.

Simple SummaryThe presence of the poliovirus receptor (known as cluster of differentiation 155 (CD155)) in human cancer is an unfavorable prognostic marker. We investigated whether CD155 expression, divided into membranous and cytoplasmic types, affects the prognosis of bladder cancer (BC) in terms of recurrence-free survival (RFS) and cancer-specific survival (CSS). We found that membranous CD155 (mCD155)-positive cases had shorter periods of both RFS and CSS, whereas there was no association between cytoplasmic CD155 (cCD155) and survival outcomes. The results showed that CD155, especially mCD155, may serve as a poor prognostic marker in BC.Objective: To investigate the relationship between clinicopathological findings and membranous CD155 (mCD155) or cytoplasmic CD155 (cCD155) expression in bladder cancer (BC). Methods: We retrospectively analyzed 103 patients with BC who underwent radical cystectomy between 1990 to 2015 at Kitasato University Hospital. Immunohistochemical staining was performed to evaluate CD155 expression in tumor cells. Cases with > 10% expression on the membrane or cytoplasm of tumor cells were positive. The Fisher′s exact test was used for categorical variables and the Kaplan–Meier method was used for survival outcomes. Univariate and multivariate Cox regression hazard models were used to evaluate the survival risk factors. Results: Cases that were mCD155-positive were associated with high-grade tumors (p = 0.02), nodal status (p < 0.01), and pT stage (p = 0.04). No association with any clinicopathological factor was observed in the cCD155 cases. Kaplan–Meier analysis showed that mCD155-positive cases had shorter periods of recurrence-free survival (p = 0.015) and cancer-specific survival (p = 0.005). Only nodal status was an independent predictor for both cancer-specific survival and recurrence-free survival in multivariate analysis (p = 0.02 and p < 0.01, respectively). Conclusion: mCD155 expression may be a marker of an aggressive phenotype and a poor prognosis in patients with BC.

Efficacy of Pre-operative 18F-FDG PET/CT in Prognostic Prediction in Patients With Renal Cell Carcinoma

Background/Aim: This study analyzed the parameters provided by preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for prognostic prediction of renal cell carcinoma (RCC). Patients and Methods: FDG-PET/CT data from 66 clear cell RCC and 19 non-clear cell RCC cases between January 2015 and October 2018 were reviewed retrospectively. We compared the two groups according to recurrence/metastasis to determine prognosis-influencing factors. Multivariate Cox hazard regression models were constructed to evaluate factors potentially predicting disease-free survival (DFS) after adjustment for confounders. DFS was then compared between groups. Results: Standardized uptake values (SUV) of the PET/CT scan were independent predictors of prognosis after adjusting for confounders. RCC cases were divided into two groups by optimal cut-off values. Differences between DFS percentages in high and low SUV groups were significant. Similar results were obtained in clear cell RCC groups. Conclusion: Increased SUV of the PET/CT scan are significant predictors of worse prognoses in patients with surgically resected RCC.

De Ritis Ratio (Aspartate Transaminase/Alanine Transaminase) as a Significant Prognostic Factor With Upper Urinary Tract Carcinoma Who Underwent Radical Nephroureterectomy and Adjuvant Chemotherapy

Purpose: To investigate the correlation between preoperative De Ritis ratio (aspartate transaminase [AST]/alanine transaminase [ALT]) and postoperative clinical outcome in patients with upper urinary tract carcinoma (UTUC) who underwent radical nephroureterectomy (RNU) and adjuvant chemotherapy (ACH).Materials and Methods: We respectively analyzed the clinical and pathological data of 102 patients who underwent RNU and ACH for UTUC. Patients were divided into 2 groups, according to the optimal value of AST/ALT ratio. The effect of the AST/ALT ratio was analyzed by the Kaplan-Meier method and Cox regression hazard models for patients’ cancer-specific survival (CSS) and overall survival (OS).Results: Mean survival time was 50.5±41.2 months. Mean age was 61.4±9.7years. Forty-one of the patients (46.5%) were in the high AST/ALT group. According to receiver operating characteristic analysis, the optimal AST/ALT ratio was 1.2. In Kaplan-Meier analyses, the high AST/ALT group showed worse outcomes in OS (p=0.007) and CSS (p=0.011). Using Cox regression models of clinical and pathological parameters to predict OS, high AST/ALT ratio (hazard ratio [HR], 5.428; 95% confidence interval [CI]; 1.803–16.334; p=0.002), pathological T3 (pT3) or higher (HR, 1.464; 95% CI; 1.156-1.857; p=0.002), and to predict CSS, high AST/ALT ratio (HR, 4.417; 95% CI; 1.545–12.632; p=0.005), and pT3 or higher (HR, 1.475; 95% CI; 1.172–1.904; p=0.002) were determined as independent prognostic factors.Conclusions: Pretreatment AST/ALT ratio is a significant independent predictor of CSS and OS in advanced UTUC patients receiving systemic ACH after RNU.

Real-world effectiveness of pharmacological treatments of opioid use disorder in a national cohort.

AimTo investigate the real‐world effectiveness of pharmacological treatments (buprenorphine, methadone) of opioid use disorder (OUD).DesignA nation‐wide, register‐based cohort study.SettingSweden.ParticipantsAll residents aged 16–64 years living in Sweden using OUD medication from July 2005 to December 2016 (n = 5757, 71.8% men) were identified from registers of prescriptions, inpatient and specialized outpatient care, causes of death, sickness absence and disability pensions.MeasurementsMain outcome: hospitalization due to OUD. Secondary outcomes: hospitalization due to any cause; death due to all, natural and external causes. Mortality was analyzed with between‐individual multivariate‐adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalizations, were analyzed with within‐individual analyses to eliminate selection bias. OUD medication use versus non‐use was modelled with PRE2DUP (from prescription drug purchases to drug use periods) method.FindingsBuprenorphine [hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.54–0.97] and methadone (HR = 0.74, 95% CI = 0.59–0.93) use were associated with significantly lower risk of OUD hospitalization, but not any‐cause hospitalizations, compared with the time‐periods when the same individual did not use OUD medication. The use of buprenorphine and methadone were both associated with significantly lower risk of all‐cause mortality (HR = 0.45, 95% CI = 0.34–0.59; HR = 0.51, 95% CI = 0.41–0.63, respectively), compared with non‐use of both medications. Similar results were found for risk of mortality due to external causes (HR = 0.39; 95% CI = 0.27–0.54; HR = 0.40; 95% CI = 0.29–0.53, respectively), but not for mortality due to natural causes. The risk of OUD hospitalization and all‐cause mortality was decreased in all duration categories of studied medications (< 30, 31–180, 181–365 and >365 days), except for methadone use less than 30 days.ConclusionsThe use of buprenorphine and methadone are both associated with a significantly lower risk of hospitalization due to opioid use disorder and death due to all and external causes, when compared with non‐use.

Concurrent Validity and Prognostic Utility of the Needs Assessment Tool: Progressive Disease Heart Failure

ContextPeople with advanced heart failure have supportive and palliative needs requiring systematic assessment. ObjectivesWe aimed to assess the validity of the Needs Assessment Tool: Progressive Disease – Heart Failure (NAT:PD-HF). MethodsSecondary analysis of routinely collected patient data from a specialist palliative care-heart disease service improvement project. NAT:PD-HF, the Integrated Palliative care Outcome Scale (IPOS), and patient and/or carer-report data were collected. Concurrent validity between NAT:PD-HF items and comparison measures (Kendall's tau; kappa); construct validity via known-group comparisons; predictive utility of NAT:PD-HF for survival (multivariable Cox hazard regression model). ResultsData from 88 patients (50% men; mean age 85; median survival 205 days; 64% left ventricular systolic dysfunction) were analyzed. Prevalence- and bias-adjusted kappa values indicated moderate agreement for physical symptom needs (k: 0.33 for patients, 0.42 for carers). Substantial agreement was observed for patient and/or carer psychological symptoms, and information needs (k ≥ 0.6). NAT:PD-HF distinguished between patients with different survival, comorbidities, functional scores, and palliative Phase of Illness with moderate to high effect sizes. NAT did not predict survival when adjusted for mortality risk score and functional status (2+ needs HR: 1.52, 95% CI: 1.01-1.74). ConclusionThe NAT:PD-HF is a valid tool for clinician assessment of physical, psychosocial, and information patient and/or carer needs.

Association of a Combination of Healthy Lifestyle Behaviors With Reduced Risk of Incident Systemic Lupus Erythematosus.

While previous studies have demonstrated an association between individual factors related to lifestyle and the risk of systemic lupus erythematosus (SLE), it is unclear how the combination of these factors might affect the risk of incident SLE. This study was undertaken to prospectively evaluate whether a combination of healthy lifestyle factors is associated with a lower risk of incident SLE and its subtypes (anti-double-stranded DNA [anti-dsDNA]-positive and anti-dsDNA-negative SLE). The study included 185,962 women from the Nurses' Health Study (NHS) and NHSII cohorts, among whom there were 203 incident cases of SLE (96 with anti-dsDNA-positive SLE, 107 with anti-dsDNA-negative SLE) during 4,649,477 person-years of follow-up. The Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 2 years during follow-up, with scores assigned for 5 healthy lifestyle factors: alcohol consumption, body mass index, smoking, diet, and exercise. A time-varying Cox proportional hazards regression model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) for the risk of SLE. In addition, the percentage of partial population attributable risk (PAR%) of SLE development was calculated. A higher HLIS was associated with a lower risk of SLE overall (HR 0.81 [95% CI 0.71-0.94]) and a lower risk of anti-dsDNA-positive SLE (HR 0.78 [95% CI 0.63-0.95]). Women with ≥4 healthy lifestyle factors had the lowest risk of SLE overall (HR 0.42, 95% CI 0.25-0.70) and lowest risk of anti-dsDNA-positive SLE (HR 0.35, 95% CI 0.17-0.75) as compared to women with only 1 healthy behavior or no healthy behaviors. The PAR% of SLE development was 47.7% (95% CI 23.1-66.6%), assuming that the entire population had adhered to at least 4 healthy lifestyle behaviors. These results indicate that the risk of developing SLE, a disease in which significant evidence of genetic involvement has been established, might be reduced by nearly 50% with adherence to modifiable healthy lifestyle behaviors.

The Pan-Immune-Inflammation Value predicts the survival of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer treated with first-line ALK inhibitor

BackgroundAnaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC). However, reliable biomarkers to predict the prognostic role of this treatment are lacking. The Pan-Immune-Inflammation Value (PIV) has recently been demonstrated as a novel comprehensive biomarker to predict survival of patients with solid tumors. Our study aimed to evaluate the prognostic power of PIV in this group of patients. Patients and methods94 patients with advanced ALK-positive NSCLC who received first-line ALK inhibitors were enrolled in this study. PIV was calculated as the product of peripheral blood neutrophil, monocyte, and platelet counts divided by lymphocyte count. Kaplan-Meier method and Cox hazard regression models were used for survival analyses. ResultsThe 1-year progression-free survival (PFS) was 63.5%, and the 5-year overall survival (OS) rate was 55.1%. Patients with higher PIV, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) had worse PFS in univariate analysis, but only the PIV (hazard ratio [HR] = 2.90, 95% confidence interval [CI]: 1.79–4.70, p < 0.001) was an independent prognostic factor in multivariate analysis. Similarly, patients with higher PIV, NLR, PLR, and SII had a worse OS in the univariate analysis, but only the PIV (HR = 4.70, 95% CI: 2.00–11.02, p < 0.001) was significantly associated with worse OS in multivariate analysis. ConclusionPIV is a comprehensive and convenient predictor of both PFS and OS in patients with ALK-positive advanced NSCLC who received first-line ALK TKIs. Prospective clinical trials are required to validate the value of this new parameter.

Pediatric respiratory hospitalizations in small for gestational age neonates born at term.

This study investigates the risk for long-term respiratory hospitalizations of offspring born small for gestational age (SGA) at term. A retrospective population-based cohort analysis was performed to examine the risk of long-term respiratory hospitalizations between SGA compared to appropriate for gestational age (AGA) newborns. The analysis included all term singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. Fetuses with congenital malformations, multiple gestation, cases of perinatal mortality and large for gestational age (LGA) were excluded. A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence up to the age of 18 years, and a Cox hazards regression model was used to control for confounders. During the study period 216,671 deliveries met the inclusion criteria; of them 4.8% (n = 10,450) were diagnosed as SGA neonates. During the follow-up period, the rate of hospitalization due to respiratory morbidity was significantly higher in the SGA group as compared to the AGA group (5.2% vs. 4.7%, OR = 1.13, 95% confidence interval [CI] = 1.03-1.24, p = 0.011). The Kaplan-Meier survival curve demonstrated a significantly higher cumulative incidence of respiratory morbidity in the SGA group (log-rank p = 0.026). In the Cox hazards regression model, controlled for relevant clinical confounders, SGA was found to be an independent risk factor for long-term pediatric respiratory morbidity (adjusted hazard ratio [HR] = 1.1, 95% CI = 1.001-1.19, p = 0.049). Being delivered SGA at term is an independent long-term risk factor for pediatric respiratory hospitalization.

Prognostic Value of HLA Class I in Patients with Hepatocellular Carcinoma.

Downregulation of HLA class I molecules is a major tumor escape mechanism from immune attack. However, its prognostic impact for patients with hepatocellular carcinoma is still unclear. This study aimed to investigate whether HLA class I has prognostic significance in patients with hepatocellular carcinoma. A cohort of 132 patients with hepatocellular carcinoma was enrolled. HLA class I expression was detected by immunohistochemistry. Levels of HLA class I expression were dichotomized as low and high according to staining intensity or staining percentage of positive tumor cells, respectively. Association of HLA class I expression with clinical characteristics and survival was analyzed. None of the clinical characteristics, including gender, age, virus infection, cirrhosis, AFP, vascular invasion, tumor size and number, was significantly associated with staining percentage of HLA class I or staining intensity (p > 0.05). Low staining percentage of HLA class I was significantly associated with a worse survival (p = 0.011), which was further confirmed by Cox regression hazards model in multivariate analysis (HR 0.416, 95% CI 0.204 - 0.849, p = 0.016). Staining intensity of HLA class I was not significantly associated with survival (p > 0.05). Expression of HLA class I might be a significant prognostic factor in hepatocellular carcinoma, and downregulation of HLA class I was significantly associated with a worse survival in terms of expression percentage of HLA class I.

Association of Red Blood Cell Distribution Width-Albumin Ratio for Acute Myocardial Infarction Patients with Mortality: A Retrospective Cohort Study.

BackgroundRed blood cell distribution width (RDW) was a risk factor for poor prognosis in acute myocardial infarction (AMI). Recent reports suggested that combining RDW with other laboratory metrics could provide a better prediction. This retrospective study aimed to investigate whether the RDW-albumin ratio (RAR) may be associated with mortality after an AMI.MethodsThis cohort study was conducted among adults (over 16 years old) with AMI in the Medical Information Mart for Intensive Care Database III V1.4 (MIMIC-III). The primary outcome was 30-day mortality, and the secondary outcome was 1-year and 3-year mortality. Cox hazard regression model and Kaplan–Meier survival curves were constructed to estimate the effect of biomarkers on mortality. We used three models to adjust for potential bias. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for the excellent performance of RAR on prognosis.ResultsA total of 826 patients were eventually enrolled in our study. In multivariate analysis, RAR was found to be associated with 30-day mortality (Model 3: HR = 1.23, 95% CI = 1.09-1.39, P < .001). In addition, Subgroup analysis showed that the effect of RAR was higher in female patients than in male patients (P for interaction = .026). Kaplan-Meier survival curves showed that patients in the lower RAR quartile tended to have higher survival rates in the short and long term. AMI patients with RAR ≥ 4 had a 122% increase in 3-year mortality. Results of ROC and AUC showed that the prognostic performance of RAR for mortality was the best (30-day mortality: 0.703; 1-year mortality: 0.729; 3-year mortality: 0.737).ConclusionsRAR is a simple and stable predictor of prognosis in AMI patients. Our results support RAR = 4.0 as a criterion for prognostic risk stratification of AMI patients.

Surgical indications for upper mediastinal dissection by sternotomy in patients with papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is a relatively indolent disease, despite the high incidence of lymph node metastases. Although less frequent, some upper mediastinal metastases of PTC cannot be removed without sternal resection. In this study, we investigated the prognostic impact of upper mediastinal dissection (UMD) by sternotomy on patients with mediastinal metastases of PTC. Charts of patients with PTC who underwent surgical treatment at our institution between 2006 and 2018 were retrospectively reviewed. Fifty-eight patients with upper mediastinal metastases were enrolled. Kaplan-Meier survival curves were compared, and Cox hazard regression models were used for analyses. Of the 58 patients with mediastinal metastasis, 12 (20.7%) underwent dissection of the prevascular nodes, 51 (87.9%) underwent dissection of the upper paratracheal nodes, and 14 (24.1%) underwent dissection of the lower paratracheal node. The preferred site of mediastinal metastasis was the upper paratracheal nodes. The 5 and 10-year disease-specific survival rates for patients after UMD were 74.6% and 58.7%, respectively. Among 25 patients (43.1%) with locoregional recurrence, 12 (20.7%) had mediastinal recurrence and 7 were eligible for additional UMD. Although distant metastasis was the predominant poor prognostic factor, mediastinal recurrences were more frequently unresectable than cervical recurrences, suggesting that mediastinal recurrence is a poor prognostic factor. Mediastinal metastases larger than 30 mm or metastases to the lower paratracheal nodes are considered a risk factor for mediastinal recurrence. UMD by sternotomy for patient with upper mediastinal metastases which are difficult to resect via transcervical approach is an effective treatment option to improve patient prognosis.

Application of Principal Component Analysis in Dealing with Multicollinearity in Modelling Clinical Data

Introduction: One of the stringent assumptions about covariates in the Cox hazard and Logistic regression modelling is that they should be independent. Incorporating correlated covariates as such into the model might distort the precision of the estimates due to multicollinearity. One way to deal with multicollinearity is by using Principal Component Analysis (PCA) technique. Aim: To demonstrate the application of PCA in dealing with correlated covariates while modelling time to event and casecontrol study data. Materials and Methods: This study was conducted at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, from February 2021 to January 2022. Two datasets were used for the demonstration i.e., data relates to a time to event outcome and a case-control study with binary outcome in which lipids were the correlated covariates. Three sets of Cox regression models were used to demonstrate change in hazard ratios with 95% Confidence Intervals (CI) for evaluating the effect of intervention at a different time of lipid measurement. Model I has evaluated treatment/ Body Mass Index (BMI) effect on the outcome by ignoring the effect of lipid parameters. Model II has evaluated treatment/ BMI effect on the outcome by incorporating lipid variables but ignoring multicollinearity. Model III has evaluated treatment/ BMI effect on the outcome by incorporating lipid variables through principal component analysis and thus adjusting for multicollinearity. Similarly, a logistic regression model was performed by using the same three sets of models to evaluate the effect of exposure (BMI). The comparability of lipids between the two groups for both datasets was tested using Hotelling’s T-squared statistic. Results: The lipids measured at 12th, 24th and 36th months between the two groups in the first data set as well as between cases and controls in the second data set were statistically significant. In the first dataset, at baseline, the Hazard Ratio’s (HR’s) were statistically similar irrespective of the models used; while decreasing successively with narrowing 95% CI’s as moving from model I to model III for the lipid measured at 12th, 24th and 36th months. Further, at 24th and 36th months, the HR in model-III found to be significant. In the second data set, the Odds Ratio (OR) were significant for all the three models and it was almost similar for model I and II but in model III it was elevated. Conclusion: The multicollinearity issue should be properly addressed before including correlated covariates in the Cox regression hazard and Logistic regression model. The PCA technique would be a favourable method.

Development of a Radiotherapy Localisation Computed Tomography-Based Radiomic Model for Predicting Survival in Patients With Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy Following Induction Chemotherapy.

BackgroundOur purpose is to develop a model combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics that can be used to estimate overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy.MethodsWe recruited 145 patients with pathologically confirmed nasopharyngeal carcinoma between February 2012 and April 2015. In total, 851 radiomic features were extracted from radiotherapy localisation computed tomography images for the gross tumour volume of the nasopharynx and the gross tumour volume of neck metastatic lymph nodes. The least absolute shrinkage and selection operator algorithm was applied to select radiomics features, build the model and calculate the Rad-score. The patients were divided into high- and low-risk groups based on their Rad-scores. A nomogram for estimating overall survival based on both radiomic and clinical features was generated using multivariate Cox regression hazard models. Prediction reliability was evaluated using Harrell’s concordance index.ResultsIn total, seven radiomic features and one clinical characteristic were extracted for survival analysis, and the combination of radiomic and clinical features was a better predictor of overall survival (concordance index = .849 [confidence interval: .782-.916]) than radiomic features (concordance index = .793 [confidence interval: .697-.890]) or clinical characteristics (concordance index = .661 [confidence interval: .673-.849]) alone.ConclusionOur results show that a nomogram combining radiomic features of radiotherapy localisation computed tomography and clinical characteristics can predict overall survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy following induction chemotherapy more effectively than radiomic features or clinical characteristics alone.