Maladaptive personality traits and older adult relationship satisfaction: A co-twin control approach to understanding associations.

OBJECTIVE: Maladaptive personality traits have been implicated in romantic relationship dissatisfaction, but the etiology of those links and the degree to which they extend to other types of relationships are unclear. The purpose of this study was to examine associations between maladaptive personality traits and satisfaction in various relationships using a co-twin control design to identify potential environmental contributions. METHOD: The sample consisted of 1340 older adult twin participants from the Minnesota Twin Registry (Mage = 70.3) that completed the Personality Inventory for DSM-5 Faceted Brief Form and Network of Relationships Inventory (Revised for Older Adults). RESULTS: Several maladaptive personality traits were phenotypically associated with relationship dissatisfaction, with detachment and negative affect having the largest effects. Further, within twin pair differences in detachment and negative affect were associated with greater relationship dissatisfaction, suggesting that observed associations were mediated partly by the unique environment, not solely the result of genetic and familial confounding. Both phenotypic and co-twin associations were strongest overall in the romantic partner relationship. CONCLUSION: These findings support the notion that maladaptive personality traits are implicated in interpersonal dysfunction across multiple domains.

Association of Nutritional Risk Index With Infection-Related Hospitalization and Death After Hospitalization in Patients Undergoing Maintenance Hemodialysis.

OBJECTIVE: Patients undergoing dialysis frequently experience hospitalization due to cardiovascular disease (CVD) and infection. This population is also at high risk of rehospitalization and subsequent death. In addition to serious outcomes, hospitalization incurs substantial medical cost. Prevention of hospitalization is accordingly an urgent matter. Here, we examined whether nutritional disorder was associated with hospitalization and subsequent death. METHODS: The study was conducted under a prospective design using data from the Japanese Dialysis Outcomes and Practice Pattern Study. The exposure was the Nutritional Risk Index for Japanese Hemodialysis (NRI-JH), through which patients were divided into low-, medium-, and high-risk groups, with the low-risk group as referent. The primary outcome was CVD-related or infection-related hospitalization. Secondary outcome was all-cause mortality. For exploratory analyses, the associations of baseline or latest NRI-JH just before hospitalization, with death after hospitalizations, were examined. RESULTS: Of 4021 patients, 566 patients had CVD-related hospitalization and 375 had infection-related hospitalization during a median follow-up of 2.6 years. NRI-JH at baseline was significantly associated with infection-related hospitalization but not with CVD-related hospitalization, in multivariable Cox models (hazard ratio [HR] 1.46, 95% confidential interval [CI]: 1.09 to 1.97, P = .012 for medium-risk vs. low-risk group) (HR 2.46, 95% CI: 1.81 to 3.35, P < .001 for high-risk vs. low-risk group). NRI-JH was also associated with all-cause mortality. In addition, the baseline and latest high-risk NRI-JH groups were significantly associated with death after both CVD-related and infection-related hospitalizations. CONCLUSIONS: A higher nutritional risk as evaluated by NRI-JH was associated with infection-related hospitalization but not with CVD-related hospitalization. However, NRI-JH was significantly associated with death after both CVD-related and infection-related hospitalizations, suggesting that nutritional risk may be separately involved in hospitalization or subsequent death. NRI-JH may be useful in the planning of individual care to improve outcomes.

Prognostic value of the nutritional risk index in patients with newly diagnosed multiple myeloma.

The nutritional risk index (NRI), which is based on weight and albumin levels, is closely associated with the prognosis of many cancers. However, its prognostic value has not been investigated in patients with newly diagnosed multiple myeloma (NDMM). We aimed to assess the association between the NRI and survival outcomes in patients with NDMM. We retrospectively collected and analyzed clinical and laboratory data from patients with NDMM between 2005 and 2019 at our center. Patients were stratified into the high NRI (> 89) and low NRI (≤ 89) groups for prognostic analysis. The NRI and other variables were also explored to evaluate their prognostic value for overall survival (OS). A total of 638 patients diagnosed with NDMM were retrospectively included. Patients in the high NRI group had a significantly better median OS than those in the low NRI group (64 months vs 43 months, p < 0.001). In the multivariate analysis, a high NRI was shown to be an independent prognostic factor for OS (hazard ratio, 0.758; 95% confidence interval, 0.587-0.977; p = 0.033). Age, performance status, transplant status, and lactate dehydrogenase level were also independent prognostic factors for OS. In conclusion, our study demonstrates that the NRI is a simple and useful predictor of survival outcomes in patients with NDMM.

Setting epidemiological cut-off values for Vibrio harveyi relevant to MIC data generated by a standardised microdilution method.

The lack of internationally harmonised criteria for interpreting the data generated by standardised susceptibility testing methods presents a serious obstacle for the development of prudent use of antimicrobials in aquaculture. The data required to set epidemiological cut-off values for minimum inhibitory concentrations for antibiotic agents against Vibrio harveyi was determined using a standard microdilution method that specified the use of cation-adjusted Mueller Hinton broth and incubation at 28°C for 24 to 28 h. In total, 120 observations were made in 4 independent laboratories from 109 unique isolates. The aggregated data from these laboratories were analysed by the normalised resistance method and by ECOFFinder to calculate epidemiological cut-off values. The data for chloramphenicol, meropenem and sulfamethoxazole were not considered as suitable for analysis. The data for ampicillin indicated that this species is innately resistant to this agent. No acceptable ranges for quality control strains have been set for ceftazidime and, therefore, only provisional cut-off values could be generated for this agent. The epidemiological cut-off values were, however, calculated for the other 6 agents. These values were ≤0.5 µg ml-1 for enrofloxacin, ≤1 µg ml-1 for florfenicol, oxolinic acid and oxytetracycline, ≤4 µg ml-1 for gentamicin and ≤0.5/9.5 µg ml-1 for trimethoprim/sulfamethoxazole. Evidence is presented demonstrating that the data for these 6 antimicrobial agents was of sufficient quantity and quality that they could be used by the relevant authorities to set internationally harmonised, consensus epidemiological cut-off values for V. harveyi.

Tick-borne encephalitis epidemiology and surveillance in Poland, and comparison with selected European countries before and during the COVID-19 pandemic, 2008 to 2020.

BackgroundTick-borne encephalitis (TBE) is the most common viral central nervous system (CNS) infection in Poland. Previous research suggests that its incidence was underestimated in the pre-pandemic period. The COVID-19 pandemic caused a considerable burden on surveillance systems, which could further impact reporting.AimWe aimed to assess the completeness of reporting of TBE in the years 2008 to 2020 and explore the potential impact of the COVID-19 pandemic on reporting to the epidemiological surveillance system, compared with hospitalisations for TBEV and other viral neuro-infections.MethodsWe compared the Polish epidemiology of TBE and other viral infections of the CNS from national surveillance reports with data on hospitalisations from 2008 to 2020 and data from selected European countries.ResultsBetween 2008 and 2020, 3,016 TBE cases were reported to surveillance compared with 3,620 hospitalisations. There was an increasing trend in hospitalisations, while surveillance data demonstrated the opposite, with the largest discrepancy observed in the first pandemic year (354 hospitalisations vs 159 cases reported to surveillance). Serological testing for TBE was used more in the known endemic region of north-eastern Poland and less in non-endemic areas. Other European countries reported higher TBE case numbers and an increase during the COVID-19 pandemic, whereas Poland observed an opposite trend.ConclusionThe sensitivity of TBE surveillance in Poland requires improvement. There are considerable regional differences. Regions that test for TBE intensively report most cases. Policymakers should be made aware of the value of quality epidemiological data for planning prophylactic measures in risk areas.

Association of the nutritional risk index for Japanese hemodialysis patients with long-term mortality: The Q-Cohort Study.

BACKGROUND: Protein-energy wasting (PEW) is a risk factor for mortality in patients undergoing hemodialysis. Recently, a nutritional risk index for Japanese hemodialysis patients (NRI-JH) has been proposed as a surrogate index of PEW. However, no study has determined the association of the NRI-JH with long-term mortality in patients undergoing hemodialysis. Furthermore, the validity of the NRI-JH has not been confirmed. METHODS: In total, 3046 patients undergoing hemodialysis and registered in the Q-Cohort Study were followed up for 10 years. The NRI-JH was calculated on the basis of body mass index and serum levels of albumin, total cholesterol, and creatinine. The patients were divided into four groups according to the NRI-JH scores: 0-3 (G1, n = 1343), 4-7 (G2, n = 1136), 8-10 (G3, n = 321), and 11-13 (G4, n = 246). We examined the association between the NRI-JH and the 4-year and 10-year risks of all-cause, cardiovascular, and infection-related deaths using the Cox proportional hazards model. RESULTS: During the follow-up period, 647 patients died during the first 4 years, and 1503 patients died within 10 years. The 4-year prognosis was analyzed and compared with the lowest NRI-JH score group. Multivariable-adjusted hazard ratios (95% confidence intervals) for all-cause death were 1.93 (1.57-2.38), 2.68 (2.05-3.50), and 3.16 (2.40-4.16) in the G2, G3, and G4 groups, respectively. Similarly, a higher NRI-JH score was associated with an increased risk of cardiovascular and infection-related deaths. CONCLUSION: A higher NRI-JH score was associated with an increased risk of long-term mortality in patients undergoing maintenance hemodialysis. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN ID: 000000556).

Poor dental condition is a factor of imbalance of the nutritional status at the outset of management of head and neck cancer.

OBJECTIVES: To determine whether deterioration of dental condition at the outset of management of head and neck cancer (HNC) is a nutritional risk and whether social deprivation is a cause of the poor dental condition observed in HNC patients. MATERIAL AND METHODS: A nutritional assessment form (NAF) and the Nutrition Risk Index (NRI) were used to standardize the nutritional status of 108 patients at the outset of management of HNC (2017-2019). The NAF includes assessment of weight loss over the past 3 months, the amount and difficulty of food intake, and the presence of digestive disorders. Dental condition was assessed by the decayed, filled, and missing teeth acopre (DFM) index and the masticatory coefficient (MC). Dental status and social deprivation were correlated with the EPICES score. RESULTS: A correlation was found between the extent of weight loss and dental condition. The MC was higher in absence of weight loss (46% vs. 27%, p = 0.03) and the DMF lower when weight loss was less than 5% (22.3 vs. 26.9 if > 5% loss of weight, p = 0.005). No correlation was found between dental status and nutritional status. Social deprivation was associated with a lower MC (26% vs. 50%, p < 0.001). CONCLUSION: Dental condition is a risk factor for weight loss at the outset of management of HNC but is not a determinant of nutritional status. Clinical relevance Dental condition is no longer considered simply as a source of potential complications after radiotherapy but also as an important factor for nutritional status.

Genetic polymorphisms at 19q13.33 are associated with [-2]proPSA (p2PSA) levels and provide additional predictive value to prostate health index for prostate cancer.

BACKGROUND: Prostate health index (phi), a derivative of [-2]proPSA (p2PSA), has shown better accuracy than prostate-specific antigen (PSA) in prostate cancer (PCa) detection. The present study was to investigate whether previously identified PSA-associated single nucleotide polymorphisms (SNPs) influence p2PSA or phi levels and lead to potential clinical utility. METHODS: We conducted an observational prospective study with 2268 consecutive patients who underwent prostate biopsy in three tertiary medical centers from August 2013 to March 2019. Genotyping data of the 46 candidate genes with a ± 100 kb window were tested for association with p2PSA and phi levels using linear regression. Multivariable logistic regression models were performed and internally validated using repeated tenfold cross-validation. We further calculated personalized phi cutoff values based on the significant genotypes. Discriminative performance was assessed using decision curve analysis and net reclassification improvement (NRI) index. RESULTS: We detected 11 significant variants at 19q13.33 which were p2PSA-associated independent of PCa. The most significant SNP, rs198978 in KLK2 (Pcombined = 5.73 × 10-9 ), was also associated with phi values (Pcombined = 3.20 × 10-6 ). Compared to the two commonly used phi cutoffs of 27.0 and 36.0, the personalized phi cutoffs had a significant NRI for PCa ranged from 5.23% to 9.70% among men carrying variant types (all p < .01). CONCLUSION: Rs198978, is independently associated with p2PSA values, and can improve the diagnostic ability of phi for PCa using personalized cutoff values.

Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial.

PURPOSE: In neurogenic orthostatic hypotension, blood pressure falls when upright owing to impaired release of norepinephrine, leading to dizziness. Ampreloxetine, a selective norepinephrine reuptake inhibitor, increases circulating norepinephrine levels. This study explored the safety of ampreloxetine and its effect on blood pressure and symptoms in patients with neurogenic orthostatic hypotension. METHODS: A multicenter ascending-dose trial (range 1-20 mg, Part A) was followed by a 1 day, double-blind, randomized, placebo-controlled study (median dose 15 mg, Part B). Eligible patients then enrolled in a 20-week, open-label, steady-state extension phase (median dose 10 mg, Part C) followed by a 4-week withdrawal. Assessments included the Orthostatic Hypotension Symptom Assessment Scale (item 1), supine/seated/standing blood pressure, and safety. RESULTS: Thirty-four patients (age 66 ± 8 years, 22 men) were enrolled. Part A: The proportion of participants with a positive response (i.e., increase from baseline in seated systolic blood pressure of ≥ 10 mmHg) was greater with the 5 and 10 mg ampreloxetine doses than with placebo or other active ampreloxetine doses. Part B: Seated blood pressure increased 15.7 mmHg 4 h after ampreloxetine and decreased 14.2 mmHg after placebo [least squares mean difference (95% CI) 29.9 mmHg (7.6-52.3); P = 0.0112]. Part C: Symptoms of dizziness/lightheadedness improved 3.1 ± 3.0 points from baseline and standing systolic blood pressure increased 11 ± 12 mmHg. After 4 weeks of withdrawal, symptoms returned to pretreatment levels. The effect of ampreloxetine on supine blood pressure was minimal throughout treatment duration. CONCLUSION: Ampreloxetine was well tolerated and improved orthostatic symptoms and seated/standing blood pressure with little change in supine blood pressure. TRIAL REGISTRATION: NCT02705755 (first posted March 10, 2016).

Measures for evaluation of prognostic improvement under multivariate normality for nested and nonnested models.

When comparing performances of two risk prediction models, several metrics exist to quantify prognostic improvement, including the change in the area under the Receiver Operating Characteristic curve, the Integrated Discrimination Improvement, the Net Reclassification Index at event rate, the change in Standardized Net Benefit, the change in Brier score, and the change in scaled Brier score. We explore the behavior and interrelationships between these metrics under multivariate normality in nested and nonnested model comparisons. We demonstrate that, within the framework of linear discriminant analysis, all six statistics are functions of squared Mahalanobis distance, a robust metric that properly measures discrimination by quantifying the separation between the risk scores of events and nonevents. These relationships are important for overall interpretability and clinical usefulness. Through simulation, we demonstrate that the performance of the theoretical estimators under normality is comparable or superior to empirical estimation methods typically used by investigators. In particular, the theoretical estimators for the Net Reclassification Index and the change in Standardized Net Benefit exhibit less variability in their estimates as compared to their empirically estimated counterparts. Finally, we explore how these metrics behave with potentially nonnormal data by applying these methods in a practical example based on the sex-specific cardiovascular disease risk models from the Framingham Heart Study. Our findings aim to give greater insight into the behavior of these measures and the connections existing among them and to provide additional estimation methods with less variability for the Net Reclassification Index and the change in Standardized Net Benefit.

Asymptotic distribution of ∆AUC, NRIs, and IDI based on theory of U-statistics.

The change in area under the curve (∆AUC), the integrated discrimination improvement (IDI), and net reclassification index (NRI) are commonly used measures of risk prediction model performance. Some authors have reported good validity of associated methods of estimating their standard errors (SE) and construction of confidence intervals, whereas others have questioned their performance. To address these issues, we unite the ∆AUC, IDI, and three versions of the NRI under the umbrella of the U-statistics family. We rigorously show that the asymptotic behavior of ∆AUC, NRIs, and IDI fits the asymptotic distribution theory developed for U-statistics. We prove that the ∆AUC, NRIs, and IDI are asymptotically normal, unless they compare nested models under the null hypothesis. In the latter case, asymptotic normality and existing SE estimates cannot be applied to ∆AUC, NRIs, or IDI. In the former case, SE formulas proposed in the literature are equivalent to SE formulas obtained from U-statistics theory if we ignore adjustment for estimated parameters. We use Sukhatme-Randles-deWet condition to determine when adjustment for estimated parameters is necessary. We show that adjustment is not necessary for SEs of the ∆AUC and two versions of the NRI when added predictor variables are significant and normally distributed. The SEs of the IDI and three-category NRI should always be adjusted for estimated parameters. These results allow us to define when existing formulas for SE estimates can be used and when resampling methods such as the bootstrap should be used instead when comparing nested models. We also use the U-statistic theory to develop a new SE estimate of ∆AUC. Copyright © 2017 John Wiley & Sons, Ltd.

Statistical evaluation of adding multiple risk factors improves Framingham stroke risk score.

BACKGROUND: Framingham Stroke Risk Score (FSRS) is the most well-regarded risk appraisal tools for evaluating an individual's absolute risk on stroke onset. However, several widely accepted risk factors for stroke were not included in the original Framingham model. This study proposed a new model which combines an existing risk models with new risk factors using synthesis analysis, and applied it to the longitudinal Atherosclerosis Risk in Communities (ARIC) data set. METHODS: Risk factors in original prediction models and new risk factors in proposed model had been discussed. Three measures, like discrimination, calibration and reclassification, were used to evaluate the performance of the original Framingham model and new risk prediction model. RESULTS: Modified C-statistics, Hosmer-Lemeshow Test and classless NRI, class NRI were the statistical indices which, respectively, denoted the performance of discrimination, calibration and reclassification for evaluating the newly developed risk prediction model on stroke onset. It showed that the NEW-STROKE (new stroke risk score prediction model) model had higher modified C-statistics, smaller Hosmer-Lemeshow chi-square values after recalibration than original FSRS model, and the classless NRI and class NRI of the NEW-STROKE model over the original FSRS model were all significantly positive in overall group. CONCLUSION: The NEW-STROKE integrated with seven literature-derived risk factors outperformed the original FSRS model in predicting the risk score of stroke. It illustrated that seven literature-derived risk factors contributed significantly to stroke risk prediction.

Atomoxetine, a norepinephrine reuptake inhibitor, reduces seizure-induced respiratory arrest.

Sudden unexpected death in epilepsy (SUDEP) is a devastating epilepsy complication, and no effective preventive strategies are currently available for this fatal disorder. Clinical and animal studies of SUDEP demonstrate that seizure-induced respiratory arrest (S-IRA) is the primary event leading to death after generalized seizures in many cases. Enhancing brain levels of serotonin reduces S-IRA in animal models relevant to SUDEP, including the DBA/1 mouse. Given that serotonin in the brain plays an important role in modulating respiration and arousal, these findings suggest that deficits in respiration and/or arousal may contribute to S-IRA. It is well known that norepinephrine is an important neurotransmitter that modulates respiration and arousal in the brain as well. Therefore, we hypothesized that enhancing noradrenergic neurotransmission suppresses S-IRA. To test this hypothesis, we examined the effect of atomoxetine, a norepinephrine reuptake inhibitor (NRI), on S-IRA evoked by either acoustic stimulation or pentylenetetrazole in DBA/1 mice. We report the original observation that atomoxetine specifically suppresses S-IRA without altering the susceptibility to seizures evoked by acoustic stimulation, and atomoxetine also reduces S-IRA evoked by pentylenetetrazole in DBA/1 mice. Our data suggest that the noradrenergic signaling is importantly involved in S-IRA, and that atomoxetine, a medication widely used to treat attention deficit hyperactivity disorder (ADHD), is potentially useful to prevent SUDEP.

Development and validation of a comorbidity scoring system for patients with cirrhosis.

BACKGROUND & AIMS: At least 40% of patients with cirrhosis have comorbidities that increase mortality. We developed a cirrhosis-specific comorbidity scoring system (CirCom) to help determine how these comorbidities affect mortality and compared it with the generic Charlson Comorbidity Index. METHODS: We used data from nationwide health care registries to identify Danish citizens diagnosed with cirrhosis in 1999-2008 (n = 12,976). They were followed through 2010 and characterized by 34 comorbidities. We used Cox regression to assign severity weights to comorbidities with an adjusted mortality hazard ratio (HR) ≥ 1.20. Each patient's CirCom score was based on, at most, 2 of these comorbidities. Performance was measured with Harrell's C statistic and the Net Reclassification Index (NRI) and results were compared with those obtained using the Charlson Index (based on 17 comorbidities). Findings were validated in 2 separate cohorts of patients with alcohol-related cirrhosis or chronic hepatitis C. RESULTS: The CirCom score included chronic obstructive pulmonary disease, acute myocardial infarction, peripheral arterial disease, epilepsy, substance abuse, heart failure, nonmetastatic cancer, metastatic cancer, and chronic kidney disease; 24.2% of patients had 1 or more of these, and mortality correlated with the CirCom score. Patients' CirCom score correlated with their Charlson Comorbidity Index (Kendall's τ = 0.57; P < .0001). Compared with the Charlson Index, the CirCom score increased Harrell's C statistic by 0.6% (95% confidence interval: 0.3%-0.8%). The NRI for the CirCom score was 5.2% (95% confidence interval: 3.7%-6.9%), and the NRI for the Charlson Index was 3.6% (95% confidence interval: 2.3%-5.0%). Similar results were obtained from the validation cohorts. CONCLUSIONS: We developed a scoring system to predict mortality among patients with cirrhosis based on 9 comorbidities. This system had higher C statistic and NRI values than the Charlson Comorbidity Index, and is easier to use. It could therefore be a preferred method to predict death or survival of patients and for use in epidemiologic studies.

Predictive value of semi-quantitative MRI-based scoring systems for future knee replacement: data from the osteoarthritis initiative.

PURPOSE: To evaluate, in a confirmatory fashion, whether baseline and change from baseline to 24-month follow-up in cartilage damage, bone marrow lesions and meniscal damage are predictors of knee replacement (KR) in subjects with a high risk of osteoarthritis (OA), independent of the level of physical activity, symptom severity and radiographic abnormalities. METHODS: Data from the Osteoarthritis Initiative's (OAI) baseline and 24-month follow-up knee MRIs of 115 patients (age range: 45-78 years; 48 % female; BMI: 20.9-48.7) were analyzed. Cartilage, bone marrow and menisci were semi-quantitatively scored according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) and Boston-Leeds Osteoarthritis Knee Score (BLOKS) systems in all compartments. Baseline and 24-month interval changes in structural tissue damage assessed by BLOKS and WORMS were used as predictors of KR independent of clinical and radiographic parameters using Cox hazard analysis. Adjustments were performed for age, gender, BMI and physical activity (Physical Activity Scale for the Elderly: PASE), Western Ontario and McMaster Questionnaire (WOMAC) total score and radiographic Kellgren-Lawrence (KL) score. RESULTS: BLOKS and WORMS baseline cartilage scores were predictors of KR independent of the PASE, WOMAC and KL score. One score increase in the average baseline BLOKS full-thickness cartilage defect score was associated with a [hazard ratio (95 % CI)] 13.55 (3.61-50.89) times greater risk of KR independent of the PASE, WOMAC and KL score. Net reclassification improvements (NRIs) of the additional evaluation of 24-month follow-up MRI scores and assessment of changes were not significant for prediction of KR (NRI range: - 7.23 - 24.8 %). CONCLUSIONS: The BLOKS cartilage score for full-thickness cartilage defects had the highest hazard for KR. Follow-up MRI changes in structural tissue damage, detected by BLOKS and WORMS cartilage, bone marrow or meniscus scores (up to 24 months) had no significant predictive value in addition to the baseline MRI.

Key concepts and limitations of statistical methods for evaluating biomarkers of kidney disease.

Interest in developing and using novel markers of kidney injury is increasing. To maintain scientific rigour in these endeavors, a comprehensive understanding of statistical methodology is required to rigorously assess the incremental value of novel biomarkers in existing clinical risk prediction models. Such knowledge is especially relevant, because no single statistical method is sufficient to evaluate a novel biomarker. In this review, we highlight the strengths and limitations of various traditional and novel statistical methods used in the literature for biomarker studies and use biomarkers of AKI as examples to show limitations of some popular statistical methods.

A note on the evaluation of novel biomarkers: do not rely on integrated discrimination improvement and net reclassification index.

The 'integrated discrimination improvement' (IDI) and the 'net reclassification index' (NRI) are statistics proposed as measures of the incremental prognostic impact that a new biomarker will have when added to an existing prediction model for a binary outcome. By design, both measures were meant to be intuitively appropriate, and the IDI and NRI formulae do look intuitively plausible. Both have become increasingly popular. We shall argue, however, that their use is not always safe. If IDI and NRI are used to measure gain in prediction performance, then poorly calibrated models may appear advantageous, and in a simulation study, even the model that actually generates the data (and hence is the best possible model) can be improved on without adding measured information. We illustrate these shortcomings in actual cancer data as well as by Monte Carlo simulations. In these examples, we contrast IDI and NRI with the area under ROC and the Brier score. Unlike IDI and NRI, these traditional measures have the characteristic that prognostic performance cannot be accidentally or deliberately inflated.

What to expect from net reclassification improvement with three categories.

The net reclassification improvement (NRI) has become a popular measure of incremental usefulness of markers added to risk prediction models. However, the expected magnitude of the three-category NRI is not well understood, leading researchers to rely on statistical significance. In this paper, we describe a slight modification to the original definition of the NRI, which weighs each reclassification by the number of categories by which a given individual is reclassified. This modification resolves some recent criticisms of the three-category NRI and at the same time has a minimal impact on its magnitude. Then we show that using this modified definition, the event and nonevent NRIs have simple interpretations as sums of changes in sensitivities and specificities calculated at the risk thresholds. We exploit this relationship to arrive at closed-form solutions for the NRI under normality within the event and nonevent subgroups. We observe that the size of the intermediate risk category and the event rate have limited impact on the magnitude of the NRI. As expected, the NRI increases with the strength of the added marker, and this relationship appears fairly proportional for markers with non-weak net effect size (above 0.25). Furthermore, we conclude that using the NRI as a metric, it is harder to improve models that already perform well.

Prevalence and prognostic value of malnutrition in patients with IPF using three scoring systems.

BACKGROUND: To describe the nutritional status of IPF patients, report clinical associations and evaluate the prognostic value of them in IPF. METHODS: 264 IPF patients diagnosed with IPF at the Second Xiangya Hospital of Central South University between January 2011 and January 2021 were recruited. Three different scoring systems, including nutritional risk index (NRI), controlling nutritional status (CONUT) score, and prognostic nutritional index (PNI) were used to describe the nutritional status of IPF patients. RESULT: This study investigated the prevalence of malnutrition in 264 IPF patients, of which the percentage with malnutrition varied from 37.5 % with the NRI, to 47.4 % with the CONUT score, and to 6.4 % with the PNI. The moderate to severe malnutrition ranged from 10.2 % to 31.1 % across these indices, with PNI identifying only 4.9 % in this category. Worsening malnutrition status was associated with significantly higher incidence of all-cause mortality and IPF death regard of the malnutrition index as NRI (p < 0.05). When the normal nutrition of NRI was used as a reference, patients in the moderate to severe risk remained at a higher risk of all-cause death (HR = 2.06(1.25-3.41)) and IPF death(HR = 2.36(1.35-4.15)). The adjusted multivariate analysis, identified age(HR = 1.13(1.08-1.20)), DLCO <60, % predicted (HR = 3.31(1,24-9.42)) and the use of anti-fibrotic drugs (HR = 0.25(0.10-0.60)) as independent predictors of mortality. CONCLUSIONS: Malnutrition is common among patients with IPF and the baseline as diagnosis of IPF is strongly related to increased mortality.

Prognostic value of three clinical nutrition scoring system (NRI, PNI, and CONUT) in elderly patients with prostate cancer.

Background: Most of patients with prostate cancer (PCa) are elderly and have a long course of disease. Preoperative assessment of the patient's clinical nutritional status facilitates early intervention and improves patient prognosis. Methods: We assessed the nutritional status of PCa patients utilizing the Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) scoring systems. Survival comparisons between groups were conducted using Kaplan-Meier curve analysis and log-rank tests, while Cox proportional hazards regression analysis was employed to identify independent prognostic factors. Furthermore, we implemented bootstrap-based optimism correction methods to validate the scoring systems and applied decision curve analysis to evaluate the non-inferiority of these three clinical nutrition scoring systems relative to the conventional American Joint Committee on Cancer (AJCC) staging. Results: In this study, malnutrition was diagnosed in 31.51% of the patients using the NRI, 13.02% using the PNI, and 88.28% using the CONUT score. After adjusting for confounders, normal nutritional status as defined by NRI and PNI emerged as an independent prognostic factor for prostate-specific antigen progression-free survival (PSA-PFS). However, nutritional status assessed by CONUT inaccurately predicted PSA-PFS. Normal nutritional status, as determined by all three scoring systems, was found to be an independent prognostic factor for progression-free survival (PFS). Following adjustments for optimistic estimates, the C-index for NRI in predicting both PSA-PFS and PFS remained the highest among the three scoring systems. The results of the DCA indicated that the C-index of all three scoring systems was higher than that of AJCC stage. Conclusions: NRI, PNI, and CONUT are convenient and clinically applicable scoring systems. A clinical malnutrition intervention may improve the prognosis of prostate cancer patients.