National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Development and external validation of a machine learning model for the prediction of persistent acute kidney injury stage 3 in multi-centric, multi-national intensive care cohorts.

BACKGROUND: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). METHODS: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. RESULTS: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92-0.95) in the US external validation cohort and 0.85 (95% CI 0.83-0.88) in the Italian external validation cohort. CONCLUSIONS: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice.

Parental practices that influence children's development: how often are they implemented and by whom-results from the NASCITA birth cohort study.

This study aims to assess how commonly 15 parental practices, known to have positive effects on child and adult health, are carried out by families in Italy, if they are related, and which characteristics are associated with implementation. Children participating in the NASCITA Cohort, a prospective study in which family pediatricians in Italy collect data on children and their families, were included if they had sufficient data. Data on practice implementation, socio-demographic characteristics, and interrelatedness between practices were analyzed. In all, 3337 children were included. Their mothers had an average age at birth of 33 years (range 17-52) and medium-high levels of education (86% of mothers) and employment (72%). No smoking or alcohol in pregnancy, supine infant sleeping position, and tummy time were the most commonly implemented practices (by over 85% of mothers, each), while the least common was exclusive breastfeeding at 6 months (28%). Parental practices are related and several socio-demographic characteristics influence their implementation, with mother's educational level and geographic area of residence influencing most of the practices (each influencing 12 of 15 practices). Low educational level (OR 0.34; 95% CI 0.26-0.44), being born abroad (OR 0.43; 95% CI 0.34-0.56), and residing in the South (OR 0.49; 95% CI 0.41-0.58) most reduce the probability of implementing numerous supportive practices (all three P < 0.001).    Conclusion: Socio-demographic factors contribute significantly to carrying out supportive practices. Future interventions should address the identified inequalities, prioritizing families most in need. Direct involvement of pediatricians is warranted given their favorable position for promoting positive behaviors. What is Known: • Several parental actions in the early life of a child are known to have positive effects on later child health and development. • While folic acid supplementation and exclusive breastfeeding have been promoted for years, other supporting actions are less well-known. What is New: • Rates of parental adherence to the different supportive actions varied greatly and actions were often scantly adopted. • Socio-demographic characteristics influenced adherence, with young, unemployed mothers with low educational levels, living in the South, or who were born abroad adhering significantly less.

Management and outcomes in critically ill nonagenarian versus octogenarian patients.

BACKGROUND: Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. METHODS: We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80-89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. RESULTS: The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90-1.74; p = 0.19)). CONCLUSION: After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered- together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. TRIAL REGISTRATION: NCT03134807 and NCT03370692 .

The Hematocrit Affects the Volume of Plasma Treated With Coupled Plasma Filtration and Adsorption With Predilution.

Coupled plasma filtration and adsorption (CPFA) is an extracorporeal blood purification technique proposed for the treatment of septic-shock. By removing pro- and anti-inflammatory mediators from plasma, CPFA is supposed to have a therapeutic effect on the abnormal inflammatory response seen in this condition. Recently, blood predilution with citrate solution has been adopted to prevent clotting in the CPFA circuit-one of the main problems of the technique. Taking into account the patient's hematocrit, we worked out a formula for the volume of plasma effectively treated by CPFA after predilution. Neglecting this effect, as is commonly done, introduces significant distortions in the estimation of the volume, possibly causing under-treatment. The distortion is stronger when the hematocrit and the predilution fraction are large and weaker when both values shrink. By correctly indicating the daily dose of plasma adsorption received by patients, this formula is essential for assessing the therapeutic efficacy of CPFA and, subsequently, establishing its optimal doses.

A new test and graphical tool to assess the goodness of fit of logistic regression models.

A prognostic model is well calibrated when it accurately predicts event rates. This is first determined by testing for goodness of fit with the development dataset. All existing tests and graphic tools designed for the purpose suffer several drawbacks, related mainly to the subgrouping of observations or to heavy dependence on arbitrary parameters. We propose a statistical test and a graphical method to assess the goodness of fit of logistic regression models, obtained through an extension of similar techniques developed for external validation. We analytically computed and numerically verified the distribution of the underlying statistic. Simulations on a set of realistic scenarios show that this test and the well-known Hosmer-Lemeshow approach have similar type I error rates. The main advantage of this new approach is that the relationship between model predictions and outcome rates across the range of probabilities can be represented in the calibration belt plot, together with its statistical confidence. By readily spotting any deviations from the perfect fit, this new graphical tool is designed to identify, during the process of model development, poorly modeled variables that call for further investigation. This is illustrated through an example based on real data.

A new calibration test and a reappraisal of the calibration belt for the assessment of prediction models based on dichotomous outcomes.

Calibration is one of the main properties that must be accomplished by any predictive model. Overcoming the limitations of many approaches developed so far, a study has recently proposed the calibration belt as a graphical tool to identify ranges of probability where a model based on dichotomous outcomes miscalibrates. In this new approach, the relation between the logits of the probability predicted by a model and of the event rates observed in a sample is represented by a polynomial function, whose coefficients are fitted and its degree is fixed by a series of likelihood-ratio tests. We propose here a test associated with the calibration belt and show how the algorithm to select the polynomial degree affects the distribution of the test statistic. We calculate its exact distribution and confirm its validity via a numerical simulation. Starting from this distribution, we finally reappraise the procedure to construct the calibration belt and illustrate an application in the medical context.

Cardiogenic shock diagnosis and management in general intensive care: a nationwide survey.

BACKGROUND: the epidemiology of cardiogenic shock has evolved over the years: in the last decades an increasing prevalence of cardiogenic shock related to acute decompensated heart failure was observed. Therefore, treatment bundles should be updated according to the underlying pathophysiology. No data exist regarding the diagnostic/therapeutic strategies in general intensive care units. METHODS: A 27-questions survey was spread through the GiViTi (Italian Group for the Evaluation of Interventions in Intensive Care Medicine). The results were then divided according to level of hospitals (1st-2nd versus 3rd). RESULTS: Sixty-nine general intensive care units replied to the survey. The shock team is present in 13% of institutions; Society for Cardiovascular Angiography and Interventions shock classification is applied only in 18.8%. Among the ICUs, 94.2% routinely use a cardiac output monitoring device (pulmonary artery catheter more frequently in 3rd level centers). The first-line adrenergic drug are vasopressors in 27.5%, inotrope in 21.7% or their combination in 50.7%; 79.7% applies fluid challenge. The first vasopressor of choice is norepinephrine (95.7%) (maximum dosage tolerated higher than 0.5 mcg/kg/min in 29%); the first line inotrope is dobutamine (52.2%), followed by epinephrine in 36.2%. The most frequently used mechanical circulatory supports are intra-aortic balloon pump (71%), Impella (34.8%) and VA-ECMO (33.3%); VA-ECMO is the first line strategy in refractory cardiogenic shock (60.8%). CONCLUSIONS: According to this survey, there is no standardized approach to cardiogenic shock amongst Italian general intensive care units. The application of shock severity stratification and the treatment bundles may play a key role in improving the outcome.

Cardiogenic shock in general intensive care unit: a Nationwide prospective analysis of epidemiology and outcome.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening disease burdened by a mortality up to 50%. The epidemiology has changed with non-ischemic aetiologies being predominant although data was mainly derived from patients admitted to dedicated acute cardiac care. We report the epidemiology and outcome of patients with CS admitted to general intensive care unit (ICU). METHODS: Prospective multicentric epidemiological study including 314 general ICU adhering to the GiViTI Nationwide registry from 2011 to 2018, excluding cardiac arrest. The primary endpoint of the study was mortality. The association between clinical factors and mortality was evaluated using a logistic regression model. The Odds Ratios of the covariates quantify their association with mortality during hospitalization. RESULTS: 11052 patients admitted to general ICU (incidence 2.17%; median age 72 (IQR [66-81]), 38.7% were women) with CS were included. Fourthy-seven percent of patients had more than 3 organ insufficiency at the time of admission. The most common CS aetiologies were: left heart failure LHF- 5247-47.5%), acute myocardial infarction (AMI - 3612-32.6%); right heart failure (RHF- 515-4.6%) and biventricular failure (532- 4.8%). 85.5% were mechanically ventilated during the ICU hospitalization. The overall ICU mortality was 44.8%, increasing to 53.4% during the hospitalization in the index hospital and to 54.3% at the latest hospital. RHF-CS patients exhibited the highest mortality risk (OR: 1.19 95% CI [0.94 - 1.50]; p < 0.001), followed by biventricular-CS OR 1.04 95% CI [0.82-1.32]. Respiratory failure (OR 1.13 [95%CI 1.08-1.19]), coagulation disorder (1.17 (95% CI 1.1-1.24), renal dysfunction (OR 1.55 [95% CI 1.50-1.61] and neurological alteration (OR 1.45 [95% CI 1.39-1.50]) were associated with worsen outcome along with severe hypotension (systolic blood pressure < 70 mmHg- OR 2.35 95% CI [2.06-2.67]), increasing age (OR 2.21 95% CI [2.01-2.42] and longer ICU stay prior to admission (2-fold increase for each 4.7 days). CONCLUSIONS: In the general ICU the aetiology of CS, excluding cardiac arrest, remains characterized mostly by LHF with RHF-CS burdened by higher mortality. Multiorgan failure at admission and longer hospital stay before ICU admission predispose to worsen outcome.