A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis.

BACKGROUND & AIMS: The prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis. METHODS: A total of 617 outpatients with cirrhosis from two Italian tertiary centers (Padua and Milan) were enrolled from January 2003 to June 2021 and followed prospectively until the end of the study, death or liver transplantation. The complications registered during follow-up were considered as AD if they required hospitalization, or NAD if managed at the outpatient clinic. RESULTS: During follow-up, 154 patients (25.0% of total patients) developed complications, 69 patients (44.8%) developed NAD and 85 (55.2%) developed AD, while 29 patients with NAD (42.0%) developed a further episode of AD during follow-up. Sixty-month survival was significantly higher in patients with no decompensation than in patients with NAD or AD. On multivariable analysis, AD (hazard ratio [HR] 21.07, p <0.001), NAD (HR 7.13, p <0.001), the etiological cure of cirrhosis (HR 0.38, p <0.001) and model for end-stage liver disease score (HR 1.12, p = 0.003) were found to be independent predictors of mortality. CONCLUSIONS: The first decompensation is non-acute in almost 50% of outpatients, though such events are still associated with decreased survival compared to no decompensation. Patients who develop NAD must be treated with extreme care and monitored closely to prevent the development of AD. IMPACT AND IMPLICATIONS: This multicenter study is the first to investigate the role of non-acute decompensation (NAD) in patients with cirrhosis. In fact, while the unfavorable impact of acute decompensation is well known, there is currently a dearth of evidence on NAD, despite it being a common occurrence in clinical practice. Our data show that almost half of decompensations in patients with cirrhosis can be considered NAD and that such events are associated with a higher risk of mortality than no decompensation. This study has important clinical implications because it highlights the need to carefully consider patients who develop NAD, in order to prevent further decompensation and reduce mortality.

Impact of bacterial infections prior to liver transplantation on post-transplant outcomes in patients with cirrhosis.

Background & Aims: Bacterial infections are frequent in patients with cirrhosis and increase the risk of death and drop-out from liver transplant (LT) waiting list. In patients with bacterial infections, LT is frequently delayed because of the fear of poor outcomes. We evaluated the impact of pre-LT infections on post-LT complications and survival. Methods: From 2012 to 2018, consecutive patients transplanted at the Hospital of Padua were identified and classified in two groups: patients surviving an episode of bacterial infection within 3 months before LT (study group) and patients without infections before LT (control group). Post-LT outcomes (complications, new infections, survival) were collected. Results: A total of 466 LT recipients were identified (study group n = 108; control group n = 358). After LT, the study group had a higher incidence of new bacterial (57% vs. 20%, p <0.001) and fungal infections (14% vs. 5%, p = 0.001) and of septic shock (8% vs. 2%, p = 0.004) than the control group. Along with the model for end-stage liver disease (MELD) score and alcohol-related cirrhosis, bacterial infection pre-LT was an independent predictor of post-LT infections (odds ratio = 3.92; p <0.001). Nevertheless, no significant difference was found in 1-year (88% vs. 89%, p = 0.579) and 5-year survival rates (76% vs. 75%, p = 0.829) between the study group and control group. Within the study group, no association was found between the time elapsed from infection improvement/resolution to LT and post-LT outcomes. Conclusions: Patients with pre-LT infections have a higher risk of new bacterial and fungal infections and of septic shock after LT. However, post-LT survival is excellent. Therefore, as soon as the bacterial infection is improving/resolving, transplant should not be delayed, but patients with pre-transplant bacterial infections require active surveillance for infections after LT. Impact and Implications: Bacterial infections increase mortality and delay transplant in patients with cirrhosis awaiting liver transplantation (LT). Little is known about the impact of adequately treated infections before LT on post-transplant complications and outcomes. The study highlights that pre-LT infections increase the risk of post-LT infections, but post-LT survival rates are excellent despite the risk. These findings suggest that physicians should not delay LT because of concerns about pre-LT infections, but instead should actively monitor these patients for infections after surgery.

Etiological cure prevents further decompensation and mortality in patients with cirrhosis with ascites as the single first decompensating event.

BACKGROUND AND AIMS: Removal/suppression of the primary etiological factor reduces the risk of decompensation and mortality in compensated cirrhosis. However, in decompensated cirrhosis, the impact of etiologic treatment is less predictable. We aimed to evaluate the impact of etiological treatment in patients with cirrhosis who developed ascites as single index decompensating event. APPROACH AND RESULTS: Patients with cirrhosis and ascites as single first decompensation event were included and followed until death, liver transplantation, or Q3/2021. The etiology was considered "cured" (alcohol abstinence, hepatitis C cure, and hepatitis B suppression) versus "controlled" (partial removal of etiologic factors) versus "uncontrolled." A total of 622 patients were included in the study. Etiology was "cured" in 146 patients (24%), "controlled" in 170 (27%), and "uncontrolled" in 306 (49%). During follow-up, 350 patients (56%) developed further decompensation. In multivariable analysis (adjusted for age, sex, varices, etiology, Child-Pugh class, creatinine, sodium, and era of decompensation), etiological cure was independently associated with a lower risk of further decompensation (HR: 0.46; p = 0.001). During follow-up, 250 patients (40.2%) died, while 104 (16.7%) underwent LT. In multivariable analysis, etiological cure was independently associated with a lower mortality risk (HR: 0.35, p < 0.001). CONCLUSIONS: In patients with cirrhosis and ascites as single first decompensating event, the cure of liver disease etiology represents a main treatment goal since this translates into considerably lower risks of further decompensation and mortality.

Thirty-day complications after laparoscopic or open cholecystectomy: a population-based cohort study in Italy.

OBJECTIVE: The objective of the study is to evaluate short-term complications after laparoscopic (LC) or open cholecystectomy (OC) in patients with gallstones by using linked hospital discharge data. DESIGN: Population-based cohort study. SETTING: Data were obtained from the Regional Hospital Discharge Registry Lazio Region in Central Italy (around 5 million inhabitants) in 2007-2008. PARTICIPANTS: All patients admitted to hospitals of Lazio with symptomatic gallstones (International Classification of disease, 9th Revision, Clinical Modification (ICD-9-CM)=574) who underwent LC (ICD-9-CM 51.23) or OC (ICD-9-CM 51.22). OUTCOME MEASURES: (1)'30-day surgical-related complications' defined as any complication of the biliary tract (including postoperative infection, haemorrhage or haematoma or seroma complicating a procedure, persistent postoperative fistula, perforation of bile duct and disruption of wound). (2) '30-day systemic complications' defined as any complications of other organs (including sepsis, infections from other organs, major cardiovascular events and selected adverse events). RESULTS: 13 651 patients were included; 86.1% had LC, 13.9% OC. 2.0% experienced surgical-related complications (SRC), 2.1% systemic complications (SC). The OR of complications after LC versus OC was 0.60 (p<0.001) for SRC and 0.52 (p<0.001) for SC. In relation to SRC, the advantage of LC was consistent across age categories, severity of gallstones and previous upper abdominal surgery, whereas there was no advantage among people with emergency admission (OR=0.94, p=0.764). For SC, no significant advantage of LC was seen among very old people (OR=0.99, p=0.975) and among those with previous upper abdominal surgery (OR=0.86, p=0.905). CONCLUSIONS: This large observational study confirms that LC is more effective than OC with respect to 30-day complications. Population-based linkage of administrative datasets can enlarge evidence of treatment benefits in clinical practice.

P.Re.Val.E.: outcome research program for the evaluation of health care quality in Lazio, Italy.

BACKGROUND: P.Re.Val.E. is the most comprehensive comparative evaluation program of healthcare outcomes in Lazio, an Italian region, and the first Italian study to make health provider performance data available to the public. The aim of this study is to describe the P.Re.Val.E. and the impact of releasing performance data to the public. METHODS: P.Re.Val.E. included 54 outcome/process indicators encompassing many different clinical areas. Crude and adjusted rates were estimated for the 2006-2009 period. Multivariate regression models and direct standardization procedures were used to control for potential confounding due to individual characteristics. Variable life-adjusted display charts were developed, and 2008-2009 results were compared with those from 2006-2007. RESULTS: Results of 54 outcome indicators were published online at http://www.epidemiologia.lazio.it/prevale10/index.php. Public disclosure of the indicators' results caused mixed reactions but finally promoted discussion and refinement of some indicators. Based on the P.Re.Val.E. experience, the Italian National Agency for Regional Health Services has launched a National Outcome Program aimed at systematically comparing outcomes in hospitals and local health units in Italy. CONCLUSIONS: P.Re.Val.E. highlighted aspects of patient care that merit further investigation and monitoring to improve healthcare services and equity.

[Final results from four clinical studies in the field of cardiovascular diseases integrated in the "Mattoni del SSN - Mattone Outcome" Project]. / Le sperimentazioni dell'area cardiovascolare del Progetto Mattoni del SSN - Mattone Outcome: risultati finali. Sperimentazione dell'integrazione di fonti informative cliniche e amministrative del Programma PROGRESSI.

Observational outcome studies represent a valid approach to evaluating comparative treatment effectiveness in real populations. The main objective of outcome research is to underline what works and what does not work in the field of health assistance. In 2004 the Italian Ministry of Health launched the Project "Mattone Misura dell'Outcome" aimed at assessing the introduction of procedures and methods for the systematic evaluation of outcomes in the national health system. A new experience, the PROGRESSI program (PROGRamma ESiti per SIVeAS e LEA), started in 2008 with the aim to further develop the methodologies for outcome evaluation. In this Supplement the final results from four clinical studies named "Sperimentazioni dell'area cardiovascolare del Progetto Mattoni" are presented. These studies started between 2005 and 2007 and their main objectives were to evaluate: --the contribution of information from current informative systems and clinical studies in risk-adjustment methodologies; --the advisability of introducing some clinical items in current informative systems to improve outcome estimates; --the goodness of follow-up procedures from current informative systems; and --the role of disease registries in the validation of comparative evaluation measures. The four studies were designed as voluntary prospective multicentre studies. Results concerning the characteristics of the enrolled populations as well as the risk-adjustment models built using information from current informative systems and/or clinical information are presented. As expected, each study produced specific remarks both in terms of clinical findings and contribution of different informative systems to the risk-adjustment models. In general, models built with information from both current informative systems and clinical information show the best performance. Findings from these analyses will provide the public health system with suitable indications to improve statistical methodologies for outcome estimates.

Spie charts, target plots, and radar plots for displaying comparative outcomes of health care.

OBJECTIVE: Comparative evaluations of clinical outcomes (e.g., in-hospital mortality, complications after a surgical procedure) or health care processes involve the definition of several indicators for each study unit. Graphical displays are best suited for highlighting the main patterns in the data. The aim of this study was to compare different graphical techniques, including target plots, radar plots, and "spie" charts, for comparing the performances of different health care providers. STUDY DESIGN AND SETTING: Thirteen indicators were calculated and combined in eight composite indices for eight clinical categories of interest. The indices were displayed with target plots, radar plots, and "spie" charts. RESULTS: All the three techniques had an immediate interpretation and were easy to implement. However, target plots failed to highlight small differences between indicators, whereas radar plots were strongly influenced by the order in which the indicators were displayed. Both target and radar plots assumed equal weights for the indicators, and did not allow predetermined judgments on the relative importance of the indicators. "Spie" charts overcame the primary limitations of the other two techniques. Furthermore, they are well suited to summarize the overall performance of a health care provider with a single score. CONCLUSION: "Spie" charts represented the best graphical tool for displaying multivariate health care data in comparative evaluations of clinical outcomes and processes of care among health care providers.

Effectiveness of invasive reperfusion therapy and standard medical treatment in AMI.

OBJECTIVE: Coronary revascularization methods are among the most common major medical procedures performed in industrialized countries. The short- and long-term comparative effectiveness of different techniques remains undetermined. METHODS AND RESULTS: The study population included all adult patients (94,864 subjects) admitted for acute myocardial infarction (AMI) in 2004 in Italy, as recorded in the National Hospital Discharge Records. Invasive reperfusion therapy (coronary artery bypass graft, percutaneous coronary intervention), and standard medical treatments were compared. End points were short-term (30-day) in-hospital mortality and any combination of new revascularizations, re-AMI, stroke, or death (MACCE) occurring within 6 and 12 months from initial treatment. Risk factors and comorbidities were used to define patients' health status. The Cox model was applied to evaluate risk-adjusted hazard ratios (HR) for different approaches. Medical treatment was used as the reference category. Propensity score matching was performed to evaluate selection bias in the allocation to CABG or percutaneous coronary intervention (PCI). Both short-term mortality and 6- and 12-month MACCE risk for invasive reperfusion therapy was significantly lower than the reference (HR: 0.50, P < 0.001; 0.54, P < 0.001; 0.64, P < 0.001, respectively). In the matched population, while short-term mortality was significantly lower for PCI (HR 0.36, P < 0.001), long-term MACCE risk was lower for CABG (6-month HR 2.93, P < 0.001; 12-month HR 3.01, P < 0.001). CONCLUSIONS: In spite of adjustments for patients' health status, medical treatment resulted in a higher mortality and increased MACCE risk. While PCI gave the best short-term results, after 1 year the risk of re-interventions or further events was significantly lower for patients undergoing CABG.

Effects of socioeconomic position on 30-day mortality and wait for surgery after hip fracture.

OBJECTIVE: In countries where the National Health Service provides universal health coverage, socioeconomic position should not influence the quality of health care. We examined whether socioeconomic position plays a role in short-term mortality and waiting time for surgery after hip fracture. DESIGN: Retrospective cohort study. SETTING: and participants From the Hospital Information System database, we selected all patients, aged at least 65 years and admitted to acute care hospitals in Rome for a hip fracture between 1 January 2006 and 30 November 2007. The socioeconomic position of each individual was obtained using a city-specific index of socioeconomic variables based on the individual's census tract of residence. MAIN OUTCOME MEASURES: Three different outcomes were defined: waiting times for surgery, mortality within 30 days and intervention within 48 h of hospital arrival for hip fracture. We used a logistic regression to estimate 30-day mortality and a Cox proportional hazard model to calculate hazard ratios of intervention within 48 h. Median waiting times were estimated by adjusted Kaplan-Meyer curves. Analyses were adjusted for age, gender and coexisting medical conditions. RESULTS: Low socioeconomic level was significantly associated with higher risk of mortality [adjusted relative risk (RR) = 1.51; P < 0.05] and lower risk of early intervention (adjusted RR = 0.32; P < 0.001). Socioeconomic level had also an effect on waiting times within 30 days. CONCLUSIONS: Individuals living in disadvantaged census tracts had poorer prognoses and were less likely than more affluent people to be treated according to clinical guidelines despite universal healthcare coverage.

Risk adjustment for inter-hospital comparison of primary cesarean section rates: need, validity and parsimony.

BACKGROUND: Cesarean section rates is often used as an indicator of quality of care in maternity hospitals. The assumption is that lower rates reflect in developed countries more appropriate clinical practice and general better performances. Hospitals are thus often ranked on the basis of caesarean section rates. The aim of this study is to assess whether the adjustment for clinical and sociodemographic variables of the mother and the fetus is necessary for inter-hospital comparisons of cesarean section (c-section) rates and to assess whether a risk adjustment model based on a limited number of variables could be identified and used. METHODS: Discharge abstracts of labouring women without prior cesarean were linked with abstracts of newborns discharged from 29 hospitals of the Emilia-Romagna Region (Italy) from 2003 to 2004. Adjusted ORs of cesarean by hospital were estimated by using two logistic regression models: 1) a full model including the potential confounders selected by a backward procedure; 2) a parsimonious model including only actual confounders identified by the "change-in-estimate" procedure. Hospital rankings, based on ORs were examined. RESULTS: 24 risk factors for c-section were included in the full model and 7 (marital status, maternal age, infant weight, fetopelvic disproportion, eclampsia or pre-eclampsia, placenta previa/abruptio placentae, malposition/malpresentation) in the parsimonious model. Hospital ranking using the adjusted ORs from both models was different from that obtained using the crude ORs. The correlation between the rankings of the two models was 0.92. The crude ORs were smaller than ORs adjusted by both models, with the parsimonious ones producing more precise estimates. CONCLUSION: Risk adjustment is necessary to compare hospital c-section rates, it shows differences in rankings and highlights inappropriateness of some hospitals. By adjusting for only actual confounders valid and more precise estimates could be obtained.

Risk adjustment and outcome research. Part I.

OBJECTIVE: The increasing demand for comparative evaluation of outcomes requires the development and diffusion of epidemiologic research, the ability to correctly formulate hypotheses, to conduct analyses and to interpret the results. The purpose of this paper is to provide a detailed but easy-reading review of epidemiologic methods to compare healthcare outcomes, particularly risk-adjustment methods. METHODS: The paper is divided into three parts. Part I describes confounding in observational studies, the ways confounding is identified and controlled (propensity adjustment and risk adjustment), and the methods for constructing the severity measures in risk-adjustment procedures. CONCLUSIONS: It is becoming increasingly important for policy makers and planners to identify which factors may improve or worsen the effectiveness of treatments and services and to compare the performances of providers. Politicians, managers, epidemiologists, and clinicians should make their decisions based on the validity and precision of study results, by using the best scientific knowledge available. The statistical methods described in this review cannot measure 'reality' as it 'truly' is, but can produce 'images' of it, defining limits and uncertainties in terms of validity and precision. Studies that use credible risk-adjustment strategies are more likely to yield reliable and applicable findings.

[Introduction to risk adjustment methods in comparative evaluation of outcomes]. / Introduzione ai metodi di risk adjustment nella valutazione comparativa degli esiti.

The increasing demand for comparative evaluation of outcomes requires the development and diffusion of epidemiologic research, the ability to correctly conduct analyses and to interpret results. When healthcare outcomes are used for comparing quality of care across providers, failure to use methods of risk adjustment to account for any variation in patient populations can lead to misinterpretation of the findings. The purpose of this paper is to provide a detailed but easy-reading review of different risk adjustment methodologies to compare health care outcomes. The paper is divided in two parts. Introduction describes the difference between experimental and observational studies, the role of confounding in observational studies and the ways confounding is identified and controlled (propensity adjustment and risk adjustment), Specific part on risk adjustment describes: (1) the methods for constructing the severity measures; (2) the methods that use the severity measures to obtain "adjusted" outcome measures for valid comparison between groups (stratified analysis, indirect and direct standardization); (3) identification and management of effect modification; (4) the methods to gain the precision of the estimates; (5) the risk adjustment methods used with multiple comparisons and (6) introduction to other models (multi-level models) used for risk adjustment. For policy makers and planners, epidemiologists and clinicians it is important to understand which factors can improve or worsen the effectiveness of treatments and services and to compare the performances of hospitals and healthcare providers. Decisions should be based on the validity and precision of study results, by using the best scientific knowledge available. The statistical methods described in this review cannot measure reality as it truly is, but can produce images of it, defining limits and uncertainties in terms of validity and precision. Since any risk-adjustment model used for comparative evaluation of outcomes must be time- and population-specific, only the studies that use credible risk adjustment strategies are more likely to yield reliable findings.

[Evidence-based emergency pathways for patients with acute coronary syndrome]. / Esperienze di reti regionali percorso clinico assistenziale in emergenza--sindromi coronariche acute.

We present an evidence-based diagnostic and therapeutic pathway for the treatment of subjects with suspected acute elevated ST-segment myocardial infarction (STEMI). The pathway was developed to aid the reorganization of the emergency service (ES) of the Lazio Region of Italy. Pathway development followed several phases: a) setting up of a multidisciplinary panel comprising all professional figures involved in the management of STEMI subjects; b) drafting of a list of important research questions with a particular focus on areas of clinical and organization uncertainty; c) systematic searches for relevant international scientific evidence to answer research questions; d) assessment, synthesis and classification of identified evidence according to the quality of evidence; e) formulation of management recommendations by their strength according to the methods used by the national guidelines program; f) presentation of draft findings and recommendations; g) external peer review of the draft document; h) editing the final version of the document. Our document identifies possible action scenarios (community, emergency room, major accident and emergency departments) and the following critical points: 1) quick diagnosis and individual risk definition; 2) rapid transmission of the electrocardiogram and vital parameters to the ES control center or to the competent coronary care unit (CCU) depending on where the event took place; 3) a direct link between the ES control center and the competent CCU; 4) the structuring of the regional CCU into a Hub & Spoke model; 5) electronic communication of data between ambulance, ES control center and the competent CCU. Our document also defines Hub regional reference centers and local Spoke centers. The pathway details roles and responsibilities of all players in the emergency chain for STEMI sufferers and critical points for the delivery of the pathway: regional programs on early warning, functions of relevant ES personnel and of emergency room physicians, efficiency of the electronic network and identification and organization of the regional Hub & Spoke network.