Dementia and Related Comorbidity: Analysis of 2 Years of Admissions to Italian Hospitals.

BACKGROUND: The aim of the present study was to examine the prevalence of dementia, related comorbidities, and mortality rates in hospitalized elderly patients in Italy. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged 65 years or above admitted to acute Internal Medicine during 2 years (n=3,695,278 admissions). Discharge diagnoses were re-classified into 24 clusters, each including homogeneous diseases by the ICD-9-CM code classification. Dementia was identified by the presence of ICD-9-CM codes 290, 294, or 331 series. RESULTS: Patients with dementia represented 7.5% of the sample; compared with those without dementia, they were older and more often female, had a greater length of hospital stay and higher mortality rate. Besides delirium [odds ratio (OR): 54.20], enthesopaties (OR: 2.19), diseases of fluids and electrolytes (OR:1.96), diseases of arteries (OR: 1.69), skin diseases (OR: 1.64), and pneumonia and pleurisy (OR: 1.53) were the diseases more strongly associated with the diagnosis of dementia, independent of other clusters, age, sex, and length of stay. CONCLUSIONS: Some comorbidities are specifically associated with the diagnosis of dementia among hospitalized elderly patients. Overall, these comorbidities describe the typical clinical profile of the patient with advanced dementia and could be treated in the context of the primary care, since they do not require specific skills belonging to hospital settings.

Dementia and in-hospital mortality: retrospective analysis of a nationwide administrative database of elderly subjects in Italy.

AIMS:  To evaluate the relationship between comorbidity and in-hospital mortality in elderly patients affected by dementia. METHODS: Data were obtained from the Italian Ministry of Health and included all discharge records from Italian hospitals concerning subjects aged ≥ 65 years admitted to acute Internal Medicine or Geriatrics wards between January 2015 and December 2016 (3.695.278 admissions). The variables analyzed included age, sex, and in-hospital death. Twenty-five homogeneous clusters of diseases were identified in discharge codes according to the ICD-9-CM classification. RESULTS: Patients with dementia represented 7.5% of the sample (n. 278.149); they were older, more often males (51.9%), and had a higher in-hospital mortality (24.3%) compared to patients without dementia (9.7%). Dementia per se doubled the odds of death (OR 1.98; 95% CI 1.95-2.00), independent of age, sex, and comorbidities. Seven clusters of disease (pneumonia, heart failure, kidneys disease, cancer, infectious diseases, diseases of fluids/electrolytes and general symptoms) were associated with increased in-hospital mortality, independent of the presence/absence of dementia. Among patients with dementia, heart failure, pneumonia and kidney disease on their own substantially doubled/tripled mortality risk. The risk increased from 10.1% (none of selected conditions), up to 28.9% when only one of selected comorbidities was present, rising to 52.3% (OR: 9.34; p < 0.001) when two or more comorbidities were simultaneously diagnosed, besides general symptoms. CONCLUSIONS: Our study confirmed an important increase of in-hospital mortality in older subjects with dementia. Despite a different comorbidity, the conditions associated with in-hospital mortality were substantially the same in patients with or without dementia. Heart failure, pneumonia, and kidney disease identified a high risk of in-hospital mortality among subjects with dementia.

Acute cholestasis as uncommon onset of Kawasaki disease: a case report.

BACKGROUND: Kawasaki disease (KD) or mucocutaneous lymph node syndrome is a vasculitis that mostly occurs in young children. Adult-onset KD (AKD) is rare and often misdiagnosed. Here we report a rare case of KD with cholestasis as principal symptom. CASE PRESENTATION: A 43-year-old caucasian man was admitted to our hospital for high fever, lack of appetite related to nausea and vomiting, headache and significant malaise. Physical examination highlighted fever, increasing jaundice, bilateral laterocervical lymph nodes, erythema of the palms, and strikingly red lips and conjunctiva. The clinical course was complicated by arterial hypotension, tachycardia, decreasing haemoglobin, increasing acute phase reactants tests, and multiorgan failure. Due to cardiovascular instability the patient was admitted to the local Intensive Care Unit. Chest X-ray, abdominal ultrasound, chest and abdominal CT and Colangio Magnetic Resonance were normal. Jaundice was investigated and infections, autoimmune diseases or drugs adverse reactions, were excluded. Also coronary artery computed tomography was carried out excluding coronary artery aneurysms. Broad-spectrum antibiotics were not effective. After exclusion other possible conditions, diagnosis of KD was set. He was treated with high doses of corticosteroids and acetylsalicylic acid and clinical conditions as well as laboratory exams improved. CONCLUSIONS: This report dealing with an adult onset of atypical KD may be of benefit to physicians of various specialties, including primary care doctors, hospital internists, intensivists and gastroenterologists due to its peculiarities. It demonstrates that a case of prolonged fever unresponsive to antibiotics and related to cholestatic jaundice, oedema or erythema of the extremity associated with desquamation of feet and hands, and red eyes, may suggest atypical form of KD.

Validation and Comparison of a Modified Elixhauser Index for Predicting In-Hospital Mortality in Italian Internal Medicine Wards.

PURPOSE: Burden of comorbidities appears to be related to clinical outcomes in hospitalized patients. Clinical stratification of admitted patients could be obtained calculating a comorbidity score, which represents the simplest way to identify the severity of patients' clinical conditions and a practical approach to assess prevalent comorbidities. Our aim was to validate a modified Elixhauser score for predicting in-hospital mortality (IHM) in internal medicine admissions and to compare it with a different one derived from clinical data previously used in a similar setting, having a good prognostic accuracy. PATIENTS AND METHODS: A single-center retrospective study enrolled all patients admitted to internal medicine department between January and June 2016. A modified Elixhauser score was calculated from chart review and administrative data; moreover, a second prognostic index was calculated from chart review only. Comorbidity scores were compared using c-statistic. RESULTS: We analyzed 1614 individuals without selecting the reason for admission, 224 (13.9%) died during hospital stay. Deceased subjects were older (83.3±9.1 vs 78.4±13.5 years; p<0.001) and had higher burden of comorbidities. The modified Elixhauser score calculated by administrative data and by chart review and the comparator one was 18.13±9.36 vs 24.43±11.27 vs 7.63±3.3, respectively, and the c-statistic was 0.758 (95% CI 0.727-0.790), 0.811 (95% CI 0.782-0.840) and 0.740 (95% CI 0.709-0.771), respectively. CONCLUSION: The new modified Elixhauser score showed a similar performance to a previous clinical prognostic index when it was calculated using administrative data; however, its performance improved if calculation was based on chart review.

Acute Kidney Injury and In-Hospital Mortality: A Retrospective Analysis of a Nationwide Administrative Database of Elderly Subjects in Italy.

BACKGROUND: The aim of this study was to investigate the association between acute kidney injury (AKI) and in-hospital mortality (IHM) in a large nationwide cohort of elderly subjects in Italy. METHODS: We analyzed the hospitalization data of all patients aged ≥65 years, who were discharged with a diagnosis of AKI, which was identified by the presence of the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), and extracted from the Italian Health Ministry database (January 2000 to December 2015). Data regarding age, gender, dialysis treatment, and comorbidity, including the development of sepsis, were also collected. RESULTS: We evaluated 760,664 hospitalizations, the mean age was 80.5 ± 7.8 years, males represented 52.2% of the population, and 9% underwent dialysis treatment. IHM was 27.7% (210,661 admissions): Deceased patients were more likely to be older, undergoing dialysis treatment, and to be sicker than the survivors. The population was classified on the basis of tertiles of comorbidity score (the first group 7.48 ± 1.99, the second 13.67 ± 2,04, and third 22.12 ± 4.13). IHM was higher in the third tertile, whilst dialysis-dependent AKI was highest in the first. Dialysis-dependent AKI was associated with an odds ratios (OR) of 2.721; 95% confidence interval (CI) 2.676-2.766; p < 0.001, development of sepsis was associated with an OR of 1.990; 95% CI 1.948-2.033; p < 0.001, the second tertile of comorbidity was associated with an OR of 1.750; 95% CI 1.726-1.774; p < 0.001, and the third tertile of comorbidity was associated with an OR of 2.522; 95% CI 2.486-2.559; p < 0.001. CONCLUSIONS: In elderly subjects with AKI discharge codes, IHM is a frequent complication affecting more than a quarter of the investigated population. The increasing burden of comorbidity, dialysis-dependent AKI, and sepsis are the major risk factors.

Impact of hospital admissions subsequent to renal transplantation on Italian regional resources: a retrospective study in the Italian region of Emilia-Romagna.

BACKGROUND: Aim of this retrospective study was to investigate costs and resource consuming, expressed by diagnosis related groups (DRG), related only to hospitalizations of renal transplant recipients (RTRs) for all causes in the Region Emilia Romagna (RER) in Italy. METHODS: We included all hospital admissions of RTRs (International Classification of Diseases 9th Revision, Clinical Modification [ICD-9-CM] code V420) between 2001 and 2015. We calculated number of admissions, RTRs and inhabitants of RER for each year, mean age, length of stay (LOS) in the hospital as total number of days, mean and median days, mean value of DRG and costs of admissions during the 15-year period of the study. RESULTS: RTRs admitted in the 15 years study period were 9,197 and mean age 56.6±1.6 years. Admissions were 14,558, and mean rate of admitted RTRs (*100,000) was 14.21. Total, mean and median LOS were 122,966, 8.7 and 6 days, respectively. Total costs of admissions during the study period were €72,717,232 with mean DRG values of €3,409. Number of admissions and total number of days required for RTRs as well as mean age of admitted patients increased from 2001 to 2015, however mean and median LOS remained stable. CONCLUSIONS: Costs due to admissions of RTRs appeared to gradually increase in the long term probably due to the increasing number of admissions and increasing mean age of admitted RTRs.

Infections and internal medicine patients: Could a comorbidity score predict in-hospital mortality?

Infectious diseases (ID) are frequently cause of internal medicine wards (IMW) admission. We aimed to evaluate risk factors for in-hospital mortality (IHM) in IMW patients with ID, and to test the usefulness of a comorbidity score (CS).This study included ID hospital admissions between January 2013, and December 2016, recorded in the database of the local hospital. ICD-9-CM codes were selected to identify infections, development of sepsis, and to calculate a CS.We analyzed 12,173 records, (age 64.8 ±â€Š25.1 years, females 66.2%, sepsis 9.3%). Deceased subjects (1545, 12.7%) were older, had higher percentage of sepsis, pulmonary infections, and endocarditis. Mean value of CS was also significantly higher. At multivariate analysis, the odds ratio (OR) for sepsis (OR 5.961), endocarditis (OR 4.247), pulmonary infections (OR 1.905), other sites of infection (OR 1.671), and urinary tracts infections (OR 0.548), were independently associated with IHM. The CS (OR 1.070 per unit of increasing score), was independently associated with IHM as well. The calculated weighted risk, obtained by multiplying 1.070 for the mean score value in deceased patients, was 19.367. Receiver operating characteristic (ROC) analysis showed that CS and development of sepsis were significant predictors for IHM (area under the curve, AUC: 0.724 and 0.670, respectively).Careful evaluation of comorbidity in internal medicine patients is nowadays matter of extreme importance in IMW patients hospitalized for ID, being IHM related to severity of disease, type and site of infection, and also to concomitant comorbidities. In these patients, a careful evaluation of CS should represent a fundamental step in the disease management.

Weekend Versus Weekday Admission and In-Hospital Mortality for Pulmonary Embolism: A 14-Year Retrospective Study on the National Hospital Database of Italy.

We assessed the association between weekday (WD) or weekend (WE) admission and mortality for patients hospitalized with acute pulmonary embolism (PE). Weekend included holidays. We analyzed hospital administrative data of all patients discharged with a diagnosis of PE extracted from the Italian Health Ministry database (January 2001 to December 2014). A total of 265 035 hospitalizations with a diagnosis of PE were retrieved, in which PE was the primary diagnosis in 198 565 (74.9%); 200 166 (75.5%) patients were admitted on WD and 64 869 (24.5%) on WE. Admissions for PE were more frequent on Mondays (41 917 admissions, 15.8% of all events) and less frequent on Saturdays (32 295 admissions, 12.2%) and Sundays (32 574 admissions, 12.3%). Patients admitted on WE were on average 1 year older, presented more frequently with respiratory failure, and had more common comorbidities. After adjustment for age, gender, comorbidities, and presence of respiratory failure, in-hospital mortality for patients admitted on WE was greater (odds ratio: 1.15, 95% confidence interval: 1.13-1.18; P < .001). This study supports that, in Italy, hospitalization for PE on WE is associated with a significantly higher mortality rate than on WD.

Circaseptan Periodicity of Cardiovascular Diseases.

The occurrence of cardiovascular events shows a different distribution during the week, with many studies reporting a Monday peak, possibly related to the role of stress associated with commencing weekly activities. Furthermore, a higher mortality has been observed among patients hospitalized for cardiovascular and other disorders on weekends, a phenomenon known as "weekend effect." Such effect may be explained by a higher level of disease severity among patients admitted over the weekend, and/or by a poorer quality of care associated with shortage of staff, lower experience of personnel, and limited availability of therapeutic and diagnostic procedures.

A modified Elixhauser score for predicting in-hospital mortality in internal medicine admissions.

BACKGROUND: In-hospital mortality (IHM) is an indicator of the quality of care provided. The two most widely used scores for predicting IHM by International Classification of Diseases (ICD) codes are the Elixhauser (EI) and the Charlson Comorbidity indexes. Our aim was to obtain new measures based on internal medicine ICD codes for the original EI, to detect risk for IHM. MATERIAL AND METHODS: This single-center retrospective study included hospital admissions for any cause in the department of internal medicine between January 1, 2000, and December 31, 2013, recorded in the hospital database. The EI was calculated for evaluation of comorbidity, then we added age, gender and diagnosis of ischemic heart disease. IHM was our outcome. Only predictors positively associated with IHM were taken into consideration and the Sullivan's method was applied in order to modify the parameter estimates of the regression model into an index. RESULTS: We analyzed 75,586 admissions (53.4% females) and mean age was 72.7±16.3years. IHM was 7.9% and mean score was 12.1±7.6. The points assigned to each condition ranged from 0 to 16, and the possible range of the score varied between 0 and 89. In our population the score ranged from 0 to 54, and it was higher in the deceased group. Receiver operating characteristic curve of the new score was 0.721 (95% CI 0.714-0.727, p<0.001). CONCLUSIONS: In order to make prognostic assessment, the use of a score could be of help in targeting interventions in older adults, identifying subjects at high risk for IHM.

Lung and kidney: a dangerous liaison? A population-based cohort study in COPD patients in Italy.

BACKGROUND: COPD is among the major causes of death, and it is associated with several comorbid conditions. Chronic kidney disease (CKD) is frequently diagnosed in older people living in Western societies and could impact COPD patients' mortality. We evaluated the relationship between burden of comorbidities, CKD, and mortality in a population-based cohort of patients discharged with a diagnosis of COPD. METHODS: A longitudinal cohort study was conducted evaluating 27,272 COPD patients. Recruitment of COPD subjects and identification of CKD and other comorbidities summarized by the Charlson comorbidity index (CCI) were based on claims data coded according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Severity of COPD was classified by hospital diagnosis or exemption from medical charges due to respiratory failure or previous hospitalizations for COPD. The impact of comorbidities on survival was assessed by Cox regression. RESULTS: Less than 40% of patients were still alive at the end of a median follow-up of 37 months (17 months for patients who died and 56 months for those alive at the end of follow-up). After adjustment for age, gender, and severity score of COPD, CKD (hazard ratio =1.36, 95% confidence interval 1.30-1.42) independently from comorbidities summarized by the CCI was a significant risk factor for mortality. CONCLUSION: In spite of limitations due to the use of claims data, long-term survival of COPD patients was heavily affected by the presence of CKD and other comorbidities.

Marital Status, Cardiovascular Diseases, and Cardiovascular Risk Factors: A Review of the Evidence.

BACKGROUND: There is evidence showing that marital status (MS) and marital disruption (i.e., separation, divorce, and being widowed) are associated with poor physical health outcomes, including for all-cause mortality. We checked for the available evidence on the association between MS and cardiovascular (CV) diseases, outcomes, and CV risk factors. METHODS: A search across the PubMed database of all articles, including the term "marital status" in their title, was performed. All articles were then manually checked for the presence of the following terms or topic: CV diseases, acute myocardial infarction, acute coronary syndrome, coronary artery disease, cardiac arrest, heart failure, heart diseases, and CV mortality. Moreover, other search terms were: CV risk factors, hypertension, cholesterol, obesity, smoking, alcohol, fitness and/or physical activity, and health. Systematic reviews, meta-analyses, controlled trials, cohort studies, and case-control studies were potentially considered pertinent for inclusion. Case reports, comments, discussion letters, abstracts of scientific conferences, articles in other than English language, and conference abstracts or proceedings were excluded. RESULTS: In total, 817 references containing the title words "marital status" were found. After elimination of articles dealing with other topics, 70 records were considered pertinent. Twenty-two were eliminated for several reasons, such as old articles, no abstract, full text unavailable, other than English language, comments, and letters. Out of the remaining 48 articles, 13 were suitable for the discussion, and 35 (accounting for 1,245,967 subjects) were included in this study. CONCLUSIONS: Most studies showed better outcomes for married persons, and men who were single generally had the poorest results. Moreover, being married was associated with lower risk factors and better health status, even in the presence of many confounding effects.

Lack of a "Weekend Effect" for Renal Transplant Recipients.

The "weekend (WE) effect" defines the association between WE hospital admissions and higher rate of mortality. The aim of this study was to evaluate the relationship between WE effect and renal transplant recipients (RTRs) using the database of the Emilia-Romagna region (ERR), Italy. We included ERR admissions of RTRs ( International Classification of Diseases, Ninth Revision, Clinical Modification [ ICD-9-CM] code V420) between 2000 and 2013. In-hospital mortality, admissions due to cardiovascular events (CVEs), and the Elixhauser score were evaluated on the basis of ICD-9-CM codification. Out of 9063 hospital admissions related to 3648 RTRs (mean age 53 ± 13 years, 62.9% male), 1491 (16.5%) were recorded during the WE. During the follow-up period, 1581 (17.4%) patients deceased and 366 (4%) had CVEs. Length of hospital stay (LOS) was 9.7 ± 12.1 days. Logistic regression analysis showed that only LOS was independently associated with WE admissions (odds ratio: 1594, confidence interval: 1.385-1.833; P < .001). Renal transplant recipients are not exposed to higher risk of adverse outcome during WE admissions. However, WE admissions were characterized by an increased duration of hospitalization.

Renal Transplantation and Outcome.

Emergency surgery represents an independent risk factor for death and postoperative complications. The aim of this study was to investigate the literature data regarding outcome of daytime or nighttime renal transplantation surgery. Relevant papers, focused on renal transplantation surgery, time of the day, and complications, were searched across the PubMed database. We used the following search terms: "renal", "transplantation", "surgery", "daytime", "nighttime", and "outcome". A total of five papers, including 6,991 adult patients were evaluated. All patients received renal transplantation from deceased donor. Daytime or nighttime surgery do not seem to negatively impact on graft survival in renal transplantation. However, two out five studies reported higher odds of complications after nighttime operation. Since it is not possible to predict the availability of a deceased donor, nighttime surgery remains a valid option when necessary, maybe deserving a higher level of caution to reduce or avoid complications.

Chronobiology of Takotsubo Syndrome and Myocardial Infarction: Analogies and Differences.

Several pathophysiologic factors, not harmful if taken alone, are capable of triggering unfavorable events when presenting together within the same temporal window (chronorisk), and the occurrence of many cardiovascular events is not evenly distributed in time. Both acute myocardial infarction and takotsubo syndrome seem to exhibit a temporal preference in their onset, characterized by variations according to time of day, day of the week, and month of the year, although with both analogies and differences.

Contemporary burden of excess cardiovascular mortality on Monday. A retrospective study in the Veneto region of Italy.

BACKGROUND: An increased risk for adverse cardiovascular events on Monday has been consistently reported in the literature. It remains to be assessed if a Monday peak in cardiovascular deaths can still be detected within the contemporary context of decreasing mortality rates from circulatory diseases in developed countries. METHODS: Mortality records were extracted from January 2000 to December 2013 in the Veneto region (Italy). The Monday excess in mortality from cerebrovascular diseases, ischemic heart diseases, and other circulatory diseases was investigated in subjects aged 35-74years by means of Poisson regression models adjusted by age, gender, time trend and seasonality. RESULTS: Among 41,024 deaths from circulatory diseases registered in the study population, mortality rates on Monday were increased by 13% (CI 9-17%) with respect to Sunday and by 6% (CI 4-9%) with respect to the overall daily mean. The Monday peak could be detected in both genders and in all the analyzed disease categories, and was more pronounced in younger age classes and in more recent years. CONCLUSIONS: The persistency of the Monday effect on cardiovascular mortality is confirmed by recent large population-based data. Further research is warranted to investigate causal mechanisms.

Impact of renal dysfunction on in-hospital mortality of patients with severe chronic obstructive pulmonary disease: a single-center Italian study.

BACKGROUND: We conducted a study, based on discharge hospital sheets [International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM)], in order to evaluate the relationship between chronic kidney disease (CKD), acute kidney injury (AKI), multi-morbidity, and in-hospital mortality (IHM). METHODS: This study included all hospital admissions for chronic obstructive pulmonary disease (COPD) exacerbations between January 1, 2000, and December 31, 2013, recorded in the database of the University Hospital St. Anna of Ferrara. Age, sex, and diagnosis of CKD and AKI were collected, and Charlson comorbidity index (CCI) was calculated by ICD-9-CM codes. IHM was our main outcome. RESULTS: We analyzed 7073 subjects with COPD exacerbation; they were more frequently male (56.9 vs 43.1 %), and mean age was 76.7 ± 9.8 years. Diagnosis of CKD was present in 771 patients (10.9 %), while AKI was diagnosed in 354 cases (5 %). A total of 554 patients (7.8 %) died during hospitalization, and LOS was 10.3 ± 11.2 days (median 8 days); the CCI corrected for CKD was 2.30 ± 1.65. Univariate analysis showed that IHM group had higher age (81.2 ± 7.9 vs 76.3 ± 9.9 years, p < 0.001), CCI (2.61 ± 2.21 vs 2.28 ± 1.62, p = 0.001), and LOS (11.1 ± 15.1 vs 10.3 ± 10.8 days, p = 0.001) and developed AKI more frequently (16.6 vs 4 %, p < 0.001) than survivors. Multivariate logistic regression analysis showed an independent association of IHM with age (OR 1.063; 95 % CI 1.050-1.075, p < 0.001), male sex (OR 1.229; 95 % CI 1.016-1.486, p = 0.033), logCCI (OR 2.051; 95 % CI 1.419-2.964, p < 0.001), and AKI (OR 3.849; 95 % CI 2.874-5.155, p < 0.001). CONCLUSIONS: Acute kidney injury (AKI) represents a very important predictive factor of IHM in male older adult with multi-morbidity admitted because of COPD exacerbations.

Impact of comorbidity on outcome in kidney transplant recipients: a retrospective study in Italy.

The aim of this study was to relate in-hospital mortality (IHM), cardiovascular events (CVEs) and non-immunologic comorbidity evaluated on the basis of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codification, in Italian kidney transplant recipients (KTRs). We evaluated IHM and admissions due to CVEs between 2000 and 2013 recorded in the database of the region Emilia Romagna. The Elixhauser score was calculated for evaluation of non-immunologic comorbidity. Three main outcomes (i.e. IHM, admission due to major CVEs and combined outcome) were the dependent variables of the multivariate models, while age, gender and Elixhauser score were the independent ones. During the examined period, a total of 9063 admissions in 3648 KTRs were recorded; 1945 patients were males (53.3 %) and 1703 females (46.7 %) and the mean age was 52.9 ± 13.1 years. The non-immunological impaired status of the KTRs, examined by the Elixhauser score, was 3.88 ± 4.29. During the 14-year follow-up period, IHM for any cause was 3.2 % (n = 117), and admissions due to CVEs were 527 (5.8 %). Age and comorbidity were independently associated with CVEs, IHM and the combined outcome. Male gender was independently associated with IHM and combined outcome, but not with CVEs. Evaluation of non-immunological comorbidity is important in KTRs and identification of high-risk patients for major clinical events could improve outcome. Moreover, comorbidity could be even more important in chronic kidney disease patients who are waiting for a kidney transplant.

"Timing" of arrival and in-hospital mortality in a cohort of patients under anticoagulant therapy presenting to the emergency departments with cerebral hemorrhage: A multicenter chronobiological study in Italy.

Therapy with oral anticoagulants (OACs) is a risk factor for cerebral hemorrhage (CH). Although different studies have been undertaken to investigate the timing of the onset of major cardiovascular events, no data exist on temporal patterns of the onset of CH in subjects treated with OACs. The aim of this study is to evaluate the timing of CH in patients treated with OACs. All patients who developed CH under OACs therapy and admitted to 28 Italian Emergency Departments (EDs) between September 2011 and July 2013 were enrolled. Age, sex, time and location of the hemorrhagic lesion, type of the bleeding events (idiopathic or post-traumatic), anticoagulant therapy (warfarin or new oral anticoagulants - NOAs) and time of ED admission (i.e., hour, day, month and season) were recorded. Five hundred and seventeen patients (63.2% male aged 80 ± 7.9 yrs) with CH were involved. Warfarin was taken by 494 patients (95.6%), and NOAs by 23 (4.4%). In-hospital mortality (IHM) was recorded in 208 cases (40.2%). Cosinor analysis showed a peak of CH arrival between 12:00 and 14:00 h both in the whole population (PR 73.9%, p = 0.002) and the male subgroup (PR 65.2%, p = 0.009), whereas females showed an anticipated morning peak between 08:00 and 10:00 h (PR 65.7%, p = 0.008). A further analysis between idiopathic and post-traumatic CH confirmed the presence of a 24 h pattern with a peak between 12:00 and 14:00 h (PR 58.5%, p = 0.019) and between 08:00 and 10:00 h (PR80.1%, p < 0.001) for idiopathic events and post-traumatic hemorrhages, respectively. Moreover, a seasonal winter peak was identified for idiopathic forms (PR 74%, p = 0.035), and a summer peak for post-traumatic forms (PR 77%, p = 0.025). The present study suggests the presence of a temporal pattern of ED arrivals in CH patients treated with OACs.