Clinical Characteristics And Health Care Resources In Patients Treated With Oral Anticoagulants: Evidences From Italian Administrative Databases.

OBJECTIVES: 1) To evaluate anticoagulation treatment patterns and health care resource use in adult patients with a discharge diagnosis of non-valvular atrial fibrillation (NVAF) in an Italian real-world setting and 2) to describe the characteristics of NVAF patients in relation to treatment. DESIGN: A retrospective cohort study in a "real-world" setting. SETTING: Data were analysed by integrating administrative databases that included approximately 2,000,000 individuals assisted by the National Health System from two Italian Local Health Units. PARTICIPANTS: All adult patients with at least one hospital discharge or ≥2 outpatient visits with a diagnosis code for NVAF from 1/01/2011 to 31/12/2015 were included. MAIN OUTCOME MEASURES: Anticoagulation treatment patterns, health care resource use and major bleeding events that occurred during the follow-up period were evaluated. RESULTS: 32,863 NVAF patients were included, of whom 7,831 had at least one prescription of oral anticoagulants. Among them, 6,876 patients were vitamin K antagonists (VKA) users and 955 were non-vitamin K antagonist oral anticoagulant (NOAC) users at index date (ID). During the follow-up period, the use of antiplatelet drugs was higher among VKA-naïve users than the NOAC-naïve users. Among NOAC users, 76.1% showed an adherence level ≥80% during follow-up. The rate of bleeding events resulted higher for VKA patients compared to NOAC patients. The unadjusted incidence rate was 10.46 per 1000 person-year for VKA patients and 4.55 per 1,000 person-years for NOAC patients. The overall annual cost (in term of drugs, hospitalisations and outpatient specialist services) was € 5,156.13 for VKA and € 4,630.57 for NOAC. CONCLUSION: This unselected cohort study, on NVAF patients being prescribed oral anticoagulants, highlights that VKA was largely prescribed and the great majority of patients on NOACs were adherent to treatment. Most of the OAC patients still received antiplatelet agents in combination, and in NOAC patients, we registered a lower number of bleeding events compared with VKA.

Therapeutic strategies utilization and resource consumption in patients treated for psoriatic arthritis: findings from a real-world analysis in an Italian setting.

PURPOSE: The purpose of this study was to analyze the therapeutic strategies and estimate the health care resource consumption in patients with psoriatic arthritis (PsA). PATIENTS AND METHODS: An observational retrospective cohort analysis of administrative databases of six Italian Local Health Units was performed. Patients ≥18 years with a hospitalization discharge diagnosis of PsA (International Classification of Diseases, Ninth Revision code: 696.0) or exemption code (045.696.0) for PsA from January 1, 2010 to December 31, 2015 (inclusion period), with at least one prescription of any therapy used for PsA were included. The index date (ID) was the first date matching with at least one of the inclusion criteria during the inclusion period. All patients were followed up after the ID until the end of data availability. Baseline C-reactive protein (CRP) levels (±6 months in relation to the ID) were also analyzed. RESULTS: A total of 2,408 (prevalence 0.83 per 1,000) patients with PsA (male 52%; median age 54 years) were included in the study; patients were already treated for PsA in 42.4% of cases. At 1 year of follow-up, 73% of the patients received one systemic drug, while 22% of patients received two systemic drugs; in addition, our results show an increase in the number of add-on or switches in a longer follow-up period. The utilization of biologic agents was higher among patients with previous PsA treatment, showing a progression of the pathology. Overall, a medium/high level of CRP at baseline was observed among more than half of the overall sample, with slight changes across subgroups in analysis. The average health care costs were €1,966.4 and €13,914 per year for patients treated with conventional systemic therapy and biological agents, respectively. CONCLUSION: A better knowledge of prescription therapeutic scheme and economic burden of PsA could stimulate the rational development of health programs aimed at potentiating services for its management.

Establishing an ICD-10 code based SARI-surveillance in Germany - description of the system and first results from five recent influenza seasons.

BACKGROUND: Syndromic surveillance of severe acute respiratory infections (SARI) is important to assess seriousness of disease as recommended by WHO for influenza. In 2015 the Robert Koch Institute (RKI) started to collaborate with a private hospital network to develop a SARI surveillance system using case-based data on ICD-10 codes. This first-time description of the system shows its application to the analysis of five influenza seasons. METHODS: Since week 40/2015, weekly updated anonymized data on discharged patients overall and on patients with respiratory illness including ICD-10 codes of primary and secondary diagnoses are transferred from the network data center to RKI. Retrospective datasets were also provided. Our descriptive analysis is based on data of 47 sentinel hospitals collected between weeks 1/2012 to 20/2016. We applied three different SARI case definitions (CD) based on ICD-10 codes for discharge diagnoses of respiratory tract infections (J09 - J22): basic CD (BCD), using only primary diagnoses; sensitive CD (SCD), using primary and secondary diagnoses; timely CD (TCD), using only primary diagnoses of patients hospitalized up to one week. We compared the CD with regard to severity, age distribution and timeliness and with results from the national primary care sentinel system. RESULTS: The 47 sentinel hospitals covered 3.6% of patients discharged from all German hospitals in 2013. The SCD comprised 2.2 times patients as the BCD, and 3.6 times as many as the TCD. Time course of SARI cases corresponded well to results from primary care surveillance and influenza virus circulation. The patients fulfilling the TCD had been completely reported after 3 weeks, which was fastest among the CD. The proportion of SARI cases among patients was highest in the youngest age group of below 5-year-olds. However, the age group 60 years and above contributed most SARI cases. This was irrespective of the CD used. CONCLUSIONS: In general, available data and the implemented reporting system are appropriate to provide timely and reliable information on SARI in inpatients in Germany. Our ICD-10-based approach proved to be useful for fulfilling requirements for SARI surveillance. The exploratory approach gave valuable insights in data structure and emphasized the advantages of different CD.

Hyperuricemia is associated with increased hospitalization risk and healthcare costs: Evidence from an administrative database in Italy.

BACKGROUND AND AIM: Chronic hyperuricemia is responsible for a relevant burden of articular diseases and cardio-nephrometabolic disorders. We evaluated the effect of high serum uric acid (SUA) levels on hospitalization risk and mortality and on healthcare costs in a real-life setting. METHODS AND RESULTS: We conducted a retrospective analysis using a large administrative database and a clinical registry among 112,170 subjects from three Italian local health units. Individuals were divided into four groups according to their SUA levels: <6 mg/dL (66.5%), >6 mg/dL and ≤7 mg/dL (19.3%), >7 mg/dL and ≤8 mg/dL (8.7%), and >8 mg/dL (5.5%). Compared to those with SUA level of <6 mg/dL, the risk of hospitalization related to gout and/or nephrolithiasis was higher in the three groups of patients with higher SUA levels (1.51, P = 0.100; 2.21, P = 0.005; and 1.17, P = 0.703, respectively). A similar trend was also observed for hospitalization due to chronic kidney disease (CKD) (1.31, P < 0.001; 1.40, P < 0.001; and 2.18, P < 0.001, respectively) and cardiovascular disease (CVD) (1.08, P < 0.001; 1.23, P < 0.001; and 1.67, P < 0.001, respectively) and for all-cause mortality (0.97, P = 0.309; 1.21, P < 0.001; and 2.15, P < 0.001). The mean annual healthcare costs were higher in patients with higher SUA level (€2752, €2957, €3386, and €4607, respectively) mainly because of a progressive increase in hospitalization costs per patient (from € 1515 for SUA <6 mg/dL to € 3096 for SUA >8 mg/dL). CONCLUSIONS: Increased SUA levels are associated with an increased risk of hospitalizations related to hyperuricemia, CKD, and CVDs and total mortality, and consequently with higher total healthcare costs and hospitalization costs per patient.

Poultry food products--a source of avian influenza virus transmission to humans?

Global human mobility and intercontinental connectivity, expansion of livestock production and encroachment of wildlife habitats by invasive agricultural land use contribute to shape the complexity of influenza epidemiology. The OneHealth approach integrates these and further elements into considerations to improve disease control and prevention. Food of animal origin for human consumption is another integral aspect; if produced from infected livestock such items may act as vehicles of spread of animal pathogens, and, in case of zoonotic agents, as a potential human health hazard. Notifiable zoonotic avian influenza viruses (AIV) have become entrenched in poultry populations in several Asian and northern African countries since 2003. Highly pathogenic (HP) AIV (e.g. H5N1) cause extensive poultry mortality and severe economic losses. HPAIV and low pathogenic AIV (e.g. H7N9) with zoonotic propensities pose risks for human health. More than 1500 human cases of AIV infection have been reported, mainly from regions with endemically infected poultry. Intense human exposure to AIV-infected poultry, e.g. during rearing, slaughtering or processing of poultry, is a major risk factor for acquiring AIV infection. In contrast, human infections through consumption of AIV-contaminated food have not been substantiated. Heating poultry products according to kitchen standards (core temperatures ≥70°C, ≥10 s) rapidly inactivates AIV infectivity and renders fully cooked products safe. Nevertheless, concerted efforts must ensure that poultry products potentially contaminated with zoonotic AIV do not reach the food chain. Stringent and sustained OneHealth measures are required to better control and eventually eradicate, HPAIV from endemic regions.

Age-related prevalence of cross-reactive antibodies against influenza A(H3N2) variant virus, Germany, 2003 to 2010.

To estimate susceptibility to the swine-origin influenza A(H3N2) variant virus (A(H3N2)v) in the German population, we investigated cross-reactive antibodies against this virus and factors associated with seroprotective titre using sera from representative health examination surveys of children and adolescents (n = 815, 2003­06) and adults (n = 600, 2008­10). Antibodies were assessed by haemagglutination inhibition assay (HI); in our study an HI titre ≥ 40 was defined as seroprotective. We investigated associated factors by multivariable logistic regression. Overall, 41% (95% confidence interval (CI): 37­45) of children and adolescents and 39% (95% CI: 34­44) of adults had seroprotective titres. The proportion of people with seroprotective titre was lowest among children younger than 10 years (15%; 95% CI: 7­30) and highest among adults aged 18 to 29 years (59%; 95% CI: 49­67). Prior influenza vaccination was associated with higher odds of having seroprotective titre (odds ratio (OR) for children and adolescents: 3.4; 95% CI: 1.8­6.5; OR for adults: 2.4; 95% CI: 1.7­3.4). Young children showed the highest and young adults the lowest susceptibility to the A(H3N2)v virus. Our results suggest that initial exposure to circulating seasonal influenza viruses may predict long-term cross-reactivity that may be enhanced by seasonal influenza vaccination.

[Occupational health and practice management of primary care practitioners during influenza pandemic 2009/10 in Germany - a survey of 1150 physicians participating in syndromic influenza surveillance at Robert Koch Institute]. / Praxismanagement und Arbeitsschutz während der Influenza-Pandemie 2009/2010 - Eine Umfrage unter 1150 Ärzten der Arbeitsgemeinschaft Influenza am Robert Koch-Institut.

BACKGROUND: In preparation of an influenza pandemic, public health authorities and professional organisations recommend physicians to change practice management for patients with acute respiratory infections (ARI), in order to reduce transmission and protect practice staff. This study evaluates the implementation of these recommendations during the influenza pandemic 2009/10. METHODS: In 2010, we sent a standardised paper-and-pencil questionnaire on information sources, practice management, occupational safety and vaccination to physicians participating in the national sentinel syndromic influenza surveillance in Germany. Taken measures were compared according to specialisation of physicians. RESULTS: Out of 1,150 physicians, 760 replied (66%). The recommendations were considered reasonable by 64%. Physicians used hand disinfection (76%), gloves (62%) and facial masks (52%) more frequently than usual. Overall, 68% changed their practice management during the pandemic. Physicians separated ARI patients spatially (74%) and in time (38%) from others. In 72%, physicians were vaccinated against pandemic influenza. The physicians found time and effort spent on the sentinel appropriate (82%), even during the influenza pandemic. Paediatricians considered the recommendations less practicable than GPs or internists. CONCLUSION: The majority of participating physicians considered the recommendations on occupational safety reasonable and changed their practice management accordingly. However, the recommendations might not reflect the special needs of paediatricians.

Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012.

On 24 October 2012, a patient with acute respiratory distress syndrome of unknown origin and symptom onset on 5 October was transferred from Qatar to a specialist lung clinic in Germany. Late diagnosis on 20 November of an infection with the novel Coronavirus (NCoV) resulted in potential exposure of a considerable number of healthcare workers. Using a questionnaire we asked 123 identified contacts (120 hospital and three out-of-hospital contacts) about exposure to the patient. Eighty-five contacts provided blood for a serological test using a two-stage approach with an initial immunofluorescence assay as screening test, followed by recombinant immunofluorescence assays and a NCoV-specific serum neutralisation test. Of 123 identified contacts nine had performed aerosol-generating procedures within the third or fourth week of illness, using personal protective equipment rarely or never, and two of these developed acute respiratory illness. Serology was negative for all nine. Further 76 hospital contacts also tested negative, including two sera initially reactive in the screening test. The contact investigation ruled out transmission to contacts after illness day 20. Our two-stage approach for serological testing may be used as a template for similar situations.

[Detection of local influenza outbreaks and role of virological diagnostics]. / Erkennung von Influenzaausbrüchen und Rolle der virologischen Diagnostik.

For many years, the Working Group on Influenza (AGI) has been the most important influenza surveillance system in Germany. An average sample of the population is covered by both syndromic and virological surveillance, which provides timely data regarding the onset and course of the influenza wave as well as its burden of disease. However, smaller influenza outbreaks cannot be detected by the AGI sentinel system. This is achieved by the information reported by the mandatory notification system (Protection Against Infection Act, IfSG), which serves as the second pillar of the national influenza surveillance. Approaches to recognize such outbreaks are based either on reported influenza virus detection and subsequent investigations by local health authorities or by notification of an accumulation of respiratory diseases or nosocomial infections and subsequent laboratory investigations. In this context, virological diagnostics plays an essential role. This has been true particularly for the early phase of the 2009 pandemic, but generally timely diagnostics is essential for the identification of outbreaks. Regarding potential future outbreaks, it is also important to keep an eye on animal influenza viruses that have repeatedly infected humans. This mainly concerns avian influenza viruses of the subtypes H5, H7, and H9 as well as porcine influenza viruses for which a specific PCR has been established at the National Influenza Reference Centre. An increased incidence of respiratory infections, both during and outside the season, should always encourage virological laboratory diagnostics to be performed as a prerequisite of further extensive investigations and an optimal outbreak management.

Adherence to therapeutic and diagnostic recommendations in patients with femur fracture and at risk of re-fracture or death: results of an analysis of administrative databases.

The aim of the present study was to evaluate the application into clinical practice of therapeutic and diagnostic recommendations for the prevention of bone re-fracture in postmenopausal women after an hospitalization for hip fracture in clinical practice and to assess the relationship between the application of diagnostic recommendations and re-fracture or death risk. A retrospective cohort analysis was conducted. All female patients, at least 65 years old, and with an hospitalization with main or secondary diagnosis of hip fracture during the period 1 January 2006 - 31 December 2008, were included. Besides demographic characteristics and comorbidities, drug treatment prescriptions related to bone fracture or supplementary with calcium or vitamin D and prescriptions of recommended laboratory and instrumental diagnostic tests (e.g. spine radiography), were analysed. A total of 5,636 patients were included in the study. The prescription of a drug treatment aimed to reduce the risk of re-fracture was found in 16.3% of patients, among them 76.3% (699 patients) used bisphosphonates only, 17.1% (157 patients) strontium ranelate only and 4.9% (45 patients) used more than one treatment during the observation period. Among the patients who did not receive drug treatment, 17.5% made use of only supplemental calcium and vitamin D. The remaining part of patients (69.1%) received no treatment. The prescription of at least one laboratory test of first and second level was performed, respectively, on 53.7% and 43.1% of included patients, whereas the prescription of at least one instrumental test of first and second level was performed, respectively, on 5.9% and 0.8%. Although it is established that the prescription of the recommended tests and appropriate drug treatment are significantly associated with reduced risk of re-fracture and death, today the application of these recommendations is reduced.

Avian influenza A(H5N1) in humans: new insights from a line list of World Health Organization confirmed cases, September 2006 to August 2010.

The threat of avian influenza (AI) viruses to humans in Europe in 2005 prompted the Robert Koch Institute to establish a routine monitoring instrument condensing information on all human AI cases worldwide reported from the World Health Organization (WHO) and other sources into a line list for further analysis. The 235 confirmed AI cases captured from September 2006 to August 2010 had a case fatality rate of 56% (132/235), ranging from 28% (27/98) in Egypt to 87% (71/82) in Indonesia. In a multivariable analysis, odds of dying increased by 33% with each day that passed from symptom onset until hospitalisation (OR: 1.33, p=0.002). In relation to children of 0­9 years, odds of fatal outcome were more than six times higher in 10­19 year-olds and 20­29 year-olds (OR: 6.06, 95% CI: 1.89­19.48, p=0.002 and OR: 6.16, 95% CI: 2.05­ 18.53, p=0.001, respectively), and nearly five times higher in patients of 30 years and older (OR: 4.71, 95% CI: 1.56­14.27, p=0.006) irrespective of the country, which had notified WHO of the cases. The situation in Egypt was special in that case number and incidence in children were more than twice as high as in any other age group or country. With this study, we show that data from the public domain yield important epidemiological information on the global AI situation. This approach to establish a line list is time-consuming but a line list is a prerequisite to such evaluations. We thus would like to encourage the placing of a publicly accessible line list of anonymised human AI cases, e.g. directly by WHO. This might enhance our understanding of AI in humans and permit the rapid detection of changes in its epidemiology with implications for human health.

Mortality of 2009 pandemic influenza A(H1N1) in Germany.

The mortality in Germany caused by the 2009 pandemic influenza A(H1N1) seems to have been one of the lowest in Europe. We provide a detailed analysis of all 252 fatal cases of confirmed infection with the pandemic virus notified between 29 April 2009 and 31 March 2010. The overall mortality was 3.1 (95% confidence interval (CI): 2.7 to 3.5) per one million inhabitants. We observed an increase in the case fatality rate of notified cases over time; notified cases aged 60 years or older had the highest case fatality rate (2.16%; 95% CI: 1.61 to 2.83; odds ratio: 5.4; p<0.001; reference group: 35­59 years). The median delay of four days (interquartile range (IQR): 2­7) between symptom onset and antiviral treatment was significantly longer in fatal cases than for non-fatal cases (median: two days (IQR: 1­3; p<0.001). Analysis of the underlying medical conditions of fatal cases, based on the observed frequency of the conditions in the general population, confirms the risk for fatal outcome, which is most notably due to immunosuppression, diabetes and respiratory diseases. Our results suggest that early treatment might have had an impact on overall mortality. Identification of risk groups for targeted intervention to prevent fatalities needs to take into account the distribution of underlying conditions in the population.

[Epidemiological characteristics of the influenza pandemic (H1N1) 2009 in Germany based on the mandatory notification of cases]. / Epidemiologischer Steckbrief der pandemischen Influenza (H1N1) 2009 basierend auf Einzelfallmeldungen nach Infektionsschutzgesetz.

The aim of the investigation is the descriptive analysis of case-based information from mandatory notifications in the first year of the influenza pandemic (H1N1) 2009 in order to identify and describe epidemiological characteristics and risk factors for severe outcome. Four distinct time periods were defined to describe the age distribution of hospitalized and fatal cases. In contrast, stratified (age, sex) analysis of risk factors was carried out for the whole time period of pandemic influenza activity (notification weeks 18/2009 to 17/2010). Characteristic differences in the age distribution of reported cases were observed according to the time period. Among the reported risk factors, immunosuppression exhibited the highest probability for hospitalization or a fatal outcome (OR=8.82; CI95% 7.3-10.6 and OR=37.4; CI95% 25.5-54.8, respectively). The stratified analysis showed that this was especially pronounced for patients in the age group 60 years and above. Single case-based notifications of pandemic influenza have proven to be an invaluable source of information for assessing the epidemiological characteristics of the influenza pandemic 2009 in Germany. In addition, it allows comparative analysis of certain risk groups for severe disease. The information, thus, provides an important contribution for further developing and improving of public health recommendations.

Household transmissibility and other characteristics of seasonal oseltamivir-resistant influenza A(H1N1) viruses, Germany, 2007-8.

During the influenza season 2007-8, the proportion of seasonal influenza A(H1N1) viruses resistant to the neuraminidase inhibitor oseltamivir increased worldwide. We conducted an investigation to compare patients infected with oseltamivir-resistant (ose-R) and oseltamivir- susceptible (ose-S) influenza A(H1N1) viruses regarding risk factors for resistance and the capability to transmit in the household setting. Within a cohort of 396 laboratory confirmed influenza patients from sentinel physicians we conducted a nested case-control study among patients infected with A(H1N1). Thirty patients in the cohort were infected with influenza B, none with influenza A(H3N2) and 366 with A(H1N1). Of the 366 A(H1N1) viruses 52 (14%) were ose-R. Demographic characteristics, oseltamivir exposure, travel history and outcome were not significantly different between ose-S and ose-R patients. Among 133 households in the nested case-control study, secondary household attack rates in households with ose-R cases and households with ose-S cases were similar (23 versus 26%; p-value=0.54). Ose-R household status and occurrence of secondary cases were associated with an odds ratio of 0.85 (95% confidence interval 0.38-1.88). We conclude that seasonal ose-R influenza A(H1N1) viruses have transmitted well in the household setting.

Oseltamivir-resistant influenza A(H1N1) viruses detected in Europe during season 2007-8 had epidemiologic and clinical characteristics similar to co-circulating susceptible A(H1N1) viruses.

During the 2007-08 influenza season, high levels of oseltamivir resistance were detected among influenza A(H1N1) viruses ina number of European countries. We used surveillance data to describe influenza A(H1N1) cases for whom antiviral resistance testing was performed. We pooled data from national studies to identify possible risk factors for infection with a resistant virus and to ascertain whether such infections led to influenza illness of different severity. Information on demographic and clinical variables was obtained from patients or their physicians. Odds ratios for infection with an oseltamivir resistant virus and relative risks for developing certain clinical outcomes were computed and adjusted through multivariable analysis. Overall, 727 (24.3%) of 2,992 tested influenza A(H1N1) viruses from 22 of 30 European countries were oseltamivir-resistant. Levels of resistance ranged from 1% in Italy to 67% in Norway. Five countries provided detailed case-based data on 373 oseltamivir resistant and 796 susceptible cases. By multivariable analysis, none of the analysed factors was significantly associated with an increased risk of infection with anoseltamivir-resistant virus. Similarly, infection with an oseltamivir-resistant virus was not significantly associated with a different risk of pneumonia, hospitalisation or any clinical complication. The large-scale emergence of oseltamivir-resistant viruses in Europe calls for a review of guidelines for influenza treatment.