Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates.

Background: In Italy, during the first epidemic wave of 2020, the peak of coronavirus disease 2019 (COVID-19) mortality was reached at the end of March. Afterward, a progressive reduction was observed until much lower figures were reached during the summer, resulting from the contained circulation of SARS-CoV-2. This study aimed to determine if and how the pathological patterns of the individuals deceased from COVID-19 changed during the phases of epidemic waves in terms of: (i) main cause of death, (ii) comorbidities, and (iii) complications related to death. Methods: Death certificates of persons who died and tested positive for SARS-CoV-2, provided by the National Surveillance system, were coded according to ICD rev10. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Results: The percentage of COVID-19 deaths varied over time. It decreased in the downward phase of the epidemic curve (76.6 vs. 88.7%). In February-April 2020, hypertensive heart disease was mentioned as a comorbidity in 18.5% of death certificates, followed by diabetes (15.9% of cases), ischemic heart disease (13.1%), and neoplasms (12.1%). In May-September, the most frequent comorbidity was neoplasms (17.3% of cases), followed by hypertensive heart disease (14.9%), diabetes (14.8%), and dementia/Alzheimer's disease (11.9%). The most mentioned complications in both periods were pneumonia and respiratory failure with a frequency far higher than any other condition (78.4% in February-April 2020 and 63.7% in May-September 2020). Discussion: The age of patients dying from COVID-19 and their disease burden increased in the May-September 2020 period. A more serious disease burden was observed in this period, with a significantly higher frequency of chronic pathologies. Our study suggests better control of the virus' lethality in the second phase of the epidemic, when the health system was less burdened. Moreover, COVID-19 care protocols had been created in hospitals, and knowledge about the diagnosis and treatment of COVID-19 had improved, potentially leading to more accurate diagnosis and better treatment. All these factors may have improved survival in patients with COVID-19 and led to a shift in mortality to older, more vulnerable, and complex patients.

The Role of COVID-19 in the Death of SARS-CoV-2-Positive Patients: A Study Based on Death Certificates.

Background: Death certificates are considered the most reliable source of information to compare cause-specific mortality across countries. The aim of the present study was to examine death certificates of persons who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to (a) quantify the number of deaths directly caused by coronavirus 2019 (COVID-19); (b) estimate the most common complications leading to death; and (c) identify the most common comorbidities. Methods: Death certificates of persons who tested positive for SARS-CoV-2 provided to the National Surveillance system were coded according to the 10th edition of the International Classification of Diseases. Deaths due to COVID-19 were defined as those in which COVID-19 was the underlying cause of death. Complications were defined as those conditions reported as originating from COVID-19, and comorbidities were conditions independent of COVID-19. Results: A total of 5311 death certificates of persons dying in March through May 2020 were analysed (16.7% of total deaths). COVID-19 was the underlying cause of death in 88% of cases. Pneumonia and respiratory failure were the most common complications, being identified in 78% and 54% of certificates, respectively. Other complications, including shock, respiratory distress and pulmonary oedema, and heart complications demonstrated a low prevalence, but they were more commonly observed in the 30-59 years age group. Comorbidities were reported in 72% of certificates, with little variation by age and gender. The most common comorbidities were hypertensive heart disease, diabetes, ischaemic heart disease, and neoplasms. Neoplasms and obesity were the main comorbidities among younger people. Discussion: In most persons dying after testing positive for SARS-CoV-2, COVID-19 was the cause directly leading to death. In a large proportion of death certificates, no comorbidities were reported, suggesting that this condition can be fatal in healthy persons. Respiratory complications were common, but non-respiratory complications were also observed.

Logical Rules and a Preliminary Prototype for Translating Mortality Coding Rules from ICD-10 to ICD-11.

Iris is a system for coding multiple causes of death in ICD-10 and for the selection of the underlying cause of death, based on a knowledge base composed by a large number of rules. With the adoption of ICD-11, those rules need translation to ICD-11. A pre-project has been carried out to evaluate feasibility of transition to ICD-11, which included the analysis of the logical meta-rules needed for rule translation and development of a prototype support system for the expert that will translate the coding rules.

[Impact of the implementation of ICD-10 2016 version and Iris software on mortality statistics in Italy]. / Impatto dell'implementazione della versione 2016 dell'ICD-10 e del software Iris sulle statistiche di mortalità in Italia.

OBJECTIVES: to assess the impact of coding causes of death with the ICD-10 2016 version and the software Iris on Italian official statistics on mortality. DESIGN: coding of a sample of death certificates with two different coding systems (bridge coding). SETTING AND PARTICIPANTS: a sample of 63,525 deaths occurred throughout 2015 among people aged over one year, already coded using the ICD-10 2009 version and the Mortality Medical Data System (MMDS) software, was re-coded through the ICD-10 2016 version and the Iris software. MAIN OUTCOME MEASURES: the transition matrix between the two coding systems was realized and the agreement percentages between the two coding systems, the comparability ratios, and the relative 95% confidence intervals were calculated. Comparability ratios have been calculated for both the underlying cause of death and the multiple causes. RESULTS: overall, 79% of deaths showed exactly the same underlying cause of death (ICD-10 code, 4 digits) in the two coding systems. On the three-digit level, the agreement was 89%; on ICD-10 chapter level, the agreement was 95%. At the chapter level, the most important changes were observed for: • certain infectious and parasitic diseases (-18% in ICD-10 2016/Iris); • diseases of the genitourinary system (-17%); • diseases of the respiratory system (+7%); • diseases of the nervous system and sense organs (+5%); • external causes of morbidity and mortality (+5%). Analyzing the multiple causes, the most important changes were observed for: • certain infectious and parasitic diseases (-19% in ICD-10 2016/Iris); • external causes of morbidity and mortality (+28%); • symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified (+7%). CONCLUSION: the results are very useful to explain any change in the Italian statistics on mortality comparing 2015 with the following years.

Physical, psychological and economic burden of two-wheel users after a road traffic injury: Evidence from intensive care units of three EU countries.

INTRODUCTION: This study aimed to assess the physical, psychological, and economic burden shouldered by severely injured two-wheel users in three European countries as well as the cost resulting from their hospitalization. METHODS: A total of seven public hospitals were involved in three countries: Greece, Italy, and Germany. Participants enrolled during a 12-month period starting in April 2013. Eligibility criteria included an injury sustained at Road Traffic Crashes (RTC) irrespective of the type of vehicle, hospitalization 1 day in the Intensive Care Unit (ICU) or sub-ICU, and age 18 years or over. Patients were interviewed at 1, 6, and 12 months upon admission. The study used widely recommended classifications for injury severity (Abbreviated Injury Severity [AIS]; Maximum Abbreviated Injury Severity [MAIS]) and standardized measures such as the Disability Assessment Schedule II (WHODAS 2.0), "Impact of Event Scale" (IES-R), Center for Epidemiological Studies Depression Scale (CES-D Scale). Health Care Expenditure was assessed through the Monash University Accident Research Centre (MUARC's) framework, which included measures of 'Direct' and 'Indirect' costs. Diagnosis-related groups (DRGs) were used to estimate hospitalization costs. RESULTS: A total of 54 two-wheel users enrolled in the study in all the countries and 32 completed all follow-up questionnaires. Physical disability increased over 12 months following the injury. Post Traumatic Stress Disorder (PTSD) symptoms of avoidance remained at high levels over the study period. PTSD symptoms of intrusion improved significantly during the second half of the year under investigation. The total annual cost of injury for the two-wheel users who were hospitalized in the selected ICU of all the partner countries for severe injury in 2013/2014, was estimated at €714,491 made up of €123,457 direct and €591,034 indirect costs. Men, aged 50-64 years and those who sustained slight injuries primarily at the lower extremities presented higher indirect costs per person. A total of €1032.092 was spent on hospitalization payments. Women, aged 65+ and those who sustained severe injuries at the central body region presented higher direct costs per person. Women, aged 50-64 years, those with severe injuries and a major injury at the central body and the upper body region presented the highest hospitalization costs per person. CONCLUSIONS: There is a need for effective strategies to early detect and treat groups at risk of being confronted with prolonged psychosocial and economic consequences. PRACTICAL IMPLICATIONS: A holistic understanding of the impact of injury on individuals is important in order to achieve effective treatment of psychological co-morbidities in a timely manner.

Bicycle helmet use patterns in Italy. A description and analysis of survey data from an Italian friends of cycling association.

Cycling is becoming one of the most popular forms of recreation and transport the world over, but cyclists still have a high level of vulnerability. A bicycle helmet is an important safety device available to cyclists, but little is known regarding possible determinants of helmet use among adults. This study aims at providing information on helmet usage patterns in Italy and identifying the factors associated with bicycle helmet use. Data on 2072 bicycle riders from an Italian friends of cycling association aged 18 years or older who had ridden a bicycle in the last month were collected using an ad-hoc questionnaire via the web. The sample was equally distributed among subjects who always, most of the time, sometimes, rarely, or never use a helmet. To evaluate the association among socio-demographic and bicycle use characteristics and helmet use, a multinomial logistic regression model was performed. The results show a higher propensity to use a helmet among males, riders coming from Central and Southern Italy, people who cycles more than 60kilometres in a week, cyclists who have already had a crash, people who do not cycle daily or almost daily, riders of sport bikes. Moreover, the propensity to use a helmet increases with age. The survey provided a first step in approaching the lack of data on cycling behaviour and the wearing of a helmet in Italy.

Road accidents involving bicycles: configurations and injuries.

This study analyzed the most common types of accident involving bicycles and compared the frequency of injuries. The data source was the database of German In-Depth Accident Study (GIDAS). Cases consist of bicycles and their riders involved in accidents between 2000 and 2010. In most collisions, the bicycle impacted with a car. The percentage of injured bicyclists was higher in collisions with a heavy vehicle and decreased when the bicycle impacted with lighter vehicles. A high percentage of injured bicyclists in single accidents was observed; the most severe injury was more frequently to head and extremities. Accidents involving a car and a bicycle with the right of way in a bicycle path represented about 20% of involved and injured bicyclists. The ten most frequent configurations represented about 60% of involved and injured bicyclists. These results contribute to understand the dangerous scenarios for bicyclists and to suggest preventive actions.

Psychological distress and physical disability in patients sustaining severe injuries in road traffic crashes: Results from a one-year cohort study from three European countries.

The current study aimed to follow-up a group of road crash survivors for one year and assesses the impact of injury on their psychological and physical condition. All crash survivors that were admitted to the intensive or sub-intensive care units of selected hospitals in Greece, Germany and Italy over one year period (2013-2014), were invited to participate in the study and were interviewed at three different time-points as follows: (a) at one month (baseline data), (b) at six months, and (c) at twelve months. The study used widely recommended classifications for injury severity (AIS, MAIS) and standardized health outcome measures such as the Disability Assessment Schedule II (WHODAS 2.0) to measure disability, "Impact of Event Scale" (IES-R) to measure Post-Traumatic Stress Disorder (PTSD), Center for Epidemiological Studies Depression Scale (CES-D Scale) to measure depression. A total of 120 patients were enrolled in the study in all the partner countries and 93 completed all follow up questionnaires. The risk of physical disability was 4.57 times higher [CI 1.98-2.27] at the first follow up and 3.43 times higher [CI 1.43-9.42] at the second follow up as compared with the time before the injury. There was a 79% and an 88% lower risk of depression at the first and the second follow up respectively, as compared with the baseline time. There was also a 72% lower risk of Post-Traumatic Stress at the second follow up as compared with the baseline time. A number of factors relevant to the individuals, the road crash and the injury, were shown to distinguish those at higher risk of long-lasting disability and psychological distress including age, marital status, type of road user, severity and type of the injury, past emotional reaction to distress. The study highlights the importance of a comprehensive and holistic understanding of the impact of injury on an individual and further underlines the importance of screening and treating psychological comorbidities in injury in a timely manner.

Radiosurgery reirradiation for high-grade glioma recurrence: a retrospective analysis.

Despite various treatment strategies being available, recurrent high-grade gliomas (r-HGG) are difficult to manage. To obtain local control, radiosurgery (SRS) reirradiation has been considered as potential treatment. In the present study, a retrospective analysis was performed on r-HGG patients treated with salvage single- (s-SRS) or multi-fraction SRS (m-SRS). The aim of this study was to evaluate the effectiveness of salvage SRS in terms of overall survival (OS); toxicity was analyzed as well. Between 2004 May and 2011 December, 128 r-HGG patients (161 lesions) treated with CyberKnife(®) SRS reirradiation were retrospectively analyzed. Toxicity was graded according to Radiation Therapy Oncology Group and by Common Terminology Criteria for Adverse Events v.3 criteria. OS from the diagnosis date and OS from reirradiation were estimated using the Kaplan-Meier method. Median follow-up was 9 months (range 15 days-82 months). All patients completed SRS without high-grade toxicity. Radiation necrosis was observed in seven patients (6 %) with large volume lesions. The median survival from initial diagnosis was 32 months. The 1-, 2-, and 3-years survival rates from diagnosis were 95, 62, and 45 % respectively. Median survival following SRS was 11.5 months. The 1-, 2-, and 3-years survival rate following SRS was 48, 20, and 17 % respectively. On multivariate analysis, age <40 years, salvage surgery before SRS, and other post-SRS therapies (second-line chemotherapy and/or surgery) were found to significantly improve survival (p = 0.03). SRS represents a safe and feasible option to treat r-HGG patients with low complication rates and potential survival benefit.

Is fluorescein-guided technique able to help in resection of high-grade gliomas?

OBJECT: Fluorescein, a dye that is widely used as a fluorescent tracer, accumulates in cerebral areas where the blood-brain barrier is damaged. This quality makes it an ideal dye for the intraoperative visualization of high-grade gliomas (HGGs). The authors report their experience with a new fluorescein-guided technique for the resection of HGGs using a dedicated filter on the surgical microscope. METHODS: The authors initiated a prospective Phase II trial (FLUOGLIO) in September 2011 with the objective of evaluating the safety of fluorescein-guided surgery for HGGs and obtaining preliminary evidence regarding its efficacy for this purpose. To be eligible for participation in the study, a patient had to have suspected HGG amenable to complete resection of the contrast-enhancing area. The present report is based on the analysis of the short- and long-term results in 20 consecutive patients with HGGs (age range 45-74 years), enrolled in the study since September 2011. In all cases fluorescein (5-10 mg/kg) was injected intravenously after intubation. Tumor resection was performed with microsurgical technique and fluorescence visualization by means of BLUE 400 or YELLOW 560 filters on a Pentero microscope. RESULTS: The median preoperative tumor volume was 30.3 cm(3) (range 2.4-87.8 cm(3)). There were no adverse reactions related to fluorescein administration. Complete removal of contrast-enhanced tumor was achieved in 80% of the patients. The median duration of follow-up was 10 months. The 6-months progression-free survival rate was 71.4% and the median survival was 11 months. CONCLUSIONS: Analysis of these 20 cases suggested that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high rate of complete resection of contrast-enhanced tumor as determined on early postoperative MRI. Clinical trial registration no.: 2011-002527-18 (EudraCT).

Alcohol consumption, helmet use and head trauma in cycling collisions in Germany.

Cycling, being easy, inexpensive and healthy, is becoming one of the most popular means of transport. Cyclists, however, are among the most vulnerable road users in traffic collisions. The aims of this study were to establish which cyclist and cycling accident characteristics are associated with alcohol consumption and helmet use in Germany and to identify risk factors related to head trauma sustained in cycling accidents. The source used for the present analysis was the database of the German in-depth accident study (GIDAS). All cyclists who had been involved in a road accident between 2000 and 2010 and submitted to an alcohol test were selected. Logistic regression analyses were carried out to evaluate various aspects: alcohol consumption, helmet use, head trauma, and cyclist/accident characteristics. Female riders were less likely to have consumed alcohol (OR=0.23, 95% CI: 0.08-0.66); cyclists who did not wear a helmet were more likely to have consumed alcohol (OR=2.41, 95% CI: 1.08-5.38); cyclists who were not responsible for the collision were less likely to have consumed alcohol than those who were partially responsible for the accident (OR=0.22, 95% CI: 0.08-0.61). Cyclists involved in collisions with another vehicle, motorised or not, had a lower risk of suffering a head injury compared with those involved in single-vehicle accidents (OR=0.27, 95% CI: 0.12-0.62, and OR=0.08, 95% CI: 0.03-0.22, respectively). The prevention or limiting of alcohol consumption among cyclists and the corresponding testing of cyclists must be improved. Training initiatives on helmet protection should be encouraged.

Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases.

BACKGROUND: Fluorescein is widely used as a fluorescent tracer for many applications. Its capability to accumulate in cerebral areas with blood-brain barrier damage makes it an ideal dye for intraoperative visualization of malignant gliomas (MG). We report our preliminary experience in fluorescein-guided removal of grade IV gliomas using a dedicated filter on the surgical microscope. METHODS: In September 2011 we started a prospective phase II trial (FLUOGLIO) to evaluate the safety and obtain initial indications about the efficacy of fluorescein-guided surgery for MG. Patients with suspected MG amenable to complete resection of contrast-enhancing areas were eligible to participate in this study. This report is based on a preliminary analysis of the results of 12 patients with grade IV gliomas out of 15 consecutive cases (age range 48-72 years) enrolled since September 2011. Fluorescein was injected intravenously (i.v.) after intubation (5-10 mg/kg). The tumor was removed using a microsurgical technique and fluorescence visualization by BLU 400 or YELLOW 560 filters on a Pentero microscope (Carl Zeiss, Germany). The study was approved by our ethics committee and registered on the European Regulatory Authorities website (EudraCT no. 2011-002527-18). RESULTS: Histological analysis confirmed grade IV gliomas in 12/15 cases. Median preoperative tumor volume was 33.15 cm(3) (9.6-87.8 cm(3)). No adverse reaction related to the administration of fluorescein was registered. Contrast-enhanced tumor was completely removed in 75 % of the patients. CONCLUSION: This preliminary analysis suggested that the use of intravenous fluorescein during surgery on grade IV gliomas is safe and allows a high rate of complete resection of contrast-enhanced tumor at the early postoperative MRI.

Clinical and molecular cross-sectional study of a cohort of adult type III spinal muscular atrophy patients: clues from a biomarker study.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations of the SMN1 gene. Based on severity, three forms of SMA are recognized (types I-III). All patients usually have 2-4 copies of a highly homologous gene (SMN2), which produces insufficient levels of functional survival motor neuron (SMN) protein due to the alternative splicing of exon 7. The availability of potential candidates to the treatment of SMA has raised a number of issues, including the availability of biomarkers. This study was aimed at evaluating whether the quantification of SMN2 products in peripheral blood is a suitable biomarker for SMA. Forty-five adult type III patients were evaluated by Manual Muscle Testing, North Star Ambulatory Assessment scale, 6-min walk test, myometry, forced vital capacity, and dual X-ray absorptiometry. Molecular assessments included SMN2 copy number, levels of full-length SMN2 (SMN2-fl) transcripts and those lacking exon 7 and SMN protein. Clinical outcome measures strongly correlated to each other. Lean body mass correlated inversely with years from diagnosis and with several aspects of motor performance. SMN2 copy number and SMN protein levels were not associated with motor performance or transcript levels. SMN2-fl levels correlated with motor performance in ambulant patients. Our results indicate that SMN2-fl levels correlate with motor performance only in patients preserving higher levels of motor function, whereas motor performance was strongly influenced by disease duration and lean body mass. If not taken into account, the confounding effect of disease duration may impair the identification of potential SMA biomarkers.