[What factors contributed to the higher incidence rate of in-hospital falls at the time of Covid 19? A paradigm shift?] / Quali sono I fattori contribuenti la caduta dei pazienti in ospedale al tempo del Covid 19? Un cambio di paradigma?

The COVID-19 pandemic has put a strain on all health systems as there has been a growing rapidity in the demand for health care from COVID 19 positive patients in hospitals around the world. With the intensification of the pandemic, determining in real time the consequent needs for health resources (beds, personnel, equipment) has in fact become the fundamental priority for many countries to ensure health services consistent with the health needs expressed by the population. In Italy, the demand has often been satisfied with the conversion of existing beds and the remodeling of the healthcare offer or where the available resources allow it also with the opening of new beds dedicated to pandemic assistance. This work analyzes the falls detected at the time of COVID in patients and hospitalized in direct hospital beds (600 beds) of a Local Health Authority of Lazio (ASL ROMA 2). Although the data on the incidence of falls recorded in the three centers were equal to 2.21 every 1000 days of beds occupied and that the data recorded are lower than those reported in the literature, it is also true that the increase in average hospital stay and the reduction in the rotation rate of beds had an impact on the still low occupancy rates compared to the literature data.The COVID-19 pandemic has put a strain on all health systems as there has been a growing rapidity in the demand for health care from COVID 19 positive patients in hospitals around the world. With the intensification of the pandemic, determining in real time the consequent needs for health resources (beds, personnel, equipment) has in fact become the fundamental priority for many countries to ensure health services consistent with the health needs expressed by the population. In Italy, the demand has often been satisfied with the conversion of existing beds and the remodeling of the healthcare offer or where the available resources allow it also with the opening of new beds dedicated to pandemic assistance. This work analyzes the falls detected at the time of COVID in patients and hospitalized in direct hospital beds (600 beds) of a Local Health Authority of Lazio (ASL ROMA 2). Although the data on the incidence of falls recorded in the three centers were equal to 2.21 every 1000 days of beds occupied and that the data recorded are lower than those reported in the literature, it is also true that the increase in average hospital stay and the reduction in the rotation rate of beds had an impact on the still low occupancy rates compared to the literature data. In fact, the scientific literature shows that in England and Wales, whose national health service is very similar to the Italian one, the falls of patients in hospitals with optimal bed occupancy rates and optimal average hospitalization rates (equal to 4.5 days in general medicine, 3.5 days in general surgery, 3 days in orthopedics) represent the first sentinel event in terms of incidence and frequency, albeit with a very variable damage detection. The average falls is 6.63 falls per 1,000 bed-occupied days, which equates to approximately 1,700 falls per year in an 800-bed hospital with an optimal occupancy rate. Regarding damage, the literature documents that physical injuries and fractures occur in 30-50% of events and fractures occur in 1-3% of cases. The data collected in ASL ROMA 2 have documented that despite the increase in staff dedicated to assistance by 15 - 30%, an increase due to the application of COVID pathways and to the activities of compression of the risk of circulation of the virus among hospitalized patients , the rate of falls has nevertheless increased by 13.5% despite the persistence of standards of quality and safety of patients in care activities, debunking the paradigm that falls can be caused by an undersizing of the care staff and by the possible overcrowding of the emergency departments - urgency.

Correction to: New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice.

The original version of the article unfortunately contained few errors.

The epistemic and aleatory uncertainties of the ETAS-type models: an application to the Central Italy seismicity.

Stochastic models provide quantitative evaluations about the occurrence of earthquakes. A basic component of this type of models are the uncertainties in defining main features of an intrinsically random process. Even if, at a very basic level, any attempting to distinguish between types of uncertainty is questionable, an usual way to deal with this topic is to separate epistemic uncertainty, due to lack of knowledge, from aleatory variability, due to randomness. In the present study this problem is addressed in the narrow context of short-term modeling of earthquakes and, specifically, of ETAS modeling. By mean of an application of a specific version of the ETAS model to seismicity of Central Italy, recently struck by a sequence with a main event of Mw6.5, the aleatory and epistemic (parametric) uncertainty are separated and quantified. The main result of the paper is that the parametric uncertainty of the ETAS-type model, adopted here, is much lower than the aleatory variability in the process. This result points out two main aspects: an analyst has good chances to set the ETAS-type models, but he may retrospectively describe and forecast the earthquake occurrences with still limited precision and accuracy.

New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice.

Recently several variants of clotting factors have shown a peculiar behavior so that they appear as new defects. The factors involved are FII, FV and FIX. Prothrombin deficiency is usually associated with bleeding. Recently a few prothrombin abnormalities involving Arg396 mutations, have been demonstrated to show antithrombin resistance with the consequent appearance of a thrombophilic state and venous thromboses in young age. The same is true for an abnormal FIX (FIX Padua). The thrombotic manifestations in the latter condition are also venous. The abnormal FIX (FIX Padua) is characterized by a great increase in FIX activity whereas FIX antigen is only slightly increased. The condition is due to an Arg338Lys mutation. The increased intrinsic clotting activity of this abnormal FIX is being investigated as a useful therapeutic approach in homophile B patients. Another new clotting disorder is represented by two abnormal FV (FV East Texas and FV Amsterdam). These are characterized by a deletion of part of the B domain of FV resulting in a "short" FV. The condition is characterized by a mild bleeding tendency due to high levels of Tissue Factor pathway inhibitor. The "short" factor V is in fact resistant to the action of Tissue Factor pathway inhibitor which is sharply increased in these patients. These new clotting entities have again demonstrated that the study of patients who show a tendency to venous thrombosis or a mild bleeding condition that cannot be explained on the basis of our current concepts of blood coagulation, may represent "new" coagulation disorders. All persons interested in thrombotic or hemorrhagic disorders should be informed about these new clinical and laboratory conditions.

SEDA: A software package for the Statistical Earthquake Data Analysis.

In this paper, the first version of the software SEDA (SEDAv1.0), designed to help seismologists statistically analyze earthquake data, is presented. The package consists of a user-friendly Matlab-based interface, which allows the user to easily interact with the application, and a computational core of Fortran codes, to guarantee the maximum speed. The primary factor driving the development of SEDA is to guarantee the research reproducibility, which is a growing movement among scientists and highly recommended by the most important scientific journals. SEDAv1.0 is mainly devoted to produce accurate and fast outputs. Less care has been taken for the graphic appeal, which will be improved in the future. The main part of SEDAv1.0 is devoted to the ETAS modeling. SEDAv1.0 contains a set of consistent tools on ETAS, allowing the estimation of parameters, the testing of model on data, the simulation of catalogs, the identification of sequences and forecasts calculation. The peculiarities of routines inside SEDAv1.0 are discussed in this paper. More specific details on the software are presented in the manual accompanying the program package.

Prethrombotic, prothrombotic, thrombophilic states, hypercoagulable state, thrombophilia etc.: semantics should be respected even in medical papers.

The study of prothrombotic or thrombophilic states have drawn considerable attention during the past two decades. This was the result of the increasing number of thrombotic events, both arterial and venous reported all over the world but especially in the developed countries. This wealth of studies and papers have not always respected the semantical significance of the various terms used, namely prethrombotic state, hypercoagulable state, thrombophilic or prothrombotic state, thrombophilia, susceptibility to thrombosis and procoagulant state. This review is an attempt to adhere to a correct Semantic format in order to avoid confusion and misinterpretations. This is of fundamental importance in order to avoid the wrong attribution of a thrombosis to a hypercoagulable or a prethrombotic state.

Thrombotic Events in Asymptomatic FXII Deficiency versus Symptomatic FXI Deficiency: Surprising Observations.

OBJECTIVE: To evaluate the impact of an asymptomatic congenital clotting defect (FXII deficiency) versus that of a similar but symptomatic defect (FXI deficiency) on protection from thrombosis. PATIENTS AND METHODS: All patients with FXII or FXI deficiency and thrombosis were gathered from a time-unlimited PubMed search that was carried out twice and from personal records. Combined defects were excluded. The defect had to be proven by the demonstration of a suited hereditary pattern and by a specific clotting assay. Only patients with a factor activity level of <30% of normal were selected. RESULTS: Twenty-eight patients with an FXII deficiency presented with arterial thrombosis, mainly myocardial infarction, and 29 showed venous thrombosis; for FXI deficiency, these figures were 43 and 10, respectively. The ratio of arterial and venous thrombosis was 0.96 and 4.3, respectively, for FXII and FXI deficiency. CONCLUSIONS: Factor FXII deficiency supplies no protection from arterial or venous thrombosis. FXI deficiency shows no protection from arterial thrombosis but appears to guarantee protection from venous thrombosis. A symptomatic, namely bleeding, condition (FXI deficiency) provides protection from venous thrombosis whereas an asymptomatic one (FXII deficiency) does not.

Linac4 H⁻ ion sources.

CERN's 160 MeV H(-) linear accelerator (Linac4) is a key constituent of the injector chain upgrade of the Large Hadron Collider that is being installed and commissioned. A cesiated surface ion source prototype is being tested and has delivered a beam intensity of 45 mA within an emittance of 0.3 π ⋅ mm ⋅ mrad. The optimum ratio of the co-extracted electron- to ion-current is below 1 and the best production efficiency, defined as the ratio of the beam current to the 2 MHz RF-power transmitted to the plasma, reached 1.1 mA/kW. The H(-) source prototype and the first tests of the new ion source optics, electron-dump, and front end developed to minimize the beam emittance are presented. A temperature regulated magnetron H(-) source developed by the Brookhaven National Laboratory was built at CERN. The first tests of the magnetron operated at 0.8 Hz repetition rate are described.

Upgrade of the beam extraction system of the GTS-LHC electron cyclotron resonance ion source at CERN.

Linac3 is the first accelerator in the heavy ion injector chain of the Large Hadron Collider (LHC), providing multiply charged heavy ion beams for the CERN experimental program. The ion beams are produced with GTS-LHC, a 14.5 GHz electron cyclotron resonance ion source, operated in afterglow mode. Improvement of the GTS-LHC beam formation and beam transport along Linac3 is part of the upgrade program of the injector chain in preparation for the future high luminosity LHC. A mismatch between the ion beam properties in the ion source extraction region and the acceptance of the following Low Energy Beam Transport (LEBT) section has been identified as one of the factors limiting the Linac3 performance. The installation of a new focusing element, an einzel lens, into the GTS-LHC extraction region is foreseen as a part of the Linac3 upgrade, as well as a redesign of the first section of the LEBT. Details of the upgrade and results of a beam dynamics study of the extraction region and LEBT modifications will be presented.

Congenital factor XI and factor VII deficiencies assure an apparent opposite protection against arterial or venous thrombosis: An intriguing observation.

OBJECTIVE: To investigate the prevalence and type of thrombotic events reported in patients with congenital factor XI (FXI) or factor VII (FVII) deficiency. PATIENTS AND METHODS: Data on all patients with congenital FXI or FVII deficiency and a thrombotic event were gathered by means of a time unlimited PubMed search carried out in June 2014 and in February 2015. Appropriate keywords including the medical subject headings were used in both instances. Side tables were also consulted and cross-checking of the references was carried out to avoid omissions. The thrombosis event had to be proven by objective methods. RESULTS: Forty-three patients with FXI deficiency had arterial thrombosis and only eight had venous thrombosis. On the contrary, only five patients with FVII deficiency had arterial thrombosis whereas 31 patients had venous thrombosis. The arterial/venous ratios were 5.37 and 0.17 for FXI or FVII, respectively. CONCLUSIONS: Arterial thrombosis is frequent in FXI deficiency whereas venous thrombosis is rare. The reverse is true for FVII deficiency. The significance of these findings is discussed especially in view of the recent use of synthetic anti-FXI compounds in the prophylaxis of post-orthopedic surgery of venous thrombosis complications.

Pathogenetic role of Factor VII deficiency and thrombosis in cross-reactive material positive patients.

Congenital Factor VII (FVII) deficiency can be divided into two groups: cases of "true" deficiency, or cross-reactive material (CRM) negative and variants that are cross-reactive material positive.The first form is commonly recognized as Type I condition whereas the second one is known as Type II. FVII deficiency has been occasionally associated with thrombotic events, mainly venous. The reasons underlying this peculiar manifestation are unknown even though in the majority of associated patients thrombotic risk factors are present. The purpose of the present study was to investigate if a thrombotic event was more frequent in Type I or in Type II defect.The majority of patients with FVII deficiency and thrombosis belong to Type II defects. In the following paper we discuss the possible role of the dysfunctional FVII cross-reaction material as a contributory cause for the occurrence of thrombosis.

Homozygous FVII deficiencies with different reactivity towards tissue thromboplastins of different origin.

The reagents most frequently used for FVII activity assay are obtained by rabbit brain or human placenta. In recent years, human recombinant thromboplastins have received great attention. FVII activity in FVII deficiency is usually low, regardless of the thromboplastin used. There are a few exceptions to this rule. These are represented by FVII Padua (Arg304Gln), FVII Nagoya (Arg304Trp), and FVII (Arg79Gln). In these three instances, clear discrepancies were noted in the FVII activity depending on the thromboplastin used. This indicates that at least two areas of FVII are involved in tissue binding, namely an epidermal growth factor domain of the light chain (Arg79Gln) and the catalytic domain (Arg304), controlled by exons 4 and 8, respectively. Since these three variants are cross reactive material positive, namely they are Type 2 defects, all other variants with normal antigen should be investigated by a panel of at least three tissue thromboplastins (rabbit brain, human tissue or human recombinant, and ox brain derived) in order to obtain a satisfactory classification.

[Epidemiology of syphilis: new cases of neurosyphilis]. / Epidemiologia della sifilide: nuovi casi di neurolue.

The Authors report three cases of ophthalmic neurosyphilis in patients who complained a visual decrease monocular. The diagnosis was performed with physical and fundus examination, electrophysiological, hemato-chemical and microbiological tests, fluorangiografy and RMN. The physical examination provided standard results about eyes interested while the fundus examination, as well as the electrofunctional and fuorangiografy examinations, showed some alterations. The sockets and encephalon RMN were normal. Moreover; the patients were submitted to specific haematic and microbiological laboratory tests which showed positivity for syphilis. To sum up all patients received an incidental diagnosis of syphilis. This trend could be attributable to an extensive use of antibiotics that changing the natural course of disease, mask clinical evidences and make them harder to diagnose.

Persistent validity of a classification of congenital factor X defects based on clotting, chromogenic and immunological assays even in the molecular biology era.

An adequate classification of congenital bleeding disorders is of great importance in clinical practice. This is true also for factor X (FX) deficiency. This defect is classified in two forms: type I (cases with low activity and antigen) and type II (cases with low activity and variable levels of antigen). The introduction of molecular biology techniques has allowed a classification based on the site of mutation (propeptide, Gla-domain, catalytic domain etc.) or on the type of mutation (missense, nonsense, deletion etc.). However, with a partial exception for defects in the Gla-domain, no site or type of mutation yields a constant and/or typical phenotype. Due to these difficulties, a classification based on clotting, chromogenic or immunological assays is still the most suited for clinical purposes. A satisfactory classification that takes into account recent advances of FX deficiency could read today as follows: • Type I (cross-reacting material (CRM) negative) (Stuart like) • Type II (CRM positive with inert protein) (Prower like) • Type III (CRM positive with disreactive protein) 1. Defects in all activity systems but for RVV activation (Friuli like) 2. Defects only or predominantly in the extrinsic-Xase system (Padua like) 3. Defects only or predominant in the intrinsic-Xase system (Melbourne like) 4. Defects with discrepant (high) chromogenic assays. Finally, type IV should be added to include cases of FX deficiency associated with FVII deficiency usually due to chromosome 13 abnormalities. By using this nosographic approach, all reported cases of FX deficiency can be adequately allocated to one of these groups.

[The scientific contributions by the Roman School of Hygiene on the microbiological quality of the surface waters of Rome and her County from 1890 to 2010. A systemic review]. / La produzione scientifica della Scuola Romana di Igiene sulla qualità microbiologica dei corpi idrici superficiali di Roma e Provincia dal 1890 al 2010. Una review sistematica.

Research on quality of surface waters has been performed also in Italy during the development of the large urban areas, and in Rome this has been the duty of the Istituto di Igiene of the Sapienza University since 1890. Using MedLine--and also traditional consultation for papers printed before 1968--we identified 100 articles printed in the period 1890-2010. Thirty of them met the inclusion criteria (to have been written by researchers belonging to the Rome universities and to contain microbiological informations about the surface waters of Rome). The majority of papers identified (46.6%) were produced during the years Sixties and Seventies of the 20th century, and 30% in the twenty years to follow (1980-1999). The most frequent microbiological descriptors were "Total coliforms" and "Streptococci". The waterbodies most investigated were the Tiber river and the coastal waters around Fiumicino, where the Tiber flows into the Tyrrhenian sea. The quality of surface waters has always been a central interest of the research performed by the Hygienists of the Roman School. The good quality of the past research and the renovated interest of International Organizations and of the European Union should encourage the public health researchers toward a strategic field of investigation which has strong interconnections with the protection of the individual and community health and also with the protection of the environment.

Unexplained discrepancies in the activity--antigen ratio in congenital FX deficiencies with defects in the catalytic domain.

Studies on molecular biology have considerably enhanced our understanding of congenital coagulation disorders but have failed so far to supply tools for an adequate classification of defects. In fact, mutations in the same domain may give rise to different phenotypes. Conversely, mutations in different domains, controlled by different exons, may cause similar patterns. The 37 kindreds with congenital factor X (FX) deficiency, known to have a defect in the catalytic domain, have been evaluated in an attempt to investigate the genotype-phenotype relation. Discrepant results were obtained because about half kindreds showed a type I pattern, namely a concomitant decrease in FX activity and antigen. The other half showed a type II pattern, namely a decrease in FX activity with a normal or near normal FX antigen. In a few instances, the allocation of the kindred either to type I or to type II defect could not be reached, due to the lack of information about the antigen. The comparison of the kindreds in which the same mutation has been discovered by different investigations is not always possible also for lack of information. The study analyzes the need to have a multipronged approach to the study of congenital FX deficiency. The indication of a mutation in a given domain does not provide clear information about the phenotype.

Control of ovulation-induced hemoperitoneum by oral contraceptives in a patient with congenital hypoprothrombinemia and in another with congenital factor V deficiency.

Hemoperitoneum is a serious and often life-threatening bleeding manifestation. This is particularly true for women who carry congenital bleeding disorders. We describe here a hemoperitoneum occurring in 1 patient with congenital prothrombin deficiency and another with congenital factor V deficiency. Both patients have been followed by us for many years. The patient with prothrombin deficiency underwent laparoscopy but was treated consecutively with whole blood, plasma transfusions and 1,000 units of prothrombin complex concentrates. Response was good and she was then placed on oral contraceptives (OC) which prevented any recurrence. The patient with factor V deficiency presented several episodes of ovulation-related bleeding which required hospitalization and fresh frozen plasma transfusions. On the fifth occasion, the patient had to undergo surgery, and a left oophorectomy was carried out. After this last episode, she was also placed on OC which were very effective in preventing further recurrences. Both patients tolerated the medications very well which, in addition, were able to control menometrorrhagia with a consequent decrease over time in transfusional needs. OC are the treatment of choice in congenital bleeding disorders to control both the menorrhagia and, more importantly, ovulation-related hemoperitoneum.