[Implementing clinical pathways: some practical notes]. / L'implementazione dei percorsi: note pratiche.

The traditional biomedical paradigm is no longer a guarantee of quality for health care, facing increasingly difficult challenges caused by chronic diseases and increasingly fragmented resources that current healthcare systems are dealing with. Health care organizations, considered to be the most complex enterprises of the modern era, must be able to focus on the flow of patients, integrating primary and secondary care through tools such as the Integrated Care Pathways (ICP). This brief discussion attempts to define the ICP its purposes, the elements that characterize it, its limitations and the mechanisms to push for a successful implementation. In order to highlight the elements and basic steps for the creation of an ICP, the authors have compared five different clinical pathways, whose implementation they have contributed to. The comparison was made using two grids: the first showing the essential elements for the definition of lCP and the second one with features that can facilitate their effectiveness. The conclusions of the work show what, pursuing the construction of a pathway, we must never forget: to analyze the gap between the clinical-care activities performed and the theoretical framework provided by the evidence; to see the barriers to change that may impede the implementation; to involve all actors in the system, with particular attention to patients and their associations, and finally to provide a plan for information and education, addressed to health professionals and patients as well.

The role of extracellular conditions during CaCo-2 cells growth: a preliminary study for numerical model validation.

OBJECTIVES: One important limitation in cell therapy protocols, and regenerative medicine (an innovative and promising strategy for different pathologies treatment), is the lack of knowledge about cells engraftment, proliferation and differentiation. In order to allow an efficient and successful cell transplant, it is necessary to predict the logistics, economic and timing issues during cellular injection. It has been reported that several parameters, such as cells number, temperature and extracellular pH (pH0) value can influence metabolic pathways and cellular growth. Numerical analysis and model can help to reduce and understand the effects of the above environmental conditions on cell survival. The aim of this paper is to develop the first step of cells transplantation in order to identify "in vitro", which parameters can be useful to develop and validate a numerical model, able to evaluate "in vivo" cells engraftment and proliferation. MATERIAL AND METHODS: We studied the variation of extracellular parameters--such as medium volume, buffer system, nutrient concentrations and temperature on human colon carcinoma cells (CaCo-2) "in vitro culture"--pursuing the goal of understanding in deeper details cellular processes such as growth, metabolic activity, survival and pH0. RESULTS: Results showed that CaCo-2 cells growth and mortality increase after two days in culture when cells were suspended in 3.5 ml volume to respect of 10 ml volume. Different temperature values influenced CaCo-2 cells growth and metabolic activity showing a direct relationship with the volume of the medium. CONCLUSIONS: Our results describe as CaCo-2 cell growth, metabolic activity, mortality and extracellular pH were influenced by extracellular parameters, enabling us to develop and validate a numerical model to be use to predict cells engraftment and proliferation.

Cardiac resynchronization therapy: could a numerical simulator be a useful tool in order to predict the response of the biventricular pacemaker synchronization?

BACKGROUND AND OBJECTIVES: Cardiac resynchronization therapy (CRT) can be considered as an established therapy for patients with moderate or severe heart failure (HF), depressed systolic function and a wide QRS complex. Biventricular stimulation through the CRT is applied at patients with an intra and/or inter-ventricular conduction delay. The goal of this technique is to resynchronize contraction between and within ventricles. A numerical model of the cardiovascular system, together with the numerical model of the biventricular pacemaker (BPM), can be an useful tool to study the better synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay. SUBJECTS AND METHODS: Within a group of patients which were representative of the most common disease etiologies of heart failure, seven patients, affected by dilated cardiomyopathy undergoing CRT with BPM, were studied and simulated using the numerical model of the cardiovascular system CARDIOSIM. The patients were submitted to echocardiographic evaluation (with pulsate Doppler and tissue Doppler imaging) and electrocardiography evaluation in order to evaluate intra-ventricular and/or inter-ventricular dyssynchrony. These evaluations were made three times: the first one before BPM implantation, the second and the third one respectively within seven days and six months after BPM implantation. Also haemodynamic parameters were measured. Using the software simulator, the pathological conditions before CRT, within seven days and within six months since CRT were reproduced for each patients in order to evaluate the following haemodynamic parameters: the end-systolic and end-diastolic left ventricular volume, the systolic pulmonary arterial pressure, the systolic, diastolic and mean aortic blood pressure and the ejection fraction. Also the trend of the left ventricular elastance was studied for each patient in order to evaluate the benefits produced by the CRT. RESULTS: The results obtained by means the numerical simulator were in good agreement with clinical data measured on the patients. For each patient also the evolution of the left ventricular elastance was in accordance with the literature data. CONCLUSION: The cardiovascular numerical model seems to be a useful tool to study the synchronization of the BPM in order to reduce the inter-ventricular and/or intra-ventricular conduction delay and to reproduce the condition of a patient.

[An organizational model for safety management in health services]. / Un modello organizzativo per la gestione della sicurezza in Sanità.

The authors are reporting a practical experience about safety management of health workers through the adoption of a management model inspired to the indications of International Standard for Quality Management. In the discussion they describe the integration path between the Prevention and protection Service and the Quality Office of the University Hospital of Bologna in order to promote the accomplishment of a progressive spirit of collaboration through the implementation of a shared and common management system which helped in the adoption of appropriate Improvement solutions in order to protect the safety of the health workers.

Virtual cycling effort is dependent on power update rate.

Cycling ergometer protocols are commonly integrated with a virtual reality environment (VRE), especially because of its static position that also allows multiple exercise experiments. Concerning VRE scenarios, visually delayed situations like the ones produced at excessive low update rates can also affect the sense of presence and physiological responses. However, the main interface between the subject and a cycling VRE is the power applied over the crank, and there are only a few experiments to evaluate the effect of delayed situations on this particular interface. Thus, this work aims to investigate the effects of the power update rate (PUR) over the subject`s performance on an avatar-based simulator during a drafting task. A custom cycling VRE was built, and 21 male recreational cyclists (175.9 ± 7.5 cm; 76.5 ± 13.9 kg) were tested at six different PUR levels from 100 to 3000 ms. As a result, PUR affects performance scores (virtual distance, efficiency, and heart rate, p < 0.01) at the given VRE conditions. The case-by-case analysis of the groups reveals that higher update rates always lead to a statistical equivalent or superior performance. Nevertheless, no parameter shows any group difference between 500 ms and lower PUR. These results suggest that virtual cycling protocols should consider PUR and other delay-related mechanisms as possible intervening factors over physiological responses and performance scores.

Application of a user-friendly comprehensive circulatory model for estimation of hemodynamic and ventricular variables.

PURPOSE: Application of a comprehensive, user-friendly, digital computer circulatory model to estimate hemodynamic and ventricular variables. METHODS: The closed-loop lumped parameter circulatory model represents the circulation at the level of large vessels. A variable elastance model reproduces ventricular ejection. The circulatory model has been modified embedding an algorithm able to adjust the model parameters reproducing specific circulatory conditions. The algorithm reads input variables: heart rate, aortic pressure, cardiac output, and left atrial pressure. After a preliminary estimate of circulatory parameters and ventricular elastance, it adjusts the amount of circulating blood, the value of the systemic peripheral resistance, left ventricular elastance, and ventricular rest volume. Input variables and the corresponding calculated variables are recursively compared: the procedure is stopped if the difference between input and calculated variables is within the set tolerance. At the procedure end, the model produces an estimate of ventricular volumes and Emaxl along with systemic and pulmonary pressures (output variables). The procedure has been tested using 4 sets of experimental data including left ventricular assist device assistance. RESULTS: The algorithm allows the reproduction of the circulatory conditions defined by all input variable sets, giving as well an estimate of output variables. CONCLUSIONS: The algorithm permits application of the model in environments where the simplicity of use and velocity of execution are of primary importance. Due to its modular structure, the model can be modified adding new circulatory districts or changing the existing ones. The model could also be applied in educational applications.

[Prospective observational study of pneumonia in an Italian hospital]. / Studio osservazionale prospettico delle polmoniti in un ospedale italiano.

A prospective observational study was conducted during a two-year period to evaluate the prevalence of hospitalized pneumonia in six hospital units of the Bologna S.Orsola-Malpighi hospital (Italy). The selected units were: general surgery, general medicine, internal medicine, geriatrics, respiratory physiopathology and pneumology, with a total of 205 beds and around 4,800 admissions per year. Data were collected from the clinical cards and cases of pneumonia were distinguished by origin (community-acquired or hospital-acquired according to CDC definition), individual and clinical characteristics, and aetiology. The study involved 486 cases of pneumonia: 75 hospital-acquired and 411 community-acquired (84.6%). Patients affected by hospital-acquired pneumonia were older (average age 77 years) compared to community-acquired cases (74 years) and show a more homogeneous gender distribution (males: 48.0% vs 59.4%). Hospital stays (42 vs 21 days) and mortality rates (24.0% vs 11.7%) were significantly higher in hospital-acquired pneumonia. The incidence rate of nosocomial pneumonia was 7.4 per 1000 hospitalized patients and increased to 17-23 per 1000 in the pneumology and respiratory physiopathology units. Only 16.9% of cases had an aetiological diagnosis (14.1% community-acquired; 31.8% hospital-acquired); the most common isolates were S. aureus and P. aeruginosa. The hospital-acquired cases were caused by Gram-negative bacilli more often than the community-acquired cases, and infections were more frequently polymicrobial (37.5% vs 3.4%). In order to reduce morbidity and mortality due to pneumonia it is important to implement prevention measures in the community (i.e. specific vaccination campaigns), improve clinical protocols for aetiological diagnosis in hospitalised patients and increase epidemiological surveillance of hospital-acquired infections.

Right ventricular assistance by continuous flow device. A numerical simulation.

OBJECTIVES: This work is another step in the development of the circulatory model CARDIOSIM and of its model library. Continuous flow assistance is often used to support the right ventricular failure. Computer simulation is one of the methods to study the effect of this assistance on the failing ventricle. The purpose of this study was to evaluate the effect of this support on some hemodynamic variables, when different right ventricular end-systolic elastance and pump speed values were applied. METHODS: The rotary blood pump model was included into the software package CARDIOSIM, which reproduces the cardiovascular system. Lumped parameters models were used to reproduce the circulatory phenomena. Variable elastance models reproduced the Starling's law of the heart for both ventricles. In the study right ventricular end-systolic elastance (EmaxRIGHT) and the rotational speed of the pump took three different values. All the other parameters of the model were constants. RESULTS: The rotational speed of the pump had a significant influence on right ventricular end-diastolic and end-systolic volumes, right atrial pressure (Pra), right ventricular (Qro) and pump flows. The effects on pulmonary arterial pressure (Pap) were more evident when the right ventricular end-systolic elastance was low. When the speed of the device increased the mean value of Pra decreased for each value of EmaxRIGHT. The total flow (Qro+pump flow) increased when the speed of the pump increased. CONCLUSIONS: Our simulation (in good agreement with the results presented in literature) showed that Hemopump produces a rise in total flow, a drop in blood flow pumped out by the right ventricle and a drop in right atrial pressure.

The impact of rotary blood pump in conjunction with mechanical ventilation on ventricular energetic parameters - numerical simulation.

OBJECTIVES: Aim of this work is to study the impact of left ventricular rotary blood pump assistance, on energetic variables, when mechanical ventilation (MV) of the lungs is applied. METHODS: Computer simulation was used to perform this study. Lumped parameter models reproduce the circulatory system. Variable elastance models reproduce the Starling's law of the heart for each ventricle. After the reproduction of ischemic heart disease left ventricular assistance was applied using a model of rotary blood pump. The pump speed was changed in steps and was assumed to be constant during each step. The influence of mechanical ventilation was introduced by different values of positive mean thoracic pressure. RESULTS: The increase of the rotational speed has a significant influence on some ventricular energetic variables. In fact it decreased left ventricular external work, left and right ventricular pressure-volume area and the left ventricular efficiency. Finally, it increased the right ventricular efficiency but had no influence on the right ventricular external work. The increase of thoracic pressure from -2 to +5 mmHg caused a significant decrease of external work, pressure-volume area (right ventricular pressure-volume area dropped up to 50%) and an increase of right ventricular efficiency (by 40%) while left ventricular efficiency remained almost stable. CONCLUSIONS: Numerical simulation is a very suitable tool to predict changes of not easily measurable parameters such as energetic ventricular variables when mechanical assistance of heart and/or lungs is applied independently or simultaneously.

Modelling in the study of interaction of Hemopump device and artificial ventilation.

The aim of this work is to evaluate in different ventricular conditions the influence of joint mechanical ventilation (MV) and Hemopump assistance. To perform this study, we used a computer simulator of human cardiovascular system where the influence of MV was introduced changing thoracic pressure to positive values. The simulation confirmed that haemodynamic variables are highly sensitive to thoracic pressure changes. On the other hand, Hemopump assistance raises, among the others, mean aortic pressure, total cardiac output (left ventricular output flow plus Hemopump flow) and coronary flow. The simulation showed that the joint action of Hemopump and positive thoracic pressure diminishes these effects.

Repeated plasticization and recovery of cuticular stiffness in the blood-sucking bug Triatoma infestans in the feeding context.

Triatominae bugs experience changes in the mechanical properties of their cuticle prior to feeding. This process-plasticization-allows a rapid stretching of the unsclerotized abdominal cuticle of triatominae larvae and it is evoked by sensory inputs related to feeding. We tested: (a) whether the cuticle recovers its original mechanical properties after plasticization, (b) whether repeated stimulation would be able to evoke recurrent plasticization along the same larval instar, (c) the temporal course of recovering cuticular stiffness. We injected Ringer solution into the body cavity of the bugs at constant pressure, using the injection rate (ml/min) as a measure of the cuticle extensibility. To trigger plasticization, individuals were allowed to feed on blood from an artificial feeder at 32+/-2 degrees C. After plasticization occurred, the abdominal cuticle gradually recovered its original mechanical properties. Bugs were capable of plasticizing for a second time when repeatedly stimulated. The effects of plasticization vanished between 1 and 2 h after stimulation. Although one full meal could suffice to accomplish moult in other Triatomine species, Triatoma infestans is able to feed repeatedly during a single larval instar. Accordingly to this, their cuticle recovers stiffness in some hours and becomes able to respond repeatedly to sensory inputs associated with feeding.

In vivo and simulation study of artificial ventilation effects on energetic variables in cardiosurgical patients.

OBJECTIVES: The analysis of energetic ventricular variable changes during artificial ventilation, obtained by numerical simulation was done. Twenty-one sets of hemodynamic parameters for eight cardiosurgical patients were used to estimate left and right stroke work. The data were collected for three methods of ventilation: conventional, lung-protective (with minute ventilation diminished by half) and high frequency ventilation (with frequency 5, 10, or 15 Hz). METHODS: The computer simulator (CARDIOSIM) of the cardiovascular system, was used as a tool to calculate values of energetic ventricular variables for conditions that corresponded to these during in vivo measurements. Different methods of ventilation caused differences of intrathoracic pressure, haemodynamic and finally energetic ventricular variables. The trends of these variable changes were the same in in vivo and simulation studies, in the whole range of intrathoracic pressure changes (Pt = 1.5-3.5 mmHg). RESULTS: As values of main hemodynamic variables like cardiac output or arterial, systemic and pulmonary pressures were very close in both studies. Cardiac index and left ventricular stroke work also differed less than 10% for all examined patients and computer simulation. In a case of right ventricular stroke work the difference between in vivo data and simulation was a bit greater than 10% for two of eight patients under study. CONCLUSIONS: Our comparative analysis proved that numerical simulation is a very useful tool to predict changes of main hemodynamic and energy-related ventricular variables caused by different levels of positive Pt. It means that it can help an anesthesiologist to choose an appropriate method of artificial ventilation for cardiosurgical patients.

Development of a hybrid (numerical-hydraulic) circulatory model: prototype testing and its response to IABP assistance.

Merging numerical and physical models of the circulation makes it possible to develop a new class of circulatory models defined as hybrid. This solution reduces the costs, enhances the flexibility and opens the way to many applications ranging from research to education and heart assist devices testing. In the prototype described in this paper, a hydraulic model of systemic arterial tree is connected to a lumped parameters numerical model including pulmonary circulation and the remaining parts of systemic circulation. The hydraulic model consists of a characteristic resistance, of a silicon rubber tube to allow the insertion of an Intra-Aortic Balloon Pump (IABP) and of a lumped parameters compliance. Two electro-hydraulic interfaces, realized by means of gear pumps driven by DC motors, connect the numerical section with both terminals of the hydraulic section. The lumped parameters numerical model and the control system (including analog to digital and digital to analog converters)are developed in LabVIEW environment. The behavior of the model is analyzed by means of the ventricular pressure-volume loops and the time courses of arterial and ventricular pressures and flows in different circulatory conditions. A simulated pathological condition was set to test the IABP and verify the response of the system to this type of mechanical circulatory assistance. The results show that the model can represent hemodynamic relationships in different ventricular and circulatory conditions and is able to react to the IABP assistance.

Lung assist devices influence cardio-energetic parameters: Numerical simulation study.

We aim at an analysis of the effects mechanical ventilators (MVs) and thoracic artificial lungs (TALs) will have on the cardiovascular system, especially on important quantities, such as left and right ventricular external work (EW), pressure-volume area (PVA) and cardiac mechanical efficiency (CME). Our analyses are based on simulation studies which were carried out by using our CARDIOSIM(©) software simulator. At first, we carried out simulation studies of patients undergoing mechanical ventilation (MV) without a thoracic artificial lung (TAL). Subsequently, we conducted simulation studies of patients who had been provided with a TAL, but did not undergo MV. We aimed at describing the patient's physiological characteristics and their variations with time, such as EW, PVA, CME, cardiac output (CO) and mean pulmonary arterial/venous pressure (PAP/PVP). We were starting with a simulation run under well-defined initial conditions which was followed by simulation runs for a wide range of mean intrathoracic pressure settings. Our simulations of MV without TAL showed that for mean intrathoracic pressure settings from negative (-4 mmHg) to positive (+5 mmHg) values, the left and right ventricular EW and PVA, right ventricular CME and CO decreased, whereas left ventricular CME and the PAP increased. The simulation studies of patients with a TAL, comprised all the usual TAL arrangements, viz. configurations "in series" and in parallel with the natural lung and, moreover, hybrid configurations. The main objective of the simulation studies was, as before, the assessment of the hemodynamic response to the application of a TAL. We could for instance show that, in case of an "in series" configuration, a reduction (an increase) in left (right) ventricular EW and PVA values occurred, whereas the best performance in terms of CO can be achieved in the case of an in parallel configuration.

Mortality among drug users in the AIDS era.

BACKGROUND: Infection with human immunodeficiency virus type 1 (HIV-1) causes progressive immune deficiency, the acquired immunodeficiency syndrome (AIDS), and death. Mortality, however, particularly with causes other than AIDS, deserves further study. A retrospective cohort study among drug users in Italy was performed to estimated absolute and proportional mortality rates due to AIDS and other causes, with or without HIV-1 infection. METHODS: All subjects who enrolled between January 1980 and July 1990 in the drug treatment programme in the Province of Bologna, Italy, were included in the cohort. Each subject was categorized for HIV-1 antibody status (positive, negative, untested), vital status (in 1990 by national surveillance), and causes of death (by death certificate). Data were analysed with actuarial and time-dependent covariate methods. RESULTS: There were 332 deaths among 4962 drug users who were followed for 21,130 person-years. This mortality rate (1.57 per 100 person-years) was increased 18-fold compared to the general population. Actuarial 10-year mortality estimates were 28.2% for the 2040 HIV-1 positive subjects, 12.1% for the 1859 HIV-1 untested subjects, and 2.5% for the 1063 HIV-1 negative subjects. AIDS contributed to 150 deaths, followed by drug overdose (64 deaths) and trauma (39 deaths). Compared to others in the cohort, mortality with AIDS and non-AIDS causes was reduced for HIV-1 negative subjects. In contrast, mortality for HIV-1 positive subjects was increased with AIDS, trauma, overdose, various bacterial infections, hepatitis, and cirrhosis. CONCLUSIONS: Mortality with HIV-1 infection was associated not only with opportunistic infections and malignancies but also with competing causes of death, particularly hepatic disease. Further investigation is needed to clarify whether alcohol, analgesics, hepatitis viruses, or other agents have enhanced hepatotoxicity for HIV-1 infected patients.

Temperature preference in Rhodnius prolixus, effects and possible consequences.

The present work examines the thermal preference of adult Rhodnius prolixus along a temperature gradient. The mean preferred temperature differed slightly between sexes: 25.0 degrees C for males versus 25.4 degrees C for females. This preference was not constant, but varied daily by about 0.2 degrees C for both sexes, and reached its highest value at the onset of the dark phase and was lowest during the light phase. A change in the preferred temperature with the level of starvation was also observed (about 1 degrees C lower after 20 days of starvation). Changes in environmental temperature strongly affected the rate of weight loss for both sexes. When insects were maintained for 20 days in a chamber at 32 degrees C, they lost significantly more weight than when kept at 24 degrees C; both water loss and nutrient conversion processes are involved. This increase in weight loss rate with increasing temperature would cause a higher biting rate and consequently higher probability of Chagas' disease transmission. Females oviposit across a range of temperatures from 22 to 33 degrees C with a peak at 25-26 degrees C. These results are compared with patterns of thermopreference in other species of triatomine, as related to differences in their distribution and tolerance to starvation.

Temperature and relative humidity affect the selection of shelters by Triatoma infestans, vector of Chagas disease.

The preference of Triatoma infestans for shelters at different temperatures or relative humidities (RH) was tested in laboratory assays. The insects preferred refuges at a temperature of 34 degrees C rather than 26 degrees C, and chose to stay in refuges with an RH of 20% rather than 80%. Temperature and RH records made inside and outside experimental chicken-houses under natural climatic conditions showed that such habitats tend to maintain an inner climate favourable to T. infestans. Typical refuges in adobe walls showed strongly damped fluctuations in minimum and maximum temperatures, and delayed changes in these parameters when compared with an external reference. Similarly, the jarilla (Larrea sp.), a plant used for constructing roofing, damps fluctuations in minimum and maximum RH and delays these RH fluctuations when compared to an external reference. We discuss possible effects of environmental factors on the distribution of insects in human dwellings, and analyse the environmental characteristics of normally available refuges in materials used for house building in endemic zones.

Activity pattern in relation to refuge exploitation and feeding in Triatoma infestans (Hemiptera: Reduviidae).

The pattern of locomotion activity was studied in Triatoma infestans, in relation to the use of an artificial refuge offered to the bugs in an experimental arena. In assays performed with insects that had a post-ecdysis starvation period of 1 week, the activity was low and mainly related to refuge leaving or entering. Insects that had gone through a longer period of starvation (6 weeks) exhibited a high locomotory activity throughout the night. Specific temporal windows were detected for refuge leaving and entering after dusk and before dawn, which were not modified by different levels of starvation of the insects. T. infestans exhibits a higher motivation for feeding during the first night hours, in comparison to that observed at the end of the scotophase. The activity peaks previously reported for T. infestans are therefore related to host and refuge search.

Comparison of disturbance stridulations in five species of triatominae bugs.

It has been observed that Triatoma infestans and Rhodnius prolixus females stridulate to reject copulatory attempts performed by males. In addition, triatomines stridulate when disturbed or handled. In the present study, the temporal structure and frequency spectra of vibrational signals produced by mechanically disturbed T. infestans, T. sordida, T. guasayana, R. prolixus and Dipetalogaster maxima were analysed and compared. The inter-ridge distances of the prosternal stridulatory organ of the same species were also measured. The frequency spectra and repetition rates were similar, despite individuals of these five species have different sizes, their stridulatory grooves have different inter-ridge distances, and also their vibratory signals exhibited different temporal patterns. The hypothesis that disturbance stridulations are non-specific signals and could function to deter predators was discussed.