[Safety Walkround as a risk assessment tool: the first Italian experience]. / La Safety WalkRoundTM un'opportunità per l'assessment del rischio: la prima esperienza italiana.

In 2007 the Study Group "Clinical Risk Management" of the Italian Society of Anaesthesia and Intensive Care Unit (SIAARTI) performed a multicentric study in Intensive Care Unit (ICU) to assess the feasibility and efficacy of the Safety WalkRound (SWR) as a tool for the risk assessment. As the environment and organization of ICU are more complex than anaesthesia ones, mainly due to the severity of patients, high number of involved healthcare givers and different kinds of procedures, the Study Group decided that a check list is not fit for ICU and , after a careful review of the literature, chose to test the Safety WalkRound. in four Italian General ICUs. The SWR was born in 2003 when Frankel plans a structured interview of 15 questions (about 50% open) to collect operators' opinion about rate and type of errors, near misses, communication, problems regarding the report of adverse events and suggestions to increase patient safety. Consequently SWR is a tool of risk assessment alternative to the Incident Reporting which is marked by a diffuse underreporting of operators. Although the SWR is a new tool not validated in Italian language neither published in Italy on PubMed journals , the Study Group has decided that it might be fit for the organization of Italian Healthcare System. A back translation of the validated model of Joint Commission was provided and the translated version has been lightly changed to be employed in hospitals with and without Incident Reporting . The questions have been changed or introduced on the basis of the organization vulnerabilities detected with observational techniques or Focus Group. The interview performed in Italy contains 16 questions classified into five groups: a) error, b) error prevention, c) communication, teamwork and leadership, d) error discussion and e) relationship with patients and their families. The answers collected have been analyzed to detect the vulnerabilities in the organizations and specify the improvements to implement in every ICU. A statistical analysis was performed to verify the correlation between the answers collected and the results of the other techniques of risk assessment previously used ( observations and Focus Group ) . The value of k Pearson found ( mean value 0,976) has demonstrated this correlation and the efficacy of SWR in detecting system vulnerabilities already found with the other assessment techniques. The value of a Cronbach ( mean value 0,798) has demonstrated an internal consistency reliability. The results of this study have demonstrated that the Italian translation is fit for the model by Frankel and makes available a lot of information useful to improve patient safety. The study has demonstrated the sensibility, efficacy and efficiency of this tool in detecting the vulnerabilities in every ICU of the four ones. SWR is marked by feasibility, high compliance of operators and low costs; besides increases safety culture in the staff and demonstrating.

Novel Genetic Variants in Carboxylesterase 1 Predict Severe Early-Onset Capecitabine-Related Toxicity.

An important concern with the anticancer drug capecitabine (Cp), an oral prodrug of 5-fluorouracil, are dose-limiting adverse effects, in particular hand-foot syndrome (HFS) and diarrhea. Here we evaluated the association of genetic variability in all enzymes of the Cp-activation pathway to 5-fluorouracil with Cp-related early-onset toxicity in 144 patients receiving Cp. We identified a haplotype encompassing five variants in the carboxylesterase 1 (CES1) gene region including an expression quantitative trait locus associated with early-onset Cp-toxicity (Haplotype A3: ORadditive = 2.2, 95% CI 1.2-4.0, Padjusted = 0.012; ORrecessive = 10.3, 95% CI 2.1-49.4, Padjusted = 0.0038). Furthermore, the association of two linked cytidine deaminase (CDA) promoter variants (c.1-451C>T: ORdominant = 4.3, 95% CI 1.3-14.2, Padjusted = 0.017; and c.1-92A>G: ORdominant = 4.4, 95% CI 1.3-14.5, Padjusted = 0.015) with Cp-related diarrhea was replicated. This first study identifying an association of genetic variation in CES1 with Cp-related toxicity provides further evidence for the existence of a functional noncoding CES1-variant with a possible regulatory impact.

Dogs as victims of their own worms: Serodiagnosis of canine alveolar echinococcosis.

BACKGROUND: Besides acting as definitive hosts for Echinococcus multilocularis, dogs can become infected by the larval form of this parasite and thereby develop life-threatening alveolar echinococcosis (AE). Although AE is a zoonotic disease, most therapeutic and diagnostic approaches have been developed for human patients. In dogs, AE is typically diagnosed in the advanced stage of the disease when the parasitic mass has already caused abdominal distension. At that stage, complete resection of the parasitic mass is often impossible, leaving a guarded prognosis for the affected dogs. For humans, sensitive and specific diagnostic protocols relying on serology have been validated and are now widely used. In contrast, sensitive and specific laboratory diagnostic tools that would enable early diagnosis of canine AE are still lacking. The aim of the current study was to establish a serological protocol specifically adapted to dogs. METHODS: We tested several native and recombinant antigens (EmVF, Em2, recEm95, recEm18) in in-house ELISA, an in-house Western blot (WB), as well as a commercially available WB developed for serodiagnosing human AE (Anti-Echinococcus EUROLINE-WB®), using a panel of known status dog sera. RESULTS: RecEm95-antigen was revealed to be the most promising antigen for use in ELISA, demonstrating 100% (95% CI: 72-100%) sensitivity and 100% (95% CI: 93-100%) specificity in our study. The in-house WB using EmVF antigen performed as well as the recEm95-ELISA. The commercial WB also correctly identified all infected dogs, coupled with a specificity of 98% (95% CI: 91-100%). CONCLUSION: The recEm95-ELISA alone or in combination with either the in-house WB or the Anti-Echinococcus EUROLINE-WB® (IgG) with a minor modification should be considered as the best current approach for the serological diagnosis of dogs infected with the larval stage of E. multilocularis. However, larger studies with a focus on potentially cross-reacting sera should be undertaken to verify these findings.

[Neutropenia in glycogenesis I B]. / Neutropenia nella glicogenosi IB.

Type IB Glycogen storage disease (GSD) is a new variant of type I Glycogen storage disease. It is characterized by same clinical findings: hepatomegaly, fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis, renal enlargement, short stature; but it distinguish for normal glucose-6-phosphatase hepatic activity in vitro. The involvement is in G-6-P transport system. Recently has been described in some patients with GSD IB, neutropenia and defective neutrophil mobility. In this report the authors described two family cases of GDS IB that one characterized by severe neutropenia.

[Lawrence Moon Biedl Bardet, a polymorphic syndrome]. / Laurence Moon Biedl Bardet, una sindrome polimorfa.

The Laurence Moon Biedl Bardet syndrome is a polymorphous disease whose pathogenesis is still obscure. It is characterize by obesity, oligophrenia, polidactylia, retinitis pigmentosa, hipogonadism, but often there are various others symptoms. AA describe two cases. After a short explanation of de main features of this disease, they dwell upon the study of clinical objective symtomatology and upon instrumental and laboratory parameters regarding hormonal, metabolic and functional order of various organs and apparatuses. Both cases present all classic symptoms of this disease. In the first case we have noticed a deficit in LH and FSH, besides we have also noticed an asymmetry of the lateral ventricles of the brain prevalently on the right and a small increase in 17-KS and 17-OH-KS urinary. On the contrary in the second case we have noticed an EEG of epileptic type.

Effects of high altitude acclimatization on heart rate variability in resting humans.

The sympatho-vagal nerve interaction at the heart was studied by means of power spectrum analysis of heart rate variability in seven Caucasians (aged 27-35 years) in resting supine and sitting positions before and during 35 days of a sojourn at 5050 m above sea level (asl) and in six Sherpas (aged 22-30 years) at high altitude only. A high frequency peak (HF)-central frequency between 0.20 and 0.33 Hz, a low frequency peak (LF)-central frequency between 0.08 and 0.14 Hz, and a very low frequency component (< 0.05 Hz), no peak observed, were found in the power spectrum in both positions and independent of altitude. The peak powers, as a percentage of the total power, were affected by both body position and altitude. At sea level the change from a supine to a sitting position yielded a decrease in percentage HF from 25 (SEM 1.9)% to 6.2 (SEM 1.5)% (P < 0.05) and a significant increase in the ratio between LF and HF powers (LF:HF) from 1.7 (SEM 0.4) to 6.9 (SEM 1.6). At altitude compared to sea level in the supine position, percentage HF decreased from 25% to 10.9 (SEM 1.0)% (P < 0.05) and the LF:HF ratio increased from 1.7 to 4.8 (SEM 0.7) (P < 0.05). No changes occurred at altitude in the sitting position either in the peak powers or in the LF:HF ratio, but the central frequency of HF peak increased significantly from 0.25 (SEM 0.02) Hz to 0.32 (SEM 0.01) Hz. In the Sherpas comparable results to the Caucasians were found in both body positions. The high LF:HF ratios observed at altitude in both body positions and groups would suggest that hypoxia caused a shift of sympatho-vagal nerve interaction at rest toward a dominance of the sympathetic system, which was found at sea level only in the sitting position. An acclimatization period of 10 days higher than 2850 m asl and 1 month at 5050 m asl did not modify the interactions of the autonomic systems.

Metabolic and cardiorespiratory responses to maximal intermittent knee isokinetic exercise in young healthy humans.

There have been many studies on the effects of isokinetic exercise on muscle performance in training and rehabilitative programmes. On the other hand, the cardiovascular and metabolic responses elicited by this type of exercise have been poorly investigated. This study was specifically designed to describe the relationships, if any, between metabolic and cardiorespiratory responses and power output during maximal intermittent knee isokinetic exercise when a steady state is reached. A group of 18 healthy subjects (10 men and 8 women, age range 25-30 years) were requested to perform at maximal concentric isokinetic knee extensions/flexions 60 degrees. s(-1) and 180 degrees. s(-1) for 5 min, with a 5-s pause interposed between consecutive repetitions. The power output (W) was calculated; before and during the tasks heart rate (f(c)) and arterial blood pressure (AP(a)) were continuously monitored. Pulmonary ventilation (V(E)) and oxygen uptake (VO(2)) were measured at the 4th and at the 5th min of exercise and blood lactate concentration at rest and at the 3rd min of recovery. From the 4th to the 5th min only a slight decrease in W was observed, both at 60 degrees. s(-1) and 180 degrees. s(-1). The VO(2), V(E), f(c) and AP(a) showed similar values in the last 2 min of exercise, suggesting that a steady state had been reached. The VO(2) increased linearly as a function of +W, showing a significantly steeper slope at 60 degrees. s(-1) than at 180 degrees. s(-1). The f(c), in spite of a large interindividual variation, was linearly related to metabolic demand, and was not affected by angular velocity. Systolic and diastolic AP(a) were not related either to VO(2) or to angular velocity. In conclusion it would appear that the metabolic response to maximal intermittent knee isokinetic exercise resembles that of dynamic exercise. Conversely, the cardiocirculatory responses would seem to reflect a relevant role of the isometric postural component, the importance of which should be carefully evaluated in each subject.

Effects of 17 days bed rest on the maximal isometric torque of the flexors and extensors of the ankle.

NASA: Researchers examined the extent to which short-term bed rest affects maximal isometric force produced by the plantar and dorsal flexors of the ankle. Results indicate an increase in average values of maximal isometric torque throughout the study, a significant increase in isometric EMG between control and bed rest subjects, and a significant isometric EMG augmentation in bed rest subjects by the end of the study. The effects of training on maximal isometric torque and muscle function impairment are discussed.^ieng

Heart rate variability during dynamic exercise in elderly males and females.

It has been proposed that cardiac control is altered in the elderly. Power spectral analysis of heart rate variability (HRV) was performed on 12 male and 11 female elderly subjects (mean age 74 years) while at rest in supine and sitting positions, and at steady states during 5 min of exercise (35-95% peak oxygen consumption, VO2peak). There were no differences in power, measured as a percentage of the total of the high frequency peak (HF, centred at about 0.25 Hz; 13% in males vs 12% in females), low frequency peak (LF, centred at 0.09 Hz; 25% in males and 22% in females), and very low frequency component (VLF, at 0.03 Hz; 66% in males and 69% in females) between body positions at rest. There was no difference in spectral power between male and female subjects. Total power decreased as a function of oxygen consumption during exercise, LF% did not change up to about 14 ml x kg(-1) x min(-1) (40% and 80% VO2peak in males and females, respectively), then decreased towards minimal values in both genders. HF% power and central frequency increased linearly with metabolic demand, reaching higher values in male subjects than in female subjects at VO2peak, while VLF% remained unchanged. Thus, the power spectra components of HRV did not reflect the changes in autonomic activity that occur at increasing exercise intensities, confirming previous findings in young subjects, and indicated similar responses in both genders.

Effects of 17 days bedrest on the maximal voluntary isometric torque and neuromuscular activation of the plantar and dorsal flexors of the ankle.

Maximal voluntary isometric torque values of the ankle plantar (Tim,PF) and dorsal flexors (Tim,DF) were assessed in eight healthy adult males at 5 degrees and 15 degrees of dorsal flexion (DF) and at 5 degrees, 15 degrees and 25 degrees of plantar flexion (PF) with the knee at right angles, before (two times), during (three times) and after (three times) 17 days of 6 degrees head-down tilt bedrest (BR). Integrated electromyograms (iEMG) were also recorded from the gastrocnemius medialis and tibialis anterior. Tim,PF and the iEMG of the gastrocnemius medialis were significantly larger (by 14% and by 27%, respectively) at the end of recovery than before BR. This was probably the consequence of training and/or habituation leading to: (1) increased activation of the plantar flexors; and (2) decreased co-activation of the antagonist muscles. Neither Tim,DF nor the tibialis anterior iEMG changed significantly. The effects of BR on muscle performance were evaluated as follows. The net torque generated by a given muscle group was assumed to be the algebraic sum of the torque generated by the agonists and by the antagonists. Thus, for the plantar flexors Tim,PF = alpha iEMGGm - beta iEMGTa, where: (1) iEMGGm and iEMGTa are the iEMGs of gastrocnemius medialis and of tibialis anterior during maximal PF; and (2) the constants alpha and beta represent the electromechanical coupling of the plantar (alpha) and dorsal (beta) flexors. Similarly for the dorsal flexors: Tim,DF = beta iEMGTa - alpha iEMGGm, where iEMGTa and iEMGGm are the iEMGs of tibialis anterior and gastrocnemius medialis during maximal DF. Torque and iEMG values were assessed for all subjects under all experimental conditions. Thus, since the biomechanical leverage of the system was constant, alpha and beta could be calculated. During BR, alpha decreased by 25% and it dropped by a further 30% during recovery. In contrast, beta remained almost unchanged. This suggests that, in spite of training and/or habituation, BR significantly impaired the maximal isometric performance of the plantar flexors, an effect that continued during the initial 10 days of recovery.

Body composition and maximum alactic anaerobic performance during a one month stay at high altitude.

Prolonged altitude exposure usually leads to considerable weight loss of which a large part is from muscle tissue. This loss reduces maximum alactic anaerobic muscle power. It was hypothesized that most of the weight loss may simply be the result of malnutrition due to lack of palatable food in an uncomfortable environment. To test this hypothesis eight healthy male subjects (age 33.7 +/- 4.6 S.C. yr), well acclimatized to prevent symptoms of acute mountain sickness, were exposed for 4 weeks to an altitude of 5050 m with access to a large choice of palatable food in comfortable conditions. Body weight (with a scale), body composition (from skinfolds), arm muscle plus bone cross-sectional area (Am + b) and muscle plus bone leg volume (Vm+b) (from skinfolds and circumferences), maximum voluntary contraction force of the elbow flexors (MVC, with a load cell) and maximum jumping height (Hmax, on a platform) were measured before departure (SL) and in the first (ALT1), second (ALT2) and fourth week (ALT4) of their altitude sojourn. Three-day dietary records were obtained at SL and at ALT4. Body mass had decreased significantly at ALT2 (-3.8%) and at ALT4 (-4.6%) likely reflecting changes in body water homeostasis. No changes were found in %fat, Am+b, Vm+b, MVC or Hmax. Average dietary intake at SL was 8.96 +/- 1.45 MJ and had increased to 13.59 +/- 3.07 MJ at ALT4. In conclusion, up to an altitude of 5050 m loss of body mass from fat and muscle tissue, and hence impairment of maximum anaerobic muscle power (alactic) appears to be avoidable by food intake matched to energy expenditure. The latter may be achieved simply by proper acclimatization, sufficient comfort and availability of palatable food.

Body position affects the power spectrum of heart rate variability during dynamic exercise.

The power spectrum analysis of R-R interval variability (RRV) has been estimated by means of an autoregressive method in six men in supine (S) and sitting (C) postures at rest and during steady-state cycle exercise at about 14%, 28%, 45%, 67% of the maximal oxygen consumption (% VO2max). The total power of RRV decreased exponentially as a function of exercise intensity in a similar way in both postures. Three components were recognized in the power spectra: firstly, a high frequency peak (HF), an expression of respiratory arrhythmia, the central frequency (fcentral) of which increased in both S and C from a resting value of about 0.26 Hz to 0.42 Hz at 67% VO2max; secondly, a low frequency peak (LF) related to arterial pressure control, the fcentral of which remained constant at 0.1 Hz in C, whereas in S above 28% VO2max decreased to 0.07 Hz; and thirdly, a very low frequency component (VLF; less than 0.05 Hz, no fcentral). The power of the three components (as a percentage of the total power) depended on the body posture and the metabolic demand. HF% at rest was 30.3 (SEM 6.6) % in S and 5.0 (SEM 0.8) % in C. During exercise HF% decreased by about 30% in S and increased to 19.7 (SEM 5.5) % at 28% VO2max in C. LF% was lower in S than in C at rest [31.6 (SEM 5.7) % vs 44.9 (SEM 6.4) %; P < 0.05], remaining constant up to 28% VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variability in exercising humans: effect of water immersion.

Power spectrum analysis of heart-rate variability was made in seven men [mean age 22 (SEM 1) years] in head-out water immersion (W) and in air (A, control) at rest and during steady-state cycling to maximal intensity (maximum oxygen uptake, VO2max). At rest W resulted in a trebled increase in the total power (P < 0.05), coupled with minimal changes in the power (as a percentage of the total) of the high frequency peak (HF, centred at 0.26 Hz; 18% vs 28%) and of the low frequency peak (LF, 0.1 Hz; 24% vs 32%). A third peak at about 0.03 Hz (very low frequency, VLF) represented the remaining power both in W and A. These changes as a whole indicated that immersion caused a vagal dominance in cardiac autonomic interaction, due to the central pooling of blood and/or the pressure of water on the trunk. Exercise caused a decrease in the total power in W and A. The LF% did not change up to about 50% V02max, thereafter decreasing towards nil in both conditions. The HF% decreased in similar ways in W and A to about half at 55%-60% VO2max and then increased to reach 1.5 times the resting values at VO2max. The central frequency of HF increased linearly with oxygen uptake, showing a tendency to be higher in W than in A at medium to high intensities. The VLF% remained unchanged. The lack of differences in the LF peak between W and A during exercise would suggest that blood distribution had no effect on the readjustments in control mechanisms of arterial pressure. On the other hand, the findings of similar HF powers and the very similar values for ventilation in W and A confirmed the direct effect of the respiratory activity in heart rate modulation during exercise.

The hemodynamic and metabolic effects of tourniquet application during knee surgery.

UNLABELLED: We evaluated the effects of tourniquet application on the cardiovascular system and metabolism in 10 young men undergoing knee surgery with general anesthesia. The duration of inflation was from 75 to 108 min. Heart rate, mean arterial pressure, cardiac index (CI) by pulse contour method, and systemic vascular resistance were measured before, during, and after tourniquet inflation. pH, PaO(2), PaCO(2), and lactate blood concentrations were also measured. VO(2) and VCO(2) were assessed every minute from tracheal intubation up to 15 min after tourniquet deflation and VO(2) in excess of the basal value over the 15 min after deflation (VO(2)exc) was calculated. Mean arterial pressure increased 26% (P: < 0.05) during inflation and returned to basal values after deflation. CI did not change immediately after inflation; although, thereafter, it increased 18% (P: < 0.05). Five minutes after deflation, CI further increased to a value 40% higher than the basal value. Therefore, systemic vascular resistance increased 20% suddenly after inflation (P: < 0.05) and decreased 18% after deflation (P: < 0.05). VO(2) and VCO(2) remained stable during inflation and increased (P: < 0.05) after deflation. VO(2)exc depended on duration of tourniquet inflation time (Tisch) (P: < 0.05). After deflation, PaCO(2) and lactate increased (P: < 0.05) while Tisch increased. We conclude that tourniquet application induces modifications of the cardiovascular system and metabolism, which depend on tourniquet phase and on Tisch. Whether these modifications could be relevant in patients with poor physical conditions is not known. IMPLICATIONS: The clinical effects of tourniquet application were evaluated in 10 young men undergoing knee surgery. Our data indicate that tourniquet application causes hemodynamic and metabolic changes which may become clinically relevant after a long period of tourniquet inflation, particularly in patients with concomitant cardiovascular diseases.