How to reduce erroneous Emergency Department admissions for the frail elderly.

Background: Readmission after a first hospitalization is a common occurrence. It may be due to incomplete treatment, poor care for underlying problems or reflect bad coordination with health services at the time of discharge. The aim of this study was to identify the factors and classify the pathologies that expose elderly patients to erroneous access to the Emergency/Urgency Department (EUD). Study design: Retrospective observational study. Materials and methods: From January 2016 to December 2019 we studied patients who had at least one readmission to the EUD in the six months following discharge. All EUD accesses of the same patient that occurred for the problem treated during the previous hospitalization were identified. Data was provided by the University Hospital of Siena. Patients were stratified by age, gender, and municipality of residence. We used an ICD-9-CM coding system to describe health problems. Statistical analysis was carried out with Stata software. Results: We studied 1,230 patients (46.6% females) the mean age was 78.2 ± 14.3. Most of them, 721 (58.6%) were ≥80 years old, 334 (27.1%) were 65-79, 138 (11.2%) were 41-64, and only 37 (3.0%) were ≤40. Patients who lived in Municipality of Siena had a lower probability to return than to those living in other municipalities (OR 0.76; 95%CI: 0.62-0.93; p<0,05). The main causes of readmission for ≥65 years old were "symptoms, signs and ill-defined conditions" (18.3%), "respiratory diseases" (15.0%), "injury and poisoning" (14.1%), "cardiovascular diseases" (11.8%), "classification of factors influencing health status and contact with health services" (9.8%), "genitourinary diseases" (6.6%) and "digestive diseases (5.7%). Conclusions: We observed that patients residing a greater distance from the hospital facilitates the risk of readmission. The factors that were exposed could be used to identify frequent users and initiate measures to reduce their access.

Comparison of two molecular methods used for subtyping of Legionella pneumophila 1 strains isolated from a hospital water supply.

The results of the pulsed-field gel electrophoresis and the sequence-based typing (using the loci flaA, pilE, asd, mip, mompS and proA) were compared for subtyping of Legionella pneumophila 1 strains isolated from a hospital water supply. Molecular typing was carried out on 61 isolates (38% of the positive samples) selected on space and temporal criteria in order to follow the evolution of the water-system colonization. For all the 61 isolates, the sequence of the amplified mip gene fragment identified Legionella pneumophila strain Wadsworth. Genotype testing by PFGE analysis showed three different patterns, correspondent to three SBT types according to the allelic profiles. Both PFGE and SBT indicated the circulation and the persistence in the hospital potable water-system of three types randomly distributed in space and time. The two molecular methods adopted showed a 100% concordance, although a low degree of genetic heterogeneity characterized the isolates. The electrophoretic patterns were sufficiently unambiguous to consider PFGE a highly discriminatory typing method, but the SBT technique besides accurately characterizing isolates, was able to identify Legionella strains through analysis of the mip gene. A typing method with this level of discriminatory power has great potential for assisting in epidemiological studies.

Laparoscopic cholecystectomy in children with chronic hemolytic anemia. Is the outcome related to the timing of the procedure?

BACKGROUND: The aim of this study was to evaluate whether the outcome in children with chronic hemolytic anemia (CHA) and cholelithiasis undergoing laparoscopic cholecystectomy (LC) is related to the operation timing. METHODS: From June 1995 to December 2004, 46 children with CHA were referred to our division of surgery for cholelithiasis. All 46 children were asymptomatic at the time of the first visit, and an elective LC was proposed to all of them before the onset of symptoms. The operation was accepted in the period of study by 24 children and refused by 22. The patients were divided into three groups (group A, asymptomatic; group B, symptomatic; and group C, emergency admitted) depending on clinical presentation and operation timing, and the respective outcomes were compared. RESULTS: Elective LC in asymptomatic children (group A) is safe with no major complications reported. In children who refused surgery (groups B and C), we observed four sickle cell crises, four acute cholecystitis, and two choledocholithiasis, and all these complications were related to waiting. Two sickle cell crises occurred in symptomatic children waiting for surgery during biliary colic. The risk of emergency admission in children with cholelithiasis and CHA awaiting surgery was found to be high: 28% of the children admitted in emergency after a mean of 32 months (range, 22-36). Morbidity rate and postoperative stay increased when children with hemoglobinopathies underwent emergency LC. CONCLUSIONS: Elective LC should be the gold standard in children with CHA and asymptomatic cholelithiasis in order to prevent the potential complications of cholecystitis and choledocholithiasis, which lead to major risks, discomfort, and longer hospital stay.

Auditory thalamus, dorsal hippocampus, basolateral amygdala, and perirhinal cortex role in the consolidation of conditioned freezing to context and to acoustic conditioned stimulus in the rat.

On the basis of previous experimental evidence, it is known that the auditory thalamus (AT), the dorsal hippocampus (DH), the basolateral amygdala (BLA), and the perirhinal cortex (PC) are involved in the mnemonic processing of conditioned freezing. In particular, BLA and PC appear to be involved both in conditioned stimulus (CS) and context conditioned freezing. Through AT, the auditory CS is sent to other sites, whereas DH is involved in context conditioning. Nevertheless, the existing evidence does not make it possible to assess AT, DH, BLA, and PC involvement during the consolidation phase of conditioned freezing. To address this question, fully reversible tetrodotoxin (TTX) inactivation was performed on adult male Wistar rats having undergone CS and context fear training. Anesthetized animals were injected stereotaxically with TTX (either 5 or 10 ng in 0.5 or 1.0 microliter of saline, according to site dimensions) at increasing post-acquisition delays. Context and CS freezing durations were measured during retention testing, always performed 48 and 72 hr after TTX administration. The results showed that AT inactivation does not disrupt consolidation of either contextual or auditory fear memories. In contrast, inactivation of the other three structures disrupted consolidation. For the DH, this disruption was specific to contextual cues and only occurred when inactivation was performed early (up to 1.5 hr) after training. The BLA and PC were shown to be involved in the consolidation of both contextual and auditory fear. Their involvement persisted for longer periods of time (2d for BLA and 8 d for PC). These findings provide information to build a temporal profile for the post-training processing of fear memories in structures known to be important for this form of learning. The results are discussed in relation to previous studies on conditioned freezing and other aversive conditioned response neural correlates.

A peculiar pattern of temporal involvement of rat perirhinal cortex in memory processing.

By means of the fully reversible tetrodotoxin inactivation technique, perirhinal cortex (PC) mnemonic function was investigated in rats trained to a passive avoidance response (PAR). It was shown that PC functional integrity is necessary during PAR acquisition, during late and very late consolidation (from 24 hr up to 192 hr after the training session), and during retrieval. An unexpected finding was that the PC was not involved in the early consolidation period. Thus the PC may play a relatively simple relay or connective role during acquisition, but its very late and very long consolidative involvement may indicate a peculiar function in consolidation and possibly in the storage of the PAR engram. The results are discussed in terms of the mnemonic characteristics of other neural sites (amygdala, hippocampus, and entorhinal cortex) involved in the same learning process.

Role of the perirhinal cortex in rats' conditioned taste aversion response memorization.

The role of the perirhinal cortex (PC) in conditioned taste aversion (CTA) learning was investigated in Long Evans rats. CTA was induced by the intraperitoneal administration of LiCl 60 min after saccharin-sweetened water drinking. The PC was reversibly inactivated by the stereotaxic administration of tetrodotoxin (TTX) 60 min before saccharin drinking, immediately after saccharin drinking (Experiment 1), 6 or 24 hr after LiCl administration (Experiment 2), and 60 min before CTA retrieval testing (Experiment 3). Only pre-saccharin drinking PC inactivation disrupted CTA. Thus, PC integrity is necessary only during the earliest phases of CTA mnemonic processing, that is, taste information acquisition and early gustatory memory elaboration. The results are discussed in relation to PC connectivity and PC temporal involvement in the memorization process of other aversive responses.

Post-training nucleus basalis magnocellularis functional tetrodotoxin blockade effects on passive avoidance consolidation in the rat.

The tetrodotoxin (TTX) functional ablation technique was employed in order to evaluate the temporal coordinates of the rat's nucleus basalis magnocellularis (NBM) involvement in memory trace processing. Under ketamine general anesthesia, TTX (10 ng in 1 microliter saline) was stereotaxically administered to rats, either in one or both NBMs. TTX was injected to different groups of rats, respectively 15 min, 6, 24, 48, 96 h after passive avoidance acquisition testing. The rats underwent retrieval testing 48 h later, i.e. after full recovery from TTX effects. Results show that: (1) monolateral TTX blockade significantly impairs PAR conditioned responding if induced up to 6 h but not 24 h after acquisition testing; (2) bilateral TTX blockade dramatically impairs passive avoidance responding up to a 48-h delay but not 96 h after acquisition testing. The results indicate a very profound involvement of NBM in passive avoidance response consolidation. The experimental evidence is discussed together with previous functional ablation findings concerning amygdala, parabrachial nuclei and neocortex.

Role of dorsal hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response: a tetrodotoxin functional inactivation study.

By means of local administration of tetrodotoxin (TTX) fully reversible functional inactivation of rat's dorsal hippocampus (DH) was obtained in order to define the role of this structure in the memorization of a conditioned passive avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX (10 ng in 1.0 microliter saline) or saline (1.0 microliter) was injected uni- or bilaterally in the DH, respectively 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that both pre-acquisition and pre-retrieval DH uni- or bilateral blockades were followed by significant PAR retention impairment, while in post-acquisition only the bilateral blockade determined PAR retention impairment. In Experiment 2, on three different groups of rats, TTX (10 ng in 1 microliter) saline) was bilaterally administered, under general ketamine anesthesia (100 mg/kg), into the DH at different post-acquisition delays (0.25, 1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition bilateral DH blockade caused PAR impairment only when performed 0.25 or 1.5 h after acquisition. The results indicate a well defined mnemonic role of DH during the acquisition, consolidation and retrieval of PAR engram. The experimental evidence is discussed in relation to other reports and to DH connectivity with the medial septal area and the amygdala.

Effects of combined medial septal area, fimbria-fornix and entorhinal cortex tetrodotoxin inactivations on passive avoidance response consolidation in the rat.

On the basis of previous experimental evidence, it has been concluded that the entorhinal cortex (EC), the fimbria-fornix (FF) complex and medial septal area (MSA) do not take part in the consolidation phase of passive avoidance response (PAR) memorization. On the other hand, a mnemonic role during consolidation of at least two of these structures has been argued, based on several considerations. In order to ascertain whether the EC and FF are still involved in PAR memorization during consolidation, the coupled fully reversible functional tetrodotoxin (TTX) inactivation of MSA, FF and EC was performed in rats having undergone a PAR training. In Experiment 1 MSA, FF and EC were inactivated pair-wise (FF and EC always bilaterally). Permanently cannulated animals were injected stereotaxically with TTX (5 ng in 0.5 microliter saline) or saline (0.5 microliter) immediately following PAR acquisition. It was shown that combined FF-EC inactivation induced PAR retention impairment, whereas FF-MSA and EC-MSA inactivation was not followed by amnesic effects. Having obtained a positive result, in Experiment 2 the combined FF-EC inactivation was performed at different post-acquisition delays (0.25 h, 1.5 h, 6 h), so as to assess the duration of their involvement in PAR consolidation. It was shown that only the coupled inactivation performed at the shortest post-acquisition delay was followed by amnesic effects. Thus EC and FF play a definite role during early consolidation. The results are discussed in relation to EC, FF, MSA, and hippocampal involvement in PAR memorization, as reported in previous studies, and to their connectivity.

Entorhinal cortex and fimbria-fornix role in rat's passive avoidance response memorization.

The stereotaxic administration of tetrodotoxin (TTX) was employed to induce the fully reversible inactivation of the fimbria-fornix complex (FF) and of the entorhinal cortex (EC), in order to ascertain the role of these structures in the memorization of a passive avoidance response (PAR). On permanently cannulated rats TTX (5 ng in 0.5 microliter saline) or saline (0.5 microliter) was injected uni- or bilaterally, respectively, in the FF and in the EC, 60 min before PAR acquisition, immediately after PAR acquisition and 60 min before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that EC unilateral or bilateral pre-acquisition inactivation was followed by amnesia, while TTX inactivation in post-acquisition and pre-retrieval had no effects. Identical results were obtained by TTX administration in FF. The experimental evidence indicates that both EC and FF play a role during acquisition of PAR engram. The results are discussed in comparison with previous ones concerning dorsal and ventral hippocampus TTX inactivation effects on rat's PAR, and in relation to hippocampal and medial septal area connectivity.

Role of ventral hippocampus in acquisition, consolidation and retrieval of rat's passive avoidance response memory trace.

By means of local administration of tetrodotoxin (TTX) a fully reversible functional inactivation of rat's ventral hippocampus (VH) was obtained in order to characterize the role of this structure in the memorization of a conditioned passive avoidance response (PAR). In Experiment 1, on permanently cannulated animals, TTX (10 ng in 1.0 microl saline) or saline (1.0 microl) was injected uni- or bilaterally in the VH, respectively, 1 h before PAR acquisition, immediately after PAR acquisition, and 1 h before PAR retrieval, always performed 48 h after the acquisition trial. It was shown that both pre-acquisition and pre-retrieval VH uni- or bilateral blockades were followed by significant PAR retention impairment, while in post-acquisition only the bilateral blockade determined PAR retention impairment. In Experiment 2, on three different groups of rats, TTX (10 ng in 1 microl saline) was bilaterally administered, under general ketamine anesthesia (100 mg/kg b.w.), into the VH at different post-acquisition delays (0.25, 1.5, 6 h). Retrieval testing, 48 h after treatment, showed that post-acquisition bilateral VH blockade caused PAR impairment only when performed 0.25 h after acquisition. The results clearly indicate a role of VH during acquisition, consolidation and retrieval of PAR engram. The experimental evidence is discussed in comparison to previous results concerning TTX dorsal hippocampus blockade effects on rat's PAR and in relation to hippocampal connectivity with the medial septal area and the amygdala.

Effects of coupled perirhinal cortex and medial septal area, fimbria-fornix, entorhinal cortex tetrodotoxin inactivations on passive avoidance consolidation in the rat.

In order to ascertain the rat perirhinal cortex (PC) function during early consolidation of a passive avoidance response (PAR), and to ascertain whether there are some functional interactions with the medial septal area (MSA), the fimbria-fornix complex (FF) and the entorhinal cortex (EC), PC-MSA, PC-FF, and PC-EC coupled inactivations were performed immediately after the PAR acquisition session. Anesthetized male adult Wistar rats aged 60 days were treated with stereotaxical bilateral injections of TTX (5 ng in 0.5 microl saline) in the appropriate sites. Retrieval testing was performed 48 h later. It was shown that all three coupled inactivations were followed by significant PAR disruption. It may be concluded that PC is somehow active even during the first mnemonic phase following the acquisition session, thus better defining PC mnemonic involvement chronology. These results may be taken as indicating that during initial consolidation the engram is concurrently processed in more than one septal and parahippocampal site, each of which by itself is not absolutely necessary for the final engram formation.

Analysis of mnemonic processing by means of totally reversible neural inactivations.

The irreversible lesions technique precludes the analysis of the possibly critical role played by discrete brain sites in the several distinct stages of mnemonic processing (acquisition, consolidation, retrieval) during which these may be specifically but transiently active. On the contrary, the reversible functional inactivation techniques, by means of stereotaxic local microinjection of active compounds, make it possible to suppress the neuronal function of a discrete volume of nervous tissue, for a pre-determined time, with the assurance of complete functional recovery within a known duration. This technique makes it possible to block the neural activity of a chosen neural site at a given stage of memory processing without any interference with the function of the same structure either during earlier or later stages of the same process. Thus, the reversible ablation results may provide information not only on the qualitative topographical but also on the quantitative temporal dimension of learning and memory. The technique employed to cause totally reversible neural inactivation is detailed. The employment of several agents to obtain functional inactivation is discussed. Of these, perhaps the safest and most manageable is tetrodotoxin when a fairly long functional inactivation (e.g., 1 h) is desired. The effects of a reversible inactivation can be quite easily and accurately assessed by observing the severity of the amnesic disruption, if any, of a conditioned response. In order to do this as well as possible, it is advantageous to employ a very simple behavioral paradigm. The passive avoidance response in the light-dark box apparatus fulfills this requirement. Moreover, this paradigm, being one-trial, provides the necessary condition of a single well-defined temporal beginning. The present protocol has been successfully employed in learning and memory research, to assess when the functional integrity of a given neural structure is necessary in order that a conditioned response may be acquired, consolidated or retrieved. The employment of this protocol in relation to the intrinsic functional characteristics of a given subcortical neural site is discussed.

Effects of detention and illumination on rats' exploratory behavior in a two-box apparatus.

The effects of detention and lighting intensity on the exploratory behavior of male Wistar rats have been investigated by means of several types of two-box apparatus. Experiments consisted of six consecutive daily trials. Step-through latency values were taken up to 180 sec. Even a very short detention (10 sec) within the starting box exerted a powerful inhibitory influence on the exploratory behavior of the subjects. Uniformly well-lighted surroundings (both boxes) exerted an equally powerful inhibitory influence on the same behavior. This inhibition was only slightly decreased by the availability of visual cues. Only in the apparatus in which at least one box was dark was the exploratory behavior well maintained. Both detention and bright lighting inhibited selectively the exploratory, locomotor behavior of these animals and did not inhibit other motor activities. In fact, groomings and attempts (abortive passages from one box into the other) were repeatedly performed during the increased step-through latency. These activities are discussed as indicators of a conflict between drives.

Some factors influencing conditioned and spontaneous behavior of rats in the light-dark box test.

Step-through and exit latencies in the light-dark box test were used to examine the effects of unconditioned exploration, the physical characteristics of the apparatus and detention on passive and active avoidance. Experiment 1, in which the subjects (Ss) received inescapable shocks in the dark chamber, shows that omission of the free exploration of the apparatus does not significantly affect acquisition and retention of either of the learned responses. Further, passive avoidance, compared with active avoidance is, by far, the better consolidated response. Experiment 2, which is the reverse of Experiment 1, (the dark chamber becomes the safe box, and the punishments are administered in the light chamber) emphasizes the role played by the physical characteristics of the two chambers of the apparatus. This role is shown by the improvement of the active avoidance response. Experiment 3 confirms the importance of detention in influencing the behavior of conditioned and control Ss. These results underscore the basic differences of active and passive avoidance responses.

Passive and active avoidance behavior in the light-dark box test.

The temporal evolution of passive and active avoidance behaviors has been followed in rats, using the light-dark box test, by measuring step-through and exit latencies. The employed schedule consisted of three 7 day periods (free exploration, reinforced learning, forced extinction-retention). The data show clearly that the two learned behaviors are both rapidly established and exhibit significant differences only during extinction, active avoidance apparently depending on close temporal reinforcement. The diverse role of several behavioral and neurological mechanisms is hypothesized.

Forced extinction as a means to evaluate consolidation gradient of a passive avoidance response in the rat.

Passive avoidance response (PAR) consolidation gradient, and US (footshock) intensity/engram strength relationship were investigated by means of specific forced extinction procedure (30 min detention in the shock box without receiving punishment) in Wistar rats trained in the light-dark box apparatus. Different groups of rats (punished either with 0.8 or 1.2 mA footshock intensity) underwent detention at different postacquisition time delays: immediately or 1, 2, 4 days after acquisition training. By means of this purely behavioral paradigm, designed to investigate a specific PAR memory trace, previous results obtained by using diverse and sometimes unspecific memory-disrupting agents were fully confirmed: PAR strength and consolidation gradient are positively related to US intensity. The influence of differential generalization effects on extinction is discussed. An unexpected finding was that from engrams that are experimentally shown to be of unequal resistance to disruption, equal conditioned responses are obtained.

Effects of nucleus basolateralis amygdalae neurotoxic lesions on some spontaneous activities in the rat.

Drinking, feeding, locomotion and exploratory activity of male Wistar rats were assessed after bilateral stereotaxic administration of ibotenic acid in the nucleus basolateralis amygdalae. Feeding, drinking and locomotion were measured in an activity cage, while exploratory activity was determined in a multiple Y-maze. In the 24-hour cycle, lesioned animals exhibited unvaried feeding, decreased drinking and increased locomotion. Exploration was also increased. The results show that this nucleus is not involved in quantitative feeding control, while it does exert a significant facilitatory influence on drinking. It also exerts an inhibitory influence on exploration and on locomotion.

Effects of nucleus basolateralis amygdalae neurotoxic lesions on aversive conditioning in the rat.

After bilateral stereotaxic administration of ibotenic acid on the n. basolateralis amygdalae, male adult rats were tested in the light-dark box apparatus to measure the time-course of the acquisition and retention of passive and active avoidance responses. The results show that after the lesions both passive avoidance and active avoidance acquisition were impaired. Passive avoidance responses were retained quite well, while active avoidance responses disappeared quickly. Conditioned freezing was almost completely absent. Thus it appears that the n. basolateralis plays a facilitatory role in all the conditioned responses which were investigated.

Aversive conditioning of homozygous and heterozygous D.I. Brattleboro rats in the light-dark box.

Active and passive avoidance, and conditioned freezing acquisition and retention were studied in HODI and HEDI Brattleboro rats. All animals were from the same source and of the same age and sex. The light-dark box test was employed. 0.6 and 2.0 mA footshocks were administered for the same number (7) of daily trials. Extinction time-course was followed for seven consecutive daily trials. Passive avoidance: the conditioned response was acquired and retained equally well by all Ss and for both shock intensities. Active avoidance: for 0.6 mA shocks HODI Ss acquired and retained the response significantly better than HEDI Ss; for 2.0 mA shocks the response was acquired equally by both groups of Ss, and retained significantly better by HODI Ss. Freezing: in general, HODI Ss exhibited less freezing then HEDI Ss. The diverse conditioned behavior of HODI and HEDI Ss in this paradigm, which allows the contemporaneous investigation of several aversive responses, does not support the hypothesis that vasopressin deficiency impairs learning and memory in the rat.