Aims
Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary oedema ...(ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.
Methods and results
A randomized, multicentre, open‐label, blinded endpoint clinical trial was performed in seven Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnoea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in‐hospital all‐cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and the composite endpoint included 30‐day mortality and SAE. Analyses were made on an intention‐to‐treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no significant differences in the primary endpoint (in‐hospital mortality for midazolam vs. morphine 12.7% vs. 17.9%; risk ratioRR 0.71, 95% confidence interval CI 0.29–1.74; p = 0.60). SAE were less common with midazolam versus morphine (18.2% vs. 42.9%; RR 0.42, 95% CI 0.22–0.80; p = 0.007), as were the composite endpoint (23.6% vs. 44.6%; RR 0.53, 95% CI 0.30–0.92; p = 0.03).
Conclusion
Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.
There were no significant differences in mortality between morphine and midazolam but the rate of serious adverse events was significantly higher in the morphine group, although the number of patients was too small to draw final conclusions.
•The type of household is associated with elderly patients' prognosis at one year.•Living in a nursing home is associated with higher mortality.•Living at home but not alone is associated with a ...lower rate of rehospitalization/revisit.
To investigate whether the type of household is associated with prognosis at one year in patients ≥65 years of age discharged after medical consultation requiring emergency department care.
Data from the Emergency Department and Elder Needs (EDEN) cohort were used. This retrospective cohort included all patients ≥65 years of age seen in 52 Spanish emergency departments over one week (April 1–7, 2019) in whom the type of household was recorded and categorized as living at home alone, with relatives, with professional caregivers, or in a nursing home. Patient demographic and other baseline characteristics and management during the index emergency department episode were recorded and used to adjust the following 1-year outcomes: all-cause mortality, hospitalization and emergency department revisit. Associations between type of household and outcomes are expressed as adjusted hazard ratios with 95% confidence intervals using living alone as the reference category.
13,442 patients with a median age of 79 years (interquartile range 72–86) were included; 56% were women, 12.2% of patients lived alone, 74.9% with relatives, 3.9% with a professional caregiver, and 9.1% in a nursing home. During the year following discharge, the mortality rate was 14.0%, the hospitalization rate 29.7%, and the emergency department revisit rate 59.3%. In the fully adjusted model, the risk of death was associated only with living in a nursing home (hazard ratio 1.366 (1.101–1.695)). On the other hand, the risk of hospitalization was lower in individuals living in nursing homes (hazard ratio 0.783 0.676–0.907) and at home with relatives (hazard ratio 0.897 0.810–0.992), while the risk of emergency department revisit was lower in individuals living in nursing homes (hazard ratio 0.826 0.742–0.920) or at home with caregivers (hazard ratio 0.856 0.750–0.976).
The type of household was modestly associated with the one-year prognosis of patients ≥65 years of age discharged after attendance at an emergency department. Living in a nursing home is associated with an increased risk of death but a decreased risk of rehospitalization or emergency department revisit, while living at home with relatives or professional caregivers is associated only with a decreased risk of hospitalization and emergency department revisit, respectively.
AIM: To analyze the attitude of Spanish medical students toward living liver donation(LLD) and to establish which factors have an influence on this attitude.METHODS: Study type: A sociological, ...interdisciplinary, multicenter and observational study. Study population: Medical students enrolled in Spain(n = 34000) in the university academic year 2010-2011. Sample size: A sample of 9598 students stratified by geographical area and academic year. Instrument used to measure attitude: A validated questionnaire(PCID-DVH RIOS) was self-administered and completed anonymously. Data collection procedure: Randomly selected medical schools. The questionnaire was applied to each academic year at compulsory sessions. Statistical analysis: Student′s t test, χ2 test and logistic regression analysis.RESULTS: The completion rate was 95.7%(n = 9275). 89%(n = 8258) were in favor of related LLD, and 32%(n = 2937) supported unrelated LLD. The following variables were associated with having a more favorable attitude:(1) age(P = 0.008);(2) sex(P < 0.001);(3) academic year(P < 0.001);(4) geographical area(P = 0.013);(5) believing in the possibility of needing a transplant oneself in the future(P < 0.001);(6) attitude toward deceased donation(P < 0.001);(7) attitude toward living kidney donation(P < 0.001);(8) acceptance of a donated liver segment from a family member if one were needed(P < 0.001);(9) having discussed the subject with one’s family(P < 0.001) and friends(P < 0.001);(10) a partner’s opinion about the subject(P < 0.001);(11) carrying out activities of an altruistic nature; and(12) fear of the possible mutilation of the body after donation(P < 0.001).CONCLUSION: Spanish medical students have a favorable attitude toward LLD.
The MIMO clinical trial showed that patients with acute cardiogenic pulmonary edema (ACPE) treated with midazolam had fewer serious adverse events than those treated with morphine. Atrial ...fibrillation (AF) is a common comorbidity in heart failure and affects patient's outcome.
The primary endpoint of this substudy is to know if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine. The first secondary endpoint is to know if AF modified the reduced risk of serious adverse events or death at 30 days in the midazolam arm. The second secondary objective of this substudy is to analyze whether AF modified the reduced risk of midazolam against morphine on the total number of serious adverse events per patient.
We conducted a secondary analysis of the MIMO trial. Patients more than 18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at emergency department arrival to receive either intravenous midazolam or morphine.
In this post hoc analysis, we calculated the relative risk (RR) of serious adverse events in patients with and without AF. Calculating the Cochran-Mantel-Haenszel interaction test, we evaluated if AF modified the reduced risk of serious adverse events in the midazolam arm compared to morphine.
One hundred eleven patients (median = 78.9 years; IQR, 72.3-83.7; women, 52.2%) were randomized in the MIMO trial, 55 to receive midazolam and 56 to morphine. All randomized patients received the assigned drug and there were no losses to follow-up. Forty-four patients (39.6%) had AF. In the AF group, the RR for the incidence of serious adverse events in the midazolam versus morphine arm was 0.42 (95% CI, 0.14-1.3). In the group without AF, the RR was 0.46 (95% CI, 0.21-1). The presence of AF did not modify the reduced risk of serious adverse events in the midazolam arm compared with morphine ( P for interaction = 0.88).
This post hoc analysis of the MIMO trial suggests that the reduced risk of serious adverse events in the midazolam group compared to morphine is similar in patients with and without AF.
In adult albino mice the effects of increased intraocular pressure on the outer retina and its circuitry was investigated at intervals ranging 3–14 weeks. Ocular hypertension (OHT) was induced by ...cauterizing the vessels draining the anterior part of the mice eye, as recently reported (Salinas-Navarro et al., 2009a). Electroretinographic (ERG) responses were recorded simultaneously from both eyes and compared each other prior to and at different survival intervals of 2, 8 or 12 weeks after lasering. Animals were processed at 3, 9 or 14 weeks after lasering, and radial sections were obtained in the cryostat and further processed for immunocytochemistry using antibodies against recoverin, γ-transducin, Protein Kinase C-α (PKC-α), calbindin or synaptophysin. The synaptic ribbons were identified using an antibody against the protein bassoon, which labels photoreceptor ribbons and nuclei were identified using TO-PRO. Laser photocoagulation of the perilimbar and episcleral veins of the left eye resulted in an increase in mean intraocular pressure to approximately over twice its baseline by 24
h that was maintained for approximately five days reaching basal levels by 1 week. ERG recordings from the different groups of mice showed their a-, b-wave and scotopic threshold response (STR) amplitudes, when compared to their contralateral fellow eye, reduced to 62%, 52% and 23% at 12 weeks after lasering.
Three weeks after lasering, immunostaining with recoverin and transducin antibodies could not document any changes in the outer nuclear layer (ONL) but both ON-rod bipolar and horizontal cells had lost their dendritic processes in the outer plexiform layer (OPL). Sprouting of horizontal and bipolar cell processes were observed into the ONL. Fourteen weeks after lasering, protein kinase-C antibodies showed morphologic changes of ON-rod bipolar cells and calbindin staining showed abnormal horizontal cells and a loss of their relationship with their presynaptic input. Moreover, at this time, quantitative studies indicate significant diminutions in the number of photoreceptor synaptic ribbons/100 μm, and in the thickness of the outer nuclear and plexiform layer, when compared to their fellow eyes. Increased intraocular pressure in Swiss mice results in permanent alterations of their full field ERG responses and in changes of the inner and outer retinal circuitries.
► Effects of optic nerve transection on the dark adapted ERG of mice. ► Persistent changes in the n- and pSTR amplitude following axotomy. ► Persistent changes in the n- and pSTR implicit time ...following axotomy. ► ERG–STR is a useful parameter to monitor RGC functionality in adult mice.
Optic nerve transection (ONT) triggers retinal ganglion cell (RGC) death. By using this paradigm, we have analyzed for the first time in adult albino and pigmented mice, the effects of ONT in the scotopic threshold response (STR) components (negative and positive) of the full-field electroretinogram. Two weeks after ONT, when in pigmented mice approximately 18% of the RGC population survive, the STR-implicit time decreased and the p and nSTR waves diminished approximately to 40% or 55%, in albino or pigmented, respectively, with respect to the values recorded from the non-operated contralateral eyes. These changes were maintained up to 12
weeks post-ONT, demonstrating that the ERG–STR is a useful parameter to monitor RGC functionality in adult mice.
To investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC), as well as on the function ...of retinal layers.
Adult albino Swiss mice (35-45 g) received laser photocoagulation of limbal and episcleral veins in the left eye. Mice were sacrificed at 8, 17, 35, and 63 days. Intraocular pressure (IOP) in both eyes was measured with a Tono-Lab before LP and at various days after LP. Flash electroretinogram (ERG) scotopic threshold response (STR) and a- and b-wave amplitudes were recorded before LP and at various times after LP. RGCs were labeled with 10% hydroxystilbamidine methanesulfonate (OHSt) applied to both superior colliculi before sacrifice and in some mice, with dextran tetramethylrhodamine (DTMR) applied to the ocular stump of the intraorbitally transected optic nerve. Retinas were immunostained for RT97 or Brn3a. Retinas were prepared as whole-mounts and photographed under a fluorescence microscope. Labeled RGCs were counted using image analysis software, and an isodensity contour plot was generated for each retina.
IOP increased to twice its basal values by 24 h and was maintained until day 5, after which IOP gradually declined to reach basal values by 1 wk. Similar IOP increases were observed in all groups. The mean total number of OHSt(+) RGCs was 13,428+/-6,295 (n=12), 10,456+/-14,301 (n=13), 12,622+/-14,174 (n=21), and 10,451+/-13,949 (n=13) for groups I, II, III, and IV, respectively; these values represented 28%, 23%, 26%, and 22% of the values found in their contralateral fellow retinas. The mean total population of Brn3a(+) RGCs was 24,343+/-5,739 (n=12) and 10,219+/-8,887 (n=9), respectively, for groups I and III; these values represented 49% and 20%, respectively, of the values found in their fellow eyes. OHT retinas showed an absence of OHSt(+) and DTMR(+) RGCs in both focal wedge-shaped and diffuse regions of the retina. By 1 wk, there was a discrepancy between the total number of surviving OHSt(+) RGCs and Brn3a(+) RGCs, suggesting that a large proportion of RGCs had impaired retrograde axonal transport. In the retinal areas lacking backlabeled RGCs, neurofibrillar staining revealed aberrant expression of RT97 within axons and RGC bodies characteristic of axotomy. Elevated IOP induced significant reductions in the registered ERG waves, including positive STR, a- and b-waves, that were observed by 24 h and remained throughout the period of study for the three groups analyzed.
LP of the perilimbal and episcleral veins resulted in OHT leading to a lack of retrograde axonal transport in approximately 75% of the original RGC population. This lack did not progress further between 8 and 63 days, and it was both focal (in sectors with the apex located in the optic disc) and diffuse within the retina. In addition, severe amplitude diminutions of the STR and a- and b-waves of the ERG appeared as early as 24 h after lasering and did not recover throughout the period of study, indicating that increased IOP results in severe damage to the innermost, inner nuclear, and outer nuclear layers of the retina.
To investigate the different components of full-field flash electroretinogram (ERG) responses in adult albino and pigmented rats at various time intervals following optic nerve transection (ONT).
In ...adult Sprague-Dawley (SD, albino) and Piebald-Viral-Glaxo (PVG, pigmented) rats, the left optic nerve was transected intraorbitally to induce retinal ganglion cell (RGC) death. ERG responses were recorded simultaneously from both eyes beforehand and at 1, 2, 4, and 12 week intervals after ONT. The ERG a- and b-waves and the scotopic threshold responses (STR) were analyzed in scotopic conditions. White light stimuli of intensities ranging from 10(-6) to 10(-4) cd.s.m(-2) were used to record the positive and negative scotopic threshold responses (pSTR and nSTR), while stimulus light intensities ranging from 10(-4) to 10(2) cd.s.m(-2) were used to analyze the a- and b-wave amplitudes of standard ERG recordings.
In the albino rats, one week after intraorbital ONT, the STR mean amplitude decreased significantly, to approximately 60% of the values registered for the contralateral eye (p<0.05), which had not been operated on; standard ERG a- and b-waves showed a small reduction in amplitude-to approximately 85%. By two weeks after ONT, the STR mean amplitude was approximately 40% that of the contralateral eye, while the a- and b-wave amplitudes had further decreased to approximately 75%. Four weeks after ONT, the STR had fallen to 60% of that of the contralateral eyes, whereas the a- and b-waves reached values of approximately 90%. Twelve weeks after ONT, the STR remained significantly reduced to approximately 45%, whereas the a- and b-waves reached values of approximately 90%. In the pigmented rats, one week after intraorbital ONT, the mean amplitude had decreased significantly, to approximately 60% for the pSTR and to 80% for the nSTR of the values registered for the intact contralateral eye (p<0.05); while the standard ERG a- and b-waves showed a small reduction in amplitude to approximately 90%. Two weeks after ONT, the STR mean amplitude was approximately 55%, while the a- and b-wave amplitudes had further decreased to approximately 65%. Four weeks after ONT, the STR also was significantly reduced, to only 40%, whereas the a- and b-waves reached values of approximately 60%. Twelve weeks after ONT, the pSTR and nSTR remained significantly reduced to approximately 40% and 70%, respectively; whereas the a- and b-waves reached values of approximately 80%.
Optic nerve injury results in transient reductions of the major ERG components, the a- and b-waves, as well as permanent reductions of the early components of the ERG, the negative and positive scotopic threshold responses. Because ONT induces massive RGC loss, it is likely that permanent reduction in the STR represents a lack of the RGC population, thus highlighting the importance of the STR recordings as an electrophysiological tool for the assessment of RGC function.
Introduction
Research into the transplantation of solid organs from animals (xenotransplantation) is generating interest and curiosity given that this could be a way of resolving the shortage in ...transplant organs. However, the fact is that currently xenotransplantation is far from becoming a clinical practice.
Objective
To analyse the attitude of medical students from Spanish universities towards the donation of organs from animals and to determine the factors affecting their attitudes.
Material and Methods
Type of study: A sociological, interdisciplinary, observational and multicentre study in Spain. Study population: Students enrolled on the medical degree in Spain (n = 34 000). Sample size: A sample of 9598 students (a confidence level of 99% and precision of ± 1%) stratified by geographical area and academic year. Instrument of measurement: A validated questionnaire of attitude towards organ xenotransplantation (PCID‐XenoTx RIOS) which was self‐administered and completed anonymously.
Results
A completion rate of 95.7% (n = 9275) was obtained. If the results of xenotransplantation were as good as in human donation, 81% (n = 7491) would be in favour, 3% (n = 308) against and 16% (n = 1476) undecided. The following variables affected this attitude: sex (P < 0.001); academic year (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); the opinion of one's partner (P < 0.001); the respondent's attitude towards organ donation (P < 0.001); religion (P < 0.001); and participation in altruistic activities (P < 0.001). The following variables persisted in the multivariate analysis: (1) being a female (OR = 1.794; P < 0.001); (2) academic year (OR = 2.487; P < 0.001); (3) having spoken about the issue with one's family (OR = 1.200; P = 0.019); (4) the favourable opinion of one's partner (OR = 1.526; P = 0.028); (5) an attitude in favour of donation (OR = 2.087; P < 0.001); (6) being an atheist/agnostic, (OR = 2.5; P < 0.001); and (7) a belief that one's religion is in favour of transplantation (OR = 1.317; P = 0.005).
Conclusions
Spanish medical students have a favourable attitude towards xenotransplantation. This willingness and interest could be a decisive platform for the development and strengthening of research, both for centres with a pre‐clinical xenotransplantation programme and new healthcare centres.
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