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Biomedical subjects

Oscar Miró

Publications and source records attributed to Oscar Miró.

At least 19 recordsLinked to original sources

Reversible inhibition of mitochondrial protein synthesis during linezolid-related hyperlactatemia.

The objective of the present study was to determine the mitochondrial toxicity mechanisms of linezolid-related hyperlactatemia. Five patients on a long-term schedule of linezolid treatment were studied during the acute phase of hyperlactatemia and after clinical recovery and lactate normalization following linezolid withdrawal. Mitochondrial studies were performed with peripheral blood mononuclear cells and consisted of measurement of mitochondrial mass, mitochondrial protein synthesis homeostasis (cytochrome c oxidase [COX] activity, COX-II subunit expression, COX-II mRNA abundance, and mitochondrial DNA [mtDNA] content), and overall mitochondrial function (mitochondrial membrane potential and intact-cell oxidative capacity). During linezolid-induced hyperlactatemia, we found extremely reduced protein expression (16% of the remaining content compared to control values [100%], P < 0.001) for the mitochondrially coded, transcribed, and translated COX-II subunit. Accordingly, COX activity was also found to be decreased (51% of the remaining activity, P < 0.05). These reductions were observed despite the numbers of COX-II mitochondrial RNA transcripts being abnormally increased (297%, P = 0.10 [not significant]) and the mitochondrial DNA content remaining stable. These abnormalities persisted even after the correction for mitochondrial mass, which was mildly decreased during the hyperlactatemic phase. Most of the mitochondrial abnormalities returned to control ranges after linezolid withdrawal, lactate normalization, and clinical recovery. Linezolid inhibits mitochondrial protein synthesis, leading to decreased mitochondrial enzymatic activity, which causes linezolid-related hyperlactatemia, which resolves upon discontinuation of linezolid treatment.

Acetamides↗

[Estimation of emergency department activity and its relationship with inhospital bed disposition].

BACKGROUND AND OBJECTIVE: To find out if the daily emergency department (ED) census and daily ED admittances can accurately be foreseen based on the number of visits arrived on ED within the first shift hours. PATIENTS AND METHOD: For 6 consecutively months, the number of ED visits from 6 AM to 10 AM (early visits), and from 10 AM to next day 6 AM (daily ED census) was recorded, along with the number of both daily hospital and ED admittances from 6 AM to 6 AM. The analysis was performed for the ED as a whole, and for each one of its sections. RESULTS: A significant direct correlation was seen between the early visits and daily ED census. This relationship was even greater as considered the ED as a whole (R2 = 0.25; p < 0.001). A direct correlation was also found between daily ED census and daily admittances (R2 = 0.19; p < 0.001). CONCLUSIONS: The number of early ED visits is an important tool to accurately predict the daily ED census and the number of in-hospital beds needed for ED patients.

Emergency Service, Hospital↗

Teaching basic life support to 12-16 year olds in Barcelona schools: views of head teachers.

AIM: To determine the opinion of head teachers on the educational and logistical characteristics required for a basic cardiopulmonary resuscitation (b-CPR) programme for secondary school teenagers to succeed. MATERIAL AND METHODS: The study was carried out in Barcelona which has 227 public and private secondary schools. Secondary school is started at 12 years old, and finished around 16 once teenagers pass grade 4. A hypothetical b-CPR program split into two parts (concepts and training) was introduced to all Barcelona secondary school head teachers, and a 23 question survey on the programme characteristics was mailed to them three times. RESULTS: One hundred out of 227 (44%) surveys were sent back: 63% from private and 37% from public secondary schools with 85% of head teachers being interested in incorporating a b-CPR programme in the school curriculum. Interested head teachers did not differ in age, sex, or kind of degree compared to their non-interested counterparts. Neither were differences found in secondary school characteristics (ownership, religious orientation, size, and neighborhood average income) of both groups of head teachers. Overall, it was considered that the programme could increase the students' self-esteem (86%), and be useful for saving lives (72%). It was also felt that both theoretical (77%) and practical classes (97%) should be given by healthcare providers. However, up to 69% thought that school teachers would be willing to give theoretical classes if trained previously. The school was identified as the best setting to perform the programme (83%), which should be given to grades 3 or 4 (97%), should last less than 5 h (83%), and should be completed within a time frame of less than 1 week (86%). The greatest programme barrier would be its cost if this was over 5-10 euro per student (55%). CONCLUSIONS: In Barcelona, most secondary schools surveyed were highly interested in a b-CPR programme for their teenagers in grades 3 or 4. Teachers would prefer healthcare providers to give the programme but would be willing to teach b-CPR theory if trained previously.

Adolescent↗

[Lack of inhospital beds: impact on emergency department performance].

BACKGROUND AND OBJECTIVE: To determine the effect that the lack of inhospital beds exerts on emergency department performance. MATERIAL AND METHOD: Two different time periods with comparable daily census, but significantly different bed availability. Variables assessed were general emergency department performance markers, emergency department effectiveness markers and objective and subjective quality markers. RESULTS: All variables got worse within lower bed availability period, and reached a change magnitude between 0% and 300% when compared with control period. However, a statistical difference was only achieved in emergency department occupation rate (+14%; p < 0.001), rate of patients waiting to be admitted (+100%; p < 0.001), patients waiting to be seen (+60%; p < 0.01), waiting time to be seen (+83%; p < 0.001), time to employed for first medical assessment and treatment (+44%; p < 0.01), and patients left without being seen (+90%; p < 0.05). CONCLUSIONS: The lack of inhospital beds for patients admitted from the emergency department leads to a remarkable worsening in its function and performance.

Emergency Service, Hospital↗

[Direct discharge from triage in emergency departments: assessment, risks and patient satisfaction].

BACKGROUND AND OBJECTIVE: After triage assessment, some hospitals refer emergency department (ED) patients with minor chief complaints to off-site clinics. The potential for 2 different referral models introduced in 2 urban hospitals was assessed, as well as the suitability of this measure. PATIENTS AND METHOD: After triage assessment, patients with minor complaints were identified. ED from Hospital Clínic of Barcelona (HCB) proposed that these patients should be referred to a hospital affiliated off-site clinic, whereas ED from Hospital Mútua de Terrassa (HMT) tried to refer such patients to their primary care setting. Within a year, we assessed on both ED the following items: number of arrivals, percentage of proposed referrals (PR), percentage of accepted referrals (AR), percentage of carried-out referrals (CR: patients who, once discharged, really attended the other setting), and percentage of returned referrals (RR) to the ED, as well as return reasons, and the percentage of returned patients finally admitted. The degree of patient satisfaction was evaluated by means of a telephone survey. RESULTS: From both ED, 44,764 arrivals and 7,297 (16.3%) PR were registered. The percentage of AR and CR was 94.3% and 75.3%, respectively. The percentage of PR from HMT was higher (18.7% vs 13.1%; p < 0.001), yet HCB obtained a greater percentage of AR (98.9% vs 92%, p < 0.001) and CR (93.7% vs 65%; p < 0.001). The percentage of RR from both ED was 1.5% (2.8% vs 0.4%; p < 0.001). Among returned patients, 12 of them (0.17% respect to AR) were finally admitted. Only 41% of patients who were found to be eligible for direct discharge would have agreed with being referred to another clinical setting, but after the experience, up to 93% of them said they would go through it again. HMT gave referral information to patients faster than HCB (p < 0.05), but HCB got a better model evaluation (p < 0.01), a greater medical complaint solution (p < 0.05), and generated a smaller number of subsequent consultations (p < 0.05). CONCLUSIONS: After a rapid triage assessment, a percentage of patients arriving on EDs may be directly and safely discharged and referred to other clinical settings. This is achieved by both proposed models without additional risks for patients. However, patients feel more satisfied with an hospital-affiliated off-site clinic instead of their primary care setting.

Adult↗

Longitudinal study on mitochondrial effects of didanosine-tenofovir combination.

Tenofovir disoproxil fumarate (TDF) has been reported to be free of adverse effects on mitochondria. We evaluate the effects of the introduction of TDF in a didanosine (ddI)-based highly active antiretroviral therapy (HAART) on mitochondrial DNA (mtDNA) content, mitochondrial mass (MM), and cytochrome c oxidase (COX) activity of the oxidative phosphorylation (OXPHOS) system over a 12-month period. Forty-four asymptomatic HIV patients with undetectable viral load receiving a ddI-based HAART were recruited and switched to ddI plus TDF (ddI + TDF) and nevirapine (n = 22) or maintained with the same baseline ddIbased HAART scheme (n = 22). Peripheral blood mononuclear cells were obtained at 0, 6, and 12 months. COX activity and MM were determined by spectrophotometry and the mtDNA content by quantitative realtime PCR. The mtDNA content showed a progressive decrease over the 12-month period of the study for the two groups with respect to baseline, with such a decrease statistically significant only in the ddI + TDF group (55% decrease, p < 0.001). In addition, the decrease of mtDNA content over time was statistically different between both groups (p < 0.001). Consistently, MM and COX activity decreased significantly at 12 months with respect to baseline only in the ddI < TDF group (28% decrease for MM, p < 0.05; 47% decrease for COX activity, p < 0.001). We conclude that switching to a HAART regimen containing ddI + TDF is associated with evolutive mitochondrial damage expressed as mtDNA depletion, loss of MM, and decrease in COX efficiency. The particular relevance of either ddI, TDF, or any interaction between them in such a mitochondrial dysfunction remains to be established.

Adenine↗

Short communication metabolic and mitochondrial effects of switching antiretroviral-experienced patients to enfuvirtide, tenofovir and saquinavir/ritonavir.

OBJECTIVE: Investigate the metabolic and mitochondrial effects of switching a highly active antiretroviral therapy (HAART) regimen with a high mitochondrial toxicity profile to a HAART with a theoretically low mitochondrial toxicity. PATIENTS AND METHODS: Six consecutive HAART-experienced patients receiving at least one dideoxy-nucleoside reverse transcriptase inhibitor (NRTI) switched to enfuvirtide plus tenofovir plus saquinavir/ritonavir (T20+TDF+SQV/r). Blood samples were collected at baseline, 12 and 24 weeks after the switch, and viral load (VL) and lymphocyte CD4+ T-cell count were determined. Metabolic parameters consisted of fasting serum triglycerides, cholesterol (total and fractions), glucose, insulin, C-peptide and lactate. Mitochondrial assessment consisted on mitochondrial DNA (mtDNA) quantification, COX-II mitochondrial protein expression rate, mitochondrial respiratory chain complex III and IV activities, and oxygen consumption in peripheral blood mononuclear cells. For baseline mitochondrial comparisons, we included six HIV-infected patients naive for ART. RESULTS: Switched patients exhibited a mean increase of 26 CD4+ T-cells/mm3 and a mean decrease of 1.1 log in VL (P = NS for both). Lactate, lipids and glycaemia remained stable during the study; only insulin levels increased significantly (P < 0.05). Switched patients exhibited, at baseline, low mitochondrial measurements, being significant only for complex III and IV activities with respect to naive patients (P < 0.05 for both). MtDNA content did not rise significantly during the study. However, we observed increases in COX-II mitochondrial protein synthesis (124%, P < 0.05), complex III activity (127%, P < 0.05), complex IV activity (86%, P = 0.37) and oxygen consumption (194%, P < 0.05). CONCLUSION: Switching a HAART-containing dideoxy-NRTI to T20+TDF+SQV/r minimally alters metabolic parameters and exerts beneficial effects on mitochondrial function at 24 weeks. Mitochondrial improvement should be considered as an additional advantage of this rescue therapy.

Adenine↗

[Treatment of symptomatic hyperlactatemia and lactic acidosis in HIV+ patients under nucleoside reverse transcriptase inhibitors].

BACKGROUND AND OBJECTIVE: We intended to find out the effectiveness of lactic acidosis therapy for mitochondrial toxicity. PATIENTS AND METHOD: HIV-patients receiving nucleoside reverse transcriptase inhibitors (NRTIs), hospitalized with lactic acidosis or symptomatic hyperlactatemia. Venous hyperlactatemia was considered at > 2.2 mmol/l. Treatment consisted of a daily vitamin regime of L-carnitine, thiamine, vitamin B6, hydroxicobalamine, and vitamin C; any glucose intake was discontinued. NRTIs treatment was stopped immediately. RESULTS: Nine patients on current therapy were identified who had symptomatic hyperlactatemia (n = 4) or lactic acidosis (n = 5) from 1/2001 to 9/2002. All were patients with AIDS, receiving NRTIs with a mean duration of 5 years: ddI (n = 7), d4T (n = 5), AZT(n = 3), 3TC (n = 2), abacavir (n = 1). Most common symptoms were tachypnea, slight fever, abdominal pain, nausea, vomiting and diarrhea. All patients had a favourable prognosis after administration of L-carnitine and vitamin complexes, with discontinuation of NRTIs and glucose intake. Clinical features lasted 7 days. After 15 (5) months of follow up, none had a recurrence of the syndrome. CONCLUSION: The application of this therapy could play a role in the treatment of NRTI - related lactic acidosis.

Acidosis, Lactic↗

[Emergency department activity during the 2003 summer heat wave].

BACKGROUND AND OBJECTIVE: Several thousands deaths were attributed to a heatwave during the summer of 2003 in Europe. The aim of this study was to analyze its consequences in an emergency department. PATIENTS AND METHOD: We performed a descriptive observational study of the patients admitted to our emergency unit between 15 July and 31 August, 2003. We also carried out a comparative study of these patients with those admitted during the same period of 2002. RESULTS: A total of 5197 patients were admitted in our unit during the summer of 2003, in comparison with 4672 in the same interval in 2002. An increase in rates of total fever (17% versus 12%; p < 0.001), non-infectious fever (29% versus 26%; p < 0.001), decompensation of a chronic cardiovascular or respiratory disease (14% versus 11%; p < 0.001), admission (28% versus 22%; p < 0.001), and mortality (2% versus 1%; p < 0.001) were registered during the summer of 2003, in comparison with the previous year. A multivariate study showed a higher risk of death in patients older than 70 years (p < 0.01), in fragile dependent people (p < 0.05), and upon the presence of abnormal blood levels of creatinine (p < 0.05) on arrival at the emergency department. We also found an association between daily maxim temperature and number of daily emergency visits (R2 = 0.15; p < 0.001), total percentage of patients with fever (R2 = 0.26; p < 0.001), percentage of patients with non-infectious fever (R2 = 0.07; p = 0.01), percentage of decreases (R2 = 0.04; p < 0.05), and percentage of hospital admissions (R2 = 0.15; p < 0.001). CONCLUSIONS: The summer 2003 heatwave resulted in an elevation of the total number of emergency visits and hospital admissions, and higher mortality and morbidity rates, especially in old people. In the future, preventive measures must be taken to limit the health consequences of any heatwaves to come.

Aged↗

[Effect of the incorporation of a general practitioner on emergency department effectiveness].

BACKGROUND AND OBJECTIVES: To know the effect that the presence of a general practitioner (GP) has on emergency department's effectiveness, efficiency and health care. PATIENTS AND METHOD: Prospective interventional study carried out in the emergency medicine unit fast track area (FTA), which is ideally opened from 8 am to 12 am, and staffed by 2 residents. INTERVENTION: 8 resident hours (from 4 pm to 12 am) were substituted by 8 GP hours. The study period was August 2002 (GP presence), and the control period, October 2002. From each period, 10 days and 100 patients were randomly selected. From each day, FTA census (P), percentage of revisits and patients leaving without being seen, elapsed time to FTA actual closing (OT), percentage of patients moved to the observation area, and percentage of admissions were recorded. From each patient, epidemiological and clinical characteristics, waiting time to be seen (WT), number of tests performed, elapsed time to treatment (TT), and length of stay (LOS) were collected along with the number of patients finally discharged without hospital specialist consultation and those discharged with no test ordered. To assess perceived care quality, a telephone survey was performed. Three effectiveness indexes were defined and determined: P/WT (E1), P/OT (E2), and perceived care quality/perceived WT (E3). Finally, fixed and variables costs (C) from both periods were calculated, and cost-effectiveness analysis for each effectiveness index and period performed. RESULTS: Periods showed no differences regarding daily census and patient characteristics. In the study period (GP presence), all time variables significantly improved: 20% reduction in WT, 25% in TT, 36% in LOS, and 17.5% in OT. A decrease in the number of tests ordered (41% less), in the percentage of patients moved to the observation area (78% less), and in the revisit rate (75% less) was also noted. Finally, E1 improved in 77% and E2 in 51%. Cost-effectiveness analysis clearly supported the study period, showing a decrease in C/E1 (55% less), in C/E2 (33% less), and in C/E3 (6% less). From the telephone survey, no differences between periods were detected except a perceived WT in the study period lower than that in the control period. CONCLUSIONS: The presence of a GP in a FTA leads to an improvement in the effectiveness and quality of care received by attended patients. In addition of these important features, this presence is also efficient. Therefore, it is an intervention that could be taken into account by administrators to better manage emergency departments.

Adult↗

[Basic cardiopulmonary resuscitation program for high school students (PROCES). Results from the pilot program].

BACKGROUND AND OBJECTIVE: The PROCES (Programa de Reanimació Cardiopulmonar Orientat a Centres d'Ensenyament Secundari) program is aimed at teaching basic cardiopulmonary resuscitation (b-CPR) to teenagers within high school. Our aim was to analyze the results obtained from the pilot program. SUBJECTS AND METHOD: PROCES was splitted in 7 sessions: 5 of them (5 hours) were taught by teachers at high school and 2 of them (4 hours, including how to perform b-CPR) were taught by emergency physicians. To assess the degree of students' learning, they were administered a 20-question test before and after the program. Epidemiological characteristics and students' opinions (all them were requested to rate the program from 0 to 10) were also collected. RESULTS: Students were 14 years-old in 38%, 15 in 38% and 16 or more in 24%. Before PROCES, the mean mark (over 20 points) was 8.5 (2.4). After PROCES, marks improved up to 13.5 (3.2) (p < 0.001). Participants who had previously taken a first-aid course or were in the 4th course obtained significantly better marks than the rest. These differences disappeared after PROCES completion. Students rated the theoretical part as 7.9 (1.1), the skill part as 8.2 (1.2), and the emergency physicians classes as 8.4 (1.1). CONCLUSIONS: PROCES is an useful tool for teaching and improving teenagers' knowledge and skills in b-CPR, with no exceptions associated with teenagers' characteristics.

Adolescent↗

Lopinavir/ritonavir plus nevirapine as a nucleoside-sparing approach in antiretroviral-experienced patients (NEKA study).

OBJECTIVES: To compare the efficacy and safety of a nucleoside-sparing approach with a conventional highly active antiretroviral therapy (HAART) regimen in antiretroviral-experienced patients with prolonged viral suppression. METHODS: Pilot study including 31 antiretroviral-experienced patients with HIV RNA <80 copies/mL. Subjects were randomly assigned to lopinavir/ritonavir (LPV/rtv) 400/100 mg BID plus nevirapine (NVP) 200 mg BID (NVP group, n = 16) or LPV/rtv plus the 2 previous NRTIs (NRTI group, n = 15). The primary endpoint was the percentage of subjects who maintained viral suppression at week 48. Changes in lipid metabolism, mitochondrial parameters, and LPV trough levels were also assessed. RESULTS: All patients maintained viral suppression after 48 weeks. No subject discontinued therapy because of adverse events. HDL cholesterol increased by 28% at week 24 (P < 0.0001) and 10% after 48 weeks of follow-up (P = 0.319) in the NVP group. In the NRTI group, LDL cholesterol increased by 14% at week 48 (P = 0.076). Mitochondrial DNA/nuclear DNA ratio and mitochondrial respiratory chain complex IV activity showed a trend toward increasing in the NVP group. Mean (SD) LPV trough levels were 6340 (2129) ng/mL in the NRTI group and 5161 (2703) ng/mL in the NVP group (P = 0.140). CONCLUSIONS: In antiretroviral-experienced subjects with sustained viral suppression, dual therapy with NVP plus LPV/rtv at standard dosage was as potent and safe as standard-of-care HAART at 48 weeks of follow-up. This approach may reduce mitochondrial toxicity and improve LPV/rtv-associated lipid abnormalities. The results of this pilot study support the study of this approach in a larger, randomized trial.

Adult↗

Mitochondrial respiratory chain in brain homogenates: activities in different brain areas in patients with Alzheimer's disease.

BACKGROUND AND AIMS: The potential influence of impaired oxidative metabolism in the modulation of manifestations in sporadic Alzheimer's disease (AD) has attracted much attention in the last 50 years. Unfortunately, many clinical and experimental results aiming at proving this hypothesis are still controversial. The aim was to study the enzymatic activities of respiratory chain (RC) complexes I through V in three brain areas of a group of patients with definite AD, and to compare the results with a group of normal brains. We simultaneously assessed the lipid peroxidation of the samples as a measure of free radical damage. METHODS: The specific activity of the individual complexes of the RC was measured spectrophotometrically, and the loss of cis-parinaric acid fluorescence was used to determine the chemical process of lipid peroxidation. RESULTS: We were not able to detect differences in any of the analyzed RC enzymatic activities, or in the level of lipid peroxidation between patients with AD and controls. Instead, differences were found in the number of mitochondria and in the intrinsic enzymatic activities of complexes III and IV in various brain areas. CONCLUSIONS: Spectrophotometric enzymatic analyses of respiratory complexes in brain homogenates do not support the primary contribution of mitochondrial RC dysfunction in the pathogenesis of AD.

Aged↗