Results of Infrainguinal Bypass in Acute Limb Ischaemia.

OBJECTIVE/BACKGROUND: To assess the outcomes of infrainguinal bypass performed for acute limb ischaemia, as well as the predictors of patency, mortality, and amputation. METHODS: This was a retrospective cohort study of patients undergoing infrainguinal bypass between 1998 and 2014. The cohort was stratified according to the indication for surgery into two groups: group A (acute limb ischaemia) and group B (chronic lower extremity ischaemia). Comparative analysis was performed on comorbidities, surgical technique, and outcomes, as well as prognostic factors in group A. RESULTS: In total, 702 bypasses were performed (group A, n = 107; group B, n = 595). Differences between groups were detected in age (65.9 vs. 70.9 years; p = .03), diabetes (16% vs. 49%; p < .01), renal insufficiency (6% vs. 13%; p = .05), stroke (7% vs. 14%; p = .04), and coronary artery disease (13% vs. 28%; p < .01). Patients with acute limb ischaemia more often required general anaesthesia (47% vs. 12%; p < .01) and a short bypass was more often performed (32% vs. 7%; p < .01). Median follow up was 23 and 24 months for groups A and B, respectively. No differences were found in patency rates at 1, 12, and 24 months between groups, but group B had a higher re-intervention rate during follow up. Primary patency in group A was 84%, 63%, and 58%, and in group B it was 88%, 62%, and 53% at 1, 12, and 24 months, respectively (p = .77). Assisted primary patency in group A was 85%, 72%, and 67%, and in group B it was 90%, 74%, and 66% at 1, 12, and 24 months, respectively (p = .61). Secondary patency in group A was 90%, 78%, and 75%, and in group B it was 94%, 80%, and 74% at 1, 12, and 24 months, respectively (p = .80). The freedom from re-intervention rate in group A was 91%, 74%, and 68%, and in group B it was 92%, 76%, and 71%, respectively (p = .04). Acute limb ischaemia was an independent risk factor for amputation (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.74-14.09; p < .01) and mortality (OR 4.13, 95% CI 1.53-11.14; p = .01) at 30 days. In group A, female sex, prosthetic conduit, and need of distal thrombectomy were independently associated with worse patency rates. Poor intra-operative runoff was correlated with higher amputation rates. CONCLUSION: Among those undergoing infrainguinal bypass, patients who present with acute limb ischaemia constitute a subset showing higher early rates of amputation and death. In this subset of patients, worse outcomes may be expected for women, prosthetic conduits, need for distal thrombectomy, and patients with poor intra-operative runoff.

Obesity/overweight and dental caries experience in children and adolescents: an umbrella review.

PURPOSE: The present umbrella review aimed to synthesize and critically assess the methodological and reporting quality of previous systematic reviews about the potential relationship between obesity or overweight and caries dental experience in pediatric patients. METHOD: Electronic database and manual searches were conducted in PubMed, Embase, and Cochrane Library up to July 2023. The risk of bias assessment of eligible systematic reviews was performed using the Risk Of Bias In Systematic reviews (ROBIS) tool. A systematization of the results was carried out in order to understand the possible relationship between the two conditions. RESULTS: Electronic and manual searches identified 136 titles and abstracts. After the removal of duplicates, 15 full-text articles were assessed for eligibility. Six studies were excluded, resulting in 8 systematic reviews and 1 scoping review that met the inclusion criteria. Five were systematic reviews without meta-analysis and the rest were conducted with quantitative analysis. CONCLUSION: Conflicting findings to date from this umbrella review suggest that the relationship between obesity and dental caries in children is still inconclusive and likely to be complex.

Disease risk estimates in V30M variant transthyretin amyloidosis (A-ATTRv) from Mallorca.

BACKGROUND: Variant transthyretin amyloidosis (A-ATTRv) is an autosomal dominant disease caused by a range of TTR gene variants which entail great phenotypical heterogeneity and penetrance. In Majorca, the A-ATTRv caused by the V30M gene variant (A-ATTRV30M) is the most common. Since asymptomatic carriers are at risk of developing the disease, estimating age of onset is vital for proper management and follow-up. Thus, the aim of this study was to estimate age-related penetrance in ATTRV30M variant carriers from Majorca. METHODS: The disease risk among carriers from ATTRV30M families from Majorca was estimated by Non-parametric survival estimation. Factors potentially involved in the disease expression, namely gender and parent of origin were also analysed. RESULTS: A total of 48 heterozygous ATTRV30M families (147 affected patients and 123 were asymptomatic carriers) were included in the analysis. Penetrance progressively increased from 6% at 30 years to 75% at 90 years of age. In contrast to other European populations, we observe a similar risk for both males and females, and no difference of risk according to the parent of origin. CONCLUSIONS: In this first study assessing the age-related penetrance of ATTRV30M variant in Majorcan families, no effect of gender or parent of origin was observed. These findings will be helpful for improving management and follow-up of TTR variant carrier individuals.

[Study of drug dose calculation for morbidly obese patients]. / Estudio de la dosificación de fármacos en los pacientes con obesidad mórbida.

INTRODUCTION: The objective of this study is to analyse the appropriateness and characteristics of drug dose calculation for hospitalised, morbidly obese patients. METHODS: Retrospective, descriptive study of dose calculations for drugs prescribed to hospitalised, morbidly obese patients in a tertiary hospital in 2007. The recommendations prepared by the Pharmacy division are used as a standard. RESULTS: We included 62 patients. The mean number of medications prescribed per patient was 12.1 (4-39), and an average of 2.4 (1-10) are listed in the recommendations. A total of 135 drugs were prescribed. Dose calculations for 81 of the above (60 %) coincided with recommendations and 54 (40 %) did not; there were 51 cases of underdosing and three cases of overdosing. DISCUSSION: Improper dosing was detected for prescriptions in the systemic antibiotic and antithrombin drug groups, with underdosing being more common than overdosing.

The ICD-11 developmental field study of reliability of diagnoses of high-burden mental disorders: results among adult patients in mental health settings of 13 countries.

Reliable, clinically useful, and globally applicable diagnostic classification of mental disorders is an essential foundation for global mental health. The World Health Organization (WHO) is nearing completion of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD-11). The present study assessed inter-diagnostician reliability of mental disorders accounting for the greatest proportion of global disease burden and the highest levels of service utilization - schizophrenia and other primary psychotic disorders, mood disorders, anxiety and fear-related disorders, and disorders specifically associated with stress - among adult patients presenting for treatment at 28 participating centers in 13 countries. A concurrent joint-rater design was used, focusing specifically on whether two clinicians, relying on the same clinical information, agreed on the diagnosis when separately applying the ICD-11 diagnostic guidelines. A total of 1,806 patients were assessed by 339 clinicians in the local language. Intraclass kappa coefficients for diagnoses weighted by site and study prevalence ranged from 0.45 (dysthymic disorder) to 0.88 (social anxiety disorder) and would be considered moderate to almost perfect for all diagnoses. Overall, the reliability of the ICD-11 diagnostic guidelines was superior to that previously reported for equivalent ICD-10 guidelines. These data provide support for the suitability of the ICD-11 diagnostic guidelines for implementation at a global level. The findings will inform further revision of the ICD-11 diagnostic guidelines prior to their publication and the development of programs to support professional training and implementation of the ICD-11 by WHO member states.

Oxidative stress as a signal to up-regulate gamma-cystathionase in the fetal-to-neonatal transition in rats.

Hepatic gamma-cystathionase, a rate-limiting enzyme for the synthesis of L-cysteine from L-methionine in the trans-sulphuration pathway, exhibits significantly higher activity in the newly born infant as compared to the fetus. The aim of this work was: 1) To determine whether the increase in gamma-cystathionase activity occurring in the fetal-to-neonatal transition is due to up-regulation of its mRNA and protein, 2) To elucidate the mechanisms responsible for this increase in gamma-cystathionase activity. Our results show that expression of gamma-cystathionase at both the mRNA and protein levels was higher in newborn than in fetal liver. gamma-Cystathionase activity in fetal hepatocytes in vitro increased when incubated with tert-butyl-hydroperoxide at low concentration (0.01 mM). Hence, moderate oxidative stress would act as a signal to up-regulate gamma-cystathionase in the fetal to neonatal transition. Stress hormones, such as phenylephrine or glucagon also increased gamma-cystathionase activity in fetal hepatocytes. We also report a competitive inhibition of purified gamma-cystathionase by L-cysteine, which would help to maintain physiological low L-cysteine levels in hepatocytes. In conclusion, our results show that increased hepatic gamma-cystathionase activity in the fetal-to-neonatal transition is due to up-regulation of its gene expression mediated by stress hormones together with the physiological oxidative stress that occurs at birth.

[Comparative study of errors in electronic versus manual prescription]. / Estudio comparativo de errores con prescripción electrónica versus prescripción manual.

OBJECTIVE: Electronic prescribing is considered a basic measure for the prevention and reduction of medications errors. The goal of this survey was to assess the incidence of errors occurring with electronic versus standard prescription. METHOD: A prospective, sequential, open-label study to assess errors with electronic prescribing as compared to traditional manual prescribing in two public hospitals in Balearic Islands. Errors regarding medication, diet and/or nursing orders were assesses along four process stages: medical prescription, pharmacy transcription/validation, nursing transcription, and dispensation. RESULTS: With manual prescription 1,576 errors/18,539 therapy orders (8.50%) were identified, whereas with electronic prescription 827 errors/18,885 therapy orders (4.38%) were detected, which represents a relative risk reduction by 48% and an absolute risk reduction by 4.12% (p < 0.0001). Pharmacy transcription/validation errors decreased (1.73 vs. 0.13%, p < 0.0001), as did nursing transcription errors (2.54 vs. 0.81%, p < 0.0001) and dispensation errors (2.13 vs. 0.96%, p < 0.0001); however, the number of prescription errors increased (2.10 vs. 2.40%, p = 0.0401). CONCLUSIONS: Electronic prescription is a powerful tool, and one that in this work was shown to decrease medication-, diet-, and nursing care-related errors in a highly significant way; however, it should be developed and maintained in order to achieve safety and effectiveness as required by drug usage.

Na+ dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) in primary astrocyte cultures: effect of oxidative stress.

The Na+ -dependent L-glutamate transporters EAAT1(GLAST), EAAT2 (GLT-1) and EAAT3 (EAAC1) are expressed in primary astrocyte cultures, showing that the EAAT3 transporter is not neuron-specific. The presence of these three transporters was evaluated by RT-PCR, immunoblotting, immunocytochemical techniques, and transport activity. When primary astrocyte cultures were incubated with L-buthionine-(S,R)-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, the GSH concentration was significantly lower than in control cultures, but the expression and amount of protein of EAAT1, EAAT2 and EAAT3 and transport of L-glutamate was unchanged. Oxidative stress was created by adding H(2)O(2) or tert.-butyl hydroperoxide (t-bOOH) to the primary astrocyte cultures and cell damage was evaluated by measuring activity of lactate dehydrogenase. Under oxidative stress, GSH levels were significantly lower than in control astrocytes; but the expression and the amount of protein of the three transporters remained unchanged. However, L-glutamate uptake was significantly lower in astrocytes under oxidative conditions when compared to controls. L-Glutamate uptake was not changed in the presence of ascorbate, but was partially recovered in the presence of DTT and GSH ethyl ester. This report emphasizes that oxidative stress and not GSH depletion alters transporter activity without changing transporter expression.

[A prospective randomized study of sulphonylureas therapeutic interchange in patients with type 2 diabetes mellitus]. / Estudio prospectivo y aleatorizado de intercambio terapéutico de sulfonilureas en pacientes con diabetes mellitus tipo 2.

OBJECTIVE: To clinically assess effectiveness of therapeutic interchange from glibenclamide to gliclazide in the hospital setting. METHODS: An open-label prospective, randomized study with two groups of patients: a reference group (patients still receiving their previous outpatient regimen of glibenclamide) and an interchange group (patients with gliclazide substituted for glibenclamide according to a hospital-approved interchange protocol). The efficacy endpoint used was blood glucose at 3 and 6 days post-intervention. A patient with blood glucose < 200 mg/L was considered clinically controlled, and blood glucose changes < or > 30 mg/dL were considered significant. RESULTS: One hundred and sixteen patients were randomized. Blood glucose on the day before the intervention was 177.9 mg/dL +/- 63.4 in the reference group versus 171.3 mg/dL +/- 52.1 in the interchange group (p = 0.92). Mean blood glucose during the first 3 days post-intervention was 156.1 mg/dL +/- 47.5 and 177.7 mg/dL +/- 36.0 (p = 0.14) in the reference and interchange groups, respectively; and mean values for the first 6 days post-intervention were 142.1 mg/dL +/- 36.0 and 172.8 mg/dL +/- 28.2, respectively (p = 0.01). The overall analysis of blood glucose levels showed a better control in the reference group versus baseline values, which was not seen in the interchange group, where blood glucose remained stable and similar to baseline. In no case were 3-day and 6-day blood glucose mean levels above 200 mg/dL, which may be considered acceptable within the hospital setting. CONCLUSIONS: Therapeutic interchange may be safely performed with no clinical impairment, but better controls were achieved in the reference group.

[A prospective comparative study to assess the impact of pharmaceutical intervention in the promotion of sequential therapy with flouroquinolones]. / Estudio prospectivo y comparativo para evaluar el impacto de la intervención farmacéutica en la promoción de la terapia secuencial con fluoroquinolonas.

OBJECTIVE: To assess the impact of pharmaceutical intervention on the use of sequential therapy (ST) with fluoroquinolones. METHODS: A prospective comparative study of pharmaceutical intervention in two stages: observational stage and intervention stage for ST promotion. RESULTS: In all, 250 patients receiving intravenous therapy with fluoroquinolones (113 with levofloxacin and 137 with ciprofloxacin) were studied, with 76 and 70 patients, respectively, being eligible for a pharmaceutical intervention program to promote ST. Pharmaceutical intervention showed a decreased duration of intravenous therapy and increased duration of oral therapy for both drugs, as well as decreased medication-related costs, all in a statistically significant manner. DISCUSSION: ST promotion provides an opportunity to expand the role of hospital pharmacists and to optimize fluoroquinolone-based therapy, which results in decreased intravenous treatments and provides a more cost-effective option.

Stent-graft repair for blunt traumatic aortic injury: functional and survival outcomes.

AIM: Traumatic aortic injury is usually lethal, most often because of serious associated wounds. The short- and midterm outcome of endovascular exclusion was assessed as the current treatment of choice due to a lower mortality and morbidity than open surgical treatment. METHODS: We reviewed the cases of 8 patients (5 male, mean age 33 years) undergoing endovascular repair of a traumatic thoracic aortic lesion, confirmed by computed tomographic angiography, at our centre. Most patients showed a contained lesion limited to the aortic isthmus and severe associated injuries. RESULTS: Intrahospital mortality was 37.5% (N.=3) and mostly due to posttraumatic brain injury (N.=2). Most patients were hemodynamically stable at the time of endovascular repair (N.=6). The median time to surgery was 12 hours (3-48 hours). The endografts used were TAG® (W.L. Gore and Associates, Flagstaff) in three patients, and Valiant® (Medtronic, Santa Rosa, CA) in four. The technical success rate was 100%. In one case, the left subclavian artery was occluded without signs of arm ischemia. There were no cases of paraplegia or stroke related to treatment. No revision procedures were needed during follow-up. CONCLUSION: Endovascular repair shortly after injury seems to be effective and safe with a low associated morbidity and mortality.

Comprehensive pharmaceutical care in a vascular surgery department.

OBJECTIVE: The pharmacist must work with the clinical team across the continuum of care to develop and therefore improve the patient's quality of life. In this study, we present the results from a continuous pharmaceutical care programme for patients admitted to an angiology and vascular surgery department. MATERIAL AND METHODS: A 5-month prospective study to evaluate the results of a pharmaceutical care programme in an angiology and vascular surgery department. The pharmacist went on the rounds with the clinical team from Monday to Friday and helped make decisions on treatment, and detect and resolve conciliation discrepancies upon admission and discharge, and drug-related problems during the hospital stay. RESULTS: We detected and resolved 273 conciliation discrepancies in 99 patients and 76 drug-related problems in 46 patients. Global acceptance of pharmacist interventions was 96%. CONCLUSIONS: Seventy-four percent of patients presented conciliation discrepancies. Efficiency of pharmaceutical activity across the continuum of care is demonstrated by the high acceptance of the interventions.

The L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2): expression and regulation in rat lactating mammary gland.

The Na(+)-dependent L-glutamate transporters GLAST (EAAT1) and GLT-1 (EAAT2), were expressed in rat lactating mammary gland, but EAAC1 (EAAT3) was not. GLT-1 expression in rat lactating mammary gland was constant in all the physiological situations studied; however, the GLAST expression is under tight regulation. Fasting for 24 h decreased the GLAST expression which returned to control values after refeeding. Weaning for 24 h produced a decrease in GLAST expression through a mechanism independent of prolactin deficiency. Resuckling for 6 h returned the expression of this transporter to control values. There is a correlation between the levels of GLAST (mRNA and protein) and the in vivo uptake of L-glutamate by the lactating mammary gland during the starvation/refeeding cycle and milk accumulation process.

Elevated expression of liver gamma-cystathionase is required for the maintenance of lactation in rats.

Liver gamma-cystathionase activity increases in rats during lactation; its inhibition due to propargylglycine is followed by a significant decrease in lactation. This is reversible by N-acetylcysteine administration. To study the role of liver gamma-cystathionase and the intertissue flux of glutathione during lactation, we used lactating and virgin rats fed liquid diets. Virgin rats were divided into two groups as follows: one group was fed daily a diet containing the same amount of protein that was consumed the previous day by lactating rats (high protein diet-fed rats); the other virgin group was fed the normal liquid diet (control). The expression and activity of liver gamma-cystathionase were significantly greater in lactating rats and in high protein diet-fed virgin rats compared with control rats. The total glutathione [reduced glutathione (GSH) + oxidized glutathione (GSSG)] released per gram of liver did not differ in lactating rats or in high protein diet-fed rats, but it was significantly higher in these two groups than in control virgin rats. Liver size and the GSH + GSSG released by total liver were significantly higher in lactating rats than in high protein diet-fed virgin rats, and this difference was similar to the amount of glutathione taken up by the mammary gland (454.2 +/- 36.0 nmol/min). The uptake of total glutathione by the lactating mammary gland was much higher than the uptakes of free L-cysteine and L-cystine, which were negligible. These data suggest that the intertissue flux of glutathione is an important mechanism of L-cysteine delivery to the lactating mammary gland, which lacks gamma-cystathionase activity. This emphasizes the physiologic importance of the increased expression and activity of liver gamma-cystathionase during lactation.

Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal.

Na(+)-dependent transporters for glutamate exist on astrocytes (EAAT1 and EAAT2) and neurons (EAAT3). These transporters presumably assist in keeping the glutamate concentration low in the extracellular fluid of brain. Recently, Na(+)-dependent glutamate transport was described on the abluminal membrane of the blood-brain barrier. To determine whether the above-mentioned transporters participate in glutamate transport of the blood-brain barrier, total RNA was extracted from bovine cerebral capillaries. cDNA for EAAT1, EAAT2, and EAAT3 was observed, indicating that mRNA was present. Western blot analysis demonstrated all three transporters were expressed on abluminal membranes, but none was detectable on luminal membranes of the blood-brain barrier. Measurement of transport kinetics demonstrated voltage dependence, K(+)-dependence, and an apparent K(m) of 14 microM (aggregate of the three transporters) at a transmembrane potential of -61 mV. Inhibition of glutamate transport was observed using inhibitors specific for EAAT2 (kainic acid and dihydrokainic acid) and EAAT3 (cysteine). The relative activity of the three transporters was found to be approximately 1:3:6 for EAAT1, EAAT2, and EAAT3, respectively. These transporters may assist in maintaining low glutamate concentrations in the extracellular fluid.