Clinical evidence of parenteral glutamine supplementation in critical illness

Treballs Finals de Grau de Farmàcia, Facultat de Farmàcia, Universitat de Barcelona, 2017. Tutor/a: Maria Badia Tahull.[eng] Glutamine is a non-essential amino acid mostly synthetized and released to the blood stream by the skeletal muscle and the lungs. The enterocytes and the immune system cells are great glutamine consumers and glutamine is crucial for their correct function. Due to metabolic changes occurred during critical illness, the plasma level of glutamine becomes low and skeletal muscle becomes depleted. Treatment with glutamine tries to normalize plasma levels and improve the immune cell response. Glutamine’s chemical properties are unfavorable for their storage and so new ways of glutamine delivery are enveloped. The most current used alternative source are glutamine dipeptides. Administration of glutamine can be supplying the artificial nutrition support or being administrated independently; by parenteral or by enteral route. Traditional trials of glutamine supplementation demonstrate favorable results in patients with critical illness. However, newer trials which included more study population, among which the REDOX trial, where not able to confirm these results. A trend towards favorable outcomes were found in surgical and oncological patients with intravenous glutamine supplementation on physiological doses without renal and/or liver dysfunction. In contrast, there was also found high glutamine baseline levels in a subgroup of critically ill patients. With all the available clinical research information, it is still not clear if glutamine should be included in the routine clinical use.[cast] La glutamina es un aminoácido no esencial sintetizado y liberado a la circulación sanguínea mayoritariamente por la musculatura esquelética y los pulmones. Los enterocitos y las células del sistema inmunitario son grandes metabolizadores de la glutamina y ésta es crucial para su funcionamiento óptimo. Debido a cambios metabólicos sufridos en el paciente crítico, los niveles sanguíneos de glutamina disminuyen significativamente y se observa una depleción de glutamina en la musculatura esquelética. El tratamiento con glutamina tiene como objetivo normalizar los niveles plasmáticos y mejorar la respuesta del sistema inmunitario. Las propiedades químicas de la glutamina son desfavorables para su almacenaje y por eso se han desarrollado nuevas estructuras químicas de glutamina para ser administradas. La fuente alternativa más utilizada actualmente son los dipéptidos de glutamina. La administración de glutamina se puede realizar suplementando a la nutrición artificial o administrándose de forma independiente; por vía parenteral o bien por vía enteral. Los estudios tradicionales sobre la suplementación con glutamina demuestran resultados favorables en el paciente crítico. En cambio, estudios posteriores que incluyen un mayor número de pacientes, entre los cuales destaca el estudio REDOX, no han sido capaces de confirmar dichos resultados. Los estudios demuestran una tendencia favorable en pacientes quirúrgicos y oncológicos con suplementación de glutamina por vía parenteral en dosis fisiológicas que no presentaban insuficiencia renal y/o hepática. En cambio, también se han detectado en un subgrupo de pacientes niveles elevados de glutamina. Aun así, con toda la información clínica disponible actualmente, sigue siendo poco concluyente la inclusión de la glutamina en la práctica clínica habitual

Convé introduir el PrEP a Espanya?

Premis Pharmanews-Fedefarma 2016La teràpia PrEP ha estat aprovada per la European Medicines Agency (EMA) el mes de Juliol del 2016, per ser usada en conjunt amb altres mesures preventives (com el preservatiu) en la reducció del risc d’infecció del VIH. Són les autoritats competents de cada país i els seus sistemes sanitaris que han de decidir si volen (o no) incorporar el seu ús a la sanitat pública. França és l’únic país de la Unió Europea on actualment es troba finançat. Al 2012, als Estats Units ja va ser aprovat per la Food and Drug Administration (FDA) i s’ha posat en pràctica la seva utilització

Prescribing Errors With Low-Molecular-Weight Heparins

BACKGROUND: Low-molecular-weight heparins (LMWHs) are used in the prevention and treatment of venous thromboembolism (VTE). Bleeding is the primary major complication of LMWH therapy, which is associated with dose. The administration of appropriate dosages of LMWHs depends on the patient's risk of VTE, risk of bleeding, bodyweight, and renal function. Therefore, LMWH prescribing is prone to errors. However, no earlier study has explored the frequency of prescribing errors with LMWH. PURPOSE: The aim of the study was to determine the frequency and determinants of in-hospital LMWH-prescribing errors. METHODS: A cross-sectional study was conducted to examine the frequency and determinants of LMWH prescribing errors between April and August 2014. We randomly selected 500 patients 18 years and older with at least one LMWH prescription during inpatient hospitalization. A prescribing error was a deviation from the internal hospital guidelines. Logistic regression estimated determinants of prescribing error. RESULTS: A prescribing error was present with 34% of all LMWH users. The most frequently recorded error was a dose that was not adjusted to body weight and/or renal function (85%). Prophylactic LMWH prescribing in medical wards was associated with a higher risk of prescribing error as compared with surgical wards. CONCLUSIONS: The frequency of prescribing errors was 34% in a tertiary care hospital. Being a patient with prophylactic LMWH use on a medical ward is a determinant for LMWH prescribing error. Interventions that will lead to better electronic recording of body weight and more awareness among medical doctors may reduce the total number of prescribing errors

Endovascular treatment in anterior circulation stroke beyond 6.5 hours after onset or time last seen well:results from the MR CLEAN Registry

BACKGROUND: Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice. METHODS: The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death. RESULTS: Of 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, p<0.04) and had slightly lower ASPECTS (median 8 vs 9, p<0.01), but better collateral status (collateral score 2–3: 68.3% vs 57.7%, p=0.03). No differences were observed in proportions of functional independence (43.3% vs 40.5%, p=0.57) or death (24.0% vs 28.9%, p=0.28). After matching, outcomes remained similar (adjusted common OR for 1 point improvement in mRS 1.04, 95% CI 0.56 to 1.93). CONCLUSIONS: Without the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window

A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke

The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P=0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups

Coronary microvascular resistance: methods for its quantification in humans

Coronary microvascular dysfunction is a topic that has recently gained considerable interest in the medical community owing to the growing awareness that microvascular dysfunction occurs in a number of myocardial disease states and has important prognostic implications. With this growing awareness, comes the desire to accurately assess the functional capacity of the coronary microcirculation for diagnostic purposes as well as to monitor the effects of therapeutic interventions that are targeted at reversing the extent of coronary microvascular dysfunction. Measurements of coronary microvascular resistance play a pivotal role in achieving that goal and several invasive and noninvasive methods have been developed for its quantification. This review is intended to provide an update pertaining to the methodology of these different imaging techniques, including the discussion of their strengths and weaknesses

Mobile element insertions in rare diseases: a comparative benchmark and reanalysis of 60,000 exome samples

Mobile element insertions (MEIs) are a known cause of genetic disease but have been underexplored due to technical limitations of genetic testing methods. Various bioinformatic tools have been developed to identify MEIs in Next Generation Sequencing data. However, most tools have been developed specifically for genome sequencing (GS) data rather than exome sequencing (ES) data, which remains more widely used for routine diagnostic testing. In this study, we benchmarked six MEI detection tools (ERVcaller, MELT, Mobster, SCRAMble, TEMP2 and xTea) on ES data and on GS data from publicly available genomic samples (HG002, NA12878). For all the tools we evaluated sensitivity and precision of different filtering strategies. Results show that there were substantial differences in tool performance between ES and GS data. MELT performed best with ES data and its combination with SCRAMble increased substantially the detection rate of MEIs. By applying both tools to 10,890 ES samples from Solve-RD and 52,624 samples from Radboudumc we were able to diagnose 10 patients who had remained undiagnosed by conventional ES analysis until now. Our study shows that MELT and SCRAMble can be used reliably to identify clinically relevant MEIs in ES data. This may lead to an additional diagnosis for 1 in 3000 to 4000 patients in routine clinical ES.Funding The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 779257. RW received an international fellowship from the José Luis Castaño-SEQC Foundation. FM is supported by the Edmond J. Safra Foundation through the Edmond J. Safra Fellowship in Movement Disorders

Asociación entre la 25-hidroxivitamina D y el antígeno prostático específico: un estudio retrospectivo en hombres sin patologías prostáticas

Aunque estudios recientes asocian la vitamina D con el cáncer de próstata, otros estudios descartan una asociación entre esta vitamina y el cáncer de próstata o el antígeno prostático específico (PSA). Dado que no se pueden extraer conclusiones de los datos existentes, realizamos un estudio para analizar la relación entre el PSA y la 25-hidroxivitamina D [25(OH)D]

Association between serum 25-hydroxyvitamin D and prostate-specific antigen: a retrospective study in men without prostate pathology

Recently, vitamin D status has been associated with prostate cancer risk. However, some studies argue that there is no association of vitamin D with prostate cancer risk and serum prostate-specific antigen (PSA) concentrations. No clear conclusions can be drawn from the studies found in the literature. Our aim was to assess the relationship between PSA and 25-hydroxyvitamin D [25(OH)D]

Prescribing Errors With Low-Molecular-Weight Heparins

BACKGROUND: Low-molecular-weight heparins (LMWHs) are used in the prevention and treatment of venous thromboembolism (VTE). Bleeding is the primary major complication of LMWH therapy, which is associated with dose. The administration of appropriate dosages of LMWHs depends on the patient's risk of VTE, risk of bleeding, bodyweight, and renal function. Therefore, LMWH prescribing is prone to errors. However, no earlier study has explored the frequency of prescribing errors with LMWH. PURPOSE: The aim of the study was to determine the frequency and determinants of in-hospital LMWH-prescribing errors. METHODS: A cross-sectional study was conducted to examine the frequency and determinants of LMWH prescribing errors between April and August 2014. We randomly selected 500 patients 18 years and older with at least one LMWH prescription during inpatient hospitalization. A prescribing error was a deviation from the internal hospital guidelines. Logistic regression estimated determinants of prescribing error. RESULTS: A prescribing error was present with 34% of all LMWH users. The most frequently recorded error was a dose that was not adjusted to body weight and/or renal function (85%). Prophylactic LMWH prescribing in medical wards was associated with a higher risk of prescribing error as compared with surgical wards. CONCLUSIONS: The frequency of prescribing errors was 34% in a tertiary care hospital. Being a patient with prophylactic LMWH use on a medical ward is a determinant for LMWH prescribing error. Interventions that will lead to better electronic recording of body weight and more awareness among medical doctors may reduce the total number of prescribing errors