In this study, we assessed factors associated with cardiovascular risk in patients with sleep apnea-hypopnea syndrome (SAHS) through analysis of plasma concentrations of N-terminal prohormone brain ...natriuretic peptide (NTproBNP) and high-sensitivity C-reactive protein (hsCRP). In addition, we analyzed the effect of nasal continuous positive airway pressure (nCPAP) on these markers.
Forty-two patients with SAHS (mild to moderate in 15 cases and severe in 27) were compared with 14 individuals without SAHS. The participants were not receiving drug treatment and they did not have diabetes, hypertension, marked dyslipidemia, or cardiovascular disease, which was ruled out both clinically and by echocardiography and
99mTc-tetrofosmin scintigraphy at rest and during exercise. The effects of nCPAP in patients with severe SAHS were analyzed after 6 months of treatment.
Following adjustment for age, body mass index, and smoking habit, the mean concentrations of markers were not significantly higher in patients with severe SAHS than in those with mild-to-moderate SAHS or in control subjects. Nevertheless, in patients with SAHS the main factor influencing NTproBNP concentrations was the percentage of time with a nocturnal arterial oxygen saturation of less then 90% (
r=0.37,
P=.017). No variables predictive of hsCRP concentration were identified. The concentrations of the markers were reduced by nCPAP, but the differences were not statistically significant.
While nocturnal hypoxemia in SAHS is responsible for variations in the plasma concentration of NTproBNP (as a result of cardiovascular changes), SAHS appears not to be associated with the inflammatory marker hsCRP when patients with heart disease, cardiovascular risk factors, or those receiving pharmacologic treatment are excluded.
Investigamos los factores del síndrome de apneas-hipopneas durante el sueño (SAHS) que activan los mecanismos de riesgo cardiovascular, a través del estudio de las concentraciones plasmáticas del fragmento N-terminal del precursor del péptido natriurético cerebral (NTproBNP) y de la proteína C reactiva de alta sensibilidad (PCRas), así como el efecto que sobre ellos tiene el tratamiento con presión positiva continua de la vía aérea nasal (CPAPn).
Se estudió a 42 pacientes con SAHS (leve-moderado en 15 casos y grave en 27), comparados con 14 personas sin SAHS. No tomaban fármacos ni presentaban diabetes, hipertensión, dislipemia importante o enfermedad cardiovascular, que se descartó tanto clínicamente como por ecocardiografía y tomografía computarizada por emisión de fotón cínico-esfuerzo con
99mTc-tetrofosmina. En los pacientes con SAHS grave se estudiaron los efectos de 6 meses con CPAPn.
Ajustando por edad, índice de masa corporal y tabaquismo, las medias de los biomarcadores no fueron significativamente más altas en los pacientes con SAHS grave que en aquéllos con SAHS leve-moderado o en los controles. Sin embargo, en los pacientes con SAHS el principal factor que influyó en las concentraciones de NTproBNP fue el porcentaje de tiempo con saturación arterial de oxígeno nocturna menor del 90% (r = 0,37; p = 0,017), sin que se encontrara ningún predictor de los valores séricos de la PCRas. La aplicación de CPAPn hizo descender, pero no significativamente, las concentraciones de los biomarcadores.
Mientras que la hipoxemia nocturna en el SAHS es la responsable de las variaciones en los valores del NTproBNP, derivado de la afectación cardíaca, el SAHS no parece estar asociado con el biomarcador inflamatorio PCRas, cuando se excluye a los pacientes con alteraciones cardíacas, factores de riesgo cardiovascular o en tratamiento farmacológico.
BackgroundOpioids can have serious risks and side effects. Improving the way opioids are prescribed through clinical practice guidelines can ensure patients have access to safer, more effective pain ...treatment.PurposeTo assess the level of adherence to standard treatment guidelines among clinicians prescribing opioid based therapy for admitted patients.Material and methodsThis was a cross sectional study conducted on 23 May 2016 in a tertiary hospital. Electronic prescriptions were analysed. When therapy included opioids, the following data were collected: age, gender, opioid prescription and clinical service. Tramadol was excluded.‘Prescription adherence to standard treatment guidelines’ was defined as follows: (1) firstline pain therapy should be based on non-opioid analgesics; (2) when prescribing an opioid, it should be checked if another opioid was prescribed to prevent overdose; (3) the first opioid prescribed should be a normal release opioid and at a minimum effective dose; (4) an appropriate rescue opioid should be used. If one of the above conditions was not met, the prescription was classified as ‘non-adherent to standard treatment guidelines’.ResultsFrom a cohort of 1014 admitted patients with electronic prescribing, 100 with opioids were screened. 51 (51%) were men. Median age was 74 (4–99) years. 30 (30%) patients were in the surgical unit, 22 (22%) in internal medicine, 10 (10%) in oncology, 8 (8%) in palliative care, 8 (8%) in geriatrics, 6 (6%) in pneumology and 16 (16%) in ‘other units’. Patients had a mean of 1.35 (SD 0.64) opioids prescribed. As firstline therapy, most common opioids prescribed were parenteral morphine (40; 40%), transdermal fentanyl (32; 32%) and prolonged release oral morphine (13; 13%), and as secondline, parenteral morphine (12; 48%), normal release oral fentanyl (5; 20%) and normal release oral morphine (3; 12%).20 (20%) opioid prescriptions did not follow standard treatment guidelines: 5/30 (17%) of surgical unit opioid prescriptions, 5/22 (23%) of internal medicine, 2/10 (20%) of oncology, 1/8 (13%) of palliative care, 0/8 of geriatrics, 2/6 (33%) of pneumology and 5/16 (31%) of ‘other units’. Reasons for non-adherent prescriptions were: ‘do not have an non-opioid analgesic therapy prescribed’ (12/20), ‘non appropriate rescue opioid’(1/20), ‘prescription of two different rescue opioids’(4/20) and ‘regular prescription of two different opioids’ (3/20; 43%).ConclusionLevel of adherence to standard treatment guidelines could be considered adequate. Opioid prescriptions in the hospital setting could be improved facilitating access to clinical practice guidelines for opioid therapy to clinicians, especially in clinical services where opioid prescription is not a routine clinical practice.No conflict of interest
The NEXT-White detector, a high-pressure gaseous xenon time projection chamber, demonstrated the excellence of this technology for future neutrinoless double beta decay searches using photomultiplier ...tubes (PMTs) to measure energy and silicon photomultipliers (SiPMs) to extract topology information. This analysis uses \(^{83m}\text{Kr}\) data from the NEXT-White detector to measure and understand the energy resolution that can be obtained with the SiPMs, rather than with PMTs. The energy resolution obtained of (10.9 \(\pm\) 0.6) \(\%\), full-width half-maximum, is slightly larger than predicted based on the photon statistics resulting from very low light detection coverage of the SiPM plane in the NEXT-White detector. The difference in the predicted and measured resolution is attributed to poor corrections, which are expected to be improved with larger statistics. Furthermore, the noise of the SiPMs is shown to not be a dominant factor in the energy resolution and may be negligible when noise subtraction is applied appropriately, for high-energy events or larger SiPM coverage detectors. These results, which are extrapolated to estimate the response of large coverage SiPM planes, are promising for the development of future, SiPM-only, readout planes that can offer imaging and achieve similar energy resolution to that previously demonstrated with PMTs.
BackgroundAccording to international consensus, an institutional review board (IRB) report is required prior to starting a clinical trial. The majority of clinical trial applications are rejected ...following initial IRB review. Modifications are needed to these applications prior to receiving IRB approval.PurposeTo evaluate the extent to which the onset of clinical trials are delayed due to IRB rejection during their initial review because of informed consent form (ICF) deficiencies, and to evaluate the types of objections to the ICFs.Material and methodsA retrospective observational study was performed following initial reviews of clinical trials conducted by the La Paz Hospital IRB (2012–2015). The primary endpoint was the number of clinical trials evaluated and rejected by the IRB following their initial review due to deficiencies observed in the trials’ ICFs and the type of objections appealed. Data were obtained from IRB meeting min during the study period.ResultsOver the study period, 1858 clinical studies were evaluated. Of these, 1181 (63.5%) were rejected after the initial review. The objections leading to IRB rejection of a clinical study were due to defects in the ICFs (53.1%), design defects (27.4%) and other issues (30.5%). 1558 required a signed informed consent for subject participation (83.9%), of which 987 were not approved at first review because of objections to the informed consent documents (63.3%). The reasons for objections to the ICFs were primarily unreadability (11.7%) followed by inadequate information provided in accordance with Spain’s Data Protection Law, specifically regarding the rights that the data owner has to access his personal information, rectify it, cancel it or decline its use in the clinical study (9.2%), and biological sample management according to Spanish regulations (7.8%).ConclusionRejection of clinical studies by the IRB following their initial review was frequent and delayed the onset of these studies. Deficiencies found in studies’ ICFs were the main reason for research protocol rejections. There were two fundamental weaknesses in these documents: unreadability and discordance with different countries’ regulations, mainly concerning personal data protection and management of biological materials. Healthcare systems should promote integration and coordinate regulations to reduce diversity in legislation between countries to reduce waste in biomedical research.References and/or acknowledgementsLa Paz Institutional Review Board members.No conflict of interest
The imaging of individual Ba\(^{2+}\) ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana ...nature of the neutrino. In this paper we demonstrate selective single Ba\(^{2+}\) ion imaging inside a high-pressure xenon gas environment. Ba\(^{2+}\) ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1\(\times\)1~cm\(^2\) located inside 10~bar of xenon gas. This new form of microscopy represents an important enabling step in the development of barium tagging for neutrinoless double beta decay searches in \(^{136}\)Xe, as well as a new tool for studying the photophysics of fluorescent molecules and chemosensors at the solid-gas interface.
To investigate the relationship between maximum standardized uptake value (SUVmax) of ovarian lesions and histopathology subtypes, and their involvement in the response and prognosis of patients with ...epithelial ovarian carcinoma (EOC).
A retrospective analysis of 31 patients with EOC and 18F-FDG PET/CT before treatment, including an assessment of the SUVmax of ovarian lesion. Histopathological diagnosis and follow-up was performed.
A study was made on the relationship between the SUVmax and histological type (type I and II) and tumor stage, as well as the role of various parameters (SUVmax, histology, stage) on the patient outcomes (complete response CR, overall survival OS, disease-free survival DFS, and disease-free DF status, at 12 and 24 months).
The medium SUVmax in type I lesions was lower than in type II (6.3 and 9.3, respectively; p=0.03). A 7.1 cut-off was set for SUVmax in order to identify type II EOC (sensitivity: 77.8%, specificity: 69.2%; AUC=0.748; p=0.02). No significant relationship was found between tumor stage and SUVmax.
CR was more common in early stages; relative risk (RR) of 1.64; p=0.003, as well as in type I tumors and a lower SUVmax.
Tumor stage was decisive in DFS (p=0.04), LE24m (0.07) and OS (p=0.08). Longer DFS and a higher percentage of DF 24m were observed in type I tumors (RR: 1.32; p=0.26).
SUVmax was related to EOC histology, so could predict the response and prognosis of these patients. No association was found between glycolytic activity of the primary tumor with the response and prognosis.
Investigar la relación del valor máximo estandarizado de captación (SUVmáx) de la lesión ovárica con el subtipo histopatológico (I/II) y su implicación en la respuesta al tratamiento y en el pronóstico de las pacientes con carcinoma epitelial de ovario (CEO).
Análisis retrospectivo de 31 pacientes con CEO y 18F-FDG PET/TC previo al tratamiento, determinándose el SUVmáx de la lesión ovárica y realizándose diagnóstico histopatológico del tumor y seguimiento clínico-radiológico.
Se estudió la relación del SUVmáx con el tipo histológico (tipos I y II) y el estadio tumoral, así como la implicación de este y otros parámetros (histología, estadio) en la evolución de las pacientes (respuesta completa RC, supervivencia global SG, supervivencia libre de enfermedad SLE, estado libre de enfermedad a los 12 meses LE12m y a los 24 meses LE24m).
El SUVmáx medio en lesiones tipo I fue menor que en las tipo II (6,3 y 9,3, respectivamente; p=0,03). Se obtuvo un valor de corte de SUVmáx de 7,1 en la identificación del CEO tipo II (sensibilidad: 77,8%; especificidad: 69,2%; AUC=0,748; p=0,02). No se halló relación significativa entre SUVmáx y estadio tumoral.
Alcanzar RC fue más frecuente en estadios precoces; riesgo relativo (RR) de 1,64; p=0,003, en tumores tipo I y en los de menor SUVmáx.
El estadio tumoral fue determinante en la SLE (p=0,04), en el LE24m (p=0,07) y en la SG (p=0,08). Observamos SLE más prolongadas y mayor porcentaje de pacientes LE24m en tumores tipo I (RR: 1,32; p=0,26).
El SUVmáx se relacionó con el tipo histológico del CEO. No se encontró relación entre la actividad glucolítica del tumor primario con la respuesta y el pronóstico.
C75 is a potential drug for the treatment of obesity. It was first identified as a competitive, irreversible inhibitor of fatty acid synthase (FAS). It has also been described as a malonyl-CoA ...analogue that antagonizes the allosteric inhibitory effect of malonyl-CoA on carnitine palmitoyltransferase I (CPT I), the main regulatory enzyme involved in fatty acid oxidation. On the basis of MALDI-TOF analysis, we now provide evidence that C75 can be transformed to its C75-CoA derivative. Unlike the activation produced by C75, the CoA derivative is a potent competitive inhibitor that binds tightly but reversibly to CPT I. IC50 values for yeast-overexpressed L- or M-CPT I isoforms, as well as for purified mitochondria from rat liver and muscle, were within the same range as those observed for etomoxiryl-CoA, a potent inhibitor of CPT I. When a pancreatic INS(823/13), muscle L6E9, or kidney HEK293 cell line was incubated directly with C75, fatty acid oxidation was inhibited. This suggests that C75 could be transformed in the cell to its C75-CoA derivative, inhibiting CPT I activity and consequently fatty acid oxidation. In vivo, a single intraperitoneal injection of C75 in mice produced short-term inhibition of CPT I activity in mitochondria from the liver, soleus, and pancreas, indicating that C75 could be transformed to its C75-CoA derivative in these tissues. Finally, in silico molecular docking studies showed that C75-CoA occupies the same pocket in CPT I as palmitoyl-CoA, suggesting an inhibiting mechanism based on mutual exclusion. Overall, our results describe a novel role for C75 in CPT I activity, highlighting the inhibitory effect of its C75-CoA derivative.
Objetivo Investigamos los factores del síndrome de apneas-hipopneas durante el sueño (SAHS) que activan los mecanismos de riesgo cardiovascular, a través del estudio de las concentraciones ...plasmáticas del fragmento N-terminal del precursor del péptido natriurético cerebral (NTproBNP) y de la proteína C reactiva de alta sensibilidad (PCRas), así como el efecto que sobre ellos tiene el tratamiento con presión positiva continua de la vía aérea nasal (CPAPn). Pacientes y métodos Se estudió a 42 pacientes con SAHS (leve-moderado en 15 casos y grave en 27), comparados con 14 personas sin SAHS. No tomaban fármacos ni presentaban diabetes, hipertensión, dislipemia importante o enfermedad cardiovascular, que se descartó tanto clínicamente como por ecocardiografía y tomografía computarizada por emisión de fotón cínico-esfuerzo con99m Tc-tetrofosmina. En los pacientes con SAHS grave se estudiaron los efectos de 6 meses con CPAPn. Resultados Ajustando por edad, índice de masa corporal y tabaquismo, las medias de los biomarcadores no fueron significativamente más altas en los pacientes con SAHS grave que en aquéllos con SAHS leve-moderado o en los controles. Sin embargo, en los pacientes con SAHS el principal factor que influyó en las concentraciones de NTproBNP fue el porcentaje de tiempo con saturación arterial de oxígeno nocturna menor del 90% (r = 0,37; p = 0,017), sin que se encontrara ningún predictor de los valores séricos de la PCRas. La aplicación de CPAPn hizo descender, pero no significativamente, las concentraciones de los biomarcadores. Conclusiones Mientras que la hipoxemia nocturna en el SAHS es la responsable de las variaciones en los valores del NTproBNP, derivado de la afectación cardíaca, el SAHS no parece estar asociado con el biomarcador inflamatorio PCRas, cuando se excluye a los pacientes con alteraciones cardíacas, factores de riesgo cardiovascular o en tratamiento farmacológico.
