The influence of the da Vinci surgical robot on electromagnetic tracking in a clinical environment.

Robot-assisted surgery is increasingly used in surgery for cancer. Reduced overview and loss of anatomical orientation are challenges that might be solved with image-guided surgical navigation using electromagnetic tracking (EMT). However, the robot's presence may distort the electromagnetic field, affecting EMT accuracy. The aim of this study was to evaluate the robot's influence on EMT accuracy. For this purpose, two different electromagnetic field generators were used inside a clinical surgical environment: a table top field generator (TTFG) and a planar field generator (PFG). The position and orientation of sensors within the electromagnetic field were measured using an accurate in-house developed 3D board. Baseline accuracy was measured without the robot, followed by stepwise introduction of potential distortion sources (robot and robotic instruments). The absolute accuracy was determined within the entire 3D board and in the clinical working volume. For the baseline setup, median errors in the entire tracking volume within the 3D board were 0.9 mm and 0.3° (TTFG), and 1.1 mm and 0.4° (PFG). Adding the robot and instruments did not affect the TTFG's position accuracy (p = 0.60), while the PFG's accuracies decreased to 1.5 mm and 0.7° (p < 0.001). For both field generators, when adding robot and instruments, accuracies inside the clinical working volume were higher compared to the entire tracking 3D board volume, 0.7 mm and 0.3° (TTFG), and 1.1 mm and 0.7° (PFG). Introduction of a surgical robot and robotic instruments shows limited distortion of the EMT field, allowing sufficient accuracy for surgical navigation in robotic procedures.

Efficacy of Antiresorptive Treatment in Osteoporotic Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: To investigate concerns surrounding the benefits of antiresorptive drugs in older adults, a systematic review was carried out to evaluate the efficacy of these treatments in the prevention of osteoporotic hip fractures in older adults. DESIGN: a systematic review and meta-analysis of randomized clinical trials. SETTING AND PARTICIPANTS: older adults ≥65 years with osteoporosis, with or without a previous fragility fracture. Studies with cancer-related and corticosteroid-induced osteoporosis, participants <65 years and no reported hip fracture were not included. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus databases were searched. The primary outcome was hip fracture, and subgroup analysis (≥75 years, with different drug types and secondary prevention) and sensitivity analysis was carried out using a GRADE evaluation. Secondary outcomes were any type of fractures, vertebral fracture, bone markers and adverse events. The risk of bias was assessment with the Cochrane risk of bias tool. RESULTS: A total of 12 randomised controlled trials (RCTs) qualified for this meta-analysis, with 36,196 participants. Antiresorptive drugs have a statistically significant effect on the prevention of hip fracture (RR=0.70; 95%CI 0.60 to 0.81), but with a moderate GRADE quality of evidence and a high number needed to treat (NNT) of 186. For other outcomes, there is a statistically significant effect, but with a low to moderate quality of evidence. Antiresorptives showed no reduction in the risk of hip fracture in people ≥75 years. The results for different drug types, secondary prevention and sensitivity analysis are similar to the main analyses and have the same concerns. CONCLUSIONS: Antiresorptive drugs have a statistically significant effect on preventing hip fracture but with a moderate quality (unclear/high risk of bias) and high NNT (186). This small benefit disappears in those ≥75 years, but increases in secondary prevention. More RCTs in very old osteoporotic adults are needed.

Morbi-mortality of lower respiratory tract infections in Spain, 1997-2018 / Morbimortalidad de las infecciones del tracto respiratorio inferior en España, 1997-2018

Background:Lower respiratory tract infections (LRTIs) are one of the leading causes of infectious disease mortality worldwide. The aims of the study were to determine the incidence of hospitalizations due to LRTIs, and to analyze the clinical outcomes of the hospitalized patients. Methods:An observational study of hospitalizations due to LRTIs (pneumonia and acute bronchitis/bronchio-litis) in Spain from 1997 to 2018 was carried out. Data were extracted from the national information system for hospital data. Results:Overall, 3.5 % (IQR: 3.4-3.5 %) of total hospitalizations were caused by LRTIs, with a median incidence of 31.2 (IQR: 27.8-33.0) per 10,000 inhabitants/year. The median incidence was higher for pneumonia than for acute bronchitis/bronchiolitis cases (22.2; IQR: 19.1-23.5 vs. 9.0; IQR: 8.4-9.6 per 10,000 inhabitants/year; p < 0.001) and increased by 65.7 % from 1997 to 2018. A 41.2 % of the hospitalizations due to LRTIs took place amongst people over 74 years. The median length of stay was 8.9 days (IQR: 7.6-10.4) and was higher for hospitalizations due to pneumonia than for acute bronchitis/bronchiolitis (9.5 days; IQR: 8.3-10.6 vs. 5.7; IQR: 5.5-6.2; p < 0,001). In 89.1 % of total hospitalizations due to LRTIs, patients were discharged home. In-hospital mortality was 6.8 %, with 9,380 deaths (IQR: 8,192-10,157) per year. Mortality was higher for pneumonia (9.0 vs. 1.7 %; p < 0.001) and doubled from 1997 to 2018 (5,257 deaths in 1997 and 10,514 in 2018). A 75.5 % of the deaths occurred amongst people over 74 years.Conclusions:LRTIs are associated with a high morbi-mortality in Spain. Effective measures that can contribute towards the prevention and treatment of LRTIs need to be adopted.(AU)

Fundamento: Las infecciones del tracto respiratorio inferior (ITRI) constituyen una de las principales causas de mortalidad por enfermedades infecciosas a nivel mundial. Los objetivos del estudio consistieron en determinar la incidencia de hospitalizaciones por ITRI, y en analizar los resultados clínicos de los pacientes hospitalizados. Métodos: Se llevó a cabo un estudio observacional de las hospitalizaciones por ITRI (neumonía y bronquitis/bronquiolitis aguda) en España entre 1997-2018. Los datos se extrajeron del Registro Español de Atención Sanitaria Especializada. Resultados: El 3,5% (RIC: 3,4-3,5%) del total de hospitalizaciones se debieron a ITRI, con una incidencia mediana de 31,2 (RIC: 27,8-33,0) por cada 10.000 habitantes/año. La mediana de incidencia fue superior para las neumonías que para las bronquitis/bronquiolitis agudas (22,2; RIC: 19,1-23,5 vs. 9,0; RIC: 8,4-9,6 por 10.000 habitantes/año; p<0,001), y entre 1997-2018 aumentó un 65,7%. Un 41,2% de las hospitalizaciones por ITRI ocurrieron en mayores de 74 años. La mediana de duración de las hospitalizaciones por ITRI fue 8,9 días (RIC: 7,6-10,4), superior para neumonías (9,5 días; RIC: 8,3-10,6 vs. 5,7; RIC: 5,5-6,2; p<0,001). En un 89,1% de las hospitalizaciones por ITRI los pacientes fueron dados de alta a domicilio. La mortalidad intrahospitalaria fue 6,8%, con 9.380 fallecimientos anuales (RIC: 8,192-10,157). La mortalidad fue superior para neumonías (9,0 vs. 1,7%; p<0,001) y se duplicó entre 1997 y 2018 (5.257 fallecimientos en 1997 y 10.514 en 2018). El 75,5% de las muertes ocurrieron en mayores de 74 años. Conclusiones: Las ITRI se asocian a una elevada morbimortalidad. Se requieren medidas efectivas para su prevención y tratamiento.(AU)

Morbi-mortality of lower respiratory tract infections in Spain, 1997-2018.

BACKGROUND: Lower respiratory tract infections (LRTIs) are one of the leading causes of infectious disease mortality worldwide. The aims of the study were to determine the incidence of hospitalizations due to LRTIs, and to analyze the clinical outcomes of the hospitalized patients. METHODS: An observational study of hospitalizations due to LRTIs (pneumonia and acute bronchitis/bronchiolitis) in Spain from 1997 to 2018 was carried out. Data were extracted from the national information system for hospital data. RESULTS: Overall, 3.5% (IQR: 3.4-3.5%) of total hospitalizations were caused by LRTIs, with a median incidence of 31.2 (IQR: 27.8-33.0) per 10,000 inhabitants/year. The median incidence was higher for pneumonia than for acute bronchitis/bronchiolitis cases (22.2; IQR: 19.1-23.5 vs. 9.0; IQR: 8.4-9.6 per 10,000 inhabitants/year; p<0.001) and increased by 65.7% from 1997 to 2018. A 41.2% of the hospitalizations due to LRTIs took place amongst people over 74 years. The median length of stay was 8.9 days (IQR: 7.6-10.4) and was higher for hospitalizations due to pneumonia than for acute bronchitis/bronchiolitis (9.5 days; IQR: 8.3-10.6 vs. 5.7; IQR: 5.5-6.2; p<0,001). In 89.1% of total hospitalizations due to LRTIs, patients were discharged home. In-hospital mortality was 6.8%, with 9,380 deaths (IQR: 8,192-10,157) per year. Mortality was higher for pneumonia (9.0 vs. 1.7%; p

Effect of “triple whammy” combination in hospitalization due to acute kidney injury: a protocol of a nested case-control study / Efecto de la combinación «triple whammy» en la hospitalización por fallo renal agudo: protocolo del estudio de casos y controles anidado en una cohorte

Objective: Acute kidney injury (AKI) is a life-threatening condition characterized by an abrupt deterioration in kidney function. The simultaneous use of diuretics, renin-angiotensin-aldosterone system inhibitors, and non-steroidal anti-inflammatory drugs (NSAIDs) or metamizol, known as «triple whammy» (TW), has been associated with an increased risk of AKI. The main objective of the study is to analyse the risk of hospitalization due to AKI with the TW combination versus non-exposure to TW. Additionally, hospitalization due to AKI according to the time and duration of the TW exposure, and depending on whether the TW includes NSAIDs or metamizol; mortality; and the requirement of renal replacement therapy will be determined.Methods: A case-control study nested in a cohort will be carried out. Data for the study will be extracted from the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP), managed by the Spanish Agency for Medicines and Medicine and Health Products (AEMPS). Adults admitted to hospital due to AKI between 2010 and 2018 (cases) will be matched with up to 10 controls per case. The exposure to TW during the 12 months prior to the index date will be determined. The association between the exposure to TW and the outcomes will be analysed using multivariate logistic regression models adjusting by potential confounding factors. A subgroup analysis will be performed to evaluate the risk of hospitalization due to AKI with the exposure to TW in patients older than 75 years. (AU)

Objetivo: El fallo renal agudo (FRA) se caracteriza por un deterioro abrupto de la función renal que puede aumentar el riesgo de mortalidad. El uso simultáneo de diuréticos, antihipertensivos inhibidores del sistema renina-angiotensina, y antiinflamatorios no esteroideos (AINE) o metamizol, conocido como “triple whammy” (TW), se ha visto asociado a un incremento del riesgo de FRA. El objetivo principal consiste en analizar el riesgo de hospitalización por FRA con la combinación TW frente a la no exposición a dicha combinación. Adicionalmente se analizará la hospitalización por FRA en función del momento de la exposición a TW y de su duración, y dependiendo de si la TW incluye AINE o metamizol; la mortalidad; y el requerimiento de terapia de reemplazo renal.Métodos: Se llevará a cabo un estudio de casos y controles anidado en una cohorte. Los datos para el estudio se extraerán de la Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), gestionada por la Agencia Española de Medicamentos y Productos Sanitarios (AEMPS). Los adultos con hospitalización por FRA entre 2010-2018 (casos) se emparejarán con hasta 10 controles por caso. La asociación entre la exposición a TW y las variables de resultado se analizará mediante modelos de regresión logística ajustados por potenciales factores de confusión. Se realizará un análisis de subgrupos para evaluar la variable principal en pacientes mayores de 75 años. (AU)

Fin whales as bioindicators of multi-decadal change in carbon and oxygen stable isotope shifts in the North Atlantic.

Global changes, and particularly the massive release of CO2 to the atmosphere and subsequent global warming, have altered the baselines of carbon and oxygen stable isotopic ratios. Temporal shifts in these baselines can be advantageously monitored through cetacean skin samples because these animals are highly mobile and therefore integrate in their tissues the heterogeneity of local environmental signals. In this study, we examine variation of δ13C and δ18O values in the skin of fin whales sampled over three decades in two different North Atlantic feeding grounds: west Iceland and northwest Spain. These locations are situated about 2700 km apart and thus represent a wide latitudinal range within the North Atlantic Ocean. The δ13C decrease in both areas is attributed to the burning of fossil fuels and increased deforestation worldwide, the so-called Suess effect. The dissimilarity in the magnitude of the shift between the two areas is coincidental with previous information on local shifts and lies within the ranges of variation observed. δ18O values experienced a minimal, yet significant change in fin whales from W Iceland (a decline of -0.44‰ between 1986 and 2013) but not in those from NW Spain. This is in concordance with a higher rise in temperatures in the former area than in the latter. The study validates the use of cetacean skin to monitor temporal and geographical shifts in stable isotopic values and alerts that, when applying this tool to ecological research, comparisons between sample sets should take into account temporal and latitudinal scales.

Validation and incidence of community-acquired pneumonia in patients with type 2 diabetes in the BIFAP database.

Oral anti-diabetic drugs (OADs) have been associated with community-acquired pneumonia (CAP). We aimed to validate the recording of CAP in the Spanish Database for Pharmacoepidemiological Research in Primary Care (BIFAP) for the future evaluation of OAD-CAP association. The incidence rate (IR/1000 person-years) of CAP in type 2 diabetes mellitus (T2DM) was also determined. In total, 2966 pneumonia records (2040 listed as diagnosis and 926 as identified from comments added by physicians) were identified from 76 009 patients with T2DM after the first OAD in 2002-2013. Data around the CAP date were reviewed: 1803 (60·9%) were classified as 'probable CAP' (confirmed by X-ray/laboratory, referral letters or CAP lung site); 589 (19·8%) as 'no-case' (486 had other illness, 78 previous CAP, 25 cancer); and 574 (19·4%) as 'possible CAP' (441 without confirmatory information, 133 with uncertain diagnosis or uncertain diagnosis date). In total, 74·2% and 31·4% of pneumonia records in the diagnosis and comments, respectively, were 'probable cases' (IR: 6·04), which increased to 90·5% and 42·9%, respectively, when the 441 'possible cases' without confirmatory information were included (IR: 7·52). In summary, diagnosis had a high positive predictive value, and adding cases automatically detected from comments decreased that value significantly.

[Modification of specialised care prescriptions by Primary Healthcare physicians]. / Modificación de la prescripción procedente del segundo nivel de asistencia por parte del médico de Atención Primaria.

OBJECTIVE: To determine the percentage of new Specialist Healthcare prescriptions received and modified by Primary Healthcare physicians. DESIGN: Descriptive, cross-sectional and multi-centre study with the participation of Primary Healthcare physicians from one Madrid Health Area during 2 months. A method was established for registering the origin of the new prescriptions in the Computerised Medical Record System. In order to register new prescriptions without any change from Specialist Healthcare, the «second level¼ option was marked when the prescription was issued. A protocol was prepared and was available on the Computerized Medical Record System, so for those cases where there was a new Specialist Healthcare prescription, the Primary Healthcare physician would not issue any prescription or issue a prescription with changes as regards the original one. RESULTS: A total of 69 Primary Healthcare physicians from 15 Primary Healthcare centres registered 46,512 new prescriptions, 3,893 (8.4%) from Specialist Healthcare. From this number, 3,544 prescriptions (91.0% 95% CI: 90.1-91.9) were issued without changes, and 298 prescriptions were modified (7.7% 95% CI: 7.0-8.7). In 46 cases (1.2% 95% CI: 0.8-1.5) no prescription was issued. Some prescriptions were changed by 51% of Primary Healthcare physicians, and the median of prescriptions changed or not issued was 3. The main reason for the modification was replacement with generics. CONCLUSIONS: A high percentage of new Specialist Healthcare prescriptions are issued without any changes being made by Primary Healthcare physicians. Modifications are concentrated in half of the participating physicians. Therefore, these data suggest that this practice is not generally adopted by the professionals.

Protein-protein/DNA interaction networks: versatile macromolecular structures for the control of gene expression.

The assembly of macromolecular structures consisting of proteins and DNA lies at the core of many fundamental cellular processes, such as transcription, recombination and replication. A common theme to all these processes is DNA looping, which provides the backbone for the required long-range interactions on DNA and results in further complexity that is exceptionally difficult to tackle with traditional quantitative approaches. Here, recent advances in mathematical and computational methods to study the assembly of protein-protein/DNA complexes with loops and their effects in the cellular behaviour through gene regulation are reviewed. The interplay between multisite DNA looping and DNA bending regulatory proteins, such as the catabolite activator protein (CAP), and on its physiological consequences is focused on. It has become clear in the last few years that the complexity that looping brings about can actively control transcriptional noise and cell-to-cell variability. Here, it is shown that the DNA looping, through the effects of CAP, can also control the balance between robustness and sensitivity of the induction of gene expression.

Influence of highly polyunsaturated lipid acyl chains of biomembranes on the NMR order parameters.

We investigate the effect of specific conformations of double-bond segments in highly polyunsaturated acyl chains on the deuterium (2)H NMR order parameters of a fully hydrated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC, 18:0/22:6 PC) lipid bilayer. The system is analyzed by performing a molecular dynamics simulation study at ambient conditions in the fluid lamellar phase. By separately calculating the different partial contributions to the total order parameter profiles measurable experimentally, we are able to get insights into the molecular origin of earlier experimental and theoretical observations. The effect of the position of the different conformations of double-bond segments along the polyunsaturated acyl chain is also examined. As in experiments performed in a series of lipid bilayers with an increasing number of cis double bonds per lipid molecule [Holte, L. L., et al. Biophys. J. 1995, 68, 2396], we find that unsaturations influence mainly the order of the bottom half of the saturated chain. Specific conformations of the polyunsaturated chain close to the lipid headgroups have a distinct effect on the order of the bottom half of the saturated chain and on the top half of the polyunsaturated chain. Our results indicate that for SDPC the conformation of the region of the polyunsaturated chain located between the first three cis double bonds is responsible for the major effects on the orientational order of both the saturated and the polyunsaturated chains.

Structural properties of a highly polyunsaturated lipid bilayer from molecular dynamics simulations.

The structure of a fully hydrated mixed (saturated/polyunsaturated) chain lipid bilayer in the biologically relevant liquid crystalline phase has been examined by performing a molecular dynamics study. The model membrane, a 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC, 18:0/22:6 PC) lipid bilayer, was investigated at constant (room) temperature and (ambient) pressure, and the results obtained in the nanosecond time scale reproduced quite well the available experimental data. Polyunsaturated fatty acids are found in high concentrations in neuronal and retinal tissues and are essential for the development of human brain function. The docosahexaenoic fatty acid, in particular, is fundamental for the proper function of the visual receptor rhodopsin. The lipid bilayer order has been investigated through the orientational order parameters. The water-lipid interface has been explored thoroughly in terms of its dimensions and the organization of the different components. Several types of interactions occurring in the system have been analyzed, specifically, the water-hydrocarbon chain, lipid-lipid and lipid-water interactions. The distribution of dihedral angles along the chains and the molecular conformations of the polyunsaturated chain of the lipids have also been studied. Special attention has been focused on the microscopic (molecular) origin of the effects of polyunsaturations on the different physical properties of membranes.

Rifampicin causes false-positive immunoassay results for urine opiates.

The treatment of tuberculosis usually includes the antibiotic rifampicin, especially in patients with concomitant human immunodeficiency virus infection. Some of these patients are in withdrawal therapy for drug abuse. When opiate screening is carried out in patients receiving rifampicin, false positive results are detected with the kinetic interaction of microparticles in solution method. We evaluated this interference in a Cobas-Integra analyzer and found a 12% cross-reactivity of rifampicin for antibiotic concentrations ranging from 0.19 to 6.08 mumol/l (156 to 5000 micrograms/l). This effect is not explained by the colour of the rifampicin solutions. Calculations assuming first order kinetics of elimination show that more than 18 hours after a single oral dose of 600 mg of rifampicin, a false positive result for opiates could be obtained. This indicates that the risk of a false positive result must always be considered when urine samples from these patients are analyzed.