A personalized clinical assessment: multi-sensor approach for understanding musculoskeletal health in the frail population.

BACKGROUND: Sarcopenia is a muscle disorder causing a progressive reduction of muscle mass and strength, but the mechanism of its manifestation is still partially unknown. The three main parameters to assess are: muscle strength, muscle volume or quality and low physical performance. There is not a definitive approach to assess the musculoskeletal condition of frail population and often the available tests to be performed in those clinical bedridden patients is reduced because of physical impairments. In this paper, we propose a novel instrumental multi-domain and non-invasive approach during a well-defined protocol of measurements for overcoming these limitations. A group of 28 bedridden elder people, subjected to surgery after hip fracture, was asked to perform voluntary isometric contractions at the 80% of their maximum voluntary contraction with the non-injured leg. The sensor employed before and/or during the exercise were: ultrasound to determine the muscle architecture (vastus lateralis); force acquisition with a load cell placed on the chair, giving an indication of the muscle strength; surface electromyography (EMG) for monitoring muscular electrical activity; time-domain (TD) near-infrared spectroscopy (NIRS) for evaluating muscle oxidative metabolism. RESULTS: A personalized "report card" for each subject was created. It includes: the force diagram (both instantaneous and cumulative, expected and measured); the EMG-force diagram for a comparison between EMG derived median frequency and measured force; two graphs related to the hemodynamic parameters for muscle oxidative metabolism evaluation, i.e., oxy-, deoxy-, total-hemoglobin and tissue oxygen saturation for the whole exercise period. A table with the absolute values of the previous hemodynamic parameters during the rest and the ultrasound related parameters are also included. CONCLUSIONS: In this work, we present the union of protocols, multi-domain sensors and parameters for the evaluation of the musculoskeletal condition. The novelties are the use of sensors of different nature, i.e., force, electrical and optical, together with a new way to visualize and combine the results, by means of a concise, exhaustive and personalized medical report card for each patient. This assessment, totally non-invasive, is focused on a bedridden population, but can be extended to the monitoring of rehabilitation progresses or of the training of athletes.

No Difference in Muscle Basal Oxygenation in a Bedridden Population Pre and Post Rehabilitation.

Long periods of bed rest for elderly population, due to a femur fracture event, can cause a deterioration in the muscular capacity. Therefore, monitoring of the muscle oxidative capacity in this fragile population is necessary to define the muscular oxidative metabolism state before and after a rehabilitation period. The time-domain near-infrared spectroscopy (TD-NIRS) technique enables the absolute values to be calculated for hemodynamic parameters such as oxy- (O2Hb), deoxy- (HHb), total- (tHb) haemoglobin, and tissue oxygen saturation (SO2) of the muscular tissue. In this work, we have characterized vastus lateralis muscle hemodynamics during a baseline period at two different time points: after the surgery (PRE) and after 15 days of rehabilitation (POST). The mean values for the absolute values of the hemodynamic parameters were: O2Hb_PRE = 49.1 ± 14.1 µM; O2Hb_POST = 47.1 ± 13.4 µM; HHb_PRE = 28.3 ± 10.3 µM; HHb_POST = 26.7 ± 9.9 µM; tHb_PRE = 77.3 ± 23.6 µM; tHb_POST = 73.8 ± 21.4 µM; SO2_PRE = 63.9 ± 4.0% and SO2_POST = 64.9 ± 5.6%. The hemodynamic parameters did not show significant differences at both group and single subject level. These results suggest that for this kind of population, the baseline of the hemodynamic parameters is not the best one to consider to assess the rehabilitation progresses in terms of muscular oxidative metabolism.

Beyond expectations: the physiological basis of sensory enhancement of satiety.

BACKGROUND/OBJECTIVES: Consumption of high-energy beverages has been implicated as a risk factor for weight gain, yet why nutrients ingested as beverages fail to generate adequate satiety remains unclear. In general, consumers do not expect drinks to be satiating, but drinks generate greater satiety when their sensory characteristics imply they may be filling. These findings challenge traditional bottom-up models of how gut-based satiety signals modify behaviour to suggest that beliefs at the point of ingestion modify gut-based satiety signalling. SUBJECTS/METHODS: Healthy volunteers (n=23) consumed four different beverages, combining an overt sensory manipulation (thin, low sensory (LS) or thicker and more creamy, enhanced sensory (ES)) and covert nutrient manipulation (low energy (LE), 78 kcal; high energy (HE), 267 kcal) on different days. Effects on satiety were assessed through rated appetite and levels of glucose, insulin, pancreatic polypeptide (PP) and cholesystokinin (CCK) recorded periodically over 90 min, and through intake at an ad libitum test lunch. RESULTS: Intake at the test lunch and rated appetite were both altered by both the sensory and nutrient manipulations, with lowest intake and greatest suppression of hunger post-drink in the ESHE condition. Insulin increased more after HE than LE drinks, and after ES than LS drinks, whereas PP levels were higher after ES than LS versions. CCK levels only increased after the ESHE drink. CONCLUSIONS: These data confirm acute sensitivity of satiety after consuming a drink both to the sensory characteristics and nutrient content of the drink, and suggest that this may be, at least in part, due to top-down modulation of release of satiety-related gut hormones.

Management and return of incidental genomic findings in clinical trials.

Whole-genome/exome sequencing used in clinical trials (CTs) to identify 'druggable' mutations and targets uncovers incidental findings unrelated to the trial objectives but of value for participants, although ethically challenging. To be disclosed to trial participants, the analytical validity, clinical validity, clinical utility, clinical relevance and actionability of incidental genomic findings (IGFs) must be established. Special considerations should be taken with minors to disclose only those findings related to early-onset conditions or diseases and in cases where early implementation of measures is necessary to prevent the occurrence of diseases. A plan for disclosing incidental findings that classifies the types that can be found, and who, when and how these findings will be disclosed to participants, should be included in the trial protocol to be approved by the relevant institutional review board. IGFs in CTs raise new ethical challenges that must be discussed by CT stakeholders, professional associations and patient advocates.

Association of common genetic variants with risperidone adverse events in a Spanish schizophrenic population.

Risperidone non-compliance is often high due to undesirable side effects, whose development is in part genetically determined. Studies with genetic variants involved in the pharmacokinetics and pharmacodynamics of risperidone have yielded inconsistent results. Thus, the aim of this study was to investigate the putative association of genetic markers with the occurrence of four frequently observed adverse events secondary to risperidone treatment: sleepiness, weight gain, extrapyramidal symptoms and sexual adverse events. A series of 111 schizophrenia inpatients were genotyped for genetic variants previously associated with or potentially involved in risperidone response. Presence of adverse events was the main variable and potential confounding factors were considered. Allele 16Gly of ADRB2 was significantly associated with a higher risk of sexual adverse events. There were other non-significant trends for DRD3 9Gly and SLC6A4 S alleles. Our results, although preliminary, provide new candidate variants of potential use in risperidone safety prediction.

Role of the EEG Theta Network During Software Production: A Connectivity Study.

Software programming is an acquired evolutionary skill originating from consolidated cognitive functions (i.e., attentive, logical, coordination, mathematic calculation, and language comprehension), but the underlying neurophysiological processes are still not completely known. In the present study, we investigated and compared the brain activities supporting realistic programming, text and code reading tasks, analyzing Electroencephalographic (EEG) signals acquired from 11 experienced programmers. Multichannel spectral analysis and a phase-based effective connectivity study were carried out. Our results highlighted that both realistic programming and reading tasks are supported by modulations of the Theta fronto-parietal network, in which parietal areas behave as sources of information, while frontal areas behave as receivers. Nevertheless, during realistic programming, both an increase in Theta power and changes in network topology emerged, suggesting a task-related adaptation of the supporting network system. This reorganization mainly regarded the parietal area, which assumes a prominent role, increasing its hub functioning and its connectivity in the network in terms of centrality and degree.

Venous thromboembolism in patients hospitalized in internal medicine wards.

Venous thromboembolism (VTE) is one of the main causes of morbility and mortality in the ospedalized patients. Epidemiologist studies have also demonstrated that VTE is an important and frequent problems in medical patients. In surgical patients is done with greater frequency, but in medical patients prophylaxis is not completely codified and less often less practiced. This review shows epidemiological data, risk factors and classification of the risk of VTE in patients with medical pathologies. Then meta-analyses studies and main studies such as Medenox, Prevent and Artemis, that have examined the prophylaxis of VTE in medical patients are described and discussed, along with their results concerning morbility and mortality. The current problems of prophylaxis in medical patients are reviewed , such as duration of treatment, optimal dosage of the low molecular weight heparin (LMWH) and the correct risk assessment of VTE. EXCLAIM Study has showed the benefit of extended prophylaxis with statistically significant reduction in VTE events.

The effects of consuming eggs for lunch on satiety and subsequent food intake.

The aim of the present work was to investigate the effects of eggs consumed for lunch on satiety, satiation and subsequent energy intake at the next meal. Thirty-one healthy male and female subjects participated in a randomized, three-way, crossover study. Following consumption of a standard breakfast, participants were asked to consume three isocaloric test lunches: omelette, jacket potato and chicken sandwich. Subjective measures of satiety were recorded using visual analog scales at regular intervals throughout the day. Energy intake at the next meal was assessed 4 h after lunch with an ad libitum meal. The egg lunch showed a significantly stronger satiating effect compared with the jacket potato meal. No effect on energy intake was seen. These data indicate that consumption of an omelette meal consumed at lunch could increase satiety to a greater extent than a carbohydrate meal and may facilitate reduction of energy consumption between meals.

Ethical problems arising from the use of placebo in clinical trials with drugs for migraine. Their analysis by the moral deliberation method.

INTRODUCTION: Migraine is characterised as episodes of headache plus a variety of accompanying symptoms. Its pharmacological control remains unsatisfactory for some patients. The use of placebo in drug clinical trials on migraine commonly leads to numerous ethical uncertainties. METHODS: The purpose of this paper is to illustrate how the deliberation method helps in analysing the issues and finding solutions to selected ethical problems. Ethical decisions that try to solve conflicts arising from placebo use in clinical trials may be adopted using the moral deliberation method. Thus, the conflict is systematically assessed by identifying the following: Relevant facts; Values in conflict; Duties, or in other words, possible courses of action. Moral duty is following the optimal course of action. To identify this, it is recommended to state extreme courses of action, then intermediate courses of action, and then to proceed to the optimal course(s) of action. RESULTS AND CONCLUSIONS: In this paper, the application of this method is shown in several conflicting situations arising in two placebo-controlled clinical trials with drugs under development for the prophylaxis and acute treatment of migraine.

Monitoring the haemodynamic response to visual stimulation in glaucoma patients.

In this paper, we used time-domain functional near infrared spectroscopy (TD-fNIRS) to evaluate the haemodynamic response function (HRF) in the occipital cortex following visual stimulation in glaucomatous eyes as compared to healthy eyes. A total of 98 subjects were enrolled in the study and clinically classified as healthy subjects, glaucoma patients (primary open-angle glaucoma) and mixed subjects (i.e. with a different classification for the two eyes). After quality check data were used from HRF of 73 healthy and 62 glaucomatous eyes. The amplitudes of the oxygenated and deoxygenated haemoglobin concentrations, together with their latencies with respect to the stimulus onset, were estimated by fitting their time course with a canonical HRF. Statistical analysis showed that the amplitudes of both haemodynamic parameters show a significant association with the pathology and a significant discriminating ability, while no significant result was found for latencies. Overall, our findings together with the ease of use and noninvasiveness of TD-NIRS, make this technique a promising candidate as a supporting tool for a better evaluation of the glaucoma pathology.

Transgenic mice expressing an intracellular fluorescent fusion of angiotensin II demonstrate renal thrombotic microangiopathy and elevated blood pressure.

We have generated transgenic mice that express angiotensin II (ANG II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole-animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung, and testes), and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating ANG II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated, and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry (n = 8 for each group), were significantly higher in transgenic mice compared with wild-type littermates. Blood pressure of line A male transgenic mice was 125 + or - 1.7 over 97 + or - 1.6 compared with 109 + or - 1.7 over 83 + or - 1.4 mmHg in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of ANG II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension.

[Sensitivity and specificity of three complementary methods in the diagnosis of carpal tunnel syndrome]. / Sensibilidad y especificidad de tres métodos complementarios para el diagnóstico de síndrome de túnel carpiano.

INTRODUCTION: Currently there is no universally accepted standard of reference for the diagnosis of carpal tunnel syndrome so it is considered a «latent class¼ pathology, that is, it lacks any diagnostic tests that absolutely certain the presence of disease. METHODS: Prospective, observational and analytical study evaluating the three diagnostic methods used for carpal tunnel syndrome (clinical examination, ultrasound and electromyography). Normality values were set for each diagnostic method. RESULTS: 50 people (14 men and 36 women) were evaluated. The clinical examination showed a positive and significant correlation with the diameter of the affected median nerve (ecography) (R = 0.694, p = 0.032). The values of the under the curve area (UCA) for median nerve conduction speed (MNCS), cubital nerve conduction speed (CNCS), and distal latency (DL) by electromyography were 0.60, 0.519 and less than 0.50 respectively. This states that the diagnostic value of electromyography characteristics is bad. CONCLUSION: Our work establishes clinical examination as a good quality tool being the most sensitive method for diagnosing carpal tunnel syndrome. If there was a need for diagnostic confirmation, the ultrasound proved to be a highly satisfactory study generating less stress, pain and invasion to the patient, decreasing health expenditure and speeding up the process.

INTRODUCCIÓN: Actualmente, no existe un estándar de referencia aceptado universalmente para el diagnóstico del síndrome de túnel carpiano, por lo que se le considera una patología de «clase latente¼, es decir, que carece de alguna prueba diagnóstica que dé certeza absoluta de la presencia de la enfermedad. MÉTODOS: Estudio prospectivo, observacional y analítico en el cual se evaluaron los tres métodos diagnósticos utilizados para el síndrome de túnel carpiano (examen clínico, ecografía y electromiografía). En él, se establecieron valores de normalidad para cada método diagnóstico. RESULTADOS: Se evaluó un total de 50 personas (14 hombres y 36 mujeres). El examen clínico presentó correlación positiva y significativa con el diámetro del nervio mediano afectado (ecografía) (R = 0.694 y p = 0.032). Los valores del área bajo la curva (AUC, por sus siglas en inglés) para la velocidad de conducción del nervio mediano (VCNM), velocidad de conducción de nervio cubital (VCNC) y latencia distal motora (LDM) por electromiografía fueron de 0.60, 0.519 y. CONCLUSIÓN: < 0.50, respectivamente, lo cual determinó que el valor diagnóstico de las características por electromiografía es malo. Nuestro trabajo establece al examen clínico como una herramienta de buena calidad, siendo el método más sensible para el diagnóstico de síndrome de túnel carpiano. Si existiera la necesidad de realizar una confirmación diagnóstica, la ecografía mostró ser un estudio altamente satisfactorio, el cual genera menos estrés, dolor e invasión al paciente, disminuyendo, a su vez, el gasto de salud y agilizando el proceso.

Sustained fatigue assessment during isometric exercises with time-domain near infrared spectroscopy and surface electromyography signals.

The effect of sustained fatigue during an upper limb isometric exercise is presented to investigate a group of healthy subjects with simultaneous time-domain (TD) NIRS and surface electromyography (sEMG) recordings on the deltoid lateralis muscle. The aim of the work was to understand which TD-NIRS parameters can be used as descriptors for sustained muscular fatigue, focusing on the slow phase of this process and using median frequency (MF) computed from sEMG as gold standard measure. It was found that oxygen saturation and deoxy-hemoglobin are slightly better descriptors of sustained fatigue, than oxy-hemoglobin, since they showed a higher correlation with MF, while total-hemoglobin correlation with MF was lower.

Drug development: assessment of pharmacogenetic studies by Spanish research ethics committees.

The decision taken by research ethics committees (RECs) while assessing pharmacogenetic (PGx) substudies as part of international clinical trials is almost unknown. A total of 255 applications of 36 PGx substudies embedded in clinical trials (12 phase 2, 24 phase 3) were submitted to 72 RECs in 2006-2007 by GlaxoSmithKline in Spain. These were trials of 17 different compounds, aimed to be conducted in the five continents. Of the 255 applications, 226 (89%) were directly approved by RECs without raising any queries to the sponsor; 1% (3/255) were plainly rejected by two RECs. The rest (10%) were followed by 64 queries asked by 16 RECs on 25 PGx substudies. Following responses from the sponsor, all but two applications were approved. Thus, the RECs involved finally approved 98% (250/255) of the submitted applications. The requirements specifically raised by two RECs (PGx samples to be transferred to a public biobank or alternatively destroyed immediately, or storage permitted only 5 years after the trial is concluded) could not be met by the sponsor. It can be inferred from the results obtained that ethical and scientific standards implemented by the sponsor in the design, conduct and sample management of PGx substudies satisfied the vast majority (70/72; 97%) of RECs involved in this study.

Prevalence of HLA-B*5701 in HIV-infected patients in Spain (results of the EPI Study).

BACKGROUND: A hypersensitivity reaction (HSR) is associated with abacavir (ABC), a nucleoside reverse transcriptase inhibitor. Genetic association of ABC HSR with the presence of HLA-B*5701 has been demonstrated in PREDICT-1 study, showing a prevalence of 5.6% in HIV-infected population. However the prevalence of this allele in HIV-infected patients in Spain has not been established yet. METHOD: This is a cross-sectional epidemiological study that included 1,198 patients in 74 centers that serve the HIV-infected population of Spain. HLA-B*5701 was checked both in the hospital lab and one central lab, showing an overall prevalence of this allele of 6%. RESULTS: HLA-B*5701 was most prevalent in Caucasian population (6.5%). Concordance between the local and central lab was very high for positive and negative results (95.7% and 99.3%, respectively). CONCLUSION: These aspects define this test as a useful tool for the management of HIV-infected patients.

Potential predatory journals are colonizing the ICMJE recommendations list of followers.

BACKGROUND: The International Committee of Medical Journal Editors (ICMJE) has expressed its concerns about predatory journals using the list of ICMJE Recommendations (ICMJE-R) followers to "gain the appearance of legitimacy." We assessed the presence of potential predatory journals on the ICMJE-R list and their adherence to ICMJE recommendations. METHODS: A random sample of 350 journals from the estimated 3,100-3,200 biomedical journals listed as ICMJE-R followers was chosen. Data collected from the ICMJE and journal webpages in English were: adherence to six ICMJE-R policies/requirements, year of journal's listing as ICMJE-R follower, discipline covered, publisher and its country of origin and existence of article processing charge. Potential predatory journal was considered as one open access journal not being a member of a recognized listing in COPE, DOAJ, OASPA, AJOL and/or INASP. RESULTS: Thirty-one percent of journals were considered to be potentially predatory; 94% of them were included in the ICMJE-R list in 2014-2018. Half were published in the United States and 62% were devoted to medicine. Adherence to five of the six policies/requirements was infrequent, ranging from 51% (plagiarism) to 7% (trial registration). Seventy-two percent of journals mentioned a policy on authors' conflicts of interest. Information on article processing charge was available for 76% journals and could not be found for 22%. Authorship policy/ instructions were significantly more present in journals with publishers from India than from the USA (53% vs 30%; p = 0.047), with no differences in the other five policies. CONCLUSION: Predatory journals should be deleted from the ICMJE-R list of followers to prevent misleading authors. ICMJE-R following journals need to be reevaluated with pre-defined published criteria.

Factors impacting on length of stay and mortality of community-acquired pneumonia.

A 1-year retrospective multicentre study was performed to identify factors influencing hospital length of stay (LOS) and mortality of patients (n = 3233) admitted to hospital because of community-acquired pneumonia (CAP). Pneumonia severity index (PSI) high-risk classes (IV and V), positive blood culture, admission to an intensive care unit (ICU), multi-lobar involvement and alcohol consumption were associated independently with prolonged LOS. Tobacco smoking was associated with a reduced LOS. The LOS varied markedly among centres. Only PSI high-risk class, admission to ICU and multi-lobar involvement were associated with early, late and global mortality. Positive blood cultures, antimicrobial therapy according to treatment guidelines and the establishment of an aetiological diagnosis were linked to reduced late and global mortality. These data suggest that early mortality associated with CAP is highly dependent on the clinical status of the patient at presentation. Conversely, late mortality seems to be associated more closely with clinical management factors; hence, an aetiological diagnosis and compliance with appropriate therapeutic guidelines have a significant influence on outcome.

Metabolic clearance and secretion rates of subunits of human thyrotropin.

Metabolic clearance rates (MCR) of the alpha and beta subunits of human thyrotropin (hTSH-alpha and hTSH-beta) were determined by a constant infusion to equilibrium method. In 15 normal individuals (six men, six premenopausal women, and three post-menopausal women), the mean MCR of hTSH-alpha (68 ml/min per m2) was significantly faster than that of hTSH-beta (48 ml/min per m2) was significantly faster than that of hTSH-beta (48 ml/min per m2); both were two to three times more rapid than the previously determined MCR of hTSH. In patients with primary hypothyroidism, MCR were significantly slower with a mean value of 55 ml/min per m2 for hTSH-alpha and 37 ml/min per m2 for hTSH-beta. However, MCR of subunits were not significantly faster than normal in hyperthyroid patients. Serum concentrations of alpha subunits and hTSH-beta were measured by radioimmunoassay, and secretion rates of alpha and hTSH-beta from the pituitary were calculated using hTSH-alpha and hTSH-beta MCR, respectively. In the normal individuals, alpha secretion rates averaged 91 mug/day per m2, greater than those previously determined for hTSH and human follicle-stimulating hormone. Alpha secretion rates were significantly elevated in the normal postmenopausal women (211 mug/day per m2) and in the premenopausal hypothyroid women (202 mug/day per m2); they were also elevated in the postmenopausal hypothyroid women (277 mug/day per m2). Alpha secretion rates were significantly decreased in the premenopausal hyperthyroid women (66 mug/day per m2). Usually, the secretion rates of hTSH-beta could not be calculated in normal individuals, and the rates in hyperthyroid patients could never be calculated because serum hTSH-beta was not detected. Six normals had detectable hTSH-beta secretion rates (17 mug/day per m2); hTSH-beta secretion rates were significantly increased in patients with primary hypothyroidism (28 mug/day per m2). Although we had previously demonstrated a 50-fold increase in hTSH secretion rates in primary hypothyroidism, there was only a 2-fold increase in alpha and hTSH-beta secretion rates. Thus, increased subunit synthesis appears to be utilized predominantly for production of complete hTSH.

Validation of the Spanish version of the Asthma Control Test (ACT).

OBJECTIVE: Validation of the Spanish version of the Asthma Control Test (ACT). METHODS: A total of 607 asthmatic patients were assessed. The psychometric properties of ACT were evaluated. The ACT capacity to predict the physician's assessment of asthma control was assessed using the area under the receiving operating characteristics (ROC) curve (AUC), sensitivity, specificity, and positive-negative predictive values. RESULTS: ACT's Cronbach alpha was 0.84. The intraclass correlation coefficient was 0.85. The AUC was 0.86, with a sensitivity of 71% and a specificity of 85% for a score of < or =19. CONCLUSIONS: The Spanish version of ACT is shown to be a reliable and valid tool for evaluating and discriminating asthma control.