Implementing Effective Noise Reduction Techniques in Implantable NIRS Sensors.

Near-Infrared Spectroscopy (NIRS) is a noninvasive optical method widely used for evaluating tissue hemodynamics and various physiological characteristics. Despite its advantages, NIRS faces limitations in light sampling depth and spatial resolution, which has led to the development of implantable NIRS sensors. However, these implantable sensors are prone to Common-Mode Voltage (CMV) interference due to their increased sensor-to-tissue capacitance, which can compromise the signal-to-noise ratio and accuracy of measurements.In this paper, we present a novel active CMV reduction technique that enhances the signal-to-noise ratio of NIRS signals. We propose an electrical model of a patient's body and NIRS sensor to characterize the CMV interference and the active CMV cancellation (ACC) electronic circuit. The ACC circuit measures CMV through a common-mode amplifier, which then inverts and introduces the amplified signal to the patient's body via an additional surface electrode. This technique effectively attenuates the CMV (50 and 60 Hz) by 80 to 90 dB, significantly improving the signal quality without causing system instability.The method has been validated through both analytical simulations and experimental measurements, demonstrating the circuit's ability to suppress CMV within a bandwidth of 0.1 to 100 Hz. Experimental verification of the active noise cancellation method was conducted by recording data from the fingertip and palm, showing effective suppression of the CMV. The proposed method has substantial clinical relevance as it enhances the reliability and accuracy of implantable NIRS sensors, enabling more precise monitoring of internal organs and improved patient care.

[Buprenorphine depot in opiate use disorder]. / Buprenorfinedepot bij een stoornis in het gebruik van opiaten.

BACKGROUND: Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that can be administered weekly or monthly are available. AIM: To describe the effectiveness and the side effects of the buprenorphine depot. METHOD: Embase was searched and cross-references were sought in the included studies and previous reviews. RESULTS: Nine articles were included. One randomized study (n = 428) compared buprenorphine depot to the sublingual form, with the depot being more effective after 12-24 weeks. The other randomized study (n = 504) compared the depot with placebo. The depot was found to be effective. In two comparative non-blinded studies, no significant difference in abstinence was reported between the depot and sublingual administration. Medium-term effectiveness (16-52 weeks) was confirmed in five follow-up studies, in which the depot preparation proved both effective and well tolerated. CONCLUSION: The buprenorphine depot is described as promising in the international literature. However, there are still several uncertainties that make its prescription should be done with great caution.

[Cognitive behavioral therapy in combination with pharmacotherapy for adults with ADHD]. / Cognitieve gedragstherapie bij medica-menteuze behandeling van ADHD bij volwassenen.

BACKGROUND: Treatment options for attention deficit hyperactivity disorder (ADHD) in adults consist of psycho-education, cognitive behavioral therapy (CBT), pharmacotherapy or a combination thereof. AIM: To investigate the effect of CBT combined with pharmacotherapy on the quality of life in adults with ADHD compared to medication alone. METHOD: In this multicenter prospective cohort study a total of 627 patients were included, 305 where included in the medication only group and 322 in de combination group (CBT and medication). The Adult ADHD Quality-of-Life scale (AAQoL) was conducted at baseline and at the end of treatment. RESULTS: The quality of life as measured by the AAQoL increased significantly in both groups but was not significantly different between the two groups (p = 0.33). CONCLUSION: To our knowledge, this is the first study to describe the effect of CBT as an addition to ADHD drug therapy on the quality of life in adults. Contrary to our expectations, there was no significant effect of CBT as an addition to drug therapy on the quality of life.

[Nabiximols as a substitute for cannabis]. / Nabiximols als substituut voor cannabis?

Cannabis addiction is worldwide one of the most prevalent addictions, without any effective pharmacotherapeutic options. Nabiximols spray, consisting of 2.7 mg tetrahydrocannabinol (THC) and 2.5 mg cannabidiol (CBD), could serve as an effective substitution therapy for cannabis addiction. Researchers reported that patients who were treated for 12 weeks with nabiximols significantly reduced the number of days on which they used cannabis (18.6 days less compared to placebo users; 95% CI: 3.5-33.7). There was no difference between groups regarding general health, the use of other substances, cannabis craving, withdrawal symptoms or achieving abstinence.

The effect of cardiac output on the pharmacokinetics and pharmacodynamics of propofol during closed-loop induction of anesthesia.

BACKGROUND AND OBJECTIVE: Intraoperative hemodynamic stability is essential to safety and post-operative well-being of patients and should be optimized in closed-loop control of anesthesia. Cardiovascular changes inducing variations in pharmacokinetics may require dose modification. Rigorous investigational tools can strengthen current knowledge of the anesthesiologists and support clinical practice. We quantify the cardiovascular response of high-risk patients to closed-loop anesthesia and propose a new application of physiologically-based pharmacokinetic-pharmacodynamic (PBPK-PD) simulations to examine the effect of hemodynamic changes on the depth of hypnosis (DoH). METHODS: We evaluate clinical hemodynamic changes in response to anesthesia induction in high-risk patients from a study on closed-loop anesthesia. We develop and validate a PBPK-PD model to simulate the effect of changes in cardiac output (CO) on plasma levels and DoH. The wavelet-based anesthetic value for central nervous system monitoring index (WAVCNS) is used as clinical end-point of propofol hypnotic effect. RESULTS: The median (interquartile range, IQR) changes in CO and arterial pressure (AP), 3 min after induction of anesthesia, are 22.43 (14.82-36.0) % and 26.60 (22.39-35.33) % respectively. The decrease in heart rate (HR) is less marked, i.e. 8.82 (4.94-12.68) %. The cardiovascular response is comparable or less enhanced than in manual propofol induction studies. PBPK simulations show that the marked decrease in CO coincides with high predicted plasma levels and deep levels of hypnosis, i.e. WAVCNS < 40. PD model identification is improved using the PBPK model rather than a standard three-compartment PK model. PD simulations reveal that a 30% drop in CO can cause a 30% change in WAVCNS. CONCLUSIONS: Significant CO drops produce increased predicted plasma concentrations corresponding to deeper anesthesia, which is potentially dangerous for elderly patients. PBPK-PD model simulations allow studying and quantifying these effects to improve clinical practice.

Motion-based prediction of external forces and moments and back loading during manual material handling tasks.

This paper evaluates a method for motion-based prediction of external forces and moments on manual material handling (MMH) tasks. From a set of hypothesized contact points between the subject and the environment (ground and load), external forces were calculated as the minimal forces at each contact point while ensuring the dynamics equilibrium. Ground reaction forces and moments (GRF&M) and load contact forces and moments (LCF&M) were computed from motion data alone. With an inverse dynamics method, the predicted data were then used to compute kinetic variables such as back loading. On a cohort of 65 subjects performing MMH tasks, the mean correlation coefficients between predicted and experimentally measured GRF for the vertical, antero-posterior and medio-lateral components were 0.91 (0.08), 0.95 (0.03) and 0.94 (0.08), respectively. The associated RMSE were 0.51 N/kg, 0.22 N/kg and 0.19 N/kg. The correlation coefficient between L5/S1 joint moments computed from predicted and measured data was 0.95 with a RMSE of 14 Nm for the flexion/extension component. In conclusion, this method allows the assessment of MMH tasks without force platforms, which increases the ecological aspect of the tasks studied and enables performance of dynamic analyses in real settings outside the laboratory.

Accuracy and kinematics consistency of marker-based scaling approaches on a lower limb model: a comparative study with imagery data.

Medical images are not typically included in protocol of motion laboratories. Thus, accurate scaling of musculoskeletal models from optoelectronic data are important for any biomechanical analysis. The aim of the current study was to identify a scaling method based on optoelectronic data, inspired from literature, which could offer the best trade-off between accurate geometrical parameters (segment lengths, orientation of joint axes, marker coordinates) and consistent inverse kinematics outputs (kinematic error, joint angles). The methods were applied on 26 subjects and assessed with medical imagery building EOS-based models, considered as a reference. The main contribution of this paper is to show that the marker-based scaling followed by an optimisation of orientation joint axes and markers local coordinates, gives the most consistent scaling and joint angles with EOS-based models. Thus, when a non-invasive mean with an optoelectronic system is considered, a marker-based scaling is preliminary needed to get accurate segment lengths and to optimise joint axes and marker local coordinates to reduce kinematic errors.AbbrevationsAJCAnkle joint centreCKEcumulative kinematic errorDoFdegree of freedomEBEOS-basedHBheight-basedHJChip joint centreKJCknee joint centreMBmarker-basedMSMmusculoskeletal modelsSPMstatistical parametric mappingSTAsoft tissue artifactEBa.m∗EOS-based with optimised joint axes, and all model markers coordinatesMBa.m∗marker-based with optimised joint axes, and all model markers coordinatesMBl.a.mmarker-based with optimised segment lengths, joint axes, and selected model markers coordinatesASISanterior superior illiac spinePSISposterior superior illiac spine.

Reversal of neuromuscular blockade with sugammadex during continuous administration of anaesthetic agents: a double-blind randomised crossover study using the bispectral index.

Sugammadex, a specific reversal agent for steroidal neuromuscular blocking drugs, has on occasion been reported to be associated with clinical signs of awakening. We performed a study to systematically search for an increase in bispectral index values and signs of awakening in patients maintained under general anaesthesia following sugammadex administration. Patients, scheduled to receive general anaesthesia with neuromuscular blockade, were included in this double-blind randomised crossover study. After surgery was completed, and while the train-of-four ratio was zero, intravenous anaesthesia was continued with the aim of maintaining the bispectral index in the range of 40-60. Patients then received either sugammadex 4 mg.kg-1 or saline. In cases of incomplete reversal of neuromuscular blockade after 5 min, patients received the other drug. Bispectral index and train-of-four monitoring were recorded every minute and clinical signs of awakening noted. Fifty-one patients completed the study. Median (IQR [range]) bispectral index values increased after sugammadex administration from 49 (43-53 [38-64]) to 63 (53-80 [45-97]) (p < 0.01) with an increase of ≥ 20 in 22 patients; 14 (27%) patients had clinical signs of awakening. Saline had no effect on bispectral index values, clinical signs of awakening or degree of neuromuscular blockade. This study confirms that reversal of neuromuscular blockade with sugammadex may be associated with clinical signs of awakening despite maintenance of anaesthesia. Intravenous anaesthesia should be maintained until complete recovery of muscle function is achieved, especially when sugammadex is administered.

[The efficacy of baclofen in alcohol dependence]. / De effectiviteit van baclofen bij de stoornis in alcoholgebruik.

BACKGROUND: In the past years numerous studies have investigated the efficacy of baclofen for alcohol dependence. After publication of several reviews a number of new randomized controlled trials have been published. Two recent meta-analyses, based on largely the same studies, reported contrary results. One meta-analysis showed a positive effect on time to relapse and abstinence at endpoint. The other meta-analysis did not show an effect on the primary outcome measures.
AIM: To clarify the clinical relevance of the effect of baclofen on alcohol use in patients with a disorder in the use of alcohol, in the light of the positive and the negative meta-analysis.
METHOD: A systematic literature search using Medline, Embase and PsycINFO (Prisma guideline).
RESULTS: We found 16 randomized controlled trials in which the effect of baclofen was studied. Seven of them showed a significant positive effect of baclofen on (one or more of the) primary outcome measures.

A smartphone oximeter with a fingertip probe for use during exercise training: usability, validity and reliability in individuals with chronic lung disease and healthy controls.

BACKGROUND AND AIM: Telehealth is a strategy to expand the reach of pulmonary rehabilitation (PR). Smartphones can monitor and transmit oxygen saturation (SpO2) and heart rate (HR) data to ensure patient safety during home-based or other exercise. The purpose of this study was to evaluate the usability, validity and reliability of a Kenek O2 pulse oximeter and custom prototype smartphone application (smartphone oximeter) during rest and exercise in healthy participants and those with chronic lung disease. METHODS: Fifteen individuals with chronic lung disease and 15 healthy controls were recruited. SpO2 and HR were evaluated at rest and during cycling and walking. SpO2 was valid if the mean bias was within +±2%, the level of agreement (LoA) was within ±4%; HR was valid if the mean bias was within ±5 beats per min (bpm), LoA was within ±10bpm. Usability was assessed with a questionnaire and direct observation. RESULTS: The smartphone oximeter was deemed easy to use. At rest, SpO2 measures were valid in both groups (bias <2%, lower bound LoA -2 to 3%). During exercise, SpO2 measurement did not meet validity and reliability thresholds in the patients with chronic lung disease, but was accurate for the healthy controls. HR recording during exercise or rest was not valid (LoA>10bpm) in either group. CONCLUSIONS: The smartphone oximeter did not record HR or SpO2 accurately in patients with chronic lung disease during exercise, although SpO2 was valid at rest. During exercise, patients with chronic lung disease should pause to ensure greatest accuracy of SpO2 and HR measurement.

MusIC method enhancement by a sensitivity study of its performance: Application to a lower limbs musculoskeletal model.

Providing a biomechanical feedback during experimental sessions is a real outcome for rehabilitation, ergonomics or training applications. However, such applications imply a fast computation of the biomechanical quantities to be observed. The MusIC method has been designed to solve quickly the muscle forces estimation problem, thanks to a database interpolation. The current paper aims at enhancing its performance. Without generating any database, the method allows to identify optimal densities (number of samples contained in the database) with respect to the method accuracy and the off-line computation time needed to generate the database. On a lower limbs model (12 degrees of freedom, 82 muscles), thanks to this work, the MusIC method exhibits an accuracy error of 0.1% with an off-line computation time lower than 10 minutes. The on-line computation frequency (number of samples computed per second) is about 58 Hz. Thanks to these improvements, the MusIC method can be used to produce a feedback during an experimentation with a wide variety of musculoskeletal models or cost functions (used to share forces into muscles). The interaction between the subject, the experimenter (e.g. trainer, ergonomist or clinician) and the biomechanical data (e.g. muscle forces) in experimental sessions is a promising way to enhance rehabilitation, training or design techniques.

Essential diseases in prescribing: A national Delphi study towards a core curriculum in pharmacotherapy education.

AIMS: Prescribing is a core skill for junior doctors, yet 8-10% of their prescriptions contain errors. To ensure adequate training in prescribing, it is important to define the diseases for which junior doctors should be competent to prescribe. The aim of the present study was therefore to identify the essential diseases in prescribing for junior doctors. METHODS: A two-round Delphi consensus study was conducted among medical specialists, general practitioners, junior doctors, pharmacists and pharmacotherapy teachers from all eight academic hospitals in the Netherlands. Using a five-point Likert scale, the participants indicated for each item on an initial questionnaire whether it should be considered an essential disease for junior doctors. The items for which ≥80% of all respondents agreed or strongly agreed were accepted as essential diseases. RESULTS: Sixty-two participants completed the Delphi survey. In total, 63 of 220 items were considered to be essential diseases. CONCLUSION: This is the first Delphi consensus study identifying exact conditions that junior doctors must be able to prescribe for. The essential diseases can be used for training in prescribing and assessment of junior doctors' prescribing competence.

The MusIC method: a fast and quasi-optimal solution to the muscle forces estimation problem.

The present paper aims at presenting a fast and quasi-optimal method of muscle forces estimation: the MusIC method. It consists in interpolating a first estimation in a database generated offline thanks to a classical optimization problem, and then correcting it to respect the motion dynamics. Three different cost functions - two polynomial criteria and a min/max criterion - were tested on a planar musculoskeletal model. The MusIC method provides a computation frequency approximately 10 times higher compared to a classical optimization problem with a relative mean error of 4% on cost function evaluation.

Patient and health care professional perspectives on using telehealth to deliver pulmonary rehabilitation.

The objective of this study was to identify the necessary features of pulmonary telerehabilitation (P-TR) from the perspectives of individuals living with chronic lung disease and health care professionals (HCPs) who deliver pulmonary rehabilitation (PR). Focus groups were carried out with patients ( n = 26) and HCPs ( n = 26) to elicit and explore their opinions about the critical elements of in-person PR and ideas for how these elements could be supported using technology. A questionnaire was used to assess technology use, PR experience, and general health status. Four key elements of PR were identified as critical to P-TR: the social aspect of PR; communicating with HCPs for education and support; using biosensors for monitoring and promoting self-knowledge; and the evolution of support with progress over time. A range of technology-enabled devices and programs were suggested as means to recreate aspects of these integral elements. Consultations with patients and HCPs suggest that users are interested in technology and want to ensure it recreates the important aspects of PR. Patients and HCPs identified similar key elements for P-TR. The opinions and suggestions of patients and HCPs should be the driving force of innovation if P-TR is to succeed in improving health outcomes.

[The effect of mood-stabilising drugs on cytokine levels in bipolar disorder: a systematic review]. / De impact van stemmingsstabiliserende geneesmiddelen op cytokineconcen-traties bij patiënten met een bipolaire stoornis: een systematisch literatuur-onderzoek1.

ACHTERGROND: Veranderde cytokineconcentraties bij personen met een bipolaire stoornis ten opzichte van controle-personen suggereren een rol van het immuunsysteem in de pathofysiologie van bipolaire stoornis. Farmacotherapie is een belangrijke verstorende factor in klinisch onderzoek naar cytokineconcentraties.
DOEL: Evalueren van cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis en van het effect van stemmingsstabiliserende geneesmiddelen op deze concentraties.
METHODE: We doorzochten systematisch PubMed en Embase naar klinische studies die cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis beschrijven of het effect van een individueel stemmingsstabiliserend geneesmiddel op deze concentraties evalueren.
RESULTATEN: Van de 564 gescreende artikelen werden er 17 geïncludeerd. Resultaten bij medicatievrije patiënten toonden stemmingsgerelateerde cytokineveranderingen. Hoewel geen data over de kortetermijneffecten van lithium beschikbaar waren, was lithiumgebruik langer dan 2 maanden geassocieerd met normale cytokineconcentraties. Twee studies rapporteerden geen effect van valproïnezuur. We vonden geen studies over carbamazepine, lamotrigine of antipsychotica.
CONCLUSIE: Dit systematisch literatuuroverzicht toont stemmingsgerelateerde cytokineveranderingen bij medicatievrije patiënten met een bipolaire stoornis met de meeste evidentie voor een pro-inflammatoire immuunrespons tijdens manie. Euthymie en langdurig lithiumgebruik zijn geassocieerd met normale cytokineconcentraties. Er is een belangrijke methodologische heterogeniteit en onvoldoende replicatie tussen studies. Longitudinale studies met medicatievrije beginmetingen, gerandomiseerde monotherapeutische behandelprotocollen en nauwkeurige monitoring van stemming zijn noodzakelijk.
BACKGROUND: Alterations of the cytokine level in persons with bipolar disorder - when compared to controls - suggest that the immune system plays a role in the pathophysiology of bipolar disorder. Pharmacotherapy is an important confounding factor in clinical research on cytokine levels.
AIM: To evaluate the evidence on cytokine levels in medication-free bipolar disorder and to study the effects that single mood-stabilising drugs have on these levels.
METHOD: We searched PubMed and Embase systematically in order to single out clinical studies that reported on cytokine levels in medication-free bipolar disorder or that commented on the effects of single mood-stabilising drugs on cytokine levels.
RESULTS: Of the 564 articles that we screened, we detected 17 that were particularly relevant for our investigation. Results for medication-free patients point to mood-related alterations in cytokine levels. Although we found no data relating to short-term effects of lithium, the use of lithium in euthymic populations was associated with normal cytokine levels. Two studies reported no effect of valproate. We did not find any studies relating to carbamazepine, lamotrigine or antipsychotics.
CONCLUSION: Our systematic review of the literature suggests the presence of mood-related changes in cytokine levels in medication-free patients with bipolar disorder, with the most evidence for a proinflammatory response during a manic episode. Euthymia and long-term use of lithium use are associated with normal cytokine levels. There is considerable heterogeneity in the methods used in these studies and too little replication. Future research will have to include longitudinal studies with medication-free baseline measurements. It will also be necessary to draw up single-drug treatment protocols and to conduct intensive mood-related monitoring.

Flow cytometry community fingerprinting and amplicon sequencing for the assessment of landfill leachate cellulolytic bioaugmentation.

Flow cytometry (FCM) is a high throughput single cell technology that is actually becoming widely used for studying phenotypic and genotypic diversity among microbial communities. This technology is considered in this work for the assessment of a bioaugmentation treatment in order to enhance cellulolytic potential of landfill leachate. The experimental results reveal the relevant increase of leachate cellulolytic potential due to bioaugmentation. Cytometric monitoring of microbial dynamics along these assays is then realized. The flow FP package is used to establish microbial samples fingerprint from initial 2D cytometry histograms. This procedure allows highlighting microbial communities' variation along the assays. Cytometric and 16S rRNA gene sequencing fingerprinting methods are then compared. The two approaches give same evidence about microbial dynamics throughout digestion assay. There are however a lack of significant correlation between cytometric and amplicon sequencing fingerprint at genus or species level. Same phenotypical profiles of microbiota during assays matched to several 16S rRNA gene sequencing ones. Flow cytometry fingerprinting can thus be considered as a promising routine on-site method suitable for the detection of stability/variation/disturbance of complex microbial communities involved in bioprocesses.

Noisy threshold in neuronal models: connections with the noisy leaky integrate-and-fire model.

Providing an analytical treatment to the stochastic feature of neurons' dynamics is one of the current biggest challenges in mathematical biology. The noisy leaky integrate-and-fire model and its associated Fokker-Planck equation are probably the most popular way to deal with neural variability. Another well-known formalism is the escape-rate model: a model giving the probability that a neuron fires at a certain time knowing the time elapsed since its last action potential. This model leads to a so-called age-structured system, a partial differential equation with non-local boundary condition famous in the field of population dynamics, where the age of a neuron is the amount of time passed by since its previous spike. In this theoretical paper, we investigate the mathematical connection between the two formalisms. We shall derive an integral transform of the solution to the age-structured model into the solution of the Fokker-Planck equation. This integral transform highlights the link between the two stochastic processes. As far as we know, an explicit mathematical correspondence between the two solutions has not been introduced until now.