Current Status and Future Directions of Pain-Related Outcome Measures for Post-Surgical Pain Trials

Background: Clinical trials remain vital in order to: A) develop new treatment interventions, and also, B) to guide optimal use of current interventions for the treatment and prevention of acute and chronic postsurgical pain. Measures of pain (e.g. intensity and relief) and opioid use have been validated for the settings of postsurgical pain and continue to effectively guide research in this field.. Methods: This narrative review considers needs for innovation in postsurgical pain trial outcomes assessment. Results: Future improvements are needed and include: A) more widespread measurement of movement-evoked pain with validation of various procedure-relevant movemen-tevoked pain maneuvers; B) new validated analytical approaches to integrate early postoperative pain scores with opioid use; and, C) closer attention to the measurement of postoperative opioid use after hospital discharge. In addition to these traditional measures, consideration is being given to the use of new pain-relevant outcome domains that include: 1) other symptoms (e.g. nausea and vomiting), 2) recovery of physiological function (e.g. respiratory, gastrointestinal, genitourinary and musculoskeletal), 3) emotional function (e.g. depression, anxiety) and, 4) development of chronic postsurgical pain. Also, there is a need to develop pain-related domains and measures for evaluating both acute and chronic post-operative pain. Finally, evidence suggests that further needs for improvements in safety assessment and reporting in postsurgical pain trials is needed, e.g. by using an agreed upon, standardized collection of outcomes that will be reported as a minimum in all postsurgical pain trials. Conclusions: These proposed advances in outcome measurement methodology are expected to improve the success by which postsurgical pain trials guide improvements in clinical care and patient outcomes

Adaptive Deep Brain Stimulation: From Experimental Evidence Toward Practical Implementation.

Closed-loop adaptive deep brain stimulation (aDBS) can deliver individualized therapy at an unprecedented temporal precision for neurological disorders. This has the potential to lead to a breakthrough in neurotechnology, but the translation to clinical practice remains a significant challenge. Via bidirectional implantable brain-computer-interfaces that have become commercially available, aDBS can now sense and selectively modulate pathophysiological brain circuit activity. Pilot studies investigating different aDBS control strategies showed promising results, but the short experimental study designs have not yet supported individualized analyses of patient-specific factors in biomarker and therapeutic response dynamics. Notwithstanding the clear theoretical advantages of a patient-tailored approach, these new stimulation possibilities open a vast and mostly unexplored parameter space, leading to practical hurdles in the implementation and development of clinical trials. Therefore, a thorough understanding of the neurophysiological and neurotechnological aspects related to aDBS is crucial to develop evidence-based treatment regimens for clinical practice. Therapeutic success of aDBS will depend on the integrated development of strategies for feedback signal identification, artifact mitigation, signal processing, and control policy adjustment, for precise stimulation delivery tailored to individual patients. The present review introduces the reader to the neurophysiological foundation of aDBS for Parkinson's disease (PD) and other network disorders, explains currently available aDBS control policies, and highlights practical pitfalls and difficulties to be addressed in the upcoming years. Finally, it highlights the importance of interdisciplinary clinical neurotechnological research within and across DBS centers, toward an individualized patient-centered approach to invasive brain stimulation. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Effect of water composition on perchlorate removal from polluted ground- water using Ion Exchange Membrane Bioreactor

Perchlorate contamination of ground water is a worldwide concern. At several sites in Israel\u27s coastal aquifer, hundreds of ppm of perchlorate was found accompanied with significant concentrations of nitrate and chlorate, consequently preventing water production from wells in the area. The IEMB hybrid process [1] allows safe treatment of high perchlorate (and nitrate and chlorate) contaminated groundwater. The Donnan dialysis process removes the perchlorate from the water compartment using an anion exchange membrane (AEM) to the bio-compartment where it undergoes microbial degradation to much safer components such as chloride. The AEM acts as a barrier and keeps both compartments completely separate. Glycerol is used as an exogenous carbon and electron source for the biodegradation process [2]. This arrangement keeps the carbon source, reaction byproducts and bacteria confined in the bio-reactor thus preventing the contamination of the treated water. The present study examines the performance of the IEMB in removing perchlorate and other anions (nitrate and chlorate) at levels of hundreds mg L-1 from polluted ground water from the Ramat HaSharon (RHGW) contaminated site. The IEMB removal of the polluting anions was studied initially for synthetic and actual ground water fed to the water side while feeding 0.1 N of NaCl to the bio-compartment. We further studied the effect of adding bacteria and bio-media to the bio-compartment. In all experiment setups it is obvious that perchlorate dominates the flux across the AEM. Even though perchlorate concentration is considerably lower than nitrate and chlorate, its flux is greater than the sum of the other anion fluxes. At an effective driving force (EDF) value above 0.7 [mM] perchlorate had a negative effect on the other anions transport across the membrane. Adding bacteria to bio-compartment side fed with RHGW and bio-media increased anions total flux by 15%-23% at the first two runs. A thick biofilm has developed on the membrane bio-side during the following two runs, resulting in a total flux decline of 18%-22% when compared to the pure Donnan dialysis experiment. Throughout all the bio-degradation experiment regardless of the anion load to the bio-compartment the bio-degradation efficiency of the trace anions was above 99%. This study is the first to treat highly polluted complex ground water in an IEMB. It further established the perchlorate strong interaction with the AEM, consequently affecting the flux of other anions in the treatment process. This research is the basis for upscaling the IEMB technology into the field Please click Additional Files below to see the full abstract

What's in a pattern? Examining the Type of Signal Multivariate Analysis Uncovers At the Group Level

Multivoxel pattern analysis (MVPA) has gained enormous popularity in the neuroimaging community over the past few years. At the group level, most MVPA studies adopt an "information based" approach in which the sign of the effect of individual subjects is discarded and a non-directional summary statistic is carried over to the second level. This is in contrast to a directional "activation based" approach typical in univariate group level analysis, in which both signal magnitude and sign are taken into account. The transition from examining effects in one voxel at a time vs. several voxels (univariate vs. multivariate) has thus tacitly entailed a transition from directional to non-directional signal definition at the group level. While a directional group-level MVPA approach implies that individuals have similar multivariate spatial patterns of activity, in a non-directional approach each individual may have a distinct spatial pattern. Using an experimental dataset, we show that directional and non-directional group-level MVPA approaches uncover distinct brain regions with only partial overlap. We propose a method to quantify the degree of spatial similarity in activation patterns over subjects. Applied to an auditory task, we find higher values in auditory regions compared to control regions.Comment: Revised versio

Seawater desalination for agriculture by integrated forward and reverse osmosis: Improved product water quality for potentially less energy

Seawater desalination for agricultural irrigation will be an important contributor to satisfying growing water demands in water scarce regions. Irrigated agriculture for food production drives global water demands, which are expected to increase while available supplies are further diminished. Implementation of reverse osmosis, the current leading technology for seawater desalination, has been limited in part because of high costs and energy consumption. Because of stringent boron and chloride standards for agricultural irrigation water, desalination for agriculture is more energy intensive than desalination for potable use, and additional post-treatment, such as a second pass reverse osmosis process, is required. In this perspective, we introduce the concept of an integrated forward osmosis and reverse osmosis process for seawater desalination. Process modeling results indicate that the integrated process can achieve boron and chloride water quality requirements for agricultural irrigation while consuming less energy than a conventional two-pass reverse osmosis process. The challenges to further development of an integrated forward and reverse osmosis desalination process and its potential benefits beyond energy savings are discussed

The circadian clock at the intercept of sleep and pain

Peer reviewe