Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence.

With emerging information about the potential for morbidity and reduced life expectancy with long-term use of opioids, it is logical to evaluate nonopioid analgesic treatments to manage pain states. Combinations of drugs can provide additive and/or synergistic effects that can benefit the management of pain states. In this regard, tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate nociceptive signals and have been studied for chronic pain treatment. Psilocybin, commonly known as "magic mushrooms", works at the serotonin receptor, 5-HT2A. Psilocybin has been found in current studies to help with migraines since it has a tryptamine structure and works similarly to triptans. Psilocybin also has the potential for use in chronic pain treatment. However, the studies that have looked at alternative plant-based medications such as THC, CBD, and psilocybin have been small in terms of their sample size and may not consider the demographic or genetic differences in the population because of their small sample sizes. At present, it is unclear whether the effects reported in these studies translate to the general population or even are significant. In summary, additional studies are warranted to evaluate chronic pain management with alternative and combinations of medications in the treatment of chronic pain.

Fall Creek Monitoring Station: Highly Resolved Temporal Sampling to Prioritize the Identification of Nontarget Micropollutants in a Small Stream.

The goal of this research was to comprehensively characterize the occurrence and temporal dynamics of target and nontarget micropollutants in a small stream. We established the Fall Creek Monitoring Station in March 2017 and collected daily composite samples for one year. We measured water samples by means of high-resolution mass spectrometry and developed and optimized a postacquisition data processing workflow to screen for 162 target micropollutants and group all mass spectral (MS) features into temporal profiles. We used hierarchical clustering analysis to prioritize nontarget MS features based their similarity to target micropollutant profiles and developed a high-throughput pipeline to elucidate the structures of prioritized nontarget MS features. Our analyses resulted in the identification of 31 target micropollutants and 59 nontarget micropollutants with varying levels of confidence. Temporal profiles of the 90 identified micropollutants revealed unexpected concentration-discharge relationships that depended on the source of the micropollutant and hydrological features of the watershed. Several of the nontarget micropollutants have not been previously reported including pharmaceutical metabolites, rubber vulcanization accelerators, plasticizers, and flame retardants. Our data provide novel insights on the temporal dynamics of micropollutant occurrence in small streams. Further, our approach to nontarget analysis is general and not restricted to highly resolved temporal data acquisitions or samples collected from surface water systems.

Four hand injuries not to miss: avoiding pitfalls in the emergency department.

The clinical and radiological findings in some hand injuries can be subtle and easily misinterpreted, leading to irreversible changes and profound functional loss. The importance of early and accurate diagnosis is clear. This study looks at four such injuries, with reference to pertinent anatomy, typical mechanisms of injury, examination and radiological findings, with emphasis on avoiding pitfalls in the emergency department.

"Replicated" genome wide association for dependence on illegal substances: genomic regions identified by overlapping clusters of nominally positive SNPs.

Declaring "replication" from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication may be unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity, and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally significant association in each of several independent samples. This approach provides one "nontemplate" approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 million (1M) SNP Affymetrix and Illumina GWA results for dependence on illegal substances. This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally significant SNPs from samples of the same racial/ethnic background identify the same chromosomal regions. There is more modest confidence in: (a) identification of individual chromosomal regions and genes and (b) overlap between results from samples of different racial/ethnic backgrounds. The strong overlap identified among the samples with similar racial/ethnic backgrounds, together with prior work that identified overlapping results in samples of different racial/ethnic backgrounds, support contributions to individual differences in vulnerability to addictions that come from both relatively older allelic variants that are common in many current human populations and newer allelic variants that are common in fewer current human populations.

The effect of combined use of botulinum toxin type A and functional electric stimulation in the treatment of spastic drop foot after stroke: a preliminary investigation.

OBJECTIVE: To investigate the effect of combined botulinum toxin type A (BTX) and functional electric stimulation (FES) treatment on spastic drop foot in stroke. DESIGN: Nonblinded randomized controlled trial. SETTING: Hospitals. PARTICIPANTS: Consecutive sample of 21 ambulant adults within 1 year after stroke with a spastic drop foot, of whom 18 completed the study. INTERVENTIONS: The treatment group received BTX injections (Dysport) on 1 occasion into the medial and lateral heads of the gastrocnemius (200U each) and tibialis posterior (400U each) muscles and FES, used on a daily basis for 16 weeks to assist walking. Both groups continued with physiotherapy at the same rate. MAIN OUTCOME MEASURES: Walking speed, Physiological Cost Index, Modified Ashworth Scale, Rivermead Motor Assessment, and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Walking speed increased over 12 weeks in both control (P=.020) and treatment groups (nonstimulated, P=.004; stimulated, P=.042). The baseline corrected (analysis of covariance) increase in mean walking speed at 12 weeks, relative to controls, was.04m/s (95% confidence interval [CI],.003-.090) without stimulation, and.09m/s (95% CI,.031-.150) with stimulation. CONCLUSIONS: Combined treatment effectively improved walking and function. A larger study is needed to quantify the treatment effect and to investigate its impact on quality of life.

A pilot study to investigate the combined use of botulinum neurotoxin type a and functional electrical stimulation, with physiotherapy, in the treatment of spastic dropped foot in subacute stroke.

The objective was to inform sample size calculations for a full randomized controlled trial (RCT). The design included an RCT pilot trial with a 16 week study period, including a 4 week baseline phase. The subjects were adults within 1 year of first stroke, ambulant with a spastic dropped foot. Twenty-one participants were recruited from the stroke services of 4 centers. For intervention all participants received physiotherapy; the treatment group also received botulinum neurotoxin Type A (BoNTA) intramuscular injections to triceps surae (800 U Dysport) and functional electrical stimulation (FES) of the common peroneal nerve to assist walking. The main outcome measure was walking speed. The result was a significant upward trend in median walking speed for both the control (p = 0.02) and treatment groups (nonstimulated p = 0.004, stimulated p = 0.042). Trend lines were different in location (p = 0.04 and p = 0.009, respectively). In conclusion, there is evidence of an additional, beneficial effect of BoNTA and FES. Sufficient information has been gained on the variability of the primary outcome measure to inform sample size calculations for a full RCT to quantify the treatment effect with precision.