Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Background: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens. Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions. Methods: Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change). Results: Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or "stockpiling" medication. By comparison, physicians rated all participants as either "totally compliant" or "mostly compliant". UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P<0.001). Conclusion: These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making. Trial Registration: This study was preregistered on ClinicalTrials.gov (NCT03752411).

Behavioral and neurocognitive factors distinguishing post-traumatic stress comorbidity in substance use disorders.

Significant trauma histories and post-traumatic stress disorder (PTSD) are common in persons with substance use disorders (SUD) and often associate with increased SUD severity and poorer response to SUD treatment. As such, this sub-population has been associated with unique risk factors and treatment needs. Understanding the distinct etiological profile of persons with co-occurring SUD and PTSD is therefore crucial for advancing our knowledge of underlying mechanisms and the development of precision treatments. To this end, we employed supervised machine learning algorithms to interrogate the responses of 160 participants with SUD on the multidimensional NIDA Phenotyping Assessment Battery. Significant PTSD symptomatology was correctly predicted in 75% of participants (sensitivity: 80%; specificity: 72.22%) using a classification-based model based on anxiety and depressive symptoms, perseverative thinking styles, and interoceptive awareness. A regression-based machine learning model also utilized similar predictors, but failed to accurately predict severity of PTSD symptoms. These data indicate that even in a population already characterized by elevated negative affect (individuals with SUD), especially severe negative affect was predictive of PTSD symptomatology. In a follow-up analysis of a subset of 102 participants who also completed neurocognitive tasks, comorbidity status was correctly predicted in 86.67% of participants (sensitivity: 91.67%; specificity: 66.67%) based on depressive symptoms and fear-related attentional bias. However, a regression-based analysis did not identify fear-related attentional bias as a splitting factor, but instead split and categorized the sample based on indices of aggression, metacognition, distress tolerance, and interoceptive awareness. These data indicate that within a population of individuals with SUD, aberrations in tolerating and regulating aversive internal experiences may also characterize those with significant trauma histories, akin to findings in persons with anxiety without SUD. The results also highlight the need for further research on PTSD-SUD comorbidity that includes additional comparison groups (i.e., persons with only PTSD), captures additional comorbid diagnoses that may influence the PTSD-SUD relationship, examines additional types of SUDs (e.g., alcohol use disorder), and differentiates between subtypes of PTSD.

Habitual physical activity levels of adults with heart failure: systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to quantify habitual physical activity (PA) levels of patients with heart failure (HF) and assess the quality of reporting of device-assessed PA. METHODS: Eight electronic databases were searched up to 17 November 2021. Data on the study and population characteristics, method of PA measurement and PA metrics were extracted. A random-effects meta-analysis (restricted maximum likelihood with Knapp-Hartung SE adjustment) was conducted. RESULTS: Seventy-five studies were included in the review (n=7775 patients with HF). Meta-analysis was restricted to mean steps per day, encompassing 27 studies (n=1720 patients with HF). Pooled mean steps per day were 5040 (95% CI: 4272 to 5807). The 95% prediction interval for mean steps per day in a future study was 1262 to 8817. Meta-regression at the study level revealed that a 10-year increment in the mean age of patients was associated with 1121 fewer steps per day (95% CI: 258 to 1984). CONCLUSIONS: Patients with HF are a low-active population. These findings have implications for the way in which PA is targeted in patients with HF, and interventions should focus on addressing the age-related decline observed as well as increasing PA to improve HF symptoms and quality of life. PROSPERO REGISTRATION NUMBER: CRD42020167786.

Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.

Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.

Impact of Daily Consumption of Whole-Grain Quinoa-Enriched Bread on Gut Microbiome in Males.

Diets rich in whole grains are associated with improved health and a lower risk of non-communicable diseases, but the mechanisms through which these health benefits are conveyed are uncertain. One mechanism may be improvements in the gut environment by the delivery of fermentable substrates and associated phytochemicals to the lower gut and modification of the gut microbiome. Quinoa is included in the whole-grain category because of its structural similarities to cereals but the effects of its consumption on the gut microbiome have not been investigated to date. Our aim was to examine the impact of daily quinoa consumption on the gut microbiome in a 4-week randomised cross-over intervention separated by a 4-week wash-out period involving 28 adult males. Participants consumed either a quinoa-enriched wheat-bread roll providing 20 g quinoa flour each day, or a control wheat-only bread roll. Stool samples were collected in sterile collection tubes immediately before and at the end of each intervention period. DNA was then extracted, and the 16S rRNA V4 region of extracted DNA was amplified and sequenced. For both the control and quinoa bread periods, there were no changes at the phyla or genus level between baseline and week 4 (all p > 0.05). Diversity in the microbiome profile was not different from baseline after either intervention arms. The results show that small changes in the type of cereal consumed­substituting 20 g of refined wheat flour with whole-grain quinoa flour­was not able to significantly modulate the gut microbiome. Further studies with higher levels of quinoa or longer exposure periods are needed to ascertain if there is a dose−response effect of quinoa, and if these effects are able to translate into clinical outcomes.

The Distinctive Plant and Insect Assemblages of An Experimental Forest in Northern Lower Michigan (United States).

The effects of plants on insects are not completely clear due to potential covariation of weather or location affecting both assemblages. To address this question, plant and insect assemblages were described during summer 2019 and 2020 in two different forest habitats of northern Lower Michigan. The first habitat was a hardwood forest typical of secondary succession in the region. The second was a hydric forest located ~20 m from the hardwood forest which developed after lake sediment was deposited into a 10-ha area in the early 2000s. Reflecting this sediment deposition, soil of the hydric forest had higher water content and organic matter, and was dominated by the plant genera Solidago (Asterales: Asteraceae), Rubus (Rosales: Rosaceae), and Salix (Malpighiales: Salicaceae). In contrast, the hardwood forest had greater inorganic sediment and was dominated by Pteridium (Polypodiales: Dennstaedtiaceae), Carex (Poales: Cyperaceae), and Acer. Nearly 140,000 insect specimens were sampled using pitfall trapping, sweep netting, flight intercept trapping, ultraviolet light trapping, and yellow and blue pan trapping. The first three methods each sampled a unique insect assemblage, whereas the last three overlapped in taxa sampled. Insect assemblages of the two forests were distinct from each other using any of the six methods, with abundance of Pteridium and Salix (Sapindales: Sapindaceae) generally associating with changes in insect composition. A total of 41 insect taxa indicated the hydric forest and 14 indicated the hardwood forest. Insect richness increased with that of plants. These results demonstrate that differences in soil composition and plant assemblages associate with differences in forest insect assemblages, even of forests in very close proximity.

Attentional function and inhibitory control in different substance use disorders.

Attentional function in substance use disorder (SUD) is not well understood. To probe attentional function in SUD as a function of primary substance of abuse, we administered the attentional network task (ANT) to 44 individuals with Cocaine Use Disorder (CoUD), 49 individuals with Cannabis Use Disorder (CaUD), 86 individuals with Opioid Use Disorder (OUD), and 107 controls with no SUD, along with the stop-signal task (SST). The ANT quantifies the effects of (temporal) alerting cues and (spatial) orienting cues to reduce reaction time (RT) to targets, as well as probing how conflicting (target-incongruent) stimuli slow RT. The SST quantifies individuals' ability to inhibit already-initiated motor responses. After controlling for sex representation and age, OUD and CaUD participants showed blunted alerting effects compared to controls, whereas CaUD and CoUD participants showed greater stimulus conflict (flanker) effects. Finally, CoUD participants showed a trend toward increased orienting ability. In SST performance, no SUD group showed a prolonged stop-signal reaction compared to controls. However, the OUD group (and CoUD group at trend level) showed prolonged "go" RT to targets and reduced hit rates. These data indicate differences in attentional function in persons with SUD as a function of the primary substance use.

Checklist of the caddisflies (Insecta, Trichoptera) of the Upper Midwest region of the United States.

Five hundred and fifty-two caddisfly species are reported from the Upper Midwest region of the United States, an area that includes 13 states and ~ 2 million km2. Of these, 62 species are reported for the first time from the state of Iowa, 25 from Wisconsin, 18 from South Dakota, 12 from Illinois, five from Indiana, four from North Dakota, four from Minnesota, and one from Nebraska. The Upper Midwest fauna contains nearly 40% of all species known from the United States and Canada, as well as 22 species endemic to the region. Overall species richness was highest in Michigan (319 species), Kentucky (296), Minnesota (292), and Wisconsin (284). Differences in state species assemblages within the region largely followed a geographic pattern, with species richness declining in the western prairie states. There are almost certainly further species remaining to be found in this large region.

Comparison of caddisfly (Insecta, Trichoptera) assemblages from lake and river habitats of the Huron Mountains of Michigan (USA).

The caddisfly assemblages of six lakes and 12 1st-4th order streams of the Huron Mountains of northern Upper Michigan (USA) were sampled monthly with ultraviolet lights during June-September 2019. A total of 169 species representing 63 genera and 19 families was collected, including five species not found elsewhere in Michigan and two species endemic to the state. Species assemblages between lotic and lentic habitats were distinct from each other, with 11 species indicating lakes and 23 indicating rivers. Despite the taxonomic differences, biomass of functional feeding groups (FFGs) was similar between lakes and rivers, except for higher biomass of predators in the former and higher biomass of filtering collectors in the latter. The FFG biomass of both habitat types was dominated (50-70%) by shredders. Considering the undisturbed condition of the habitats, the caddisfly assemblages and FFG biomass of the Huron Mountains can serve as regional biological monitoring reference conditions.

Social Information Processing in Substance Use Disorders: Insights From an Emotional Go-Nogo Task.

Positive social connections are crucial for recovery from Substance Use Disorder (SUD). Of interest is understanding potential social information processing (SIP) mediators of this effect. To explore whether persons with different SUD show idiosyncratic biases toward social signals, we administered an emotional go-nogo task (EGNG) to 31 individuals with Cocaine Use Disorder (CoUD), 31 with Cannabis Use Disorder (CaUD), 79 with Opioid Use Disorder (OUD), and 58 controls. Participants were instructed to respond to emotional faces (Fear/Happy) but withhold responses to expressionless faces in two task blocks, with the reverse instruction in the other two blocks. Emotional faces as non-targets elicited more "false alarm" (FA) commission errors as a main effect. Groups did not differ in overall rates of hits (correct responses to target faces), but participants with CaUD and CoUD showed reduced rates of hits (relative to controls) when expressionless faces were targets. OUD participants had worse hit rates [and slower reaction times (RT)] when fearful faces (but not happy faces) were targets. CaUD participants were most affected by instruction effects (respond/"go" vs withhold response/"no-go" to emotional face) on discriminability statistic A. Participants were faster to respond to happy face targets than to expressionless faces. However, this pattern was reversed in fearful face blocks in OUD and CoUD participants. This experiment replicated previous findings of the greater salience of expressive face images, and extends this finding to SUD, where persons with CaUD may show even greater bias toward emotional faces. Conversely, OUD participants showed idiosyncratic behavior in response to fearful faces suggestive of increased attentional disruption by fear. These data suggest a mechanism by which positive social signals may contribute to recovery.

A new species of Setodes Rambur (Trichoptera: Leptoceridae) from northern Michigan, USA.

Setodes truncatus n. sp. is illustrated and described herein based on specimens collected from 2 adjacent watersheds of the Huron Mountains in northern Michigan (USA). Both known populations inhabit undisturbed sandy rivers. Males of S. truncatus appear most similar to those of S. incertus (Walker) but can be separated based on their short and truncate inferior appendages and by other differences in the genitalia. The larva and female both remain unknown. A revised key to males of the 10 North American species of Setodes is provided.

Age-associated mitochondrial complex I deficiency is linked to increased stem cell proliferation rates in the mouse colon.

One of the hallmarks of aging is an accumulation of cells with defects in oxidative phosphorylation (OXPHOS) due to mutations of mitochondrial DNA (mtDNA). Rapidly dividing tissues maintained by stem cells, such as the colonic epithelium, are particularly susceptible to accumulation of OXPHOS defects over time; however, the effects on the stem cells are unknown. We have crossed a mouse model in which intestinal stem cells are labelled with EGFP (Lgr5-EGFP-IRES-creERT2) with a model of accelerated mtDNA mutagenesis (PolgAmut/mut ) to investigate the effect of OXPHOS dysfunction on colonic stem cell proliferation. We show that a reduction in complex I protein levels is associated with an increased rate of stem cell cycle re-entry. These changes in stem cell homeostasis could have significant implications for age-associated intestinal pathogenesis.

Age-associated mitochondrial DNA mutations cause metabolic remodelling that contributes to accelerated intestinal tumorigenesis.

Oxidative phosphorylation (OXPHOS) defects caused by somatic mitochondrial DNA (mtDNA) mutations increase with age in human colorectal epithelium and are prevalent in colorectal tumours, but whether they actively contribute to tumorigenesis remains unknown. Here we demonstrate that mtDNA mutations causing OXPHOS defects are enriched during the human adenoma/carcinoma sequence, suggesting they may confer a metabolic advantage. To test this we deleted the tumour suppressor Apc in OXPHOS deficient intestinal stem cells in mice. The resulting tumours were larger than in control mice due to accelerated cell proliferation and reduced apoptosis. We show that both normal crypts and tumours undergo metabolic remodelling in response to OXPHOS deficiency by upregulating the de novo serine synthesis pathway (SSP). Moreover, normal human colonic crypts upregulate the SSP in response to OXPHOS deficiency prior to tumorigenesis. Our data show that age-associated OXPHOS deficiency causes metabolic remodelling that can functionally contribute to accelerated intestinal cancer development.

Transoral laser microsurgery and radiotherapy for oropharyngeal squamous cell carcinoma: Equitable survival and enhanced function compared with contemporary standards of care.

INTRODUCTION: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported. MATERIALS AND METHODS: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis. RESULTS: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%. CONCLUSIONS: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay.

Effects of Medical Comorbidities on the Surgical Outcomes of Deep Brain Stimulation for Parkinson Disease: A Retrospective, Single-Institution Study.

OBJECTIVE: Advancing age and greater number of medical comorbidities are well-known risk factors for higher rates of surgical complications and undesirable outcomes. We sought to determine the risk of increasing medical comorbidities on surgical outcomes for patients with Parkinson disease undergoing deep brain stimulation (DBS) surgery. METHODS: We retrospectively reviewed 107 consecutive patients who underwent DBS for Parkinson disease at Ochsner Medical Center in 2008-2018. Patients were stratified into 3 groups based on Elixhauser comorbidity index (ECI) at the time of surgery: 0, 1, or ≥2. Outcome measures were changes in Unified Parkinson's Disease Rating Scale III scores, changes in medications, and surgical complications. Analysis of variance, paired t test, and nonparametric equivalents were used for statistical analysis. RESULTS: Of patients, 31 (29.0%) had ECI score 0, 44 (41.1%) had ECI score 1, and 32 (29.9%) had ECI score ≥2. For all groups, Unified Parkinson's Disease Rating Scale III scores decreased significantly postoperatively (P = 0.0014, P < 0.0001, P < 0.0001). All groups had a reduction in mean levodopa equivalent daily dose after surgery; however, only the group with ≥2 comorbidities achieved statistical significance (P = 0.0026). The rate of postoperative complications was significantly correlated with comorbidity score on univariate logistic regression analysis (P = 0.0425). CONCLUSIONS: Our findings indicate that DBS is efficacious in patients with multiple medical comorbidities. However, patients with ≥1 medical comorbidities may be more likely to have complications. The most common observed complication was wound infection. Patients with medical comorbidities may still benefit significantly from DBS when performed at experienced centers.

Ash-free dry mass values for northcentral USA caddisflies (Insecta, Trichoptera).

Ash-free dry mass (AFDM) values are presented for the adult stage of 63 caddisfly species commonly found throughout the northcentral US. Weights ranged from 0.01 mg for the smallest species to 7.22 mg for the largest. These values represent the first published data on the AFDM of the adult stage of Trichoptera, and can be used in other studies for more precise assessments of stream conditions without destruction of specimens. This increased precision is demonstrated herein by re-analyzing a previously published data set.

Registered nurse perceptions of factors contributing to the inconsistent brand image of the nursing profession.

BACKGROUND: Nurses have been overlooked as autonomous healthcare providers due to an inaccurate image which projects them as caring and trusted, yet lacking in influence and autonomy. It is important for nurses to understand the image their profession wishes to convey, how the image falls short, and what can be done to improve it. PURPOSE: To examine responses of Registered Nurses (n = 286) describing factors influencing nursing's inconsistent brand image. METHODS: Qualitative data were thematically coded, analyzed, and grouped into eight influencing factors. FINDINGS: Factors contributing to nursing's inconsistent image included: variety of education/credentials, image not a priority, lack of leadership development, lack of professionalism, portrayals in the media and online, patients' personal experiences, treatment by other professional colleagues and gender role assumptions. DISCUSSION: A strong brand image could dispel outdated and inaccurate views while communicating new visionary leadership which aligns with priorities for the nursing profession.

The relevance of surgical margins in clinically early oral squamous cell carcinoma.

OBJECTIVES: There is controversy regarding surgical margins in the management of early oral squamous cell carcinoma (OSCC). The main objectives of this study were to assess the: relevance of the margin independent of tumour variables; threshold for a safe margin; relevance of dysplasia at the margin. MATERIALS & METHODS: UK based retrospective multicenter cohort study of patients with previously untreated and clinically early OSCC between 1998 and 2016. All patients had surgery as the primary modality and had surgical staging of the neck. Minimum follow-up was 2 years. Margins were classified as: clear ≥5.0 mm; close 1.0-4.9 mm; involved not cut-through (INC-T) 0.1-0.9 mm; cut-through (C-T) 0 mm. RESULTS: 669 patients were included. After adjusting for tumour variables Cox multivariate regression analysis demonstrated that close margins had similar survival outcomes to clear margins (Hazard Ratio(HR) 0.99 (95%CI 0.50-1.95) for Local Recurrence Free Survival (LRFS); HR 1.08 (95%CI 0.7-1.66) for Disease Free Survival (DFS); HR 0.74 (95%CI 0.44-1.25) for Disease Specific Survival (DSS); HR 0.80 (95%CI 0.58-1.11) for Overall Survival (OS)). C-T margins had significantly worse LRFS (HR 5.01 (95%CI 2.02-12.39)) and DFS (HR 2.58 (95%CI 1.28-5.20)). INC-T margins had significantly worse DFS (HR 1.98 (95% CI 1.01-3.87)). Time dependent receiver operating characteristic curve analysis did not demonstrate a clear margin threshold for LRFS within 24 months (AUC = 0.53 (95%CI 0.41-0.64)). Dysplasia at the margin did not influence LRFS or DFS. CONCLUSION: Only resection margins <1 mm independently affected survival outcomes. This should be considered when making decisions regarding adjuvant treatment.

It's No Has Bean: A Review of the Effects of White Kidney Bean Extract on Body Composition and Metabolic Health.

The rising prevalence of overweight and obesity is a global concern, increasing the risk of numerous non-communicable diseases and reducing quality of life. A healthy diet and exercise remain the cornerstone treatments for obesity. However, adherence rates can be low and the effectiveness of these interventions is often less than anticipated, due to compensatory changes in other aspects of the energy balance equation. Whilst some alternative weight-loss therapies are available, these strategies are often associated with side effects and are expensive. An alternative or adjunct to traditional weight-loss approaches may be the use of bioactive compounds extracted from food sources, which can be incorporated into habitual diet with a low cost and minimal burden. One product which has attracted attention in this regard is white kidney bean extract (WKBE), which has been suggested to inhibit the enzyme α-amylase, limiting carbohydrate digestion and absorption with small but potentially meaningful attendant beneficial effects on body weight and metabolic health. In this review, drawing evidence from both human and animal studies, we discuss the current evidence around the effects of WKBE on body composition and metabolic health. In addition, we discuss evidence on the safety of this supplement and explore potential directions for future research.