Impact of the COVID-19 pandemic on the rate of lower limb amputation in Veterans.

BACKGROUND: The COVID-19 pandemic led to changes in health care, including postponement of nonurgent appointments. These changes, combined with overall decreased activity levels, may have placed individuals with vascular disease at increased risk for skin ulceration and amputation. OBJECTIVE: To determine the rates of lower limb amputation in Veterans due to complications of diabetes and/or vascular disease in the year following onset of the COVID-19 pandemic (March 2020-March 2021) compared to the previous 3 years (March 2017-March 2020). DESIGN: Retrospective chart review. SETTING: Minneapolis Veterans Affairs Health Care System. PARTICIPANTS: Veterans with a vascular consult appointment note between March 1, 2017, and February 28, 2021. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcome was lower limb amputation rate in the year following onset of the COVID-19 pandemic compared to the previous 3 years. Secondary outcome was the rate of lower limb wounds in the same time frame. We hypothesized that rates of lower limb amputation and wounds increased during the pandemic. RESULTS: Vascular consult appointments (n = 4183) were reviewed between March 1, 2017, and February 28, 2021. Significantly higher rates of amputation (7.52% vs. 5.19%; p = .006) and wound presence (16.77% vs. 11.66%; p < .001) were found 1 year postpandemic compared to the previous 3 years. Amputation and wound rates did not significantly increase between pairs of consecutive years prior to the pandemic but significantly increased between the year preceding the pandemic and the first year of the pandemic (amputation p = .047; wound p = .004). CONCLUSIONS: Increased rates of amputation and wounds in Veterans following the onset of the COVID-19 pandemic are likely due to disruption of care, lifestyle changes, and other pandemic-related factors. Awareness of COVID-19-related negative health effects is imperative for health care providers to ensure appropriate allocation of resources and alternate models for care delivery for amputation and preventative care as part of disaster response.

Effectiveness of Prefrontal Transcranial Magnetic Stimulation for Depression in Older US Military Veterans.

OBJECTIVE: While typical aging is associated with decreased cortical volume, major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) likely exacerbates this process. Cerebral atrophy leads to increased coil-to-cortex distance and when using transcranial magnetic stimulation (TMS), potentially reducing effectiveness in older adults. METHODS: Data from a large-scale quality improvement project was used. Included veterans eligible for TMS and completed TMS treatment. Age was assessed as a predictive factor of depression outcomes after TMS treatment among veterans. Secondary analyses examined the impact of age on 1) MDD response and remission and 2) MDD change within MDD-only verses comorbid MDD and PTSD groups. RESULTS: The entire sample included 471 veterans. Primary analysis revealed age as a negative predictor of depression outcomes (p = 0.019). Secondary analyses found age to be a significant predictor of remission (p = 0.004), but not clinical response. Age was not a predictive factor in depression outcomes between those with MDD-only compared to MDD+PTSD. CONCLUSIONS: Increased age predicts greater MDD symptom reduction after TMS. Although age did not predict response rates, it did predict increased rates of remission in veterans. Age did not differentially predict depression outcomes between those with or without PTSD. The sample size was sufficient to discern a difference in efficaciousness, and limitations were those inherent to registry studies in veterans. This data indicates that TMS can be an important treatment option for older individuals.

Evaluation of a Virtual Reality Platform to Train Stress Management Skills for a Defense Workforce: Multisite, Mixed Methods Feasibility Study.

BACKGROUND: Psychological stress-related injuries within first-responder organizations have created a need for the implementation of effective stress management training. Most stress management training solutions have limitations associated with scaled adoption within the workforce. For instance, those that are effective in civilian populations often do not align with the human performance culture embedded within first-responder organizations. Programs involving expert-led instructions that are high in quality are often expensive. OBJECTIVE: This study sought to evaluate a tailored stress management training platform within the existing training schedule of the Australian Defense Force (ADF). The platform, known as Performance Edge (PE), is a novel virtual reality (VR) and biofeedback-enabled stress management skills training platform. Focusing on practical training of well-established skills and strategies, the platform was designed to take advantage of VR technology to generate an immersive and private training environment. This study aimed to assess the feasibility of delivering the VR platform within the existing group-based training context and intended training population. In this setting, the study further aimed to collect data on critical predictors of user acceptance and technology adoption in education, including perceived usability, usefulness, and engagement, while also assessing training impacts. METHODS: This study used a mixed methods, multisite approach to collect observational, self-reported, and biometric data from both training staff and trainers within a real-world "on-base" training context in the ADF. Validated scales include the Presence Questionnaire and User Engagement Scale for perceived usefulness, usability, and engagement, as well as the State Mindfulness Scale and Relaxation Inventory, to gain insights into immediate training impacts for specific training modules. Additional surveys were specifically developed to assess implementation feedback, intention to use skills, and perceived training impact and value. RESULTS: PE training was delivered to 189 ADF trainees over 372 training sessions. The platform was easy to use at an individual level and was feasible to deliver in a classroom setting. Trainee feedback consistently showed high levels of engagement and a sense of presence with the training content and environment. PE is overall perceived as an effective and useful training tool. Self-report and objective indices confirmed knowledge improvement, increased skill confidence, and increased competency after training. Specific training elements resulted in increased state mindfulness, increased physical relaxation, and reduced breathing rate. The ability to practice cognitive strategies in a diverse, private, and immersive training environment while in a group setting was highlighted as particularly valuable. CONCLUSIONS: This study found the VR-based platform (PE) to be a feasible stress management training solution for group-based training delivery in a defense population. Furthermore, the intended end users, both trainers and trainees, perceive the platform to be usable, useful, engaging, and effective for training, suggesting end-user acceptance and potential for technology adoption.

Correction: Evaluation of a Virtual Reality Platform to Train Stress Management Skills for a Defense Workforce: Multisite, Mixed Methods Feasibility Study.

[This corrects the article DOI: 10.2196/46368.].

Learning, Hope, and Empowerment: A Reflexive Thematic Analysis of Feedback on a Group Intervention for Parents of Youth With Chronic Pain.

OBJECTIVES: Limited research has investigated parent-targeted interventions in pediatric chronic pain, though these interventions may be an important part of family-centered care. Further, parent perspectives and feedback regarding these interventions are scant in the literature, even though they are crucial for developing, refining, and optimizing treatment options. This study aimed to understand how parents experience and perceive their participation in a cognitive-behavioral therapy-based, parent-targeted group intervention that was delivered either in-person or virtually, with a focus on the treatment components they found most important. METHODS: Data from semistructured focus groups/interviews within 1week post-treatment with 32 parents (n=11 in-person, n=21 virtual) were analyzed using an inductive reflexive thematic analysis. RESULTS: Three overarching themes were generated from the thematic analysis: building a foundation of knowledge, finding normalization and hope through connection and lived experiences, and sharing collective responsibility for pain management. DISCUSSION: Parents perceived a range of benefits from participating in a cognitive-behavioral therapy-based, parent-targeted group intervention, both on themselves and for their youth. Overall, parent perceptions across in-person and virtual intervention delivery were consistent, except for a drawback of virtual participation for developing a deeper social connection among parents. Thus, a relatively brief parent-targeted group intervention was perceived to be a positive experience for parents, though considerations for adapting to virtual delivery and facilitating social connection among parents seem to be important.

Triple-Barrel Ultramicroelectrodes for Multipurpose, Submilliliter Electroanalysis.

Here, we have developed and applied a triple-barrel microelectrode. This device incorporates a platinum disk working electrode, a platinum disk counter electrode, and a low-leakage Ag/AgCl reference electrode into a small probe. We demonstrate that the incorporated low-leakage reference electrode shows similar voltammetry, potentiometry, and drift when compared to a commercial reference electrode in bulk solution. We also demonstrate the versatility of such a small three-channel system via voltammetry in nanoliter droplets and through electroanalysis of captured aerosols. Finally, we demonstrate the probe's potential utility in single-cell electroanalysis by making measurements within salmon eggs.

On the mechanism of the bipolar reference electrode.

Commercial silver/silver chloride (Ag/AgCl) reference electrodes are some of the most commonly used reference electrodes, but they suffer from a number of issues due to their porous frits. Such issues include difficulty miniaturizing, silver and chloride ion leakage, charge screening effects at low ionic strength, frit drying if left unattended in air, and incompatibility with organic solvents. To solve these issues, we recently designed a reference electrode that is leakless in principle by replacing the porous frit with a sealed, conductive wire, where the ends of the wire are exposed to the reference electrode solution and the working electrode solution. We hypothesized that the reference electrode operated like a closed, bipolar electrochemical cell, and we termed the name bipolar reference electrode (BPRE). Here, we provide evidence that the BPRE can either act as a reference electrode by operating through an ion transfer mechanism via leakage through the imperfect seal, or it can act as a highly stable quasi-reference electrode through a bipolar electron transfer mechanism (BPQRE). Finally, we demonstrate the effectiveness of the BPRE in other types of common electrochemical studies, including chronoamperometry, linear sweep voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy.

Amputation-specific and generic correlates of participation among Veterans with lower limb amputation.

Participation in valued interpersonal and community activities is a key component of rehabilitation for Veterans with amputation. The purpose of this study was to identify specific factors that promote or inhibit participation to inform development of interventions that may facilitate participation in desired life activities. A convenience sample of 408 Veterans with at least one lower limb amputation and who had received outpatient care from the Regional Amputation Center (RAC) completed a mailed survey. Participation was measured using the Community Participation Indicators (CPI) Importance, Control, and Frequency scales and the Patient Reported Outcome Measurement Information System (PROMIS) Ability to Participate in Social Roles and Satisfaction with Social Participation scales. Multiple imputation procedures were used to address missing data. Correlates of participation were examined through multiple linear regression. A total of 235 participants completed the survey, a response rate of 58%. Levels of participation, measured with the PROMIS instruments, were 43.2 (SD = 8.1) for Ability and 46.4 (SD = 8.6) for Satisfaction. Regression analyses found robust amputation-specific correlates for participation, including body image and balance confidence. Generic (non-amputation specific) correlates for participation included depression and pain interference. Development of treatment approaches and devices that can address body image, balance confidence, pain, and mental health concerns such as depression have the potential to enhance the participation and rehabilitation of Veterans with lower limb amputation.

Versatile potentiometric metabolite sensing without dioxygen interference.

The field of electrochemical biosensors has been dominated by amperometric and voltammetric sensors; however, these are limited greatly in their signal dependence on electrode size. Open circuit potentiometric sensors are emerging as an alternative due to their signal insensitivity to electrode size. Here, we present a second-generation biosensor that uses a modified chitosan hydrogel to entrap a dehydrogenase or other oxidoreductase enzyme of interest. The chitosan is modified with a desired electron mediator such that in the presence of the analyte, the enzyme will oxidize or reduce the mediator, thus altering the measured interfacial potential. Using the above design, we demonstrate a swift screening method for appropriate enzyme-mediator pairs based on open circuit potentiometry, as well as the efficacy of the biosensor design using two dehydrogenase enzymes (FADGDH and ADH) and peroxidase. Using 1,2-naphthoquinone as the mediator for FADGDH, dynamic ranges from 0.1 to 50 mM glucose are achieved. We additionally demonstrate the ease of fabrication and modification, a lifetime of ≥28 days, insensitivity to interferents, miniaturization to the microscale, and sensor efficacy in the presence of the enzyme's natural cofactor. These results forge a foundation for the generalized use of potentiometric biosensors for a wide variety of analytes within biologically-relevant systems where oxygen can be an interferent.

Salmonella Typhimurium DT 104 response to Lytic bacteriophage and Lactobionic acid on raw chicken breast.

Bacterial food poisoning cases due to Salmonella have been linked with a variety of poultry products. This study evaluated the effects of a Salmonella-specific Lytic bacteriophage and Lactobionic acid (LBA) on Salmonella Typhimurium DT 104 growth on raw chicken breast meat. Each chicken breast was randomly assigned to a treatment group (Control, DI water, phage 1%, phage 5%, LBA 10 mg/mL, LBA 20 mg/mL, and phage 5% + LBA 20 mg/mL) with four chicken breasts per group. Samples were inoculated with 106 CFU/mL of Salmonella and stored at 4 °C for 30 min. The inoculated chicken breasts were randomly assigned to different storage time (0 h, 1 h, 24 h, or 48 h). Both time and treatment showed significance reduction (P < 0.0001) of microbial growth. The weight loss was significantly different (P < 0.0001) between treatments. The LBA treatments were not effective when compared to the control group, but Lytic bacteriophage significantly reduced the amount of microbial growth.

Leakless, Bipolar Reference Electrodes: Fabrication, Performance, and Miniaturization.

Reference electrodes must maintain a well-defined potential for long periods of time to be useful. The silver/silver chloride (Ag/AgCl) reference electrode is arguably the most widely used reference electrode, but it leaks silver and chloride ions into the sample solution through the porous frit over time. Further, the porous frit makes miniaturization to the micro- and nanoscale challenging. Here, we present an alternative, where the traditional Ag/AgCl reference electrode porous frit is replaced by a conductive wire, preventing ion leakage and allowing miniaturization to the microscale. Charge balance is maintained through a closed bipolar electrochemical mechanism, where faradaic processes occur on each end of the sealed wire. Using the above design, we demonstrate the efficacy of the leakless, bipolar reference electrode (BPRE) and miniaturize it to the microscale (µ-leakless BPRE). Importantly, we demonstrate that leakless and µ-leakless BPREs behave the same as commercial reference electrodes during potentiometric measurements and leakless BPREs perform similarly during voltammetric measurements on ultramicroelectrodes. We demonstrate that the drift during voltammetry using a leakless BPRE on a macroelectrode is slightly more appreciable compared to the drift seen with a commercial reference electrode. We detail design principles for the use of leakless BPREs in nonaqueous solvents and in sealing other conductive materials (e.g., gold and carbon). Using mass spectrometry, we show that the maximum leakage of methylene blue is 0.36 fmol/s, at least 2 orders of magnitude smaller than that of commercial reference electrodes. Finally, we demonstrate the efficacy of using leakless BPREs in potentiometric glucose sensing.

Recent Advances in Potentiometric Biosensing.

Potentiometric biosensors are incredibly versatile tools with budding uses in industry, security, environmental safety, and human health. This mini-review on recent (2018-2020) advances in the field of potentiometric biosensors is intended to give a general overview of the main types of potentiometric biosensors for novices while still providing a brief but thorough summary of the novel advances and trends for experienced practitioners. These trends include the incorporation of nanomaterials, graphene, and novel immobilization materials, as well as a strong push towards miniaturized, flexible, and self-powered devices for in-field or at-home use.

Oxidase-loaded hydrogels for versatile potentiometric metabolite sensing.

Continuous monitoring of biological metabolites of interest necessitates sensors that are robust, versatile, miniaturizable, and reliable. Electrochemical biosensors have dominated the field of biosensors for decades due to their robust and inexpensive nature. Classically, these sensors use amperometric and voltammetric methods as the sensing modality. One of the greatest limitations with these methods is the dependence of the signal (current, i) on the electrode size, which can change with respect to time due to fouling. Here, we present open circuit potential, an electrochemical technique that is relatively insensitive to electrode size, as a reliable alternative to amperometric and voltammetric techniques for monitoring metabolites of interest. The sensor operates by trapping an oxidase enzyme in a chitosan hydrogel. The oxidase enzyme is required for metabolite specificity. When the oxidase enzyme meets its substrate, oxygen is consumed, and hydrogen peroxide is generated. Hydrogen peroxide generation dominates a half reaction at the platinum surface, resulting in a change in potential. Using the above criteria, we demonstrate the efficacy, long lifetime, sensitivity, and ease of fabrication of glucose sensors, and miniaturize the sensors from macro- to microelectrodes. Additionally, we demonstrate the ease with which this platform can be extended to detect other analytes in the form of a galactose sensor. Our results set a foundation for the generalized use of potentiometric sensors for a broad range of metabolites and applications.

Development of a modular stress management platform (Performance Edge VR) and a pilot efficacy trial of a bio-feedback enhanced training module for controlled breathing.

This paper describes the conceptual design of a virtual reality-based stress management training tool and evaluation of the initial prototype in a pilot efficacy study. Performance Edge virtual-reality (VR) was co-developed with the Australian Defence Force (ADF) to address the need for practical stress management training for ADF personnel. The VR application is biofeedback-enabled and contains key stress management techniques derived from acceptance and commitment and cognitive behavioural therapy in a modular framework. End-user-provided feedback on usability, design, and user experience was positive, and particularly complimentary of the respiratory biofeedback functionality. Training of controlled breathing delivered across 3 sessions increased participants' self-reported use of breath control in everyday life and progressively improved controlled breathing skills (objectively assessed as a reduction in breathing rate and variability). Thus the data show that a biofeedback-enabled controlled breathing protocol delivered through Performance Edge VR can produce both behaviour change and objective improvement in breathing metrics. These results confirm the validity of Performance Edge VR platform, and its Controlled Breathing module, as a novel approach to tailoring VR-based applications to train stress management skills in a workplace setting.

Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression.

BACKGROUND: Although repetitive transcranial magnetic stimulation ('TMS') is becoming a gold standard treatment for pharmacoresistant depression, we lack neural target biomarkers for identifying who is most likely to respond to TMS and why. To address this gap in knowledge we evaluate neural targets defined by activation and functional connectivity of the dorsolateral prefrontal cortex-anchored cognitive control circuit, regions of the default mode network and attention circuit, and interactions with the subgenual anterior cingulate. We evaluate whether these targets and interactions between them change in a dose-dependent manner, whether changes in these neural targets correspond to changes in cognitive behavioral performance, and whether baseline and early change in neural target and cognitive behavioral performance predict subsequent symptom severity, suicidality, and quality of life outcomes. This study is designed as a pragmatic, mechanistic trial partnering with the National Clinical TMS Program of the Veteran's Health Administration. METHODS: Target enrollment consists of 100 veterans with pharmacoresistant Major Depressive Disorder (MDD). All veterans will receive a clinical course of TMS and will be assessed at 'baseline' pre-TMS commencement, 'first week' after initiation of TMS (targeting five sessions) and 'post-treatment' at the completion of TMS (targeting 30 sessions). Veterans will be assessed using functional magnetic resonance imaging (fMRI), a cognitive behavioral performance battery, and established questionnaires. Multivariate linear mixed models will be used to assess whether neural targets change with TMS as a function of dose (Aim 1), whether extent and change of neural target relates to and predicts extent of behavioral performance (Aim 3), and whether extent of neural target change predicts improvement in symptom severity, suicidality, and quality of life (Aim 3). For all three aims, we will also assess the contribution of baseline moderators such as biological sex and age. DISCUSSION: To our knowledge, our study will be the first pragmatic, mechanistic observational trial to use fMRI imaging and cognitive-behavioral performance as biomarkers of TMS treatment response in pharmacoresistant MDD. The results of this trial will allow providers to select suitable candidates for TMS treatment and better predict treatment response by assessing circuit connectivity and cognitive-behavioral performance at baseline and during early treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04663481 , December 5th, 2020, retrospectively registered. The first veteran was enrolled October 30th, 2020.

Deeply Discrediting: A Systematic Review Examining the Conceptualizations and Consequences of the Stigma of Working in Aged Care.

BACKGROUND AND OBJECTIVES: The stigma of working in aged care can discredit and devalue those working in gerontology. This overlooked workforce issue may underpin complex staffing challenges like chronic worker shortages and inadequate care delivery. Our review synthesizes the existing literature and introduces a conceptual framework based on linguistics to reconcile disparate conceptualizations and negative consequences of this stigma. RESEARCH DESIGN AND METHODS: We conducted a systematic review and assessed peer-reviewed articles published from 1973 to 2019 across 5 databases. Fifty-nine articles were selected based on criteria grounded in stigma theory. RESULTS: Only 10 articles explicitly used the term "stigma" when conceptualizing the stigma of working in aged care. An additional 49 articles conceptualized this stigma in terms of stigma processes (e.g., status loss). Findings from a deeper examination using a linguistic analysis revealed societal groups predominantly conceptualized stigma in 3 distinct ways based on (a) unfavorable character judgment of aged care workers, (b) lower value placed on aged care work, and (c) negative emotional reactions towards working in aged care. Last, stigma was associated with adverse psychological and job-related consequences. DISCUSSION AND IMPLICATIONS: Reconceptualizing this workforce issue and recognizing it as a societal challenge will enable policymakers to design evidence-based interventions at industry and societal levels. We propose workforce challenges in the aged care sector such as attraction, retention, and well-being may lessen with interventions aimed at mitigating the stigma of working in aged care.

Worth the Wait: Delayed Recall after 1 Week Predicts Cognitive and Medial Temporal Lobe Trajectories in Older Adults.

METHOD: Clinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics. RESULTS: Worse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044). CONCLUSIONS: Memory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx).

Baseline neuropsychological profiles in prion disease predict survival time.

OBJECTIVE: Few studies have captured the neuropsychological profile of sporadic Creutzfeldt-Jakob disease (sCJD) with neuropsychological testing, and little is known about cognitive predictors of survival. We characterized baseline neuropsychological performance in sCJD and investigated associations with survival. METHODS: sCJD participants who completed the MMSE (n = 118), 61 sCJD of whom also completed a neuropsychological battery at baseline, and 135 age-matched healthy controls, were included. Composite scores of global cognition, memory, executive functions, visuospatial, and language were derived. Cox proportional hazard models estimated survival time, controlling for age and education. Additional models adjusted for Barthel Index and PRNP codon 129 polymorphism. RESULTS: sCJD participants performed significantly worse than controls on all cognitive tasks and composites with most showing very large effect sizes. The three tests showing the largest group differences were delayed verbal recall (Hedges'g = 4.08, P < 0.0001), Stroop Inhibition (Hedges'g = 3.14, P < 0.0001), and Modified Trails (Hedges'g = 2.94, P < 0.0001). Memory (95%) and executive functioning (87%) composites were most commonly impaired. Poorer global (HR = 0.65, P < 0.0001), visuospatial (HR = 0.82, P < 0.0001), and memory (HR = 0.82, P = 0.01) composites predicted shorter survival. Visuospatial cognition remained a significant predictor even after adjusting for all other cognitive composites; each standard deviation decrease in visuospatial cognition was associated with an 18% higher chance of death (HR = 0.82, P < 0.003). Global (HR = 0.68, P = 0.03) and visuospatial (HR = 0.82, P = 0.001) composites remained significant predictors after controlling for Barthel Index and codon 129. INTERPRETATION: sCJD participants exhibit a broad range of cognitive impairments, with memory and executive functioning deficits in the vast majority. Neuropsychological assessment, particularly of visuospatial abilities, informs prognostication in sCJD.