Advances in Interventional Therapies for Painful Diabetic Neuropathy: A Systematic Review.

BACKGROUND: Painful diabetic neuropathy (PDN) is one of the major complications of diabetes mellitus. It is often debilitating and refractory to pharmaceutical therapies. Our goal was to systematically review and evaluate the strength of evidence of interventional management options for PDN and make evidence-based recommendations for clinical practice. METHODS: We searched PubMed, Scopus, Google Scholar, and Cochrane Llibrary and systematically reviewed all types of clinical studies on interventional management modalities for PDN. RESULTS: We identified and analyzed 10 relevant randomized clinical trials (RCTs), 8 systematic reviews/meta-analyses, and 5 observational studies of interventional modalities for PDN using pain as primary outcome. We assessed the risk of bias in grading of evidence and found that there is moderate to strong evidence to support the use of dorsal column spinal cord stimulation (SCS) in treating PDN in the lower extremities (evidence level: 1B+), while studies investigating its efficacy in the upper extremities are lacking. Evidence exists that acupuncture and injection of botulinum toxin-A provide relief in pain or muscle cramps due to PDN with minimal side effects (2B+/1B+). Similar level of evidence supports surgical decompression of lower limb peripheral nerves in patients with intractable PDN and superimposed nerve compression (2B±/1B+). Evidence for sympathetic blocks or neurolysis and dorsal root ganglion (DRG) stimulation is limited to case series (2C+). CONCLUSIONS: Moderate to strong evidence exists to support the use of SCS in managing lower extremity pain in patients who have failed conventional medical management for PDN. Acupuncture or injection of botulinum toxin-A can be considered as an adjunctive therapy for PDN. Surgical decompression of peripheral nerves may be considered in patients with PDN superimposed with nerve compression. High-quality studies are warranted to further evaluate the safety, efficacy, and cost-effectiveness of interventional therapies for PDN.

Pain Management Stewardship Programs, Part I: A Review of Legislative and Regulatory Changes.

Background: Opioid use is classified as an epidemic by many due to the impact of these medications on society. Federal and state laws for prescribing and dispensing opioids have changed rapidly in a short period of time to hopefully balance proper pain control with their use. Pharmacy directors must be informed of these rapid changes to effectively work as part of any opioid stewardship team. Objective: The objective of this study was to provide foundational leadership guidance to pharmacy directors on current opioid legislation, literature, and best practices to assist in improving opioid use. Methods: A review of the literature from 2003 to the present was conducted along with collating important up to date resources and other publications that provide foundational information to help support a comprehensive management of opioid use. A summary of these data has been collated into an easy to use table and summarized throughout this article. Conclusion: The information provided in this article helps to properly inform pharmacy leaders to the resources available to improve the prescribing, dispensing, and monitoring of opioids and alternatives.

A Systematic Review of Growth Hormone in Pain Medicine: From Rodents to Humans.

OBJECTIVE: Growth hormone (GH) and GH-related signaling molecules play an important role in nociception and development of chronic pain. This review aims to examine the potential molecular mechanisms through which GH-related signaling modulates sensory hypersensitivity in rodents, the clinical pharmacology of GH, and the clinical evidence of GH treatment for several common pain syndromes. METHODS: A search was conducted using the PUBMED/MEDLINE database, Scopus, and the Cochrane library for all reports published in English on GH in pain management from inception through May 2018. A critical review was performed on the mechanisms of GH-related signaling and the pharmacology of GH. The levels of clinical evidence and implications for recommendations of all of the included studies were graded. RESULTS: The search yielded 379 articles, of which 201 articles were deemed irrelevant by reading the titles. There were 53 reports deemed relevant after reading abstracts. All of these 53 articles were retrieved for the analysis and discussion. CONCLUSIONS: Dysfunction of the GH/insulin-like growth factor 1 (IGF-1)/ghrelin axis was linked to hyperalgesia and several common clinical pain syndromes. Low levels of GH and IGF-1 were linked to pain hypersensitivity, whereas ghrelin appeared to provide analgesic effects. Pretreatment of GH reversed mechanical and thermal hypersensitivity in an animal model of inflammatory pain. Clinical trials support GH treatment in a subgroup of patients with fibromyalgia syndrome (level of evidence: 1B+) or chronic lower back pain syndrome (level of evidence: 2C+).

Supra-Segmental Changes in Speech Production as a Result of Spectral Feedback Degradation: Comparison with Lombard Speech.

Perturbations to acoustic speech feedback have been typically localized to specific phonetic characteristics, for example, fundamental frequency (F0) or the first two formants (F1/F2), or affect all aspects of the speech signal equally, for example, via the addition of background noise. This paper examines the consequences of a more selective global perturbation: real-time cochlear implant (CI) simulation of acoustic speech feedback. Specifically, we examine the potential similarity between speakers' response to noise vocoding and the characteristics of Lombard speech. An acoustic analysis of supra-segmental characteristics in speaking rate, F0 production, and voice amplitude revealed changes that paralleled the Lombard effect in some domains but not others. Two studies of speech intelligibility complemented the acoustic analysis, finding that intelligibility significantly decreased as a result of CI simulation of speaker feedback. Together, the results point to differences in speakers' responses to these two superficially similar feedback manipulations. In both cases we see a complex, multi-faceted behavior on the part of talkers. We argue that more instances of global perturbation and broader response assessment are needed to determine whether such complexity is present in other feedback manipulations or if it represents a relatively rare exception to the typical compensatory feedback response.

Lack of interaction between enzalutamide and warfarin in a metastatic castration-resistant prostate cancer patient.

Enzalutamide is an androgen receptor antagonist used for the treatment of metastatic castration-resistant prostate cancer. Enzalutamide is classified as a strong cytochrome P450 3A4 inducer, a moderate 2C9 and 2C19 inducer, and a time-dependent inducer of 1A2. Warfarin's more potent enantiomer is primarily metabolized by cytochrome P450 2C9 and has a narrow therapeutic window. Enzalutamide is thought to decrease therapeutic warfarin concentrations per pharmacokinetic studies performed during drug development. This case report describes a 59-year-old man undergoing treatment with enzalutamide for metastatic castration-resistant prostate cancer with a history of femoral vein thrombosis. The patient was receiving a total weekly warfarin dose of 37.5 mg prior to starting enzalutamide. Enzalutamide was initiated and warfarin continued at a constant dose without decrease in the patient's INR. The patient continued on enzalutamide and warfarin for 1 year without having any documented subtherapeutic INRs. This report illustrates one case in which the interaction between warfarin and enzalutamide was not clinically significant.

Speaker responses to indirect evidence of acoustic signal transmission conditions.

Evidence has been accumulating that speakers adjust their speech production to account for conditions of signal transmission to an interlocutor, in addition to speaker- and listener-related influences. This study manipulated acoustic transmission conditions between speakers and a researcher while they completed dyadic cooperative puzzle tasks. Speakers heard evidence of four transmission perturbations (intensity increase/decrease, pitch increase/decrease) only indirectly, i.e., via changes in the researcher's voice. Analysis of speakers' conversational turns across conditions (baseline + four partner-voice manipulations) showed significant group-level imitation of transmission manipulations of partner voice intensity, with no general response to shifts in partner voice pitch. Significant voice alterations were also observed for individual speakers in intensity, with substantial inter-talker variability in responses. Thirteen of 29 speakers exclusively imitated the manipulation of partner intensity, 4/29 speakers exclusively opposed the transmission manipulation, and 4/29 speakers showed both response types. The presence of opposition responses coupled with a relatively low-magnitude group-level convergence suggests the possibility of a compensatory force at work in at least some speakers, adjusting for changes made during signal transmission despite their lack of direct experience with the transmission manipulation effects.

Effects of real-time cochlear implant simulation on speech production.

Investigations using normal-hearing subjects listening to simulations of cochlear implant (CI) acoustic processing have provided substantial information about the impact of these distorted listening conditions on the accuracy of auditory perception, but extensions of this method to the domain of speech production have been limited. In the present study, a portable, real-time vocoder was used to simulate conditions of CI auditory feedback during speech production in NH subjects. Acoustic-phonetic characteristics of sibilant fricatives, aspirated stops, and F1/F2 vowel qualities were analyzed for changes as a result of CI simulation of acoustic speech feedback. Significant changes specific to F1 were observed; speakers reduced their phonological vowel height contrast, typically via talker-specific raising of the low vowels [æ] and [ɑ] or lowering of high vowels [i] and [u]. Comparisons to the results of both localized feedback perturbation procedures and investigations of speech production in deaf adults with CIs are discussed.

Pet ownership and mental health in United States adults during COVID-19.

The COVID-19 pandemic was associated with declines in mental health and increased interest in pet ownership. We aimed to extend past theories and research linking pet ownership and mental health by investigating whether pet ownership was associated with mental health during the initial phases of the COVID-19 pandemic in a sample of American adults. We also tested whether the association of pet ownership and mental health was moderated by relationship status. Participants were 2,906 American adults who were recruited for an online survey study between May 2020 and May 2021. Pet ownership was assessed via dichotomous self-report (yes/no) and mental health was assessed using a 13-item questionnaire. The sample was 69.2% female with an average age of 46.0 years. 36.1% of the sample owned a pet and 68.5% of the sample was currently partnered. There was no overall association of pet ownership and mental health during the COVID-19 pandemic (estimated mean difference (EMD) = 0.35, 95CI = -0.10, 0.80, p = 0.12). However, we found evidence for an association that was moderated by relationship status. Pet ownership was associated with better mental health among partnered individuals (EMD = 0.76, 95CI = 0.21, 1.30, p = 0.006). There was no association of pet ownership and mental health among unpartnered individuals (EMD = -0.41, 95CI = -1.20, 0.37, p = 0.30). Our findings suggest that relationship status may represent a critical moderator of the link between pet ownership and mental health. Future studies are needed to identify specific mechanisms of pet ownership that could explain its varied impact on the mental health of partnered and unpartnered individuals.

Speaker compensation for local perturbation of fricative acoustic feedback.

Feedback perturbation studies of speech acoustics have revealed a great deal about how speakers monitor and control their productions of segmental (e.g., formant frequencies) and non-segmental (e.g., pitch) linguistic elements. The majority of previous work, however, overlooks the role of acoustic feedback in consonant production and makes use of acoustic manipulations that effect either entire utterances or the entire acoustic signal, rather than more temporally and phonetically restricted alterations. This study, therefore, seeks to expand the feedback perturbation literature by examining perturbation of consonant acoustics that is applied in a time-restricted and phonetically specific manner. The spectral center of the alveopalatal fricative [∫] produced in vowel-fricative-vowel nonwords was incrementally raised until it reached the potential for [s]-like frequencies, but the characteristics of high-frequency energy outside the target fricative remained unaltered. An "offline," more widely accessible signal processing method was developed to perform this manipulation. The local feedback perturbation resulted in changes to speakers' fricative production that were more variable, idiosyncratic, and restricted than the compensation seen in more global acoustic manipulations reported in the literature. Implications and interpretations of the results, as well as future directions for research based on the findings, are discussed.

Ketamine Safety and Use in the Emergency Department for Pain and Agitation/Delirium: A Health System Experience.

INTRODUCTION: Two protocols were developed to guide the use of subdissociative dose ketamine (SDDK) for analgesia and dissociative sedation ketamine for severe agitation/excited delirium in the emergency department (ED). We sought to evaluate the safety of these protocols implemented in 18 EDs within a large health system. METHODS: We conducted a retrospective chart review to evaluate all adult patients who received intravenous (IV) SDDK for analgesia and intramuscular (IM) dissociative sedation ketamine for severe agitation/excited delirium in 12 hospital-based and six freestanding EDs over a one-year period from the protocol implementation. We developed a standardized data collection form and used it to record patient information regarding ketamine use, concomitant medication use, and any comorbidities that could have impacted the incidence of adverse events. RESULTS: Approximately 570,000 ED visits occurred during the study period. SDDK was used in 210 ED encounters, while dissociative sedation ketamine for severe agitation/excited delirium was used in 37 ED encounters. SDDK was used in 83% (15/18) of sites while dissociative sedation ketamine was used in 50% (9/18) of sites. Endotracheal intubation, non-rebreather mask, and nasal cannula ≥ four liters per minute were identified in one, five, and three patients, respectively. Neuropsychiatric adverse events were identified in 4% (9/210) of patients who received SDDK. CONCLUSION: Patients experienced limited neuropsychiatric adverse events from SDDK. Additionally, dissociative sedation ketamine for severe agitation/excited delirium led to less endotracheal intubation than reported in the prehospital literature. The favorable safety profile of ketamine use in the ED may prompt further increases in usage.

The Viability of Media Interviews as Materials for Auditory Training.

Purpose Rehabilitative auditory training for people with hearing loss faces 2 primary challenges: generalization of learning to novel contexts and user adherence to training goals. We hypothesized that using interview excerpts from popular media as training materials would have the potential to positively influence both of these areas. Interviews contain predictable, structured complexity that promotes perceptual generalization and are also designed to be engaging for consumers. This study tested the viability of such popular media interviews as training materials, comparing their effectiveness to that obtained with sentence transcription training. Method Young adults with normal hearing ( N = 60) completed 1 hr of transcription training using noise-vocoded materials, simulating acoustic perception through an 8-channel cochlear implant. Participants completed pre- and posttraining assessments of vocoded speech perception in quiet and in noise, along with posttraining high-variability sentence recognition and cued isolated word recognition. Scores on all tests were compared across 4 randomly assigned groups differing in training materials: audiovisual interviews, audio-only interviews, isolated sentences, and undegraded isolated sentences (providing an untrained control comparison group). Results Recognition in quiet and in noise improved with both types of interview-based training, and interview training groups outperformed the control group on all generalization tests. Participants in the audiovisual interview group also reported significantly higher, more sustained engagement in a retrospective survey. Conclusions Media interviews appear to be at least as effective as isolated sentences for transcription-based auditory training in simulated hearing loss settings with young adults and may improve engagement and generalization of benefit in auditory training applications.

Auditory Training With Multiple Talkers and Passage-Based Semantic Cohesion.

Purpose: Current auditory training methods typically result in improvements to speech recognition abilities in quiet, but learner gains may not extend to other domains in speech (e.g., recognition in noise) or self-assessed benefit. This study examined the potential of training involving multiple talkers and training emphasizing discourse-level top-down processing to produce more generalized learning. Method: Normal-hearing participants (N = 64) were randomly assigned to 1 of 4 auditory training protocols using noise-vocoded speech simulating the processing of an 8-channel cochlear implant: sentence-based single-talker training, training with 24 different talkers, passage-based transcription training, and a control (transcribing unvocoded sentence materials). In all cases, participants completed 2 pretests under cochlear implant simulation, 1 hr of training, and 5 posttests to assess perceptual learning and cross-context generalization. Results: Performance above the control was seen in all 3 experimental groups for sentence recognition in quiet. In addition, the multitalker training method generalized to a context word-recognition task, and the passage training method caused gains in sentence recognition in noise. Conclusion: The gains of the multitalker and passage training groups over the control suggest that, with relatively small modifications, improvements to the generalized outcomes of auditory training protocols may be possible.

Auditory Learning Using a Portable Real-Time Vocoder: Preliminary Findings.

PURPOSE: Although traditional study of auditory training has been in controlled laboratory settings, interest has been increasing in more interactive options. The authors examine whether such interactive training can result in short-term perceptual learning, and the range of perceptual skills it impacts. METHOD: Experiments 1 (N = 37) and 2 (N = 21) used pre- and posttest measures of speech and nonspeech recognition to find evidence of learning (within subject) and to compare the effects of 3 kinds of training (between subject) on the perceptual abilities of adults with normal hearing listening to simulations of cochlear implant processing. Subjects were given interactive, standard lab-based, or control training experience for 1 hr between the pre- and posttest tasks (unique sets across Experiments 1 & 2). RESULTS: Subjects receiving interactive training showed significant learning on sentence recognition in quiet task (Experiment 1), outperforming controls but not lab-trained subjects following training. Training groups did not differ significantly on any other task, even those directly involved in the interactive training experience. CONCLUSIONS: Interactive training has the potential to produce learning in 1 domain (sentence recognition in quiet), but the particulars of the present training method (short duration, high complexity) may have limited benefits to this single criterion task.

Nonword repetition as a predictor of long-term speech and language skills in children with cochlear implants.

HYPOTHESIS: The rapid phonological processing skills of children with cochlear implants early in life (ages 8-10), as measured by nonword repetition performance, will predict their language development 8 years later (ages 16-18). This core processing ability will also correlate with concurrent measures of language at both ages of testing. BACKGROUND: Understanding the causes of the wide range of performance in pediatric cochlear implant users currently constitutes a major barrier to clinical and research progress in the field. Research into children's neurocognitive abilities such as working memory capacity and verbal rehearsal speed, in addition to conventional demographic variables, has shown that these foundational skills play a key role in determining outcomes. Here, we investigate the impact of rapid phonological processing, an ability which is critical in spoken language use, for children with cochlear implants. METHODS: Fifty-two deaf children with cochlear implants completed a battery of 14 clinical and research measures of language, neurocognitive, and nonword repetition skills in 2 testing sessions 8 years apart. RESULTS: Performance on the nonword repetition task at both testing sessions correlated significantly with concurrent language abilities. Importantly, nonword repetition accuracy at age 8 to 10 also significantly predicted performance on measures of language ability at age 16 to 18 in a wide range of domains, from speech intelligibility to sentence recognition in noise. These relations were significant even when other neurocognitive measures were controlled. CONCLUSION: Early nonword repetition performance in children with cochlear implants predicts later language development and, therefore, may identify those children at high risk for poor outcomes.

Active prospective control is required for effective sensorimotor learning.

Passive modeling of movements is often used in movement therapy to overcome disabilities caused by stroke or other disorders (e.g. Developmental Coordination Disorder or Cerebral Palsy). Either a therapist or, recently, a specially designed robot moves or guides the limb passively through the movement to be trained. In contrast, action theory has long suggested that effective skill acquisition requires movements to be actively generated. Is this true? In view of the former, we explicitly tested the latter. Previously, a method was developed that allows children with Developmental Coordination Disorder to produce effective movements actively, so as to improve manual performance to match that of typically developing children. In the current study, we tested practice using such active movements as compared to practice using passive movement. The passive movement employed, namely haptic tracking, provided a strong test of the comparison, one that showed that the mere inaction of the muscles is not the problem. Instead, lack of prospective control was. The result was no effective learning with passive movement while active practice with prospective control yielded significant improvements in performance.

Speech perception and production.

Until recently, research in speech perception and speech production has largely focused on the search for psychological and phonetic evidence of discrete, abstract, context-free symbolic units corresponding to phonological segments or phonemes. Despite this common conceptual goal and intimately related objects of study, however, research in these two domains of speech communication has progressed more or less independently for more than 60 years. In this article, we present an overview of the foundational works and current trends in the two fields, specifically discussing the progress made in both lines of inquiry as well as the basic fundamental issues that neither has been able to resolve satisfactorily so far. We then discuss theoretical models and recent experimental evidence that point to the deep, pervasive connections between speech perception and production. We conclude that although research focusing on each domain individually has been vital in increasing our basic understanding of spoken language processing, the human capacity for speech communication is so complex that gaining a full understanding will not be possible until speech perception and production are conceptually reunited in a joint approach to problems shared by both modes. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.