Self-Coding of Fidelity as a Potential Active Ingredient of Consultation to Improve Clinicians’ Fidelity

A key goal for implementation science is the identification of evidence-based consultation protocols and the active ingredients within these protocols that drive clinician behavior change. The current study examined clinicians’ self-coding of fidelity as a potential active ingredient of consultation for the Attachment and Biobehavioral Catch-up (ABC) intervention. It also examined two other potential predictors of clinician fidelity in response to consultation: dosage of consultation and working alliance. Twenty-nine clinicians (97% female, 62% White, M age?=?34 years) participated in a year of weekly fidelity-focused ABC consultation sessions, for which clinicians self-coded fidelity and received consultant feedback on both their coding and their fidelity. Data from the ABC fidelity measure were available for 1067 sessions coded by consultants, and clinicians’ self-coding accuracy was calculated from 1044 sessions coded by both clinicians and consultants. Alliance was measured with the Working Alliance Inventory—Trainee and Supervisor Versions. The study was observational, and fidelity and self-coding accuracy were modeled across time using hierarchical linear modeling. Clinicians’ ABC fidelity, as well as their self-coding accuracy, increased over the course of consultation. Clinicians’ self-coding accuracy predicted their initial fidelity and growth in fidelity. Working alliance was also linked to fidelity and self-coding accuracy. These results suggest that clinician self-coding should be further examined as an active ingredient of consultation. The study has important implications for the design of consultation procedures and fidelity assessments.

     

Patients Requiring Conversion to General Anesthesia during Endovascular Therapy Have Worse Outcomes: A Post Hoc Analysis of Data from the SAGA Collaboration

BACKGROUND AND PURPOSE:Endovascular therapy for acute ischemic stroke is often performed with the patient under conscious sedation. Emergent conversion from conscious sedation to general anesthesia is sometimes necessary. The aim of this study was to assess the functional outcome in converted patients compared with patients who remained in conscious sedation and to identify predictors associated with the risk of conversion.MATERIALS AND METHODS:Data from 368 patients, included in 3 trials randomizing between conscious sedation and general anesthesia before endovascular therapy (SIESTA, ANSTROKE, and GOLIATH) constituted the study cohort. Twenty-one (11%) of 185 patients randomized to conscious sedation were emergently converted to general anesthesia.RESULTS:Absence of hyperlipidemia seemed to be the strongest predictor of conversion to general anesthesia, albeit a weak predictor (area under curve = 0.62). Sex, hypertension, diabetes, smoking status, atrial fibrillation, blood pressure, size of the infarct, and level and side of the occlusion were not significantly associated with conversion to general anesthesia. Neither age (mean age, 71.3   ± 13.8 years for conscious sedation versus 71.6  ± 12.3 years for converters, P = .58) nor severity of stroke (mean NIHSS score, 17 ± 4 versus 18 ± 4, respectively, P = .27) were significantly different between converters and those who tolerated conscious sedation. The converters had significantly worse outcome with a common odds ratio of 2.67 (P = .015) for a shift toward a higher mRS score compared with the patients remaining in the conscious sedation group.CONCLUSIONS:Patients undergoing conversion had significantly worse outcome compared with patients remaining in conscious sedation. No factor was identified that predicted conversion from conscious sedation to general anesthesia.

Five studies published in 2015 proved the efficacy of endovascular therapy (EVT) for acute ischemic stroke caused by a large-vessel occlusion.¹ However, numerous questions remain regarding how to best deliver this treatment, including evaluation of the optimal thrombectomy technique,² the most effective method of patient triage,³ or whether EVT should be performed with the patient under either general anesthesia (GA) or conscious sedation (CS).Observational studies have suggested that EVT with the patient under CS is associated with better neurologic outcome and lower mortality compared with GA.⁴ However, 3 randomized trials reported similar outcomes between CS and GA.^5-7 Proposed benefits of CS include stable hemodynamics, clinical monitoring, and a potentially shorter procedure. The disadvantages are an unprotected airway and patient movement, which sometimes may require emergent conversion to GA. Patients who need conversion might be sicker (larger strokes, more medical complications), but the conversion procedure itself may also have a potentially deleterious influence on outcome due to the emergent anesthetic induction, associated hypotension, and added time delay before reperfusion.Although most patients can be treated under the less complex CS, it is of interest to identify factors that can predict the risk of conversion and hence the requirement for GA. We undertook a detailed analysis of the patients who were converted from CS to GA in our individual patient data base from the 3 randomized trials to examine the outcome of the converted patients compared with patients who remained in CS. We also aimed to identify possible predictors associated with a need for GA with EVT.     

Pit and fissure sealant: review of the literature

For this literature review of pit and fissure sealant, 1,465 references were selected by a search for "sealants" on PubMed. References were limited to dental journals and papers in the English language. The search comprised papers from 1971 to October 2001. Additional papers of historical significance prior to 1971 were added from memory and from reference lists published in early papers. This paper reviewed the literature on pit and fissure sealants under the following subheadings: (1) laboratory studies, (2) clinical technique and tooth preparation, (3) etching time, (4) auxiliary application of pit and fissure sealant, (5) retention and caries prevention, (6) fluoride used with sealants and fluoride-containing sealant, (7) glass ionomer materials as sealants, (8) options in sealant: filled vs unfilled; colored vs clear; autocure vs light-initiated, (9) sealant placed over caries in a therapeutic manner, (10) cost effectiveness of sealant application, (11) underuse of pit and fissure sealant, (12) the estrogenicity issue, (13) use of an intermediate bonding layer to improve retention, (14) new developments and projections, and (15) summary and conclusions. From a careful and thorough review of peer-reviewed publications on pit and fissure sealant, it is clear that sealants are safe, effective and underused (at least underused in the United States). Pit and fissure sealant is best applied to high-risk populations by trained auxiliaries using sealant that incorporates the benefit of an intermediate bonding layer, applied under the rubber dam or with some alternative short-term, but effective, isolation technique, onto an enamel surface that has been cleaned with an air polishing technique and etched with 35% phosphoric acid for 15 seconds. The dental profession awaits with enthusiasm, and some impatience, the incorporation of dentin-bonding technology into the development of a modern, more durable, resin-based sealant.     

The effects of resin-bonded and conventional fixed partial dentures on the periodontium: restoration type evaluated

The purpose of this study was to compare the long-term and short-term periodontal response to three different modalities of fixed prosthodontic tooth replacement. Posterior proximal sites adjacent to abutment teeth supporting etched metal and two designs of conventional fixed partial dentures (FPDs) were assessed 6 months to 5 years after insertion. For the long-term observation, the etched metal resin-bonded FPDs had significantly greater plaque scores than both of the conventional designs. The resin-bonded FPD group had statistically, but not clinically, significant increased probing depths than the supragingival FPD group. In spite of the increased levels of supragingival plaque associated with the etched metal FPD, this type of fixed prosthesis was no more injurious to the periodontium than the subgingival conventional FPD designs.     

In Vivo Feedback Predicts Parent Behavior Change in the Attachment and Biobehavioral Catch-up Intervention

Understanding mechanisms and active ingredients of intervention is critical to training clinicians, particularly when interventions are transported from laboratories to communities. One promising active ingredient of parenting programs is clinicians’ in vivo feedback regarding parent–child interactions. The present study examined whether a form of in vivo feedback, in the moment commenting, predicted treatment retention and parent behavior change when the Attachment and Biobehavioral Catch-up (ABC) intervention was implemented in a community setting. Observational data were collected from 78 parent–child dyads (96% mothers; M age = 29 years; 81% minority; infants’ M age = 12 months; 90% minority) across 640 sessions conducted by 9 clinicians (100% female, M age = 39; 67% minority) in Hawaii. Parental behavior was assessed with a semistructured play task before and after intervention. Clinicians’ in-the-moment feedback to parents was assessed from intervention session videos. Clinicians’ frequency and quality of in-the-moment feedback predicted change in parental intrusiveness and sensitivity at posttreatment. Frequency of in-the-moment feedback also predicted likelihood of retention. Hierarchical linear modeling demonstrated strong support for these associations at the between-clinician level, and limited additional support at the within-clinician (i.e., between-case) level. Thus, a hypothesized active ingredient of treatment, in-the-moment feedback, predicted community-based ABC outcomes. The results complement lab-based evidence to suggest that in vivo feedback may be a mechanism of change in parenting interventions. Helping clinicians to provide frequent, high-quality in vivo feedback may improve parenting program outcomes in community settings.     

Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain

We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1–688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ⁹-tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist {"type":"entrez-nucleotide","attrs":{"text":"HC030031","term_id":"262060681","term_text":"HC030031"}}HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1–688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca²⁺, or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).A number of vertebrate and invertebrate transient receptor potential (TRP) ion channels have been implicated in temperature sensation (1–3), but only the rat menthol receptor TRP subtype M8 (TRPM8) and the rat capsaicin receptor TRP subtype V1 (TRPV1) have been shown to possess intrinsic thermosensitivity (4, 5). In 2003, Story et al. (6) proposed that the mouse TRPA1 is a noxious cold sensor. Story et al. (6) showed that TRPA1 was present in nociceptive primary sensory neurons and that CHO cells heterologously expressing the mouse TRPA1 displayed cold sensitivity. Most subsequent studies of cold responses in heterologous TRPA1 expression systems, isolated primary sensory neurons, and whole animals have provided evidence in support of mouse and rat TRPA1 being involved in noxious cold transduction (7). Interestingly, a familial episodic pain syndrome triggered by cold is caused by a gain-of-function mutation in the TRPA1 gene, indicating that TRPA1 may have a key role in human noxious cold sensation (8). Thus, human TRPA1 (hTRPA1) may be a relevant drug target for treatment of this condition and other pathological conditions, such as inflammation, nerve injury, and chemotherapy-induced neuropathy, that are characterized by TRPA1-dependent cold allodynia or hypersensitivity (7). However, in vitro studies of the expressed hTRPA1 have generated conflicting findings (8–15), and no study has provided evidence that mammalian TRPA1 channels are, indeed. intrinsically cold-sensitive proteins, which would require examination of the purified protein in a defined membrane environment.Heterologous expression studies of chimeric or mutated TRPA1 channels have proposed that the N-terminal region plays an important role in thermal and chemical sensitivity of both mammalian and insect TRPA1 (14, 16–19). Initial studies indicated that mammalian TRPA1 is activated by cysteine-reactive electrophilic compounds and oxidants, such as diallyl disulfide in garlic (9, 10, 20, 21). Targeted gene mutations have identified cysteines present in the N terminus of TRPA1 as important for electrophilic and oxidative TRPA1 channel activation (22, 23). Because several of these cysteines are involved in protein disulfide formation (24–26), it is not unlikely that such mutations will have pronounced effects on the overall TRPA1 channel structure and function (7). Electrophilic compounds can also covalently bind to cysteines in the transmembrane segments and the C-terminal domain of mammalian TRPA1 (23, 26), and the electrophiles p-benzoquinone, isovelleral, and polygodial robustly activate the heterologously expressed triple mutant hTRPA1-3C (27, 28) that was initially used to identify certain N-terminal cysteine residues in hTRPA1 as key targets for electrophiles (22). However, it is yet to be shown that covalent binding sites outside the N-terminal ankyrin repeat domain (ARD) contribute to the regulation of channel gating.Another key feature of mammalian TRPA1 is the responsiveness to nonelectrophilic compounds with very different chemical structures, such as menthol and the cannabinoids Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and Δ⁹-tetrahydrocannabiorcol (C16) (7). However, if nonelectrophilic compounds activate TRPA1 directly and at the same site on TRPA1 is not known. The site of action of nonelectrophilic TRPA1 activators is important to clarify, because some TRPA1 activators are antinoiceptive (29, 30), and nontissue-damaging TRPA1 activators may be used clinically for pharmacological regulation of TRPA1 channel activity (29).Here, we have purified and inserted hTRPA1 with and without its N-terminal ARD (Δ1–688 hTRPA1) into lipid bilayers for functional studies using patch-clamp electrophysiology to explore the inherent thermo- and chemosensitivity of hTRPA1. Because of the great potential of TRPA1 as a drug target for treatment of human pain and the existence of mammalian TRPA1 species differences (7), the human variant of TRPA1 was chosen for these studies. We addressed the role of the N-terminal ARD in cold and chemical sensitivity by deleting the N-terminal ARD, something that cannot be studied in cells heterologously expressing TRPA1, because the N-terminal ARD is needed for insertion of the ion channel into the plasma membrane (31). Our findings consolidate hTRPA1 as a multimodal nocisensor responding to cold and chemicals. It is suggested that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophilic compounds are important in hTRPA1 channel gating. Targeting chemical interaction sites outside the N-terminal ARD may provide possibilities to fine tune TRPA1-based drug therapies [e.g., for treatment of pain associated with cold hypersensitivity (7) and cardiovascular disease (32)].     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.