Direct Recordings from the Auditory Cortex in a Cochlear Implant User

Electrical stimulation of the auditory nerve with a cochlear implant (CI) is the method of choice for treatment of severe-to-profound hearing loss. Understanding how the human auditory cortex responds to CI stimulation is important for advances in stimulation paradigms and rehabilitation strategies. In this study, auditory cortical responses to CI stimulation were recorded intracranially in a neurosurgical patient to examine directly the functional organization of the auditory cortex and compare the findings with those obtained in normal-hearing subjects. The subject was a bilateral CI user with a 20-year history of deafness and refractory epilepsy. As part of the epilepsy treatment, a subdural grid electrode was implanted over the left temporal lobe. Pure tones, click trains, sinusoidal amplitude-modulated noise, and speech were presented via the auxiliary input of the right CI speech processor. Additional experiments were conducted with bilateral CI stimulation. Auditory event-related changes in cortical activity, characterized by the averaged evoked potential and event-related band power, were localized to posterolateral superior temporal gyrus. Responses were stable across recording sessions and were abolished under general anesthesia. Response latency decreased and magnitude increased with increasing stimulus level. More apical intracochlear stimulation yielded the largest responses. Cortical evoked potentials were phase-locked to the temporal modulations of periodic stimuli and speech utterances. Bilateral electrical stimulation resulted in minimal artifact contamination. This study demonstrates the feasibility of intracranial electrophysiological recordings of responses to CI stimulation in a human subject, shows that cortical response properties may be similar to those obtained in normal-hearing individuals, and provides a basis for future comparisons with extracranial recordings.     

Novel synthetic analogue of ACTH 4–10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia

This work investigates whether nitric oxide production and lipid peroxidation contribute to the pathophysiology of ischemia and whether glycine and a novel Russian compound, Semax are neuroprotective via a mechanism involving the regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and indices of lipid peroxidation were elevated following global ischemia. While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning.     

Nondestructive quantification of analyte diffusion in cornea and sclera using optical coherence tomography

PURPOSE: Noninvasive functional imaging, monitoring, and quantification of analytes transport in epithelial ocular tissues are extremely important for therapy and diagnostics of many eye diseases. In this study the authors investigated the capability of optical coherence tomography (OCT) for noninvasive monitoring and quantification of diffusion of different analytes in sclera and cornea of rabbit eyes. METHODS: A portable time-domain OCT system with wavelength of 1310 +/- 15 nm, output power of 3.5 mW, and resolution of 25 mum was used in this study. Diffusion of different analytes was monitored and quantified in rabbit cornea and sclera of whole eyeballs. Diffusion of water, metronidazole (0.5%), dexamethasone (0.2%), ciprofloxacin (0.3%), mannitol (20%), and glucose solution (20%) were examined, and their permeability coefficients were calculated by using OCT signal slope and depth-resolved amplitude methods. RESULTS: Permeability coefficients were calculated as a function of time and tissue depth. For instance, mannitol was found to have a permeability coefficient of (8.99 +/- 1.43) x 10(-6) cm/s in cornea and (6.18 +/- 1.08) x 10(-6) cm/s in sclera. The permeability coefficient of drugs with small concentrations (where water was the major solvent) was found to be in the range of that of water in the same tissue type, whereas permeability coefficients of higher concentrated solutions varied significantly. CONCLUSIONS: Results suggest that the OCT technique might be a powerful tool for noninvasive diffusion studies of different analytes in ocular tissues. However, additional methods of OCT signal acquisition and processing are required to study the diffusion of agents of small concentrations.     

Adaptation minimizes distance-related audiovisual delays

A controversial hypothesis within the domain of sensory research is that observers are able to use visual and auditory distance cues to maintain perceptual synchrony--despite the differential velocities of light and sound. Here we show that observers are categorically unable to utilize such distance cues. Nevertheless, given a period of adaptation to the naturally occurring audiovisual asynchrony associated with each viewing distance, a temporal recalibration mechanism helps to perceptually compensate for the effects of distance-induced auditory delays. These effects demonstrate a novel functionality of temporal recalibration with clear ecological benefits.     

Thermodynamics of norbornene,of its polymerization process and of polynorbornene from 0 to 400 K at standard pressure

Thermodynamic properties of norbornene

1 System: name: bicyclo[2.2.1]hept-2-ene.

and polynorbornene, viz. isobaric heat capacity of the monomer and polymer between 10 and 330–400 K, parameters of physical transitions of the monomer and polymer, and energy of combustion for the polymer were studied by means of precise adiabatic and isothermal calorimetry. From the experimental data, the thermodynamic functions H°(T)–H°(0), S°(T) and G°(T)–H°(0) in the range of 0 to 330–400 K as well as enthalpies of combustion and thermochemical quantities of formation ΔH, and ΔS for polynorbornene were calculated. The results were used to calculate enthalpies, entropies and Gibbs functions of bulk polymerization for norbornene between 0 and 330 K and to evaluate the ceiling temperature of polymerization.     

Patient-acceptable symptom state for the Oxford Hip Score and Forgotten Joint Score at 3 months, 1 year,and 2 years following total hip arthroplasty: a registry-based study of 597 cases

Background and purpose — Patient-acceptable symptom states (PASS) represent the level on a patient-reported outcome measure (PROM) at which patients are satisfied with postoperative outcomes. We defined the PASS for the Oxford Hip Score (OHS) and Forgotten Joint Score (FJS-12) at 3-month, 1-year, and 2-year intervals after primary total hip arthroplasty (THA).Patients and methods — Between July 2018 and April 2019, primary THA patients in an academic medical center’s registry completed the OHS, FJS-12, and a satisfaction anchor question at 3-month (n = 230), 1-year (n = 180), or 2-year (n = 187) postoperative intervals. PASS thresholds were derived with receiver operating characteristic analysis using the 80% specificity method. 95% confidence intervals (CI) were calculated using 1,000 non-parametric bootstrap replications.Results — 74%, 85%, and 86% of patients reported having a satisfactory symptom state at 3 months, 1, and 2 years after surgery, respectively. At 3-month, 1-year, and 2-year intervals, PASS thresholds were 34 (CI 31–36), 40 (CI 36–44), and 39 (CI 35–42) points for the OHS and 59 (CI 54–64), 68 (CI 61–75), and 69 (CI 62–75) points for the FJS-12.Interpretation — PASS thresholds varied with time for both the OHS and the FJS-12, with lower 3-month compared with 1-year and 2-year thresholds. These PASS thresholds represent OHS and FJS-12 levels at which the average patient is satisfied with THA outcomes, helping to interpret PROMs and serving as clinically significant benchmarks and patient-centered outcomes for research.

Patient-reported outcome measures (PROMs) are commonly used to evaluate preoperative and postoperative symptom states of patients undergoing procedures such as total hip arthroplasty (THA) (Rolfson et al. 2016). Although measures such as revision or infection rates may reliably identify significant outliers in arthroplasty outcomes, the absence of such negative outcomes is not sufficient to determine whether the outcome of a procedure was satisfactory from a patient’s point of view (American Academy of Orthopedic Surgeons 2018). Within arthroplasty, there is a focus on joint-specific PROMs, but even between these PROMs there remains variation in the ways in which joint-related health is measured.The Oxford Hip Score (OHS) and the Forgotten Joint Score (FJS-12) are 2 such PROMs. The OHS assesses hip pain and function, and has been widely used in hip arthroplasty since its development in 1996 (Dawson et al. 1998). The FJS-12, designed in 2012, is a joint-specific questionnaire that focuses on the patient’s awareness of the affected joint (Behrend et al. 2012). 3 studies comparing these 2 PROMs found a smaller ceiling effect (proportion of respondents achieving the maximum score) in the FJS-12 compared with the OHS, suggesting that the FJS-12 may be better at distinguishing between patients with good postoperative outcomes in comparison with the OHS within their respective constructs (Hamilton et al. 2016, 2017, Larsson et al. 2019).The patient acceptable symptom state (PASS) is the threshold on a PROM most closely associated with patient satisfaction, which is assessed on a separate questionnaire (Tubach et al. 2005, Sayers et al. 2017). PASS values allow for the interpretation of PROMs within the context of a given treatment, and they may fulfil a variety of roles: as clinically significant benchmarks for procedures, as clinically relevant, patient-centered outcomes for research, and as guides for physicians to contextualize a patient’s postoperative symptom state.Although 2 studies have presented PASS values for the OHS following THA, they have not been externally validated (Judge et al. 2012, Keurentjes et al. 2014). Furthermore, these studies did not investigate the time-dependence of the PASS. The PASS may change within the first year of surgery in accordance with changes in patient expectations during rehabilitation. 1 study established the OHS PASS 6 months after arthroplasty, while the other derived the PASS on a cohort of patients ranging between 1.5 and 6 years following THA. Another study applied a composite questionnaire-based satisfaction anchor criterion to establish an OHS value associated with patient satisfaction 1 year following THA of 37.5 points (Hamilton et al. 2018). To our knowledge, while no THA PASS values have been established for the FJS-12, a composite anchor questionnaire-based “successful treatment” anchor was used by 1 study to establish a threshold value of 74 and 70 points at 1- and 2-year intervals following THA, respectively (Rosinsky et al. 2019).We defined PASS values for the OHS and FJS-12 at 3 months, 1 year, and 2 years following primary THA.     

Which Oxford Knee Score level represents a satisfactory symptom state after undergoing a total knee replacement?

Background and purpose — Meaningful interpretation of postoperative Oxford Knee Score (OKS) levels is challenging. We established Patient Acceptable Symptoms State (PASS) and Treatment Failure (TF) values for the OKS in patients undergoing primary total knee replacement (TKR) in Denmark.Patients and methods — Data from patients undergoing primary TKR between February 2015 and January 2019 was extracted from the arthroplasty registry at the Copenhagen University Hospital, Hvidovre in Denmark. Data included 3, 12, and 24 months postoperative responses to the OKS and 2 anchor questions asking whether they considered their symptom state to be satisfactory, and if not, whether they considered the treatment to have failed. PASS and TF threshold values were calculated using the adjusted predictive modeling method. Non-parametric bootstrapping was used to derive 95% confidence intervals (CI).Results — Complete 3, 12, and 24 months postoperative data was obtained for 187 of 209 (89%), 884 of 915 (97%), and 575 of 586 (98%) patients, with median ages from 68 to 70 years (59 to 64% female). 72%, 77%, and 79% considered as having satisfactory symptoms, while 6%, 11%, and 11% considered the treatment to have failed, at 3, 12, and 24 months postoperatively, respectively. OKS PASS values (CI) were 27 (26–28), 30 (29–31), and 30 (29–31) at 3, 12, and 24 months postoperatively. TF values were 27 (26–28) and 27 (26–29) at 12 and 24 months postoperatively.Interpretation — The OKS PASS values can be used to guide the interpretation of TKR outcome and support quality assessment in institutional and national registries.

The patient perspective on outcome of total knee replacement (TKR) is captured with patient-reported outcome measures (PROMs) (Price et al. 2018). The Oxford Knee Score (OKS) measures the degree of knee pain and functional status of the knee on a scale ranging from 0 to 48 (worst to best score) (Dawson et al. 1998). Registry-based data suggest that 6-months postoperative OKS results are on average 36 points (NHS 2020). However, judging whether the outcome of surgery was successful or not can be challenging, because it is not clear which symptom level patients consider to be satisfactory. The Patient Acceptable Symptom State (PASS) concept was defined by Tubach et al. (2005) as the score on a PROM above which patients consider themselves well. The contrary concept, Treatment Failure (TF), was introduced for patients undergoing ACL reconstruction, to define patients who consider their symptom levels unsatisfactory to a degree that they find the treatment has failed (Ingelsrud et al. 2015).Suggested satisfaction thresholds for the OKS range from 30 to 38 points after knee replacement (Judge et al. 2012, Keurentjes et al. 2014, Petersen et al. 2017). The time-points evaluated in these studies were either 6 months or shorter/longer than 3 years postoperatively. A dichotomized visual analogue scale (VAS) or a numeric rating scale (NRS) was used as anchor question to measure patients’ satisfaction. However, having the patients’ explicit judgements of whether they have reached a satisfactory symptom state or not after surgery is necessary to derive credible PASS values. Moreover, interpretation characteristics of PROMs are context dependent (Tubach et al. 2007), which highlights the relevance of evaluateing the time-dependency of PASS values for the OKS after TKR. We therefore defined PASS and TF values for the OKS at 3 months, and 1 and 2 years after a TKR.     

Electrical Excitation of the Acoustically Sensitive Auditory Nerve: Single-Fiber Responses to Electric Pulse Trains

Nearly all studies on auditory-nerve responses to electric stimuli have been conducted using chemically deafened animals so as to more realistically model the implanted human ear that has typically been profoundly deaf. However, clinical criteria for implantation have recently been relaxed. Ears with “residual” acoustic sensitivity are now being implanted, calling for the systematic evaluation of auditory-nerve responses to electric stimuli as well as combined electric and acoustic stimuli in acoustically sensitive ears. This article presents a systematic investigation of single-fiber responses to electric stimuli in acoustically sensitive ears. Responses to 250 pulse/s electric pulse trains were collected from 18 cats. Properties such as threshold, dynamic range, and jitter were found to differ from those of deaf ears. Other types of fiber activity observed in acoustically sensitive ears (i.e., spontaneous activity and electrophonic responses) were found to alter the temporal coding of electric stimuli. The electrophonic response, which was shown to greatly change the information encoded by spike intervals, also exhibited fast adaptation relative to that observed in the “direct” response to electric stimuli. More complex responses, such as “buildup” (increased responsiveness to successive pulses) and “bursting” (alternating periods of responsiveness and unresponsiveness) were observed. Our findings suggest that bursting is a response unique to sustained electric stimulation in ears with functional hair cells.     

Self-assessment of treatment compliance with antimuscarinic drugs and lower urinary tract condition among women with urinary incontinence

Aim

Our aim was to determine the efficiency of the Medication Compliance Self-Report Inventory (MASRI) in self-reporting antimuscarinic drug treatment compliance among women with urinary incontinence (UI).

Materials and methods

The study assessed 347 women aged 18–65 (averaging 49.7) years with more than one urinary incontinence (UI) episode per day. Treatment compliance was tested at the beginning and at weeks 4, 8, and 12 using the MASRI, the Brief Medication Questionnaire (BMQ), and visual pill counts. The MASRI’s constructive, concurrent, and discriminate validity was studied in comparison with an external standard that uses the chi-square and Spearman coefficient. Receiver operating characteristic (ROC) analysis was performed to identify optimum MASRI cutoffs that would predict noncompliance. Furthermore, the functional condition of the lower urinary tract was tested using voiding diaries, uroflowmetry, and cystometry.

Result

The correlation between the percentage of noncompliant women according to the MASRI, and individuals with a belief barrier with respect to the BMQ screen was r = 0.81 (p ≤0.05), r = 0.84 (p ≤0.05), and r = 0.79 (p ≤0.05). The correlation between the percentage of noncompliant women according to the MASRI and of women who missed >20% of their doses according to the Regimen Screen of the BMQ was r = 0.79, p ≤0.05, r = 0.82, p ≤0.01, r = 0.77, and p ≤0.05 at the control points. Finally, the percentage of noncompliant patients who self-reported correctly according to the MASRI data compared with the BMQ was 95.6%, 95.7%, and 96.6% at the control points.

Conclusion

The MASRI entails acceptable validity for accurately predicting treatment compliance with antimuscarinic drugs among women who have had UI for >3 months.