Efficacy of Sound Therapy for Tinnitus Using an Enriched Acoustic Environment with Hearing-Loss Matched Broadband Noise

Background: Tinnitus is a rather heterogeneous chronic condition/disorder which is difficult to treat. Some tinnitus treatments combine sound therapy with counselling. The main goal of this study is to report the efficacy of a customized sound therapy combined with counselling on a cohort of 83 tinnitus patients. Methods: 119 tinnitus subjects, recruited between January 2018 and June 2021, were subjected to a treatment consisting of a combination of an initial counselling session and four-month sound therapy. The sound stimulus was a personalized broadband noise colored by the audiometry of the subjects. These stimuli were given to the patients in mp3 format to be heard 1 h per day over 4 months. The tinnitus severity of the patients was evaluated monthly through the validated Spanish version of the Tinnitus Handicap Inventory. Results: Of the patients, 30% (36 of 119) withdrew from the treatment before finishing, and 96% (80 of 83) of the subjects completing the therapy attained some relief after 4 months. The overall average THI decrease of these 80 participants was 23. However, when the THI was analyzed by severity scales, it was found that patients with initial mild, moderate, severe and catastrophic handicap had an average THI decrease of 14, 20, 31 and 42 points, respectively. Thus, the average THI decrease depended on the baseline severity scale of patients. Conclusions: Consequently, the proposed treatment was demonstrated to be effective in providing clinically relevant relief in tinnitus distress patients in just 4 months.

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time.Methods: The STAR Network “Depot Study” was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41).Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions—conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently—showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline.Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders.

127 SARS-CoV-2 pandemic: post-lockdown subclinic cardiovascular events detected by 12-leads electrocardiogram at Emergency Department

Aims Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-directed medical therapy (GDMT) in heart failure (HF). We evaluated the evolution and impact of MR after GDMT in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Methods and results A retrospective post hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate–severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate–severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate–severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint [unadjusted hazard ratio (HR), 2.03; 95% confidence interval (CI), 1.57–2.63; P < 0.001], also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI, 1.43–2.39; P < 0.001). Younger age, LVEF ≥50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of moderate–severe MR at 9 months, whereas older age was the only predictor of worsening MR. Conclusions Among patients with HF undergoing GDMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate–severe MR after GRMT was associated with worse outcome.

P.038 Impact of Disease Severity on Presentation Subtype and OnabotulinumtoxinA Utilization in Patients with Cervical Dystonia in the CD PROBE Completer Population

Background: The impact of cervical dystonia (CD) severity on presentation subtype and onabotulinumtoxinA utilization was examined in the completer population from CD PROBE (CD Patient Registry for Observation of BOTOX® Efficacy). Methods: In this multicenter, prospective, observational registry, patients with CD were treated with onabotulinumtoxinA according to injectors’ standard of care. Completers were patients that completed all 3 treatment sessions and had accompanying data. Results: Of N=1046 patients enrolled, n=350 were completers. Completers were on average 57.3 years old, 74.9% female, 94.6% white, and 60.6% toxin-naïve. Baseline severity was mild in 32.6%, moderate in 54.3%, and severe in 13.1%. Torticollis was the most common presentation at baseline (mild: 44.7%, moderate: 55.8%, severe: 63.0%), followed by laterocollis (mild: 42.1%, moderate: 32.6%, severe: 26.1%). Median onabotulinumtoxinA dose increased over time; 160U–200U for torticollis and 170U–200U for laterocollis. For all severities, median total dose increased from injection 1 to injection 3 (mild: 138U–165U, moderate: 183U–200U, severe: 200U–285U). Eighty-one patients (23.1%) reported 139 treatment-related adverse events. There were no treatment-related serious adverse eventsand no new safety signals. Conclusions: CD severity impacted presentation subtype frequency and onabotulinumtoxinA utilization in CD PROBE, with higher and tailored dosing observed over time and with increasing disease severity.

Metaraminol and Noradrenaline in Septic Shock: A Retrospective Comparison

IntroductionVasopressor use is an important facet of septic shock management, in order to maintain hemodynamic targets and end organ perfusion. Traditionally, Noradrenaline has been the ‘gold standard’ drug of choice for septic shock. Metaraminol is an alternative vasopressor that has been used for septic shock. However, there has been minimal research in comparing the two drugs in septic patients, particularly with regards to total time spent on infusion. ObjectivesTo compare total time spent on either Metaraminol or Noradrenaline infusion by septic shock patients, whilst adjusting for baseline severity of illness. Secondary outcomes included incidence of mechanical ventilation and new requirement of renal replacement therapy, and mortality. MethodsA retrospective medical records review was undertaken, looking at all septic shock patients admitted to ICU in 2019, who received either Metaraminol or Noradrenaline. Data extracted from eRIC (the ICU database) included total time spent on infusion, APACHE III scores, incidence of mechanical ventilation, incidence of renal replacement therapy, and mortality. ResultsOur review yielded 174 patients who were eligible for further statistical analysis (63 in Metaraminol group, and 111 in the Noradrenaline group). The mean duration of infusion in the Metaraminol group was 1655 minutes, and 2663 minutes in the Noradrenaline group. The mean APACHE III Scores were 62 in the Metaraminol group and 77 in the Noradrenaline group. A one-way ANCOVA test found that there was a statistically significant [F(1, 171)=4.511, p=0.035] reduction in time spent on Metaraminol infusion, compared with Noradrenaline, after adjusting for baseline severity of illness by way of APACHE III Score. ConclusionOur study found a statistically significant reduction in time spent on a Metaraminol infusion compared with Noradrenaline by septic shock patients, after controlling for severity of illness. However, due to its retrospective study design, we were unable to account for bias and confounders, such as antibiotic and fluid administration, or clinician preference for one drug over the other. Nevertheless, our study adds to the paucity of literature comparing Metaraminol to Noradrenaline, and paves the way for future randomized trials comparing the two drugs in septic shock.

Ultrasensitive and quantitative toxin measurement correlates with baseline severity, severe outcomes, and recurrence among hospitalized patients with Clostridioides difficile infection

Background Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C. difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence. Methods We enrolled 615 hospitalized adults (≥ 18y) with CDI (acute diarrhea, positive stool NAAT, and decision to treat). Baseline stool toxin A and B concentrations were measured by Single Molecule Array. Subjects were classified by baseline CDI severity (four scoring methods) and outcomes within 40 days (death, ICU stay, colectomy, and recurrence). Results Among 615 patients (median 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P<0.01). Nineteen subjects (3.1%) had a severe outcome primarily-attributed to CDI (group 1). This group had higher median toxin A+B [14,303 pg/mL (IQR 416.0, 141,967)] than subjects in whom CDI only contributed to the outcome [group 2, 163.2 pg/mL(0.0, 8423.3)], subjects with severe outcome unrelated to CDI [group 3, 158.6 pg/mL (0.0, 1795.2)], or no severe outcome [group 4, 209.5 pg/mL (0.0, 8566.3)](P=0.003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5-66.1%)(P=0.02). Individuals with recurrence had higher toxin A+B [2266.8 pg/mL(188.8, 29411)] than those without [154.0 pg/mL(0.0, 5864.3)](P<0.001) and higher rates of detectable toxin (85.7% versus 64.0%, P=0.004). Conclusions In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.

Identifying organ dysfunction trajectory-based subphenotypes in critically ill patients with COVID-19

COVID-19-associated respiratory failure offers the unprecedented opportunity to evaluate the differential host response to a uniform pathogenic insult. Understanding whether there are distinct subphenotypes of severe COVID-19 may offer insight into its pathophysiology. Sequential Organ Failure Assessment (SOFA) score is an objective and comprehensive measurement that measures dysfunction severity of six organ systems, i.e., cardiovascular, central nervous system, coagulation, liver, renal, and respiration. Our aim was to identify and characterize distinct subphenotypes of COVID-19 critical illness defined by the post-intubation trajectory of SOFA score. Intubated COVID-19 patients at two hospitals in New York city were leveraged as development and validation cohorts. Patients were grouped into mild, intermediate, and severe strata by their baseline post-intubation SOFA. Hierarchical agglomerative clustering was performed within each stratum to detect subphenotypes based on similarities amongst SOFA score trajectories evaluated by Dynamic Time Warping. Distinct worsening and recovering subphenotypes were identified within each stratum, which had distinct 7-day post-intubation SOFA progression trends. Patients in the worsening suphenotypes had a higher mortality than those in the recovering subphenotypes within each stratum (mild stratum, 29.7% vs. 10.3%, p = 0.033; intermediate stratum, 29.3% vs. 8.0%, p = 0.002; severe stratum, 53.7% vs. 22.2%, p < 0.001). Pathophysiologic biomarkers associated with progression were distinct at each stratum, including findings suggestive of inflammation in low baseline severity of illness versus hemophagocytic lymphohistiocytosis in higher baseline severity of illness. The findings suggest that there are clear worsening and recovering subphenotypes of COVID-19 respiratory failure after intubation, which are more predictive of outcomes than baseline severity of illness. Distinct progression biomarkers at differential baseline severity of illness suggests a heterogeneous pathobiology in the progression of COVID-19 respiratory failure.

Specific Features of the Coagulopathy Signature in Severe COVID-19 Pneumonia

Rationale: COVID-19 displays distinct characteristics that suggest a unique pathogenesis. The objective of this study was to compare biomarkers of coagulopathy and outcomes in COVID-19 and non-COVID-19 patients with severe pneumonia.Methods: Thirty-six non-COVID-19 and 27 COVID-19 non-immunocompromised patients with severe pneumonia were prospectively enrolled, most requiring intensive care. Clinical and biological characteristics (including plasma biomarkers of coagulopathy) were compared.Results: At similar baseline severity, COVID-19 patients required mechanical ventilation (MV) for significantly longer than non-COVID-19 patients (p = 0.0049) and more frequently developed venous thrombotic complications (p = 0.031). COVID-19 patients had significantly higher plasma concentrations of soluble VCAM1 (sVCAM1) (5,739 ± 3,293 vs. 3,700 ± 2,124 ng/ml; p = 0.009), but lower levels of D-dimers, vWF-A2, sICAM1, sTREM1, VEGF, and P-selectin, compared to non-COVID-19 patients. Principal component analysis identified two main patterns, with a clear distinction between non-COVID-19 and COVID-19 patients. Multivariable regression analysis confirmed that sVCAM1 rising levels were independently associated with a longer duration of MV. Finally, we identified close correlations between sVCAM1 and some features of COVID-19 immune dysregulation (ie. CXCL10, GM-CSF, and IL-10).Conclusion: We identified specific features of the coagulopathy signature in severe COVID-19 patients, with higher plasma sVCAM1 levels, that were independently associated with the longer duration of mechanical ventilation.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT03505281.