Correction: Subjective and objective measures of cognitive function are correlated in persons with Post-COVID-19 Condition: a secondary analysis of a Randomized Controlled Trial.

Kwan ATH ，Lakhani M ，Le GH ，Singh G ，Teopiz KM ，Ceban F ，Nijjar CS ，Meshkat S ，Badulescu S ，Ho R ，Rhee TG ，Di Vincenzo JD ，Gill H ，McIntyre RS ... -  《-》

Subjective and objective measures of cognitive function are correlated in persons with Post-COVID-19 Condition: a secondary analysis of a Randomized Controlled Trial.

It remains unclear whether subjective and objective measures of cognitive function in Post COVID-19 Condition (PCC) are correlated. The extent of correlation has mechanistic and clinical implications. This post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial contains baseline data of subjective and objective measures of cognition in a rigorously characterized cohort living with PCC. Herein, we evaluated the association between subjective and objective condition function, as measured by the Perceived Deficits Questionnaire, 20-item (PDQ-20) and the Digit Symbol Substitution Test (DSST) and Trails Making Test (TMT)-A/B, respectively. A total of 152 participants comprised the baseline sample. Due to missing data, our statistical analyses included 150 for self-reported PDQ-20, 147 individuals for combined DSST-measured cognitive function (composite z-score of the Pen/Paper plus Online CogState Version, NcombinedDSST), 71 for in-person DSST-measured cognitive function (Pen/Paper Version), 70 for TMT-A-measured cognitive function, and 70 for TMT-B-measured cognitive function. After adjusting for age, sex, and education, PDQ-20 was significantly correlated with pen-and-paper DSST (β = -0.003, p = 0.002) and TMT-B (β = 0.003, p = 0.008) scores, but not with TMT-A scores (β = -0.001, p = 0.751). Overall, a statistically significant correlation was observed between subjective and objective cognitive functions. Clinicians providing care for individuals with PCC who have subjective cognitive function complaints may consider taking a measurement-based approach to cognition at the point of care that focuses exclusively on patient-reported measures.

Kwan ATH ，Lakhani M ，Le GH ，Singh G ，Teopiz KM ，Ceban F ，Nijjar CS ，Meshkat S ，Badulescu S ，Ho R ，Rhee TG ，Di Vincenzo JD ，Gill H ，McIntyre RS ... -  《-》

Quality of Voice in Patients With Partial Deafness Before and After Cochlear Implantation.

Partial deafness is a condition characterised by normal hearing thresholds in low frequencies and increased hearing thresholds (nearly deafness) for high frequencies. Typical hearing aids are rather of a very limited use in this condition as they do not improve understanding of speech. Patients with partial deafness can be presently treated with cochlear implants, which had not been used before due to the risk of damage of hearing remains by electrode introduced into cochlea. The purpose of our study was an objective and subjective assessment of voice quality in partial deafness patients before and after cochlear implantation. The subjects in this study were 25 post-lingual, bilaterally partially deaf patients, 13 females and 12 males. The reference group composed of 55 normal hearing individuals (28 females and 27 males). The acoustic analysis was performed with a multidimensional voice analysis MDVP (Multi Dimension Voice Program), and the subjective assessment was done with GRBAS scale. Initial analysis of voice changes in partial deafness patients was performed versus normal hearing individuals, then voice parameters were measured and perceptual voice assessment was done before and 9 months after cochlear implantation. Measurements of acoustic voice parameters in partially deaf patients showed changes in most of frequency, amplitude, noise and subharmonic components versus normal hearing control group. The most significant, statistically important changes were observed in fundamental frequency variation (vF0), absolute jitter (Jita), jitter percent (Jitt), amplitude perturbation quotient (APQ), smoothed amplitude perturbation quotient (sAPQ), relative average perturbation (RAP), peak amplitude variation (vAm), relative amplitude modulation (Shim), percent shimmer (%Shim), pitch perturbation quotient (PPQ), smoothed pitched perturbation quotient (sPPQ), degree of subharmonics (DSH), degree of voiceless (DUV), number of subharmonic segments (NSH), noise-to-harmonic ratio (NHR), voice turbulence index (VTI). All patients in the study group were subjects to cochlear implantation. After 9 months objective and subjective assessment of patients` voices were performed again. Statistically important changes were identified in average fundamental frequency variability (vF0), relative amplitude modulation index (ShdB), noise-to-harmonic ratio (NHR), number of subharmonics NSH, degree of subharmonics (DSH) and the degree of voiceless (DUV). Comparison of the objective voice parameters changes after cochlear implantation with subjective, perceptual voice quality assessments leads to observation, that improvement of subjective voice quality after cochlear implantation takes place parallelly with improvement of certain objective acoustic voice parameters and some correlations exist. We found, that G correlates with vF0 and Shim, R correlates with DSH and NSH, B correlates with NSH and NHR, A correlates with DUV. We did not prove correlation of S with any of the objective parameters in our research group. Our study proved, that acoustic and perceptual features of voice in partially deaf adults are different than in normally hearing people and cochlear implantation in partial deafness patients is an effective tool to improve hearing and leads to improvement of the acoustic structure of the voice.Partial deafness is a condition characterised by normal hearing thresholds in low frequencies and increased hearing thresholds (nearly deafness) for high frequencies. Typical hearing aids are rather of a very limited use in this condition as they do not improve understanding of speech. Patients with partial deafness can be presently treated with cochlear implants, which had not been used before due to the risk of damage of hearing remains by electrode introduced into cochlea. The purpose of our study was an objective and subjective assessment of voice quality in partial deafness patients before and after cochlear implantation. The subjects in this study were 25 post-lingual, bilaterally partially deaf patients, 13 females and 12 males. The reference group composed of 55 normal hearing individuals (28 females and 27 males). The acoustic analysis was performed with a multidimensional voice analysis MDVP (Multi Dimension Voice Program), and the subjective assessment was done with GRBAS scale. Initial analysis of voice changes in partial deafness patients was performed versus normal hearing individuals, then voice parameters were measured and perceptual voice assessment was done before and 9 months after cochlear implantation. Measurements of acoustic voice parameters in partially deaf patients showed changes in most of frequency, amplitude, noise and subharmonic components versus normal hearing control group. The most significant, statistically important changes were observed in fundamental frequency variation (vF0), absolute jitter (Jita), jitter percent (Jitt), amplitude perturbation quotient (APQ), smoothed amplitude perturbation quotient (sAPQ), relative average perturbation (RAP), peak amplitude variation (vAm), relative amplitude modulation (Shim), percent shimmer (%Shim), pitch perturbation quotient (PPQ), smoothed pitched perturbation quotient (sPPQ), degree of subharmonics (DSH), degree of voiceless (DUV), number of subharmonic segments (NSH), noise-to-harmonic ratio (NHR), voice turbulence index (VTI). All patients in the study group were subjects to cochlear implantation. After 9 months objective and subjective assessment of patients` voices were performed again. Statistically important changes were identified in average fundamental frequency variability (vF0), relative amplitude modulation index (ShdB), noise-to-harmonic ratio (NHR), number of subharmonics NSH, degree of subharmonics (DSH) and the degree of voiceless (DUV). Comparison of the objective voice parameters changes after cochlear implantation with subjective, perceptual voice quality assessments leads to observation, that improvement of subjective voice quality after cochlear implantation takes place parallelly with improvement of certain objective acoustic voice parameters and some correlations exist. We found, that G correlates with vF0 and Shim, R correlates with DSH and NSH, B correlates with NSH and NHR, A correlates with DUV. We did not prove correlation of S with any of the objective parameters in our research group. Our study proved, that acoustic and perceptual features of voice in partially deaf adults are different than in normally hearing people and cochlear implantation in partial deafness patients is an effective tool to improve hearing and leads to improvement of the acoustic structure of the voice.

Myszel K ，Szkiełkowska A 《-》

Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition.

The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms 'COVID', 'amyloid', 'fibrin', 'fibrinogen'. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID-19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre-developed methods for laboratory studies. We planned to perform synthesis without meta-analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post-COVID-19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria. In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.

Fox T ，Hunt BJ ，Ariens RA ，Towers GJ ，Lever R ，Garner P ，Kuehn R ... -  《Cochrane Database of Systematic Reviews》

Booster-free anti-retroviral therapy for persons living with HIV and multidrug resistance (B-Free): protocol for a multicentre, multistage, randomised, controlled, non-inferiority trial.

Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART. B-Free is a multistage, randomised, multicentre, open-label, non-inferiority trial, embedded within the Swiss HIV Cohort Study and conducted in collaboration with cohorts of PWH in the Netherlands and France. Cohort participants with a history of ART change due to virologic failure and who maintain HIV virologic suppression with an ART regimen consisting of a pharmacological booster and at least two drugs from classes other than nucleoside reverse transcriptase inhibitors are included. Patients with major drug resistance mutations against DTG or DOR and individuals with chronic hepatitis B virus infection are not eligible for the study. Individuals are randomised 1:1 to either receiving co-formulated DTG/3TC and DOR once daily or continuing their boosted ART regimen. The primary outcome is the proportion of individuals lacking virologic control (HIV-RNA ≥50 cp/mL) at 48 weeks, according to the Food and Drug Administration snapshot algorithm. Changes in DDI burden (assessed using a DDI score), treatment satisfaction (assessed using the HIV Treatment Satisfaction Questionnaire), quality of life and mental health represent key secondary outcomes. Additional secondary outcomes include the proportion of individuals developing new resistance-associated mutations and changes in quality of life and mental health. In a qualitative substudy, we will conduct semistructured interviews with a subset of participants to assess their expectations and experiences towards HIV treatment and clinical research in general. Enrolling 210 individuals will provide 80% power to demonstrate non-inferiority, defined as less than 8% absolute increase in loss of viral suppression in individuals randomised to DOR/DTG/3TC (one-sided type I error rate of 0.025). The study was approved by the competent ethics committees (reference number BASEC 2023-01060) and the regulatory authority Swissmedic (reference number 701655) in Switzerland before the enrolment of the first participant. Approval by the European Medicines Agency and local ethical committees in the Netherlands and France will be obtained prior to including participants in these countries. Participant's written informed consent is obtained by the investigators before enrolment. The results of all major B-Free study outcomes will be submitted to peer-reviewed journals that enable Open Access publication. Swiss National Clinical Trials Portal (SNCTP000005686, registered on 06 November 2023) and Clinicaltrials.gov (NCT06037564, registered on 07 September 2023).

Ballif M ，Braun D ，Calmy A ，Bernasconi E ，Cavassini M ，Tissot F ，Stoeckle M ，Schmid P ，Fux CA ，Van der Valk M ，Brinkman K ，Mudrikova T ，Bonnet F ，Leleux O ，Saúde M ，Hirter D ，Schwab N ，Limacher A ，Rintelen F ，Kouyos R ，Haerry D ，Zambrano SC ，Egloff M ，Akre C ，Peytremann-Bridevaux I ，Rauch A ，Wandeler G ，Surial B ... -  《BMJ Open》