Association between age-related hearing loss and gait disorders in older fallers.

INTRODUCTION: Falls are associated with hearing loss, which might be explained by the onset of gait disorders. The objective of this study was to examine the association between Age-Related Hearing Loss (ARHL) and gait disorders assessed with GAITrite® walkway in a population of fallers aged 75 and over while accounting for the vestibular function. METHODS: We examined data from 53 older patients (mean 84.2 ± 5.1 years; 64% women) included after a GAITrite® walkway assessment together with hearing and vestibular tests. People with high-frequency hearing loss, higher than 10% of the age and sex-matched population with the worst hearing, composed untimely ARHL group (n = 30), whereas all others had expected ARHL (n = 23). Presbyvestibulopathy was assessed accordingly to Barany Society criteria. RESULTS: After adjustment for age, sex, body mass index, Mini-Mental State Examination score and presbyvestibulopathy, we found an increase in stride length mean in the untimely ARHL group (p = 0.046), but no between-group differences in stride length variability, cadence or velocity. Untimely ARHL was not associated with presbyvestibulopathy. CONCLUSIONS: Untimely ARHL in older fallers was not associated with gait disorders in the studied population.

Ultrarare heterozygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis.

Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls (P = 0.001); half were previously unknown (AF < 0.000002). MYO6, MYO7A, PTPRQ, and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1N321I/+ mice, carrying the TMC1:p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

Capturing sexual violence experiences among battered women using the revised sexual experiences survey and the revised conflict tactics scales.

The assessment of intimate partner sexual violence (IPSV) has garnered increased attention in recent years. However, uncertainty about which measure best captures experiences of IPSV remains. The present study focused on the direct comparison of two widely used measures of IPSV: the revised Sexual Experiences Survey (SES) and the revised Conflict Tactics Scales (CTS2). A secondary aim of the study was to extend the scope of IPSV acts by evaluating the presence of pornographic acts and experiences of forced sexual relations with other individuals. The current sample consisted of 138 battered women using the services of shelters. Results indicated that 79.7 % of women reported at least one incident of IPSV on either the CTS2 or the SES. The concordance rate between both measures was 76.8 %, with the highest concordance being for severe sexual violence. The Sexual Violence scale of the CTS2, which is more concise than the SES, identified 16.7 % more cases of IPSV. In addition, 26.1 % of women reported at least one incident involving pornography and 9.4 % had been forced to engage in sexual activities with other individuals. Women who reported experiences associated with pornography were 12-20 times more likely to be victims of severe sexual violence on the two measures. Such findings confirm the high prevalence of sexual violence among this population and indicate how rates can vary depending on the measures used. This study also underscores the relevance of investigating diverse types of violent acts to better understand how IPSV manifests itself.

Total lower eyelid reconstructions with septal chondromucosal graft and pedicled flap on the superficial temporal artery.

BACKGROUND: Subtotal and total lower eyelid tissue loss after tumour excision is a complex issue for reconstructive surgeons. The anterior and posterior flaps must be restored to avoid compromising the functional and aesthetic prognosis of the eye. This study used a septal chondromucosal graft for the posterior lamella and a fasciocutaneous flap pedicled on the temporal artery for the anterior lamella. METHOD: We conducted a 10-year monocentric retrospective study, including 18 patients who were treated using a septal chondromucosal graft with a temporal artery pedicle flap following tumour excision. We collected demographic and medico-surgical data related to flap survival, absence of ectropion, lagophthalmos and other post-operative complications. The aesthetic outcome was judged using a grading scale during the last follow-up consultation. RESULTS: All grafts and flaps survived, whereas 2 patients required early repeat surgery (1 for ectropion and 1 for graft site haematoma). None of the patients developed lagophthalmos. Two patients had distal flap injuries that healed with local care. All patients were satisfied with the aesthetic outcome at the last follow-up visit. CONCLUSION: Combining a septal chondromucosal graft with a fasciocutaneous flap pedicled to the temporal artery for total lower eyelid reconstruction is a reliable method with satisfactory functional and cosmetic outcomes.

Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health.

Hearing impairment (HI) is a prevalent neurosensory condition globally, impacting 5% of the population, with over 50% of congenital cases attributed to genetic etiologies. In Tunisia, HI underdiagnosis prevails, primarily due to limited access to comprehensive clinical tools, particularly for syndromic deafness (SD), characterized by clinical and genetic heterogeneity. This study aimed to uncover the SD spectrum through a 14-year investigation of a Tunisian cohort encompassing over 700 patients from four referral centers (2007-2021). Employing Sanger sequencing, Targeted Panel Gene Sequencing, and Whole Exome Sequencing, genetic analysis in 30 SD patients identified diagnoses such as Usher syndrome, Waardenburg syndrome, cranio-facial-hand-deafness syndrome, and H syndrome. This latter is a rare genodermatosis characterized by HI, hyperpigmentation, hypertrichosis, and systemic manifestations. A meta-analysis integrating our findings with existing data revealed that nearly 50% of Tunisian SD cases corresponded to rare inherited metabolic disorders. Distinguishing between non-syndromic and syndromic HI poses a challenge, where the age of onset and progression of features significantly impact accurate diagnoses. Despite advancements in local genetic characterization capabilities, certain ultra-rare forms of SD remain underdiagnosed. This research contributes critical insights to inform molecular diagnosis approaches for SD in Tunisia and the broader North-African region, thereby facilitating informed decision-making in clinical practice.

Corrigendum: Current phenotypic and genetic spectrum of syndromic deafness in Tunisia: paving the way for precision auditory health.

[This corrects the article DOI: 10.3389/fgene.2024.1384094.].

Masseter muscle pressure injury: First report of a prone position complication in patients with COVID-19.

We report the case of a 59-year-old, obese woman who underwent prolonged prone position during the medical management of an acute respiratory distress syndrome induced by SARS-CoV-2 infection, complicated by a masseter muscle pressure injury. Such side effect may be underestimate in intensive care units and should be prevent by prophylactic dressings on facial weight-bearing sites. The understanding of facial deep tissue injury is essential to guide clinical detection and management of such a complication in COVID-19 patients.

Contributions of Age-Related and Audibility-Related Deficits to Aided Consonant Identification in Presbycusis: A Causal-Inference Analysis.

The decline of speech intelligibility in presbycusis can be regarded as resulting from the combined contribution of two main groups of factors: (1) audibility-related factors and (2) age-related factors. In particular, there is now an abundant scientific literature on the crucial role of suprathreshold auditory abilities and cognitive functions, which have been found to decline with age even in the absence of audiometric hearing loss. However, researchers investigating the direct effect of aging in presbycusis have to deal with the methodological issue that age and peripheral hearing loss covary to a large extent. In the present study, we analyzed a dataset of consonant-identification scores measured in quiet and in noise for a large cohort (n = 459, age = 42-92) of hearing-impaired (HI) and normal-hearing (NH) listeners. HI listeners were provided with a frequency-dependent amplification adjusted to their audiometric profile. Their scores in the two conditions were predicted from their pure-tone average (PTA) and age, as well as from their Extended Speech Intelligibility Index (ESII), a measure of the impact of audibility loss on speech intelligibility. We relied on a causal-inference approach combined with Bayesian modeling to disentangle the direct causal effects of age and audibility on intelligibility from the indirect effect of age on hearing loss. The analysis revealed that the direct effect of PTA on HI intelligibility scores was 5 times higher than the effect of age. This overwhelming effect of PTA was not due to a residual audibility loss despite amplification, as confirmed by a ESII-based model. More plausibly, the marginal role of age could be a consequence of the relatively little cognitively-demanding task used in this study. Furthermore, the amount of variance in intelligibility scores was smaller for NH than HI listeners, even after accounting for age and audibility, reflecting the presence of additional suprathreshold deficits in the latter group. Although the non-sense-syllable materials and the particular amplification settings used in this study potentially restrict the generalization of the findings, we think that these promising results call for a wider use of causal-inference analysis in audiology, e.g., as a way to disentangle the influence of the various cognitive factors and suprathreshold deficits associated to presbycusis.

Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial.

OBJECTIVES: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. METHODS: We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. RESULTS: The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45-2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. CONCLUSION: In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04325893 (https://clinicaltrials.gov/ct2/show/NCT04325893).

[Childhood experiences of the Duplessis children: consequences 50 years later]. / Les expériences vécues par les enfants de Duplessis institutionnalisés : les conséquences après plus de 50 ans.

In this article, the authors present qualitative results, derived from questionnaires and semi-structured interviews, to describe past and present experiences of the Duplessis children. Examples representative of their experience and a detailed description of two cases are provided. Results indicate that childhood abuse and negligence are related to poorer long-term psychological adjustment. The findings also demonstrate that reporting at least four strengths in childhood can have long-term protective effects.

Neovascularized Best Disease in Child: Contribution of Optical Coherence Tomography Angiography.

Choroidal neovascularization (CNV) is a rare but severe complication in Best disease and autosomal recessive bestrophinopathy. However, the visualization of the neovascular membrane is difficult on fluorescein angiography (FA) and indocyanine green angiography (ICGA) because of dye leakage due to the accumulation of material. The authors' study reports a case series of pediatric Best disease where optical coherence tomography angiography (OCTA) contributed to the diagnosis of CNV and prompt treatment. Five eyes of three patients were included (two Best disease and one autosomal recessive bestrophinopathy). The mean age at diagnosis was 6.8 years ± 1.8 years (range: 5 years to 10 years). OCTA showed the typical "sea fan-shaped" neovascular membrane in all five eyes, whereas, in most cases, conventional imaging by FA and ICGA did not show clearly the neovascularization due to masking effect of the vitelliform material. OCTA seems to be a good alternative to diagnosing CNV in Best disease, especially in children, as it is a noninvasive, rapid technique for imaging, and does not require the administration of dyes. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:597-601.].

[Consequences of an institutionalized childhood: the case of the "Duplessis orphans"]. / Répercussions d'une enfance vécue en institution : le cas des Enfants de Duplessis.

Whereas the immediate consequences of institutionalized placements on children have been documented, no study has investigated adults who were raised in orphanages or institutions. In Quebec, les enfants de Duplessis offer a unique testimony of the long term consequences of an institutionalized childhood. Stories collected from 40 men and 41 women who grew up in institution in Duplessis'era indicate a high number of abuse and aversive experiences, including physical, psychological and sexual aggressions. In addition, the environment was poor in stimulation and opportunities to develop positive attachment relationships with adults. When matched and compared to adults from the Santé-Québec survey, les enfants de Duplessis report a higher number of health problems associated with stress and more psychological distress. Moreover, our results indicate that those who had fewer strengths and aptitudes in childhood are the most affected by unfavourable experiences.

Seven institutionalized children and their adaptation in late adulthood: the children of Duplessis (Les Enfants de Duplessis).

War, societal and familial upheaval, disease, and natural disasters have resulted in orphaned children throughout time. One societal response to providing care for orphans has been institutionalization or the orphanage. We studied a sample of adults, known as les enfants de Duplessis or Duplessis's children, who were raised in Quebec institutions from birth onward and followed up in late adulthood. Systematic study indicated a high prevalence of adverse outcomes and found high levels of gross psychological trauma and adversity which, moderated by the childhood strengths of the individuals, had adverse effects on adult outcome (Sigal, Perry, Rossignol, & Ouimet, 2003; Perry, Sigal, Boucher, Paré, & Ouimet, 2005a; Perry, Sigal, Boucher, Paré, Ouimet, Norman, & Henry, 2005b). This report describes the experiences of seven individuals in the institutions and their subsequent life history and current functioning. The individual cases reflect a wide range of childhood strengths and experiences of trauma and other adversity in relationship to adult caretakers. While the group overall appears to have had seriously diminished functioning in late adulthood, several individuals had positive outcomes. We hope that by highlighting the potentially adverse effects of institutional rearing on subsequent development into late adulthood, these stories may inform those concerned with the care of orphans.

Fibrin glue versus autologous blood for conjunctival autograft fixation in pterygium surgery.

OBJECTIVE: To compare the outcomes between autologous blood- and fibrin glue-fixated conjunctival autografts in pterygium excision surgery. DESIGN: Retrospective case series. PARTICIPANTS: Forty eyes of 40 patients who had a primary nasal pterygium excision. METHODS: A retrospective comparative case series of 40 eyes (40 patients) that had a primary nasal pterygium excision. All eyes had a conjunctival autograft from the superior bulbar conjunctiva to cover the scleral bed. Twenty eyes (20 patients) had fixation of the autograft using autologous blood (AB), and 20 eyes (20 patients) had fixation using fibrin glue (FG). One year of follow-up data included conjunctival graft stability (graft loss, graft retraction), pterygium recurrence, visual acuity, and postoperative complications. Descriptive and inferential statistics were performed. RESULTS: Intraoperatively, no complications occurred in either group. Graft loss occurred in 6 patients in the AB group, compared with none in the FG group. Graft retraction occurred in 3 patients in the AB group and 2 patients in the FG group. At 1 year postoperatively, pterygium recurrence occurred in 4 patients in the AB group and 1 patient in the FG group. One patient in the AB group developed a small pyogenic granuloma that resolved by 6 months with conservative management. Visual acuity remained stable in both groups. CONCLUSIONS: Conjunctival autograft fixation with autologous blood resulted in less stable conjunctival autografts and a higher recurrence rate compared with fixation with fibrin glue.

Personal strengths and traumatic experiences among institutionalized children given up at birth (Les Enfants de Duplessis--Duplessis' children): I: Early experiences.

We examined childhood and early adult strengths and adverse experiences of a group of orphans given up at or near birth and raised in Quebec institutions into early adulthood. A follow-up interview of 81 adults (41 women, 40 men) at a mean age of 59.2 years included retrospective assessments of childhood experiences. Most participants reported multiple early adverse experiences, including, in descending order, unfair rules and excessive punishment, physical abuse, emotional neglect, witnessing violence, verbal abuse, physical neglect, sexual abuse, and serious illness. Adverse experiences were mainly due to lay caretakers, not peers or nuns. Twelve childhood strengths, such as self-protectiveness and athletic talent, were scored at each of four age periods, yielding a median score equivalent to one strength at each period. Over half had significant childhood attachments, but of limited intimacy. Childhood variables correlated with their respective variables in later adulthood. Overall, these older adults reported a high prevalence of adverse or traumatic childhood experiences, counterbalanced by modest levels of individual strengths and attachment relationships. Institutionalization of children--if unavoidable--must build in effective safeguards against adverse experiences.