Substantial health and economic burden of COVID-19 during the year after acute illness among US adults at high risk of severe COVID-19.

BACKGROUND: Post-COVID conditions encompass a range of long-term symptoms after SARS-CoV-2 infection. The potential clinical and economic burden in the United States is unclear. We evaluated diagnoses, medications, healthcare use, and medical costs before and after acute COVID-19 illness in US patients at high risk of severe COVID-19. METHODS: Eligible adults were diagnosed with COVID-19 from April 1 to May 31, 2020, had ≥ 1 condition placing them at risk of severe COVID-19, and were enrolled in Optum's de-identified Clinformatics® Data Mart Database for ≥ 12 months before and ≥ 13 months after COVID-19 diagnosis. Percentages of diagnoses, medications, resource use, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified by age and COVID-19 severity. RESULTS: The cohort included 19,558 patients (aged 18-64 y, n = 9381; aged ≥ 65 y, n = 10,177). Compared with baseline, patients during the post-acute phase had increased percentages of blood disorders (16.3%), nervous system disorders (11.1%), and mental and behavioral disorders (7.7%), along with increases in related prescriptions. Overall, there were substantial increases in inpatient and outpatient healthcare utilization, along with a 23.0% increase in medical costs. Changes were greatest among older patients and those admitted to the intensive care unit for acute COVID-19 but were also observed in younger patients and those who did not require COVID-19 hospitalization. CONCLUSIONS: There is a significant clinical and economic burden of post-COVID conditions among US individuals at high risk for severe COVID-19.

Substantial health and economic burden of COVID-19 during the year after acute illness among US adults not at high risk of severe COVID-19.

BACKGROUND: Patients recovering from SARS-CoV-2 infection and acute COVID-19 illness can experience a range of long-term post-acute effects. The potential clinical and economic burden of these outcomes in the USA is unclear. We evaluated diagnoses, medications, healthcare utilization, and medical costs before and after acute COVID-19 illness in US patients who were not at high risk of severe COVID-19. METHODS: This study included eligible adults who were diagnosed with COVID-19 from April 1 to May 31, 2020, who were 18 - 64 years of age, and enrolled within Optum's de-identified Clinformatics® Data Mart Database for 12 months before and 13 months after COVID-19 diagnosis. Patients with any condition or risk factor placing them at high risk of progression to severe COVID-19 were excluded. Percentages of diagnoses, medications, healthcare utilization, and costs were calculated during baseline (12 months preceding diagnosis) and the post-acute phase (12 months after the 30-day acute phase of COVID-19). Data were stratified into 3 cohorts according to disposition during acute COVID-19 illness (i.e., not hospitalized, hospitalized without intensive care unit [ICU] admission, or admitted to the ICU). RESULTS: The study included 3792 patients; 56.5% of patients were men, 44% were White, and 94% did not require hospitalization. Compared with baseline, patients during the post-acute phase had percentage increases in the diagnosis of the following disorders: blood (166%), endocrine and metabolic (123%), nervous system (115%), digestive system (76%), and mental and behavioral (75%), along with increases in related prescriptions. Substantial increases in all measures of healthcare utilization were observed among all 3 cohorts. Total medical costs increased by 178% during the post-acute phase. Those who were hospitalized with or without ICU admission during the acute phase had the greatest increases in comorbidities and healthcare resource utilization. However, the burden was apparent across all cohorts. CONCLUSIONS: As evidenced by resource use in the post-acute phase, COVID-19 places a significant long-term clinical and economic burden among US individuals, even among patients whose acute infection did not merit hospitalization.

Health-related quality of life in mild-to-moderate COVID-19 in the UK: a cross-sectional study from pre- to post-infection.

BACKGROUND: The aim of this study was to estimate the impact of mild-to-moderate COVID-19 on health-related quality of life (HRQoL) over time among individuals in the United Kingdom, adding to the evidence base that had focussed on severe COVID-19. METHODS: A bespoke online survey was administered to individuals who self-reported a positive COVID-19 test. An amended version of a validated generic HRQoL instrument (EQ-5D-5L) was used to measure HRQoL retrospectively at different timepoints over the course of an infection: pre-COVID-19, acute COVID-19, and long COVID. In addition, HRQoL post-COVID-19 was captured by the original EQ-5D-5L questionnaire. A mixed-effects model was used to estimate changes in HRQoL over time, adjusted for a range of variables correlated with HRQoL. RESULTS: The study recruited 406 participants: (i) 300 adults and 53 adolescents with mild-to-moderate COVID-19 who had not been hospitalised for COVID-19 during acute COVID-19, and (ii) 53 adults who had been hospitalised for COVID-19 in the acute phase and who had been recruited for validation purposes. Data were collected between January and April 2022. Among participants included in the base-case analysis, EQ-5D-5L utility scores were lower during both acute COVID-19 (ß=-0.080, p = 0.001) and long COVID (ß=-0.072, p < 0.001) compared to pre COVID-19. In addition, EQ-5D-5L utility scores post-COVID-19 were found to be similar to the EQ-5D-5L utility scores before COVID-19, including for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID. Moreover, being hospitalised in the acute phase was associated with additional utility decrements during both acute COVID-19 (ß=-0.147, p = 0.026) and long (ß=-0.186, p < 0.001) COVID. CONCLUSION: Patients perceived their HRQoL to have varied significantly over the course of a mild-to-moderate COVID-19 infection. However, HRQoL was found to return to pre-COVID-19 levels, even for patients who had been hospitalised for COVID-19 during the acute phase or for those who had experienced long COVID.

A Two-Step, Trajectory-Focused, Analytics Approach to Attempt Prediction of Analgesic Response in Patients with Moderate-to-Severe Osteoarthritis.

INTRODUCTION: We sought to predict analgesic response to daily oral nonsteroidal anti-inflammatory drugs (NSAIDs) or subcutaneous tanezumab 2.5 mg (every 8 weeks) at week 16 in patients with moderate-to-severe osteoarthritis, based on initial treatment response over 8 weeks. METHODS: Data were derived from three randomized controlled trials of osteoarthritis. A two-step, trajectory-focused, analytics approach was used to predict patients as responders or non-responders at week 16. Step 1 identified patients using a data-element combination method (based on pain score at baseline, pain score at week 8, pain score monotonicity at week 8, pain score path length at week 8, and body site [knee or hip]). Patients who could not be identified in step 1 were predicted in step 2 using a k-nearest neighbor method based on pain score and pain response level at week 8. RESULTS: Our approach predicted response with high accuracy in NSAID-treated (83.2-90.2%, n = 931) and tanezumab-treated (84.6-91.0%, n = 1430) patients regardless of the efficacy measure used to assess pain, or the threshold used to define response (20%, 30%, or 50% improvement from baseline). Accuracy remained high using 50% or 20% response thresholds, with 50% and 20% yielding generally slightly better negative and positive predictive value, respectively, relative to 30%. Accuracy was slightly better in patients aged ≥ 65 years relative to younger patients across most efficacy measure/response threshold combinations. CONCLUSIONS: Analyzing initial 8-week analgesic responses using a two-step, trajectory-based approach can predict future response in patients with moderate-to-severe osteoarthritis treated with NSAIDs or 2.5 mg tanezumab. These findings demonstrate that prediction of treatment response based on a single dose of a novel therapeutic is possible and that predicting future outcomes based on initial response offers a way to potentially advance the approach to clinical management of patients with osteoarthritis. GOV IDENTIFIERS: NCT02528188, NCT02709486, NCT02697773.

Characterizing 16-Week Responder Profiles Using Group-Based Trajectory Modeling in Over 4300 Clinical Trial Participants Receiving Pharmaceutical Treatment for Moderate to Severe Osteoarthritis.

INTRODUCTION: We sought to identify and characterize distinct responder profiles among osteoarthritis (OA) subjects treated with tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), or placebo. METHODS: Subject-level data were derived from three randomized, double-blind, placebo- or NSAID-controlled trials of tanezumab in subjects with moderate-to-severe OA. Subjects received subcutaneous tanezumab (2.5 mg, n = 1527; 5 mg, n = 1279) every 8 weeks, oral NSAIDs (n = 994) daily, or placebo (n = 513). Group-based trajectory modeling (GBTM, an application of finite mixture statistical modeling that uses response trajectory to identify and summarize complex patterns in longitudinal data) was used to identify subgroups of subjects following similar patterns of response in each treatment arm, based on daily pain intensity scores from baseline through Week 16. We then examined whether subject-related variables were associated with any of the subgroups using multinomial logistic regression. RESULTS: A three-subgroup/four-inflection point trajectory model was selected based on clinical and statistical considerations. The subgroups were high responders (substantial pain improvement and a large majority of members achieved ≥ 30% improvement before Week 16), medium responders (gradual pain improvement and a majority of members achieved ≥ 30% improvement by Week 16), and non-responders (little to no pain improvement over 16 weeks). Across all treatments, fluctuation in pain intensity in the week prior to treatment was consistently associated with treatment response. Other variables were positively (age, body mass index, days of rescue medication use) or negatively (severity of disease based on Kellgren-Lawrence grading) associated with response but effects were small and/or varied across treatments. CONCLUSIONS: Across all treatments, GBTM identified three subgroups of subjects that were characterized by extent of treatment response (high, medium, and non-responders). Similar analyses (e.g., grouping of subjects based on response trajectory and identification of subgroup-related variables) in other studies of OA could inform clinical trial design and/or treatment approaches. (NCT02697773; NCT02709486; NCT02528188).

Evaluation of a specialist cognitive clinic for the Deaf community.

There are significant health inequalities between Deaf and hearing people, including barriers to accessing care and communication difficulties in consultations. Such problems have particularly affected Deaf people with acquired cognitive deficits, leading to late and missed diagnoses. We therefore established a specialist cognitive clinic for the Deaf community in 2011 at the National Hospital for Neurology and Neurosurgery, which to our knowledge is the first of its kind in the world. In this study, we retrospectively analysed electronic patient records to evaluate the service and its impact since inception. We found that Deaf patients who use British sign language had difficulty obtaining an accurate diagnosis before attending our specialist clinic, highlighting the importance of tailored services for Deaf people. Our results show that the clinic improved communication for patients and accessibility to specialist investigations, ensuring diagnostic accuracy and overall reducing health inequality for this population.

Expressive Vocabulary Predicts Nonverbal Executive Function: A 2-year Longitudinal Study of Deaf and Hearing Children.

Numerous studies suggest an association between language and executive function (EF), but evidence of a developmental relationship remains inconclusive. Data were collected from 75 deaf/hard-of-hearing (DHH) children and 82 hearing age-matched controls. Children were 6-11 years old at first time of testing and completed a battery of nonverbal EF tasks and a test of expressive vocabulary. These tasks were completed again 2 years later. Both groups improved their scores on all tasks over this period. DHH children performed significantly less well than hearing peers on some EF tasks and the vocabulary test at both time points. Cross-lagged panel models showed that vocabulary at Time 1 predicted change in EF scores for both DHH and hearing children but not the reverse.

Assessing Deaf patients in the neurology clinic.

There are over 87 000 Deaf people in the UK with British Sign Language (BSL) as their first language.1 Few healthcare professionals receive training in Deaf awareness or in BSL, and missed diagnoses and inadequate treatment of Deaf patients are estimated to cost the National Health Service £30 million per year.2 Neurologists are likely to encounter Deaf BSL users in their practice, but without prior experience may find consultations challenging, especially within the time constraints and pressure of a standard clinic. In this article, we provide guidance on consulting with Deaf people in a neurology clinic, drawing on experience from our cognitive clinic for Deaf BSL users where effective communication is essential.

Signing with the Face: Emotional Expression in Narrative Production in Deaf Children with Autism Spectrum Disorder.

This study examined facial expressions produced during a British Sign Language (BSL) narrative task (Herman et al., International Journal of Language and Communication Disorders 49(3):343-353, 2014) by typically developing deaf children and deaf children with autism spectrum disorder. The children produced BSL versions of a video story in which two children are seen to enact a language-free scenario where one tricks the other. This task encourages elicitation of facial acts signalling intention and emotion, since the protagonists showed a range of such expressions during the events portrayed. Results showed that typically developing deaf children produced facial expressions which closely aligned with native adult signers' BSL narrative versions of the task. Children with ASD produced fewer targeted expressions and showed qualitative differences in the facial actions that they produced.

Nonverbal Executive Function is Mediated by Language: A Study of Deaf and Hearing Children.

Studies have suggested that language and executive function (EF) are strongly associated. Indeed, the two are difficult to separate, and it is particularly difficult to determine whether one skill is more dependent on the other. Deafness provides a unique opportunity to disentangle these skills because in this case, language difficulties have a sensory not cognitive basis. In this study, deaf (n = 108) and hearing (n = 125) children (age 8 years) were assessed on language and a wide range of nonverbal EF tasks. Deaf children performed significantly less well on EF tasks, even controlling for nonverbal intelligence and speed of processing. Language mediated EF skill, but the reverse pattern was not evident. Findings suggest that language is key to EF performance rather than vice versa.

Synesthesia for manual alphabet letters and numeral signs in second-language users of signed languages.

Many synesthetes experience colors when viewing letters or digits. We document, for the first time, an analogous phenomenon among users of signed languages who showed color synesthesia for fingerspelled letters and signed numerals. Four synesthetes experienced colors when they viewed manual letters and numerals (in two cases, colors were subjectively projected on to the hands). There was a correspondence between the colors experienced for written graphemes and their manual counterparts, suggesting that the development of these two types of synesthesia is interdependent despite the fact that these systems are superficially distinct and rely on different perceptual recognition mechanisms in the brain.

Detecting Memory Impairment in Deaf People: A New Test of Verbal Learning and Memory in British Sign Language.

OBJECTIVE: Most existing tests of memory and verbal learning in adults were created for spoken languages, and are unsuitable for assessing deaf people who rely on signed languages. In response to this need for sign language measures, the British Sign Language Verbal Learning and Memory Test (BSL-VLMT) was developed. It follows the format of the English language Hopkins Verbal Learning Test Revised, using standardized video-presentation with novel stimuli and instructions wholly in British Sign Language, and no English language requirement. METHOD: Data were collected from 223 cognitively healthy deaf signers aged 50-89 and 12 deaf patients diagnosed with dementia. Normative data percentiles were derived for clinical use, and receiver-operating characteristic curves computed to explore the clinical potential and diagnostic sensitivity and specificity. RESULTS: The test showed good discrimination between the normative and clinical samples, providing preliminary evidence of clinical utility for identifying learning and memory impairment in older deaf signers with neurodegeneration. CONCLUSIONS: This innovative video testing approach transforms the ability to accurately detect memory impairments in deaf people and avoids the problems of using interpreters, with international potential for adapting similar tests into other signed languages.

Detecting Cognitive Impairment and Dementia in Deaf People: The British Sign Language Cognitive Screening Test.

To provide accurate diagnostic screening of deaf people who use signed communication, cognitive tests must be devised in signed languages with normative deaf samples. This article describes the development of the first screening test for the detection of cognitive impairment and dementia in deaf signers. The British Sign Language Cognitive Screening Test uses standardized video administration to screen cognition using signed, rather than spoken or written, instructions and a large norm-referenced sample of 226 deaf older people. Percentiles are provided for clinical comparison. The tests showed good reliability, content validity, and correlation with age, intellectual ability, and education. Clinical discrimination was shown between the normative sample and 14 deaf patients with dementia. This innovative testing approach transforms the ability to detect dementia in deaf people, avoids the difficulties of using an interpreter, and enables culturally and linguistically sensitive assessment of deaf signers, with international potential for adaptation into other signed languages.

Deaf children's non-verbal working memory is impacted by their language experience.

Several recent studies have suggested that deaf children perform more poorly on working memory tasks compared to hearing children, but these studies have not been able to determine whether this poorer performance arises directly from deafness itself or from deaf children's reduced language exposure. The issue remains unresolved because findings come mostly from (1) tasks that are verbal as opposed to non-verbal, and (2) involve deaf children who use spoken communication and therefore may have experienced impoverished input and delayed language acquisition. This is in contrast to deaf children who have been exposed to a sign language since birth from Deaf parents (and who therefore have native language-learning opportunities within a normal developmental timeframe for language acquisition). A more direct, and therefore stronger, test of the hypothesis that the type and quality of language exposure impact working memory is to use measures of non-verbal working memory (NVWM) and to compare hearing children with two groups of deaf signing children: those who have had native exposure to a sign language, and those who have experienced delayed acquisition and reduced quality of language input compared to their native-signing peers. In this study we investigated the relationship between NVWM and language in three groups aged 6-11 years: hearing children (n = 28), deaf children who were native users of British Sign Language (BSL; n = 8), and deaf children who used BSL but who were not native signers (n = 19). We administered a battery of non-verbal reasoning, NVWM, and language tasks. We examined whether the groups differed on NVWM scores, and whether scores on language tasks predicted scores on NVWM tasks. For the two executive-loaded NVWM tasks included in our battery, the non-native signers performed less accurately than the native signer and hearing groups (who did not differ from one another). Multiple regression analysis revealed that scores on the vocabulary measure predicted scores on those two executive-loaded NVWM tasks (with age and non-verbal reasoning partialled out). Our results suggest that whatever the language modality-spoken or signed-rich language experience from birth, and the good language skills that result from this early age of acquisition, play a critical role in the development of NVWM and in performance on NVWM tasks.

How do typically developing deaf children and deaf children with autism spectrum disorder use the face when comprehending emotional facial expressions in British sign language?

Facial expressions in sign language carry a variety of communicative features. While emotion can modulate a spoken utterance through changes in intonation, duration and intensity, in sign language specific facial expressions presented concurrently with a manual sign perform this function. When deaf adult signers cannot see facial features, their ability to judge emotion in a signed utterance is impaired (Reilly et al. in Sign Lang Stud 75:113-118, 1992). We examined the role of the face in the comprehension of emotion in sign language in a group of typically developing (TD) deaf children and in a group of deaf children with autism spectrum disorder (ASD). We replicated Reilly et al.'s (Sign Lang Stud 75:113-118, 1992) adult results in the TD deaf signing children, confirming the importance of the face in understanding emotion in sign language. The ASD group performed more poorly on the emotion recognition task than the TD children. The deaf children with ASD showed a deficit in emotion recognition during sign language processing analogous to the deficit in vocal emotion recognition that has been observed in hearing children with ASD.

Modality-dependent and -independent factors in the organisation of the signed language lexicon: insights from semantic and phonological fluency tasks in BSL.

We used fluency tasks to investigate lexical organisation in Deaf adults who use British sign language (BSL). The number of responses produced to semantic categories did not differ from reports in spoken languages. However, there was considerable variability in the number of responses across phonological categories, and some signers had difficulty retrieving items. Responses were richly clustered according to semantic and/or phonological properties. With respect to phonology, there was significantly more clustering around the parameters "handshape" and "location" compared to "movement". We conclude that the BSL lexicon is organised in similar ways to the lexicons of spoken languages, but that lexical retrieval is characterised by strong links between semantics and phonology; movement is less readily retrieved than handshape and location; and phonological fluency is difficult for signers because they have little metaphonological awareness in BSL and because signs do not display the onset salience that characterises spoken words.

Identifying specific language impairment in deaf children acquiring British Sign Language: implications for theory and practice.

This paper presents the first ever group study of specific language impairment (SLI) in users of sign language. A group of 50 children were referred to the study by teachers and speech and language therapists. Individuals who fitted pre-determined criteria for SLI were then systematically assessed. Here, we describe in detail the performance of 13 signing deaf children aged 5-14 years on normed tests of British Sign Language (BSL) sentence comprehension, repetition of nonsense signs, expressive grammar and narrative skills, alongside tests of non-verbal intelligence and fine motor control. Results show these children to have a significant language delay compared to their peers matched for age and language experience. This impaired development cannot be explained by poor exposure to BSL, or by lower general cognitive, social, or motor abilities. As is the case for SLI in spoken languages, we find heterogeneity within the group in terms of which aspects of language are affected and the severity of the impairment. We discuss the implications of the existence of language impairments in a sign language for theories of SLI and clinical practice.

The effects of cerebellar ataxia on sign language production: a case study.

Speech and sign production both require precise coordination of multiple articulators. The characteristics of dysarthria following ataxia have been well-documented, but less is known about the consequences of ataxia for sign language, which uses the hands and arms as articulators. This is the first study to examine ataxic dysarthria in a sign language user. What is novel in this research is that the limbs are employed for both linguistic and non-linguistic movements. Notably, sign production deficits broadly resembled ataxic dysarthria, while non-linguistic movement deficits were similar to those previously reported for ataxic limb movement.

Exploring the perceptual characteristics of voice-hallucinations in deaf people.

INTRODUCTION: Previous research has not taken account of the possibility that deaf people will show greater heterogeneity in how they experience voice-hallucinations due to individual differences in experience with language and residual hearing. This study aims to explore how deaf participants perceive voice-hallucinations and whether the perceptual characteristics reported reflect individual experience with language and sensory input. METHOD: A statement-sorting task generated data about perceptual characteristics of voice-hallucinations for exploratory factor analysis. The sample included 27 deaf participants with experience of voice-hallucinations, and a range of hearing loss and language backgrounds. RESULTS: Perceptual characteristics of voice-hallucinations map closely onto individual auditory experience. People born profoundly deaf loaded onto nonauditory factors. Deaf people with experience of hearing speech, through residual hearing, hearing aids, or predeafness experience, reported auditory features or uncertainty about mode of perception. CONCLUSIONS: This is the first study to systematically explore voice-hallucinations in deaf people and to advance a model of subvocal articulation to account for such counterintuitive phenomena.