Revisiting the diagnosis of Gaucher disease in a family with multiple GBA1 variants.

Our ability to identify different variants in GBA1, the gene mutated in the lysosomal storage disorder Gaucher disease (GD), has greatly improved. We describe a multigenerational family with type 1 GD initially evaluated over three decades ago. Re-evaluating both the genotype and phenotype, we determined that one family member with genotype N370S/T369M (p.N409S/p.T408M), was likely erroneously diagnosed with GD. This case substantiates that GBA1 variant T369M, while mildly reducing glucocerebrosidase activity, does not result in GD. The observation has clinical relevance as cases with this genotype will increasingly be ascertained through screening programs in newborns and in movement disorder clinics.

The D409H variant in GBA1: Challenges in predicting the Gaucher phenotype in the newborn screening era.

Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase deficiency due to pathologic variants in GBA1. While clinically heterogeneous, GD encompasses three types, non-neuronopathic (GD1), acute neuronopathic (GD2), and chronic neuronopathic (GD3). Newborn screening (NBS), which has made remarkable inroads in detecting certain diseases before detrimental health consequences and fatality ensues, is now being piloted for GD in several states and countries. Early on, clinical features of GD2 can overlap with GD3; hence, predicting outcome is challenging. As NBS for GD becomes more available, the increased detection of GD in neonates is inevitable. As a result, health care providers and families will be faced with uncertainty with respect to clinical management. Since more severe GBA1 variants are generally associated with neuronopathic GD, there has been an increased dependence on genotypic information. We present an infant detected by NBS with genotype D409H(p.Asp448His)/RecNciI (p.Leu483Pro; p.Ala495Pro;p.Val499=). To assist in genetic counseling, we performed a retrospective review of other patients in our cohort carrying D409H and reviewed the literature. The study illustrates the challenges faced in counseling for infants with neuronopathic GD, even with known GBA1 variants, and the tough management decisions that can ensue from detection in newborns.

Men's gendered experiences of rehabilitation and recovery following traumatic brain injury: A reflexive thematic analysis.

Research shows that gender influences men's health-related beliefs and behaviours - including those within the context of traumatic brain injury (TBI) - making it a factor that should be considered when designing and implementing interventions for this population. To incorporate an understanding of such gendered influences in future educational materials for men with TBI, as well as their caregivers and clinicians, this qualitative study was informed by social constructionism, and aimed to explore how gender is related to men's post-TBI perceptions and behaviours in rehabilitation and recovery. Semi-structured interviews were conducted with 22 men with mild and moderate-severe TBI at the acute (≤ 3 months post-TBI) and chronic (> 3 months post-TBI) phases of injury. A reflexive thematic analysis approach was applied to interview data, guided by the concept of hegemonic masculinity as described by Connell, R.W. (2005. Masculinities [2nd ed.]. Polity). Three key themes were identified: (1) "I'm a man, I'm a rock": Undermining treatment, (2) "I'm going to face that challenge": Facilitation of recovery, and (3) "I don't feel as useful as a guy as I was before": Perceptions on return to work. These findings may be translated into gender-informed therapy strategies and materials.

Risk of COVID-19 death in cancer patients: an analysis from Guy's Cancer Centre and King's College Hospital in London.

BACKGROUND: Using an updated dataset with more patients and extended follow-up, we further established cancer patient characteristics associated with COVID-19 death. METHODS: Data on all cancer patients with a positive reverse transcription-polymerase chain reaction swab for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Guy's Cancer Centre and King's College Hospital between 29 February and 31 July 2020 was used. Cox proportional hazards regression was performed to identify which factors were associated with COVID-19 mortality. RESULTS: Three hundred and six SARS-CoV-2-positive cancer patients were included. Seventy-one had mild/moderate and 29% had severe COVID-19. Seventy-two patients died of COVID-19 (24%), of whom 35 died <7 days. Male sex [hazard ratio (HR): 1.97 (95% confidence interval (CI): 1.15-3.38)], Asian ethnicity [3.42 (1. 59-7.35)], haematological cancer [2.03 (1.16-3.56)] and a cancer diagnosis for >2-5 years [2.81 (1.41-5.59)] or ≥5 years were associated with an increased mortality. Age >60 years and raised C-reactive protein (CRP) were also associated with COVID-19 death. Haematological cancer, a longer-established cancer diagnosis, dyspnoea at diagnosis and raised CRP were indicative of early COVID-19-related death in cancer patients (<7 days from diagnosis). CONCLUSIONS: Findings further substantiate evidence for increased risk of COVID-19 mortality for male and Asian cancer patients, and those with haematological malignancies or a cancer diagnosis >2 years. These factors should be accounted for when making clinical decisions for cancer patients.

Women's Gendered Experiences of Traumatic Brain Injury.

Despite recognizing that women have worse outcomes after traumatic brain injury (TBI), little is known about how gender influences their experiences of this critical injury. Past research has been dominated by androcentrism and quantitative approaches, leaving the lived experience of women with TBI insufficiently examined. To gain insight into their experiences, this qualitative study interviewed 19 Canadian women with mild and moderate-to-severe TBIs. Applying a thematic analysis, we discerned three themes: Gender prevails considers choosing to do gender over complying with physician advice; Consequences of TBI impeding performativity explores how women frame themselves as terrible people for being unable to do gender post-TBI; and Perceptions of receiving care looks at gendered caregiving expectations. These results broadly align with research on how doing gender influences recovery and health outcomes. We discuss the implications of our findings for knowledge translation, future research on women's TBI recovery, and clinical practice.

First report of pharmaceuticals and personal care products in two tropical rivers of southwestern India.

The occurrence of selected pharmaceuticals (trimethoprim, sulfamethoxazole, chloramphenicol, bezafibrate, ceftriaxone, and naproxen) in two west-flowing tropical rivers (Swarna and Nethravati) of southwestern India is reported for the first time. Water samples were collected during the monsoon and post-monsoon seasons from river water end members and further downstream up to their confluence with the adjacent Arabian Sea. Samples were analyzed using HPLC-MS/MS. Results revealed that there were no significant seasonal variations in concentrations of target analytes in both the rivers. Of the total number of samples analyzed (n = 24), trimethoprim was detected in 100% of the samples, whereas sulfamethoxazole (SMX), chloramphenicol (CAP), ceftriaxone (CTX), and naproxen (NPX) were detected in between 91 and 58% of the samples. Bezafibrate (BZF) was not detected in the samples. Nethravathi river showed higher concentrations of pharmaceuticals than the Swarna river which may be attributed to comparatively larger human population in the basin. Possible impacts of PPCPs on aquatic life offer further scope for study.

Post-Traumatic Sleep-Wake Disorders.

All living organisms that face a traumatic life event are susceptible to sleep-wake disturbances. Stress, which can result in trauma, evokes a high level of physiological arousal associated with sympathetic nervous system activation, during both sleep and wakefulness. Heredity, sex hormones, early losses, developmental factors and intra- and interpersonal conflicts, contribute to the level of baseline physiological arousal, producing either subclinical, clinical or complex clinical traits, acutely and at any time after exposure to a traumatic event. The risk of acute sleep-wake disturbances becoming disorders and syndromes depends on the type of traumatic event and all of the aforementioned factors. Taken together, with consideration for behavioural and environmental heterogeneity, in research, will aid identification and understanding of susceptibility factors in long-term sleep and wakefulness pathology after exposure to traumatic events.

Sleep and Psychiatric Disorders in Persons With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) frequently challenges the integrity of sleep function by affecting multiple brain areas implicated in controlling the switch between wakefulness and sleep and those involved in circadian and homeostatic processes; the malfunction of each causes a variety of disorders. In this review, we discuss recent data on the dynamics between disorders of sleep and mental/psychiatric disorders in persons with mTBI. This analysis sets the stage for understanding how a variety of physiological, emotional and environmental influences affect sleep and mental activities after injury to the brain. Consideration of the intricate links between sleep and mental functions in future research can increase understanding on the underlying mechanisms of sleep-related and psychiatric comorbidity in mTBI.

A thematic analysis of patients' and their informal caregivers' gendered experiences in traumatic brain injury.

PURPOSE: Research shows that patients' perceptions of themselves and others, in addition to their understanding of the concept of gender, changes after traumatic brain injury (TBI). Little is known about gendered experiences in TBI and care delivery. This study aims to explore perceptions of gender through life experiences and interactions between adult patients with TBI and their informal caregivers. MATERIALS AND METHODS: Seven patients with mild and moderate-severe TBI and eight informal caregivers were interviewed. Transcripts were coded and analysed according to Braun and Clarke's thematic analysis. The Consolidated Criteria for Reporting Qualitative Research guidelines were followed in reporting results. RESULTS: The participants described a transformation of their understanding and experiences of gender following the TBI event. Three themes were identified: (1) Gender designations of "man" and "woman";( 2) Post-injury performativity of gender; and (3) Gender in giving and receiving care. CONCLUSIONS: The findings emphasize the importance of raising awareness among researchers and practitioners on gender as a transformative process for patients with TBI and informal caregivers after the injury. The diversity of patient-caregiver experiences and critical needs based on gender call for intervention approaches that mitigate gender disparities in giving and receiving care. Implications for RehabilitationHistorically, rehabilitation of persons with traumatic brain injury has targeted physical and cognitive impairments, with little attention to their gendered demands in the lived environment.Gender prevails in the lived experiences of persons with traumatic brain injury, and their informal caregivers, and in giving and receiving quality care.A major challenge for clinicians is identifying harmful gendered roles, norms, and relations and the affective/behavioral problems they produce to alleviate enduring distress and reduce disability.Rehabilitation interventions focusing on flexible and adaptive responses to gendered demands in the lived environment of persons with traumatic brain injury are timely.

Facial features of lysosomal storage disorders.

INTRODUCTION: The use of facial recognition technology has diversified the diagnostic toolbelt for clinicians and researchers for the accurate diagnoses of patients with rare and challenging disorders. Specific identifiers in patient images can be grouped using artificial intelligence to allow the recognition of diseases and syndromes with similar features. Lysosomal storage disorders are rare, and some have prominent and unique features that may be used to train the accuracy of facial recognition software algorithms. Noteworthy features of lysosomal storage disorders (LSDs) include facial features such as prominent brows, wide noses, thickened lips, mouth, and chin, resulting in coarse and rounded facial features. AREAS COVERED: We evaluated and report the prevalence of facial phenotypes in patients with different LSDs, noting two current examples when artificial intelligence strategies have been utilized to identify distinctive facies. EXPERT OPINION: Specific LSDs, including Gaucher disease, Mucolipidosis IV and Fabry disease have recently been distinguished using facial recognition software. Additional lysosomal disorders LSDs lysosomal storage disorders with unique and distinguishable facial features also merit evaluation using this technology. These tools may ultimately aid in the identification of specific LSDs and shorten the diagnostic odyssey for patients with these rare and under-recognized disorders.

Perceptions of Digital Technology Experiences and Development Among Family Caregivers and Technology Researchers: Qualitative Study.

BACKGROUND: Caregiving is highly stressful and is associated with poor mental and physical health. Various technologies, including mobile and eHealth apps, have been developed to address caregiver needs. However, there is still a paucity of research examining the technology perceptions of informal caregivers, especially from the perspectives of sex, gender, and diversity. OBJECTIVE: To address the research gap and inform the development of future caregiving technologies, this study aims to examine how family caregivers perceive using technology to assist with their caregiving routines; identify the sex, gender, and diversity factors that shape these perceptions; and understand how these perceptions and needs are reflected within the current technology development process. METHODS: Semistructured interviews were conducted with 16 informal caregivers of individuals with a range of chronic medical conditions and 8 technology researchers involved in caregiving technology projects. RESULTS: Three main themes with subthemes were developed. The first main theme is that caregivers see a need for technology in their lives, and it comprises the following 3 subthemes: caregiving is a challenging endeavor, technology is multifaceted, and caregiver preferences facilitate technology use. The second main theme is that relationships play a vital role in mediating technology uptake, and it comprises the following 2 subthemes: the caregiver-care recipient dynamic shapes technology perceptions and caregivers rely on external sources for technology information. Finally, the third main theme is that barriers are present in the use and adoption of technology, and it comprises the following 2 subthemes: technology may not be compatible with personal values and abilities and technology that is not tailored toward caregivers lacks adoption. CONCLUSIONS: The findings highlight the multifaceted role that technology can play in aiding caregiving while drawing attention to the perceived drawbacks of these technologies among caregivers. The inclusion of technology researchers in this study provides a more holistic understanding of technologies in caregiving from their initial development to their eventual uptake by caregivers.

Knowledge of sex and gender and related information needs in patients with traumatic brain injury: in-depth interview study.

AIM: This research aimed to gain an understanding of biological sex and social gender phenomena experienced by patients with traumatic brain injury in recovery, and to understand the educational needs of this group. METHODS: We conducted semi-structured interviews of 40 adult patients (22 men, 18 women) of different ages, education levels, and ethnicities, with diagnoses of mild and moderate-severe traumatic brain injury at the acute and chronic stages post-injury. RESULTS: Applying classic content analysis with inductive coding, three overarching themes that limited patients' knowledge and subsequent efforts to obtain information on the topic emerged: (1) the complexity of sex and gender subject matters, (2) patients' dependence on others, and (3) uncertainty about the course of recovery. The first diminished the patient's desire to seek further information. Dependence on others and trust that others were in a better position to use the information, compelled patients to redirect the need for education to clinicians, significant others, and the public on the unique post-injury experiences of men and women. Uncertainty about what to expect in the acute phases, and a feeling of identity loss in the chronic phases, established patients' desire to seek out only the information they believed to be necessary for them to carry on with life. CONCLUSIONS: In developing recommendations for patient education, variations in patients' knowledge and desire for information, and the reasons behind these variations, should be considered. Improving injury prognosis requires taking into account the gendered context of injury and recovery from it.IMPLICATIONS FOR REHABILITATIONSex/gender issues in traumatic brain injury are complex; the challenge is identifying which information is most relevant for patients; this research assessed patients' knowledge of and interest in sex/gender-related topics in traumatic brain injury.Evidence shows most patients unable to differentiate between sex and gender, but when asked about living as a man or woman with traumatic brain injury, disturbed gender roles and identities became evident.Gender shapes the health status trajectory and outcomes of patients with traumatic brain injury which becomes evident when attention is paid to patients' personal life stories.To improve traumatic brain injury prognosis, clinicians should tailor management plans taking into account gender, an amalgamation of biological, behavioural, cultural, and social characteristics of their patients.In research, explicit and consistent consideration of the interrelated constructs of sex and gender would produce a better understanding of the different mechanisms that shape the course of traumatic brain injury.

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients.

Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1st March and 31st July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London.

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71-4.26)], presenting with fever [6.21 (1.76-21.99)], dyspnea [2.60 (1.00-6.76)], gastro-intestinal symptoms [7.38 (2.71-20.16)], or higher levels of C-reactive protein [9.43 (0.73-121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28-10.91)], receiving palliative treatment [5.74 (1.15-28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04-4.44)], dyspnea [4.94 (1.99-12.25)], and increased CRP levels [10.35 (1.05-52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01-0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients.

The course and prognostic factors of cognitive outcomes after traumatic brain injury: A systematic review and meta-analysis.

Despite indications that TBI may be a precursor of cognitive decline and subsequent development of Alzheimer's disease, little is known about the time course of this relationship and the factors involved. This systematic review summarizes the evidence pertinent to this subject matter. All English language studies of longitudinal design, and works cited within them, found in six literature databases, were considered, and their quality assessed. Of 65 articles appraised, 44 studies were selected. Results were organized by timing of assessments, injury severity, and cognitive domains assessed. Differences in the course of cognitive performance were observed across injury severity groups and cognitive domains, with differential proportions of reports of improvement, decline, or no change over time. The evidence for genetic, sex-, age-, and injury-related factors as determinants of cognitive outcome was inconsistent. The non-uniform trajectory of cognitive performance post-TBI supports the notion that this construct is non-homogeneous, and that different factors influence its course. Agreement on a core set of predictors and consideration of psychometric properties of outcome measures is needed.

Measuring Change Over Time: A Systematic Review of Evaluative Measures of Cognitive Functioning in Traumatic Brain Injury.

Objectives: The purpose of evaluative instruments is to measure the magnitude of change in a construct of interest over time. The measurement properties of these instruments, as they relate to the instrument's ability to fulfill its purpose, determine the degree of certainty with which the results yielded can be viewed. This work systematically reviews all instruments that have been used to evaluate cognitive functioning in persons with traumatic brain injury (TBI), and critically assesses their evaluative measurement properties: construct validity, test-retest reliability, and responsiveness. Data Sources: MEDLINE, Central, EMBASE, Scopus, PsycINFO were searched from inception to December 2016 to identify longitudinal studies focused on cognitive evaluation of persons with TBI, from which instruments used for measuring cognitive functioning were abstracted. MEDLINE, instrument manuals, and citations of articles identified in the primary search were then screened for studies on measurement properties of instruments utilized at least twice within the longitudinal studies. Study Selection: All English-language, peer-reviewed studies of longitudinal design that measured cognition in adults with a TBI diagnosis over any period of time, identified in the primary search, were used to identify instruments. A secondary search was carried out to identify all studies that assessed the evaluative measurement properties of the instruments abstracted in the primary search. Data Extraction: Data on psychometric properties, cognitive domains covered and clinical utility were extracted for all instruments. Results: In total, 38 longitudinal studies from the primary search, utilizing 15 instruments, met inclusion and quality criteria. Following review of studies identified in the secondary search, it was determined that none of the instruments utilized had been assessed for all the relevant measurement properties in the TBI population. The most frequently assessed property was construct validity. Conclusions: There is insufficient evidence for the validity and reliability of instruments measuring cognitive functioning, longitudinally, in persons with TBI. Several instruments with well-defined construct validity in TBI samples warrant further assessment for test-retest reliability and responsiveness. Registration Number: www.crd.york.ac.uk/PROSPERO/, identifier CRD42017055309.

A gender-transformative approach to improve outcomes and equity among persons with traumatic brain injury.

INTRODUCTION: The initiation and translation of sex-sensitive and gender-sensitive research programmes into clinically useful considerations for patients with traumatic brain injury (TBI) have been difficult. Clinical frameworks are currently not specific according to sex and gender, despite evidence that these constructs influence the incidence, course and outcome of patients with TBI. The present protocol outlines a strategy for a research programme, supported by the Canadian Institutes of Health Research (CIHR) Institute of Gender and Health, which explores sex and gender topics in the context of TBI, with the goal of building an infrastructure to facilitate the implementation of sex/gender-sensitive research findings into clinical considerations. METHODS AND ANALYSIS: A comprehensive multistep research programme is proposed to support three research objectives: (1) documentation of important concepts and ideas for education on topics of sex and gender in the TBI context using a knowledge-user feedback framework, current scientific evidence and the research team's expertise; (2) development of educational materials for patients with TBI, significant others and clinicians providing care that account for sex/gender and (3) testing the application of these educational materials for feasibility and effectiveness. This programme supports the CIHR Institute's mission by facilitating partnership with knowledge users across clinical, research, academic and community sectors, through a range of platforms and activities. ETHICS AND DISSEMINATION: The Research Ethics Board of the University Health Network has approved the programme. It is anticipated that this work will add significant value to the advancement of the field of sex, gender and health by serving as a model to foster the integration of these constructs across the spectrum of disorders. This will transform clinical practices and ensure that generated knowledge is translated into improved training programmes, policies and health services that are responsive to the diverse needs of men and women with TBI. PROSPERO REGISTRATION NUMBER: CRD42018098697.

The course and prognostic factors of cognitive status after central nervous system trauma: a systematic review protocol.

INTRODUCTION: Traumatic brain injury (TBI) is among the most disabling injuries, resulting in a range of cognitive impairments. Traumatic spinal cord injury (SCI) often occurs in conjunction with TBI; the two are best considered together in the context of trauma to the central nervous system (CNS). Despite strong indications of cognitive dysfunction in CNS trauma, little is known about its natural history or relationship with other factors. The current protocol outlines a strategy for a systematic review of the current evidence examining CNS trauma as a prognostic factor of cognitive decline in the adult population. METHODS AND ANALYSIS: The review will be conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All peer-reviewed English language publications with a longitudinal design that focus on cognition in adults (ages 18 and older) with either TBI or SCI, or both from inception to December 2016 found through Medline, Central, Embase, Scopus, PsycINFO, supplemental PubMed and bibliographies of identified articles will be considered eligible. Quality will be evaluated using published guidelines. Results will be grouped by: (1) prognostic factors of cognitive deficits; and (2) development of, or time until development of, cognitive deficit in patients with CNS trauma. Close attention will be paid to the evaluative properties of the measurements used to assess cognition. ETHICS AND DISSEMINATION: The authors will publish findings from this review in a peer-reviewed scientific journal(s) and present the results at national and international conferences. This work will advance scientific certainty regarding natural history and prognostic factors of cognitive status in males and females with CNS trauma, informing clinicians, policymakers and future researchers on the topic. PROSPERO REGISTRATION NUMBER: CRD42017055309.