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The design of drugs from natural products is a re-emerging area due to the need for bioactive compounds. The exploitation of natural products and their derivatives obtained by biocatalysis is in line with the higher attention given today to new sustainable technologies that better preserve the environment (green chemistry). The research field of cytochromes P450 (CYPs) is continuously providing new enzymes and mutants that produce metabolites suitable for late-stage functionalization for new potential drugs. This review provides an overview of the exploitation of CYPs as biocatalysts in drug synthesis. Additionally, recent progress in protein and metabolic engineering is provided to show how these enzymes offer a toolbox that can be combined with other biocatalytic or chemical processes to build new platforms for the green production of new drugs.
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Produtos Biológicos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Preparações Farmacêuticas , Biocatálise , Oxirredução , Engenharia de Proteínas , Especificidade por SubstratoRESUMO
INTRODUCTION: The objective of this study was to comprehensively understand the burden experienced by caregivers (CGs) providing home-based, end-of-life care to patients with cancer. We examined the relationship between objective and subjective burden including whether and how burden changes over time. METHODS: A case series of terminal cancer patient-caregiver dyads (nâ =â 223) were recruited from oncology clinics and followed for 12 months or until patient death. Data were collected every other week and in-person from CGs in their homes using quantitative surveys, diaries, and monthly structured observations. RESULTS: Bivariate correlations revealed a significant association between subjective burden and activities of daily living (ADLs), instrumental activities of daily living (IADL), high-intensity tasks, and time spent on ADLs; these correlations varied over time. Models examining the slope of subjective burden revealed little systematic change; spouse caregiver and patient functional limitations were positively, and Black caregiver was negatively associated with subjective burden. Generally, the slopes for measures of objective burden were significant and positive. Models showed subjective burden was positively associated with most measures of objective burden both within caregiver (concurrent measures were positively associated) and between CGs (those with higher subjective also had higher objective). CONCLUSIONS: Cancer caregiving is dynamic; CGs must adjust to the progression of the patient's disease. We found an association between subjective and objective burden both within and between CGs. Black CGs were more likely to report lower subjective burden compared to their White counterparts. More detailed investigation of the sociocultural components that affect caregiver experience of burden is needed to better understand how and where to best intervene with targeted supportive care services.
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Atividades Cotidianas , Cuidadores , Neoplasias , Humanos , Neoplasias/psicologia , Masculino , Feminino , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso , Assistência Terminal/psicologia , Efeitos Psicossociais da Doença , Adulto , Sobrecarga do Cuidador/psicologia , Idoso de 80 Anos ou maisRESUMO
Studying the complex and intricate retinoids metabolic pathways by chemical biology approaches requires design and synthesis of biologically functional molecular probes. Only few of such molecular retinoid probes could be found in literature, most of them bearing a molecular structure quite different from natural retinoids. To provide close-to-native retinoid probes, we have developed a versatile late-stage method for the insertion of azide function at the C4 position of several retinoids. This one-step process opens straightforward access to different retinoid and carotenoid probes from commercially available precursors. We have further demonstrated that the different molecular probes retain ability of the original compound to activate genes' transcription, despite azide insertion, highlighting biological activities that were further validated in zebrafish inâ vivo model. The present work paves the way to future studies on vitamin A's metabolism.
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The natural product FR900359 (FR) has generated significant attention lately, due to its characteristics as potent and selective inhibitor of Gq/11 mediated signal transduction of associated G protein-coupled receptors (GPCRs). This makes FR both a widely used pharmacological tool compound and a lead molecule for targeted cancer therapy. The exploration of structure-activity-relationship (SAR) of the scaffold by total synthesis has been complicated by its structural complexity and its incompatibility with standard approaches of solid-phase peptide synthesis. Options for late-stage functionalization of FR are limited due to a lack of tractable functional groups. Here we present a mixed approach combining i) genetic engineering of the FR-assembly line in Chromobacterium vaccinii, to obtain a novel FR analog featuring a primary amine, with ii) its subsequent synthetic modification and biological profiling for further SAR exploration of the FR scaffold.
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Replicated secondary contact zones can provide insights into the barriers to gene flow that are important during speciation and can reveal to which degree secondary contact may result in similar evolutionary outcomes. Here, we studied two secondary contact zones between highly differentiated Alpine butterflies of the genus Erebia using whole-genome resequencing data. We assessed the genomic relationships between populations and species and found hybridization to be rare, with no to little current or historical introgression in either contact zone. There are large similarities between contact zones, consistent with an allopatric origin of interspecific differentiation, with no indications for ongoing reinforcing selection. Consistent with expected reduced effective population size, we further find that scaffolds related to the Z-chromosome show increased differentiation compared to the already high levels across the entire genome, which could also hint towards a contribution of the Z chromosome to species divergence in this system. Finally, we detected the presence of the endosymbiont Wolbachia, which can cause reproductive isolation between its hosts, in all E. cassioides, while it appears to be fully or largely absent in contact zone populations of E. tyndarus. We discuss how this rare pattern may have arisen and how it may have affected the dynamics of speciation upon secondary contact.
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Borboletas , Fluxo Gênico , Especiação Genética , Genética Populacional , Hibridização Genética , Isolamento Reprodutivo , Wolbachia , Animais , Borboletas/genética , Wolbachia/genéticaRESUMO
Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators.
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Proteína Glial Fibrilar Ácida , HIV-1 , Humanos , HIV-1/imunologia , HIV-1/patogenicidade , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , África Subsaariana , Proteína Glial Fibrilar Ácida/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Infecções por HIV/patologia , Gânglios da Base/imunologia , Gânglios da Base/patologia , Gânglios da Base/virologia , Proteínas de Ligação ao Cálcio/imunologia , Proteínas de Ligação ao Cálcio/genética , Lobo Frontal/imunologia , Lobo Frontal/patologia , Lobo Frontal/virologia , Proteína do Núcleo p24 do HIV/imunologia , Complexo AIDS Demência/imunologia , Complexo AIDS Demência/patologia , Complexo AIDS Demência/virologia , Antígenos CD4/imunologia , Linfócitos T CD8-Positivos/imunologia , Gliose/imunologia , Gliose/patologia , Gliose/virologia , Astrócitos/imunologia , Astrócitos/patologia , Astrócitos/virologia , Encéfalo/patologia , Encéfalo/imunologia , Encéfalo/virologia , Proteínas dos MicrofilamentosRESUMO
There are many indole alkaloids that contain diverse functional groups attached to the benzene ring on the indole core. Promising biological activities of these alkaloids have been reported. Herein, we report the indole C5-selective bromination of indolo[2,3-a]quinolizidine alkaloids by adding nearly equimolar amounts of Br3 â PyH and HCl in MeOH. The resulting reaction plausibly proceeds through an indoline intermediate by the nucleophilic addition of MeOH to the C3-brominated indolenine intermediate. Data support the intermediacy of a C3-, C5-dibrominated indolenine intermediate as a brominating agent. These conditions demonstrate excellent selectivity for indole C5 bromination of natural products and their derivatives. Thus, these simple, mild, and metal-free conditions allow for selective, late-stage bromination followed by further chemical modifications. The utility of the brominated product prepared from naturally occurring yohimbine was demonstrated through various derivatizations, including a bioinspired heterodimerization reaction.
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An efficient and rapid protocol for the oxidative halogenation of tryptamines with 10 % aqueous NaClO has been developed. This reaction is featured by its operational simplicity, metal-free conditions, no purification, and high yield. Notably, the resulting key intermediates are suitable for further functionalization with various nucleophiles, including amines, N-aromatic heterocycles, indoles and phenols. The overall transformation exhibits broad functional-group tolerance and is applicable to the late-stage functionalization of complex biorelevant molecules.
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Anilines are core motifs in a variety of important molecules including medicines, materials and agrochemicals. We report a straightforward procedure that allows access to new chemical space of anilines via their para-C-H alkylation. The method utilizes commercially available catalytic H2 O â B(C6 F5 )3 and is highly selective for para-C-alkylation (over N-alkylation and ortho-C-alkylation) of anilines, with a wide scope in both the aniline substrates and alkene coupling partners. Readily available alkenes are used, and include new classes of alkene for the first time. The mild reaction conditions have allowed the procedure to be applied to the late-stage-functionalization of non-steroidal anti-inflammatory drugs (NSAIDs), including fenamic acids and diclofenac. The formed novel NSAID derivatives display improved anti-inflammatory properties over the parent NSAID structure.
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Alcenos , Compostos de Anilina , Alcenos/química , Compostos de Anilina/química , Alquilação , Anti-Inflamatórios não Esteroides , CatáliseRESUMO
Using organic dyes as photocatalysts is an innovative approach to photocatalytic organic transformations. These dyes offer advantages such as widespread availability, adaptable absorption properties, and diverse chemical structures. Recent progress has led to the development of organic photocatalysts that can utilize visible light to modify chemically inert C-H bonds. These catalysts are sustainable, selective, and versatile, enabling mild reactions, late-stage functionalization, and various transformations in line with green chemistry principles. As catalysts in photoredox chemistry, they contribute to the development of efficient and environmentally friendly synthetic pathways. Acridinium-based organic photocatalysts have proved valuable in late-stage C-H functionalization, enabling transformative reactions under mild conditions. This review emphasizes their innovative features, such as organic frameworks, efficient light absorption properties, and their applications in modifying complex molecules. It provides an overview of recent advancements in the use of acridinium-based organic photocatalysts for late-stage C-H bond functionalization without the need for transition metals, showcasing their potential to expedite the development of new molecules and igniting excitement about the prospects of this research in the field.
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Developed here is a robust electrochemical cross-coupling reaction between aroyl hydrazine and NH-sulfoximine via concomitant cleavage and formation of C(sp2 )-N bonds with the evolution of H2 and N2 as innocuous by-products. This sustainable protocol avoids the use of toxic reagents and occurs at room temperature. The reaction proceeds via the generation of an aroyl and a sulfoximidoyl radical via anodic oxidation under constant current electrolysis (CCE), affording N-aroylated sulfoximine. The strategy is applied to late-stage sulfoximidation of L-menthol, (-)-borneol, D-glucose, vitamin-E derivatives, and marketed drugs such as probenecid, ibuprofen, flurbiprofen, ciprofibrate, and sulindac. In addition, the present methodology is mild, high functional group tolerance with broad substrate scope and scalable.
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INTRODUCTION: Screening of cancer is the maximum effort and critical element for providing health related care in order to decrease cancer related dealt because of the disease burden is in its advanced stages. Unfortunately, advanced-stage presentation and late diagnosis of cancers endure a problem in low-income countries including Ethiopia. However, there is scarcity of published articles about the problem in Ethiopia. OBJECTIVE: This study aimed to assess the prevalence of advanced-stage -stage presentation of cancer at the time of diagnosis and associated factors among adult cancer patients at Northwest Amhara comprehensive Specialized Hospitals, oncology treatment units, Northwest Ethiopia, 2022. METHODS: An institution based cross-sectional study was conducted in Northwest Amhara public referral hospitals on 422 study participants. A systematic random sampling technique was performed. The data were collected through face to face interview and document review via structured, pretested questionnaires. Epi. Data version 4.6 and Stata version 14.0 software's were used for data entry and analysis respectively. Logistic regression were carried out to recognize factors associated with advanced-stage -stage presentation of cancer at the time of diagnosis. Adjusted odds ratio with a 95% confidence interval were used to measure the strength of association. Variables having p-value less than 0.2 in bivariable analysis were entered in to multivariable analysis; variables with a p-value < 0.05 were declared significantly associated with advanced-stage -stage presentation of cancer at the time of diagnosis. RESULTS: The overall prevalence of advanced-stage presentation of cancer at the time of diagnosis was found to be 67.57%. Age ≥ 60 years old patients (AOR = 6.10, 95%: (1.16-32.1)), patients had have a feeling of burden (AOR = 1.82, 95%, CI: (1.04-3.20)), and cancer patients with comorbidity illness (AOR = 2.40, 95%, CI: (1.40-4.12)) were significantly associated with advanced-stage presentation of cancer at the time of diagnosis. CONCLUSION: The prevalence of advanced-stage presentation of cancer at the time of diagnosis was found to be high. Its better, health care providers in oncology treatment facilities need to give special attention to older patients, having feeling of burden and cancer patient with comorbidity to reduce the risk of developing late stage presentation of cancer.
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Neoplasias , Adulto , Humanos , Pessoa de Meia-Idade , Etiópia/epidemiologia , Estudos Transversais , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Instalações de Saúde , HospitaisRESUMO
BACKGROUND: In Saudi Arabia, approximately one-third of colorectal cancer (CRC) patients are diagnosed at an advanced stage. Late diagnosis is often associated with a worse prognosis. Understanding the risk factors for late-stage presentation of CRC is crucial for developing targeted interventions enabling earlier detection and improved patient outcomes. METHODS: We conducted a retrospective cohort study on 17,541 CRC patients from the Saudi Cancer Registry (1997-2017). We defined distant CRCs as late-stage and localized and regional CRCs as early-stage. To assess risk factors for late-stage CRC, we first used multivariable logistic regression, then developed a decision tree to segment regions by late-stage CRC risk, and finally used stratified logistic regression models to examine geographical and sex variations in risk factors. RESULTS: Of all cases, 29% had a late-stage diagnosis, and 71% had early-stage CRC. Young (< 50 years) and unmarried women had an increased risk of late-stage CRC, overall and in some regions. Regional risk variations by sex were observed. Sex-related differences in late-stage rectosigmoid cancer risk were observed in specific regions but not in the overall population. Patients diagnosed after 2001 had increased risks of late-stage presentation. CONCLUSION: Our study identified risk factors for late-stage CRC that can guide targeted early detection efforts. Further research is warranted to fully understand these relationships and develop and evaluate effective prevention strategies.
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Neoplasias Colorretais , Estadiamento de Neoplasias , Sistema de Registros , Humanos , Arábia Saudita/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Fatores de Risco , Adulto , Diagnóstico Tardio/estatística & dados numéricos , Fatores Sexuais , Detecção Precoce de CâncerRESUMO
BACKGROUND: Patients in late-stage Parkinson's disease (PDLS) are caregiver-dependent, have low quality of life, and higher healthcare costs. OBJECTIVE: To estimate the prevalence of PDLS patients in the current US healthcare system. METHODS: We downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 US healthcare sites. PD was identified using standard diagnosis codes, and PDLS was identified by the usage of wheelchair dependence, personal care assistance, and/or presence of diagnoses of dementia. Age of PDLS identification and survival information were obtained and stratified by demographic and the disability subgroups. RESULTS: We identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fitted our definition of PDLS (n = 194,297), and 10.2% met two or more late-stage criteria. Among all PDLS, the mean age of PDLS identification was 78.1 (±7.7) years, and 49% were already reported as deceased. PDLS patients were predominantly male (58.5%) with similar distribution across PDLS subgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information >90% (n = 53,162) were White, 8.2% (n = 5121) Hispanic/Latino, 7.8% (n = 4557) Black, and <0.01% (n = 408) Asian. Of the PDLS cohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair-bound. CONCLUSIONS: Late-stage patients are a significant part of the PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. OBJECTIVE: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. METHODS: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. RESULTS: During the 3-month period, the costs were 20,573 (France), 19,959 (Germany), 18,319 (the Netherlands), 25,649 (Sweden), and 12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. CONCLUSION: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Doenças Neurodegenerativas , Doença de Parkinson , Transtornos Parkinsonianos , Humanos , Transtornos Parkinsonianos/epidemiologia , Transtornos Parkinsonianos/terapia , Europa (Continente)/epidemiologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/terapia , AlemanhaRESUMO
An electrochemical N-acylation of sulfoximine has been achieved via the coupling of α-keto acids and NH-sulfoximines. This process involves the sequential cleavage of C-C bond followed by C(sp2)-N bond formation, with the liberation of H2 and CO2 as the by-products. A library of N-aroylated sulfoximines is produced via the coupling of aroyl and sulfoximidoyl radicals by anodic oxidation under constant current electrolysis (CCE). The compatibility of the present protocol has been demonstrated by coupling of various bio-active compounds, such as NH-sulfoximine derived from (-)-borneol, L-menthol, D-glucose derivative, and some commercial drugs such as flurbiprofen, and ibuprofen. This late-stage functionalization highlights the importance of this sustainable protocol. Besides this, various control experiments and detection of H2 evolution have been performed to support the proposed mechanism.
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The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear), and from deceased controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e., interplay) between the proteins in each group. More proteins were increased in early-OA versus controls than late-stage OA versus controls. For most of these proteins, the fold changes between late-stage OA versus controls and early-stage OA versus controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.
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Osteoartrite do Joelho , Líquido Sinovial , Humanos , Espectrometria de Massas , Osteoartrite do Joelho/metabolismo , Proteoma/metabolismo , Proteômica/métodos , Líquido Sinovial/químicaRESUMO
A 12-keto-type oleanolic acid derivative (4) has been identified as a potent anti-human immunodeficiency virus type-1 (HIV-1) compound that demonstrates synergistic effects with several types of HIV-1 neutralizing antibodies. In the present study, we used a common key synthetic intermediate to carry out the late-stage derivatization of an anti-HIV compound based on the chemical structure of a 12-keto-type oleanolic acid derivative. To execute this strategy, we designed a diketo-type oleanolic acid derivative (5) for chemoselective transformation, targeting the carboxy group and the hydroxyl group on the statine unit, as well as the 3-carbonyl group on the oleanolic acid unit, as orthogonal synthetic handles. We carried out four types of chemoselective transformations, leading to identification of the indole-type derivative (16) as a novel potent anti-HIV compound. In addition, further optimization of the ß-hydroxyl group on the statine unit provided the R-4-isobutyl γ-amino acid-type derivative (6), which exhibited potent anti-HIV activity comparable to that of 4 but with reduced cytotoxicity.
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HIV-1 , Ácido Oleanólico , Ácido Oleanólico/químicaRESUMO
BACKGROUND: Older adults with major depression are at risk of frailty and long-term care needs. Consequently, screening for major depression is imperative to prevent such risks. In Japan, the Late-Stage Elderly Questionnaire was developed to evaluate older adults' holistic health, including mental well-being. It comprises one specific question to gauge life satisfaction, but the effectiveness of this question to screen for major depression remains unclear. Therefore, we aimed to assess the usability of this question to screen for major depression. METHODS: This retrospective cohort study used a large, commercially available claims database in Japan. Participants were older adults aged ≥75 years who completed the Late-Stage Elderly Questionnaire and were classified with and without new major depression within 1 year. We evaluated the questionnaire's ability to screen for major depression using C-statistics, developing three models to assess the cut-off value based on responses to the life satisfaction question ('Satisfied', 'Somewhat satisfied', 'Somewhat unsatisfied', or 'Unsatisfied'), estimating the sensitivity and specificity of each model. RESULTS: Among 11 117 older adults, 77 newly experienced major depression within 1 year. The C-statistic for screening major depression was 0.587. The model setting the cut-off between 'Somewhat unsatisfied' and 'Unsatisfied' the demonstrated lowest sensitivity and highest specificity, while the model setting the cut-off between 'Satisfied' and 'Somewhat satisfied' demonstrated highest sensitivity and lowest specificity. CONCLUSIONS: Our results suggest that due to its poor screening ability and high rate of false negatives, the question assessing life satisfaction in the Late-Stage Elderly Questionnaire may not be useful for screening major depression in older adults and may require modification.
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Transtorno Depressivo Maior , Programas de Rastreamento , Humanos , Idoso , Japão , Masculino , Feminino , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Inquéritos e Questionários , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Programas de Rastreamento/métodos , Satisfação Pessoal , Avaliação Geriátrica/métodos , Sensibilidade e Especificidade , População do Leste AsiáticoRESUMO
CONTEXT: Among many unanticipated changes, access to rehabilitation was disrupted during the onset of the COVID-19 pandemic. It is unclear how the timing of late-stage rehabilitation following anterior cruciate ligament with surgical reconstruction (ACLR) during the initial months of the pandemic affected outcomes. The purpose of this study was to compare physical performance outcome measures in patients following ACLR prior to and following COVID-19-related restrictions. DESIGN: Retrospective cohort study. METHODS: Data from patients who underwent return-to-sport testing following ACLR were analyzed based on date. December 2018 through March of 2020 (n = 66) was defined as the baseline period, and June through October 2020 (n = 27) was defined as the surveillance period. Outcome measures included single leg hop, triple hop, single leg vertical jump, and the lower-extremity functional test (LEFT). Linear mixed models were used to compare outcome measures before and after the onset of pandemic-related restrictions, clustered by sex and sport. A 1-way analysis of variance was performed to analyze the association between the number of virtual rehabilitation visits and outcome measures for subjects in the surveillance period. RESULTS: Subjects in the surveillance period performed significantly worse in the LEFT (+7.88 s; 95% confidence interval, 1.11 to 14.66; P = .02) and single leg vertical jump on the unaffected side (-4.32 cm; 95% confidence interval, -7.44 to -1.19, P < .01), and performed better with single leg vertical jump symmetry (+6.3%; 95% confidence interval, 1.0% to 11.5%; P = .02). There were no other statistically significant differences. There was no significant association between having virtual rehabilitation visits and any of the performance outcomes. CONCLUSIONS: There was a decline in physical performance outcome measures in patients following ACLR who did not attend regular in-person physical therapy sessions in the late-stage rehabilitation due to COVID-19-related restrictions. Other factors during this unique time period, such as access to training facilities or psychosocial stressors, may have also influenced outcomes.