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The global demographic and epidemiological transition have led to a rapidly increasing burden of cancer, particularly among older adults. There are scant data on the prevalence and demographic pattern of cancer in older Indian persons. This was a multicentric observational study conducted between January 2019 and December 2020. Data were retrieved from existing electronic databases to gather information on two key variables: the total number of patients registered with oncologists and the number of patients aged 60 years and above. The primary objective was to determine the percentage of older adults among patients with cancer served by these hospitals. Secondary objectives included understanding the prevalence of different types of cancer in the older population, and the sex- and geographic distribution of cancer in older Indian patients. We included 272,488 patients with cancer from 17 institutes across India. Among them, 97,962 individuals (36â¯%) were aged 60 years and above. The proportion of older adults varied between 20.6â¯% and 53.6â¯% across the participating institutes. The median age of the older patients with cancer was 67 (interquartile range, 63-72) years. Of the 54,281 patients for whom the details regarding sex were available, 32,243 (59.4â¯%) were male. Of the 56,903 older patients, head and neck malignancies were the most prevalent, accounting for 11,158 cases (19.6â¯%), followed by breast cancer (6260 cases, 11â¯%), genitourinary cancers (6242 cases, 10.9â¯%), lung cancers (6082 cases, 10.7â¯%), hepatopancreaticobiliary (6074, 10.7â¯%), and hematological malignancies (5226 cases, 9.2â¯%). Over one-third of Indian patients with cancer are aged 60 years and above, with a male predominance. Head and neck, breast, and genitourinary cancers are the most prevalent in this age group. Characterizing the burden of cancer in older adults is crucial to enable tailored interventions and additional research to improve the care and support for this vulnerable population.
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BACKGROUND AND OBJECTIVE: Gait impairment leads to increased dependence, morbidity, institutionalization, and mortality in older people. We intended to assess gait parameters with the continuum of cognitive impairment and observe variation with the severity of cognitive impairment. MATERIALS AND METHODS: This cross-sectional, observational study was conducted at the memory clinic of a tertiary care center. One hundred and twelve subjects were recruited, and cognition was assessed by the Clinical Dementia Rating scale. Usual gait was assessed by a 6-m walk test, and the dynamic gait was assessed using Biodex Gait Trainer™. Apart from crude analysis, adjusted linear regression was used to find the association of spatiotemporal gait parameters with cognitive decline. RESULTS: Subjects were divided into subjective cognitive decline (SCD; n = 38), mild cognitive impairment (MCI; n = 40), and major neurocognitive disorder (MNCD; n = 34) groups. History of falls (23.7% vs. 30.0% vs. 67.7%, P < 0.001) and impaired activities of daily living (ADLs) (5.3% vs. 15.0% vs. 100%, P < 0.001) were significantly higher with cognitive decline. Age- and gender-adjusted regression analysis revealed that usual gait speed (0.8 vs. 0.6 vs. 0.5, P < 0.001) (m/s), total time (3.9 vs. 2.9 vs. 2.6, P = 0.022) (min), total distance (65.6 vs. 55.8 vs. 46.6, P = 0.025) (m), step cycle time (0.6 vs. 0.8 vs. 0.8, P = 0.020) (cycles/s), and step lengths were significant. CONCLUSION: Gait speed and other parameters worsened with increasing cognitive impairment. Changes in gait parameters might be a useful marker of declining cognition, though a long-term follow-up study is required to establish this association. Early intervention could be beneficial in preserving autonomy in patients with cognitive impairment.
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Disfunção Cognitiva , Marcha , Humanos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/fisiopatologia , Masculino , Estudos Transversais , Feminino , Idoso , Marcha/fisiologia , Pessoa de Meia-Idade , Atividades Cotidianas , Idoso de 80 Anos ou maisRESUMO
Introduction: SuperAgers (SA) are older adults who exhibit cognitive capacities comparable to individuals who are three or more decades younger than them. The current study aimed to identify the characteristics of Indian SA by categorizing 55 older adults into SA and Typical Older Adults (TOA) and comparing their performance with a group of 50 younger participants (YP) (aged 25-50). Methods: A total of 105 participants were recruited after obtaining informed written consent. The cognitive abilities of the participants were assessed using Wechsler Adult Intelligence Scale (WAIS)-IVINDIA, Color Trails Test, Boston Naming Test (BNT), and Rey Auditory Verbal Learning Test. Results: SA outperformed TOA in all cognitive assessments (P < 0.001) and surpassed YP in BNT and WAIS-IV. SA's delayed recall scores were notably higher (12.29 ± 1.51) than TOA (6.32 ± 1.44). Conclusion: SA excelled in all cognitive domains demonstrating resilience to age-related cognitive decline. This study highlights Indian SuperAgers' exceptional cognitive prowess.
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INTRODUCTION: Frailty, characterized by ageing-related vulnerability, influences outcomes in older adults. Our study aimed to investigate the relationship between frailty and clinical outcomes in older Indian patients with cancer. MATERIALS AND METHODS: Our observational single-centre study, conducted at Tata Memorial Hospital from February 2020 to July 2022, enrolled participants aged 60 years and above with cancer. Frailty was assessed using the Clinical Frailty Scale (CFS), G8, and Vulnerable Elders Survey (VES)-13. The primary objective was to explore the correlation between baseline frailty and overall survival. Statistical analyses include Kaplan-Meier, Cox proportional hazards, and Harrell's C test. RESULTS: A total of 1,177 patients (median age 68, 76.9% male) were evaluated in the geriatric oncology clinic. Common malignancies included lung (40.0%), gastrointestinal (35.8%), urological (11.9%), and head and neck (9.0%), with 56.5% having metastatic disease. Using CFS, G8, and VES-13 scales, 28.5%, 86.4%, and 38.0% were identified as frail, respectively. Median follow-up was 11.6 months, with 43.3% deaths. Patients fit on CFS (CFS 1-2) had a median survival of 28.02 months, pre-frail (CFS 3-4) 13.24 months, and frail (CFS ≥5) 7.79 months (p < 0.001). Abnormal G8 (≤14) and VES-13 (≥3) were associated with significantly lower median survival (p < 0.001). Multivariate analysis confirmed CFS's predictive power for mortality (p < 0.001), with hazard ratios [HRs] for pre-frail at 1.61(95% confidence interval [CI] 1.25 to 2.06) and frail at 2.31 (95%CI 1.74 to 3.05). G8 ≤ 14 had HR 2.00 (95%CI 1.42 to 2.83), and abnormal VES-13 had HR 1.36 (95%CI 1.11-1.67). In the likelihood ratio test, CFS significantly improved the model fit (p < 0.001). Harrell's C index for survival prediction was 0.62 for CFS, 0.54 for G8, and 0.58 for VES-13. DISCUSSION: In conclusion, our study highlights varying frailty prevalence and prognostic implications in older Indian patients with cancer, emphasizing the need for personalized care in oncology for this aging population. We would recommend using CFS as a tool to screen for frailty for older Indian patients with cancer.
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Fragilidade , Neoplasias , Humanos , Masculino , Idoso , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Neoplasias/terapia , Neoplasias/patologia , Prognóstico , Modelos de Riscos Proporcionais , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Polypharmacy and potentially inappropriate medication (PIM) use are common problems in older adults. Safe prescription practices are a necessity. The tools employed for the identification of PIM sometimes do not concur with each other. METHODS: A retrospective analysis of patients ≥60 years who visited the Geriatric Oncology Clinic of the Tata Memorial Hospital, Mumbai, India from 2018 to 2021 was performed. Beer's-2015, STOPP/START criteria v2, PRISCUS-2010, Fit fOR The Aged (FORTA)-2018, and the EU(7)-PIM list-2015 were the tools used to assess PIM. Every patient was assigned a standardized PIM value (SPV) for each scale, which represented the ratio of the number of PIMs identified by a given scale to the total number of medications taken. The median SPV of all five tools was considered the reference standard for each patient. Bland-Altman plots were utilized to determine agreement between each scale and the reference. Association between baseline variables and PIM use was determined using multiple logistic regression analysis. RESULTS: Of the 467 patients included in this analysis, there were 372 (79.66%) males and 95 (20.34%) females with an average age of 70 ± 5.91 years. The EU(7)-PIM list was found to have the highest level of agreement given by a bias estimate of 0.010, the lowest compared to any other scale. The 95% CI of the bias was in the narrow range of -0.001 to 0.022, demonstrating the precision of the estimate. In comparison, the bias (95%) CI of Beer's criteria, STOPP/START criteria, PRISCUS list, and FORTA list were -0.039 (-0.053 to -0.025), 0.076 (0.060 to 0.092), 0.035 (0.021 to 0.049), and -0.148 (-0.165 to -0.130), respectively. Patients on polypharmacy had significantly higher PIM use compared to those without (OR = 1.47 (1.33-1.63), p = <0.001). CONCLUSIONS: The EU(7)-PIM list was found to have the least bias and hence can be considered the most reliable among all other tools studied.
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Prescrição Inadequada , Neoplasias , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Humanos , Feminino , Masculino , Idoso , Neoplasias/tratamento farmacológico , Índia , Estudos Retrospectivos , Prescrição Inadequada/estatística & dados numéricos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodosRESUMO
OBJECTIVES: To identify factors associated with malnutrition (undernutrition and overnutrition) and determine appropriate cut-off values for mid-arm circumference (MAC) and calf circumference (CC) among community-dwelling Indian older adults. DESIGN: Data from the first wave of harmonised diagnostic assessment of dementia for Longitudinal Ageing Study in India (LASI-DAD) were used. Various sociodemographic factors, comorbidities, geriatric syndromes, childhood financial and health status were included. Anthropometric measurements included body mass index (BMI), MAC and CC. SETTING: Nationally representative cohort study including 36 Indian states and union territories. PARTICIPANTS: 4096 older adults aged >60 years from LASI DAD. OUTCOME MEASURES: The outcome variable was BMI, categorised as low (<18.5 kg/m2), normal (18.5-22.9 kg/m2) and high (>23 kg/m2). The cut-off values of MAC and CC were derived using ROC curve with BMI as the gold standard. RESULTS: 902 (weighted percentage 20.55%) had low BMI, 1742 (44.25%) had high BMI. Undernutrition was associated with age, wealth-quintile and impaired cognition, while overnutrition was associated with higher education, urban living and comorbidities such as hypertension, diabetes and chronic heart disease. For CC, the optimal lower and upper cut-offs for males were 28.1 cm and >31.5 cm, respectively, while for females, the corresponding values were 26 cm and >29 cm. Similarly, the optimal lower and upper cut-offs for MAC in males were 23.9 cm and >26.9 cm, and for females, they were 22.5 cm and >25 cm. CONCLUSION: Our study identifies a high BMI prevalence, especially among females, individuals with higher education, urban residents and those with comorbidities. We establish gender-specific MAC and CC cut-off values with significant implications for healthcare, policy and research. Tailored interventions can address undernutrition and overnutrition in older adults, enhancing standardised nutritional assessment and well-being.
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Antropometria , Desnutrição , Hipernutrição , Idoso , Feminino , Humanos , Masculino , Envelhecimento , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Índia/epidemiologia , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
Understanding the factors influencing survival in oldest old population is crucial for providing appropriate care and improving outcomes. This prospective observational study aimed to investigate the determinants of survival in acutely ill oldest old patients during acute hospitalization and 1-month follow-up. Various geriatric domains and biochemical markers were assessed. Among the 70 included patients with a median age of 87 (Inter quartile range: 85-90), the presence of diabetes, delirium, tachypnea, and high sirtuin-5 levels were associated with reduced in-hospital survival. Non-survivors had raised levels of Sirtuin 1 and Sirtuin 5, with an increase of 43% and 70%, respectively. At 1 month, delirium and diabetes were still associated with reduced survival. These findings suggest that type-2 diabetes, delirium, tachypnea, and high sirtuin-5 levels could serve as predictors of reduced survival in acutely ill, hospitalized oldest old patients.
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Geriatric oncology in India is relatively new. The number of older persons with cancer is increasing exponentially; at our institution, 34% of patients registered are 60 years and over. Apart from the Tata Memorial Hospital in Mumbai, there are currently no other Indian centers that have a dedicated geriatric oncology unit. Geriatric assessments (GAs) are done sporadically, and older patients with cancer are usually assessed and treated based on clinical judgement. Challenges to increasing the uptake of GA include a lack of training/time/interest or knowledge of the importance of the GA. Other challenges include a lack of trained personnel with expertise in geriatric oncology, and a paucity of research studies that seek to advance the outcomes in older Indian patients with cancer. We anticipate that over the next 10 years, along with the inevitable increase in the number of older persons with cancer in India, there will be a commensurate increase in the number of skilled personnel to care for them. Key goals for the future include increased research output, increased number of dedicated geriatric oncology units across the country, India-specific geriatric oncology guidelines, geriatric oncology training programs, and a focus on collaborative work across India and with global partners. In this narrative review, we provide a broad overview of the status of geriatric oncology in India, along with a description of the work done at our center. We hope to spark interest and provide inspiration to readers to consider developing geriatric oncology services in other settings.
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Malnutrition in low- and middle-income countries causes cognitive decline and other health problems. Harmonized Diagnostic Assessment of Dementia for Longitudinal Aging Study in India (LASI DAD) is an extensive study on late-life cognition and dementia. This study examines the link between nutrition and cognitive abilities in older adults using data from the LASI DAD. We conducted descriptive statistics on nutritional parameters (body-mass index, waist-hip ratio, and Mini-Nutritional Assessment), cognitive functions, and socio-demographic variables in 2,892 adults aged ≥60 years. Cognitive domains assessed included delayed recall, orientation, language, executive function, abstract reasoning, and attention. Cognitive impairment was defined as impaired performance in two or more domains. Mean age was 69.3 ± 7.1 years, 52.9% were female, and 57.5% were illiterate. Low body-mass index (adjusted OR: 1.88, p < .001), at risk of malnutrition (adjusted OR: 1.89, p < .001) and malnourished (adjusted OR: 2.86, p < .001) on Mini-Nutritional Assessment were associated with the presence of cognitive impairment. Better cognitive performance was associated with increased body mass index (adjusted OR: 0.74, p-.03), hemoglobin (adjusted OR: 0.91, p-.006), and serum albumin (adjusted OR: 0.38, p < .001). This study shows that nutritional status assessed by anthropometric measures and blood markers is strongly linked to cognitive performance in older adults.
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INTRODUCTION: The number of older patients with cancer is increasing exponentially worldwide, and a similar trend has also been noted in India. The Multidimensional Prognostic Index (MPI) strongly correlates the presence of individual comorbidities with mortality, and the Onco-MPI prognosticates patients accurately for overall mortality. However, limited studies have evaluated this index in patient populations beyond Italy. We evaluated the performance of the Onco-MPI index in predicting mortality in older Indian patients with cancer. MATERIALS AND METHODS: This observational study was conducted between October 2019 and November 2021 in the Geriatric Oncology Clinic at Tata Memorial Hospital in Mumbai, India. The data of patients aged ≥60 years with solid tumors who underwent a comprehensive geriatric assessment was analysed. The study's primary aim was to calculate the Onco-MPI for patients in the study and correlate it with one-year mortality. RESULTS: A total of 576 patients aged ≥60 years were included in the study. The median age (range) of the population was 68 (60-90) years, and 429 (74.5%) were male. After a median follow-up of 19.2 months, 366 (63.7%) patients had died. The proportion of patients classified as low risk (0-0.46), moderate risk (0.47-0.63) and high risk (0.64-1.0) were 38% (219 patients), 37% (211 patients) and 25% (145 patients), respectively. There was a significant difference in one-year mortality rates between the low-risk patients compared to medium and high-risk patients (40.6% vs 53.1% vs 71.7%; p < 0.001). DISCUSSION: The current study validates the Onco-MPI as a predictive tool for estimating short-term mortality in older Indian patients with cancer. Further prospective studies need to build on this index to obtain a score with greater discrimination in the Indian population.
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Neoplasias , Idoso , Humanos , Masculino , Feminino , Estudos Prospectivos , Prognóstico , Avaliação Geriátrica/métodos , Fatores de TempoRESUMO
Background: Intrinsic capacity (IC) is conceptualized by World Health Organization (WHO) with a focus on healthy aging. Identifying impairment could help in making a person-centred plan for the care of older adults. Objectives: Establish the prevalence of IC among community-dwelling older adults age >60, the prevalence of impairment in each domain, and identify factors associated with an impairment in IC. Methods: This cross-sectional observational study in the community setting included 1000 older adults aged 60 years and above in two-year study period. The 6 domains of IC including cognition, locomotor capacity, psychological, vitality, hearing, and vision were derived from the comprehensive geriatric assessment. The IC composite score was calculated based on these domains, and a higher IC score indicated greater IC. Results: During the study period, 1000 older adults, with the median age of 66.5 (IQR-63-73) were included, and 629 (62.9%) were women. Only in 157 (15.7%) community-dwelling older adults, all 6 domains were intact. Impairment in one, two, and three domains was seen in 442 (42.2%), 305 (30.5%), and 91 (9.1%), respectively. The most prevalent impaired domain was locomotor (593, 59.3%), followed by vision (441, 44.1%), hearing (193, 19.3%), cognition (106, 10.6%), mood (38, 3.8%), and vitality (37, 3.7%). The factors associated with lower IC included increasing age (ß-coefficient -0.01, 95% CI: -0.02 to -0.01, p value = 0.002), impaired activities of daily living (ß-coefficient -0.13, 95% CI: -0.49 to -0.18, p value <0.001), and chronic neurologic illness (ß-coefficient -0.10, 95% CI: -0.77 to -0.18, p value = 0.001). Conclusions: In conclusion, we found that impairment in IC was frequent in community-dwelling older adults, and it is associated with age, presence of chronic neurologic illness, and declining functionality. The adoption of IC should be seen as an opportunity to disseminate geriatric care in our healthcare systems which lack the necessary attention to the needs of older persons.
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BACKGROUND: The coronavirus disease (COVID) pandemic caused disruption globally and was particularly distressing in low- and middle-income countries such as India. This study aimed to provide population representative estimates of COVID-related outcomes in India over time and characterize how COVID-related changes and impacts differ by key socioeconomic groups across the life course. METHODS: The sample was leveraged from an existing nationally representative study on cognition and dementia in India: Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). The wave-1 of LASI-DAD enrolled 4096 older adults aged 60 years and older in 3316 households from 18 states and union territories of India. Out of the 3316 LASI-DAD households, 2704 with valid phone numbers were contacted and invited to participate in the Real-Time Insights COVID-19 in India (RTI COVID-India) study. RTI COVID-India was a bi-monthly phone survey that provided insight into the individual's knowledge, attitudes, and behaviour towards COVID-19 and changes in the household's economic and health conditions throughout the pandemic. The survey was started in May 2020 and 9 rounds of data have been collected. FINDINGS TILL DATE: Out of the 2704 LASI-DAD households with valid phone numbers, 1766 households participated in the RTI COVID-India survey at least once. Participants were in the age range of 18-102 years, 49% were female, 66% resided in rural area. Across all rounds, there was a higher report of infection among respondents aged 60-69 years. There was a greater prevalence of COVID-19 diagnosis reported in urban (23.0%) compared to rural areas (9.8%). Respondents with higher education had a greater prevalence of COVID-19 diagnosis compared to those with lower or no formal education. Highest prevalence of COVID-19 diagnosis was reported from high economic status compared to middle and low economic status households. Comparing education gradients in experiencing COVID-19 symptoms and being diagnosed, we observe an opposite pattern: respondents with no formal schooling reported the highest level of experiencing COVID-19 symptoms, whereas the greatest proportion of the respondents with secondary school or higher education reported being diagnosed with COVID-19. FUTURE PLANS: The study group will analyse the data collected showing the real-time changes throughout the pandemic and will make the data widely available for researchers to conduct further studies.
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COVID-19 , Demência , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Adolescente , Adulto Jovem , Adulto , Idoso de 80 Anos ou mais , Masculino , COVID-19/epidemiologia , Teste para COVID-19 , Envelhecimento , Fatores Socioeconômicos , Índia/epidemiologiaRESUMO
The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD) is a nationally representative in-depth study of cognitive aging and dementia. We present a publicly available dataset of harmonized cognitive measures of 4,096 adults 60 years of age and older in India, collected across 18 states and union territories. Blood samples were obtained to carry out whole blood and serum-based assays. Results are included in a venous blood specimen datafile that can be linked to the Harmonized LASI-DAD dataset. A global screening array of 960 LASI-DAD respondents is also publicly available for download, in addition to neuroimaging data on 137 LASI-DAD participants. Altogether, these datasets provide comprehensive information on older adults in India that allow researchers to further understand risk factors associated with cognitive impairment and dementia.
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Disfunção Cognitiva , Demência , Idoso , Humanos , Envelhecimento , Demência/genética , Genômica , Estudos Longitudinais , ÍndiaRESUMO
INTRODUCTION: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. METHODS: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informant interview in 2018 through 2020. We obtained a clinical consensus rating of dementia status for a subsample (N = 2528), fitted a logistic model for dementia status on this subsample, and then imputed dementia status for all other LASI respondents aged 60+ (N = 28,949). RESULTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%, with significant age and education gradients, sex and urban/rural differences, and cross-state variation. DISCUSSION: An estimated 8.8 million Indians older than 60 years have dementia. The burden of dementia cases is unevenly distributed across states and subpopulations and may therefore require different levels of local planning and support. HIGHLIGHTS: The estimated dementia prevalence for adults ages 60+ in India is 7.4%. About 8.8 million Indians older than 60 years live with dementia. Dementia is more prevalent among females than males and in rural than urban areas. Significant cross-state variation exists in dementia prevalence.
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Demência , Masculino , Feminino , Humanos , Demência/epidemiologia , Prevalência , Envelhecimento , Testes Neuropsicológicos , Índia/epidemiologiaRESUMO
The number of older adults in the world is projected to increase steeply over the next 30 years; most older adults will live in low- and middle-income countries. This will have a direct impact on the global cancer burden, as cancer is largely a disease of aging. A revolution in the way we care for older adults in low- and middle-income settings is needed to meet rapidly rising demands. Regardless of a nation's relative wealth or resources, implementing the geriatric assessment in cancer care has presented a challenge because of omission of the principles of geriatric oncology from formal training and continuing education, lack of time, and a shortage of qualified personnel. To meet the challenge of caring for older adults globally, we must: (1) re-imagine aging-focused training for providers and nurses, (2) create and strengthen collaborations/partnerships between geriatric oncology teams and aging-service organizations, and (3) increase advocacy for age-friendly health care policy. By harnessing technology, the reach of specialized oncology education and care can be extended even-or especially-to low- and middle-income settings.
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Oncologia , Neoplasias , Idoso , Envelhecimento , Avaliação Geriátrica , Política de Saúde , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
Recent mouse knockout studies identified adapter protein-2-associated kinase 1 (AAK1) as a viable target for treating neuropathic pain. BMS-986176/LX-9211 (4), as a highly selective, CNS-penetrable, and potent AAK1 inhibitor, has advanced into phase II human trials. On exploring the structure-activity relationship (SAR) around this biaryl alkyl ether chemotype, several additional compounds were found to be highly selective and potent AAK1 inhibitors with good druglike properties. Among these, compounds 43 and 58 showed very good efficacy in two neuropathic pain rat models and had excellent CNS penetration and spinal cord target engagement. Both compounds also exhibited favorable physicochemical and oral pharmacokinetic (PK) properties. Compound 58, a central pyridine isomer of BMS-986176/LX-9211 (4), was 4-fold more potent than 4 in vitro and showed lower plasma exposure needed to achieve similar efficacy compared to 4 in the CCI rat model. However, both 43 and 58 showed an inferior preclinical toxicity profile compared to 4.
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Anestésicos Gerais , Neuralgia , Animais , Éteres/uso terapêutico , Camundongos , Neuralgia/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Ratos , Medula Espinal , Relação Estrutura-AtividadeRESUMO
Recent mouse knockout studies identified adapter protein-2 associated kinase 1 (AAK1) as a viable target for treating neuropathic pain. Potent small-molecule inhibitors of AAK1 have been identified and show efficacy in various rodent pain models. (S)-1-((2',6-Bis(difluoromethyl)-[2,4'-bipyridin]-5-yl)oxy)-2,4-dimethylpentan-2-amine (BMS-986176/LX-9211) (34) was identified as a highly selective, CNS penetrant, potent AAK1 inhibitor from a novel class of bi(hetero)aryl ethers. BMS-986176/LX9211 (34) showed excellent efficacy in two rodent neuropathic pain models and excellent central nervous system (CNS) penetration and target engagement at the spinal cord with an average brain to plasma ratio of 20 in rat. The compound exhibited favorable physicochemical and pharmacokinetic properties, had an acceptable preclinical toxicity profile, and was chosen for clinical trials. BMS-986176/LX9211 (34) completed phase I trials with good human pharmacokinetics and minimum adverse events and is currently in phase II clinical trials for diabetic peripheral neuropathic pain (ClinicalTrials.gov identifier: NCT04455633) and postherpetic neuralgia (ClinicalTrials.gov identifier: NCT04662281).
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Aminas , Neuralgia , Animais , Encéfalo , Camundongos , Neuralgia/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Ratos , Medula EspinalRESUMO
Parkinsonism has a complex and multifactorial aetiology and the role of post viral infection parkinsonism has been documented. The recent pandemic has made it clear that COVID-19 causes respiratory disease and affects multiple organs, which includes the central nervous system. Here we report three cases of post COVID parkinsonism occurring in older adults, age 60 years and above, and their response to levodopa-carbidopa.
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Xanthogranulomatous pyelonephritis is a rare condition characterised by destructive granulomatous inflammation of renal parenchyma. Primary renal Aspergillosis has been reported in patients with immunocompromised states such as diabetes, retroviral disease, organ transplant recipients, etc. We present a unique case of an older adult in his early 60s, presenting with fever and left flank pain with renal angle tenderness, diagnosed with primary renal aspergillosis with xanthogranulomatous pyelonephritis. These symptoms resolved with a long duration of antifungal (itraconazole) therapy and nephrectomy. The unique features are the development of fungal pyelonephritis in the absence of any immunocompromising conditions and the development of xanthogranulomatous changes with no risk factors.