Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
1.
J Am Geriatr Soc ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34850967

RESUMO

BACKGROUND: Research has shown the associations between negative aging perceptions and cognitive and physical decline may be mediated through behavioral and psychological pathways, but they are rarely examined simultaneously. We aimed at assessing the difference in the probability of following a high-, mid-, or low-performing cognitive trajectory, and a high- or low-performing physical function trajectory by negative aging perceptions. We sought to test two competing pathway mechanisms for the associations. METHODS: This longitudinal study used data from the Irish Longitudinal Study on Ageing (TILDA), a nationally representative study of community-dwelling adults in Ireland. Adults aged ≥50 years who participated in two or more waves of TILDA (n = 6121) were included. An analysis of the population aged 65 years and above was also conducted (n = 2359). We identified latent class trajectories of Mini-Mental State Examination (MMSE), Instrumental Activities of Daily Living (IADL), ADL, and Timed-Up-and-Go (TUG) performance using Latent Growth Class Analysis (LGCA) on data collected every 2 years over 5 waves. Multinomial logistic regression was used to estimate the likelihood of membership to each trajectory class by negative aging perceptions (APQ). Finally, we tested possible behavioral, psychological, and social mechanisms. RESULTS: LCGA identified three trajectory classes in cognitive and two in each physical function measure. People with the highest tertile of negative APQ were more likely to be in the declining MMSE class and the increasing IADL, ADL, and TUG classes. These associations for cognitive function were partially mediated by psychosocial pathways and for physical function were fully mediated by both psychosocial and health behavior pathways. CONCLUSIONS: Negative aging perceptions were associated with cognitive and physical function declines. Poor self-rated health, depressive symptoms, loneliness, and low exercise seem to explain the relationships; however, the possibility of reverse causation remains.

2.
Eur J Ageing ; 18(4): 565-574, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34790085

RESUMO

Religious attendance is sometimes associated with better health outcomes, although the link between religion and cognitive ageing is inconclusive. We aimed to assess differences in cognitive performance trajectories by religious affiliation and religious attendance. We further sought to test possible mechanisms for an association.Data from the Irish Longitudinal Study on Ageing (TILDA), a nationally representative study of the over 50 s population in Ireland, was used. We identified latent class trajectories of Mini Mental State Examination (MMSE) performance over five waves using Latent Growth Class Analysis (LGCA) on data from 7325 individuals. Multinomial logistic regression was used to estimate the likelihood of membership to each trajectory class by religious affiliation or non-affiliation, and by religious attendance and importance. Finally, we tested possible behavioural, psychological and social mechanisms. LGCA identified three trajectory classes, a 'high start' class, a 'medium start' class and a 'low start' class. There were no differences in class membership by religious affiliation or non-affiliation. Women who attended religious services were less likely to be in the low declining MMSE class. This effect was mediated by depressive symptoms, social network and smoking. Women who said religion was very important were more likely to be in the medium performing class, and this was not mediated. The cognitive trajectories of the over 50 s in Ireland vary. Variation was not influenced by religious affiliation. Religious attendance and importance had mixed effects on women's cognition trajectories. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-020-00597-0.

3.
J Am Med Dir Assoc ; 22(11): 2251-2257, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34597531

RESUMO

OBJECTIVES: It is a concern that public health measures to prevent older people contracting COVID-19 could lead to a rise in mental health problems such as depression. The aim of this study therefore is to examine trends of depressive symptoms before and during the COVID-19 pandemic in a large cohort of older people. DESIGN: Observational study with 6-year follow-up. SETTING & PARTICIPANTS: More than 3000 community-dwelling adults aged ≥60 years participating in The Irish Longitudinal Study on Ageing (TILDA). METHODS: Mixed effects multilevel models were used to describe trends in depressive symptoms across 3 waves of TILDA: wave 4 (2016), wave 5 (2018), and a final wave conducted July-November 2020. Depressive symptoms were measured using the 8-item Center for Epidemiologic Studies Depression Scale (CES-D), with a score ≥9 indicating clinically significant symptoms. RESULTS: The prevalence of clinically significant depressive symptoms at waves 4 and 5 was 7.2% [95% confidence interval (CI) 6.5, 7.9] and 7.2% (95% CI 6.5, 8.0), respectively. This more than doubled to 19.8% (95% CI 18.5, 21.2) during the COVID-19 pandemic. There was no change in CES-D scores between waves 4 and 5 (ß = 0.09, 95% CI -0.04, 0.23), but a large increase in symptoms was observed during the pandemic (ß = 2.20, 95% CI 2.07, 2.33). Age ≥70 years was independently associated with depressive symptoms (ß = 0.45, 95% CI 0.18, 0.72) during the pandemic but not from wave 4 to 5 (ß = 0.09, 95% CI -0.18, 0.36). Living with others was associated with a lower burden of symptoms during the pandemic (ß = -0.40, 95% CI -0.71, -0.09) but not between waves 4 and 5 (ß = -0.40, 95% CI -0.71, -0.09). CONCLUSIONS AND IMPLICATIONS: This study demonstrates significant increases in the burden of depressive symptoms among older people during the COVID-19 pandemic, particularly those aged ≥70 years and/or living alone. Even a small increase in the incidence of late life depression can have major implications for health care systems and societies in general. Improving access to age-attuned mental health care should therefore be a priority.


Assuntos
COVID-19 , Pandemias , Idoso , Depressão/epidemiologia , Humanos , Estudos Longitudinais , SARS-CoV-2
4.
Cancers (Basel) ; 13(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34680193

RESUMO

Rare ovarian cancers (ROCs) are OCs with an annual incidence of fewer than 6 cases per 100,000 women. They affect women of all ages, but due to their low incidence and the potential clinical inexperience in management, there can be a delay in diagnosis, leading to a poor prognosis. The underlying causes for these tumors are varied, but generally, the tumors arise due to alterations in gene/protein expression in cellular processes that regulate normal proliferation and its checkpoints. Dysregulation of the cellular processes that lead to cancer includes gene mutations, epimutations, non-coding RNA (ncRNA) regulation, posttranscriptional and posttranslational modifications. Long non-coding RNA (lncRNA) are defined as transcribed RNA molecules, more than 200 nucleotides in length which are not translated into proteins. They regulate gene expression through several mechanisms and therefore add another level of complexity to the regulatory mechanisms affecting tumor development. Since few studies have been performed on ROCs, in this review we summarize the mechanisms of action of lncRNA in OC, with an emphasis on ROCs.

5.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589

RESUMO

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

6.
GastroHep ; 3(4): 212-228, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34539248

RESUMO

Background: The current COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), has drastically impacted societies worldwide. Vaccination against SARS-CoV-2 is expected to play a key role in the management of this pandemic. Inflammatory conditions such as inflammatory bowel disease (IBD) often require chronic immunosuppression, which can influence vaccination decisions. Aim: This review article aims to describe the most commonly available SARS-CoV-2 vaccination vectors globally, assess the potential benefits and concerns of vaccination in the setting of immunosuppression and provide medical practitioners with guidance regarding SARS-CoV-2 vaccination in patients with IBD. Methods: All published Phase 1/2 and/or Phase 3 and 4 studies of SARS-CoV-2 vaccinations were reviewed. IBD international society position papers, safety registry data and media releases from pharmaceutical companies as well as administrative and medicines regulatory bodies were included. General vaccine evidence and recommendations in immunosuppressed patients were reviewed for context. Society position papers regarding special populations, including immunosuppressed, pregnant and breast-feeding individuals were also evaluated. Literature was critically analysed and summarised. Results: Vaccination against SARS-CoV-2 is supported in all adult, non-pregnant individuals with IBD without contraindication. There is the potential that vaccine efficacy may be reduced in those who are immunosuppressed; however, medical therapies should not be withheld in order to undertake vaccination. SARS-CoV-2 vaccines are safe, but data specific to immunosuppressed patients remain limited. Conclusions: SARS-CoV-2 vaccination is essential from both an individual patient and community perspective and should be encouraged in patients with IBD. Recommendations must be continually updated as real-world and trial-based evidence emerges.

7.
Int J Mol Sci ; 22(15)2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34360598

RESUMO

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as 'rare' due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).


Assuntos
Neoplasias dos Genitais Femininos/patologia , RNA Longo não Codificante/genética , Animais , Feminino , Neoplasias dos Genitais Femininos/genética , Humanos
9.
Int J Mol Sci ; 22(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204445

RESUMO

Choriocarcinoma (CC), a subtype of trophoblastic disease, is a rare and highly aggressive neoplasm. There are two main CC subtypes: gestational and non-gestational, (so called when it develops as a component of a germ cell tumor or is related to a somatic mutation of a poorly differentiated carcinoma), each with very diverse biological activity. A therapeutic approach is highly effective in patients with early-stage CC. The advanced stage of the disease also has a good prognosis with around 95% of patients cured following chemotherapy. However, advancements in diagnosis and treatment are always needed to improve outcomes for patients with CC. Long non-coding (lnc) RNAs are non-coding transcripts that are longer than 200 nucleotides. LncRNAs can act as oncogenes or tumor suppressor genes. Deregulation of their expression has a key role in tumor development, angiogenesis, differentiation, migration, apoptosis, and proliferation. Furthermore, detection of cancer-associated lncRNAs in body fluids, such as blood, saliva, and urine of cancer patients, is emerging as a novel method for cancer diagnosis. Although there is evidence for the potential role of lncRNAs in a number of cancers of the female genital tract, their role in CC is poorly understood. This review summarizes the current knowledge of lncRNAs in gestational CC and how this may be applied to future therapeutic strategies in the treatment of this rare cancer.


Assuntos
Coriocarcinoma/genética , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Neoplasias Uterinas/genética , Biomarcadores Tumorais , Coriocarcinoma/diagnóstico , Coriocarcinoma/metabolismo , Feminino , Humanos , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Gravidez , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismo
11.
Burns ; 47(5): 1045-1052, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34034954

RESUMO

INTRODUCTION: Burn injury and reconstructive operations often result in severe pain, particularly at skin graft donor sites. Traditional local anesthetics administered intraoperatively control pain at donor sites, but the duration of action is short. Liposomal bupivacaine, a novel local anesthetic, can provide sustained-release analgesia for 72h. The primary aim of this study was to describe the efficacy of liposomal bupivacaine for postoperative donor site pain control for patients undergoing skin graft procedures. METHODS: A retrospective cohort study was performed on patients who received a donor site liposomal bupivacaine field block and was compared to a matched control. Patients rated donor site pain on post-operative day 0 and 1, and stated whether the donor or graft site was more painful. RESULTS: Fifty-eight patients were included. Twenty-nine patients received liposomal bupivacaine. Eighty-six percent of patients in the treatment group rated donor site pain as three or less on postoperative day 0 and 1, compared to 3.4% in the control (p<0.0001). Also, 76% of patients in the treatment group stated donor site pain was less than graft site pain, compared to 3.4% in the control (p<0.0001). CONCLUSION: Patients who received liposomal bupivacaine reported less postoperative donor site pain and found the donor site to be less bothersome without major complications. Liposomal bupivacaine may be a safe and promising agent for prolonging postoperative analgesia and minimizing donor site pain.

12.
Mol Cancer ; 20(1): 59, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789677

RESUMO

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Humanos , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/etiologia , Neoplasias/patologia
13.
Int J Geriatr Psychiatry ; 36(7): 1004-1010, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33792969

RESUMO

BACKGROUND: There is an established bidirectional relationship between mental and heart health in later life but the link between wish to die (WTD) and cardiovascular mortality is less well-defined. METHODS: This is a longitudinal study examining the association between WTD and mortality over 9-year follow-up in a large population-representative sample of older adults. Individual-level survey data was linked to official death registration data, divided into cardiovascular and noncardiovascular causes. WTD was defined as answering affirmatively when asked 'In the last month, have you felt that you would rather be dead?' Regression models were used to obtain hazard ratios for the association between WTD at Wave 1 and mortality. Kaplan-Meier plots were used to compare survival across groups. RESULTS: Just over 3% (275/8124) of participants reported WTD. Mortality data was available for 9% of participants (755/8124). WTD was significantly associated with all-cause mortality, with a hazard ratio of 1.41 (95% confidence interval [CI]: 1.00-1.99). Findings were attenuated and no longer significant after excluding participants with heart disease or depression/anxiety/other psychiatric illness. WTD was significantly associated with cardiovascular mortality (hazard ratio: 2.14 [95% CI: 1.21-3.78]), even after excluding participants with depression/anxiety/other illnesses but not heart disease. WTD was not associated with an increased risk of death due to non-cardiovascular causes. CONCLUSIONS: Older people who report a wish to die have double the risk of death from cardiovascular disease in the following 9 years, even when those with depression, anxiety or other mental health problems are excluded.


Assuntos
Doenças Cardiovasculares , Transtornos Mentais , Idoso , Ansiedade , Atitude Frente a Morte , Humanos , Estudos Longitudinais , Fatores de Risco
14.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917022

RESUMO

Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of ∼22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 3' untranslated region (3'-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.


Assuntos
Biomarcadores Tumorais , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/genética , MicroRNAs/genética , MicroRNA Circulante , Tomada de Decisão Clínica , Gerenciamento Clínico , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias dos Genitais Femininos/terapia , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Gravidez , Prognóstico , Interferência de RNA , RNA Mensageiro , Resultado do Tratamento
15.
Dig Dis Sci ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33763785

RESUMO

BACKGROUND: Data on outcomes following de-escalation of intensified anti-TNF therapy in inflammatory bowel disease (IBD) are limited and concerns about relapse limit willingness to de-escalate. AIMS: To evaluate rates of successful de-escalation at 12 months and to determine factors that may predict success. METHODS: Single-centre experience of IBD patients that were de-escalated following deep remission on dose-intensified infliximab (IFX) or adalimumab (ADA) for secondary loss of response. Patients were classified as 'successes' if remaining on reduced anti-TNF or 'failures' if requiring re-escalation, steroids, surgery or enrolment into a clinical trial at 12 months. Patient demographics, disease characteristics, biomarkers (faecal calprotectin, C-reactive protein, albumin) and anti-TNF drug levels were collected 6-monthly. RESULTS: Of 25 patients (20 CD, 5 UC), 16 (64%) were successes 12 months post-de-escalation. Median time to failure was 6 months. Six of the nine failures required anti-TNF re-escalation and three entered a clinical trial. Re-escalation recaptured response in all six patients. There was no significant difference in baseline biomarker activity between the two groups. There was no difference in infliximab levels between successes and failures at the time of de-escalation (5.5 vs. 5.3, p = 0.63) as well as 6 months (3.1 vs. 4.6, p = 0.95) and 12 months (3.2 vs. 4.5, p = 0.58) post-de-escalation. CONCLUSION: Nearly two-thirds of patients remained on reduced anti-TNF dosing 12 months after de-escalation. All patients who failed de-escalation were recaptured after dose re-escalation. De-escalation with close monitoring may be considered in patients on intensified anti-TNF therapy in sustained remission.

16.
Inflamm Bowel Dis ; 27(12): 1909-1918, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-33704467

RESUMO

BACKGROUND: There is considerable interest in improving the education and care of women with inflammatory bowel disease (IBD) to improve pregnancy outcomes. Despite increased awareness, not all women with IBD have access to pregnancy-related education and the quality of counseling is variable. We aimed to assess the effectiveness of a simple educational intervention for improving pregnancy-related knowledge and to evaluate the effect of education on patient outcomes including anxiety, depression, and quality of life in women with IBD. METHODS: This prospective study of women with IBD who were pregnant or planning a pregnancy evaluated the effectiveness of a single gastroenterologist-led educational intervention in improving pregnancy-related knowledge, measured using the Crohn's and Colitis Pregnancy Knowledge score 1 month postintervention. Secondary outcomes included the effect on anxiety and depression, quality of life, medication adherence, and patient satisfaction. RESULTS: One hundred women with IBD were recruited. Fifty percent were pregnant at the time of the intervention. Baseline knowledge scores were similar independent of the patients' pregnancy status or whether they had previously received counseling from their gastroenterologist. Median Crohn's and Colitis Pregnancy Knowledge scores postintervention (n = 82) were higher than preintervention scores (14/17 vs 10/17; P < 0.001). In addition, 32% of patients had poor knowledge at baseline (score ≤7/17), compared to only 5% after the intervention (P < 0.001). There was a significant improvement in total anxiety and depression and quality of life scores postintervention. Medication adherence and patient satisfaction were excellent. CONCLUSIONS: Uptake of this gastroenterologist-led educational intervention has the potential to improve pregnancy knowledge, promote medication adherence, and enhance quality of life for women with IBD globally.

17.
Age Ageing ; 50(4): 1329-1335, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-33570566

RESUMO

BACKGROUND: Social distancing and similar measures in response to the coronavirus disease 2019 pandemic have greatly increased loneliness and social isolation among older adults. Understanding the association between loneliness and mortality is therefore critically important. We examined whether combinations of loneliness and social isolation, using a metric named social asymmetry, was associated with increased mortality risk. METHODS: The sample was derived from participants in The Irish Longitudinal Study on Ageing, a nationally representative sample of community-dwelling older adults aged ≥50. Survey data were linked to official death registration records. Cox proportional hazards regressions and competing risk survival analyses were used to examine the association between social asymmetry and all-cause and cause-specific mortality. RESULTS: Of four social asymmetry groups, concordant low lonely (low loneliness, low isolation) included 35.5% of participants; 26.4% were concordant high lonely (high loneliness, high isolation); 19.2% were discordant robust (low loneliness, high isolation) and 18.9% discordant susceptible (high loneliness, low isolation). The concordant high lonely (hazard ratio [HR] = 1.43, 95% confidence interval [CI]: 1.09-1.87) and discordant robust (HR = 1.37, 95% CI: 1.04-1.81) groups had an increased mortality risk compared to those in the concordant low lonely group. The concordant high lonely group had an increased risk of mortality due to diseases of the circulatory system (sub-distribution hazard ratio = 1.52, 95% CI: 1.03-2.25). CONCLUSION: We found that social asymmetry predicted mortality over a 7-year follow-up period. Our results confirm that a mismatch between subjective loneliness and objective social isolation, as well as the combination of loneliness and social isolation, were associated with an increased all-cause mortality risk.


Assuntos
COVID-19 , Solidão , Idoso , Envelhecimento , Humanos , Estudos Longitudinais , SARS-CoV-2 , Isolamento Social
18.
Age Ageing ; 50(4): 1321-1328, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-33570600

RESUMO

BACKGROUND: 'Wish to Die' (WTD) involves thoughts of or wishes for one's own death or that one would be better off dead. OBJECTIVE: To examine the prevalence, longitudinal course and mortality-risk of WTD in community-dwelling older people. DESIGN: Observational study with 6-year follow-up. SETTING: The Irish Longitudinal Study on Ageing, a nationally representative cohort of older adults. SUBJECTS: In total, 8,174 community-dwelling adults aged ≥50 years. METHODS: To define WTD, participants were asked: 'In the last month, have you felt that you would rather be dead?' Depressive symptoms were measured using the CES-D. Mortality data were compiled by linking administrative death records to individual-level survey data from the study. RESULTS: At Wave 1, 3.5% of participants (279/8,174) reported WTD. Both persistent loneliness (OR 5.73 (95% CI 3.41-9.64)) and depressive symptoms (OR 6.12 (95% CI 4.33-8.67)) were independently associated with WTD.Of participants who first reported WTD at Wave 1 or 2, 72% did not report WTD when reassessed after 2 years, and the prevalence of depressive symptoms (-44%) and loneliness (-19%) was more likely to decline in this group at follow-up.Fifteen per cent of participants expressing WTD at Wave 1 died during a 6-year follow-up. CONCLUSIONS: WTD amongst community-dwelling older people is frequently transient and is strongly linked with the course of depressive symptoms and loneliness. An enhanced focus on improving access to mental health care and addressing social isolation in older people should therefore be a public health priority, particularly in the current context of the Covid-19 pandemic.


Assuntos
COVID-19 , Pandemias , Idoso , Depressão/diagnóstico , Depressão/epidemiologia , Humanos , Solidão , Estudos Longitudinais , Prevalência , SARS-CoV-2
19.
Thromb Res ; 200: 91-98, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33571724

RESUMO

INTRODUCTION: Ovarian cancer patients are at high risk of thrombosis particularly during chemotherapy treatment however the mechanism is not understood. The aim of this study is to investigate the role of the activated protein C (aPC) pathway in the procoagulant activity observed in ovarian cancer patients undergoing neoadjuvant chemotherapy. PATIENTS AND METHODS: Thrombin generation was determined before and after addition of thrombomodulin (TM) in high grade serous ovarian cancer (HGSOC) patients treated with neoadjuvant chemotherapy (n = 29) compared with HGSOC patients who were chemo naïve (n = 23) and patients with benign tumours (n = 29). Plasma expression of proteins from the aPC pathway was analysed. mRNA expression was determined in endothelial (EA.hy926) and ovarian (OAW42) cell lines following addition of carboplatin and paclitaxel. RESULTS: Lower levels of ETP (p < 0.007; p < 0.003) and peak thrombin (p < 0.0008; p < 0.0018) were found in the neoadjuvant group compared with both chemo naïve and benign groups. Following addition of TM, ETP (p < 0.0005) and peak thrombin (p < 0.0049) were higher in the neoadjuvant group compared with the benign controls indicating an increase in aPC resistance. Increased TM and lower levels of protein S were found in the neoadjuvant group compared with benign controls (p < 0.05; p < 0.003). Factor V levels were increased in the neoadjuvant group compared with the chemo naïve group (p < 0.05). Carboplatin and paclitaxel altered the expression of EPCR and thrombomodulin in OAW42 cells with a modest effect on EA.hy926 cells. CONCLUSION: Chemotherapy induced procoagulant activity in HGSOC is associated with an alteration in expression of key members of the aPC pathway. This acquired aPC resistance may explain the procoagulant phenotype associated with ovarian cancer patients undergoing chemotherapy.


Assuntos
Neoplasias Ovarianas , Proteína C , Carboplatina/uso terapêutico , Feminino , Humanos , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico
20.
Ther Drug Monit ; 43(5): 692-695, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33492105

RESUMO

BACKGROUND: The optimal use of infliximab depends on the measurement of trough levels with subsequent appropriate dose adjustment. With the introduction of biosimilars, it is important to demonstrate that the biosimilar behaves similarly in the assay used as the originator-infliximab, for which the assays were developed. In this study, the authors aimed to compare the concentrations of SB2-infliximab (Renflexis) with that of originator-infliximab (Remicade) when added to serum from healthy subjects and those with inflammatory bowel disease when measured by commonly used commercial assays. METHODS: Sera from 2 healthy controls, 2 patients with ulcerative colitis (1 with quiescent disease and 1 with active disease), and 2 patients with Crohn disease (1 with quiescent disease and 1 with active disease) were spiked with SB2-infliximab or originator-infliximab at 0-20 mcg/mL. Concentrations were measured using 3 commonly used assay kits (Lisa-Tracker, Shikari Q-Inflix, Promonitor IFX) and one rapid test (Quantum Blue). The results were compared using Bland-Altman techniques. RESULTS: Close agreement was observed between measured concentrations for all assays, irrespective of the origin of the serum. Limits of agreement varied between at worst -0.302 and 0.465 mcg/mL, with the mean difference between the molecules being at worst 0.04 mcg/mL (95% confidence intervals, -0.011 to 0.093). CONCLUSIONS: The originator and SB-2 biosimilar-infliximab behaved similarly in several currently used assays in their concentrations in biological fluids. Clinicians can be confident that therapeutic drug monitoring using platforms designed and developed for the originator-infliximab can be applied to SB-2-infliximab.


Assuntos
Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Infliximab , Anticorpos Monoclonais , Medicamentos Biossimilares/sangue , Medicamentos Biossimilares/farmacocinética , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/sangue , Infliximab/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...