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BACKGROUND: Managing multiple sclerosis (MS) in people of reproductive age can be challenging as treatment decisions often need to balance efficacy, safety to reproductive health and an understanding of reproductive intentions. There has been limited examination of how family planning (FP) is approached in people with MS (pwMS) in Australia. This study aimed to explore the experiences and perspectives of Australian MS clinical specialists on managing FP in the context of MS. METHODS: We conducted one-on-one semi-structured interviews with nine neurologists and ten MS nurses across Australia who regularly provide care to pwMS of reproductive age. Interview topics examined current approaches to managing FP, availability of FP resources, and opportunities for improvement. Interview recordings were transcribed verbatim and analysed thematically. RESULTS: Two main themes emerged. First, 'inconsistent approaches in providing family planning', where neurologists and MS nurses recognised FP provision as essential but revealed differences in the content, timing and extent of FP discussions; conflicts between reproductive considerations and DMT prescriptions according to teratogenic risk; and variable implementation of interdisciplinary approaches. Second, 'barriers in providing family planning' emerged which included a lack of local information resources on FP, lack of contemporary data on safety of DMTs, and a range of patient and professional factors, including time constraints. CONCLUSION: MS clinical specialists saw FP as an essential part of the care of their patients and expressed a need for information and service provision consistency in order to improve FP and reproductive care to pwMS.
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Serviços de Planejamento Familiar , Esclerose Múltipla , Humanos , Esclerose Múltipla/tratamento farmacológico , Austrália , Reprodução , PacientesRESUMO
BACKGROUND: In cases of brain pathology, current levels of cognition can only be interpreted reliably relative to accurate estimations of pre-morbid functioning. Estimating levels of pre-morbid intelligence is, therefore, a crucial part of neuropsychological evaluation. However, current methods of estimation have proven problematic. OBJECTIVE: To evaluate if standardised leaving certificate (LC) performance can predict intellectual functioning in a healthy cohort. The LC is the senior school examination in the Republic of Ireland, taken by almost 50 000 students annually, with total performance distilled into Central Applications Office points. METHODS: A convenience sample of university students was recruited (n = 51), to provide their LC results and basic demographic information. Participants completed two cognitive tasks assessing current functioning (Vocabulary and Matrix Reasoning (MR) subtests - Wechsler Abbreviated Scale of Intelligence, Second Edition) and a test of pre-morbid intelligence (Spot-the-Word test from the Speed and Capacity of Language Processing). Separately, LC results were standardised relative to the population of test-takers, using a computer application designed specifically for this project. RESULTS: Hierarchical regression analysis revealed that standardised LC performance [F(2,48) = 3.90, p = 0.03] and Spot-the-Word [F(2,47) = 5.88, p = 0.005] significantly predicted current intellect. Crawford & Allen's demographic-based regression formula did not. Furthermore, after controlling for gender, English [F(1,49) = 11.27, p = 0.002] and Irish [F(1,46) = 4.06, p = 0.049) results significantly predicted Vocabulary performance, while Mathematics results significantly predicted MR [F(1,49) = 8.80, p = 0.005]. CONCLUSIONS: These results suggest that standardised LC performance may represent a useful resource for clinicians when estimating pre-morbid intelligence.
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Inteligência , Humanos , Testes Neuropsicológicos , IrlandaRESUMO
BACKGROUND: US military service members have characteristically poor sleep, even when 'in garrison' or at one's home base. The physical sleeping environment, which is often poor in military-provided housing or barracks, may contribute to poor sleep quality in soldiers. The current study aimed to assess whether the sleeping environment in garrison is related to sleep quality, insomnia risk and military readiness. METHODS: Seventy-four US army special operations soldiers participated in a cross-sectional study. Soldiers were queried on their sleeping surface comfort and the frequency of being awakened at night by excess light, abnormal temperatures and noise. Subjective sleep quality and insomnia symptoms were also queried, via the Pittsburgh Sleep Quality Index and Insomnia Severity Index, respectively. Lastly, measures of soldier readiness, including morale, motivation, fatigue, mood and bodily pain, were assessed. RESULTS: Soldiers reporting temperature-related and light-related awakenings had poorer sleep quality higher fatigue and higher bodily pain than soldiers without those disturbances. Lower ratings of sleeping surface comfort were associated with poorer sleep quality and lower motivation, lower morale, higher fatigue and higher bodily pain. Each 1-point increase in sleeping surface comfort decreased the risk for a positive insomnia screen by 38.3%, and the presence of temperature-related awakenings increased risk for a positive insomnia screen by 78.4%. Those living on base had a poorer sleeping environment than those living off base. CONCLUSION: Optimising the sleep environment-particularly in on-base, military-provided housing-may improve soldier sleep quality, and readiness metrics. Providers treating insomnia in soldiers should rule out environment-related sleep disturbances prior to beginning more resource-intensive treatment.
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Militares , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Estudos Transversais , Sono , Dor , FadigaRESUMO
Cognitive impairment is a core feature of psychosis. Full cognitive assessments are not often conducted in routine clinical practice as administration is time-consuming. Here, we investigated whether brief tests of cognition could be used to predict broader neurocognitive performance in a manner practical for screening use in mental health services. We carried out a principal component analysis (PCA) to obtain an estimate of general cognitive function (N = 415). We investigated whether brief tests of memory accounted for a significant percentage of variation in the PCA scores. We used discriminant function analysis to determine if measures could predict classification as lower, intermediate or higher level of cognitive function and to what extent these groups overlapped with groups based on normative data. Memory tests correctly classified 65% of cases in the highest scoring group, 35% of cases in the intermediate group, and 77% of cases in the lowest scoring group. These PCA-derived groups and groups based on normative scores for the two tests were significantly associated (χ2 = 164.00, p < 0.001). These measures accurately identified three quarters of the low performing group, the group of greatest interest from the perspective of identifying those likely to need greater supports as part of clinical care. In so doing they suggest a potentially useful approach to screening for cognitive impairment in clinical services, upon which further assessment can be built if required.
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OBJECTIVE: Ensuring an efficient response to COVID-19 requires a degree of inter-system coordination and capacity management coupled with an accurate assessment of hospital utilization including length of stay (LOS). We aimed to establish optimal practices in inter-system data sharing and LOS modeling to support patient care and regional hospital operations. MATERIALS AND METHODS: We completed a retrospective observational study of patients admitted with COVID-19 followed by 12-week prospective validation, involving 36 hospitals covering the upper Midwest. We developed a method for sharing de-identified patient data across systems for analysis. From this, we compared 3 approaches, generalized linear model (GLM) and random forest (RF), and aggregated system level averages to identify features associated with LOS. We compared model performance by area under the ROC curve (AUROC). RESULTS: A total of 2068 patients were included and used for model derivation and 597 patients for validation. LOS overall had a median of 5.0 days and mean of 8.2 days. Consistent predictors of LOS included age, critical illness, oxygen requirement, weight loss, and nursing home admission. In the validation cohort, the RF model (AUROC 0.890) and GLM model (AUROC 0.864) achieved good to excellent prediction of LOS, but only marginally better than system averages in practice. CONCLUSION: Regional sharing of patient data allowed for effective prediction of LOS across systems; however, this only provided marginal improvement over hospital averages at the aggregate level. A federated approach of sharing aggregated system capacity and average LOS will likely allow for effective capacity management at the regional level.
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BACKGROUND: Complicated grief involves the experience of grief-related symptoms at a time, and severity, beyond which could be considered adaptive, while persistent complex bereavement disorder (PCBD) has been identified as a condition that requires further study in the typical population. The aims of this study are to (1) explore the symptoms of complicated grief associated with parental bereavement as self-reported by adults with intellectual disabilities (IDs) who have experienced a parental bereavement and (2) conduct an initial examination of how the existing criteria for PCBD apply to this group. METHODS: This study uses a comparative group design, assessing self and staff (proxy) reports for a group of parentally bereaved individuals and a matched group of non-bereaved individuals using the Complicated Grief Questionnaire - ID Self-Report. Participants were 46 individuals with ID, 30 (65%) of whom who had experienced a parental bereavement within the previous 2 years. The age range was 23-67 years (mean = 43.8; SD = 10.3). RESULTS: The results highlight the presence of a range of symptoms of complicated grief in individuals' self-reports, although there was some evidence that separation distress-related symptoms were more apparent. An analysis of individual symptoms showed patterns of higher reports among the bereaved group as would be expected. Comparing staff and self-reports, key criteria showed higher levels in self-reports among the bereaved group. CONCLUSIONS: This study has demonstrated the capacity of people with ID to self-report personal experience of symptoms of complicated grief, when appropriate and accessible assessment tools are used. Some symptoms were more evident among bereaved individuals (compared with non-bereaved participants), and they tended to be from separation distress criteria. This may indicate the relevance of these symptoms for people with ID and question the existing criteria for PCBD in this population, which may have clinical implications for supporting people with ID experiencing a more complicated bereavement response.
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Luto , Deficiência Intelectual , Adulto , Idoso , Pesar , Humanos , Pessoa de Meia-Idade , Autorrelato , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVES: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC. MATERIALS AND METHODS: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA). RESULTS: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPSâ¯≥â¯50%, 1232 (52%) had PD-L1 TPSâ¯≥â¯1%, and 1136 (48%) had PD-L1 TPSâ¯<â¯1%. The most common reason for not having PD-L1 data (nâ¯=â¯249) was insufficient tumor cells (<100) on the slide (nâ¯=â¯170 [6%]). Percentages of patients with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1%, respectively, were 27% and 53%. CONCLUSIONS: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPSâ¯≥â¯50% and TPSâ¯≥â¯1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations.
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Antígeno B7-H1/genética , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Expressão Gênica , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prevalência , Estudos RetrospectivosRESUMO
OBJECTIVES: There are conflicting reports on the levels of anxiety and depression in individuals with alcohol problems and whether these conditions are substance-related or independent of the alcohol problem. The aim of this study was to characterise rates of co-morbid psychiatric symptoms among a group of individuals commencing treatment for alcohol dependence, and to examine the stability of these symptoms following treatment of the alcohol problem. METHODS: Symptoms of anxiety and depression were examined in a group of individuals (n=93) undergoing residential treatment for alcohol dependence. Symptoms were measured at treatment entry and again at treatment completion using the Beck Anxiety Inventory and the Beck Depression Inventory - II. RESULTS: High levels of anxiety and depressive symptoms were reported at treatment entry, but on completion of treatment (28 days later) the majority of participants were no longer reporting symptoms suggestive of a possible co-morbid condition. CONCLUSIONS: The significant change in rates of reported symptoms following completion of treatment suggests that a large proportion of symptoms reported at treatment entry were substance related. Diagnosing co-morbid conditions is best left until after a period of abstinence during which the alcohol problem has been treated. Assessing for co-morbidity at time of treatment seeking is likely to result in inappropriate co-morbid diagnoses being made and inappropriate or unnecessary treatments being prescribed for such individuals.
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Transtornos Relacionados ao Uso de Álcool/terapia , Ansiedade/terapia , Depressão/terapia , Avaliação de Resultados em Cuidados de Saúde/métodos , Tratamento Domiciliar/métodos , Adulto , Transtornos Relacionados ao Uso de Álcool/complicações , Alcoolismo/complicações , Alcoolismo/terapia , Ansiedade/etiologia , Depressão/etiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: The aims of this study were (a) to examine the effectiveness of an inpatient treatment programme for alcohol dependence based on the 'Minnesota Model' and (b) to examine potential predictors of outcomes from such treatment. METHODS: Demographics and data relating to psychosocial functioning of a group of individuals who commenced treatment for alcohol dependence were gathered at the point of treatment entry. These individuals were then followed up 6 months after they were to complete their inpatient treatment to establish their alcohol-related outcomes. Outcomes from treatment were identified as an index of treatment effectiveness and the outcome data were analysed to determine whether any of the baseline variables could be used to predict outcomes from treatment. RESULTS: Of those who were contacted at 6-month follow-up, 81.5% had a 'good outcome'. This represented 66.7% of the total group who participated in the study. The only variable that was found to predict outcomes at 6-month follow-up was severity of alcohol dependence at treatment entry, with more severe alcohol problems associated with poorer outcomes. CONCLUSIONS: This study provides evidence of the potential for a Minnesota-based treatment programme to be effective in helping people with alcohol dependence to reduce the amount of alcohol they consume and sustain this reduction beyond the treatment period.
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Transtornos Relacionados ao Uso de Álcool/reabilitação , Tratamento Domiciliar/métodos , Resultado do Tratamento , Feminino , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype or because our concept of personality and the stability of behaviour needs to be revised.
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Comportamento Animal/fisiologia , Pardais/fisiologia , Animais , Personalidade , Característica Quantitativa Herdável , Comportamento Social , Pardais/genéticaRESUMO
Quaking aspen (Populus tremuloides Michx.), a widespread and keystone tree species in North America, experienced heat and drought stress in the years 2002 and 2003 in the southwestern United States. This led to widespread aspen mortality that has altered the composition of forests, and is expected to occur again if climate change continues. Understanding interactions between aspen and its environments is essential to understanding future mortality risk in forests. Polyploidy, which is common in aspen, can modify plant structure and function and therefore plant-environment interactions, but the influence of polyploidy on aspen physiology is still not well understood. Furthermore, the ploidy types of aspen have different biogeographies, with triploids being most frequent at lower latitudes in generally warmer and drier climates, while the northerly populations are virtually 100% diploid. This suggests that ploidy-environment interactions differ, and could mean that the ploidy types have different vulnerabilities to environmental stress. In this study, to understand aspen ploidy-environment interactions, we measured 38 different traits important to carbon uptake, water loss and water-use efficiency in diploid and triploid aspen in Colorado. We found that triploid aspen had lower stand density, and greater leaf area, leaf mass, leaf mass per area, percent nitrogen content, chlorophyll content and stomatal size. These differences corresponded to greater potential net carbon assimilation (A, measured using A/Ci curves, and chlorophyll fluorescence) and stomatal conductance (gs) in triploids than diploids. While triploid aspen had higher intrinsic water-use efficiency (iWUE, calculated from measurements of δ13C in leaf tissue), they also had greater potential water loss from higher measured gs and lower stomatal sensitivity to increasing vapor pressure deficit. Therefore, despite greater iWUE, triploids may have lower resilience to climate-induced stress. We conclude that ploidy type strongly influences physiological traits and function, and mediates drought stress responses in quaking aspen.
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Isótopos de Carbono/metabolismo , Interação Gene-Ambiente , Fotossíntese/fisiologia , Poliploidia , Populus/fisiologia , Água/fisiologia , Folhas de Planta/genética , Folhas de Planta/fisiologia , Estômatos de Plantas/genética , Estômatos de Plantas/fisiologia , Populus/genéticaRESUMO
KRAS, NRAS and BRAF mutations are among the most important oncogenic drivers in many major cancer types, such as melanoma, lung, colorectal and pancreatic cancer. There is currently no effective therapy for the treatment of RAS mutant cancers. LY3009120, a pan-RAF and RAF dimer inhibitor advanced to clinical study has been shown to inhibit both RAS and BRAF mutant cell proliferation in vitro and xenograft tumor growth in vivo. Abemaciclib, a CDK4/6-selective inhibitor, is currently in phase III studies for ER-positive breast cancer and KRAS mutant lung cancer. In this study, we found that combinatory treatment with LY3009120 and abemaciclib synergistically inhibited proliferation of tumor cells in vitro and led to tumor growth regression in xenograft models with a KRAS, NRAS or BRAF mutation at the doses of two drugs that were well tolerated in combination. Further in vitro screen in 328 tumor cell lines revealed that tumor cells with KRAS, NRAS or BRAF mutation, or cyclin D activation are more sensitive, whereas tumor cells with PTEN, PIK3CA, PIK3R1 or retinoblastoma (Rb) mutation are more resistant to this combination treatment. Molecular analysis revealed that abemaciclib alone inhibited Rb phosphorylation partially and caused an increase of cyclin D1. The combinatory treatment cooperatively demonstrated more complete inhibition of Rb phosphorylation, and LY3009120 suppressed the cyclin D1 upregulation mediated by abemaciclib. These results were further verified by CDK4/6 siRNA knockdown. Importantly, the more complete phospho-Rb inhibition and cyclin D1 suppression by LY3009120 and abemaciclib combination led to more significant cell cycle G0/G1 arrest of tumor cells. These preclinical findings suggest that combined inhibition of RAF and d-cyclin-dependent kinases might provide an effective approach to treat patients with tumors harboring mutations in RAS or RAF genes.
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Aminopiridinas/farmacologia , Benzimidazóis/farmacologia , GTP Fosfo-Hidrolases/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana/antagonistas & inibidores , Mutação , Neoplasias/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Pirimidinas/farmacologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proliferação de Células , Ciclina D1/antagonistas & inibidores , Ciclina D1/genética , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/metabolismo , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Ratos Nus , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Understanding how species have replaced each other in the past is important to predicting future species turnover. While past species replacement is difficult to detect after the fact, the process may be inferred from present-day distribution patterns. Species with abutting ranges sometimes show a characteristic distribution pattern, where a section of one species range is enveloped by that of the other. Such an enclave could indicate past species replacement: when a species is partly supplanted by a competitor, but a population endures locally while the invading species moves around and past it, an enclave forms. If the two species hybridize and backcross, the receding species is predicted to leave genetic traces within the expanding one under a scenario of species replacement. By screening dozens of genes in hybridizing crested newts, we uncover genetic remnants of the ancestral species, now inhabiting an enclave, in the range of the surrounding invading species. This independent genetic evidence supports the past distribution dynamics we predicted from the enclave. We suggest that enclaves provide a valuable tool in understanding historical species replacement, which is important because a major conservation concern arising from anthropogenic climate change is increased species replacement in the future.
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Evolução Biológica , Hibridização Genética , Triturus/genética , Animais , DNA Mitocondrial , Filogeografia , SérviaRESUMO
PurposeThe aim of this study was to determine a sequence of structural changes in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using optical coherence tomography-angiography (OCT-A) and comparing with other imaging modalities.Patients and methodsPatients with a new diagnosis of acute-onset APMPPE referred to a regional specialist centre from October 2015 to October 2016 were included. Multimodal imaging employed on all patients from diagnosis included the following: fundus fluorescein angiography, indocyanine green angiography, fundus autofluorescence, spectral domain-OCT (SD-OCT), and OCT-A. All non-invasive imaging processes were repeated during follow-up.ResultsTen eyes of five patients were included in the study, three males and two females, with a mean age of 26.2 years (range: 21-32) and a mean follow-up of 6.4 months (range: 2.6-13.3). All patients presented with bilateral disease and macular involving lesions. OCT-A imaging of the choriocapillaris was supportive of hypoperfusion at the site of APMPPE lesions during the acute phase of this condition with normalisation of choroidal vasculature during follow-up. Multimodal imaging consistently highlighted four sequential phases from presentation to resolution of active disease.ConclusionsMultimodal imaging in patients with APMPPE in acute and long-term follow-up demonstrates a reversible choroidal hypoperfusion supporting the primary inciting pathology as a choriocapillaritis. The evolution shows resolution of the ischaemia through a defined sequence that results in persistent changes at the level of the retinal pigment epithelium and outer retina. OCT-A was able to detect preclinical changes and chart resolution at the level of the choriocapillaris.
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Corioidite/diagnóstico , Angiofluoresceinografia/métodos , Macula Lutea/patologia , Imagem Multimodal , Segmento Posterior do Olho/patologia , Tomografia de Coerência Óptica/métodos , Doença Aguda , Adulto , Corioidite/fisiopatologia , Progressão da Doença , Feminino , Seguimentos , Fundo de Olho , Humanos , Masculino , Coroidite Multifocal , Reprodutibilidade dos Testes , Epitélio Pigmentado da Retina/patologia , Estudos Retrospectivos , Acuidade Visual , Adulto JovemRESUMO
The aim of this multinational retrospective cohort study, conducted at academic and community oncology centres, was to describe real-world treatment patterns for patients with a confirmed diagnosis of advanced/metastatic (stage IIIB/IV) non-small cell lung cancer (NSCLC) who initiated first-line systemic therapy from January 2011 through June 2014. The study included 1265 patients in Italy, Spain, Germany, Australia, Korea, Taiwan and Brazil. The proportion of patients with squamous versus non-squamous NSCLC was approximately 20% versus 75%, and associated patient demographic characteristics were similar in all countries, excepting race. Patients with squamous NSCLC were predominantly male and current/ex-smokers. Biomarker tests were performed for the majority of patients with non-squamous NSCLC, ranging from 54% (Brazil) to 91% in Taiwan, where, of those tested, 68% with non-squamous NSCLC had positive epidermal growth factor receptor (EGFR)-mutation status; in other countries the EGFR-positive percentages ranged from 17% (Spain/Brazil) to 40% (Korea). Platinum-based regimens were the most common first-line therapy in all countries except Taiwan, where gefitinib was the most common first-line agent. Median overall survival ranged from 9.3 months (Brazil) to 25.5 months (Taiwan). The diagnostic and treatment patterns recorded in this study were heterogeneous but largely in line with NSCLC guidelines during the study period.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Padrões de Prática Médica , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Austrália , Brasil , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Estudos de Coortes , Receptores ErbB/genética , Feminino , Alemanha , Humanos , Itália , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Receptores Proteína Tirosina Quinases/genética , República da Coreia , Estudos Retrospectivos , Espanha , Taxa de Sobrevida , TaiwanRESUMO
A detailed neuropsychological assessment plays an important role in the diagnostic process of mild cognitive impairment. However, available brief cognitive screening tests for this clinical population are administered and interpreted based mainly, or exclusively, on total achievement scores. This score based approach can lead to erroneous clinical interpretations unless we also pay attention to the test taking behaviour or to the type of errors committed during the test performance. The goals of the current review are to present the grounds for the process-based approach to neuropsychological assessment, to offer a brief review of the evidence obtained so far regarding its usefulness, and to show the results of a systematic review of existing screening and neuropsychological assessment tools, some of which were already created and/or modified using this approach, and others that may benefit in their screening properties if they underwent modifications according to a process-based approach. It is expected that, in a relatively short period of time, process-based approach versions of screening tools will be available. These modified versions will not alter substantially the standard administration procedure, but will provide a way for scoring and interpretation that goes beyond total scores. This will allow clarifying with higher accuracy the underlying cognitive components involved in the successful or unsuccessful performance in cognitive tasks, and thus will facilitate an early diagnosis of mild cognitive impairment.
TITLE: Evaluacion neuropsicologica basada en los procesos: revision de la evidencia y propuesta para la mejora de las herramientas de cribado de demencia.Una evaluacion neuropsicologica detallada desempeña un papel importante en el proceso diagnostico del deterioro cognitivo leve. No obstante, las escalas de cribado cognitivo breve disponibles para esta poblacion clinica se administran e interpretan basandose mayoritaria o exclusivamente en las puntuaciones totales obtenidas. Este enfoque basado en las puntuaciones puede conducir a interpretaciones clinicas erroneas, a menos que prestemos tambien atencion a la conducta del evaluado o a los tipos de errores cometidos durante la ejecucion de los tests. Los objetivos de esta revision son exponer los fundamentos del enfoque de evaluacion neuropsicologica basada en los procesos, ofrecer una revision breve sobre la evidencia obtenida hasta la fecha sobre su utilidad, y mostrar los resultados de una revision sistematica sobre escalas de cribado cognitivo y evaluacion neuropsicologica, algunas de las cuales fueron ya elaboradas o modificadas segun este enfoque, y otras que podrian beneficiarse de mejoras en su capacidad de cribado si se sometieran a modificaciones segun un enfoque basado en los procesos. Se espera que, en un tiempo relativamente corto, se pueda contar con versiones de las escalas de cribado cognitivo con un enfoque basado en los procesos. Estas versiones modificadas no alteraran sustancialmente la administracion estandar de estas pruebas, pero aportaran un enfoque para la correccion e interpretacion que ira mas alla de las puntuaciones totales. Esto permitira dilucidar con mayor precision los componentes cognitivos implicados en la resolucion exitosa o fallida de estas pruebas cognitivas y facilitara el diagnostico precoz del deterioro cognitivo leve.
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Demência/diagnóstico , Testes de Estado Mental e Demência , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Demência/psicologia , Diagnóstico Precoce , Previsões , Humanos , Testes de Linguagem , Programas de Rastreamento , Testes Neuropsicológicos , Controle de Qualidade , Sensibilidade e EspecificidadeRESUMO
The data presented in this article are related to the research article entitled "The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of a molecular phenotype of multiple sclerosis" Fewings et al. (2017) [1]. Here we identify the set of genes correlated with ZMIZ1 in multiple cohorts, provide phenotypic details on those cohorts, and identify the genes negatively correlated with ZMIZ1 and the cells predominantly expressing those genes. We identify the metabolic pathways in which the molecular phenotype genes are over-represented. Finally, we present the flow cytometry gating strategy we have used to identify the immune cells from blood which are producing ZMIZ1 and RPS6.