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2.
Schizophr Res ; 261: 291-303, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37879227

RESUMO

Individuals with Schizophrenia Spectrum Disorders (SSDs) have significantly higher rates of suicidal thoughts, attempts, and death by suicide in comparison to the general population. Sleep disturbances (reduced duration, timing and quality of sleep) are risk factors for suicidality in the general population, with research indicating the relationship is both immediate and accumulative. Sleep disturbances are also considered to be implicated in the onset and exacerbation of psychotic symptoms in SSDs. Reducing the risk of suicidality in SSDs remains an important public health priority, thus exploration of contributing risk factors is warranted. Sleep monitoring may also offer an adjunct risk monitoring method to suicidality assessments in SSDs, and a potential treatment target for psychotic symptoms. This review aimed to explore proximal and longitudinal relationships between self-reported and objectively measured sleep and suicidality in SSDs and other psychotic disorders. A comprehensive search of four databases was conducted. Eleven studies met the inclusion criteria (10 cross sectional and 1 longitudinal). Narrative synthesis indicated that self-reported sleep disturbances and sleep disorders (e.g. insomnia) were associated with increased risk of suicidal ideation and attempt. However, one study employing polysomnography did not find sleep to be associated with suicidality. Methodological limitations of the evidence base include: i) little experimental or longitudinal evidence, (ii) self-report and/or single item assessment of sleep disturbance, (iii) limited use of validated measures of suicidality, (iv) considerable research in long-term schizophrenia but sparse evidence in early psychosis. Future research should explore (i) cross-sectional and longitudinal relationships between specific aspects of suicidality and objective sleep parameters, (ii) use qualitative or mixed-methods designs to disentangle the nuances and bidirectionality in the sleep-suicide relationship, (iii) explore the psychological processes underpinning or mediating the sleep-suicide relationship in SSDs.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Transtornos do Sono-Vigília , Suicídio , Humanos , Ideação Suicida , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Suicídio/psicologia , Estudos Transversais , Transtornos Psicóticos/psicologia , Sono , Transtornos do Sono-Vigília/complicações , Fatores de Risco
3.
Psychon Bull Rev ; 30(1): 160-173, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36221045

RESUMO

Statistical learning (SL), the ability to pick up patterns in sensory input, serves as one of the building blocks of language acquisition. Although SL has been studied extensively in developmental dyslexia (DD), much less is known about the way SL evolves over time. The handful of studies examining this question were all limited to the acquisition of motor sequential knowledge or highly learned segmented linguistic units. Here we examined memory consolidation of statistical regularities in adults with DD and typically developed (TD) readers by using auditory SL requiring the segmentation of units from continuous input, which represents one of the earliest learning challenges in language acquisition. DD and TD groups were exposed to tones in a probabilistically determined sequential structure varying in difficulty and subsequently tested for recognition of novel short sequences that adhered to this statistical pattern in immediate and delayed-recall sessions separated by a night of sleep. SL performance of the DD group at the easy and hard difficulty levels was poorer than that of the TD group in the immediate-recall session. Importantly, DD participants showed a significant overnight deterioration in SL performance at the medium difficulty level compared to TD, who instead showed overnight stabilization of the learned information. These findings imply that SL difficulties in DD may arise not only from impaired initial learning but also due to a failure to consolidate statistically structured information into long-term memory. We hypothesize that these deficits disrupt the typical course of language acquisition in those with DD.


Assuntos
Dislexia , Adulto , Humanos , Dislexia/diagnóstico , Aprendizagem , Desenvolvimento da Linguagem , Memória de Curto Prazo , Linguística
4.
Intern Med J ; 53(6): 923-929, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35319152

RESUMO

BACKGROUND: Few Australasian autologous stem cell transplantation (ASCT) programmes perform ASCT in the private sector. Relatively little is known about ASCT outcomes in the private sector, which varies in care delivery models to the public system. AIMS: To investigate transplantation activity and survival outcomes at Icon Cancer Centre's Brisbane-based private clinical and laboratory ASCT programme over a 23-year period. METHODS: Retrospective, observational study of all adults who underwent ASCT at Icon between 1996 and 2018. Main outcome measures were transplant activity, overall survival (OS) and 100-day and 1-year transplant-related mortality (TRM). Outcomes were benchmarked against the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR). RESULTS: Between 1996 and 2018, 1676 ASCT were performed in 1454 patients. From 2010 to 2018, ASCT performed at Icon contributed 40% of all South East Queensland ASCT. In the past 5 years, 21% of Icon's patients were aged ≥70 years, compared with 5% across Australasia. For the entire cohort, 100-day and 1-year TRM was 1.1% and 1.7%, respectively, while for those aged ≥70 years, it was 2.0% and 3.1%. For ASCT performed between 2014 and 2018, 100-day and 1-year TRM was 0.8% and 1.4%, which was half the TRM rates reported by the ABMTRR. The 10-year post-transplant OS at Icon was higher than the ABMTRR data, across all disease subtypes. CONCLUSION: We report excellent OS and low TRM, demonstrating the critical role of the private sector in the administration of this highly complex therapy. The Icon ASCT programme is the largest ASCT contributor in Queensland. It is inclusive of patients aged ≥70 years, demonstrating low and acceptable TRM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Estudos Retrospectivos , Transplante Autólogo , Setor Privado , Intervalo Livre de Doença , Transplante de Células-Tronco
5.
Transl Psychiatry ; 12(1): 499, 2022 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460644

RESUMO

ADHD has been associated with cortico-striatal dysfunction that may lead to procedural memory abnormalities. Sleep plays a critical role in consolidating procedural memories, and sleep problems are an integral part of the psychopathology of ADHD. This raises the possibility that altered sleep processes characterizing those with ADHD could contribute to their skill-learning impairments. On this basis, the present study tested the hypothesis that young adults with ADHD have altered sleep-dependent procedural memory consolidation. Participants with ADHD and neurotypicals were trained on a visual discrimination task that has been shown to benefit from sleep. Half of the participants were tested after a 12-h break that included nocturnal sleep (sleep condition), whereas the other half were tested after a 12-h daytime break that did not include sleep (wakefulness condition) to assess the specific contribution of sleep to improvement in task performance. Despite having a similar degree of initial learning, participants with ADHD did not improve in the visual discrimination task following a sleep interval compared to neurotypicals, while they were on par with neurotypicals during the wakefulness condition. These findings represent the first demonstration of a failure in sleep-dependent consolidation of procedural learning in young adults with ADHD. Such a failure is likely to disrupt automatic control routines that are normally provided by the non-declarative memory system, thereby increasing the load on attentional resources of individuals with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos do Sono-Vigília , Adulto Jovem , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Sono , Vigília , Aprendizagem
7.
Sleep Med ; 92: 50-58, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35334450

RESUMO

Poor glycaemic control is found in diabetes, one of the most common, serious, non-communicable diseases worldwide. Trials suggest a relationship between glycaemic control and measures of sleep including duration and quality of sleep. Currently, the relationship between specific sleep stages (including slow-wave sleep (SWS), a sleep stage mainly found early in the night and linked to restorative functioning) and glycaemic control remains unclear. This systematic review aimed to synthesise the evidence of the effectiveness of specific sleep stage manipulation on measures of glycaemic control (insulin resistance, fasting and post-prandial glucose and insulin). Public databases (eg psychINFO, MEDLINE, Academic Search Complete, psychARTICLES, OpenDissertations, Scopus and Cochrane library) were searched for randomised controlled trials. Trials were included if they involved direct manipulation of SWS and/or rapid eye-movement sleep to explore the impact on measures of glycaemic control (insulin resistance, fasting and post-prandial glucose and insulin). Eight trials met the eligibility criteria, with four providing data for inclusion in one of the three meta-analyses. Insulin resistance was significantly higher in the SWS disruption when compared to the normal sleep condition, (p = 0.02). No significant differences were found for measures of fasting or post-prandial glucose or insulin. Risk of bias was considered low for performance bias, detection bias and incomplete outcome data, with unclear selection bias. This is an emerging area of research and this review provides preliminary findings and recommendations for future research around optimising sleep stage disruption (to further explore mechanisms) and sleep stage enhancement techniques (to explore potential interventions).


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Sono de Ondas Lentas , Glicemia , Humanos , Insulina , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Behav Sleep Med ; 20(2): 241-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33896299

RESUMO

BACKGROUND: Listening to music is often used as a self-help intervention to improve sleep quality, but its efficacy among individuals without sleep disorder remains unclear. METHODS: A search was performed on five databases to identify for studies that examined the use of music-based intervention to improve sleep quality among individuals without sleep disorder. Random-effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Twenty-two articles which recruited 1,514 participants were included for review. Meta-analysis of six studies including 424 participants did not find an improvement in sleep quality among recipients of music-based intervention compared to those with standard care (mean difference: -0.80; 95% CI: -2.15 to 0.54, low-quality evidence). Subgroup analysis showed a clear improvement in sleep quality when interventions were administered for at least 3 weeks (-2.09; -3.84 to -0.34, n = 3). No difference in terms of sleep onset latency (standardized mean difference (SMD) -0.32; 95% CI -0.88 to 0.25, n = 4, very-low quality evidence) and sleep efficiency (SMD: -0.59; 95% CI -3.15 to 1.97, n = 2, very-low quality evidence) were observed. The effect of music-based intervention on anxiety, depression and quality of life were mixed with suggestions of possible benefits. CONCLUSION: Music-based intervention in addition to standard care appears to be a promising strategy to improve sleep quality when delivered for 3 week or longer. However, effects are inconsistent across studies and larger randomized controlled studies reporting long-term outcomes are needed before it can be recommended for routine use. PROSPERO REGISTRATION: CRD42018081193.


Assuntos
Musicoterapia , Música , Transtornos do Sono-Vigília , Adulto , Humanos , Qualidade de Vida , Qualidade do Sono , Transtornos do Sono-Vigília/terapia
9.
Sleep Health ; 7(5): 565-571, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34193393

RESUMO

OBJECTIVES: Emerging evidence shows that later high school start times are associated with increased sleep duration; however, little is known if this extends to the university setting. This study investigated associations of first lecture start times with sleep characteristics among university students. DESIGN: Daily diaries. SETTING: Lincoln, UK. PARTICIPANTS: One hundred and fifty-five undergraduate students completed 7-night sleep diaries MEASUREMENTS: Of the plausible lecture-day diaries (Monday-to-Friday, expected N = 755 days), 567 days were lecture days (M = 3.8 lecture-days per student, SD = 1.1). The Consensus Sleep Diary was used to collect sleep characteristics. Two-level multilevel mixed effect generalized linear models were employed in the analyses. RESULTS: Seventy-five percent of first lectures occurred before noon. Students reported short sleep (M = 7.0 hours, SD = 1.9) and fewer reported highest levels of sleep quality (42.8%) and restfulness (24.8%) when first lectures started at 09:00 or 09:30 compared to 10:00 or later. Every hour delay of first lecture start time was associated with 15.1 (95% confidence interval [CI]: 9.5; 20.7) minutes increase in sleep duration and higher odds of reporting the highest levels of sleep quality and restfulness. Focusing on attended lectures starting before noon, hourly delay of first lecture start time was associated with 37.4 (95% CI: 22.0; 52.8) minutes increased sleep duration. Bedtime, sleep time, and sleep onset latency were not significantly associated with first lecture start times. CONCLUSION: This study found that undergraduate students had longer sleep and healthier sleep quality when university first lectures started later. The earliest lecture start time that afforded sufficient sleep duration for students was 10:00.


Assuntos
Transtornos do Sono-Vigília , Sono , Humanos , Instituições Acadêmicas , Estudantes , Fatores de Tempo
11.
Blood ; 137(14): 1970-1979, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33512442

RESUMO

We determined the efficacy of tocilizumab (TCZ) in preventing grade 2-4 acute graft-versus-host disease (aGVHD) in patients with acute leukemia or myelodysplasia undergoing matched sibling donor (MSD) or volunteer unrelated donor (VUD) allogeneic stem cell transplantation after myeloablative or reduced-intensity conditioning across 5 Australian centers. A total of 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day -1. All patients received T-cell-replete peripheral blood stem cell grafts and graft-versus-host disease (GVHD) prophylaxis with cyclosporin/methotrexate. A planned substudy analyzed the VUD cohort. With a median follow-up of 746 days, the incidence of grade 2-4 aGVHD at day 100 for the entire cohort was 36% for placebo vs 27% for TCZ (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.38-1.26; P = .23) and 45% vs 32% (HR, 0.61; 95% CI, 0.31-1.22; P = .16) for the VUD subgroup. The incidence of grade 2-4 aGVHD at day 180 for the entire cohort was 40% for placebo vs 29% for TCZ (HR, 0.68; 95% CI, 0.38-1.22; P = .19) and 48% vs 32% (HR, 0.59; 95% CI, 0.30-1.16; P = .13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade 2 disease. For the entire cohort, transplant-related mortality occurred in 8% vs 11% of placebo-treated vs TCZ-treated patients, respectively (P = .56), and overall survival was 79% vs 71% (P = .27). Median day to neutrophil and platelet engraftment was delayed by 2 to 3 days in TCZ-treated patients, whereas liver toxicity and infectious complications were similar between groups. In this phase 3 randomized double-blind trial, TCZ showed nonsignificant trends toward reduced incidence of grade 2-4 aGVHD in recipients from HLA-matched VUDs but no improvements in long term-survival.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Humanos , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Efeito Placebo , Transplante Homólogo , Resultado do Tratamento
12.
Sleep Med Rev ; 56: 101405, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33360841

RESUMO

Insomnia is common in patients with tinnitus and negatively affects tinnitus symptoms and quality of life. This systematic review aimed to synthesise evidence of the effectiveness of cognitive behavioural therapy (CBT) based interventions on insomnia in adults with tinnitus. We conducted a comprehensive database search (MEDLINE, CINAHL, Web of Science, CENTRAL, ClinicalTrials.gov and PROSPERO) for published, unpublished and ongoing randomised controlled trials of CBT in adults with tinnitus. Five trials met the inclusion criteria for the systematic review, with four of these providing data for the meta-analysis. This demonstrated a statistically significant reduction in Insomnia Severity Index (a standard diagnostic questionnaire of insomnia used in clinical settings) following CBT (-3.28, 95% CI -4.51, -2.05, P=<0.001). There was no evidence of statistical heterogeneity (I2 = 0%). Risk of bias was considered low in all categories except blinding of participants, personnel, and/or the assessment of outcomes. Here, for the first time, we demonstrate that CBT-based interventions can significantly improve sleep in adults with tinnitus.


Assuntos
Terapia Cognitivo-Comportamental , Distúrbios do Início e da Manutenção do Sono , Zumbido , Adulto , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/terapia , Zumbido/terapia
13.
J Thorac Dis ; 12(Suppl 2): S163-S175, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33214921

RESUMO

BACKGROUND: The COVID-19 pandemic has led to significant changes in daily routines and lifestyle worldwide and mental health issues have emerged as a consequence. We aimed to assess the presence of sleep disturbances during the lockdown in the general population. METHODS: Cross-sectional, online survey-based study on adults living through the COVID-19 pandemic. The questionnaire included demographics and specific questions assessing the impact of the pandemic/lockdown on sleep, daytime functioning and mental health in the general population. Identification of sleep pattern changes and specific sleep-related symptoms was the primary outcome, and secondary outcomes involved identifying sleep disturbances for predefined cohorts (participants reporting impact on mental health, self-isolation, keyworker status, suspected COVID-19 or ongoing COVID-19 symptoms). RESULTS: In total, 843 participants were included in the analysis. The majority were female (67.4%), middle aged [52 years (40-63 years)], white (92.2%) and overweight to obese [BMI 29.4 kg/m2 (24.1-35.5 kg/m2)]; 69.4% reported a change in their sleep pattern, less than half (44.7%) had refreshing sleep, and 45.6% were sleepier than before the lockdown; 33.9% had to self-isolate, 65.2% reported an impact on their mental health and 25.9% were drinking more alcohol during the lockdown. More frequently reported observations specific to sleep were 'disrupted sleep' (42.3%), 'falling asleep unintentionally' (35.2%), 'difficulties falling'/'staying asleep' (30.9% and 30.8%, respectively) and 'later bedtimes' (30.0%). Respondents with suspected COVID-19 had more nightmares and abnormal sleep rhythms. An impact on mental health was strongly associated with sleep-related alterations. CONCLUSIONS: Sleep disturbances have affected a substantial proportion of the general population during the COVID-19 pandemic lockdown. These are significantly associated with a self-assessed impact on mental health, but may also be related to suspected COVID-19 status, changes in habits and self-isolation.

14.
J Thorac Dis ; 12(8): 4469-4475, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32944360
15.
Lancet Haematol ; 7(3): e226-e237, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31982039

RESUMO

BACKGROUND: Polycythaemia vera is a myeloproliferative neoplasm characterised by excessive proliferation of erythroid, myeloid, and megakaryocytic components in the bone marrow due to mutations in the Janus kinase 2 (JAK2) gene. Ruxolitinib, a JAK 1 and JAK 2 inhibitor, showed superiority over best available therapy in a phase 2 study in patients with polycythaemia vera who were resistant to or intolerant of hydroxyurea. We aimed to compare the long-term safety and efficacy of ruxolitinib with best available therapy in patients with polycythaemia vera who were resistant to or intolerant of hydroxyurea. METHODS: We report the 5-year results for a randomised, open-label, phase 3 study (RESPONSE) that enrolled patients at 109 sites across North America, South America, Europe, and the Asia-Pacific region. Patients (18 years or older) with polycythaemia vera who were resistant to or intolerant of hydroxyurea were randomly assigned 1:1 to receive either ruxolitinib or best available therapy. Patients randomly assigned to the ruxolitinib group received the drug orally at a starting dose of 10 mg twice a day. Single-agent best available therapy comprised hydroxyurea, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or observation without pharmacological treatment. The primary endpoint, composite response (patients who achieved both haematocrit control without phlebotomy and 35% or more reduction from baseline in spleen volume) at 32 weeeks was previously reported. Patients receiving best available therapy could cross over to ruxolitinib after week 32. We assessed the durability of primary composite response, complete haematological remission, overall clinicohaematological response, overall survival, patient-reported outcomes, and safety after 5-years of follow-up. This study is registered with ClinicalTrials.gov, NCT01243944. FINDINGS: We enrolled patients between Oct 27, 2010, and Feb 13, 2013, and the study concluded on Feb 9, 2018. Of 342 individuals screened for eligibility, 222 patients were randomly assigned to receive ruxolitinib (n=110, 50%) or best available therapy (n=112, 50%). The median time since polycythaemia vera diagnosis was 8·2 years (IQR 3·9-12·3) in the ruxolitinib group and 9·3 years (4·9-13·8) in the best available therapy group. 98 (88%) of 112 patients initially randomly assigned to best available therapy crossed over to receive ruxolitinib and no patient remained on best available therapy after 80 weeks of study. Among 25 primary responders in the ruxolitinib group, six had progressed at the time of final analysis. At 5 years, the probability of maintaining primary composite response was 74% (95% CI 51-88). The probability of maintaining complete haematological remission was 55% (95% CI 32-73) and the probability of maintaining overall clinicohaematological responses was 67% (54-77). In the intention-to-treat analysis not accounting for crossover, the probability of survival at 5 years was 91·9% (84·4-95·9) with ruxolitinib therapy and 91·0% (82·8-95·4) with best available therapy. Anaemia was the most common adverse event in patients receiving ruxolitinib (rates per 100 patient-years of exposure were 8·9 for ruxolitinib and 8·8 for the crossover population), though most anaemia events were mild to moderate in severity (grade 1 or 2 anaemia rates per 100 patient-years of exposure were 8·0 for ruxolitinib and 8·2 for the crossover population). Non-haematological adverse events were generally lower with long-term ruxolitinib treatment than with best available therapy. Thromboembolic events were lower in the ruxolitinib group than the best available therapy group. There were two on-treatment deaths in the ruxolitinib group. One of these deaths was due to gastric adenocarcinoma, which was assessed by the investigator as related to ruxolitinib treatment. INTERPRETATION: We showed that ruxolitinib is a safe and effective long-term treatment option for patients with polycythaemia vera who are resistant to or intolerant of hydroxyurea. Taken together, ruxolitinib treatment offers the first widely approved therapeutic alternative for this post-hydroxyurea patient population. FUNDING: Novartis Pharmaceuticals Corporation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon alfa-2/uso terapêutico , Interferon-alfa/uso terapêutico , Policitemia Vera/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Pirazóis/uso terapêutico , Quinazolinas/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Fibrinolíticos/uso terapêutico , Seguimentos , Humanos , Hidroxiureia/administração & dosagem , Nitrilas , Pipobromano/administração & dosagem , Prognóstico , Pirimidinas , Proteínas Recombinantes/uso terapêutico , Taxa de Sobrevida , Fatores de Tempo
16.
Blood Adv ; 3(20): 3013-3019, 2019 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-31648324

RESUMO

Allogeneic stem cell transplantation (SCT) is a curative therapy for patients with hematological malignancies related largely to an immunological graft-versus-leukemia (GVL) effect mediated by donor T cells and natural killer cells. Relapse of disease after SCT represents failure of GVL and is now the major cause of treatment failure. We sought to augment GVL effects in patients (n = 29) relapsing after SCT in a prospective phase I/II clinical trial of dose-escalated pegylated interferon-2α (peg-IFNα). The administration of peg-IFNα after reinduction chemotherapy, with or without subsequent donor lymphocyte infusion (DLI), resulted in a 2-year overall survival (OS) of 31% (95% confidence interval, 17.3%-49.2%), which rejects the null hypothesis of 7% generated by observations in an institutional historical cohort. As expected, peg-IFNα was associated with graft-versus-host disease (GVHD) and hematological toxicity, which was manageable with scheduled dose modifications. Progression-free survival (PFS) was greatest in patients who experienced GVHD, although the majority of those patients still eventually progressed. Higher PFS and OS were associated with pretreatment proportions of immune cell populations with regulatory function, including mucosal invariant T cells, regulatory T cells, and plasmacytoid dendritic cells, independent of any association with GVHD. Peg-IFNα administration after relapse thus constitutes a logical strategy to invoke GVL effects and should be studied in a larger, multicenter cohort. This trial was registered at www.anzctr.org.au as #ACTRN12612000728831.


Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Adulto , Idoso , Biomarcadores , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/mortalidade , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Modelos de Riscos Proporcionais , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Condicionamento Pré-Transplante , Transplante Homólogo , Adulto Jovem
17.
PLoS One ; 14(8): e0221428, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31437211

RESUMO

BACKGROUND: Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders characterised by behavioural, communication and social impairments. The prevalence of sleep disturbances in children with ASD is 40-80%, with significant effects on quality of life for the children and carers. This systematic review aimed to synthesise evidence of the effects of behavioural interventions to improve sleep among children with ASD. METHODS: Databases (MEDLINE, PsycINFO, CINAHL, ScienceDirect, Autism Data, CENTRAL, ClinicalTrials.gov and Current Controlled Trials) were searched for published, unpublished and ongoing randomised controlled trials evaluating the effect of non-pharmacological interventions for insomnia in children with autism spectrum conditions. RESULTS: Three studies met the inclusion criteria, one provided actigraphy data, one Children's Sleep Habits Questionnaire (CSHQ) data, and one both actigraphy and CSHQ data for use in meta-analyses. There were significant differences between the behavioural intervention and comparison groups (actigraphy data) for total sleep time (24.41 minutes, 95% CI 5.71, 43.11, P = 0.01), sleep latency (-18.31 minutes, 95% CI -30.84, -5.77, P = 0.004) and sleep efficiency (5.59%, 95% CI 0.87, 10.31, P = 0.02). There was also a favourable intervention effect evident for the subjective CSHQ data (-4.71, 95% CI -6.70, -2.73, P<0.00001). Risk of bias was low across several key domains (randomisation, allocation concealment and reporting), with some studies being unclear due to poor reporting. CONCLUSIONS: There are very few high quality randomised controlled trials in this area. Here we provide initial synthesised quantitative evidence of the effectiveness of behavioural interventions for treating sleep problems in children with ASD. TRIAL REGISTRATION: Protocol was registered (CRD42017081784) on the International Prospective Register of Systematic Reviews (http://www.crd.york.ac.uk/PROSPERO).


Assuntos
Transtorno do Espectro Autista/complicações , Distúrbios do Início e da Manutenção do Sono/complicações , Actigrafia , Transtorno do Espectro Autista/fisiopatologia , Criança , Humanos , Viés de Publicação , Risco , Sono , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Inquéritos e Questionários , Resultado do Tratamento
19.
Leuk Lymphoma ; 60(9): 2214-2222, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30947585

RESUMO

Outcomes for adults with relapsed/refractory acute lymphoblastic leukemia (ALL) are poor with chemotherapy, particularly in later salvage. The TOWER study examined survival, remission, bridge to allogeneic hematopoietic stem cell transplantation (HSCT), and safety with blinatumomab versus chemotherapy. This report examined outcomes separately for study treatment as first or later salvage. Adults with Philadelphia chromosome-negative B-cell precursor ALL relapsed/refractory to chemotherapy were randomly assigned 2:1 to receive blinatumomab by continuous infusion for 4 weeks in 6-week cycles, or standard salvage chemotherapy. Overall survival for blinatumomab versus chemotherapy was higher both in first salvage and in later salvage. Safety was similar between patients in first salvage and those in later salvage. Blinatumomab as later salvage was associated with higher complete remission rates and served as a bridge to allogeneic HSCT, supporting the use of blinatumomab in both settings. This study is registered at www.clinicaltrials.gov as #NCT02013167.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Recidiva Local de Neoplasia/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Terapia de Salvação/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Biespecíficos/efeitos adversos , Antineoplásicos/efeitos adversos , Quimioterapia Adjuvante/métodos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Intervalo Livre de Progressão , Indução de Remissão/métodos , Terapia de Salvação/efeitos adversos , Adulto Jovem
20.
Behav Brain Res ; 359: 17-27, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321558

RESUMO

Emotional memory may be modulated by BDNF Val66Met and 5-HTTLPR polymorphisms. However, the influence of these genetic variants on the overnight retention of emotional memories has not been investigated in humans. Thirty-six healthy female students were selected to participate in this study based on 5-HTTLPR genotype status (L'/L', L'/S', S'/S'). Participants were also genotyped for BDNF Val66Met (Val/Val, Met carriers). We measured recognition performance for positive, neutral and negative images before and after overnight sleep. We found a significant interaction between BDNF Val66Met genotype group and image valence on post-sleep recognition performance. This interaction was driven by greater memory for negative and positive images, relative to neutral images, in Met carriers. We also found that longer Rapid Eye Movement (REM) sleep duration predicted greater post-sleep recognition performance for negative images in Met carriers, but not in Val homozygotes. We observed no influence of 5-HTTLPR polymorphisms on post- sleep recognition performance for positive, neutral or negative images. Our findings support a modulatory role for BDNF Val66Met in overnight emotional memory retention in females. We discuss the implications of this finding for understanding the influence of BDNF Val66Met on depression vulnerability.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Emoções/fisiologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Sono REM/fisiologia , Adolescente , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/genética , Depressão/metabolismo , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Heterozigoto , Humanos , Polimorfismo de Nucleotídeo Único , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Fatores de Tempo , Percepção Visual/fisiologia , Adulto Jovem
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