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1.
Gene Ther ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755404

RESUMO

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4-/-) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.

2.
Clin Radiol ; 79(4): 287-295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38238147

RESUMO

AIM: To describe the (a) frequency of improving, static, and worsening chest radiograph (CXR) appearances; (b) differences in demographic, initial rudimentary haematological and CXR variables and these patterns; and (c) frequency of different trajectories of serial CXR evolution, in COVID-19 patients presenting consecutively. MATERIALS AND METHODS: This multicentre retrospective study included all COVID-19 patients admitted from 1-30 April 2020, meeting the inclusion criteria across 24 (blinded) hospitals. Follow-up CXRs on admission, the subsequent (where available), and at 4-8 weeks were scored for the presence of parenchymal opacities across six zones. Three cohorts were defined: improved, static, and/or worsened. The chi-squared and Kruskal-Wallis tests were used to compare demographic, laboratory, and CXR variables. Trajectories of CXR evolution were assessed when all three CXRs were available (226 patients). RESULTS: Of 452 included patients (median age 66 years, interquartile range 54.3-79, 262 men), 211 (46.7%) improved, 140 (31%) were static, and 101 (22.3%) worsened. Improving patients were more likely younger, with a classic COVID-19 radiograph and higher initial CXR zonal severity scores (both p<0.001), while worsening patients had lower initial lymphocyte counts (p=0.008). The most frequent trajectory was worsened then improved (n=63, 27.9%) followed by static then improved (n=46, 20.4%) and static (n=42, 18.6%). CONCLUSION: Most patients with COVID-19 during the first wave of the pandemic demonstrated radiographic improvement; these patients were more likely younger with classic COVID-19 appearances and initially more extensive abnormality. Conversely, radiographic deterioration was associated with lower lymphocyte counts. The three most common trajectories were worsening then improvement, static then improvement, and static throughout.


Assuntos
COVID-19 , Idoso , Humanos , Masculino , COVID-19/diagnóstico por imagem , Radiografia , Radiografia Torácica , Estudos Retrospectivos , Reino Unido/epidemiologia , Feminino , Pessoa de Meia-Idade
3.
Clin Radiol ; 78(4): e336-e341, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36746724

RESUMO

AIM: To understand the attitudes of UK radiology trainees towards artificial intelligence (AI) in Radiology, in particular, assessing the demand for AI education. MATERIALS AND METHODS: A survey, which ran over a period of 2 months, was created using the Google Forms platform and distributed via email to all UK training programmes. RESULTS: The survey was completed by 149 trainee radiologists with at least one response from all UK training programmes. Of the responses, 83.7% were interested in AI use in radiology but 71.4% had no experience of working with AI and 79.9% would like to be involved in AI-based projects. Almost all (98.7%) felt that AI should be taught during their training, yet only one respondent stated that their training programme had implemented AI teaching. Respondents indicated that basic understanding, implementation, and critical appraisal of AI software should be prioritized in teaching. Of the trainees, 74.2% agreed that AI would enhance the job of diagnostic radiologists over the next 20 years. The main concerns raised were information technology/implementation and ethical/regulatory issues. CONCLUSION: Despite the current limited availability of AI-based activities and teaching within UK training programmes, UK trainees' attitudes towards AI are mostly positive with many showing interest in being involved with AI-based projects, activities, and teaching.


Assuntos
Inteligência Artificial , Radiologia , Humanos , Radiologia/educação , Radiologistas , Radiografia , Inquéritos e Questionários
4.
Clin Radiol ; 78(2): e45-e51, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36411087

RESUMO

AIM: To assess the clinical performance of a commercially available machine learning (ML) algorithm in acute stroke. MATERIALS AND METHODS: CT and CT angiography (CTA) studies of 104 consecutive patients (43 females, age range 19-93, median age 62) performed for suspected acute stroke at a single tertiary institution with real-time ML software analysis (RAPID™ ASPECTS and CTA) were included. Studies were retrospectively reviewed independently by two neuroradiologists in a blinded manner. RESULTS: The cohort included 24 acute infarcts and 16 large vessel occlusions (LVO). RAPID™ ASPECTS interpretation demonstrated high sensitivity (87.5%) and NPV (87.5%) but very poor specificity (30.9%) and PPV (30.9%) for detection of acute ischaemic parenchymal changes. There was a high percentage of false positives (51.1%). In cases of proven LVO, RAPID™ ASPECTS showed good correlation with neuroradiologists' blinded independent interpretation, Pearson correlation coefficient = 0.96 (both readers), 0.63 (RAPID™ vs reader 1), 0.69 (RAPID™ vs reader 2). RAPID™ CTA interpretation demonstrated high sensitivity (92.3%), specificity (85.3%), and negative predictive (NPV) (98.5%) with moderate positive predictive value (PPV) (52.2%) for detection of LVO (N=13). False positives accounted for 12.5% of cases, of which 27.3% were attributed to arterial stenosis. CONCLUSION: RAPID™ CTA was robust and reliable in detection of LVO. Although demonstrating high sensitivity and NPV, RAPID™ ASPECTS interpretation was associated with a high number of false positives, which decreased clinicians' confidence in the algorithm. However, in cases of proven LVO, RAPID™ ASPECTS performed well and had good correlation with neuroradiologists' blinded interpretation.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Sensibilidade e Especificidade , Acidente Vascular Cerebral/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Algoritmos , Aprendizado de Máquina
5.
Psychol Med ; 52(8): 1448-1457, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-32924897

RESUMO

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.


Assuntos
Transtorno Depressivo Maior , Adulto , Transtorno Depressivo Maior/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fototerapia/métodos , Resultado do Tratamento
6.
Hong Kong Med J ; 28(3): 204-214, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35697524

RESUMO

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.


Assuntos
Recidiva Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Pré-Escolar , Intervalo Livre de Doença , Humanos , Incidência , Recidiva Local de Neoplasia/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Taxa de Sobrevida
7.
Clin Radiol ; 76(4): 302-309, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33583566

RESUMO

AIM: To inform the activity of the newly formed Radiology Academic Network for Trainees (RADIANT) regarding the current level of interest, engagement, and barriers experienced by UK radiology trainees to undertake research. MATERIALS AND METHODS: A web-based survey containing nine questions was sent to the UK radiology training programme directors for distribution to trainees. The survey was also distributed to all trainee members of the RADIANT network. This led to 224 responses over a period of 2 months. RESULTS: A large proportion of respondents indicated a desire to participate in research in the next 12 months 72.3% (n=162). The most frequently reported barriers to research were lack of time (60.7%, n=136), lack of awareness of local/departmental opportunities (53.6%, n=120), and limited experience in research statistics (46%, n=103). The most favoured factor that would improve access to research was structured research training opportunities, qualified as a project with clear goals and timeline (71%, n=159), protected time for research (68.8%, n=154), and local or national trainee research networks (40.2%, n=90 and 37.1%, n=83, respectively). CONCLUSION: Many radiology trainees would like to participate in research, but multiple barriers exist. The formation of RADIANT is seen as a key part of a multifaceted approach to improving access to quality research activity alongside support from local and regional training bodies.


Assuntos
Pesquisa Biomédica , Escolha da Profissão , Radiologia/educação , Educação de Pós-Graduação em Medicina , Humanos , Motivação , Inquéritos e Questionários , Fatores de Tempo , Reino Unido
8.
Hong Kong Med J ; 27(4): 258-265, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33632937

RESUMO

INTRODUCTION: The objective was to investigate the changes in urology practice during coronavirus disease 2019 (COVID-19) pandemic with a perspective from our experience with severe acute respiratory syndrome (SARS) in 2003. METHODS: Institutional data from all urology centres in the Hong Kong public sector during the COVID-19 pandemic (1 Feb 2020-31 Mar 2020) and a non-COVID-19 control period (1 Feb 2019-31 Mar 2019) were acquired. An online anonymous questionnaire was used to gauge the impact of COVID-19 on resident training. The clinical output of tertiary centres was compared with data from the SARS period. RESULTS: The numbers of operating sessions, clinic attendance, cystoscopy sessions, prostate biopsy, and shockwave lithotripsy sessions were reduced by 40.5%, 28.5%, 49.6%, 44.8%, and 38.5%, respectively, across all the centres reviewed. The mean numbers of operating sessions before and during the COVID-19 pandemic were 85.1±30.3 and 50.6±25.7, respectively (P=0.005). All centres gave priority to cancer-related surgeries. Benign prostatic hyperplasia-related surgery (39.1%) and ureteric stone surgery (25.5%) were the most commonly delayed surgeries. The degree of reduction in urology services was less than that during SARS (47.2%, 55.3%, and 70.5% for operating sessions, cystoscopy, and biopsy, respectively). The mean numbers of operations performed by residents before and during the COVID-19 pandemic were 75.4±48.0 and 34.9±17.2, respectively (P=0.002). CONCLUSION: A comprehensive review of urology practice during the COVID-19 pandemic revealed changes in every aspect of practice.


Assuntos
COVID-19/epidemiologia , Controle de Doenças Transmissíveis/métodos , Internato e Residência , Padrões de Prática Médica , Síndrome Respiratória Aguda Grave/epidemiologia , Procedimentos Cirúrgicos Urológicos , Urologia , Atenção à Saúde/organização & administração , Atenção à Saúde/tendências , Surtos de Doenças/estatística & dados numéricos , Hong Kong/epidemiologia , Humanos , Internato e Residência/métodos , Internato e Residência/organização & administração , Inovação Organizacional , Padrões de Prática Médica/organização & administração , Padrões de Prática Médica/tendências , SARS-CoV-2 , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/estatística & dados numéricos , Urologia/educação , Urologia/estatística & dados numéricos
9.
Ann Oncol ; 31(9): 1223-1230, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32464281

RESUMO

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.


Assuntos
Neoplasias da Mama , Quinolinas , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Humanos , Qualidade de Vida , Quinolinas/uso terapêutico , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico
10.
BMC Cancer ; 20(1): 1153, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33243173

RESUMO

BACKGROUND: The aim of this study was to translate and linguistically validate the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) into Simplified Chinese for use in Singapore. METHODS: All 124 items of the English source PRO-CTCAE item library were translated into Simplified Chinese using internationally established translation procedures. Two rounds of cognitive interviews were conducted with 96 cancer patients undergoing adjuvant treatment to determine if the translations adequately captured the PRO-CTCAE source concepts, and to evaluate comprehension, clarity and ease of judgement. Interview probes addressed the 78 PRO-CTCAE symptom terms (e.g. fatigue), as well as the attributes (e.g. severity), response choices, and phrasing of 'at its worst'. Items that met the a priori threshold of ≥20% of participants with comprehension difficulties were considered for rephrasing and retesting. Items where < 20% of the sample experienced comprehension difficulties were also considered for rephrasing if better phrasing options were available. RESULTS: A majority of PRO-CTCAE-Simplified Chinese items were well comprehended by participants in Round 1. One item posed difficulties in ≥20% and was revised. Two items presented difficulties in < 20% but were revised as there were preferred alternative phrasings. Twenty-four items presented difficulties in < 10% of respondents. Of these, eleven items were revised to an alternative preferred phrasing, four items were revised to include synonyms. Revised items were tested in Round 2 and demonstrated satisfactory comprehension. CONCLUSIONS: PRO-CTCAE-Simplified Chinese has been successfully developed and linguistically validated in a sample of cancer patients residing in Singapore.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Linguística/métodos , Medidas de Resultados Relatados pelo Paciente , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , National Cancer Institute (U.S.) , Estados Unidos
11.
Arch Toxicol ; 94(9): 3217-3230, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32561961

RESUMO

Atrazine (ATR; 2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an herbicide widely used to kill annual grasses and broadleaf weeds in crops such as corn, sorghum, and sugarcane. Studies in rodents have shown that chronic ATR exposure is associated with alterations in the nigrostriatal dopaminergic pathway such as hyperactivity, decreased striatal dopamine levels, and diminished numbers of tyrosine hydroxylase positive cells in substantia nigra pars compacta. However, the effects of ATR on neurotransmitters such as GABA and glutamate have been scarcely studied. To evaluate the impact of ATR on motor and anxiety tasks, tissue levels of GABA, glutamate, glutamine, and extracellular and potassium-evoked release of glutamate in the striatum, we daily exposed Sprague-Dawley male rats to 1 or 10 mg ATR/kg of body weight for 12-14 months. As previously reported, chronic ATR exposure causes hyperactivity in the group exposed to 10 mg ATR/kg and increased anxiety in both groups exposed to ATR. GABA, glutamate, and glutamine levels were differentially altered in brain regions related to nigrostriatal and mesolimbic systems, the amygdala, and the prefrontal cortex. The groups exposed to 10 mg ATR/kg showed increased extracellular levels and release of glutamate in the striatum. These neurochemical alterations could underlie the behavioral changes observed in rats. These results indicate that chronic exposure to the herbicide ATR disrupts the neurochemistry of several brain structures and could be a risk factor for the development of neurodegenerative diseases.


Assuntos
Atrazina/toxicidade , Encéfalo/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Herbicidas/toxicidade , Ácido gama-Aminobutírico/metabolismo , Animais , Encéfalo/fisiologia , Corpo Estriado , Dopamina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase
12.
Acute Med ; 19(4): 183-191, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33215171

RESUMO

INTRODUCTION: COVID-19 pneumonia presented a unique problem for healthcare systems with the potential to overwhelm hospitals and lead to unnecessary morbidity and mortality. Safe triage and follow up systems are required to manage this unprecedented demand. METHODS: We designed a pathway for the triage and assessment of patients based on their resting oxygen saturations and response to a 30 metre rapid walking test. We admitted patients to a 'Virtual Ward' for remote oximetry monitoring from the Emergency Department, step down from inpatient wards and from the local Primary Care 'Hot Hub'. This allowed the safe and managed readmission of those patients who deteriorated at home. RESULTS: During the first wave of COVID-19 we entered 273 onto the pathway for Virtual Ward follow up. Of these, 31 patients were readmitted to hospital, two were admitted to Intensive Care and one patient died. Median oxygen saturation at presentation was 97 % (IQR 96-98%) and following a 30 metre walk test 96% (IQR 94-97%). Median NEWS-2 score was 2 (IQR 1-3). On feedback 99.5% of patients were likely or extremely likely to recommend the service to their family and friends. There was a cost avoidance of £107,600 per month. CONCLUSION: It is safe, feasible and cost effective to set up a triage system with remote oximetry monitoring for patients with COVID-19 and overwhelmingly patients find it a positive experience.


Assuntos
Infecções por Coronavirus/diagnóstico , Serviço Hospitalar de Emergência/organização & administração , Oximetria , Pneumonia Viral/diagnóstico , Consulta Remota , Triagem , Betacoronavirus , COVID-19 , Humanos , Pandemias , Readmissão do Paciente , SARS-CoV-2
13.
Nicotine Tob Res ; 21(6): 747-754, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-29432572

RESUMO

Cognitive control (CC)-the ability to regulate attention and memory-plays an important role in a variety of health behaviors, including smoking behavior. In this theoretical review of the literature, we propose a CC and smoking behavior framework that includes (1) the positive influence of CC on the self-regulation of smoking, (2) nicotine-induced improvements in CC that may indirectly reinforce smoking (including withdrawal reversal effects), and (3) the long-term effects of smoking on the brain that may result in reduced CC. Integration of these literatures suggests that CC contributes to both self-regulation (ie, brake pedal) and nicotine-related reinforcement (ie, gas pedal) amid the catastrophic effects of long-term smoking, which may reduce self-regulatory control over smoking while also enhancing indirect reinforcement. Supportive evidence and limitations of this approach will be presented, as well as ideas for future research directions that may fully examine this multifaceted modeling of CC in relation to smoking behavior. IMPLICATIONS: There is substantial evidence that CC contributes to self-regulation (ie, brake pedal) and reinforcement (ie, gas pedal) of smoking behavior as well as evidence that long-term smoking may cause reduced CC. The proposed model delineates how these opposing influences of CC may mask the unique contribution of self-regulation and reinforcement in maintaining smoking behavior. Targeting CC for treating nicotine dependence will require more nuanced approaches that consider the independent and combined effects of self-regulation and reinforcement to improve smoking cessation success rates.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Reforço Psicológico , Autoeficácia , Abandono do Hábito de Fumar/psicologia , Fumar/psicologia , Tabagismo/prevenção & controle , Humanos , Abandono do Hábito de Fumar/métodos , Tabagismo/psicologia
15.
BJOG ; 125(7): 848-855, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29090507

RESUMO

OBJECTIVE: To investigate the pregnancy outcomes in a cohort of women who failed to obtain a result in non-invasive prenatal testing (NIPT). DESIGN: Historical cohort study. SETTING: A multicentre private practice in Sydney, Australia. POPULATION: Women who failed to obtain a result from NIPT (n = 131). METHODS: The maternal characteristics, antenatal investigations and pregnancy outcomes for these women were compared with those who obtained a result at the same practice and to the general Australian obstetric population. MAIN OUTCOME MEASURES: Antenatal investigations: pregnancy-associated plasma protein-A (PAPP-A), free ß-human chorionic gonadotrophin (ß-hCG), placental growth factor (PlGF), uterine artery pulsatility index (PI), mean arterial pressure (MAP). Pregnancy outcomes: chromosomal abnormality, pre-eclampsia, gestational diabetes, small-for-gestational-age (SGA), preterm delivery. RESULTS: Only 1.1% of NIPT samples failed to return a result. This cohort was significantly older and had significantly increased weight compared with the general Australian obstetric population. Pregnancy outcomes were available for 94% of the cohort. There were significantly higher rates of chromosomal aneuploidies (6.5% versus 0.2%, P < 0.0001), pre-eclampsia (11% versus 1.5%, P < 0.0001) and gestational diabetes (23% versus 7.5%, P < 0.0001) compared with the general obstetric population. Rates of preterm delivery and SGA were elevated but did not reach significance. Antenatal investigations demonstrated decreased PAPP-A MoM (0.75 versus 1.14, P < 0.0001), decreased free ß-hCG (0.71 versus 1.01, P < 0.0001) and increased uterine artery PI (1.79 versus 1.65, P = 0.02). CONCLUSION: Women who fail to obtain a result from NIPT are at increased risk of adverse pregnancy outcomes, in particular chromosomal aneuploidy, gestational diabetes and pre-eclampsia. FUNDING: None received. TWEETABLE ABSTRACT: Women who fail to obtain a result from cell-free DNA NIPT are at increased risk of adverse pregnancy outcomes.


Assuntos
Ácidos Nucleicos Livres/sangue , Erros de Diagnóstico/estatística & dados numéricos , Testes para Triagem do Soro Materno/estatística & dados numéricos , Pressão Arterial , Gonadotropina Coriônica Humana Subunidade beta/sangue , Aberrações Cromossômicas/estatística & dados numéricos , Estudos de Coortes , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Recém-Nascido Pequeno para a Idade Gestacional , Testes para Triagem do Soro Materno/métodos , New South Wales , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Gravidez , Resultado da Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Fluxo Pulsátil , Ultrassonografia Pré-Natal , Artéria Uterina/diagnóstico por imagem
16.
Nature ; 491(7423): 244-8, 2012 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-23135471

RESUMO

Palaeomagnetic studies of Palaeoproterozoic to Cretaceous rocks propose a suite of large and relatively rapid (tens of degrees over 10 to 100 million years) excursions of the rotation pole relative to the surface geography, or true polar wander (TPW). These excursions may be linked in an oscillatory, approximately coaxial succession about the centre of the contemporaneous supercontinent. Within the framework of a standard rotational theory, in which a delayed viscous adjustment of the rotational bulge acts to stabilize the rotation axis, geodynamic models for oscillatory TPW generally appeal to consecutive, opposite loading phases of comparable magnitude. Here we extend a nonlinear rotational stability theory to incorporate the stabilizing effect of TPW-induced elastic stresses in the lithosphere. We demonstrate that convectively driven inertia perturbations acting on a nearly prolate, non-hydrostatic Earth with an effective elastic lithospheric thickness of about 10 kilometres yield oscillatory TPW paths consistent with palaeomagnetic inferences. This estimate of elastic thickness can be reduced, even to zero, if the rotation axis is stabilized by long-term excess ellipticity in the plane of the TPW. We speculate that these sources of stabilization, acting on TPW driven by a time-varying mantle flow field, provide a mechanism for linking the distinct, oscillatory TPW events of the past few billion years.

17.
Eur J Clin Microbiol Infect Dis ; 36(10): 1801-1809, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28516201

RESUMO

The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir). Compared to INF-based treatment, DAA-based treatments yielded an incremental cost of $24,677-$31,171 per course while improving the rate of sustained virologic response (SVR) from 59-66% to 82.3-99.8%. The incremental cost-effective ratios of DAA-based treatments ranged from $9724 to $29,189 per treatment success, which were all below the cost-effectiveness threshold of local GDP per capita ($42,423 in 2015). Introducing DAAs resulted in a 126.1% ($383.7 million) budget increase on HCV infection management over 5 years. A 50% change in DAA medication costs reflected a change in the incremental budget from $55.2 to $712.3 million. DAA-based treatments are cost-effective alternatives to INF-based treatment in Hong Kong. Introducing DAAs to the public hospital formulary yields a considerable budget increase but is still economically favorable to the local government.


Assuntos
Antivirais/economia , Antivirais/uso terapêutico , Análise Custo-Benefício , Gastos em Saúde , Hepatite C Crônica/tratamento farmacológico , Hong Kong , Humanos , Resultado do Tratamento
20.
Water Sci Technol ; 74(8): 1876-1884, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27789888

RESUMO

The understanding of how the sediment deposit thickness influences the incipient motion characteristic is still lacking in the literature. Hence, the current study aims to determine the effect of sediment deposition thickness on the critical velocity for incipient motion. An incipient motion experiment was conducted in a rigid boundary rectangular flume of 0.6 m width with varying sediment deposition thickness. Findings from the experiment revealed that the densimetric Froude number has a logarithmic relationship with both the thickness ratios ts/d and ts/y0 (ts: sediment deposit thickness; d: grain size; y0: normal flow depth). Multiple linear regression analysis was performed using the data from the current study to develop a new critical velocity equation by incorporating thickness ratios into the equation. The new equation can be used to predict critical velocity for incipient motion for both loose and rigid boundary conditions. The new critical velocity equation is an attempt toward unifying the equations for both rigid and loose boundary conditions.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/análise , Movimentos da Água , Modelos Lineares
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