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1.
J Biol Chem ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690632

RESUMO

Increased carbohydrate consumption increases hepatic de novo lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids (MUFA), oleate and palmitoleate, from the saturated fatty acids, stearate and palmitate, respectively. SCD1-deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia. However, the mechanism of this protection by SCD1 deficiency is unclear. Using a liver-specific SCD1 knockout (LKO) mouse model fed a high-carbohydrate, low-fat diet (HCD), we show that hepatic SCD1 deficiency increases systemic glucose uptake. Hepatic SCD1 deficiency enhanced glucose transporter type 1 (GLUT1) expression in the liver and also up-regulated GLUT4 and adiponectin expression in the adipose tissue. The enhanced glucose uptake correlated with increased liver expression and elevated plasma levels of fibroblast growth factor 21 (FGF21), a hepatokine known to increase systemic insulin sensitivity and to regulate whole-body lipid metabolism. Feeding LKO mice with triolein-supplemented, but not tristearin-supplemented, HCD reduced FGF21 expression and plasma levels. Consistently, SCD1 inhibition in primary hepatocytes induced FGF21 expression, which was repressed by treatment with oleate but not palmitoleate. Moreover, deletion of the transcriptional coactivator PPARg coactivator 1α (PGC-1α) reduced hepatic and plasma FGF21 and white adipocyte tissue-specific GLUT4 expression and raised plasma glucose levels in the LKO mice. These results suggest that hepatic oleate regulates glucose uptake in adipose tissue either directly or partially by modulating the hepatic PGC-1α-FGF21 axis.

2.
BMC Health Serv Res ; 19(1): 841, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727071

RESUMO

BACKGROUND: In the context of increasing availability of computed tomography (CT) scans, judicious use of ionising radiation is a priority to minimise the risk of future health problems. Hence, education of clinicians on the risks and benefits of CT scans in the management of patients is important. METHODS: An educational message about the associated lifetime cancer risk of a CT scan was added to all CT scan reports at a busy acute teaching hospital in the UK. An online multiple choice survey was completed by doctors before and after the intervention, assessing education and knowledge of the risks involved with exposure to ionising radiation. RESULTS: Of 546 doctors contacted at baseline, 170 (31%) responded. Over a third (35%) of respondents had received no formal education on the risks of exposure to ionising radiation. Over a quarter (27%) underestimated (selected 1 in 30,000 or negligible lifetime cancer risk) the risk associated with a chest, abdomen and pelvis CT scan for a 20 year old female. Following exposure to the intervention for 1 year there was a statistically significant improvement in plausible estimates of risk from 68.3 to 82.2% of respondents (p < 0.001). There was no change in the proportion of doctors correctly identifying imaging modalities that do or do not involve ionising radiation. CONCLUSIONS: Training on the longterm risks associated with diagnostic radiation exposure is inadequate among hospital doctors. Exposure to a simple non-directional educational message for 1 year improved doctors' awareness of risks associated with CT scans. This demonstrates the potential of the approach to improve knowledge that could improve clinical practice. This approach is easily deliverable and may have applications in other areas of clinical medicine. The wider and longer term impact on radiation awareness is unknown, however, and there may be a need for regular mandatory training in the risks of radiation exposure.

3.
Sci Rep ; 9(1): 15761, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673045

RESUMO

Stearoyl CoA desaturase 1 (SCD1) is a key enzyme in lipogenesis as it catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate (18:1n9) and palmitoleate (16:1n7) from saturated fatty acids (SFA), stearate (18:0) and palmitate (16:0), respectively. Studies on SCD1 deficiency in mouse models demonstrated beneficial metabolic phenotypes such as reduced adiposity and improved glucose tolerance. Even though, SCD1 represents a potential target to resolve obesity related metabolic diseases; SCD1 deficiency causes endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR). The induction of ER stress in response to SCD1 deficiency is governed by the cofactor, PGC-1α. However, the mechanism by which SCD1 deficiency increases PGC-1α and subsequently induces ER stress still remains elusive. The present study demonstrates that despite reduced lipogenesis, liver specific SCD1 deficiency activates the mechanistic target of rapamycin complex 1 (mTORC1) along with induction of PGC-1α and ER stress. Further, mTORC1 inhibition attenuates SCD1 deficiency-mediated induction of both PGC-1α and ER stress. Similar observations were seen by restoring endogenously synthesized oleate, but not palmitoleate, suggesting a clear mTORC1-mediated regulation of ER stress during SCD1 deficiency. Overall, our results suggest a model whereby maintaining adequate levels of hepatic oleate is required to suppress mTORC1-mediated ER stress. In addition, the activation of mTORC1 by SCD1 deficiency reveals an important function of fatty acids in regulating different cellular processes through mTORC1 signaling.

4.
J Med Radiat Sci ; 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31709775

RESUMO

Artificial intelligence (AI) is heralded as the most disruptive technology to health services in the 21st century. Many commentary articles published in the general public and health domains recognise that medical imaging is at the forefront of these changes due to our large digital data footprint. Radiomics is transforming medical images into mineable high-dimensional data to optimise clinical decision-making; however, some would argue that AI could infiltrate workplaces with very few ethical checks and balances. In this commentary article, we describe how AI is beginning to change medical imaging services and the innovations that are on the horizon. We explore how AI and its various forms, including machine learning, will challenge the way medical imaging is delivered from workflow, image acquisition, image registration to interpretation. Diagnostic radiographers will need to learn to work alongside our 'virtual colleagues', and we argue that there are vital changes to entry and advanced curricula together with national professional capabilities to ensure machine-learning tools are used in the safest and most effective manner for our patients.

5.
JAMA Netw Open ; 2(10): e1914149, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31664443

RESUMO

Importance: Clostridioides difficile infection (CDI) remains a leading cause of health care facility-associated infection. A greater understanding of the regional epidemiologic profile of CDI could inform targeted prevention strategies. Objectives: To assess trends in incidence of health care facility-associated and community-acquired CDI among hospitalized patients over time and to conduct a subanalysis of trends in the NAP1 strain of CDI over time. Design, Setting, and Participants: This long-term multicenter cohort study reviewed records of patients (N = 2 025 678) admitted to a network of 43 regional community hospitals primarily in the southeastern United States from January 1, 2013, through December 31, 2017. Generalized linear mixed-effects models were used to adjust for potential clustering within facilities and changing test method (nucleic acid amplification testing or toxin enzyme immunoassay) over time. Main Outcomes and Measures: Clostridioides difficile infection incidence rates were counted as cases per 1000 admissions for community-acquired and total CDI cases or cases per 10 000 patient-days for health care facility-associated CDI. Long-term trends in the proportion of cases acquired in the community and in NAP1 strain incidence were also evaluated. Results: A total of 2 025 678 admissions and 21 254 CDI cases were included (12 678 [59.6%] female; median [interquartile range] age, 69 [55-80] years). Median (interquartile range) total CDI incidence increased slightly from 7.9 (3.5-12.4) cases per 1000 admissions in 2013 to 9.3 (4.9-13.7) cases per 1000 admissions in 2017. After adjustment, the overall incidence of health care facility-associated CDI declined (incidence rate ratio [IRR], 0.995; 95% CI, 0.990-0.999; P = .03), whereas insufficient evidence was found for either an increase or a decrease in community-acquired CDI (IRR, 1.004; 95% CI, 0.999-1.009; P = .14). The proportion of cases classified as community acquired increased over time from a mean (SD) of 0.49 (0.28) in 2013 to 0.61 (0.26) in 2017 (odds ratio, 1.010 per month; 95% CI, 1.006-1.015; P < .001). Rates of the NAP1 strain of CDI varied widely between facilities, with no statistically significant change in NAP1 strain incidence over time in the community setting (IRR, 1.007; 95% CI, 0.994-1.021) or health care facility setting (IRR, 1.011; 95% CI, 0.990-1.032). Conclusions and Relevance: The findings suggest that, despite the modest improvement in health care facility-associated CDI rates, a better understanding of community-acquired CDI incidence is needed for future infection prevention efforts.

7.
Sociol Health Illn ; 41 Suppl 1: 31-49, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599987

RESUMO

Informed by a discourse analysis, this article examines the framing of equity within the UK's digital health policies between 2010 and 2017, focusing on England's development of NHS Digital and its situation within the UK Government's wider digital strategy. Analysis of significant policy documents reveals three interrelated discourses that are engaged within England's digital health policies: equity as a neoliberal imaginary of digital efficiency and empowerment; digital health as a pathway towards democratising health care through data-sharing, co-creation and collaboration; and finally, digital health as a route towards extending citizen autonomy through their access to data systems. It advances knowledge of the relationship between digital health policy and health inequalities. Revealing that while inclusion remains a priority area for policymakers, equity is being constituted in ways that reflect broader discourses of neoliberalism, empowerment and the turn to the market for technological solutionism, which may potentially exacerbate health inequalities.

8.
Eur Respir J ; 54(4)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31537697

RESUMO

BACKGROUND: Low-dose computed tomography (LDCT) screening detects early-stage lung cancer and reduces mortality. We proposed a sequential approach targeted to a high-risk group as a potentially efficient screening strategy. METHODS: LungSEARCH was a national multicentre randomised trial. Current/ex-smokers with mild/moderate chronic obstructive pulmonary disease (COPD) were allocated (1:1) to have 5 years surveillance or not. Screened participants provided annual sputum samples for cytology and cytometry, and if abnormal were offered annual LDCT and autofluorescence bronchoscopy (AFB). Those with normal sputum provided annual samples. The primary end-point was the percentage of lung cancers diagnosed at stage I/II (nonsmall cell) or limited disease (small cell). RESULTS: 1568 participants were randomised during 2007-2011 from 10 UK centres. 85.2% of those screened provided an adequate baseline sputum sample. There were 42 lung cancers among 785 screened individuals and 36 lung cancers among 783 controls. 54.8% (23 out of 42) of screened individuals versus 45.2% (14 out of 31) of controls with known staging were diagnosed with early-stage disease (one-sided p=0.24). Relative risk was 1.21 (95% CI 0.75-1.95) or 0.82 (95% CI 0.52-1.31) for early-stage or advanced cancers, respectively. Overall sensitivity for sputum (in those randomised to surveillance) was low (40.5%) with a cumulative false-positive rate (FPR) of 32.8%. 55% of cancers had normal sputum results throughout. Among sputum-positive individuals who had AFB, sensitivity was 45.5% and cumulative FPR was 39.5%; the corresponding measures for those who had LDCT were 100% and 16.1%, respectively. CONCLUSIONS: Our sequential strategy, using sputum cytology/cytometry to select high-risk individuals for AFB and LDCT, did not lead to a clear stage shift and did not improve the efficiency of lung cancer screening.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31480371

RESUMO

Physical activity levels decline, and screen-viewing behaviours increase during childhood and adolescence. The transition to secondary school appears to coincide with a sharp decline in physical activity. Parents have the potential to influence their child's behaviours, yet little is known about their expectations for their child's physical activity and screen-viewing during this transition. This paper explores parents' expectations for their children's physical activity and screen-viewing as they transition from primary to secondary school, and their proposed strategies for managing these behaviours during this time. Forty-two parents of children aged 10-11 years participated in a semi-structured telephone interviews in July 2017 or March 2018. The interview data were analysed via inductive and deductive content analysis to explore parents' perceptions of physical activity and screen-viewing during the transition, the reasons for their perceptions, and the strategies they intended to implement to help their child balance their behaviours. Most parents expected both physical activity and screen-viewing to increase during this transition. There were several individuals, social and school-level factors influencing these expectations. Overall, parents felt that helping their child balance their activity levels, screen-viewing and homework would be challenging.

11.
PLoS Med ; 16(8): e1002893, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31390370

RESUMO

BACKGROUND: Various risk factors have been associated with epithelial ovarian cancer risk in observational epidemiological studies. However, the causal nature of the risk factors reported, and thus their suitability as effective intervention targets, is unclear given the susceptibility of conventional observational designs to residual confounding and reverse causation. Mendelian randomization (MR) uses genetic variants as proxies for risk factors to strengthen causal inference in observational studies. We used MR to evaluate the association of 12 previously reported risk factors (reproductive, anthropometric, clinical, lifestyle, and molecular factors) with risk of invasive epithelial ovarian cancer, invasive epithelial ovarian cancer histotypes, and low malignant potential tumours. METHODS AND FINDINGS: Genetic instruments to proxy 12 risk factors were constructed by identifying single nucleotide polymorphisms (SNPs) that were robustly (P < 5 × 10-8) and independently associated with each respective risk factor in previously reported genome-wide association studies. These risk factors included genetic liability to 3 factors (endometriosis, polycystic ovary syndrome, type 2 diabetes) scaled to reflect a 50% higher odds liability to disease. We obtained summary statistics for the association of these SNPs with risk of overall and histotype-specific invasive epithelial ovarian cancer (22,406 cases; 40,941 controls) and low malignant potential tumours (3,103 cases; 40,941 controls) from the Ovarian Cancer Association Consortium (OCAC). The OCAC dataset comprises 63 genotyping project/case-control sets with participants of European ancestry recruited from 14 countries (US, Australia, Belarus, Germany, Belgium, Denmark, Finland, Norway, Canada, Poland, UK, Spain, Netherlands, and Sweden). SNPs were combined into multi-allelic inverse-variance-weighted fixed or random effects models to generate effect estimates and 95% confidence intervals (CIs). Three complementary sensitivity analyses were performed to examine violations of MR assumptions: MR-Egger regression and weighted median and mode estimators. A Bonferroni-corrected P value threshold was used to establish strong evidence (P < 0.0042) and suggestive evidence (0.0042 < P < 0.05) for associations. In MR analyses, there was strong or suggestive evidence that 2 of the 12 risk factors were associated with invasive epithelial ovarian cancer and 8 of the 12 were associated with 1 or more invasive epithelial ovarian cancer histotypes. There was strong evidence that genetic liability to endometriosis was associated with an increased risk of invasive epithelial ovarian cancer (odds ratio [OR] per 50% higher odds liability: 1.10, 95% CI 1.06-1.15; P = 6.94 × 10-7) and suggestive evidence that lifetime smoking exposure was associated with an increased risk of invasive epithelial ovarian cancer (OR per unit increase in smoking score: 1.36, 95% CI 1.04-1.78; P = 0.02). In analyses examining histotypes and low malignant potential tumours, the strongest associations found were between height and clear cell carcinoma (OR per SD increase: 1.36, 95% CI 1.15-1.61; P = 0.0003); age at natural menopause and endometrioid carcinoma (OR per year later onset: 1.09, 95% CI 1.02-1.16; P = 0.007); and genetic liability to polycystic ovary syndrome and endometrioid carcinoma (OR per 50% higher odds liability: 0.89, 95% CI 0.82-0.96; P = 0.002). There was little evidence for an association of genetic liability to type 2 diabetes, parity, or circulating levels of 25-hydroxyvitamin D and sex hormone binding globulin with ovarian cancer or its subtypes. The primary limitations of this analysis include the modest statistical power for analyses of risk factors in relation to some less common ovarian cancer histotypes (low grade serous, mucinous, and clear cell carcinomas), the inability to directly examine the association of some ovarian cancer risk factors that did not have robust genetic variants available to serve as proxies (e.g., oral contraceptive use, hormone replacement therapy), and the assumption of linear relationships between risk factors and ovarian cancer risk. CONCLUSIONS: Our comprehensive examination of possible aetiological drivers of ovarian carcinogenesis using germline genetic variants to proxy risk factors supports a role for few of these factors in invasive epithelial ovarian cancer overall and suggests distinct aetiologies across histotypes. The identification of novel risk factors remains an important priority for the prevention of epithelial ovarian cancer.

12.
J Med Internet Res ; 21(8): e11506, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31407672

RESUMO

BACKGROUND: Electronic cigarettes (e-cigs) are an increasingly popular alternative to smoking, helping to prevent relapse in those trying to quit and with the potential to reduce harm as they are likely to be safer than standard cigarettes. Many women return to smoking in the postpartum period having stopped during pregnancy, and while this can affect their decisions about breastfeeding, little is known about women's opinions on using e-cigs during this period. OBJECTIVE: The aim of this study is to explore online forum users' current attitudes, motivations, and barriers to postpartum e-cig use, particularly as a breastfeeding mother. METHODS: Data were collected via publicly accessible (identified by Google search) online forum discussions, and a priori codes identified. All transcripts were entered into NVivo for analysis, with a template approach to thematic analysis being used to code all transcripts from which themes were derived. RESULTS: Four themes were identified: use, perceived risk, social support and evidence, with a number of subthemes identified within these. Women were using e-cigs to prevent postpartum return to smoking, but opinions on their safety were conflicting. They were concerned about possible transfer of harmful products from e-cigs via breastmilk and secondhand exposure, so they were actively seeking and sharing information on e-cigs from a variety of sources. Although some women were supportive of e-cig use, others provided harsh judgement for mothers who used them. CONCLUSIONS: E-cigs have the potential to reduce the number of women who return to smoking in the postpartum period and potentially improve breastfeeding rates, if breastfeeding mothers have access to relevant and reliable information. Health care providers should consider discussing e-cigs with mothers at risk of returning to smoking in the postpartum period.

13.
Public Health Nutr ; 22(17): 3238-3249, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31385561

RESUMO

OBJECTIVE: To understand non-adherence to medically recommended diets among Mayans with diabetes. DESIGN: Using partially sequential mixed methods, questionnaires, semi-structured brief and in-depth interviews were applied. Questionnaire data were analysed with Pearson's χ2 and Student's t tests and qualitative interviews with grounded theory microanalysis. SETTING: Rural, predominantly Mayan communities in Chiapas, Quintana Roo and Yucatan, Mexico, 2008-2012. PARTICIPANTS: Purposive sample of Mayans with type 2 diabetes; using public health care; 168 women and twenty-seven men; age 21-50+ years. RESULTS: Participants understood diabetes as caused by negative emotions, divine punishment, revenge via spells, chemicals in food and high sugar/fat consumption. Eliminating corn, pork, sugary beverages and inexpensive industrialized foods was perceived as difficult or impossible. More Mayans reporting not understanding physician instructions (30 v. 18 %) reported difficulty reducing red meat consumption (P = 0·051). Non-adherence was influenced by lack of patient-provider shared knowledge and medical recommendations misaligned with local culture. Men whose wives prepared their meals, women who liked vegetables and young adults whose mothers prepared their meals reported greater adherence to dietary recommendations. Partial adherents said it made life tolerable and those making no physician-recommended dietary changes considered them too restrictive (they meant 'starving to death'). Over half (57 %) of participants reported non-adherence; the two principal reasons were dislike of recommended foods (52·5 %) and high cost (26·2 %). CONCLUSIONS: Adherence to dietary regimens in diabetes treatment is largely related to social and cultural issues. Taking cultural diversity, food preferences, local food availability and poverty into consideration is essential when developing health-promotion activities related to diabetes.

14.
Clin Med (Lond) ; 19(4): 290-293, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308105

RESUMO

Computed tomography (CT) is readily available in developed countries. As one of the side effects includes an increased risk of cancer, interventions that may encourage more judicious use of CT are important. Behavioural economics theory includes the use of nudges that aim to help more informed decisions to be made, although these have been rarely used in hospitals to date. We aimed to evaluate the impact of a simple educational message appended to the CT report on subsequent numbers of CT completed using a controlled interrupted time series design based in two teaching hospitals in the UK. The intervention was the addition of a non-directional educational message on the risk of ionising radiation to all CT reports. There was a statistically significant reduction in the number of CT requested in the intervention hospital compared to the control hospital (-4.6%, 95% confidence intervals -7.4 to -1.7, p=0.002) in the 12 months after the intervention was implemented. We conclude that a simple, non-directional nudge intervention has the capacity to modify clinician use of CT. This approach is cheap, and has potential in helping support doctors make informed decisions.

15.
J Med Imaging Radiat Sci ; 50(3): 416-424.e2, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31327666

RESUMO

INTRODUCTION: Locally-initiated research studies in radiation therapy (RT) aim to substantiate clinical processes and are an effective approach to gather evidence for advances in patient care, new techniques, and protocols. The aim of this study was to retrospectively quantify recruitment challenges at a radiation oncology network (RON). METHODS: Five locally initiated studies were included for analysis through the criteria of being undertaken within 2001-2017, initiated through local research teams, and having recruitment records available. Data extraction from each study included duration, aims, patient activities, recruitment strategy, target number of participants, and number of participants who were recruited/not recruited and who withdrew from the study. Reasons for nonregistration and withdrawal were recorded if available. Two studies are presented as case studies. RESULTS: Included studies were diverse in patient population and study aim and included patient immobilization (lung and breast cancer), evaluation of radiation-induced esophagitis, documentation of anatomical and dosimetric changes in patients with head and neck cancer, and education (breast cancer). The exclusion of non-English-speaking patients, which is significant for the RON, which covers a wide cultural and linguistic diversity, was an important limiting factor, along with RT patients' disinterest in participation. DISCUSSION: Challenges experienced in the evaluated RON studies are similar to non-RT clinical trials and included difficulties with patients interacting with study protocol, health practitioners' influence, and patient-related inclusion issues. CONCLUSION: The resulting database provides a foundation for continued monitoring and documentation of study recruitment practice, which could elicit positive effects on planning and implementation of future patient recruitment strategies in RT locally initiated studies.

16.
Subst Use Misuse ; 54(13): 2207-2217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31299868

RESUMO

Background: A relatively large body of evidence indicates that coping motives for cigarette smoking are associated with a number of problematic outcomes (e.g., greater smoking frequency) among adolescents. Evidence also indicates that lower distress tolerance (or higher distress intolerance) is related to higher levels of coping motives for cigarette smoking among adults and adolescents. Therefore, it is critical to improve our understanding of factors that may increase the likelihood of smoking to cope among adolescents. In addition, evidence suggests that a number of parenting behaviors may affect adolescent smoking behavior. No work to date, however, has examined the relation between parental distress intolerance and adolescent smoking motives, or adolescent smoking behavior. Objective/methods: The current study involving adolescents (n = 46) and one of their parents aimed to address this gap in the literature by examining the association between parent-reported parental distress intolerance, self-reported adolescent motives for cigarette use, and self-reported adolescent cigarette smoking levels. Results: Results indicated that parental distress intolerance was related to greater adolescent coping motives for cigarette smoking, but not to other motives for adolescent cigarette use. Furthermore, results indicated that parental distress intolerance was indirectly associated with higher adolescent cigarette smoking levels through adolescent coping motives for cigarette smoking. Conclusions: Parental distress intolerance is associated with coping motives for adolescent cigarette smoking. This suggests parental emotional factors may be associated with adolescent cigarette use.

17.
Medicine (Baltimore) ; 98(26): e15858, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261494

RESUMO

This analysis aims to describe the outcomes of two nonambulatory patients with Duchenne muscular dystrophy (DMD) who participated in two clinical studies. The two consecutive trials of eteplirsen (studies 201 and 202) were conducted in patients with DMD (N = 12) and confirmed genetic mutations amenable to exon 51 skipping.In study 201, 12 patients were randomized to receive once-weekly, double-blind intravenous infusions of eteplirsen 30 or 50 mg/kg or placebo for 24 weeks; patients then received open-label eteplirsen during weeks 25 through 28. All 12 patients continued onto open-label extension study 202 and received long-term treatment with eteplirsen. We compared cardiac, pulmonary, and upper limb function and dystrophin production in the nonambulatory twin patients versus the 10 ambulatory patients through 240 combined treatment weeks.Ten study patients remained ambulatory through both studies, while the identical twin patients both experienced early, rapid loss of ambulation. The twin patients had greater disease severity at baseline (6-minute walk test [6MWT], 330 and 256 m) versus the other patients (n = 10; 6MWT range, 341-418 m). They maintained cardiac and upper limb function through combined week 240, with outcomes similar to those of the patients who remained ambulatory. Dystrophin production was confirmed following eteplirsen treatment.Despite the loss of ambulation, other markers of disease progression remained relatively stable in the eteplirsen-treated twin patients and were similar to those of the ambulatory patients.


Assuntos
Morfolinos/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Criança , Progressão da Doença , Doenças em Gêmeos , Método Duplo-Cego , Distrofina/genética , Distrofina/metabolismo , Humanos , Masculino , Morfolinos/efeitos adversos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/fisiopatologia , Processamento Pós-Transcricional do RNA/efeitos dos fármacos , Índice de Gravidade de Doença , Resultado do Tratamento , Teste de Caminhada , Caminhada
18.
BMJ Open ; 9(7): e024923, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31300493

RESUMO

OBJECTIVE: To investigate relationships between maternal smoking status in pregnancy and infant development. The largest randomised controlled trial of nicotine replacement therapy (NRT) for smoking cessation in pregnancy, the smoking, nicotine and pregnancy (SNAP) trial, found that at 1 month after randomisation, smoking cessation rates were doubled in the NRT group compared with the placebo group. At delivery, there was no significant difference in cessation rates between groups. Surprisingly, infants born to women randomised to NRT were more likely to have unimpaired development at 2 years. We hypothesised that this apparently protective effect was due to smoking cessation caused by NRT and so, investigate this relationship using the same cohort. DESIGN: Secondary analysis of a randomised controlled trial. SETTING: Seven antenatal hospitals in the Midlands and North-West England. PARTICIPANTS: Eight hundred and eighty-four pregnant smokers randomised to receive either NRT patches or visually-identical placebo in the SNAP trial. Participants' smoking behaviour were recorded at randomisation, 1 month after their target quit date and at delivery. METHODS: Using logistic regression models, we investigated associations between participants' smoking measures and infant development (assessed using the Ages and Stages questionnaire) at 2 years. MAIN OUTCOME MEASURES: 2 year infant development. RESULTS: Developmental impairment was reported for 12.7% of study 2 year olds. Maternal heaviness of smoking at randomisation (OR: 1.26, 95% CI: 0.82 to 1.96, p=0.091), validated smoking abstinence recorded at 1 month after a quit date (OR: 1.02, 95% CI: 0.60 to 1.74, p=0.914) and validated smoking abstinence recorded at both 1 month after a quit date and at the end of pregnancy (OR: 1.52, 95% CI: 0.81 to 2.85, p=0.795) were not independently associated with infant developmental impairment at 2 years. CONCLUSION: We found no evidence that NRT treatment improved infants' developmental outcomes through smoking cessation. TRIAL REGISTRATION NUMBER: CTA03057/0002/001-0001; Post-results.

19.
Implement Sci ; 14(1): 61, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196123

RESUMO

BACKGROUND: Stroke Early Supported Discharge (ESD) is a service innovation that facilitates discharge from hospital and delivery of specialist rehabilitation in patients' homes. There is currently widespread implementation of ESD services in many countries, driven by robust clinical trial evidence. In England, the type of ESD service patients receive on the ground is variable, and in some regions, ESD is still not offered at all. This protocol presents a study designed to investigate the mechanisms and outcomes of implementing ESD at scale in real-world conditions. This will help to establish which models of ESD are most effective and in what context. METHODS: A realist evaluation approach composed of two interlinking work packages will be adopted to investigate how and why ESD works, for whom and in what circumstances. Work package 1 (WP1) will begin with a rapid evidence synthesis to formulate preliminary realist hypotheses. Quantitative analyses of historical prospective Sentinel Stroke National Audit Programme (SSNAP) data will be performed to evaluate service outcomes based on the degree to which evidence-based ESD has been implemented. Work package 2 (WP2) will involve the qualitative investigation of purposively selected case study sites featuring in WP1 and covering different regions in England. The perspectives of clinicians, managers, commissioners, and service users will be explored qualitatively. Cost implications of ESD models will be examined using a cost-consequence analysis. Cross-case comparisons and triangulation of the data sources from both work packages will be performed to test, revise, and refine initial programme theories and address research aims. DISCUSSION: This study will investigate whether and how current large-scale implementation of ESD is achieving the outcomes suggested by the evidence base. The theory-driven evaluation approach will highlight key mechanisms and contextual conditions necessary to optimise outcomes and allow us to draw transferable lessons to inform the effective implementation and sustainability of ESD in clinical practice. In addition, the methodological framework will progress the theoretical understanding of implementation and evaluation of complex rehabilitation interventions in stroke care. TRIAL REGISTRATION: ISRCTN: 15568163, registration date: 26 October 2018.


Assuntos
Implementação de Plano de Saúde , Serviços Hospitalares de Assistência Domiciliar/organização & administração , Alta do Paciente/normas , Reabilitação do Acidente Vascular Cerebral/normas , Inglaterra , Humanos , Inovação Organizacional , Avaliação de Programas e Projetos de Saúde , Projetos de Pesquisa
20.
J Med Imaging Radiat Sci ; 50(2): 289-296, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176437

RESUMO

PURPOSE: Obesity is increasing in prevalence globally, with increased demands placed on radiology departments to image obese patients to assist with diagnosis and management. The aim of this study was to determine perceived best practice techniques currently used in clinical practice for projectional radiography of the abdomen for obese patients with the aim to help elucidate areas for future research and education needs in this field. EXPERIMENTAL DESIGN: A two round e-Delphi study was undertaken to establish a consensus within a reference group of expert Australian clinical educator diagnostic radiographers (CEDRs). Initially, a conceptual map of issues regarding imaging obese patients was undertaken by analysing interview transcripts of 12 CEDRs. This informed an online questionnaire design used in Delphi rounds 1 and 2. A consensus threshold was set <75% "agreement/disagreement", with 15 and 14 CEDRs participating in rounds 1 and 2, respectively. RESULTS: Seven of the 11 statements reach consensus after round 2. Consensus on using a combination of higher peak kilovoltage (kVp) and milliampere-seconds (mAs) to increase radiation exposure increased source-to-image distance and tighter collimation was achieved. There was no consensus regarding patient positioning practices or patient communication strategies. The expert group reported the importance of personal confidence and treating patients as individuals when applying techniques. CONCLUSION: Diversity of experts' opinions and current practice may be due to the variations in obese patients' size and presentation. Therefore, there is a need for extensive empirical evidence to underpin practice and education resources for radiographers when imaging obese patients.

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