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1.
J Clin Epidemiol ; 114: 60-71, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31212001

RESUMO

OBJECTIVES: European regulations do not allow modification or waiver of informed consent for medicines randomized controlled trials (RCTs) where the three 2016 Council for International Organizations of Medical Sciences (CIOMS) provisions are met (consent would be impractical or unfeasible, yet the trial would have high social value and pose no or minimal risk to participants). We aimed to identify whether any such trials of medicines were being conducted in Europe. STUDY DESIGN AND SETTING: This is a survey of all phase 4 "ongoing" RCTs on the EU clinical trial register between July 1, 2016 and June 30, 2018, to identify those with potentially high levels of pragmatism. Trials that were excluded were as follows: those conducted on rare diseases; conducted on healthy volunteers (except those assessing vaccines); masked (single-, double-blind) trials; single-center trials; those where one could expect to lead patients to prefer one intervention over the other; and miscellaneous reasons. The degree of pragmatism of the RCTs was self-assessed by trials' investigators by means of the PRECIS-2 tool. Investigators of those trials considered to be highly pragmatic assessed the fulfillment of the three CIOMS provisions. Seven patients assessed the social value of the RCTs. Finally, 33 members of 11 research ethics committees (RECs) assessed the social value of the trials and whether they posed no more than minimal risk to participants. Investigators, patients, and REC members assessed the fulfillment of the CIOMS provisions as "yes," "not sure" or "no." RESULTS: Of the 638 phase 4 trials, 420 were RCTs, and 21 of these (5%) were candidates to be pragmatic. Investigators of 15 of these 21 RCTs self-assessed their trial's degree of pragmatism: 14 were highly pragmatic. Of these 14, eight fulfilled the three CIOMS provisions. Assessments by patients and RECs were inconsistent for several trials. CONCLUSIONS: We found few low-risk participant-level pragmatic RCTs that could be suitable for modified or waived participants' informed consent. European regulators should consider amending the current regulation and encouraging the conduct of such trials.

2.
Lancet Oncol ; 20(5): 649-662, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30948276

RESUMO

BACKGROUND: Biologically distinct subtypes of diffuse large B-cell lymphoma can be identified using gene-expression analysis to determine their cell of origin, corresponding to germinal centre or activated B cell. We aimed to investigate whether adding bortezomib to standard therapy could improve outcomes in patients with these subtypes. METHODS: In a randomised evaluation of molecular guided therapy for diffuse large B-cell lymphoma with bortezomib (REMoDL-B), an open-label, adaptive, randomised controlled, phase 3 superiority trial, participants were recruited from 107 cancer centres in the UK (n=94) and Switzerland (n=13). Eligible patients had previously untreated, histologically confirmed diffuse large B-cell lymphoma with sufficient diagnostic material from initial biopsies for gene-expression profiling and pathology review; were aged 18 years or older; had ECOG performance status of 2 or less; had bulky stage I or stage II-IV disease requiring full-course chemotherapy; had measurable disease; and had cardiac, lung, renal, and liver function sufficient to tolerate chemotherapy. Patients initially received one 21-day cycle of standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP; rituximab 375 mg/m2, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 [to a maximum of 2 mg total dose] intravenously on day 1 of the cycle, and prednisolone 100 mg orally once daily on days 1-5). During this time, we did gene-expression profiling using whole genome cDNA-mediated annealing, selection, extension, and ligation assay of tissue from routine diagnostic biopsy samples to determine the cell-of-origin subtype of each participant (germinal centre B cell, activated B cell, or unclassified). Patients were then centrally randomly assigned (1:1) via a web-based system, with block randomisation stratified by international prognostic index score and cell-of-origin subtype, to continue R-CHOP alone (R-CHOP group; control), or with bortezomib (RB-CHOP group; experimental; 1·3 mg/m2 intravenously or 1·6 mg/m2 subcutaneously) on days 1 and 8 for cycles two to six. If RNA extracted from the diagnostic tissues was of insufficient quality or quantity, participants were given R-CHOP as per the control group. The primary endpoint was 30-month progression-free survival, for the germinal centre and activated B-cell population. The primary analysis was on the modified intention-to-treat population of activated and germinal centre B-cell population. Safety was assessed in all participants who were given at least one dose of study drug. We report the progression-free survival and safety outcomes for patients in the follow-up phase after the required number of events occurred. This study was registered at ClinicalTrials.gov, number NCT01324596, and recruitment and treatment has completed for all participants, with long-term follow-up ongoing. FINDINGS: Between June 2, 2011, and June 10, 2015, 1128 eligible patients were registered, of whom 918 (81%) were randomly assigned to receive treatment (n=459 to R-CHOP, n=459 to RB-CHOP), comprising 244 (26·6%) with activated B-cell disease, 475 (51·7%) with germinal centre B cell disease, and 199 (21·7%) with unclassified disease. At a median follow-up of 29·7 months (95% CI 29·0-32·0), we saw no evidence for a difference in progression-free survival in the combined germinal centre and activated B-cell population between R-CHOP and RB-CHOP (30-month progression-free survival 70·1%, 95% CI 65·0-74·7 vs 74·3%, 69·3-78·7; hazard ratio 0·86, 95% CI 0·65-1·13; p=0·28). The most common grade 3 or worse adverse event was haematological toxicity, reported in 178 (39·8%) of 447 patients given R-CHOP and 187 (42·1%) of 444 given RB-CHOP. However, RB-CHOP was not associated with increased haematological toxicity and 398 [87·1%] of 459 participants assigned to receive RB-CHOP completed six cycles of treatment. Grade 3 or worse neuropathy occurred in 17 (3·8%) patients given RB-CHOP versus eight (1·8%) given R-CHOP. Serious adverse events occurred in 190 (42·5%) patients given R-CHOP, including five treatment-related deaths, and 223 (50·2%) given RB-CHOP, including four treatment-related deaths. INTERPRETATION: This is the first large-scale study in diffuse large B-cell lymphoma to use real-time molecular characterisation for prospective stratification, randomisation, and subsequent analysis of biologically distinct subgroups of patients. The addition of bortezomib did not improve progression-free survival. FUNDING: Janssen-Cilag, Bloodwise, and Cancer Research UK.

3.
Artigo em Inglês | MEDLINE | ID: mdl-30837951

RESUMO

There are more than 2 billion overweight and obese individuals worldwide, surpassing for the first time, the number of people affected by undernutrition. Obesity and its comorbidities inflict a heavy burden on the global economies and have become a serious threat to individuals' wellbeing with no immediate cure available. The causes of obesity are manifold, involving several factors including physiological, metabolic, neural, psychosocial, economic, genetics and the environment, among others. Recent advances in genome sequencing and metagenomic profiling have added another dimension to this complexity by implicating the gut microbiota as an important player in energy regulation and the development of obesity. As such, accumulating evidence demonstrate the impact of the gut microbiota on body weight, adiposity, glucose, lipid metabolism, and metabolic syndrome. This also includes the role of microbiota as a modulatory signal either directly or through its bioactive metabolites on intestinal lumen by releasing chemosensing factors known to have a major role in controlling food intake and regulating body weight. The importance of gut signaling by microbiota signaling is further highlighted by the presence of taste and nutrient receptors on the intestinal epithelium activated by the microbial degradation products as well as their role in release of peptides hormones controlling appetite and energy homeostasis. This review present evidence on how gut microbiota interacts with intestinal chemosensing and modulates the release and activity of gut peptides, particularly GLP-1 and PYY.

4.
Scand J Pain ; 19(2): 397-406, 2019 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-30530911

RESUMO

Background and aims Prior research indicates that swearing increases pain tolerance and decreases pain perception in a cold pressor task. In two experiments, we extend this research by testing whether taboo hand gesticulations have a similar effect. Methods Study 1 focused on males and females who, across two trials, submerged an extended middle finger (taboo) and an extended index finger (control) in ice water until discomfort necessitated removal. Study 2 focused exclusively on pain perception in males who, across three trials, submerged their hand, flat, with extended middle finger and with extended index finger, for 45 s each. Results In study 1 taboo gesticulation did not increase pain tolerance or reduce pain perception compared with the index finger control condition, as a main effect or as part of an interaction with condition order. While there was a gesture×gender interaction for pain tolerance, this was driven by an increased pain tolerance for the index finger gesture for women but not men. The results of study 2 again showed that taboo gesticulation did not lower pain perception, although it did increase positive affect compared with both non-taboo gesture conditions. Conclusions Taken together these results provide only limited evidence that taboo gesticulation alters the experience of pain. These largely null findings further our understanding of swearing as a response to pain, suggesting that the activation of taboo schemas is not sufficient for hypoalgesia to occur.

5.
Chest ; 155(3): 502-509, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30391190

RESUMO

BACKGROUND: Clinical staging of non-small cell lung cancer (NSCLC) helps determine the prognosis and treatment of patients; few data exist on the accuracy of clinical staging and the impact on treatment and survival of patients. We assessed whether participant or trial characteristics were associated with clinical staging accuracy as well as impact on survival. METHODS: We used individual participant data from randomized controlled trials (RCTs), supplied for a meta-analysis of preoperative chemotherapy (± radiotherapy) vs surgery alone (± radiotherapy) in NSCLC. We assessed agreement between clinical TNM (cTNM) stage at randomization and pathologic TNM (pTNM) stage, for participants in the control group. RESULTS: Results are based on 698 patients who received surgery alone (± radiotherapy) with data for cTNM and pTNM stage. Forty-six percent of cases were cTNM stage I, 23% were cTNM stage II, and 31% were cTNM stage IIIa. cTNM stage disagreed with pTNM stage in 48% of cases, with 34% clinically understaged and 14% clinically overstaged. Agreement was not associated with age (P = .12), sex (P = .62), histology (P = .82), staging method (P = .32), or year of randomization (P = .98). Poorer survival in understaged patients was explained by the underlying pTNM stage. Clinical staging failed to detect T4 disease in 10% of cases and misclassified nodal disease in 38%. CONCLUSIONS: This study demonstrates suboptimal agreement between clinical and pathologic staging. Discrepancies between clinical and pathologic T and N staging could have led to different treatment decisions in 10% and 38% of cases, respectively. There is therefore a need for further research into improving staging accuracy for patients with stage I-IIIa NSCLC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Estadiamento de Neoplasias/métodos , Procedimentos Cirúrgicos Operatórios/métodos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Cuidados Pré-Operatórios/métodos , Prognóstico , Reprodutibilidade dos Testes
6.
Cancer Prev Res (Phila) ; 12(2): 89-94, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30514807

RESUMO

Colorectal cancer accounts for 11% of all cancer-related deaths in Ireland. With the aim of diagnosing these cancers at an earlier stage, and detecting premalignant lesions, the National Screening Service (NSS) offered a fecal immunochemical test (FIT) to all individuals aged 60 to 69. All individuals in the age range were contacted by post and invited to participate in the programme. Those with a positive FIT result were offered a colonoscopy in an internationally accredited unit. From an eligible population of 488,628, 196,238 individuals participated giving an uptake of 40.2%. Commencing at a FIT threshold of 20 µg Hg/g feces, the positivity rate was 8.6%, which overwhelmed colonoscopy capacity and, thus, the threshold was increased to 45 µg, resulting in an overall 5% positivity rate. A total of 520 individuals had cancer detected (68.3% stage I or II), of which 104 were removed endoscopically (pT1s). Adenomas were present in 54.2% of all colonoscopies, 17.4% deemed high risk. Despite a lower uptake, males were twice as likely to have colorectal cancers as females and had a 59% increased rate of high-risk adenomas diagnosed. Challenges facing the programme include increasing participation, especially among males, and increasing colonoscopy capacity. The ability to alter the sensitivity of FIT to match colonoscopy capacity is a valuable option for such a programme as it ensures that the maximum public health benefit can be achieved within available resources.

7.
Res Involv Engagem ; 4: 31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30214823

RESUMO

Plain English summary: Peer review is a well-established part of academic publishing. Its function is to assess the quality of a manuscript before publication in a journal. Research involvement and Engagement is the world's first co-produced journal dedicated to developing the evidence base of patient and public involvement and engagement in health and social care research. Alongside traditional academic peer review we also involve other key stakeholders, including patients, carers, the public, policy makers, funders and practitioners. Following a recent survey looking at the motivations and feedback from patient reviewers in academic journals, we consider the key findings, reflect on what we already do and based on the feedback from the survey, we outline plans for future development. These plans include improving training and guidance for reviewers, changes to systems and workflows, acknowledging and engaging reviewers, and building a sense of community. Abstract: Peer review is a well-established part of academic publishing. Its function is to assess the quality of a manuscript before publication in a journal. Research involvement and Engagement is the world's first co-produced journal dedicated to developing the evidence base of patient and public involvement and engagement in health and social care research. Alongside traditional academic peer review we also involve other key stakeholders, including patients, carers, the public, policy makers, funders and practitioners. Following a recent survey looking at the motivations and feedback from patient reviewers in academic journals, we consider the key findings, reflect on what we already do and based on the feedback from the survey, we outline plans for future development. These plans include including improving training and guidance for reviewers, changes to systems and workflows, acknowledging and engaging reviewers, and building a sense of community.

8.
BMJ Open ; 8(9): e023357, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185581

RESUMO

OBJECTIVE: In 2014/2015, The BMJ and Research Involvement and Engagement (RIE) became the first journals to routinely include patients and the public in the peer review process of journal articles. This survey explores the perspectives and early experiences of these reviewers. DESIGN: A cross-sectional survey. SETTING AND PARTICIPANTS: Patient and public reviewers for The BMJ and RIE who have been invited to review. RESULTS: The response rate was 69% (157/227) for those who had previously reviewed and 31% (67/217) for those who had not yet reviewed. Reviewers described being motivated to review by the opportunity to include the patient voice in the research process, influence the quality of the biomedical literature and ensure it meets the needs of patients. Of the 157 who had reviewed, 127 (81%) would recommend being a reviewer to other patients and carers. 144 (92%) thought more journals should adopt patient and public review. Few reviewers (16/224, 7%) reported concerns about doing open review. Annual acknowledgement on the journals' websites was welcomed as was free access to journal information. Participants were keen to have access to more online resources and training to improve their reviewing skills. Suggestions on how to improve the reviewing experience included: allowing more time to review; better and more frequent communication; a more user-friendly process; improving guidance on how to review including videos; improving the matching of papers to reviewers' experience; providing more varied sample reviews and brief feedback on the usefulness of reviews; developing a sense of community among reviewers; and publicising of the contribution that patient and public review brings. CONCLUSIONS: Patient and public reviewers shared practical ideas to improve the reviewing experience and these will be reviewed to enhance the guidance and support given to them.


Assuntos
Participação da Comunidade , Pacientes , Revisão da Pesquisa por Pares , Estudos Transversais , Humanos , Motivação , Publicações Periódicas como Assunto , Inquéritos e Questionários
9.
Obesity (Silver Spring) ; 26(5): 801-809, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29687647

RESUMO

OBJECTIVE: This review summarizes the current understanding of the relationship between gut microbiota and the host as it pertains to the regulation of energy balance and obesity. METHODS: The paper begins with a brief description of the gut microbiota environment, distribution, and its unique symbiotic relationship with the host. The way that enviromental factors influence microbiota composition and subsequent impact on the host are then described. Next, the mechanisms linking gut dysbiosis with obesity are discussed, and finally current challenges and limitations in understanding the role of gut microbiota in control of obesity are presented. RESULTS: Gut microbiota has been implicated in regulation of fat storage, as well as gut dysbiosis, thus contributing to the development of obesity, insulin resistance, hyperglycemia and hyperlipidemia. However, the underlying mechanisms of these processes are far from being clear and will require complex preclinical and clinical interdisciplinary studies of bacteria and host cell-to-cell interactions. CONCLUSIONS: There is a need for a better understanding of how changes in gut microbiota composition can impact energy balance and thus control weight gain. This may represent a promising avenue in the race to develop nonsurgical treatments for obesity.


Assuntos
Disbiose/complicações , Microbioma Gastrointestinal/fisiologia , Inflamação/fisiopatologia , Obesidade/fisiopatologia , Animais , Humanos
10.
Trials ; 19(1): 95, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29415751

RESUMO

BACKGROUND: Patient and public involvement (PPI) in clinical trials aims to ensure that research is carried out collaboratively with patients and/or members of the public. However, current guidance on involving clinical trial participants in PPI activities is not consistent. METHODS: We reviewed the concept of participant involvement, based on our experience. Two workshops were held at the MRCCTU at UCL with the aim of defining participant involvement, considering its rationale; benefits and challenges; and identifying appropriate models for participant involvement in clinical trials. We considered how participant involvement might complement the involvement of other public contributors. Both workshops were attended by two patient representatives and seven staff members with experience of PPI in trials. Two of the staff members had also been involved in studies that had actively involved participants. They shared details of that work to inform discussions. RESULTS: We defined trial participants as individuals taking part in the study in question, including those who had already completed their trial treatment and/or follow-up. Because of their direct experience, involving participants may offer advantages over other public contributors; for example, in studies of new interventions or procedures, and where it is hard to identify or reach patient or community groups that include or speak for the study population. Participant involvement is possible at all stages of a trial; however, because there are no participants to involve during the design stage of a trial, prior to enrolment, participant involvement should complement and not replace involvement of PPI stakeholders. A range of models, including those with managerial, oversight or responsive roles are appropriate for involving participants; however, involvement in data safety and monitoring committees may not be appropriate where there is a potential risk of unblinding. Involvement of participants can improve the trial experience for other participants; optimising study procedures, improving communications; however, there are some specific, notably, managing participant confidentiality and practicalities relating to payments. CONCLUSIONS: Participant involvement in clinical trials is feasible and complements other forms of PPI in clinical trials. Involving active participants offers significant advantages, particularly in circumstances where trials are assessing new, or otherwise unavailable, therapies or processes. We recommend that current guidance on PPI should be updated to routinely consider including participants as valid stakeholders in PPI and potentially useful approach to PPI.


Assuntos
Ensaios Clínicos como Assunto/métodos , Relações Comunidade-Instituição , Participação do Paciente , Opinião Pública , Projetos de Pesquisa , Sujeitos da Pesquisa/psicologia , Participação dos Interessados , Consenso , Conferências de Consenso como Assunto , Humanos , Londres
11.
Pathog Dis ; 76(2)2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29390129

RESUMO

Chlamydia secrete into host cells a diverse array of effector proteins, but progress in characterizing the spatiotemporal localization of these proteins has been hindered by a paucity of genetic approaches in Chlamydia and also by the challenge of studying these proteins within the live cellular environment. We adapted a split-green fluorescent protein (GFP) system for use in Chlamydia to label chlamydial effector proteins and track their localization in host cells under native environment. The efficacy of this system was demonstrated by detecting several known Chlamydia proteins including IncA, CT005 and CT694. We further used this approach to detect two chlamydial deubiquitinases (CT867 and CT868) within live cells during the infection. CT868 localized only to the inclusion membrane at early and late developmental stages. CT867 localized to the chlamydial inclusion membrane at an early developmental stage and was concomitantly localized to the host plasma membrane at a late stage during the infection. These data suggest that chlamydial deubiquitinase play important roles for chlamydial pathogenesis by targeting proteins at both the plasma membrane and the chlamydial inclusion membrane. The split-GFP technology was demonstrated to be a robust and efficient approach to identify the secretion and cellular localization of important chlamydial virulence factors.


Assuntos
Proteínas de Bactérias/análise , Células Epiteliais/química , Fatores de Virulência/análise , Proteínas de Bactérias/genética , Células Epiteliais/microbiologia , Genes Reporter , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Células HeLa , Humanos , Proteínas Recombinantes de Fusão/análise , Proteínas Recombinantes de Fusão/genética , Análise Espaço-Temporal , Coloração e Rotulagem
12.
JAMA ; 319(5): 483-494, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29411037

RESUMO

Importance: Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. Objective: To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). Design, Setting, and Participants: The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. Results: The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n = 21) reduced this to 56 items, which were considered by 138 international stakeholder survey participants and 99 Delphi panelists. The final wording of the SPIRIT-PRO Extension was agreed on at a consensus meeting (n = 29 participants) and reviewed by external group of experts during a consultation period. Eleven extensions and 5 elaborations to the SPIRIT 2013 checklist were recommended for inclusion in clinical trial protocols in which PROs are a primary or key secondary outcome. Extension items focused on PRO-specific issues relating to the trial rationale, objectives, eligibility criteria, concepts used to evaluate the intervention, time points for assessment, PRO instrument selection and measurement properties, data collection plan, translation to other languages, proxy completion, strategies to minimize missing data, and whether PRO data will be monitored during the study to inform clinical care. Conclusions and Relevance: The SPIRIT-PRO guidelines provide recommendations for items that should be addressed and included in clinical trial protocols in which PROs are a primary or key secondary outcome. Improved design of clinical trials including PROs could help ensure high-quality data that may inform patient-centered care.


Assuntos
Protocolos Clínicos/normas , Ensaios Clínicos como Assunto/normas , Guias como Assunto , Medidas de Resultados Relatados pelo Paciente , Tomada de Decisões , Humanos
13.
Scand J Pain ; 17: 267-272, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29229213

RESUMO

BACKGROUND AND AIMS: Research suggests swearing can moderate pain perception. The present study assessed whether changes in pain perception due to swearing reflect a "scripting" effect by comparing swearing as a response to pain in native English and Japanese speakers. Cognitive psychology denotes a 'script' to be a sequence of learnt behaviours expected for given situations. Japanese participants were included as they rarely, if ever, swear as a response to pain and therefore do not possess an available script for swearing in the context of pain. It was hypothesised that Japanese participants would demonstrate less tolerance and more sensitivity to pain than English participants, and - due to a lack of an available script of swearing in response to pain - that Japanese participants would not experience swearword mediated hypoalgesia. METHODS: Fifty-six native English (mean age=23 years) and 39 Japanese (mean age=21) speakers completed a cold-pressor task whilst repeating either a swear on control word. A 2 (culture; Japanese, British)×2 (word; swear; non-swear) design explored whether Japanese participants showed the same increase in pain tolerance and experienced similar levels of perceived pain when a swearing intervention was used as British participants. Pain tolerance was assessed by the number of seconds participants could endure of cold-pressor exposure and self-report pain measurements. Levels of perceived pain were assessed using a 120-mm horizontal visual analogue scale anchored by descriptors in the participant's native language of "no pain" (left) and "terrible pain" (right). The participant was asked to mark a 10mm vertical line to indicate overall pain intensity. The score was measured from the zero anchor to the participant's mark. RESULTS: Japanese participants reported higher levels of pain (p<0.005) and displayed lower pain tolerance than British participants (p<0.05). Pain tolerance increased in swearers regardless of cultural background (p<0.001) and no interaction was found between word group and culture (p=0.96), thereby suggesting that swearing had no differential effect related to the cultural group of the participant. CONCLUSIONS: The results replicate previous findings that swearing increases pain tolerance and that individuals from an Asian ethnic background experience greater levels of perceived pain than those from a Caucasian ethnic background. However, these results do not support the idea of pain perception modification due to a "scripting" effect. This is evidenced as swearword mediated hypoalgesia occurs irrespective of participant cultural background. Rather, it is suggested that modulation of pain perception may occur through activation of descending inhibitory neural pain mechanisms. IMPLICATIONS: As swearing can increase pain tolerance in both Japanese and British people, it may be suggested that swearword mediated hypoalgesia is a universal phenomenon that transcends socio-cultural learnt behaviours. Furthermore, swearing could be encouraged as an intervention to help people cope with acute painful stimuli.


Assuntos
Grupo com Ancestrais do Continente Asiático , Comparação Transcultural , Grupo com Ancestrais do Continente Europeu , Linguagem , Percepção da Dor , Dor/psicologia , Adaptação Psicológica , Feminino , Humanos , Masculino , Medição da Dor , Comportamento Verbal , Adulto Jovem
14.
Res Involv Engagem ; 3: 24, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29152330

RESUMO

Plain English summary: Two years ago we launched Research Involvement and Engagement (RIE) as an interdisciplinary co-produced journal, focusing on patient and wider involvement and engagement in all stages of health and social care research. In this Editorial we reflect on progress and consider future directions. Now indexed in PubMed Central, RIE's prime objective is to publish papers that report public involvement in enough depth to generate a sound and robust evidence base, from which others can draw to develop best practice. Our open access publishing enables anyone who wants to read a paper to access it free of charge, a powerful way of making research more open and more democratic, with RIE a key part of this slow but necessary revolution. While we have made progress, there is still a long way to go to embed involvement and engagement as normal within research practice. Publishers and funders have a vital role to play in changing research so the co-production of knowledge becomes the norm. In this Editorial we highlight key areas that we need to develop to strengthen involvement and engagement. We draw strength from knowing we are not alone in this journey. Our Editorial Board, our authors, our reviewers, and you dear readers, are all companions on this journey, making a wide range of contributions that help us move forward, slowly but surely. Abstract: Two years ago we launched Research Involvement and Engagement (RIE) as an interdisciplinary co-produced journal, focusing on patient and wider involvement and engagement in all stages of health and social care research. In this Editorial we reflect on progress and consider future directions. Now indexed in PubMed Central, RIE's prime objective is to publish papers that report public involvement in enough depth to generate a sound and robust evidence base, from which others can draw to develop best practice. Our open access publishing enables anyone who wants to read a paper to access it free of charge, a powerful way of making research more open and more democratic, with RIE a key part of this slow but necessary revolution. While we have made progress, there is still a long way to go to embed involvement and engagement as normal within research practice. Publishers and funders have a vital role to play in changing research so the co-production of knowledge becomes the norm. In this Editorial we highlight key areas that we need to develop to strengthen involvement and engagement. We draw strength from knowing we are not alone in this journey. Our Editorial Board, our authors, our reviewers, and you dear readers, are all companions on this journey, making a wide range of contributions that help us move forward, slowly but surely.

15.
Innovations (Phila) ; 12(5): 375-377, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29023349

RESUMO

Minimally invasive, robotic-assisted cardiac surgery has been shown to decrease transfusion rates, decrease wound infection rates, shorten hospital length of stay, and allow for a faster return to full activity compared with traditional sternotomy approaches. However, its application has chiefly been limited to primary, isolated procedures such as primary mitral valve repair or replacement. We describe the first reported use of a robotic surgery platform to perform reoperative mitral valve replacement using a minimally invasive, totally endoscopic, port-access approach.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Implante de Prótese de Valva Cardíaca/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Ponte Cardiopulmonar/métodos , Ponte Cardiopulmonar/normas , Ecocardiografia Transesofagiana/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Reoperação , Resultado do Tratamento
16.
Pathog Dis ; 75(8)2017 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29040458

RESUMO

Chlamydia are gram-negative obligate intracellular bacteria that replicate within a discrete cellular vacuole, called an inclusion. Although it is known that Chlamydia require essential nutrients from host cells to support their intracellular growth, the molecular mechanisms for acquiring these macromolecules remain uncharacterized. In the present study, it was found that the expression of mammalian cell glucose transporter proteins 1 (GLUT1) and glucose transporter proteins 3 (GLUT3) were up-regulated during chlamydial infection. Up-regulation was dependent on bacterial protein synthesis and Chlamydia-induced MAPK kinase activation. GLUT1, but not GLUT3, was observed in close proximity to the inclusion membrane throughout the chlamydial developmental cycle. The proximity of GLUT1 to the inclusion was dependent on a brefeldin A-sensitive pathway. Knockdown of GLUT1 and GLUT3 with specific siRNA significantly impaired chlamydial development and infectivity. It was discovered that the GLUT1 protein was stabilized during infection by inhibition of host-dependent ubiquitination of GLUT1, and this effect was associated with the chlamydial deubiquitinase effector protein CT868. This report demonstrates that Chlamydia exploits host-derived transporter proteins altering their expression, turnover and localization. Consequently, host cell transporter proteins are manipulated during infection as a transport system to fulfill the carbon source requirements for Chlamydia.


Assuntos
Infecções por Chlamydia/patologia , Chlamydia trachomatis/crescimento & desenvolvimento , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Glucose/metabolismo , Animais , Linhagem Celular , Infecções por Chlamydia/microbiologia , Chlamydia trachomatis/patogenicidade , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 3/genética , Células HeLa , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Corpos de Inclusão/microbiologia , Camundongos , Interferência de RNA , RNA Interferente Pequeno/genética , Ubiquitinação , Regulação para Cima
18.
Psychopharmacology (Berl) ; 234(12): 1795-1802, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28303371

RESUMO

AIMS: Positive family history of alcohol use disorder (FHP), a variable associated with propensity for alcohol use disorder (AUD), has been linked with elevated hangover frequency and severity, after controlling for alcohol use. This implies that hangover experiences may be related to AUD. However, inadequate control of alcohol consumption levels, low alcohol dose and testing for hangover during the intoxication phase detract from these findings. Here, we present further data pertinent to understanding the relationship between family history and alcohol hangover. METHODS: Study 1 compared past year hangover frequency in a survey of 24 FHP and 118 family history negative (FHN) individuals. Study 2 applied a quasi-experimental naturalistic approach assessing concurrent hangover severity in 17 FHP and 32 FHN individuals the morning after drinking alcohol. Both studies applied statistical control for alcohol consumption levels. RESULTS: In Study 1, both FHP status and estimated blood alcohol concentration on the heaviest drinking evening of the past month predicted the frequency of hangover symptoms experienced over the previous 12 months. In Study 2, estimated blood alcohol concentration the previous evening predicted hangover severity but FHP status did not. CONCLUSIONS: FHP, indicating familial risk for AUD, was not associated with concurrent hangover severity but was associated with increased estimates of hangover frequency the previous year.


Assuntos
Intoxicação Alcoólica/sangue , Intoxicação Alcoólica/genética , Alcoolismo/sangue , Alcoolismo/genética , Concentração Alcoólica no Sangue , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/genética , Intoxicação Alcoólica/diagnóstico , Alcoolismo/diagnóstico , Família , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Autorrelato , Inquéritos e Questionários , Adulto Jovem
19.
Eur Heart J ; 38(21): 1632-1637, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28329235

RESUMO

Evidence generated from randomized controlled trials forms the foundation of cardiovascular therapeutics and has led to the adoption of numerous drugs and devices that prolong survival and reduce morbidity, as well as the avoidance of interventions that have been shown to be ineffective or even unsafe. Many aspects of cardiovascular research have evolved considerably since the first randomized trials in cardiology were conducted. In order to be large enough to provide reliable evidence about effects on major outcomes, cardiovascular trials may now involve thousands of patients recruited from hundreds of clinical sites in many different countries. Costly infrastructure has developed to meet the increasingly complex organizational and operational requirements of these clinical trials. Concerns have been raised that this approach is unsustainable, inhibiting the reliable evaluation of new and existing treatments, to the detriment of patient care. These issues were considered by patients, regulators, funders, and trialists at a meeting of the European Society of Cardiology Cardiovascular Roundtable in October 2015. This paper summarizes the key insights and discussions from the workshop, highlights subsequent progress, and identifies next steps to produce meaningful change in the conduct of cardiovascular clinical research.


Assuntos
Cardiologia/normas , Guias de Prática Clínica como Assunto , Saúde Pública/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Cardiologia/educação , Cardiologia/ética , Difusão de Inovações , Revelação , Humanos , Consentimento Livre e Esclarecido , Segurança do Paciente , Garantia da Qualidade dos Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Medição de Risco
20.
J Psycholinguist Res ; 46(4): 983-995, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28091853

RESUMO

This study assessed the effect of experimentally manipulated emotional arousal on swearing fluency. We hypothesised that swear word generation would be increased with raised emotional arousal. The emotional arousal of 60 participants was manipulated by having them play a first-person shooter video game or, as a control, a golf video game, in a randomised order. A behavioural measure of swearing fluency based on the Controlled Oral Word Association Test was employed. Successful experimental manipulation was indicated by raised State Hostility Questionnaire scores after playing the shooter game. Swearing fluency was significantly greater after playing the shooter game compared with the golf game. Validity of the swearing fluency task was demonstrated via positive correlations with self-reported swearing fluency and daily swearing frequency. In certain instances swearing may represent a form of emotional expression. This finding will inform debates around the acceptability of using taboo language.


Assuntos
Nível de Alerta/fisiologia , Emoções , Linguagem , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Inquéritos e Questionários , Comportamento Verbal/fisiologia , Jogos de Vídeo/psicologia , Vocabulário , Adulto Jovem
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