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  • Open Access
    Authors: 
    Greg Knoll; Robert Bell;

    Abstract Objective : To compare tacrolimus with cyclosporin for immunosuppression in renal transplantation. Design : Meta-analysis of randomised trials of two treatments after kidney transplantation. Identification : Four studies involving 1037 patients. Trials were included if they were randomised, the intervention group received tacrolimus, the control group received cyclosporin, the patients were followed for a minimum of 12 months, and patient survival, graft survival, incidence of acute rejection, need for antilymphocyte treatment, or the prevalence of diabetes mellitus after transplant was reported. Main outcome measures : Pooled estimates of patient mortality, allograft loss, and episodes of acute rejection 1 year after transplantation. Results : The odds ratio for loss of allograft with tacrolimus compared with cyclosporin was 0.95 (95% confidence interval 0.65 to 1.40). The odds ratio for mortality with tacrolimus was 1.07 (0.47 to 2.48). Treatment with tacrolimus was associated with a reduction in episodes of acute rejection (0.52; 0.36 to 0.75), a reduction in the use of antilymphocyte antibodies to treat rejection (0.37; 0.25 to 0.56), and an increased prevalence of diabetes mellitus after transplantation (5.03; 2.04 to 12.36) compared with treatment with cyclosporin. Conclusions : After renal transplantation, immunosuppression with tacrolimus results in a significant reduction in acute rejection compared with cyclosporin. Follow up studies of high methodological quality are needed to determine whether tacrolimus improves long term renal graft survival.

  • Publication . Clinical Trial . Article . Other literature type . 1994
    Open Access English
    Authors: 
    L. Glover; Kenneth N. Gannon; Lorraine Sherr; Paul D. Abel;

    Where treatment options are limited, the role of clinical consultation in providing information and support becomes more important. This study examines the immediate impact of medical consultation on male sub-fertility clinic attender's anxiety, depression, self-blame, information appraisal and perceptions of future fertility. Data were collected pre- and immediately post-consultation. Clinical information and consultation details were recorded. Results showed that anxiety levels were high before consultation. Following consultation anxiety and self-blame were both reduced while depression increased. Despite information about poor prognosis being given during consultation, participants remained overly optimistic about their chances of achieving a pregnancy. It appears that the consultation has a distinct psychological impact and possible mechanisms underlying this are discussed.

  • Publication . Clinical Trial . Other literature type . 1981
    Open Access English
  • Open Access
    Authors: 
    Carrier, Marie-Eve; Kwakkenbos, Linda; Boutron, Isabelle; Welling, Joep; Sauve, Maureen; Ende, Cornelia van den; Schouffoer, Anne A.; Hudson, Marie; Maia, Ângela; Leite, Catarina; +1 more
    Countries: Portugal, Netherlands
    Project: CIHR

    Background: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. Design and methods: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. Discussion: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. Trial registration: ClinicalTrials.gov Identifier: NCT03092024. Canadian Institutes of Health Research(undefined)

  • Publication . Other literature type . Article . Clinical Trial . 2009
    Open Access
    Authors: 
    Daisy Dulay; Stephen A. LaHaye; Karen A. Lahey; Andrew G. Day;

    Background Compared with other statins, rosuvastatin has a relatively long half-life, which may allow for the administration of this medication on an alternate day basis. Objective To compare the efficacy of administering rosuvastatin on a daily basis versus on an alternate day basis for the treatment of dyslipidemia. Methods In the present crossover study, 45 patients with documented hypercholesterolemia requiring pharmacotherapy were administered either 20mg of rosuvastatin on alternate days or 10mg of rosuvastatin daily for six weeks. After a four-week washout period, patients were then switched to the other regimen for another six weeks. The primary end point was the percentage reduction of low-density lipoprotein cholesterol (LDL-C). Results LDL-C decreased by 48.5% versus 40.9% with daily and alternate day dosing, respectively. This represented an additional absolute reduction of LDL-C of 7.6% (95% CI 1.8% to 13.4%, P=0.012) with the daily dosing regimen. Both dosing regimens provided similar improvements in high-density lipoprotein cholesterol and triglycerides. Conclusions Compared with alternate day dosing, daily dosing of rosuvastatin provides a statistically significant advantage in LDL-C reduction. However, the alternate day regimen may be a viable option for those patients in whom cost is a limitation to compliance.

  • Open Access
    Authors: 
    Tume, LN; Woolfall, K; Arch, B; Roper, L; Deja, E; Jones, AP; Latten, L; Pathan, N; Eccleson, H; Hickey, H; +8 more
    Publisher: National Institute for Health Research
    Country: United Kingdom

    The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it.To answer the question: is a trial of no gastric residual volume measurement feasible in UK paediatric intensive care units and neonatal units?A mixed-methods study involving five linked work packages in two parallel arms: neonatal units and paediatric intensive care units. Work package 1: a survey of units to establish current UK practice. Work package 2: qualitative interviews with health-care professionals and caregivers of children admitted to either setting. Work package 3: a modified two-round e-Delphi survey to investigate health-care professionals' opinions on trial design issues and to obtain consensus on outcomes. Work package 4: examination of national databases to determine the potential eligible populations. Work package 5: two consensus meetings of health-care professionals and parents to review the data and agree consensus on outcomes that had not reached consensus in the e-Delphi study.Parents of children with experience of ventilation and tube feeding in both neonatal units and paediatric intensive care units, and health-care professionals working in neonatal units and paediatric intensive care units.Baseline surveys showed that the practice of gastric residual volume measurement was very common (96% in paediatric intensive care units and 65% in neonatal units). Ninety per cent of parents from both neonatal units and paediatric intensive care units supported a future trial, while highlighting concerns around possible delays in detecting complications. Health-care professionals also indicated that a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flow chart and education package. The trial design survey and e-Delphi study gained consensus on 12 paediatric intensive care unit and nine neonatal unit outcome measures, and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed that trials were feasible in both settings in terms of patient numbers. Of 16,222 children who met the inclusion criteria in paediatric intensive care units, 12,629 stayed for 3 days. In neonatal units, 15,375 neonates 32 weeks of age met the inclusion criteria. Finally, the two consensus meetings demonstrated 'buy-in' from the wider UK neonatal communities and paediatric intensive care units, and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study.Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined as a result of differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties.Current Controlled Trials ISRCTN42110505.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inNurses looking after babies and children on intensive care units in the UK usually pass a tube and aspirate whatever food or fluid is in the baby’s stomach before they give a feed. The idea is to ensure that the stomach is not overdistended with food and prevent the baby vomiting or, worse, aspirating food into the lungs. However, there is little justification for this practice. It is rarely done in many other countries. It may not be pleasant for the child and perhaps is unnecessary. Some experts have suggested that the policy should be evaluated in a randomised controlled trial. This would mean allocating a large number of children at random to either have the stomach aspirated before feeds, or not. Such a trial would be a major undertaking and we are unsure if parents or staff would be willing to allow children to participate. The aim of this study was to see if it is possible to conduct such a large trial in the UK. Two surveys (of 119 units) showed us that regularly measuring the stomach contents when starting and increasing feeds is common practice for both newborn and older children in UK intensive care units. However, in some countries, such as France, this practice is rarely done. We asked 31 parents and 51 health-care professionals about a future study. Overall, parents were supportive of a trial if it was explained to them well by a knowledgeable and caring professional, and if they were approached at the right time. Some concerns were expressed about not picking up complications early if gastric residual volume was not measured. Health-care professionals were also mainly positive about a future trial, but mentioned similar concerns about not picking up complications early and the difficulty of changing a long-standing routine practice. Parents suggested study outcomes that were important to them. These, along with other outcomes, were voted on in a further survey of 106 professionals and at face-to-face meetings involving 41 participants. Overall, our findings suggest that a trial is feasible to perform and acceptable to parents. However, because of differences in both treatments and important outcomes between children’s intensive care units and newborn baby intensive care units, two trials would be needed, one in each type of intensive care unit. These two trials will test whether or not the benefits of not measuring gastric residual volume (e.g. improved calorie intake) outweigh the potential harms (e.g. delayed diagnosis of complications).

  • Publication . Article . Other literature type . Clinical Trial . 2021
    Open Access
    Authors: 
    Motahareh Vameghestahbanati; Miranda Kirby; François Maltais; Dennis Jensen; Dany Doiron; Wan C. Tan; Jean Bourbeau; Benjamin M. Smith; Yves Lacasse; Denis O’Donnell; +14 more
    Publisher: American Thoracic Society
  • Open Access English
    Authors: 
    Andrea H. Weinberger; Brian Hitsman; George D. Papandonatos; Kristi A. Sacco; Jennifer C. Vessicchio; Tony P. George;

    To the Editors: Adults with schizophrenia have higher rates of smoking and nicotine dependence and lower rates of smoking cessation than other adults (1-3). Further, the medical and economic burden of smoking on mentally ill persons is enormous (3, 4) so the development of safe and effective pharmacotherapies for these smokers is of considerable public health significance. FDA-approved smoking cessation pharmacotherapies like nicotine replacement therapy (NRT) and sustained-release bupropion (Zyban®, GlaxoSmithKline) appear to be safe and efficacious for smokers with schizophrenia (see (5) for review); however quit rates are modest and it is therefore important to determine characteristics of those who are responsive to interventions. Further, it is important to address the continued clinical concern that smoking cessation will exacerbate psychiatric symptoms for patients with serious mental illnesses (6). The current analyses examined predictors of smoking abstinence and changes in psychiatric symptoms in a pooled sample (N=135) from three sequential controlled clinical trials for nicotine dependent adult cigarette smokers with schizophrenia or schizoaffective disorder conducted through the Program for Research in Smokers with Mental Illness (PRISM) at the Yale University School of Medicine between 1998 and 2007 (see (7-9) for study details). The first study ((7); N=45) was an open-label trial of transdermal nicotine patch (TNP; 21mg/24h) plus one of two behavioral treatments. Participants in the second study ((8); N=32) received sustained-release bupropion (300 mg/day) or placebo and participants in the third study ((9); N=58) received TNP (21 mg/24h) with sustained-release bupropion (300 mg/day) or placebo. All studies had similar treatment protocols (e.g., 10 week duration), similar research staff, included manualized group behavioral counseling, and stratified treatment by antipsychotic medication class. Written informed consent was obtained from all participants and research protocols were approved by the Yale University School of Medicine's Human Investigation Committee. Participants in all studies completed measures of demographics, daily smoking (cigarettes per day, CPD), nicotine dependence (Fagerstrom Test for Nicotine Dependence, FTND, (10)), and psychiatric symptoms (Positive and Negative Symptoms Scale for Schizophrenia, PANSS, (11); Beck Depression Inventory-II, BDI-II, (12)). The primary outcome measures were smoking abstinence during the last week of the trials (End of Trial, EOT) and continuous abstinence (CA) over the last four weeks of the trials. Self-reported abstinence was biochemically verified by expired breath carbon monoxide (CO) levels 0.05). EOT symptoms of schizophrenia and depression were related significantly to baseline measures of the respective symptoms (positive symptoms p<0.001; negative symptoms p<0.001; depression p<0.01). EOT negative symptoms were related to between-study variability (p<0.05), confounded with TNP use. There was a trend for abstinence to be related to an increase in depression symptoms (p=0.06). Abstinence was associated with a 2.97 unit increase in BDI scores as compared to no change in BDI scores for non-abstinent participants with all other variables in the model being held constant. The results did not substantively change with CA as the measure of abstinence.

  • Publication . Article . Clinical Trial . Other literature type . 2021
    Open Access
    Authors: 
    Kurinchi Selvan Gurusamy; David Moher; Marilena Loizidou; Irfan Ahmed; Marc T. Avey; Carly C. Barron; Brian R. Davidson; Miriam Dwek; Christian Gluud; Gavin Jell; +8 more
    Publisher: PeerJ
    Country: Netherlands

    Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

  • Open Access
    Authors: 
    Laura Ann Magee;
    Project: CIHR

    Primary research question: For pregnant women with non-severe, non-proteinuric maternal hypertension at 14-33 weeks, will 'less tight' control (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours? Secondary research question: Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications? Other research questions: Will 'less tight' versus 'tight' control: 1. Increase (or decrease) the likelihood of serious perinatal complications? 2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia? 3. Increase (or decrease) the likelihood of maternal satisfaction with care? 4. Result in significant changes in dBP or health care costs? Treatment Allocation: Eligible women will be randomised centrally to either 'less tight' control (aiming for dBP of 100mmHg) or 'tight' control (aiming for dBP of 85mmHg) of their hypertension. Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational). - In the 'less tight' control group, if dBP is ≥105mmHg, then antihypertensive medication must be started or increased in dose. - In the 'tight' control group, if dBP is ≤80mmHg, then antihypertensive medication must be decreased in dose or discontinued. - In both groups, centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bedrest). Outcomes: Primary: Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for >48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later. Secondary: One/more serious maternal complication(s) until six weeks postpartum. Follow-up: Compliance (dBP and antihypertensive dose) will be assessed within 4 weeks of randomisation. Outcome data will be collected during the woman's (and baby's) hospital stay for birth (or loss). Women will be contacted 6 to 12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks corrected gestational age to enquire about satisfaction with care and any major maternal/neonatal morbidity following hospital discharge. The investigators do not know which approach to treatment of non-severe high blood pressure in pregnancy is better for women and babies. In the CHIPS Trial, the investigators seek to determine whether 'less tight' control (aiming for a diastolic blood pressure [dBP] of 100 mmHg), compared with 'tight' control (aiming for a diastolic blood pressure [dBP] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mother.

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Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
12 Research products, page 1 of 2
  • Open Access
    Authors: 
    Greg Knoll; Robert Bell;

    Abstract Objective : To compare tacrolimus with cyclosporin for immunosuppression in renal transplantation. Design : Meta-analysis of randomised trials of two treatments after kidney transplantation. Identification : Four studies involving 1037 patients. Trials were included if they were randomised, the intervention group received tacrolimus, the control group received cyclosporin, the patients were followed for a minimum of 12 months, and patient survival, graft survival, incidence of acute rejection, need for antilymphocyte treatment, or the prevalence of diabetes mellitus after transplant was reported. Main outcome measures : Pooled estimates of patient mortality, allograft loss, and episodes of acute rejection 1 year after transplantation. Results : The odds ratio for loss of allograft with tacrolimus compared with cyclosporin was 0.95 (95% confidence interval 0.65 to 1.40). The odds ratio for mortality with tacrolimus was 1.07 (0.47 to 2.48). Treatment with tacrolimus was associated with a reduction in episodes of acute rejection (0.52; 0.36 to 0.75), a reduction in the use of antilymphocyte antibodies to treat rejection (0.37; 0.25 to 0.56), and an increased prevalence of diabetes mellitus after transplantation (5.03; 2.04 to 12.36) compared with treatment with cyclosporin. Conclusions : After renal transplantation, immunosuppression with tacrolimus results in a significant reduction in acute rejection compared with cyclosporin. Follow up studies of high methodological quality are needed to determine whether tacrolimus improves long term renal graft survival.

  • Publication . Clinical Trial . Article . Other literature type . 1994
    Open Access English
    Authors: 
    L. Glover; Kenneth N. Gannon; Lorraine Sherr; Paul D. Abel;

    Where treatment options are limited, the role of clinical consultation in providing information and support becomes more important. This study examines the immediate impact of medical consultation on male sub-fertility clinic attender's anxiety, depression, self-blame, information appraisal and perceptions of future fertility. Data were collected pre- and immediately post-consultation. Clinical information and consultation details were recorded. Results showed that anxiety levels were high before consultation. Following consultation anxiety and self-blame were both reduced while depression increased. Despite information about poor prognosis being given during consultation, participants remained overly optimistic about their chances of achieving a pregnancy. It appears that the consultation has a distinct psychological impact and possible mechanisms underlying this are discussed.

  • Publication . Clinical Trial . Other literature type . 1981
    Open Access English
  • Open Access
    Authors: 
    Carrier, Marie-Eve; Kwakkenbos, Linda; Boutron, Isabelle; Welling, Joep; Sauve, Maureen; Ende, Cornelia van den; Schouffoer, Anne A.; Hudson, Marie; Maia, Ângela; Leite, Catarina; +1 more
    Countries: Portugal, Netherlands
    Project: CIHR

    Background: Significant functional impairment of the hands is nearly universal in systemic sclerosis (SSc, scleroderma). Hand exercises may improve hand function, but developing, testing and disseminating rehabilitation interventions in SSc is challenging. The Scleroderma Patient-centered Intervention Network (SPIN) was established to address this issue and has developed an online hand exercise program to improve hand function for SSc patients (SPIN-HAND). The aim of the proposed feasibility trial is to evaluate the feasibility of conducting a full-scale randomized controlled trial (RCT) of the SPIN-HAND intervention. Design and methods: The SPIN-HAND feasibility trial will be conducted via the SPIN Cohort. The SPIN Cohort was developed as a framework for embedded pragmatic trials using the cohort multiple RCT design. In total, 40 English-speaking SPIN Cohort participants with at least mild hand function limitations (Cochin Hand Function Scale ≥3) and an indicated interest in using an online hand-exercise intervention will be randomized with a 1:1 ratio to be offered to use the SPIN-HAND program or usual care for 3 months. The primary aim is to evaluate the trial implementation processes, required resources and management, scientific aspects, and participant acceptability and usage of the SPIN-HAND program. Discussion: The SPIN-HAND exercise program is a self-help tool that may improve hand function in patients with SSc. The SPIN-HAND feasibility trial will ensure that trial methodology is robust, feasible, and consistent with trial participant expectations. The results will guide adjustments that need to be implemented before undertaking a full-scale RCT of the SPIN-HAND program. Trial registration: ClinicalTrials.gov Identifier: NCT03092024. Canadian Institutes of Health Research(undefined)

  • Publication . Other literature type . Article . Clinical Trial . 2009
    Open Access
    Authors: 
    Daisy Dulay; Stephen A. LaHaye; Karen A. Lahey; Andrew G. Day;

    Background Compared with other statins, rosuvastatin has a relatively long half-life, which may allow for the administration of this medication on an alternate day basis. Objective To compare the efficacy of administering rosuvastatin on a daily basis versus on an alternate day basis for the treatment of dyslipidemia. Methods In the present crossover study, 45 patients with documented hypercholesterolemia requiring pharmacotherapy were administered either 20mg of rosuvastatin on alternate days or 10mg of rosuvastatin daily for six weeks. After a four-week washout period, patients were then switched to the other regimen for another six weeks. The primary end point was the percentage reduction of low-density lipoprotein cholesterol (LDL-C). Results LDL-C decreased by 48.5% versus 40.9% with daily and alternate day dosing, respectively. This represented an additional absolute reduction of LDL-C of 7.6% (95% CI 1.8% to 13.4%, P=0.012) with the daily dosing regimen. Both dosing regimens provided similar improvements in high-density lipoprotein cholesterol and triglycerides. Conclusions Compared with alternate day dosing, daily dosing of rosuvastatin provides a statistically significant advantage in LDL-C reduction. However, the alternate day regimen may be a viable option for those patients in whom cost is a limitation to compliance.

  • Open Access
    Authors: 
    Tume, LN; Woolfall, K; Arch, B; Roper, L; Deja, E; Jones, AP; Latten, L; Pathan, N; Eccleson, H; Hickey, H; +8 more
    Publisher: National Institute for Health Research
    Country: United Kingdom

    The routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it.To answer the question: is a trial of no gastric residual volume measurement feasible in UK paediatric intensive care units and neonatal units?A mixed-methods study involving five linked work packages in two parallel arms: neonatal units and paediatric intensive care units. Work package 1: a survey of units to establish current UK practice. Work package 2: qualitative interviews with health-care professionals and caregivers of children admitted to either setting. Work package 3: a modified two-round e-Delphi survey to investigate health-care professionals' opinions on trial design issues and to obtain consensus on outcomes. Work package 4: examination of national databases to determine the potential eligible populations. Work package 5: two consensus meetings of health-care professionals and parents to review the data and agree consensus on outcomes that had not reached consensus in the e-Delphi study.Parents of children with experience of ventilation and tube feeding in both neonatal units and paediatric intensive care units, and health-care professionals working in neonatal units and paediatric intensive care units.Baseline surveys showed that the practice of gastric residual volume measurement was very common (96% in paediatric intensive care units and 65% in neonatal units). Ninety per cent of parents from both neonatal units and paediatric intensive care units supported a future trial, while highlighting concerns around possible delays in detecting complications. Health-care professionals also indicated that a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes were addressed by developing a simple flow chart and education package. The trial design survey and e-Delphi study gained consensus on 12 paediatric intensive care unit and nine neonatal unit outcome measures, and identified acceptable inclusion and exclusion criteria. Given the differences in physiology, disease processes, environments, staffing and outcomes of interest, two different trials are required in the two settings. Database analyses subsequently showed that trials were feasible in both settings in terms of patient numbers. Of 16,222 children who met the inclusion criteria in paediatric intensive care units, 12,629 stayed for 3 days. In neonatal units, 15,375 neonates 32 weeks of age met the inclusion criteria. Finally, the two consensus meetings demonstrated 'buy-in' from the wider UK neonatal communities and paediatric intensive care units, and enabled us to discuss and vote on the outcomes that did not achieve consensus in the e-Delphi study.Two separate UK trials (one in neonatal units and one in paediatric intensive care units) are feasible to conduct, but they cannot be combined as a result of differences in outcome measures and treatment protocols, reflecting the distinctness of the two specialties.Current Controlled Trials ISRCTN42110505.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inNurses looking after babies and children on intensive care units in the UK usually pass a tube and aspirate whatever food or fluid is in the baby’s stomach before they give a feed. The idea is to ensure that the stomach is not overdistended with food and prevent the baby vomiting or, worse, aspirating food into the lungs. However, there is little justification for this practice. It is rarely done in many other countries. It may not be pleasant for the child and perhaps is unnecessary. Some experts have suggested that the policy should be evaluated in a randomised controlled trial. This would mean allocating a large number of children at random to either have the stomach aspirated before feeds, or not. Such a trial would be a major undertaking and we are unsure if parents or staff would be willing to allow children to participate. The aim of this study was to see if it is possible to conduct such a large trial in the UK. Two surveys (of 119 units) showed us that regularly measuring the stomach contents when starting and increasing feeds is common practice for both newborn and older children in UK intensive care units. However, in some countries, such as France, this practice is rarely done. We asked 31 parents and 51 health-care professionals about a future study. Overall, parents were supportive of a trial if it was explained to them well by a knowledgeable and caring professional, and if they were approached at the right time. Some concerns were expressed about not picking up complications early if gastric residual volume was not measured. Health-care professionals were also mainly positive about a future trial, but mentioned similar concerns about not picking up complications early and the difficulty of changing a long-standing routine practice. Parents suggested study outcomes that were important to them. These, along with other outcomes, were voted on in a further survey of 106 professionals and at face-to-face meetings involving 41 participants. Overall, our findings suggest that a trial is feasible to perform and acceptable to parents. However, because of differences in both treatments and important outcomes between children’s intensive care units and newborn baby intensive care units, two trials would be needed, one in each type of intensive care unit. These two trials will test whether or not the benefits of not measuring gastric residual volume (e.g. improved calorie intake) outweigh the potential harms (e.g. delayed diagnosis of complications).

  • Publication . Article . Other literature type . Clinical Trial . 2021
    Open Access
    Authors: 
    Motahareh Vameghestahbanati; Miranda Kirby; François Maltais; Dennis Jensen; Dany Doiron; Wan C. Tan; Jean Bourbeau; Benjamin M. Smith; Yves Lacasse; Denis O’Donnell; +14 more
    Publisher: American Thoracic Society
  • Open Access English
    Authors: 
    Andrea H. Weinberger; Brian Hitsman; George D. Papandonatos; Kristi A. Sacco; Jennifer C. Vessicchio; Tony P. George;

    To the Editors: Adults with schizophrenia have higher rates of smoking and nicotine dependence and lower rates of smoking cessation than other adults (1-3). Further, the medical and economic burden of smoking on mentally ill persons is enormous (3, 4) so the development of safe and effective pharmacotherapies for these smokers is of considerable public health significance. FDA-approved smoking cessation pharmacotherapies like nicotine replacement therapy (NRT) and sustained-release bupropion (Zyban®, GlaxoSmithKline) appear to be safe and efficacious for smokers with schizophrenia (see (5) for review); however quit rates are modest and it is therefore important to determine characteristics of those who are responsive to interventions. Further, it is important to address the continued clinical concern that smoking cessation will exacerbate psychiatric symptoms for patients with serious mental illnesses (6). The current analyses examined predictors of smoking abstinence and changes in psychiatric symptoms in a pooled sample (N=135) from three sequential controlled clinical trials for nicotine dependent adult cigarette smokers with schizophrenia or schizoaffective disorder conducted through the Program for Research in Smokers with Mental Illness (PRISM) at the Yale University School of Medicine between 1998 and 2007 (see (7-9) for study details). The first study ((7); N=45) was an open-label trial of transdermal nicotine patch (TNP; 21mg/24h) plus one of two behavioral treatments. Participants in the second study ((8); N=32) received sustained-release bupropion (300 mg/day) or placebo and participants in the third study ((9); N=58) received TNP (21 mg/24h) with sustained-release bupropion (300 mg/day) or placebo. All studies had similar treatment protocols (e.g., 10 week duration), similar research staff, included manualized group behavioral counseling, and stratified treatment by antipsychotic medication class. Written informed consent was obtained from all participants and research protocols were approved by the Yale University School of Medicine's Human Investigation Committee. Participants in all studies completed measures of demographics, daily smoking (cigarettes per day, CPD), nicotine dependence (Fagerstrom Test for Nicotine Dependence, FTND, (10)), and psychiatric symptoms (Positive and Negative Symptoms Scale for Schizophrenia, PANSS, (11); Beck Depression Inventory-II, BDI-II, (12)). The primary outcome measures were smoking abstinence during the last week of the trials (End of Trial, EOT) and continuous abstinence (CA) over the last four weeks of the trials. Self-reported abstinence was biochemically verified by expired breath carbon monoxide (CO) levels 0.05). EOT symptoms of schizophrenia and depression were related significantly to baseline measures of the respective symptoms (positive symptoms p<0.001; negative symptoms p<0.001; depression p<0.01). EOT negative symptoms were related to between-study variability (p<0.05), confounded with TNP use. There was a trend for abstinence to be related to an increase in depression symptoms (p=0.06). Abstinence was associated with a 2.97 unit increase in BDI scores as compared to no change in BDI scores for non-abstinent participants with all other variables in the model being held constant. The results did not substantively change with CA as the measure of abstinence.

  • Publication . Article . Clinical Trial . Other literature type . 2021
    Open Access
    Authors: 
    Kurinchi Selvan Gurusamy; David Moher; Marilena Loizidou; Irfan Ahmed; Marc T. Avey; Carly C. Barron; Brian R. Davidson; Miriam Dwek; Christian Gluud; Gavin Jell; +8 more
    Publisher: PeerJ
    Country: Netherlands

    Background Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. Methods We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. Results This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. Conclusion We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

  • Open Access
    Authors: 
    Laura Ann Magee;
    Project: CIHR

    Primary research question: For pregnant women with non-severe, non-proteinuric maternal hypertension at 14-33 weeks, will 'less tight' control (target diastolic blood pressure [dBP] of 100 mmHg) versus 'tight' control (target dBP of 85 mmHg) increase (or decrease) the likelihood of pregnancy loss or Neonatal Intensive Care Unit (NICU) admission for greater than 48 hours? Secondary research question: Will 'less tight' versus 'tight' control increase (or decrease) the likelihood of serious maternal complications? Other research questions: Will 'less tight' versus 'tight' control: 1. Increase (or decrease) the likelihood of serious perinatal complications? 2. Increase (or decrease) the likelihood of severe hypertension and pre-eclampsia? 3. Increase (or decrease) the likelihood of maternal satisfaction with care? 4. Result in significant changes in dBP or health care costs? Treatment Allocation: Eligible women will be randomised centrally to either 'less tight' control (aiming for dBP of 100mmHg) or 'tight' control (aiming for dBP of 85mmHg) of their hypertension. Randomisation will be stratified by centre and type of hypertension (pre-existing or gestational). - In the 'less tight' control group, if dBP is ≥105mmHg, then antihypertensive medication must be started or increased in dose. - In the 'tight' control group, if dBP is ≤80mmHg, then antihypertensive medication must be decreased in dose or discontinued. - In both groups, centres will provide their usual care. Data will be collected on potential co-interventions (e.g., hospitalisation, bedrest). Outcomes: Primary: Pregnancy loss (miscarriage or ectopic pregnancy, pregnancy termination, stillbirth, or neonatal death) or high level neonatal care for >48 hours in the first 28 days of life or prior to primary hospital discharge, whichever is later. Secondary: One/more serious maternal complication(s) until six weeks postpartum. Follow-up: Compliance (dBP and antihypertensive dose) will be assessed within 4 weeks of randomisation. Outcome data will be collected during the woman's (and baby's) hospital stay for birth (or loss). Women will be contacted 6 to 12 weeks after delivery (or loss) and, for preterm babies, when the baby is at 36 weeks corrected gestational age to enquire about satisfaction with care and any major maternal/neonatal morbidity following hospital discharge. The investigators do not know which approach to treatment of non-severe high blood pressure in pregnancy is better for women and babies. In the CHIPS Trial, the investigators seek to determine whether 'less tight' control (aiming for a diastolic blood pressure [dBP] of 100 mmHg), compared with 'tight' control (aiming for a diastolic blood pressure [dBP] of 85 mmHg) can decrease the risks of adverse baby outcomes without increasing the risk of problems for the mother.