Diffusion of Intervention Effects: The Impact of a Family-based Substance Use Prevention Program on Friends of Participants

PubMed Central

Rulison, Kelly L.; Feinberg, Mark; Gest, Scott D.; Osgood, D. Wayne

2015-01-01

Purpose We tested whether effects of the Strengthening Families Program for Youth 10–14 (SFP10–14) diffused from intervention participants to their friends. We also tested which program effects on participants accounted for diffusion. Methods Data are from 5,449 students (51% female; mean initial age=12.3 years) in the PROSPER community intervention trial (2001–2006) who did not participate in SFP10–14 (i.e., non-participants). At each of 5 waves, students identified up to 7 friends and self-reported past month drunkenness and cigarette use, substance use attitudes, parenting practices, and unsupervised time spent with friends. We computed two measures of indirect exposure to SFP10–14: total number of SFP-attending friends at each wave and cumulative proportion of SFP-attending friends averaged across the current and all previous post-intervention waves. Results Three years post-intervention, the odds of getting drunk (OR=1.4) and using cigarettes (OR=2.7) were higher among non-participants with 0 SFP-attending friends compared to non-participants with 3 or more SFP-attending friends. Multilevel analyses also provided evidence of diffusion: non-participants with a higher cumulative proportion of SFP-attending friends at a given wave were less likely than their peers to use drugs at that wave. Effects from SFP10–14 primarily diffused through friendship networks by reducing the amount of unstructured socializing (unsupervised time that non-participants spent with friends), changing friends’ substance use attitudes, and then changing non-participants’ own substance use attitudes. Conclusions Program developers should consider and test how interventions may facilitate diffusion to extend program reach and promote program sustainability. PMID:26210856

Current Pipelines for Neglected Diseases

PubMed Central

di Procolo, Paolo; Jommi, Claudio

2014-01-01

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials. PMID:25187946

Current pipelines for neglected diseases.

PubMed

di Procolo, Paolo; Jommi, Claudio

2014-09-01

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials.

Improving ethical and participatory practice for marginalized populations in biomedical HIV prevention trials: lessons from Thailand.

PubMed

Allman, Dan; Ditmore, Melissa Hope; Kaplan, Karyn

2014-01-01

This paper presents findings from a qualitative investigation of ethical and participatory issues related to the conduct of biomedical HIV prevention trials among marginalized populations in Thailand. This research was deemed important to conduct, as several large-scale biomedical HIV prevention trials among marginalized populations had closed prematurely in other countries, and a better understanding of how to prevent similar trial closures from occurring in the future was desired. In-depth key informant interviews were held in Bangkok and Chiang Mai, Thailand. Interviews were audio recorded, transcribed, translated and thematically analyzed. The Good Participatory Practice Guidelines for Biomedical HIV Prevention Trials (GPP) guided this work. Fourteen interviews were conducted: 10 with policymakers, academic and community-based researchers and trial staff and four with representatives of non-governmental organizations (NGOs). Suggested ways to improve ethical and participatory practice centered on standards of HIV prevention, informed consent, communication and human rights. In particular, the need to overcome language and literacy differences was identified. Key informants felt communication was the basis of ethical understanding and trust within biomedical HIV prevention trial contexts, and thus fundamental to trial participants' ability to exercise free will. Biomedical HIV prevention trials present opportunities for inclusive and productive ethical and participatory practice. Key informants suggested that efforts to improve practice could result in better relationships between research stakeholders and research investigative teams and by extension, better, more ethical participatory trials. This research took place in Thailand and its findings apply primarily to Thailand. However, given the universality of many ethical considerations, the results of this study can inform the improvement of ethical and participatory practice in other parts of the world where biomedical HIV prevention trials occur, and where clinical trials in marginalized populations continue.

JNCI and Cancer Prevention

PubMed Central

Ghosh, Sharmistha; Kramer, Barnett S.

2015-01-01

The Journal of the National Cancer Institute (JNCI), with its broad coverage of bench research, epidemiologic studies, and clinical trials, has a long history of publishing practice-changing studies in cancer prevention and public health. These include studies of tobacco cessation, chemoprevention, and nutrition. The landmark Breast Cancer Prevention Trial (BCPT)—the first large trial to prove efficacy of a preventive medication for a major malignancy—was published in the Journal, as were key ancillary papers to the BCPT. Even when JNCI was not the publication venue for the main trial outcomes, conceptual and design discussions leading to the trial as well as critical follow-up analyses based on trial data from the Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Chemoprevention Trial (SELECT) were published in the Journal. The Journal has also published important evidence on very charged topics, such as the purported link between abortion and breast cancer risk. In summary, JNCI has been at the forefront of numerous major publications related to cancer prevention. PMID:25713150

Acceptability and use of a dapivirine vaginal ring in a phase III trial

PubMed Central

Montgomery, Elizabeth T.; van der Straten, Ariane; Chitukuta, Miria; Reddy, Krishnaveni; Woeber, Kubashni; Atujuna, Millicent; Bekker, Linda-Gail; Etima, Juliane; Nakyanzi, Teopista; Mayo, Ashley J.; Katz, Ariana; Laborde, Nicole; Grossman, Cynthia I.; Soto-Torres, Lydia; Palanee-Phillips, Thesla; Baeten, Jared M.

2017-01-01

Background The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. Method Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. Results We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. Conclusion It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden. PMID:28441175

Acceptability and use of a dapivirine vaginal ring in a phase III trial.

PubMed

Montgomery, Elizabeth T; van der Straten, Ariane; Chitukuta, Miria; Reddy, Krishnaveni; Woeber, Kubashni; Atujuna, Millicent; Bekker, Linda-Gail; Etima, Juliane; Nakyanzi, Teopista; Mayo, Ashley J; Katz, Ariana; Laborde, Nicole; Grossman, Cynthia I; Soto-Torres, Lydia; Palanee-Phillips, Thesla; Baeten, Jared M

2017-05-15

The MTN-020/ASPIRE trial evaluated the safety and effectiveness of the dapivirine vaginal ring for prevention of HIV-1 infection among African women. A nested qualitative component was conducted at six of 15 study sites in Uganda, Malawi, Zimbabwe and South Africa to evaluate acceptability of and adherence to the ring. Qualitative study participants (n = 214) were interviewed with one of three modalities: single in-depth interview, up to three serial interviews or an exit Focus Group Discussion. Using semistructured guides administered in local languages, 280 interviews were audio-recorded, transcribed, translated, coded and analyzed. We identified three key findings: first, despite initial fears about the ring's appearance and potential side effects, participants grew to like it and developed a sense of ownership of the ring once they had used it. Second, uptake and sustained adherence challenges were generally overcome with staff and peer support. Participants developed gradual familiarity with ring use through trial progression, and most reported that it was easy to use and integrate into their lives. Using the ring in ASPIRE was akin to joining a team and contributing to a broader, communal good. Third, the actual or perceived dynamics of participants' male partner relationship(s) were the most consistently described influence (which ranged from positive to negative) on participants' acceptability and use of the ring. It is critical that demonstration projects address challenges during the early adoption stages of ring diffusion to help achieve its potential public health impact as an effective, long-acting, female-initiated HIV prevention option addressing women's disproportionate HIV burden.

[Defining an ethics for preventive trials].

PubMed

Chippaux, J-P

2008-04-01

Preventive trials (to prevent from infection) or prophylaxis trials (to avoid consequences of the disease) differ from other clinical trials as they apply to healthy subjects or subjects considering themselves as such: the latter do not ask for intervention even less for trial. Moreover, it is generally an experiment which aims at validating a public health intervention, the individual character of which could appear as secondary regarding the collective interest. It concerns many tools or methods: preventive or prophylactic vaccines and drugs, condoms, impregnated bed nets, etc. The field of implementation of preventive trials is large and covers routine immunization (EPI), large-scale control or eradication of endemic diseases or epidemics, for which the concept of individual risk is generally better understood. Preventive trials imply ethical obligations (high individual or collective benefits and absence of risks as there is no immediate therapeutic compensation), methodological adaptations (because the number of subjects is considerably larger than for therapeutic trials) and a sensitive valorization towards a large population who is not asking for the recommended intervention. As regard the benefits, it is also necessary to consider the costs in comparison with the expected efficacy The methodological constraints are important because the demonstration of both safety and efficacy requires a very large number of subjects to validate the product. It is often necessary to use indirect or substitutive markers and indicators (title of protective antibodies rather than definite clinical protection) which need a preliminary validation. Before carrying out a preventive or prophylactic trial, it is advisable to specify the objectives in order to assess the real profits and absence of risks during the trial and after the implementation of the tested product. Preventive trials require a phase of technological transfer to guarantee the application of the validated tools for the benefit of the population at stake. In this respect, if trials for prevention are now well codified both on ethical and methodological aspects, trials for prophylaxis (filariasis with ivermectin, schistosomiasis with praziquantel, malaria with intermittent "preventive" treatment or HIV with antiretroviral treatment, for example) still remain a difficult issue at both ethical and methodological levels.

How thin barrier metal can be used to prevent Co diffusion in the modern integrated circuits?

NASA Astrophysics Data System (ADS)

Dixit, Hemant; Konar, Aniruddha; Pandey, Rajan; Ethirajan, Tamilmani

2017-11-01

In modern integrated circuits (ICs), billions of transistors are connected to each other via thin metal layers (e.g. copper, cobalt, etc) known as interconnects. At elevated process temperatures, inter-diffusion of atomic species can occur among these metal layers, causing sub-optimal performance of interconnects, which may lead to the failure of an IC. Thus, typically a thin barrier metal layer is used to prevent the inter-diffusion of atomic species within interconnects. For ICs with sub-10 nm transistors (10 nm technology node), the design rule (thickness scaling) demands the thinnest possible barrier layer. Therefore, here we investigate the critical thickness of a titanium-nitride (TiN) barrier that can prevent the cobalt diffusion using multi-scale modeling and simulations. First, we compute the Co diffusion barrier in crystalline and amorphous TiN with the nudged elastic band method within first-principles density functional theory simulations. Later, using the calculated activation energy barriers, we quantify the Co diffusion length in the TiN metal layer with the help of kinetic Monte Carlo simulations. Such a multi-scale modelling approach yields an exact critical thickness of the metal layer sufficient to prevent the Co diffusion in IC interconnects. We obtain a diffusion length of a maximum of 2 nm for a typical process of thermal annealing at 400 °C for 30 min. Our study thus provides useful physical insights for the Co diffusion in the TiN layer and further quantifies the critical thickness (~2 nm) to which the metal barrier layer can be thinned down for sub-10 nm ICs.

Polymeric hydrogen diffusion barrier, high-pressure storage tank so equipped, method of fabricating a storage tank and method of preventing hydrogen diffusion

DOEpatents

Lessing, Paul A [Idaho Falls, ID

2008-07-22

An electrochemically active hydrogen diffusion barrier which comprises an anode layer, a cathode layer, and an intermediate electrolyte layer, which is conductive to protons and substantially impermeable to hydrogen. A catalytic metal present in or adjacent to the anode layer catalyzes an electrochemical reaction that converts any hydrogen that diffuses through the electrolyte layer to protons and electrons. The protons and electrons are transported to the cathode layer and reacted to form hydrogen. The hydrogen diffusion barrier is applied to a polymeric substrate used in a storage tank to store hydrogen under high pressure. A storage tank equipped with the electrochemically active hydrogen diffusion barrier, a method of fabricating the storage tank, and a method of preventing hydrogen from diffusing out of a storage tank are also disclosed.

Polymeric hydrogen diffusion barrier, high-pressure storage tank so equipped, method of fabricating a storage tank and method of preventing hydrogen diffusion

DOEpatents

Lessing, Paul A.

2004-09-07

An electrochemically active hydrogen diffusion barrier which comprises an anode layer, a cathode layer, and an intermediate electrolyte layer, which is conductive to protons and substantially impermeable to hydrogen. A catalytic metal present in or adjacent to the anode layer catalyzes an electrochemical reaction that converts any hydrogen that diffuses through the electrolyte layer to protons and electrons. The protons and electrons are transported to the cathode layer and reacted to form hydrogen. The hydrogen diffusion barrier is applied to a polymeric substrate used in a storage tank to store hydrogen under high pressure. A storage tank equipped with the electrochemically active hydrogen diffusion barrier, a method of fabricating the storage tank, and a method of preventing hydrogen from diffusing out of a storage tank are also disclosed.

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Selenium and Vitamin E Cancer Prevention Trial (SELECT): Questions and Answers

Cancer.gov

Learn the results of the Selenium and Vitamin E Cancer Prevention Trial. SELECT was a clinical trial to see if one or both of these substances could help prevent prostate cancer when taken as dietary supplements.

Primary and Secondary Prevention Trials in Alzheimer Disease: Looking Back, Moving Forward

PubMed Central

Hsu, David C.; Marshall, Gad A.

2015-01-01

The field of Alzheimer disease (AD) prevention has been a culmination of basic science, clinical, and translational research. In the past three years since the new 2011 AD diagnostic guidelines, large-scale collaborative efforts have embarked on new clinical trials with the hope of someday preventing AD. This review will shed light on the historical and scientific contexts in which these trials were based on, as well as discuss potential challenges these trials may face in the coming years. Primary preventive measures, such as lifestyle, multidomain, medication, and supplemental interventions, will be analyzed. Secondary prevention as represented by disease-modifying interventions, such as anti-amyloid therapy and pioglitazone, will also be reviewed. Finally, hypotheses on future directions for AD prevention trials will be proposed. PMID:27697063

Structural pathways and prevention of heart failure and sudden death.

PubMed

Pacifico, Antonio; Henry, Philip D

2003-07-01

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

The DIAN-TU Next Generation Alzheimer's prevention trial: Adaptive design and disease progression model.

PubMed

Bateman, Randall J; Benzinger, Tammie L; Berry, Scott; Clifford, David B; Duggan, Cynthia; Fagan, Anne M; Fanning, Kathleen; Farlow, Martin R; Hassenstab, Jason; McDade, Eric M; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P; Santacruz, Anna; Schneider, Lon S; Wang, Guoqiao; Xiong, Chengjie

2017-01-01

The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer's disease in autosomal dominant Alzheimer's disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation (NexGen) prevention trial. In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the National Institutes of Health, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen prevention trial. Our expanded trial toolbox consists of a disease progression model for ADAD, primary end point DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

About the Community Oncology and Prevention Trials Research Group | Division of Cancer Prevention

Cancer.gov

The Community Oncology and Prevention Trials Research Group supports clinical oncology trials in cancer prevention and control in community settings. The group also supports investigator-initiated research projects in supportive, palliative and end-of-life care, and coordinates clinical oncology research projects with other NCI programs to be done in the community setting. |

Supporting the diffusion of healthy public policy in Canada: the Prevention Policies Directory

PubMed Central

Politis, Christopher E.; Halligan, Michelle H.; Keen, Deb; Kerner, Jon F.

2014-01-01

Healthy public policy plays an essential role in a comprehensive public health approach to preventing cancer and chronic disease. Public policies spread through the ‘policy diffusion’ process, enabling governments to learn from another’s enacted policy solutions. The Prevention Policies Directory (the Directory), an online database of municipal, provincial/territorial, and federal cancer and chronic disease prevention policies from across Canada, was developed to facilitate the diffusion of healthy public policies and support the work of prevention researchers, practitioners, and policy specialists. This information technology solution was implemented, through a participatory engagement approach, as a communication channel or policy knowledge transfer tool. It also addressed the intrinsic shortcomings of environmental scanning for policy surveillance and monitoring. A combination of quantitative web metrics and qualitative anecdotal evidence have illustrated that the Directory is becoming an important tool for healthy public policy surveillance and policy diffusion in Canada. PMID:25379125

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

PubMed

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-07-08

Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen; Al-Hameed, Fahad; Burns, Karen E A; Mehta, Sangeeta; Alsolamy, Sami; Almaani, Mohammed; Mandourah, Yasser; Almekhlafi, Ghaleb A; Al Bshabshe, Ali; Finfer, Simon; Alshahrani, Mohammed; Khalid, Imran; Mehta, Yatin; Gaur, Atul; Hawa, Hassan; Buscher, Hergen; Arshad, Zia; Lababidi, Hani; Al Aithan, Abdulsalam; Jose, Jesna; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Al-Dawood, Abdulaziz

2018-03-15

The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

A Randomized Trial of an Advanced Sun Safety Intervention for Vacationers at 41 North American Resorts.

PubMed

Andersen, Peter A; Buller, David B; Walkosz, Barbara J; Scott, Michael D; Beck, Larry; Liu, Xia; Abbott, Allison; Eye, Rachel; Cutter, Gary

2017-12-01

Taking vacations in sunny locations is associated with the development of skin cancer. This study tested a multi-component sun protection intervention based on diffusion of innovations theory and transportation theory designed to increase vacationers' comprehensive sun protection, i.e., use of clothing, hats, and shade, and use, pre-application, and reapplication of sunscreen. The trial enrolled 41 warm weather resorts in North America in a pair-matched group randomized pretest-posttest design and assessed samples of adult vacationers at resort outdoor recreation venues regarding sun protection at pretest (n = 3,531) and posttest (n = 3,226). While results showed no overall effect of the intervention on comprehensive sun protection across venues, the intervention produced statistically significant improvements in sun protection at waterside venues (pools and beaches). The intervention's overall effects may have been impeded by a lack of uniformly robust implementation, low interest in skin cancer prevention by guests, or shortcomings of the theories used to create prevention messages. The intervention may have worked best with guests in the highest-risk recreation venue, i.e., waterside recreation where they exposed the most skin. Alternative approaches that alter resort organizations, such as through changes in policy, environmental features, or occupational efforts might be more effective than targeting vacationers with behavior-change messages.

Biorepository for Selenium and Vitamin E Cancer Prevention Trial (SELECT) | Division of Cancer Prevention

Cancer.gov

As the largest prostate cancer prevention trial ever undertaken, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) has assembled a substantial biorepository of specimens. To help make SELECT resources available to a wider research community, NCI and the Southwest Oncology Group are developing a plan for prostate cancer biology and nutritional science and

Parameter Variability and Distributional Assumptions in the Diffusion Model

ERIC Educational Resources Information Center

Ratcliff, Roger

2013-01-01

If the diffusion model (Ratcliff & McKoon, 2008) is to account for the relative speeds of correct responses and errors, it is necessary that the components of processing identified by the model vary across the trials of a task. In standard applications, the rate at which information is accumulated by the diffusion process is assumed to be normally…

Participant verification: prevention of co-enrolment in clinical trials in South Africa.

PubMed

Harichund, C; Haripersad, K; Ramjee, R

2013-05-15

As KwaZulu-Natal Province is the epicentre of the HIV epidemic in both South Africa (SA) and globally, it is an ideal location to conduct HIV prevention and therapeutic trials. Numerous prevention trials are currently being conducted here; the potential for participant co-enrolment may compromise the validity of these studies and is therefore of great concern. To report the development and feasibility of a digital, fingerprint-based participant identification method to prevent co-enrolment at multiple clinical trial sites. The Medical Research Council (MRC) HIV Prevention Research Unit (HPRU) developed the Biometric Co-enrolment Prevention System (BCEPS), which uses fingerprint-based biometric technology to identify participants. A trial website was used to determine the robustness and usability of the system. After successful testing, the BCEPS was piloted in July 2010 across 7 HPRU clinical research sites. The BCEPS was pre-loaded with study names and clinical trial sites, with new participant information loaded at first visit to a trial site. We successfully implemented the BCEPS at the 7 HPRU sites. Using the BCEPS, we performed real-time 'flagging' of women who were already enrolled in another study as they entered a trial at an HPRU site and, where necessary, excluded them from participation on site. This system has promise in reducing co-enrolment in clinical trials and represents a valuable tool for future implementation by all groups conducting trials. The MRC is currently co-ordinating this effort with clinical trial sites nationally.

Clinical Trials Management | Division of Cancer Prevention

Cancer.gov

Information for researchers about developing, reporting, and managing NCI-funded cancer prevention clinical trials. Protocol Information Office The central clearinghouse for clinical trials management within the Division of Cancer Prevention.Read more about the Protocol Information Office. | Information for researchers about developing, reporting, and managing NCI-funded

Integrated solutions for sustainable fall prevention in primary care, the iSOLVE project: a type 2 hybrid effectiveness-implementation design.

PubMed

Clemson, Lindy; Mackenzie, Lynette; Roberts, Chris; Poulos, Roslyn; Tan, Amy; Lovarini, Meryl; Sherrington, Cathie; Simpson, Judy M; Willis, Karen; Lam, Mary; Tiedemann, Anne; Pond, Dimity; Peiris, David; Hilmer, Sarah; Pit, Sabrina Winona; Howard, Kirsten; Lovitt, Lorraine; White, Fiona

2017-02-07

Despite strong evidence giving guidance for effective fall prevention interventions in community-residing older people, there is currently no clear model for engaging general medical practitioners in fall prevention and routine use of allied health professionals in fall prevention has been slow, limiting widespread dissemination. This protocol paper outlines an implementation-effectiveness study of the Integrated Solutions for Sustainable Fall Prevention (iSOLVE) intervention which has developed integrated processes and pathways to identify older people at risk of falls and engage a whole of primary care approach to fall prevention. This protocol paper presents the iSOLVE implementation processes and change strategies and outlines the study design of a blended type 2 hybrid design. The study consists of a two-arm cluster randomized controlled trial in 28 general practices and recruiting 560 patients in Sydney, Australia, to evaluate effectiveness of the iSOLVE intervention in changing general practitioner fall management practices and reducing patient falls and the cost effectiveness from a healthcare funder perspective. Secondary outcomes include change in medications known to increase fall risk. We will simultaneously conduct a multi-methodology evaluation to investigate the workability and utility of the implementation intervention. The implementation evaluation includes in-depth interviews and surveys with general practitioners and allied health professionals to explore acceptability and uptake of the intervention, the coherence of the proposed changes for those in the work setting, and how to facilitate the collective action needed to implement changes in practice; social network mapping will explore professional relationships and influences on referral patterns; and, a survey of GPs in the geographical intervention zone will test diffusion of evidence-based fall prevention practices. The project works in partnership with a primary care health network, state fall prevention leaders, and a community of practice of fall prevention advocates. The design is aimed at providing clear direction for sustainability and informing decisions about generalization of the iSOLVE intervention processes and change strategies. While challenges exist in hybrid designs, there is a potential for significant outcomes as the iSOLVE pathways project brings together practice and research to collectively solve a major national problem with implications for policy service delivery. Australian New Zealand Clinial Trials Registry ACTRN12615000401550.

Clinical Trial Design for HIV Prevention Research: Determining Standards of Prevention.

PubMed

Dawson, Liza; Zwerski, Sheryl

2015-06-01

This article seeks to advance ethical dialogue on choosing standards of prevention in clinical trials testing improved biomedical prevention methods for HIV. The stakes in this area of research are high, given the continued high rates of infection in many countries and the budget limitations that have constrained efforts to expand treatment for all who are currently HIV-infected. New prevention methods are still needed; at the same time, some existing prevention and treatment interventions have been proven effective but are not yet widely available in the countries where they most urgently needed. The ethical tensions in this field of clinical research are well known and have been the subject of extensive debate. There is no single clinical trial design that can optimize all the ethically important goals and commitments involved in research. Several recent articles have described the current ethical difficulties in designing HIV prevention trials, especially in resource limited settings; however, there is no consensus on how to handle clinical trial design decisions, and existing international ethical guidelines offer conflicting advice. This article acknowledges these deep ethical dilemmas and moves beyond a simple descriptive approach to advance an organized method for considering what clinical trial designs will be ethically acceptable for HIV prevention trials, balancing the relevant criteria and providing justification for specific design decisions. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

The DIAN-TU Next Generation Alzheimer’s prevention trial: adaptive design and disease progression model

PubMed Central

Bateman, Randall J.; Benzinger, Tammie L.; Berry, Scott; Clifford, David B.; Duggan, Cynthia; Fagan, Anne M.; Fanning, Kathleen; Farlow, Martin R.; Hassenstab, Jason; McDade, Eric M.; Mills, Susan; Paumier, Katrina; Quintana, Melanie; Salloway, Stephen P.; Santacruz, Anna; Schneider, Lon S.; Wang, Guoqiao; Xiong, Chengjie

2016-01-01

INTRODUCTION The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) trial is an adaptive platform trial testing multiple drugs to slow or prevent the progression of Alzheimer’s disease in autosomal dominant Alzheimer’s disease (ADAD) families. With completion of enrollment of the first two drug arms, the DIAN-TU now plans to add new drugs to the platform, designated as the Next Generation Prevention Trial (NexGen). METHODS In collaboration with ADAD families, philanthropic organizations, academic leaders, the DIAN-TU Pharma Consortium, the NIH, and regulatory colleagues, the DIAN-TU developed innovative clinical study designs for the DIAN-TU NexGen trial. RESULTS Our expanded trials toolbox consists of a Disease Progression Model for ADAD, primary endpoint DIAN-TU cognitive performance composite, biomarker development, self-administered cognitive assessments, adaptive dose adjustments, and blinded data collection through the last participant completion. CONCLUSION These steps represent elements to improve efficacy of the adaptive platform trial and a continued effort to optimize prevention and treatment trials in ADAD. PMID:27583651

Depression Prevention Research: Design, Implementation, and Analysis of Randomized Trials.

ERIC Educational Resources Information Center

Munoz, Ricardo F.; And Others

This document contains three papers concerned with prevention intervention research, a new area of depression research which has shown great promise for contributing new knowledge to the understanding of depression. The first paper, "Clinical Trials vs. Prevention Trials: Methodological Issues in Depression Research" (Ricardo F. Munoz), emphasizes…

School climate and teachers' beliefs and attitudes associated with implementation of the positive action program: a diffusion of innovations model.

PubMed

Beets, Michael W; Flay, Brian R; Vuchinich, Samuel; Acock, Alan C; Li, Kin-Kit; Allred, Carol

2008-12-01

Teacher- and school-level factors influence the fidelity of implementation of school-based prevention and social character and development (SACD) programs. Using a diffusion of innovations framework, the relationships among teacher beliefs and attitudes towards a prevention/SACD program and the influence of a school's administrative support and perceptions of school connectedness, characteristics of a school's climate, were specified in two cross-sectional mediation models of program implementation. Implementation was defined as the amount of the programs' curriculum delivered (e.g., lessons taught), and use of program-specific materials in the classroom (e.g., ICU boxes and notes) and in relation to school-wide activities (e.g., participation in assemblies). Teachers from 10 elementary schools completed year-end process evaluation reports for year 2 (N = 171) and 3 (N = 191) of a multi-year trial. Classroom and school-wide material usage were each favorably associated with the amount of the curriculum delivered, which were associated with teachers' attitudes toward the program which, in turn, were related to teachers' beliefs about SACD. These, in turn, were associated with teachers' perceptions of school climate. Perceptions of school climate were indirectly related to classroom material usage and both indirectly and directly related to the use of school-wide activities. Program developers need to consider the importance of a supportive environment on program implementation and attempt to incorporate models of successful school leadership and collaboration among teachers that foster a climate promoting cohesiveness, shared visions, and support.

Improving decision making about clinical trial participation – a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial

PubMed Central

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-01-01

Background: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. Methods: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Results: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS–DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. Conclusions: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation. PMID:24892447

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials

PubMed Central

Gilbert, Peter B.; Juraska, Michal; deCamp, Allan C.; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J.; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H.; Mayer, Kenneth H.; Magaret, Craig A.; Hural, John; Kublin, James G.; Gray, Glenda; Montefiori, David C.; Gomez, Margarita M.; Burns, David N.; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S.; Mascola, John R.; Cohen, Myron; Corey, Lawrence

2017-01-01

Background Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. Methods The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Results Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. Conclusions The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention. PMID:29218117

Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials.

PubMed

Gilbert, Peter B; Juraska, Michal; deCamp, Allan C; Karuna, Shelly; Edupuganti, Srilatha; Mgodi, Nyaradzo; Donnell, Deborah J; Bentley, Carter; Sista, Nirupama; Andrew, Philip; Isaacs, Abby; Huang, Yunda; Zhang, Lily; Capparelli, Edmund; Kochar, Nidhi; Wang, Jing; Eshleman, Susan H; Mayer, Kenneth H; Magaret, Craig A; Hural, John; Kublin, James G; Gray, Glenda; Montefiori, David C; Gomez, Margarita M; Burns, David N; McElrath, Julie; Ledgerwood, Julie; Graham, Barney S; Mascola, John R; Cohen, Myron; Corey, Lawrence

2017-01-01

Anti-HIV-1 broadly neutralizing antibodies (bnAbs) have been developed as potential agents for prevention of HIV-1 infection. The HIV Vaccine Trials Network and the HIV Prevention Trials Network are conducting the Antibody Mediated Prevention (AMP) trials to assess whether, and how, intravenous infusion of the anti-CD4 binding site bnAb, VRC01, prevents HIV-1 infection. These are the first test-of-concept studies to assess HIV-1 bnAb prevention efficacy in humans. The AMP trials are two parallel phase 2b HIV-1 prevention efficacy trials conducted in two cohorts: 2700 HIV-uninfected men and transgender persons who have sex with men in the United States, Peru, Brazil, and Switzerland; and 1500 HIV-uninfected sexually active women in seven countries in sub-Saharan Africa. Participants are randomized 1:1:1 to receive an intravenous infusion of 10 mg/kg VRC01, 30 mg/kg VRC01, or a control preparation every 8 weeks for a total of 10 infusions. Each trial is designed (1) to assess overall prevention efficacy (PE) pooled over the two VRC01 dose groups vs. control and (2) to assess VRC01 dose and laboratory markers as correlates of protection (CoPs) against overall and genotype- and phenotype-specific infection. Each AMP trial is designed to have 90% power to detect PE > 0% if PE is ≥ 60%. The AMP trials are also designed to identify VRC01 properties (i.e., concentration and effector functions) that correlate with protection and to provide insight into mechanistic CoPs. CoPs are assessed using data from breakthrough HIV-1 infections, including genetic sequences and sensitivities to VRC01-mediated neutralization and Fc effector functions. The AMP trials test whether VRC01 can prevent HIV-1 infection in two study populations. If affirmative, they will provide information for estimating the optimal dosage of VRC01 (or subsequent derivatives) and identify threshold levels of neutralization and Fc effector functions associated with high-level protection, setting a benchmark for future vaccine evaluation and constituting a bridge to other bnAb approaches for HIV-1 prevention.

Management of Non-Diffuse Large B Cell Lymphoma Post-Transplant Lymphoproliferative Disorder.

PubMed

Major, Ajay; Kamdar, Manali

2018-05-24

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common neoplasms seen after solid organ and hematopoietic stem cell transplantation, and is associated with significant morbidity and mortality. The pathogenesis is related to post-transplant immunosuppression and EBV infection. Prevention of PTLD depends upon judicious use of immunosuppression and serial EBV monitoring. Preemptive therapy consists of reduction of immunosuppression, antiviral medications, and single-agent rituximab. There are no randomized phase III trials on PTLD treatment, so current management guidelines are largely based on recent phase II trials, single-institution retrospective studies, and expert opinion. Management of PTLD is dependent upon its subtypes. Early-type and polymorphic PTLD generally respond to reduction of immunosuppression and rituximab monotherapy, whereas monomorphic PTLD often requires additional concurrent or sequential use of chemotherapy. For rare subtypes of PTLD, standard-of-care guidelines for de novo lymphomas are recommended. Surgical resection or radiotherapy may be used as adjunctive therapy depending on the extent of disease. Non-chemotherapy options such as adoptive T cell therapy have shown promising efficacy and must be explored further. Despite progress in the last decade, overall survival rates continue to be low in published series. This review highlights the need for prospective randomized trials incorporating novel agents to improve outcomes in PTLD.

Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

PubMed Central

Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2017-01-01

Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

Effect of race/ethnicity on participation in HIV vaccine trials and comparison to other trials of biomedical prevention.

PubMed

Dhalla, Shayesta; Poole, Gary

2014-01-01

Racial/ethnic minorities are underrepresented in actual HIV vaccine trials in North America, and willingness to participate (WTP) and retention in an HIV vaccine trial may differ from that in Whites. In this review, the authors identified HIV vaccine preparedness studies (VPS) in North America in high-risk populations that examined the relationship between race/ethnicity and WTP in a preventive phase 3 HIV vaccine trial, and the relationship to retention. Studies were categorized by risk group, and comparison group (Whites vs. non-Whites). Other types of trials of biomedical prevention were also identified, and WTP and retention rates were compared and contrasted to actual HIV vaccine trials. In the studies identified, WTP in a hypothetical trial HIV vaccine trial did not differ by race/ethnicity. In contrast, actual HIV vaccine trials, an HIV acquisition trial, and a phase 2B preexposure prophylaxis (PrEP) trial have enrolled a large percentage of White men. Human papilloma virus (HPV) privately-funded trials have also enrolled a large number of Whites, due to convenience sampling. Retention in the HIV acquisition trial was lower in African-Americans compared with Whites. Strategies to increase WTP and enhanced retention (ER) strategies may help in recruiting and retaining minority participants in actual HIV vaccine trials and other trials of biomedical prevention.

Innovation in sexually transmitted disease and HIV prevention: internet and mobile phone delivery vehicles for global diffusion.

PubMed

Swendeman, Dallas; Rotheram-Borus, Mary Jane

2010-03-01

Efficacious behavioral interventions and practices have not been universally accepted, adopted, or diffused by policy makers, administrators, providers, advocates, or consumers. Biomedical innovations for sexually transmitted disease (STD) and HIV prevention have been embraced but their effectiveness is hindered by behavioral factors. Behavioral interventions are required to support providers and consumers for adoption and diffusion of biomedical innovations, protocol adherence, and sustained prevention for other STDs. Information and communication technology such as the Internet and mobile phones can deliver behavioral components for STD/HIV prevention and care to more people at less cost. Recent innovations in STD/HIV prevention with information and communication technology-mediated behavioral supports include STD/HIV testing and partner interventions, behavioral interventions, self-management, and provider care. Computer-based and Internet-based behavioral STD/HIV interventions have demonstrated efficacy comparable to face-to-face interventions. Mobile phone STD/HIV interventions using text-messaging are being broadly utilized but more work is needed to demonstrate efficacy. Electronic health records and care management systems can improve care, but interventions are needed to support adoption. Information and communication technology is rapidly diffusing globally. Over the next 5-10 years smart-phones will be broadly disseminated, connecting billions of people to the Internet and enabling lower cost, highly engaging, and ubiquitous STD/HIV prevention and treatment support interventions.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations

PubMed Central

Gewandter, Jennifer S.; Dworkin, Robert H.; Turk, Dennis C.; Farrar, John T.; Fillingim, Roger B.; Gilron, Ian; Markman, John D.; Oaklander, Anne Louise; Polydefkis, Michael J.; Raja, Srinivasa N.; Robinson, James P.; Woolf, Clifford J.; Ziegler, Dan; Ashburn, Michael A.; Burke, Laurie B.; Cowan, Penney; George, Steven Z.; Goli, Veeraindar; Graff, Ole X.; Iyengar, Smriti; Jay, Gary W.; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A.; Kopecky, Ernest A.; Malamut, Richard; McDermott, Michael P.; Palmer, Pamela; Rappaport, Bob A.; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A.

2018-01-01

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (i.e., chronic post-surgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (i.e., surgery, viral infection, injury, and toxic/noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials. PMID:25887465

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

PubMed

Gewandter, Jennifer S; Dworkin, Robert H; Turk, Dennis C; Farrar, John T; Fillingim, Roger B; Gilron, Ian; Markman, John D; Oaklander, Anne Louise; Polydefkis, Michael J; Raja, Srinivasa N; Robinson, James P; Woolf, Clifford J; Ziegler, Dan; Ashburn, Michael A; Burke, Laurie B; Cowan, Penney; George, Steven Z; Goli, Veeraindar; Graff, Ole X; Iyengar, Smriti; Jay, Gary W; Katz, Joel; Kehlet, Henrik; Kitt, Rachel A; Kopecky, Ernest A; Malamut, Richard; McDermott, Michael P; Palmer, Pamela; Rappaport, Bob A; Rauschkolb, Christine; Steigerwald, Ilona; Tobias, Jeffrey; Walco, Gary A

2015-07-01

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

Ethical considerations in HIV prevention and vaccine research in resource-limited settings.

PubMed

Garner, Samual A; Anude, Chuka J; Adams, Elizabeth; Dawson, Liza

2014-09-01

HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, new biomedical prevention methods and modalities being tested, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be feasible and affordable for at-risk populations. To discuss these challenges, a meeting, Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS on April 22-23, 2013. Several themes emerged from the meeting: (1) because of both trial design and ethical complexities, choosing prevention packages and designing combination prevention research trials will need to be evaluated on a case by case basis in different clinical trials, countries, and health systems; (2) multilevel stakeholder engagement from the beginning is vital to a fair and transparent process and also to designing ethical and relevant trials; (3) research should generally be responsive to a host country's needs, and sponsors and stakeholders should work together to address potential barriers to future access; and finally, (4) another meeting including a broader group of stakeholders is needed to address many of the outstanding ethical issues raised by this meeting. We offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings.

Whom to Target for Falls-Prevention Trials

PubMed Central

Coote, Susan; Sosnoff, Jacob J.

2014-01-01

Effective falls-prevention approaches for people with multiple sclerosis (MS) are needed. A significant challenge in studying falls-prevention programs for people with MS is deciding whom to include in trials. This article presents and discusses potential criteria for selecting participants for trials of falls-prevention interventions in MS. This narrative review reports on the inaugural meeting of the International MS Falls Prevention Research Network (IMSFPRN), which was held in March 2014 in Kingston, Ontario, Canada. Criteria considered were age, assistive device use, cognition, and fall history. The IMSFPRN reached consensus agreement to recommend that participants of all ages with varying levels of cognitive ability who are able to ambulate with or without assistance and who have a history of falling should be included in their future falls-prevention trials. PMID:25694780

Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial

DTIC Science & Technology

2016-03-01

AWARD NUMBER: W81XWH-11-2-0123 TITLE: Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial PRINCIPAL INVESTIGATOR: Dr...Caring Letters for Military Suicide Prevention: A Randomized 5a. CONTRACT NUMBER Controlled Trial 5b. GRANT NUMBER W81XWH-11-2-0123 5c. PROGRAM...determine if the intervention is effective in preventing suicide and suicidal behaviors among Service Members and Veterans. The “caring letters

Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial

DTIC Science & Technology

2017-03-01

AWARD NUMBER: W81XWH-11-2-0123 TITLE: Caring Letters for Military Suicide Prevention: A Randomized Controlled Trial PRINCIPAL INVESTIGATOR: Dr...Caring Letters for Military Suicide Prevention: A Randomized 5a. CONTRACT NUMBER Controlled Trial 5b. GRANT NUMBER W81XWH-11-2-0123 5c. PROGRAM...determine if the intervention is effective in preventing suicide and suicidal behaviors among Service Members and Veterans. The “caring letters” concept

Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

Cancer.gov

Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their

South African Research Ethics Committee Review of Standards of Prevention in HIV Vaccine Trial Protocols.

PubMed

Essack, Zaynab; Wassenaar, Douglas R

2018-04-01

HIV prevention trials provide a prevention package to participants to help prevent HIV acquisition. As new prevention methods are proven effective, this raises ethical and scientific design complexities regarding the prevention package or standard of prevention. Given its high HIV incidence and prevalence, South Africa has become a hub for HIV prevention research. For this reason, it is critical to study the implementation of relevant ethical-legal frameworks for such research in South Africa. This qualitative study used in-depth interviews to explore the practices and perspectives of eight members of South African research ethics committees (RECs) who have reviewed protocols for HIV vaccine trials. Their practices and perspectives are compared with ethics guideline requirements for standards of prevention.

Exploratory analysis of glyburide as a novel therapy for preventing brain swelling.

PubMed

Sheth, Kevin N; Kimberly, W Taylor; Elm, Jordan J; Kent, Thomas A; Yoo, Albert J; Thomalla, Götz; Campbell, Bruce; Donnan, Geoffrey A; Davis, Stephen M; Albers, Gregory W; Jacobson, Sven; del Zoppo, Gregory; Simard, J Marc; Stern, Barney J; Mandava, Pitchaiah

2014-08-01

Malignant infarction is characterized by the formation of cerebral edema, and medical treatment is limited. Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. We previously reported feasibility of the GAMES-Pilot study, a two-center prospective, open label, phase IIa trial of 10 subjects at high risk for malignant infarction based on diffusion weighted imaging (DWI) threshold of 82 cm(3) treated with RP-1127 (glyburide for injection). In this secondary analysis, we tested the hypothesis that RP-1127 may be efficacious in preventing poor outcome when compared to controls. Controls suffering large hemispheric infarction were obtained from the EPITHET and MMI-MRI studies. We first screened subjects for controls with the same DWI threshold used for enrollment into GAMES-Pilot, 82 cm(3). Next, to address imbalances, we applied a weighted Euclidean matching. Ninety day mRS 0-4, rate of decompressive craniectomy, and mortality were the primary clinical outcomes of interest. The mean age of the GAMES cohort was 51 years and initial DWI volume was 102 ± 23 cm(3). After Euclidean matching, GAMES subjects showed similar NIHSS, higher DWI volume, younger age and had mRS 0-4-90% versus 50% in controls p = 0.049; with a similar trend in mRS 0-3 (40 vs. 25%; p = 0.43) and trend toward lower mortality (10 vs. 35%; p = 0.21). In this pilot study, RP-1127-treated subjects showed better clinical outcomes when compared to historical controls. An adequately powered and randomized phase II trial of patients at risk for malignant infarction is needed to evaluate the potential efficacy of RP-1127.

Introduction to the Special Series: Current Directions for Measuring Parenting Constructs to Inform Prevention Science.

PubMed

Lindhiem, Oliver; Shaffer, Anne

2017-04-01

Parenting behaviors are multifaceted and dynamic and therefore challenging to quantify. Measurement methods have critical implications for study results, particularly for prevention trials designed to modify parenting behaviors. Although multiple approaches can complement one another and contribute to a more complete understanding of prevention trials, the assumptions and implications of each approach are not always clearly addressed. Greater attention to the measurement of complex constructs such as parenting is needed to advance the field of prevention science. This series examines the challenges of measuring changes in parenting behaviors in the context of prevention trials. All manuscripts in the special series address measurement issues and make practical recommendations for prevention researchers. Manuscripts in this special series include (1) empirical studies that demonstrate novel measurement approaches, (2) re-analyses of prevention trial outcome data directly comparing and contrasting two or more methods, and (3) a statistical primer and practical guide to analyzing proportion data.

Evolving early (pre-dementia) Alzheimer's disease trials: suit the outcomes to the population and study design.

PubMed

Doody, R S

2010-04-01

Assuming that some cases of Alzheimer's disease (AD) could be prevented or delayed, prevention trials will be developed for this neurodegenerative condition. Initially, stakeholders will have to agree about the definition of prevention-true primary prevention, meaning the prevention of AD neuropathological changes; the prevention of clinical signs and symptoms that often augur AD; or preventing the progression of signs and symptoms to full-blown dementia. True primary prevention trials will have to rely completely upon neuroimaging or biomarker outcomes that reflect AD pathology. On the other hand, trials designed to prevent signs and symptoms of dementia will require researchers to agree on the phenomenology that would constitute an unequivocal endpoint: cognitive worsening on one or more measure compared to a normative group; development of Mild cognitive impairment (MCI); or development of Alzheimer's dementia. Prevention trials utilizing any of these outcomes in the general public will be large, will have to utilize low risk public health interventions, and might therefore have only a small impact (treatment effect size), especially if the studies are too short or the study populations are too diverse. An alternative to interventions aimed at the general public would be any attempt to prevent signs and symptoms of dementia in individuals thought to be at an increased risk for clinical dementia. These trials could try to reduce the development of signs and symptoms of dementia in cognitively normal subjects, or they could try to prevent progression from some form of Mild Cognitive Impairment to AD, or they could have the more subtle goal of reducing the accumulation of subclinical deficits in MCI subjects. If the populations for these trials are limited to individuals who have abnormal laboratory and neuroimaging studies associated with AD neuropathology, the results will not generalize to biomarker-negative, at risk individuals, who are likely to constitute the majority of any clinically relevant study population. Outcome measures for each study design will depend upon the characteristics of the study.

Does a fall prevention educational programme improve knowledge and change exercise prescribing behaviour in health and exercise professionals? A study protocol for a randomised controlled trial.

PubMed

Tiedemann, A; Sturnieks, D L; Hill, A-M; Lovitt, L; Clemson, L; Lord, S R; Harvey, L; Sherrington, C

2014-11-19

Falling in older age is a serious and costly problem. At least one in three older people fall annually. Although exercise is recognised as an effective fall prevention intervention, low numbers of older people engage in suitable programmes. Health and exercise professionals play a crucial role in addressing fall risk in older adults. This trial aims to evaluate the effect of participation in a fall prevention educational programme, compared with a wait-list control group, on health and exercise professionals' knowledge about fall prevention and the effect on fall prevention exercise prescription behaviour and confidence to prescribe the exercises to older people. A randomised controlled trial involving 220 consenting health and exercise professionals will be conducted. Participants will be individually randomised to an intervention group (n=110) to receive an educational workshop plus access to internet-based support resources, or a wait-list control group (n=110). The two primary outcomes, measured 3 months after randomisation, are: (1) knowledge about fall prevention and (2) self-perceived change in fall prevention exercise prescription behaviour. Secondary outcomes include: (1) participants' confidence to prescribe fall prevention exercises; (2) the proportion of people aged 60+ years seen by trial participants in the past month who were prescribed fall prevention exercise; and (3) the proportion of fall prevention exercises prescribed by participants to older people in the past month that comply with evidence-based guidelines. Outcomes will be measured with a self-report questionnaire designed specifically for the trial. The trial protocol was approved by the Human Research Ethics Committee, The University of Sydney, Australia. Trial results will be disseminated via peer reviewed journals, presentations at international conferences and participants' newsletters. Trial protocol was registered with the Australian and New Zealand Clinical Trials Registry (Number ACTRN12614000224628) on 3 March 2014. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effectiveness of complex psycho-educational interventions for smoking relapse prevention: an exploratory meta-analysis.

PubMed

Song, Fujian; Huttunen-Lenz, Maija; Holland, Richard

2010-09-01

Existing systematic reviews have concluded that psycho-educational interventions for smoking relapse prevention were ineffective. Our objective was to conduct an exploratory meta-analysis, guided by mechanisms of these complex interventions for preventing smoking relapse. Relevant trials were identified from a Cochrane review and by an updated search of MEDLINE and PsycINFO (up to August 2009). We examined theories or mechanisms underlying relapse prevention interventions, and process variables reported in trials. Odds ratios (ORs) for the rate of smoking abstinence at the longest follow-up were pooled in meta-analysis. Forty-nine trials were included, and interventions were at least partly based on the cognitive-behavioural approach to coping skills training in 41 trials. Only a few trials reported data on process variables. Coping skills training for smoking relapse prevention was effective for community quitters (OR 1.27, 95% CI: 1.08-1.49), and particularly for those who stopped smoking for at least 1 week at baseline (OR 1.52, 95% CI: 1.20-1.93). These findings were interpretable with mechanisms of coping skills training for relapse prevention. On the basis of post hoc subgroup analyses, coping skills training for smoking relapse prevention is effective for motivated community quitters. This finding has important public health implications and needs to be confirmed by further trials.

Probiotics for the Primary and Secondary Prevention of C. difficile Infections: A Meta-analysis and Systematic Review

PubMed Central

McFarland, Lynne V.

2015-01-01

Clostridium difficile infections are a global clinical concern and are one of the leading causes of nosocomial outbreaks. Preventing these infections has benefited from multidisciplinary infection control strategies and new antibiotics, but the problem persists. Probiotics are effective in preventing antibiotic-associated diarrhea and may also be a beneficial strategy for C. difficile infections, but randomized controlled trials are scarce. This meta-analysis pools 21 randomized, controlled trials for primary prevention of C. difficile infections (CDI) and four trials for secondary prevention of C. difficile recurrences and assesses the efficacy of specific probiotic strains. Four probiotics significantly improved primary CDI prevention: (Saccharomyces boulardii, Lactobacillus casei DN114001, a mixture of L. acidophilus and Bifidobacterium bifidum, and a mixture of L. acidophilus, L. casei and L. rhamnosus). None of the tested probiotics significantly improved secondary prevention of CDI. More confirmatory randomized trials are needed to establish if probiotics are useful for preventing C. difficile infections. PMID:27025619

A randomized, placebo-controlled trial of patient education for acute low back pain (PREVENT Trial): statistical analysis plan.

PubMed

Traeger, Adrian C; Skinner, Ian W; Hübscher, Markus; Lee, Hopin; Moseley, G Lorimer; Nicholas, Michael K; Henschke, Nicholas; Refshauge, Kathryn M; Blyth, Fiona M; Main, Chris J; Hush, Julia M; Pearce, Garry; Lo, Serigne; McAuley, James H

Statistical analysis plans increase the transparency of decisions made in the analysis of clinical trial results. The purpose of this paper is to detail the planned analyses for the PREVENT trial, a randomized, placebo-controlled trial of patient education for acute low back pain. We report the pre-specified principles, methods, and procedures to be adhered to in the main analysis of the PREVENT trial data. The primary outcome analysis will be based on Mixed Models for Repeated Measures (MMRM), which can test treatment effects at specific time points, and the assumptions of this analysis are outlined. We also outline the treatment of secondary outcomes and planned sensitivity analyses. We provide decisions regarding the treatment of missing data, handling of descriptive and process measure data, and blinded review procedures. Making public the pre-specified statistical analysis plan for the PREVENT trial minimizes the potential for bias in the analysis of trial data, and in the interpretation and reporting of trial results. ACTRN12612001180808 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612001180808). Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Learning From Past Failures of Oral Insulin Trials.

PubMed

Michels, Aaron W; Gottlieb, Peter A

2018-07-01

Very recently one of the largest type 1 diabetes prevention trials using daily administration of oral insulin or placebo was completed. After 9 years of study enrollment and follow-up, the randomized controlled trial failed to delay the onset of clinical type 1 diabetes, which was the primary end point. The unfortunate outcome follows the previous large-scale trial, the Diabetes Prevention Trial-Type 1 (DPT-1), which again failed to delay diabetes onset with oral insulin or low-dose subcutaneous insulin injections in a randomized controlled trial with relatives at risk for type 1 diabetes. These sobering results raise the important question, "Where does the type 1 diabetes prevention field move next?" In this Perspective, we advocate for a paradigm shift in which smaller mechanistic trials are conducted to define immune mechanisms and potentially identify treatment responders. The stage is set for these interventions in individuals at risk for type 1 diabetes as Type 1 Diabetes TrialNet has identified thousands of relatives with islet autoantibodies and general population screening for type 1 diabetes risk is under way. Mechanistic trials will allow for better trial design and patient selection based upon molecular markers prior to large randomized controlled trials, moving toward a personalized medicine approach for the prevention of type 1 diabetes. © 2018 by the American Diabetes Association.

Civil society perspectives on negative biomedical HIV prevention trial results and implications for future trials.

PubMed

Essack, Zaynab; Koen, Jennifer; Slack, Catherine; Lindegger, Graham; Newman, Peter A

2012-01-01

Community engagement is crucial to ongoing development and testing of sorely needed new biomedical HIV prevention technologies. Yet, negative trial results raise significant challenges for community engagement in HIV prevention trials, including the early termination of the Cellulose Sulfate microbicide trial and two Phase IIb HIV vaccine trials (STEP and Phambili). The present study aimed to explore the perspectives and experiences of civil society organization (CSO) representatives regarding negative HIV prevention trial results and perceived implications for future trials. We conducted in-depth interviews with 14 respondents from a broad range of South African and international CSOs, and analyzed data using thematic analysis. CSO representatives reported disappointment in response to negative trial results, but acknowledged such outcomes as inherent to clinical research. Respondents indicated that in theory negative trial results seem likely to impact on willingness to participate in future trials, but that in practice people in South Africa have continued to volunteer. Negative trial results were described as having contributed to improving ethical standards, and to a re-evaluation of the scientific agenda. Such negative results were identified as potentially impacting on funding for trials and engagement activities. Our findings indicate that trial closures may be used constructively to support opportunities for reflection and renewed vigilance in strategies for stakeholder engagement, communicating trial outcomes, and building research literacy among communities; however, these strategies require sustained resources for community engagement and capacity-building.

Process evaluation in a multisite, primary obesity-prevention trial in American Indian schoolchildren.

PubMed

Helitzer, D L; Davis, S M; Gittelsohn, J; Going, S B; Murray, D M; Snyder, P; Steckler, A B

1999-04-01

We describe the development, implementation, and use of the process evaluation component of a multisite, primary obesity prevention trial for American Indian schoolchildren. We describe the development and pilot testing of the instruments, provide some examples of the criteria for instrument selection, and provide examples of how process evaluation results were used to document and refine intervention components. The theoretical and applied framework of the process evaluation was based on diffusion theory, social learning theory, and the desire for triangulation of multiple modes of data collection. The primary objectives of the process evaluation were to systematically document the training process, content, and implementation of 4 components of the intervention. The process evaluation was developed and implemented collaboratively so that it met the needs of both the evaluators and those who would be implementing the intervention components. Process evaluation results revealed that observation and structured interviews provided the most informative data; however, these methods were the most expensive and time consuming and required the highest level of skill to undertake. Although the literature is full of idealism regarding the uses of process evaluation for formative and summative purposes, in reality, many persons are sensitive to having their work evaluated in such an in-depth, context-based manner as is described. For this reason, use of structured, quantitative, highly objective tools may be more effective than qualitative methods, which appear to be more dependent on the skills and biases of the researcher and the context in which they are used.

Co-enrollment in multiple HIV prevention trials - experiences from the CAPRISA 004 Tenofovir gel trial.

PubMed

Karim, Quarraisha Abdool; Kharsany, Ayesha B M; Naidoo, Kasavan; Yende, Nonhlanhla; Gengiah, Tanuja; Omar, Zaheen; Arulappan, Natasha; Mlisana, Koleka P; Luthuli, Londiwe R; Karim, Salim S Abdool

2011-05-01

In settings where multiple HIV prevention trials are conducted in close proximity, trial participants may attempt to enroll in more than one trial simultaneously. Co-enrollment impacts on participant's safety and validity of trial results. We describe our experience, remedial action taken, inter-organizational collaboration and lessons learnt following the identification of co-enrolled participants. Between February and April 2008, we identified 185 of the 398 enrolled participants as ineligible. In violation of the study protocol exclusion criteria, there was simultaneous enrollment in another HIV prevention trial (ineligible co-enrolled, n=135), and enrollment of women who had participated in a microbicide trial within the past 12 months (ineligible not co-enrolled, n=50). Following a complete audit of all enrolled participants, ineligible participants were discontinued via study exit visits from trial follow-up. Custom-designed education program on co-enrollment impacting on participants' safety and validity of the trial results was implemented. Shared electronic database between research units was established to enable verification of each volunteer's trial participation and to prevent future co-enrollments. Interviews with ineligible enrolled women revealed that high-quality care, financial incentives, altruistic motives, preference for sex with gel, wanting to increase their likelihood of receiving active gel, perceived low risk of discovery and peer pressure are the reasons for their enrollment in the CAPRISA 004 trial. Instituting education programs based on the reasons reported by women for seeking enrollment in more than one trial and using a shared central database system to identify co-enrollments have effectively prevented further co-enrollments. Copyright © 2011 Elsevier Inc. All rights reserved.

Evaluation of an HIV prevention intervention for African Americans and Hispanics: findings from the VOICES/VOCES Community-based Organization Behavioral Outcomes Project.

PubMed

Fisher, Holly H; Patel-Larson, A; Green, K; Shapatava, E; Uhl, G; Kalayil, E J; Moore, A; Williams, W; Chen, B

2011-11-01

There is limited knowledge about whether the delivery of evidence-based, HIV prevention interventions in 'real world' settings will produce outcomes similar to efficacy trial outcomes. In this study, we describe longitudinal changes in sexual risk outcomes among African American and Hispanic participants in the Video Opportunities for Innovative Condom Education and Safer Sex (VOICES/VOCES) program at four CDC-funded agencies. VOICES/VOCES was delivered to 922 high-risk individuals in a variety of community settings such as substance abuse treatment centers, housing complex centers, private residences, shelters, clinics, and colleges. Significant risk reductions were consistently observed at 30- and 120-days post-intervention for all outcome measures (e.g., unprotected sex, self-reported STD infection). Risk reductions were strongest for African American participants, although Hispanic participants also reported reducing their risky behaviors. These results suggest that, over a decade after the first diffusion of VOICES/VOCES across the U.S. by CDC, this intervention remains an effective tool for reducing HIV risk behaviors among high-risk African American and Hispanic individuals.

Water vapor diffusion membranes

NASA Technical Reports Server (NTRS)

Holland, F. F., Jr.; Smith, J. K.

1974-01-01

The program is reported, which was designed to define the membrane technology of the vapor diffusion water recovery process and to test this technology using commercially available or experimental membranes. One membrane was selected, on the basis of the defined technology, and was subjected to a 30-day demonstration trial.

Determinants of Dropout and Nonadherence in a Dementia Prevention Randomized Controlled Trial: The Prevention of Dementia by Intensive Vascular Care Trial.

PubMed

Beishuizen, Cathrien R L; Coley, Nicola; Moll van Charante, Eric P; van Gool, Willem A; Richard, Edo; Andrieu, Sandrine

2017-07-01

To explore and compare sociodemographic, clinical, and neuropsychiatric determinants of dropout and nonadherence in older people participating in an open-label cluster-randomized controlled trial-the Prevention of Dementia by Intensive Vascular care (preDIVA) trial-over 6 years. Secondary analysis. One hundred sixteen general practices in the Netherlands. Community-dwelling individuals aged 70 to 78 (N = 2,994). Nurse-led multidomain intervention targeting cardiovascular risk factors to prevent dementia. The associations between participant baseline sociodemographic (age, sex, education), clinical (medical history, disability, cardiovascular risk), neuropsychiatric (depressive symptoms (Geriatric Depression Scale-15), and cognitive (Mini-Mental State Examination)) characteristics and dropout from the trial and nonadherence to the trial intervention were explored using multilevel logistic regression models. Older age, poorer cognitive function, more symptoms of depression, and greater disability were the most important determinants of dropout of older people. The presence of cardiovascular risk factors was not associated with dropout but was associated with nonadherence. Being overweight was a risk factor for nonadherence, whereas people with high blood pressure or a low level of physical exercise adhered better to the intervention. The association between poorer cognitive function and symptoms of depression and dropout was stronger in the control group than in the intervention group, and vice versa for increased disability. In a large dementia prevention trial with 6-year follow-up, dropout was associated with older age, poorer cognitive function, symptoms of depression, and disability at baseline. These findings can help to guide the design of future dementia prevention trials in older adults. The associations found between cardiovascular risk factors and nonadherence need to be confirmed in other older populations receiving cardiovascular prevention interventions. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Sodium Bicarbonate for the Prevention of Contrast Induced-Acute Kidney Injury: A Systematic Review and Meta-analysis

PubMed Central

Hiremath, Swapnil; Dangas, George; Mehran, Roxana; Brar, Simerjeet K.; Leon, Martin B.

2009-01-01

Background and objectives: Infusion of sodium bicarbonate has been suggested as a preventative strategy but reports are conflicting on its efficacy. The aim of this study was to assess the effectiveness of hydration with sodium bicarbonate for the prevention of contrast-induced acute kidney injury (CI-AKI). Design, setting, participants, & measurements: Medline, EMBASE, Cochrane library, and the Internet were searched for randomized controlled trials comparing hydration between sodium bicarbonate and chloride for the prevention of CI-AKI between 1966 and November 2008. Fourteen trials that included 2290 patients were identified. There was significant heterogeneity between studies (P heterogeneity = 0.02; I2 = 47.8%), which was largely accounted for by trial size (P = 0.016). Trials were therefore classified by size. Results: Three trials were categorized as large (n = 1145) and 12 as small (n = 1145). Among the large trials, the incidence of CI-AKI for sodium bicarbonate and sodium chloride was 10.7 and 12.5%, respectively; the relative risk (RR) [95% confidence interval (CI)] was 0.85 (0.63 to 1.16) without evidence of heterogeneity (P = 0.89, I2 = 0%). The pooled RR (95% CI) among the 12 small trials was 0.50 (0.27 to 0.93) with significant between-trial heterogeneity (P = 0.01; I2 = 56%). The small trials were more likely to be of lower methodological quality. Conclusions: A significant clinical and statistical heterogeneity was observed that was largely explained by trial size and published status. Among the large randomized trials there was no evidence of benefit for hydration with sodium bicarbonate compared with sodium chloride for the prevention of CI-AKI. The benefit of sodium bicarbonate was limited to small trials of lower methodological quality. PMID:19713291

Defibrillator implantations for primary prevention in the United States: Inappropriate care or inadequate documentation: Insights from the National Cardiovascular Data ICD Registry.

PubMed

Kaiser, Daniel W; Tsai, Vivian; Heidenreich, Paul A; Goldstein, Mary K; Wang, Yongfei; Curtis, Jeptha; Turakhia, Mintu P

2015-10-01

Prior studies have reported that more than 20% of implantable cardioverter-defibrillator (ICD) implantations in the United States do not adhere to trial-based criteria. We sought to investigate the patient characteristics associated with not meeting the inclusion criteria of the clinical trials that have demonstrated the efficacy of primary prevention ICDs. Using data from the National Cardiovascular Data Registry's ICD Registry, we identified patients who received ICDs for primary prevention from January 2006 to December 2008. We determined whether patients met the inclusion criteria of at least 1 of the 4 ICD primary prevention trials: Multicenter Automatic Defibrillator Implantation Trial (MADIT), MADIT-II, Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), and the Multicenter Unsustained Tachycardia Trial (MUSTT). Among 150,264 patients, 86% met criteria for an ICD implantation based on trial data. The proportion of patients who did not meet trial-based criteria increased as age decreased. In multivariate analysis, the significant predictors for not meeting trial criteria included prior cardiac transplantation (odds ratio [OR] 2.1), pediatric electrophysiology operator (OR 2.0), and high-grade atrioventricular conduction disease (OR 1.4). Among National Cardiovascular Data Registry registrants receiving first-time ICDs for primary prevention, the majority met trial-based criteria. Multivariate analyses suggested that many patients who did not meet the trial-based criteria may have had clinical circumstances that warranted ICD implantation. These findings caution against the use of trial-based indications to determine site quality metrics that could penalize sites that care for younger patients. The planned incorporation of appropriate use criteria into the ICD registry may better characterize patient- and site-level quality and performance. Published by Elsevier Inc.

Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short?

PubMed Central

Lakey, Wanda C.; Batch, Bryan C.; Chiswell, Karen; Tasneem, Asba; Green, Jennifer B.

2016-01-01

The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention. PMID:27191848

Methodology of clinical trials evaluating the incorporation of new drugs in the first-line treatment of patients with diffuse large B-cell lymphoma (DLBCL): a critical review.

PubMed

Iacoboni, G; Zucca, E; Ghielmini, M; Stathis, A

2018-05-01

The first-line treatment of diffuse large B-cell lymphoma (DLBCL) is the combination of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, curing approximately 60% of patients. Many clinical trials have been carried out over the last 10 years trying to improve the results of this treatment, but the appropriateness of their planning strategies could be rediscussed. Reports of phase III trials evaluating the addition of molecularly targeted agents or new monoclonal antibodies to the classic R-CHOP backbone in first-line induction or maintenance treatment were reviewed. The trial design, primary end point, number of patients enrolled, patient selection criteria, treatment schedule and results were registered for each one. In addition, the phases I and II trials which preceded these phase III trials were also reviewed. Among six phase III trials with results, only one trial evaluating lenalidomide maintenance after response to R-CHOP induction was positive and reached its primary end point. The other five trials did not show an improved outcome with the addition of the new agent. The preceding phases I and II trials were very heterogeneous in their end points and design. Even though most of these trials were considered positive, thus encouraging further investigation, so far they failed to predict the results of the subsequent phase III trials. The standard of care for DLBCL is still R-CHOP. Phase I/II trials failed to predict the results of subsequent phase III trials evaluating non-chemotherapeutic agents added to R-CHOP. The methodology of phase II trials evaluating new agents in DLBCL needs to be better defined in the future.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

School-Based Violence Prevention Programs: Systematic Review of Secondary Prevention Trials.

ERIC Educational Resources Information Center

Mytton, Julie A.; DiGuiseppi, Carolyn; Gough, David A.; Taylor, Rod S.; Logan, Stuart

2002-01-01

Conducted a systematic review and meta-analysis of randomized controlled secondary prevention trials to explore the effects of school-based violence prevention programs on aggressive and violent behavior in children at high risk for violence. Results indicated that such programs produced modest reductions in aggressive and violent behaviors in…

The Integration of Biology Into the Treatment of Diffuse Intrinsic Pontine Glioma: A Review of the North American Clinical Trial Perspective.

PubMed

Clymer, Jessica; Kieran, Mark W

2018-01-01

Dramatic advances in the molecular analysis of diffuse intrinsic pontine glioma have occurred over the last decade and resulted in the identification of potential therapeutic targets. In spite of these advances, no significant improvement in the outcome has been achieved and median survival remains approximately 10 months. An understanding of the approaches that have been taken to date, why they failed, and how that information can lead the field forward is critical if we are to change the status quo . In this review, we will discuss the clinical trial landscape in North America with an overview of historical approaches that failed and what might account for this failure. We will then provide a discussion of how our understanding of the genotype of this disease has led to the development of a number of trials targeting the mutations and epigenome of diffuse intrinsic pontine gliomas and the issues related to these trials. Similarly, the introduction of methodologies to address penetration across the blood-brain barrier will be considered in the context of both targeted approaches, epigenetic modification, and immune surveillance of these tumors. The comprehensive analysis of these data, generated through cooperative groups, collaborative clinical trials, and pilot studies in North America will be the focus of the IVth Memorial Alicia Pueyo international symposium in Barcelona on March 12th, 2018 and will be compared and contrasted with a similar comprehensive analysis of the European data with the goal of bringing all of these data together to develop a uniform platform on which new rational trials can be based.

Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials.

PubMed

Warach, Steven; Al-Rawi, Yasir; Furlan, Anthony J; Fiebach, Jochen B; Wintermark, Max; Lindstén, Annika; Smyej, Jamal; Bharucha, David B; Pedraza, Salvador; Rowley, Howard A

2012-09-01

The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.

Efficacy of physical exercise in preventing falls in older adults with cognitive impairment: a systematic review and meta-analysis.

PubMed

Chan, Wai Chi; Yeung, Jerry Wing Fai; Wong, Corine Sau Man; Lam, Linda Chiu Wa; Chung, Ka Fai; Luk, James Ka Hay; Lee, Jenny Shun Wah; Law, Andrew Chi Kin

2015-02-01

Numerous studies have reported the prevention of falls through exercise among cognitively healthy older people. This study aimed to determine whether the current evidence supports that physical exercise is also efficacious in preventing falls in older adults with cognitive impairment. Two independent reviewers searched MEDLINE; EMBASE; PsycINFO; the Cumulative Index to Nursing & Allied Health Literature; the Cochrane Central Register of Controlled Trials; the Cochrane Bone, Joint, and Muscle Trauma Group Specialized Register; ClinicalTrials.gov; and the UK Clinical Research Network Study Portfolio up to July 2013 without language restriction. We included randomized controlled trials that examined the efficacy of physical exercise in older adults with cognitive impairment. The methodological qualities of the included trials were appraised according to the criteria developed for the Cochrane review of fall prevention trials. The primary outcome measure was the rate ratio of falls. A meta-analysis was performed to estimate the pooled rate ratio and summarize the results of the trials on fall prevention through physical exercise. Seven randomized controlled trials involving 781 participants were included, 4 of which examined solely older people with cognitive impairment. Subgroup data on persons with cognitive impairment were obtained from the other 3 trials that targeted older populations in general. The meta-analysis showed that physical exercise had a significant effect in preventing falls in older adults with cognitive impairment, with a pooled estimate of rate ratio of 0.68 (95% confidence interval 0.51-0.91). The present analysis suggests that physical exercise has a positive effect on preventing falls in older adults with cognitive impairment. Further studies will be required to determine the modality and frequency of exercise that are optimal for the prevention of falls in this population. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Reverse flexing as a physical/mechanical treatment to mitigate fouling of fine bubble diffusers.

PubMed

Odize, Victory O; Novak, John; De Clippeleir, Haydee; Al-Omari, Ahmed; Smeraldi, Joshua D; Murthy, Sudhir; Rosso, Diego

2017-10-01

Achieving energy neutrality has shifted focus towards aeration system optimization, due to the high energy consumption of aeration processes in modern advanced wastewater treatment plants. A study on fine bubble diffuser fouling and mitigation, quantified by dynamic wet pressure (DWP), oxygen transfer efficiency and alpha was carried out in Blue Plains, Washington, DC. Four polyurethane fine bubble diffusers were installed in a pilot reactor column fed with high rate activated sludge from a full scale system. A mechanical cleaning method, reverse flexing (RF), was used to treat two diffusers (RF1, RF2), while two diffusers were kept as a control (i.e., no reverse flexing). There was a 45% increase in DWP of the control diffuser after 17 months of operation, an indication of fouling. RF treated diffusers (RF1 and RF2) did not show significant increase in DWP, and in comparison to the control diffuser prevented about 35% increase in DWP. Hence, reverse flexing potentially saves blower energy, by reducing the pressure burden on the air blower which increases blower energy requirement. However, no significant impact of the RF treatment in preventing a decrease in alpha-fouling (αF) of the fine pore diffusers, over time in operation was observed.

Transdermal granisetron.

PubMed

Duggan, Sean T; Curran, Monique P

2009-01-01

Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

Multi-site study of diffusion metric variability: effects of site, vendor, field strength, and echo time on regions-of-interest and histogram-bin analyses.

PubMed

Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

2016-02-27

It is now common for magnetic-resonance-imaging (MRI) based multi-site trials to include diffusion-weighted imaging (DWI) as part of the protocol. It is also common for these sites to possess MR scanners of different manufacturers, different software and hardware, and different software licenses. These differences mean that scanners may not be able to acquire data with the same number of gradient amplitude values and number of available gradient directions. Variability can also occur in achievable b-values and minimum echo times. The challenge of a multi-site study then, is to create a common protocol by understanding and then minimizing the effects of scanner variability and identifying reliable and accurate diffusion metrics. This study describes the effect of site, scanner vendor, field strength, and TE on two diffusion metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA) using two common analyses (region-of-interest and mean-bin value of whole brain histograms). The goal of the study was to identify sources of variability in diffusion-sensitized imaging and their influence on commonly reported metrics. The results demonstrate that the site, vendor, field strength, and echo time all contribute to variability in FA and MD, though to different extent. We conclude that characterization of the variability of DTI metrics due to site, vendor, field strength, and echo time is a worthwhile step in the construction of multi-center trials.

Stakeholder views of ethical guidance regarding prevention and care in HIV vaccine trials.

PubMed

Moorhouse, Rika; Slack, Catherine; Quayle, Michael; Essack, Zaynab; Lindegger, Graham

2014-06-30

South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders' perspectives on ethical guidance related to prevention and care in HIV vaccine trials. Site staff, Community Advisory Board members and Research Ethics Committee members involved with current HIV vaccine trials in South Africa were invited to participate in an exploration of their views. A questionnaire listed 10 care and 10 prevention recommendations drawn from two widely available sets of ethical guidelines for biomedical HIV prevention trials. Respondents (n = 98) rated each recommendation on five dimensions: "Familiarity with", "Ease of Understanding", "Ease of Implementing", "Perceived Protection", and "Agreement with" each ethical recommendation. The ratings were used to describe stakeholder perspectives on dimensions for each recommendation. Dimension ratings were averaged across the five dimensions and used as an indication of overall merit for each recommendation. Differences were explored across dimensions, between care-oriented and prevention-oriented recommendations, and between stakeholder groups. Both care and prevention recommendations were rated highly overall, with median ratings well above the scale midpoint. In general, informed consent recommendations were most positively rated. Care-related recommendations were rated significantly more positively than prevention-related recommendations, with the five lowest-rated recommendations being prevention-related. The most problematic dimension across all recommendations was "Ease of Implementing," and the least problematic was "Agreement with," suggesting the most pressing stakeholder concerns are practical rather than theoretical; that is, respondents agree with but see barriers to the attainment of these recommendations. We propose that prevention recommendations be prioritized for refinement, especially those assigned bottom-ranking scores for "Ease of Implementing", and/ or "Ease of Understanding" in order to assist vaccine stakeholders to better comprehend and implement these recommendations. Further qualitative research could also assist to better understand nuances in stakeholder reservations about implementing such recommendations.

Stakeholder views of ethical guidance regarding prevention and care in HIV vaccine trials

PubMed Central

2014-01-01

Background South Africa is a major hub of HIV prevention trials, with plans for a licensure trial to start in 2015. The appropriate standards of care and of prevention in HIV vaccine trials are complex and debated issues and ethical guidelines offer some direction. However, there has been limited empirical exploration of South African stakeholders’ perspectives on ethical guidance related to prevention and care in HIV vaccine trials. Methods Site staff, Community Advisory Board members and Research Ethics Committee members involved with current HIV vaccine trials in South Africa were invited to participate in an exploration of their views. A questionnaire listed 10 care and 10 prevention recommendations drawn from two widely available sets of ethical guidelines for biomedical HIV prevention trials. Respondents (n = 98) rated each recommendation on five dimensions: “Familiarity with”, “Ease of Understanding”, “Ease of Implementing”, “Perceived Protection”, and “Agreement with” each ethical recommendation. The ratings were used to describe stakeholder perspectives on dimensions for each recommendation. Dimension ratings were averaged across the five dimensions and used as an indication of overall merit for each recommendation. Differences were explored across dimensions, between care-oriented and prevention-oriented recommendations, and between stakeholder groups. Results Both care and prevention recommendations were rated highly overall, with median ratings well above the scale midpoint. In general, informed consent recommendations were most positively rated. Care-related recommendations were rated significantly more positively than prevention-related recommendations, with the five lowest-rated recommendations being prevention-related. The most problematic dimension across all recommendations was “Ease of Implementing,” and the least problematic was “Agreement with,” suggesting the most pressing stakeholder concerns are practical rather than theoretical; that is, respondents agree with but see barriers to the attainment of these recommendations. Conclusions We propose that prevention recommendations be prioritized for refinement, especially those assigned bottom-ranking scores for “Ease of Implementing”, and/ or “Ease of Understanding” in order to assist vaccine stakeholders to better comprehend and implement these recommendations. Further qualitative research could also assist to better understand nuances in stakeholder reservations about implementing such recommendations. PMID:24981027

Effectiveness and implementation of an obesity prevention intervention: the HeLP-her Rural cluster randomised controlled trial.

PubMed

Lombard, Catherine B; Harrison, Cheryce L; Kozica, Samantha L; Zoungas, Sophia; Keating, Catherine; Teede, Helena J

2014-06-16

To impact on the obesity epidemic, interventions that prevent weight gain across populations are urgently needed. However, even the most efficacious interventions will have little impact on obesity prevention unless they are successfully implemented in diverse populations and settings. Implementation research takes isolated efficacy studies into practice and policy and is particularly important in obesity prevention where there is an urgent need to accelerate the evidence to practice cycle. Despite the recognised need, few obesity prevention interventions have been implemented in real life settings and to our knowledge rarely target rural communities. Here we describe the rationale, design and implementation of a Healthy Lifestyle Program for women living in small rural communities (HeLP-her Rural). The primary goal of HeLP-her Rural is to prevent weight gain using a low intensity, self-management intervention. Six hundred women from 42 small rural communities in Australia will be randomised as clusters (n-21 control towns and n = 21 intervention towns). A pragmatic randomised controlled trial methodology will test efficacy and a comprehensive mixed methods community evaluation and cost analysis will inform effectiveness and implementation of this novel prevention program. Implementing population interventions to prevent obesity is complex, costly and challenging. To address these barriers, evidence based interventions need to move beyond isolated efficacy trials and report outcomes related to effectiveness and implementation. Large pragmatic trials provide an opportunity to inform both effectiveness and implementation leading to potential for greater impact at the population level. Pragmatic trials should incorporate both effectiveness and implementation outcomes and a multidimensional methodology to inform scale-up to population level. The learnings from this trial will impact on the design and implementation of population obesity prevention strategies nationally and internationally. ANZ clinical trial registry ACTRN12612000115831. Date of registration 24/01/2012.

Types of Cancer Clinical Trials

Cancer.gov

Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

Participation and diffusion effects of a peer-intervention for HIV prevention among adults in rural Malawi.

PubMed

Crittenden, Kathleen S; Kaponda, Chrissie P N; Jere, Diana L; McCreary, Linda L; Norr, Kathleen F

2015-05-01

This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n = 415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more cost-effective than previously realized. Wider implementation of peer group interventions can help meet the global goal of reducing new HIV infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

Participation and Diffusion Effects of a Peer-Intervention for HIV Prevention among Adults in Rural Malawi

PubMed Central

Crittenden, Kathleen S.; Kaponda, Chrissie P. N.; Jere, Diana L.; McCreary, Linda L.; Norr, Kathleen F.

2015-01-01

This paper examines whether a peer group intervention that reduced self-reported risky behaviors for rural adults in Malawi also had impacts on non-participants in the same communities. We randomly assigned two districts to the intervention and control conditions, and conducted surveys at baseline and 18 months post-intervention using unmatched independent random samples of intervention and control communities in 2003-2006. The six-session peer group intervention was offered to same-gender groups by trained volunteers. In this analysis, we divided the post-intervention sample into three exposure groups: 243 participants and 170 non-participants from the intervention district (total n=415) and 413 control individuals. Controlling for demographics and participation, there were significant favorable diffusion effects on five partially overlapping behavioral outcomes: partner communication, ever used condoms, unprotected sex, recent HIV test, and a community HIV prevention index. Non-participants in the intervention district had more favorable outcomes on these behaviors than survey respondents in the control district. One behavioral outcome, community HIV prevention, showed both participation and diffusion effects. Participating in the intervention had a significant effect on six psychosocial outcomes: HIV knowledge (two measures), hope, condom attitudes, and self-efficacy for community HIV prevention and for safer sex; there were no diffusion effects. This pattern of results suggests that the behavioral changes promoted in the intervention spread to others in the same community, most likely through direct contact between participants and non-participants. These findings support the idea that diffusion of HIV-related behavior changes can occur for peer group interventions in communities, adding to the body of research supporting diffusion of innovations theory as a robust approach to accelerating change. If diffusion occurs, peer group intervention may be more cost-effective than previously realized. Wider implementation of peer group interventions can help meet the global goal of reducing new HIV infections. PMID:25864150

Rosuvastatin and the JUPITER trial: critical appraisal of a lifeless planet in the galaxy of primary prevention.

PubMed

López, Antonio; Wright, James M

2012-01-01

In November 2008, the JUPITER trial was published in the New England Journal of Medicine. JUPITER is an acronym for Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin. It was an AstraZeneca sponsored randomized double-blind trial comparing rosuvastatin 20 mg with placebo in 17,802 apparently healthy men and women with LDL cholesterol <3.4 mmol/L and elevated C-reactive protein (CRP). The results of the JUPITER trial have been widely publicized, and based on the trial, the main regulatory agencies have approved rosuvastatin for the indication of primary prevention of vascular events. However, the interpretation and clinical implications of the JUPITER trial have been questioned and remain controversial. The objective of this commentary is to evaluate the relevance, design, results, and conclusions of the JUPITER study.

Central nervous system prophylaxis with intrathecal liposomal cytarabine in a subset of high-risk patients with diffuse large B-cell lymphoma receiving first line systemic therapy in a prospective trial.

PubMed

González-Barca, E; Canales, M; Salar, A; Ferreiro-Martínez, J J; Ferrer-Bordes, S; García-Marco, J A; Sánchez-Blanco, J J; García-Frade, J; Peñalver, J; Bello-López, J L; Sancho, J M; Caballero, D

2016-05-01

The dissemination in the central nervous system (CNS) is an uncommon but fatal complication occurring in patients with diffuse large B-cell lymphoma (DLBCL). Standard prophylaxis has been demonstrated to reduce CNS relapse and improve survival rates. Intrathecal (IT) liposomal cytarabine allows maintaining elevated drug levels in the cerebrospinal fluid for an extended period of time. Data on the efficacy and safety of liposomal cytarabine as CNS prophylaxis in patients with DLBCL are still insufficient. The objective of the present study was to evaluate the effectiveness and safety of the prophylaxis with IT liposomal cytarabine in prevention of CNS relapse in high-risk patients with DLBCL who were included in a trial of first line systemic therapy with 6 cycles of dose-dense R-CHOP every 14 days. Twenty-four (18.6 %) out of 129 patients were identified to have risk factors for CNS involvement, defined as follows: >30 % bone marrow infiltration, testes infiltration, retroperitoneal mass ≥10 cm, Waldeyer ring, or bulky cervical nodes involvement. Liposomal cytarabine (50 mg) was administered by lumbar puncture the first day of the 1st, 2nd, and 6th cycle of R-CHOP14 scheme. Among 70 IT infusions, grade 3-4 adverse events reported were headache (one patient) and nausea/vomiting (one patient). With a median follow-up of 40.1 months, no CNS involvement by DLBCL was observed in any patient. In conclusion, IT liposomal cytarabine is safe, feasible, and effective for CNS prophylaxis, causing few associated risks and little discomfort to patients with DLBCL.

A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial.

PubMed

Piccini, Jonathan P; Connolly, Stuart J; Abraham, William T; Healey, Jeff S; Steinberg, Benjamin A; Al-Khalidi, Hussein R; Dignacco, Patricia; van Veldhuisen, Dirk J; Sauer, William H; White, Michel; Wilton, Stephen B; Anand, Inder S; Dufton, Christopher; Marshall, Debra A; Aleong, Ryan G; Davis, Gordon W; Clark, Richard L; Emery, Laura L; Bristow, Michael R

2018-05-01

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded "seamless" phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501). Copyright © 2017 Elsevier Inc. All rights reserved.

The process of developing and implementing a telephone-based peer support program for postpartum depression: evidence from two randomized controlled trials

PubMed Central

2014-01-01

Background A randomized controlled trial evaluated the effect of telephone-based peer support on preventing postpartum depression (PPD) among high-risk mothers. The results indicated that support provided by peer volunteers may be an effective preventative strategy. The purpose of this paper is to outline the process of developing, implementing, maintaining, and evaluating the peer support program that we used in this PPD prevention trial. Methods The peer support program had been used successfully in a pilot trial and a previous breastfeeding peer support trial. Based on our experience and lessons learned, we developed a 4-phase, 12-step approach so that the peer support model could be copied and used by different health providers in various settings. We will use the PPD prevention trial to demonstrate the suggested steps. Results The trial aim to prevent the onset of PPD was established. Peer volunteers who previously experienced and recovered from self-reported PPD were recruited and attended a four-hour training session. Volunteers were screened and those identified as appropriate to provide support to postpartum mothers were selected. Women who scored more than 9 on the Edinburgh Postnatal Depression Scale within the first two weeks after childbirth were recruited to participate in the trial and proactive, individualized, telephone-based peer support (mother-to-mother) was provided to those randomized to the intervention group. Peer volunteers maintained the intervention, supported other volunteers, and evaluated the telephone-based support program. Possible negative effects of the intervention were assessed. An in-depth assessment of maternal perspectives of the program at 12 weeks postpartum was performed. Conclusions The 4-phase, 12-step approach delineated in this paper provides clear and concise guidelines for health professionals to follow in creating and implementing community-based, peer-support interventions with the potential to prevent PPD. Trial registration Current Controlled Trials ISRCTN68337727. PMID:24742217

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

PubMed

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

Hepatitis B immunoglobulin during pregnancy for prevention of mother-to-child transmission of hepatitis B virus.

PubMed

Eke, Ahizechukwu C; Eleje, George U; Eke, Uzoamaka A; Xia, Yun; Liu, Jiao

2017-02-11

Hepatitis is a viral infection of the liver. It is mainly transmitted between people through contact with infected blood, frequently from mother to baby in-utero. Hepatitis B poses significant risk to the fetus and up to 85% of infants infected by their mothers at birth develop chronic hepatitis B virus (HBV) infection. Hepatitis B immunoglobulin (HBIG) is a purified solution of human immunoglobulin that could be administered to the mother, newborn, or both. HBIG offers protection against HBV infection when administered to pregnant women who test positive for hepatitis B envelope antigen (HBeAg) or hepatitis B surface antigen (HBsAg), or both. When HBIG is administered to pregnant women, the antibodies passively diffuse across the placenta to the child. This materno-fetal diffusion is maximal during the third trimester of pregnancy. Up to 1% to 9% infants born to HBV-carrying mothers still have HBV infection despite the newborn receiving HBIG plus active HBV vaccine in the immediate neonatal period. This suggests that additional intervention such as HBIG administration to the mother during the antenatal period could be beneficial to reduce the transmission rate in utero. To determine the benefits and harms of hepatitis B immunoglobulin (HBIG) administration to pregnant women during their third trimester of pregnancy for the prevention of mother-to-child transmission of hepatitis B virus infection. We searched the The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded (Web of Science), SCOPUS, African Journals OnLine, and INDEX MEDICUS up to June 2016. We searched ClinicalTrials.gov and portal of the WHO International Clinical Trials Registry Platform (ICTRP) in December 2016. We included randomised clinical trials comparing HBIG versus placebo or no intervention in pregnant women with HBV. Two authors extracted data independently. We analysed dichotomous outcome data using risk ratio (RR) and continuous outcome data using mean difference (MD) with 95% confidence intervals (CI). For meta-analyses, we used a fixed-effect model and a random-effects model, along with an assessment of heterogeneity. If there were statistically significant discrepancies in the results, we reported the more conservative point estimate. If the two estimates were equal, we used the estimate with the widest CI as our main result. We assessed bias control using the Cochrane Hepato-Biliary Group suggested bias risk domains and risk of random errors using Trial Sequential Analysis (TSA). We assessed the quality of the evidence using GRADE. All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo.Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I 2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I 2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I 2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

Explaining high and low performers in complex intervention trials: a new model based on diffusion of innovations theory.

PubMed

McMullen, Heather; Griffiths, Chris; Leber, Werner; Greenhalgh, Trisha

2015-05-31

Complex intervention trials may require health care organisations to implement new service models. In a recent cluster randomised controlled trial, some participating organisations achieved high recruitment, whereas others found it difficult to assimilate the intervention and were low recruiters. We sought to explain this variation and develop a model to inform organisational participation in future complex intervention trials. The trial included 40 general practices in a London borough with high HIV prevalence. The intervention was offering a rapid HIV test as part of the New Patient Health Check. The primary outcome was mean CD4 cell count at diagnosis. The process evaluation consisted of several hundred hours of ethnographic observation, 21 semi-structured interviews and analysis of routine documents (e.g., patient leaflets, clinical protocols) and trial documents (e.g., inclusion criteria, recruitment statistics). Qualitative data were analysed thematically using--and, where necessary, extending--Greenhalgh et al.'s model of diffusion of innovations. Narrative synthesis was used to prepare case studies of four practices representing maximum variety in clinicians' interest in HIV (assessed by level of serological testing prior to the trial) and performance in the trial (high vs. low recruiters). High-recruiting practices were, in general though not invariably, also innovative practices. They were characterised by strong leadership, good managerial relations, readiness for change, a culture of staff training and available staff time ('slack resources'). Their front-line staff believed that patients might benefit from the rapid HIV test ('relative advantage'), were emotionally comfortable administering it ('compatibility'), skilled in performing it ('task issues') and made creative adaptations to embed the test in local working practices ('reinvention'). Early experience of a positive HIV test ('observability') appeared to reinforce staff commitment to recruiting more participants. Low-performing practices typically had less good managerial relations, significant resource constraints, staff discomfort with the test and no positive results early in the trial. An adaptation of the diffusion of innovations model was an effective analytical tool for retrospectively explaining high and low-performing practices in a complex intervention research trial. Whether the model will work prospectively to predict performance (and hence shape the design of future trials) is unknown. ISRCTN Registry number: ISRCTN63473710. Date assigned: 22 April 2010.

Diffusion tensor imaging with direct cytopathological validation: characterisation of decorin treatment in experimental juvenile communicating hydrocephalus.

PubMed

Aojula, Anuriti; Botfield, Hannah; McAllister, James Patterson; Gonzalez, Ana Maria; Abdullah, Osama; Logan, Ann; Sinclair, Alexandra

2016-05-31

In an effort to develop novel treatments for communicating hydrocephalus, we have shown previously that the transforming growth factor-β antagonist, decorin, inhibits subarachnoid fibrosis mediated ventriculomegaly; however decorin's ability to prevent cerebral cytopathology in communicating hydrocephalus has not been fully examined. Furthermore, the capacity for diffusion tensor imaging to act as a proxy measure of cerebral pathology in multiple sclerosis and spinal cord injury has recently been demonstrated. However, the use of diffusion tensor imaging to investigate cytopathological changes in communicating hydrocephalus is yet to occur. Hence, this study aimed to determine whether decorin treatment influences alterations in diffusion tensor imaging parameters and cytopathology in experimental communicating hydrocephalus. Moreover, the study also explored whether diffusion tensor imaging parameters correlate with cellular pathology in communicating hydrocephalus. Accordingly, communicating hydrocephalus was induced by injecting kaolin into the basal cisterns in 3-week old rats followed immediately by 14 days of continuous intraventricular delivery of either human recombinant decorin (n = 5) or vehicle (n = 6). Four rats remained as intact controls and a further four rats served as kaolin only controls. At 14-days post-kaolin, just prior to sacrifice, routine magnetic resonance imaging and magnetic resonance diffusion tensor imaging was conducted and the mean diffusivity, fractional anisotropy, radial and axial diffusivity of seven cerebral regions were assessed by voxel-based analysis in the corpus callosum, periventricular white matter, caudal internal capsule, CA1 hippocampus, and outer and inner parietal cortex. Myelin integrity, gliosis and aquaporin-4 levels were evaluated by post-mortem immunohistochemistry in the CA3 hippocampus and in the caudal brain of the same cerebral structures analysed by diffusion tensor imaging. Decorin significantly decreased myelin damage in the caudal internal capsule and prevented caudal periventricular white matter oedema and astrogliosis. Furthermore, decorin treatment prevented the increase in caudal periventricular white matter mean diffusivity (p = 0.032) as well as caudal corpus callosum axial diffusivity (p = 0.004) and radial diffusivity (p = 0.034). Furthermore, diffusion tensor imaging parameters correlated primarily with periventricular white matter astrocyte and aquaporin-4 levels. Overall, these findings suggest that decorin has the therapeutic potential to reduce white matter cytopathology in hydrocephalus. Moreover, diffusion tensor imaging is a useful tool to provide surrogate measures of periventricular white matter pathology in communicating hydrocephalus.

Differential Susceptibility to Prevention: GABAergic, Dopaminergic, and Multilocus Effects

ERIC Educational Resources Information Center

Brody, Gene H.; Chen, Yi-fu; Beach, Steven R. H.

2013-01-01

Background: Randomized prevention trials provide a unique opportunity to test hypotheses about the interaction of genetic predispositions with contextual processes to create variations in phenotypes over time. Methods: Using two longitudinal, randomized prevention trials, molecular genetic and alcohol use outcome data were gathered from more than…

Gradient zone boundary control in salt gradient solar ponds

DOEpatents

Hull, John R.

1984-01-01

A method and apparatus for suppressing zone boundary migration in a salt gradient solar pond includes extending perforated membranes across the pond at the boundaries, between the convective and non-convective zones, the perforations being small enough in size to prevent individual turbulence disturbances from penetrating the hole, but being large enough to allow easy molecular diffusion of salt thereby preventing the formation of convective zones in the gradient layer. The total area of the perforations is a sizable fraction of the membrane area to allow sufficient salt diffusion while preventing turbulent entrainment into the gradient zone.

Gradient zone-boundary control in salt-gradient solar ponds

DOEpatents

Hull, J.R.

1982-09-29

A method and apparatus for suppressing zone boundary migration in a salt gradient solar pond includes extending perforated membranes across the pond at the boundaries, between the convective and non-convective zones, the perforations being small enough in size to prevent individual turbulence disturbances from penetrating the hole, but being large enough to allow easy molecular diffusion of salt thereby preventing the formation of convective zones in the gradient layer. The total area of the perforations is a sizeable fraction of the membrane area to allow sufficient salt diffusion while preventing turbulent entrainment into the gradient zone.

Prevention of Contrast-Induced AKI: A Review of Published Trials and the Design of the Prevention of Serious Adverse Events following Angiography (PRESERVE) Trial

PubMed Central

Gallagher, Martin; Kaufman, James; Cass, Alan; Parikh, Chirag R.; Chertow, Glenn M.; Shunk, Kendrick A.; McCullough, Peter A.; Fine, Michael J.; Mor, Maria K.; Lew, Robert A.; Huang, Grant D.; Conner, Todd A.; Brophy, Mary T.; Lee, Joanne; Soliva, Susan; Palevsky, Paul M.

2013-01-01

Summary Contrast-induced AKI (CI-AKI) is a common condition associated with serious, adverse outcomes. CI-AKI may be preventable because its risk factors are well characterized and the timing of renal insult is commonly known in advance. Intravenous (IV) fluids and N-acetylcysteine (NAC) are two of the most widely studied preventive measures for CI-AKI. Despite a multitude of clinical trials and meta-analyses, the most effective type of IV fluid (sodium bicarbonate versus sodium chloride) and the benefit of NAC remain unclear. Careful review of published trials of these interventions reveals design limitations that contributed to their inconclusive findings. Such design limitations include the enrollment of small numbers of patients, increasing the risk for type I and type II statistical errors; the use of surrogate primary endpoints defined by small increments in serum creatinine, which are associated with, but not necessarily causally related to serious, adverse, patient-centered outcomes; and the inclusion of low-risk patients with intact baseline kidney function, yielding low event rates and reduced generalizability to a higher-risk population. The Prevention of Serious Adverse Events following Angiography (PRESERVE) trial is a randomized, double-blind, multicenter trial that will enroll 8680 high-risk patients undergoing coronary or noncoronary angiography to compare the effectiveness of IV isotonic sodium bicarbonate versus IV isotonic sodium chloride and oral NAC versus oral placebo for the prevention of serious, adverse outcomes associated with CI-AKI. This article discusses key methodological issues of past trials investigating IV fluids and NAC and how they informed the design of the PRESERVE trial. PMID:23660180

Dissonance and Healthy Weight Eating Disorder Prevention Programs: A Randomized Efficacy Trial

ERIC Educational Resources Information Center

Stice, Eric; Shaw, Heather; Burton, Emily; Wade, Emily

2006-01-01

In this trial, adolescent girls with body dissatisfaction (N = 481, M age = 17 years) were randomized to an eating disorder prevention program involving dissonance-inducing activities that reduce thin-ideal internalization, a prevention program promoting healthy weight management, an expressive writing control condition, or an assessment-only…

Exploratory Trial of a School-Based Alcohol Prevention Intervention with a Family Component

ERIC Educational Resources Information Center

Segrott, Jeremy; Rothwell, Heather; Pignatelli, Ilaria; Playle, Rebecca; Hewitt, Gillian; Huang, Chao; Murphy, Simon; Hickman, Matthew; Reed, Hayley; Moore, Laurence

2016-01-01

Purpose: Involvement of parents/carers may increase effectiveness of primary school-based alcohol-misuse prevention projects through strengthening family-based protective factors, but rates of parental engagement are typically low. This paper reports findings from an exploratory trial of a school-based prevention intervention--Kids, Adults…

Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance.

PubMed

Helmer, K G; Chou, M-C; Preciado, R I; Gimi, B; Rollins, N K; Song, A; Turner, J; Mori, S

2016-02-27

MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables.

Demonstration of Nonlinearity Bias in the Measurement of the Apparent Diffusion Coefficient in Multicenter Trials

PubMed Central

Malyarenko, Dariya; Newitt, David; Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G.; Arlinghaus, Lori R.; Jacobs, Michael A.; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E.; Huang, Wei; Chenevert, Thomas L.

2015-01-01

Purpose Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Methods Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ±150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients and eddy currents were assessed independently. The observed bias errors were compared to numerical models. Results The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between −55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (±5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image co-registration of individual gradient directions. Conclusion The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. PMID:25940607

Demonstration of nonlinearity bias in the measurement of the apparent diffusion coefficient in multicenter trials.

PubMed

Malyarenko, Dariya I; Newitt, David; J Wilmes, Lisa; Tudorica, Alina; Helmer, Karl G; Arlinghaus, Lori R; Jacobs, Michael A; Jajamovich, Guido; Taouli, Bachir; Yankeelov, Thomas E; Huang, Wei; Chenevert, Thomas L

2016-03-01

Characterize system-specific bias across common magnetic resonance imaging (MRI) platforms for quantitative diffusion measurements in multicenter trials. Diffusion weighted imaging (DWI) was performed on an ice-water phantom along the superior-inferior (SI) and right-left (RL) orientations spanning ± 150 mm. The same scanning protocol was implemented on 14 MRI systems at seven imaging centers. The bias was estimated as a deviation of measured from known apparent diffusion coefficient (ADC) along individual DWI directions. The relative contributions of gradient nonlinearity, shim errors, imaging gradients, and eddy currents were assessed independently. The observed bias errors were compared with numerical models. The measured systematic ADC errors scaled quadratically with offset from isocenter, and ranged between -55% (SI) and 25% (RL). Nonlinearity bias was dependent on system design and diffusion gradient direction. Consistent with numerical models, minor ADC errors (± 5%) due to shim, imaging and eddy currents were mitigated by double echo DWI and image coregistration of individual gradient directions. The analysis confirms gradient nonlinearity as a major source of spatial DW bias and variability in off-center ADC measurements across MRI platforms, with minor contributions from shim, imaging gradients and eddy currents. The developed protocol enables empiric description of systematic bias in multicenter quantitative DWI studies. © 2015 Wiley Periodicals, Inc.

The design and development of a complex multifactorial falls assessment intervention for falls prevention: The Prevention of Falls Injury Trial (PreFIT).

PubMed

Bruce, Julie; Ralhan, Shvaita; Sheridan, Ray; Westacott, Katharine; Withers, Emma; Finnegan, Susanne; Davison, John; Martin, Finbarr C; Lamb, Sarah E

2017-06-01

This paper describes the design and development of a complex multifactorial falls prevention (MFFP) intervention for implementation and testing within the framework of a large UK-based falls prevention randomised controlled trial (RCT). A complex intervention was developed for inclusion within the Prevention of Falls Injury Trial (PreFIT), a multicentre pragmatic RCT. PreFIT aims to compare the clinical and cost-effectiveness of three alternative primary care falls prevention interventions (advice, exercise and MFFP), on outcomes of fractures and falls. Community-dwelling adults, aged 70 years and older, were recruited from primary care in the National Health Service (NHS), England. Development of the PreFIT MFFP intervention was informed by the existing evidence base and clinical guidelines for the assessment and management of falls in older adults. After piloting and modification, the final MFFP intervention includes seven falls risk factors: a detailed falls history interview with consideration of 'red flags'; assessment of balance and gait; vision; medication screen; cardiac screen; feet and footwear screen and home environment assessment. This complex intervention has been fully manualised with clear, documented assessment and treatment pathways for each risk factor. Each risk factor is assessed in every trial participant referred for MFFP. Referral for assessment is based upon a screening survey to identify those with a history of falling or balance problems. Intervention delivery can be adapted to the local setting. This complex falls prevention intervention is currently being tested within the framework of a large clinical trial. This paper adheres to TIDieR and CONSORT recommendations for the comprehensive and explicit reporting of trial interventions. Results from the PreFIT study will be published in due course. The effectiveness and cost-effectiveness of the PreFIT MFFP intervention, compared to advice and exercise, on the prevention of falls and fractures, will be reported at the conclusion of the trial.

Background Information | Division of Cancer Prevention

Cancer.gov

The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial is a large population-based randomized trial evaluating screening programs for these cancers. The primary goal of this long-term trial of the National Cancer Institute's (NCI) Division of Cancer Prevention (DCP) is to determine the effects of screening on cancer-related mortality and on secondary

An Effectiveness Trial of a Dissonance-Based Eating Disorder Prevention Program for High-Risk Adolescent Girls

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Gau, Jeff; Shaw, Heather

2009-01-01

Efficacy trials indicate that an eating disorder prevention program involving dissonance-inducing activities that decrease thin-ideal internalization reduces risk for current and future eating pathology, yet it is unclear whether this program produces effects under real-world conditions. The present effectiveness trial tested whether this program…

Process evaluation in a multisite, primary obesity-prevention trial in American Indian schoolchildren1–3

PubMed Central

Helitzer, Deborah L; Davis, Sally M; Gittelsohn, Joel; Going, Scott B; Murray, David M; Snyder, Patricia; Steckler, Allan B

2016-01-01

We describe the development, implementation, and use of the process evaluation component of a multisite, primary obesity prevention trial for American Indian schoolchildren. We describe the development and pilot testing of the instruments, provide some examples of the criteria for instrument selection, and provide examples of how process evaluation results were used to document and refine intervention components. The theoretical and applied framework of the process evaluation was based on diffusion theory, social learning theory, and the desire for triangulation of multiple modes of data collection. The primary objectives of the process evaluation were to systematically document the training process, content, and implementation of 4 components of the intervention. The process evaluation was developed and implemented collaboratively so that it met the needs of both the evaluators and those who would be implementing the intervention components. Process evaluation results revealed that observation and structured interviews provided the most informative data; however, these methods were the most expensive and time consuming and required the highest level of skill to undertake. Although the literature is full of idealism regarding the uses of process evaluation for formative and summative purposes, in reality, many persons are sensitive to having their work evaluated in such an in-depth, context-based manner as is described. For this reason, use of structured, quantitative, highly objective tools may be more effective than qualitative methods, which appear to be more dependent on the skills and biases of the researcher and the context in which they are used. PMID:10195608

Early-Life Obesity Prevention: Critique of Intervention Trials During the First One Thousand Days.

PubMed

Reilly, John J; Martin, Anne; Hughes, Adrienne R

2017-06-01

To critique the evidence from recent and ongoing obesity prevention interventions in the first 1000 days in order to identify evidence gaps and weaknesses, and to make suggestions for more informative future intervention trials. Completed and ongoing intervention trials have had fairly modest effects, have been limited largely to high-income countries, and have used relatively short-term interventions and outcomes. Comparison of the evidence from completed prevention trials with the evidence from systematic reviews of behavioral risk factors shows that some life-course stages have been neglected (pre-conception and toddlerhood), and that interventions have neglected to target some important behavioral risk factors (maternal smoking during pregnancy, infant and child sleep). Finally, while obesity prevention interventions aim to modify body composition, few intervention trials have used body composition measures as outcomes, and this has limited their sensitivity to detect intervention effects. The new WHO Healthy Lifestyles Trajectory (HeLTI) initiative should address some of these weaknesses. Future early obesity prevention trials should be much more ambitious. They should, ideally: extend their interventions over the first 1000 days; have longer-term (childhood) outcomes, and improved outcome measures (body composition measures in addition to proxies for body composition such as the BMI for age); have greater emphasis on maternal smoking and child sleep; be global.

The Swedish six-community alcohol and drug prevention trial: effects on youth drinking.

PubMed

Hallgren, Mats; Andréasson, Sven

2013-09-01

Local communities are increasingly targeted for alcohol and drug prevention campaigns. This study describes some of the key findings from the Swedish six-community alcohol and drug prevention trial (2003-2007) and lessons learned following an evaluation of the trial's effectiveness. The paper focuses mainly on changes in youth drinking and related harms. This was a pre- to post-intervention effect study comparing six trial communities that received added training and technical support with six control communities where regular prevention efforts were supported by national alcohol and drug action plans. A repeated, cross-sectional survey of 8092 youths aged 15-19 years assessed changes in alcohol consumption, binge drinking, perceived alcohol availability, access to alcohol via parents and adult attitudes towards the supply of alcohol to youths. National registry data were used to assess changes in hospital admissions due to alcohol intoxication. Overall, there were few significant improvements in the six trial communities compared with the control communities. The absence of program effects was largely attributable to the selection of strategies (in particular, school and parental programs) lacking evidence of effectiveness in reducing alcohol consumption at the aggregate level. Prevention programs based on efficacy studies need to be tested in community-based effectiveness trials before being disseminated. © 2013 Australasian Professional Society on Alcohol and other Drugs.

Polyp Prevention Trial

Cancer.gov

The primary objective of the Polyp Prevention Trial (PPT) is to determine whether a low fat, high fiber, high vegetable and fruit eating plan will decrease the recurrence of adenomatous polyps of the large bowel.

Rituximab and chemotherapy in diffuse large B-cell lymphoma.

PubMed

Sonet, Anne; Bosly, André

2009-06-01

Rituximab is an anti-CD20 chimeric monoclonal antibody with activity in nearly all subtypes of B-cell lymphomas. Association of rituximab with chemotherapy (mostly the cyclophosphamide, doxorubicin, vincristine and prednisolone [CHOP] regimen) in diffuse large B-cell lymphoma (DLBCL) represents an extraordinary revolution in the prognosis of DLBCL, and is the new standard of therapy in elderly and young, low-risk patients. Despite the lack of randomized, clinical trials in younger patients with high risk, rituximab is also a standard of care in these patients in clinical practice, at least in North America. The practice is based on observational trials (e.g., the British Columbia Registry) and the missing logic in classifying patients as 'younger' or 'older': 60 years old or 65 years old. In Europe, trials are ongoing to establish the best treatment for young, high-risk patients. Association of rituximab and chemotherapy deeply modifies prognostic factors defined before the rituximab era.

Diffusion theory of decision making in continuous report.

PubMed

Smith, Philip L

2016-07-01

I present a diffusion model for decision making in continuous report tasks, in which a continuous, circularly distributed, stimulus attribute in working memory is matched to a representation of the attribute in the stimulus display. Memory retrieval is modeled as a 2-dimensional diffusion process with vector-valued drift on a disk, whose bounding circle represents the decision criterion. The direction and magnitude of the drift vector describe the identity of the stimulus and the quality of its representation in memory, respectively. The point at which the diffusion exits the disk determines the reported value of the attribute and the time to exit the disk determines the decision time. Expressions for the joint distribution of decision times and report outcomes are obtained by means of the Girsanov change-of-measure theorem, which allows the properties of the nonzero-drift diffusion process to be characterized as a function of a Euclidian-distance Bessel process. Predicted report precision is equal to the product of the decision criterion and the drift magnitude and follows a von Mises distribution, in agreement with the treatment of precision in the working memory literature. Trial-to-trial variability in criterion and drift rate leads, respectively, to direct and inverse relationships between report accuracy and decision times, in agreement with, and generalizing, the standard diffusion model of 2-choice decisions. The 2-dimensional model provides a process account of working memory precision and its relationship with the diffusion model, and a new way to investigate the properties of working memory, via the distributions of decision times. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

[Prevention and handling of missing data in clinical trials].

PubMed

Jiang, Zhi-wei; Li, Chan-juan; Wang, Ling; Xia, Jie-lai

2015-11-01

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.

Preventing substance misuse: study protocol for a randomised controlled trial of the Strengthening Families Programme 10–14 UK (SFP 10–14 UK)

PubMed Central

2014-01-01

Background Prevention of alcohol, drug and tobacco misuse by young people is a key public health priority. There is a need to develop the evidence base through rigorous evaluations of innovative approaches to substance misuse prevention. The Strengthening Families Programme 10–14 is a universal family-based alcohol, drugs and tobacco prevention programme, which has achieved promising results in US trials, and which now requires cross-cultural assessment. This paper therefore describes the protocol for a randomised controlled trial of the UK version of the Strengthening Families Programme 10–14 (SFP 10–14 UK). Methods/Design The trial comprises a pragmatic cluster randomised controlled effectiveness trial with families as the unit of randomisation, with embedded process and economic evaluations. Participating families will be randomised to one of two treatment groups - usual care with full access to existing services (control group), or usual care plus SFP 10–14 UK (intervention group). The trial has two primary outcomes - the number of occasions that young people report having drunk alcohol in the last 30 days, and drunkenness during the last 30 days, both dichotomised as ‘never’ and ‘1-2 times or more’. The main follow-up is at 2 years past baseline, and short-term and intermediate outcomes are also measured at 9 and 15 months. Discussion The results from this trial will provide evidence on the effectiveness and cost-effectiveness of an innovative universal family-based substance misuse prevention programme in a UK context. Trial registration Current Controlled Trials ISRCTN63550893. PMID:24438460

Incentives and disincentives to participate in prophylactic HIV vaccine research.

PubMed

Jenkins, R A; Temoshok, L R; Virochsiri, K

1995-05-01

An anonymous cross-sectional paper-and-pencil survey was used to assess incentives and disincentives to participate in a Phase I preventive human immunodeficiency virus (HIV) vaccine trial in a potential Thai target population. A total of 255 persons employed in health care service and research settings completed questionnaires after attending informational briefings regarding the proposed vaccine product and the planned trial procedures. Willingness to participate was related to self-perceived benefits from joining a preventive vaccine trial, as well as to concerns about product safety and social discrimination that might result from participation. The distinction between positive results of enzyme-linked immunosorbent assay from vaccine administration and positivity from HIV infection was unclear for many participants. Men were more willing to participate than women, and there was a trend toward greater willingness to participate in those who were less educated. Preparations for preventive vaccine trials may be more successful if they emphasize personal benefits of trial participation, clearly address safety issues, and consider ways to prevent social discrimination against participants.

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment

PubMed Central

Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul

2014-01-01

Background Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. Objectives To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Selection criteria Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Data collection and analysis Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. Main results Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment. For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence). For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants, high quality evidence). Fewer trials evaluated spontaneous abortions, still births, perinatal deaths, or neonatal deaths, and these analyses were underpowered to detect clinically important differences. In multigravid women, chemoprevention has similar effects on antenatal parasitaemia (RR 0.38, 95% CI 0.28 to 0.50; three trials, 977 participants, high quality evidence)but there are too few trials to evaluate effects on other outcomes. In trials giving chemoprevention to all pregnant women irrespective of parity, the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia (defined by authors, but at least < 8 g/L: RR 0.19, 95% CI 0.05 to 0.75; two trials, 1327 participants, low quality evidence), but consistent benefits have not been shown for other outcomes. In an analysis confined only to intermittent preventive therapy with SP, the estimates of effect and the quality of the evidence were similar. A summary of a single trial in Thailand of prophylaxis against P. vivax showed chloroquine prevented vivax infection (RR 0.01, 95% CI 0.00 to 0.20; one trial, 942 participants). Authors' conclusions Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs, with clinically important benefits on anaemia and parasitaemia in the mother, and on birthweight in infants. PLAIN LANGUAGE SUMMARY The effect of taking antimalarial drugs routinely to prevent malaria in pregnancy Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. For this reason, women are encouraged to try and prevent malaria infection during pregnancy by sleeping under mosquito bed-nets, and by taking drugs effective against malaria throughout pregnancy as chemoprevention. This Cochrane Review looked at all drug regimens compared to placebo. The review authors sought to summarise and quantify the overall effects of chemoprevention. Seventeen trials were included, all conducted between 1957 and 2008, and all but two in countries of Africa. For women in their first or second pregnancy, malaria chemoprevention prevents moderate to severe anaemia (high quality evidence); and prevents malaria parasites being detected in the blood (high quality evidence). It may also prevent malaria illness. We don't know if it prevents maternal deaths, as this would require very large studies to detect an effect. In their infants, malaria chemoprevention improves the average birthweight (moderate quality evidence), and reduces the number of low birthweight infants (moderate quality evidence). We are not sure if chemoprevention reduces mortality of babies in the first week, month and year, as again studies would need to be very large to show these effects. PMID:25300703

Testing Mediators of Intervention Effects in Randomized Controlled Trials: An Evaluation of Three Depression Prevention Programs

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

2010-01-01

Objective: Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. Method: In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB…

Community Oncology and Prevention Trials Clinical Trials | Division of Cancer Prevention

Cancer.gov

The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

Accrual and drop out in a primary prevention randomised controlled trial: qualitative study.

PubMed

Eborall, Helen C; Stewart, Marlene C W; Cunningham-Burley, Sarah; Price, Jackie F; Fowkes, F Gerry R

2011-01-11

Recruitment and retention of participants are critical to the success of a randomised controlled trial. Gaining the views of potential trial participants who decline to enter a trial and of trial participants who stop the trial treatment is important and can help to improve study processes. Limited research on these issues has been conducted on healthy individuals recruited for prevention trials in the community. Semi-structured interviews with people who were eligible but had declined to participate in the Aspirin for Asymptomatic Atherosclerosis (AAA) trial (N = 11), and AAA trial participants who had stopped taking the trial medication (N = 11). A focus group with further participants who had stopped taking the trial medication (N = 6). (Total participants N = 28). Explanations for declining to participate could be divided into two groups: the first group were characterised by a lack of necessity to participate and a tendency to prioritise other largely mundane problems. The second group's concern was with a high level of perceived risk from participating.Explanations for stopping trial medication fell into four categories: side effects attributed to the trial medication; starting on aspirin or medication contraindicating to aspirin; experiencing an outcome event, and changing one's mind. These results indicate that when planning trials (especially in preventive medicine) particular attention should be given to designing appropriate recruitment materials and processes that fully inform potential recruits of the risks and benefits of participation. ISRCTN66587262.

Corticosteroids and ARDS: A review of treatment and prevention evidence

PubMed Central

Khilnani, G.C.; Hadda, Vijay

2011-01-01

To systematically review the role of corticosteroids in prevention of acute respiratory distress syndrome (ARDS) in high-risk patients, and in treatment of established ARDS. Primary articles were identified by English-language Pubmed/MEDLINE, Cochrane central register of controlled trials, and Cochrane systemic review database search (1960–June 2009) using the MeSH headings: ARDS, adult respiratory distress syndrome, ARDS, corticosteroids, and methylprednisolone (MP). The identified studies were reviewed and information regarding role of corticosteroids in prevention and treatment of ARDS was evaluated. Nine trials have evaluated the role of corticosteroid drugs in management of ARDS at various stages. Of the 9, 4 trials evaluated role of corticosteroids in prevention of ARDS, while other 5 trials were focused on treatment after variable periods of onset of ARDS. Trials with preventive corticosteroids, mostly using high doses of MP, showed negative results with patients in treatment arm, showing higher mortality and rate of ARDS development. While trials of corticosteroids in early ARDS showed variable results, somewhat, favoring use of these agents to reduce associated morbidities. In late stage of ARDS, these drugs have no benefits and are associated with adverse outcome. Use of corticosteroids in patients with early ARDS showed equivocal results in decreasing mortality; however, there is evidence that these drugs reduce organ dysfunction score, lung injury score, ventilator requirement, and intensive care unit stay. However, most of these trials are small, having a significant heterogeneity regarding study design, etiology of ARDS, and dosage of corticosteroids. Further research involving large-scale trials on relatively homogeneous cohort is necessary to establish the role of corticosteroids for this condition. PMID:21712921

Preventing ARDS

PubMed Central

Beitler, Jeremy R.; Schoenfeld, David A.

2014-01-01

Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality. PMID:25288000

What is the place of pre-exposure prophylaxis in HIV prevention?

PubMed

De Man, Jeroen; Colebunders, Robert; Florence, Eric; Laga, Marie; Kenyon, Christopher

2013-01-01

New tools are needed to bring down ongoing high HIV incidence. This review aims to evaluate the place of one of these new tools (pre-exposure prophylaxis) in a comprehensive prevention strategy. Several trials have demonstrated the safety and the efficacy of pre-exposure prophylaxis in HIV prevention. Two large trials have, however, failed to show such efficacy. This was likely due to poor adherence in these trials. New forms of long-acting pre-exposure prophylaxis currently in trials may deal with these problems of low adherence. Pre-exposure prophylaxis has been demonstrated to be cost-effective within certain settings. The introduction of pre-exposure prophylaxis into prevention programs needs to be carefully thought through. For example, pre-exposure prophylaxis-induced risk compensation, at both an individual and population level, could undermine other aspects of a comprehensive HIV prevention program. In conclusion, pre-exposure prophylaxis could be a useful additional tool for the prevention of HIV in specific high-risk groups. It should be implemented in a way that deals with issues such as ensuring high adherence and ensuring that pre-exposure prophylaxis does not detract from, but complements, other more fundamental elements of HIV prevention programs.

Pilot study of intravenous glyburide in patients with a large ischemic stroke.

PubMed

Sheth, Kevin N; Kimberly, W Taylor; Elm, Jordan J; Kent, Thomas A; Mandava, Pitchaiah; Yoo, Albert J; Thomalla, Götz; Campbell, Bruce; Donnan, Geoffrey A; Davis, Stephen M; Albers, Gregory W; Jacobson, Sven; Simard, J Marc; Stern, Barney J

2014-01-01

Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. We assessed the feasibility of recruiting and treating patients with severe stroke while obtaining preliminary information on the safety and tolerability of RP-1127 (glyburide for injection). We studied 10 patients with acute ischemic stroke, with baseline diffusion-weighted imaging lesion volumes of 82 to 210 cm3, whether treated with intravenous recombinant tissue-type plasminogen activator, age 18 to 80 years, and time to RP-1127≤10 hours. Recruitment was completed within 10 months. The mean age was 50.5 years, and baseline diffusion-weighted image lesion volume was 102±23 cm3. There were no serious adverse events related to drug and no symptomatic hypoglycemia. The increase in ipsilateral hemisphere volume was 50±33 cm3. The proportion of 90-day modified Rankin Scale≤4 was 90% (40% modified Rankin Scale, ≤3). RP-1127 at a dose of 3 mg/d was well tolerated and did not require any dose reductions. A clinical trial of RP-1127 is feasible. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01268683.

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol.

PubMed

Sánchez-Carracedo, David; López-Guimerà, Gemma; Fauquet, Jordi; Barrada, Juan Ramón; Pàmias, Montserrat; Puntí, Joaquim; Querol, Mireia; Trepat, Esther

2013-10-12

The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government's Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Current Controlled Trials ISRCTN47682626.

A school-based program implemented by community providers previously trained for the prevention of eating and weight-related problems in secondary-school adolescents: the MABIC study protocol

PubMed Central

2013-01-01

Background The prevention of eating disorders and disordered eating are increasingly recognized as public health priorities. Challenges in this field included moving from efficacy to effectiveness and developing an integrated approach to the prevention of a broad spectrum of eating and weight-related problems. A previous efficacy trial indicated that a universal disordered eating prevention program, based on the social cognitive model, media literacy educational approach and cognitive dissonance theory, reduced risk factors for disordered eating, but it is unclear whether this program has effects under more real-world conditions. The main aim of this effectiveness trial protocol is to test whether this program has effects when incorporating an integrated approach to prevention and when previously-trained community providers implement the intervention. Methods/design The research design involved a multi-center non-randomized controlled trial with baseline, post and 1-year follow-up measures. Six schools from the city of Sabadell (close to Barcelona) participated in the intervention group, and eleven schools from four towns neighboring Sabadell participated in the control group. A total of 174 girls and 180 boys in the intervention group, and 484 girls and 490 boys in the control group were registered in class lists prior to baseline. A total of 18 community providers, secondary-school class tutors, nurses from the Catalan Government’s Health and School Program, and health promotion technicians from Sabadell City Council were trained and delivered the program. Shared risk factors of eating and weight-related problems were assessed as main measures. Discussion It will be vital for progress in disordered eating prevention to conduct effectiveness trials, which test whether interventions are effective when delivered by community providers under ecologically valid conditions, as opposed to tightly controlled research trials. The MABIC project will provide new contributions in this transition from efficacy to effectiveness and new data about progress in the integrated approach to prevention. Pending the results, the effectiveness trial meets the effectiveness standards set down by the Society for Prevention Research. This study will provide new evidence to improve and enhance disordered eating prevention programs. Trial registration Current Controlled Trials ISRCTN47682626 PMID:24118981

"Who Is Helsinki" Sex Workers Advise Improving Communication for Good Participatory Practice in Clinical Trials

ERIC Educational Resources Information Center

Ditmore, Melissa Hope; Allman, Dan

2011-01-01

After premature closures in 2004 of biomedical human immunodeficiency virus (HIV) prevention trials involving sex workers in Africa and Asia, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Advocacy for HIV Prevention (AVAC) undertook consultations to establish better participatory guidelines for such trials in order to address…

NCORP’s First Year Reviewed | Division of Cancer Prevention

Cancer.gov

By the numbers, the first year of NCI’s Community Oncology Research Program (NCORP) has made progress in clinical trials for prevention, control, health-related quality of life, comparative effectiveness and screening; accrual to NCI National Clinical Trials Network treatment and imaging trials; and in new areas of emphasis in cancer care delivery research and cancer

Promising therapies for treating and/or preventing androgenic alopecia.

PubMed

McElwee, K J; Shapiro, J S

2012-06-01

Androgenetic alopecia (AGA) may affect up to 70% of men and 40% of women at some point in their lifetime. While men typically present with a distinctive alopecia pattern involving hairline recession and vertex balding, women normally exhibit a diffuse hair thinning over the top of their scalps. The treatment standard in dermatology clinics continues to be minoxidil and finasteride with hair transplantation as a surgical option. Here we briefly review current therapeutic options and treatments under active investigation. Dutasteride and ketoconazole are also employed for AGA, while prostaglandin analogues latanoprost and bimatoprost are being investigated for their hair growth promoting potential. Laser treatment products available for home use and from cosmetic clinics are becoming popular. In the future, new cell mediated treatment approaches may be available for AGA. While there are a number of potential treatment options, good clinical trial data proving hair growth efficacy is limited.

[The root of the deep and fast ongoing evolution of both structure and methodology of clinical research].

PubMed

Tavazzi, Luigi

2016-03-01

The growing scientific knowledge and technology development are leading to radical changes in biological and medical research. The prevalent lines of development deal with a pragmatic evolution of controlled clinical trials, a massive diffusion of observational research, which is progressively incorporated in clinical practice, new models and designs of clinical research, the systematic use of information technology to build up vast networks of medical centers producing huge amounts of shared data to be managed through the big data methodology, personalized as well as precision medicine, a reshaped physician-patient relationship based on a co-working principle. All this is leading to profound changes in public health governance, a renewal of clinical epidemiology and prevention, a modified structure of several specific sectors of medical care, hopefully guided by scientific evidences. A few aspects of such an evolving picture are discussed in this article.

Protocol for Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial: a randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services.

PubMed

Tickle, Martin; Milsom, Keith M; Donaldson, Michael; Killough, Seamus; O'Neill, Ciaran; Crealey, Grainne; Sutton, Matthew; Noble, Solveig; Greer, Margaret; Worthington, Helen V

2011-10-10

Dental caries is a persistent public health problem with little change in the prevalence in young children over the last 20 years. Once a child contracts the disease it has a significant impact on their quality of life. There is good evidence from Cochrane reviews including trials that fluoride varnish and regular use of fluoride toothpaste can prevent caries. The Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial will compare the costs and effects of a caries preventive package (fluoride varnish, toothpaste, toothbrush and standardised dental health education) with dental health education alone in young children. A randomised controlled trial on children initially aged 2 and 3 years old who are regular attenders at the primary dental care services in Northern Ireland. Children will be recruited and randomised in dental practices. Children will be randomised to the prevention package of both fluoride varnish (twice per year for three years), fluoride toothpaste (1,450 ppm F) (supplied twice per year), a toothbrush (supplied twice a year) or not; both test and control groups receive standardised dental health education delivered by the dentist twice per year. Randomisation will be conducted by the Belfast Trust Clinical Research Support Centre ([CRSC] a Clinical Trials Unit). 1200 participants will be recruited from approximately 40 dental practices. Children will be examined for caries by independent dental examiners at baseline and will be excluded if they have caries. The independent dental examiners will examine the children again at 3 years blinded to study group.The primary end-point is whether the child develops caries (cavitation into dentine) or not over the three years. One secondary outcome is the number of carious surfaces in the primary dentition in children who experience caries. Other secondary outcomes are episodes of pain, extraction of primary teeth, other adverse events and costs which will be obtained from parental questionnaires. This is a pragmatic trial conducted in general dental practice. It tests a composite caries prevention intervention, which represents an evidence based approach advocated by current guidance from the English Department of Health which is feasible to deliver to all low risk (caries free) children in general dental practice. The trial will provide valuable information to policy makers and clinicians on the costs and effects of caries prevention delivered to young children in general dental practice. EudraCT No: 2009 - 010725 - 39 ISRCTN: ISRCTN36180119 Ethics Reference No: 09/H1008/93:

Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand

PubMed Central

Simmons, Nicole; Donnell, Deborah; Ou, San-san; Celentano, David D.; Aramrattana, Apinun; Davis-Vogel, Annet; Metzger, David; Latkin, Carl

2015-01-01

Context Controlled trials of educational interventions are susceptible to contamination. Objectives To test a contamination measure based on recall of terms. Main study A randomized controlled trial of a social network peer education intervention among 1,123 injection drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand. Methods We assessed the recall of test, negative and positive control terms by intervention and control arm participants and compared the relative odds (OR) of recall of test vs. negative control terms between study arms. Results The contamination measure showed good discriminant ability only among participants from Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was evidence of diffusion and contamination of 4 of 5 terms tested. Conclusions Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in trials of educational interventions. PMID:25935214

Experiences in conducting multiple community-based HIV prevention trials among women in KwaZulu-Natal, South Africa

PubMed Central

2010-01-01

Background South Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits. Experience Our experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90 000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained. Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and referral for chronic illnesses). Social benefits included training of home-based caregivers and sustainable ongoing HIV prevention education through peer educator programmes. Challenges Several challenges were encountered, including manipulation by participants of their eligibility criteria in order to enroll in the trial. Women attempted to co-enroll in multiple trials to benefit from financial reimbursements and individualised care. The trials became ethically challenging when participants refused to take up referrals for care due to stigma, denial of their HIV status and inadequate health infrastructure. Lack of disclosure of HIV status to partners and family members was particularly challenging. Some of the ethical dilemmas put to the test our responsibility as researchers and our obligation to provide health care to research participants. Conclusion Conducting these five trials in a period of six years provided us with invaluable insights into trial implementation, community participation, recruitment and retention, provision of care and dissemination of trial results. The critical mass of scientists trained as clinical trialists will continue to address the relentless HIV epidemic in our setting and ensure our commitment to finding a biomedical HIV prevention option for women in the future. PMID:20416063

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

PubMed Central

Haak, Andrew J.; Tsou, Pei-Suen; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip; Fox, David A.; Khanna, Dinesh; Larsen, Scott D.

2014-01-01

Systemic sclerosis (SSc), or scleroderma, similar to many fibrotic disorders, lacks effective therapies. Current trials focus on anti-inflammatory drugs or targeted approaches aimed at one of the many receptor mechanisms initiating fibrosis. In light of evidence that a myocardin-related transcription factor (MRTF)–and serum response factor (SRF)–regulated gene transcriptional program induced by Rho GTPases is essential for myofibroblast activation, we explored the hypothesis that inhibitors of this pathway may represent novel antifibrotics. MRTF/SRF-regulated genes show spontaneously increased expression in primary dermal fibroblasts from patients with diffuse cutaneous SSc. A novel small-molecule inhibitor of MRTF/SRF-regulated transcription (CCG-203971) inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)–and transforming growth factor β (TGFβ)–stimulated fibroblasts. In vivo treatment with CCG-203971 also prevented bleomycin-induced skin thickening and collagen deposition. Thus, targeting the MRTF/SRF gene transcription pathway could provide an efficacious new approach to therapy for SSc and other fibrotic disorders. PMID:24706986

Impact of the JUPITER trial on statin prescribing for primary prevention.

PubMed

Teng, Jennifer F T; Gomes, Tara; Camacho, Ximena; Grundy, Scott; Juurlink, David N; Mamdani, Muhammad M

2014-01-01

As the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial identified a new population of individuals with cholesterol levels below traditional treatment thresholds but with elevated high-sensitivity C-reactive protein (hs-CRP) levels who may benefit from primary prevention with statin therapy, we sought to evaluate the impact of this trial on the incident prescription rates of rosuvastatin alone as well as all statins in a primary prevention population. Population-based, cross-sectional time-series analysis. Administrative health care databases in Ontario, Canada. A total of 299,809 incident statin users 66 years or older were identified during the study period, from January 1, 2003, to March 31, 2011, who were prescribed statin therapy for primary prevention. We evaluated the incident rate of rosuvastatin and all statin use during each quarter of the study period. Overall, no significant trends in all incident statin use were observed (p=0.99). Furthermore, no significant differences were observed in incident rates of rosuvastatin (p=0.21) or all statin (p=0.41) use after the publication of the JUPITER trial. Despite the lack of impact of the JUPITER trial on rosuvastatin or all statin utilization, the relative market share of rosuvastatin increased from 9% to 65% over the study period. The publication of the JUPITER trial did not significantly affect trends in overall statin and rosuvastatin prescribing patterns for primary prevention in this study. Increases in the relative market share of rosuvastatin may be attributed to the impact of the pharmaceutical industry on prescribing patterns. Our results highlight the need to further improve the integration of evidence-based prescribing into cost-effective clinical practice. © 2013 Pharmacotherapy Publications, Inc.

Acceptability of cancer chemoprevention trials: impact of the design

PubMed Central

Maisonneuve, Anne-Sophie; Huiart, Laetitia; Rabayrol, Laetitia; Horsman, Doug; Didelot, Remi; Sobol, Hagay; Eisinger, Francois

2008-01-01

Background: Chemoprevention could significantly reduce cancer burden. Assessment of efficacy and risk/benefit balance is at best achieved through randomized clinical trials. Methods: At a periodic health examination center 1463 adults were asked to complete a questionnaire about their willingness to be involved in different kinds of preventive clinical trials. Results: Among the 851 respondents (58.2%), 228 (26.8%) agreed to participate in a hypothetical chemoprevention trial aimed at reducing the incidence of lung cancer and 116 (29.3%) of 396 women agreed to a breast cancer chemoprevention trial. Randomization would not restrain participation (acceptability rate: 87.7% for lung cancer and 93.0% for breast cancer). In these volunteers, short-term trials (1 year) reached a high level of acceptability: 71.5% and 73.7% for lung and breast cancer prevention respectively. In contrast long-term trials (5 years or more) were far less acceptable: 9.2% for lung cancer (OR=7.7 CI95% 4.4-14.0) and 10.5 % for breast cancer (OR=6.9 CI95% 3.2-15.8). For lung cancer prevention, the route of administration impacts on acceptability with higher rate 53.1% for a pill vs. 7.9% for a spray (OR=6.7 CI95% 3.6-12.9). Conclusion: Overall healthy individuals are not keen to be involved in chemo-preventive trials, the design of which could however increase the acceptability rate. PMID:18769562

Weighing the Anti-Ischemic Benefits and Bleeding Risks from Aspirin Therapy: a Rational Approach.

PubMed

Dugani, Sagar; Ames, Jeffrey M; Manson, JoAnn E; Mora, Samia

2018-02-21

The role of aspirin in secondary cardiovascular prevention is well understood; however, the role in primary prevention is less clear, and requires careful balancing of potential benefits with risks. Here, we summarize the evidence base on the benefits and risks of aspirin therapy, discuss clinical practice guidelines and decision support tools to assist in initiating aspirin therapy, and highlight ongoing trials that may clarify the role of aspirin in cardiovascular disease prevention. In 2016, the USPSTF released guidelines on the use of aspirin for primary prevention. Based on 11 trials (n = 118,445), aspirin significantly reduced all-cause mortality and nonfatal myocardial infarction, and in 7 trials that evaluated aspirin ≤ 100 mg/day, there was significant reduction in nonfatal stroke. The USPSTF recommends individualized use of aspirin based on factors including age, 10-year atherosclerotic cardiovascular disease risk score, and bleeding risk. Several ongoing trials are evaluating the role of aspirin in primary prevention, secondary prevention, and in combination therapy for atrial fibrillation. Evidence-based approaches to aspirin use should consider the anti-ischemic benefits and bleeding risks from aspirin. In this era of precision medicine, tools that provide the personalized benefit to risk assessment, such as the freely available clinical decision support tool (Aspirin-Guide), can be easily incorporated into the electronic health record and facilitate more informed decisions about initiating aspirin therapy for primary prevention. Aspirin has a complex matrix of benefits and risks, and its use in primary prevention requires individualized decision-making. Results from ongoing trials may guide healthcare providers in identifying appropriate candidates for aspirin therapy.

Person mobility in the design and analysis of cluster-randomized cohort prevention trials.

PubMed

Vuchinich, Sam; Flay, Brian R; Aber, Lawrence; Bickman, Leonard

2012-06-01

Person mobility is an inescapable fact of life for most cluster-randomized (e.g., schools, hospitals, clinic, cities, state) cohort prevention trials. Mobility rates are an important substantive consideration in estimating the effects of an intervention. In cluster-randomized trials, mobility rates are often correlated with ethnicity, poverty and other variables associated with disparity. This raises the possibility that estimated intervention effects may generalize to only the least mobile segments of a population and, thus, create a threat to external validity. Such mobility can also create threats to the internal validity of conclusions from randomized trials. Researchers must decide how to deal with persons who leave study clusters during a trial (dropouts), persons and clusters that do not comply with an assigned intervention, and persons who enter clusters during a trial (late entrants), in addition to the persons who remain for the duration of a trial (stayers). Statistical techniques alone cannot solve the key issues of internal and external validity raised by the phenomenon of person mobility. This commentary presents a systematic, Campbellian-type analysis of person mobility in cluster-randomized cohort prevention trials. It describes four approaches for dealing with dropouts, late entrants and stayers with respect to data collection, analysis and generalizability. The questions at issue are: 1) From whom should data be collected at each wave of data collection? 2) Which cases should be included in the analyses of an intervention effect? and 3) To what populations can trial results be generalized? The conclusions lead to recommendations for the design and analysis of future cluster-randomized cohort prevention trials.

Phase 0/I/II Cancer Prevention Clinical Trials Program Clinical Trials | Division of Cancer Prevention

Cancer.gov

The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

Protocol for Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial: a randomised controlled trial to measure the effects and costs of a dental caries prevention regime for young children attending primary care dental services

PubMed Central

2011-01-01

Background Dental caries is a persistent public health problem with little change in the prevalence in young children over the last 20 years. Once a child contracts the disease it has a significant impact on their quality of life. There is good evidence from Cochrane reviews including trials that fluoride varnish and regular use of fluoride toothpaste can prevent caries. The Northern Ireland Caries Prevention in Practice Trial (NIC-PIP) trial will compare the costs and effects of a caries preventive package (fluoride varnish, toothpaste, toothbrush and standardised dental health education) with dental health education alone in young children. Methods/Design A randomised controlled trial on children initially aged 2 and 3 years old who are regular attenders at the primary dental care services in Northern Ireland. Children will be recruited and randomised in dental practices. Children will be randomised to the prevention package of both fluoride varnish (twice per year for three years), fluoride toothpaste (1,450 ppm F) (supplied twice per year), a toothbrush (supplied twice a year) or not; both test and control groups receive standardised dental health education delivered by the dentist twice per year. Randomisation will be conducted by the Belfast Trust Clinical Research Support Centre ([CRSC] a Clinical Trials Unit). 1200 participants will be recruited from approximately 40 dental practices. Children will be examined for caries by independent dental examiners at baseline and will be excluded if they have caries. The independent dental examiners will examine the children again at 3 years blinded to study group. The primary end-point is whether the child develops caries (cavitation into dentine) or not over the three years. One secondary outcome is the number of carious surfaces in the primary dentition in children who experience caries. Other secondary outcomes are episodes of pain, extraction of primary teeth, other adverse events and costs which will be obtained from parental questionnaires. Discussion This is a pragmatic trial conducted in general dental practice. It tests a composite caries prevention intervention, which represents an evidence based approach advocated by current guidance from the English Department of Health which is feasible to deliver to all low risk (caries free) children in general dental practice. The trial will provide valuable information to policy makers and clinicians on the costs and effects of caries prevention delivered to young children in general dental practice. Trial registration EudraCT No: 2009 - 010725 - 39 ISRCTN: ISRCTN36180119 Ethics Reference No: 09/H1008/93: PMID:21985746

Echinacea for preventing and treating the common cold

PubMed Central

Karsch-Völk, Marlies; Barrett, Bruce; Kiefer, David; Bauer, Rudolf; Ardjomand-Woelkart, Karin; Linde, Klaus

2014-01-01

Background Echinacea plant preparations (family Asteraceae) are widely used in Europe and North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and the addition of other components. Objectives To assess whether there is evidence that Echinacea preparations are effective and safe compared to placebo in the prevention and treatment of the common cold. Search methods We searched CENTRAL 2013, Issue 5, MEDLINE (1946 to May week 5, 2013), EMBASE (1991 to June 2013), CINAHL (1981 to June 2013), AMED (1985 to February 2012), LILACS (1981 to June 2013), Web of Science (1955 to June 2013), CAMBASE (no time limits), the Centre for Complementary Medicine Research (1988 to September 2007), WHO ICTRP and clinicaltrials.gov (last searched 5 June 2013), screened references and asked experts in the field about published and unpublished studies. Selection criteria Randomized controlled trials (RCTs) comparing mono-preparations of Echinacea with placebo. Data collection and analysis At least two review authors independently assessed eligibility and trial quality and extracted data. The primary efficacy outcome was the number of individuals with at least one cold in prevention trials and the duration of colds in treatment trials. For all included trials the primary safety and acceptability outcome was the number of participants dropping out due to adverse events. We assessed trial quality using the Cochrane ’Risk of bias’ tool. Main results Twenty-four double-blind trials with 4631 participants including a total of 33 comparisons of Echinacea preparations and placebo met the inclusion criteria. A variety of different Echinacea preparations based on different species and parts of plant were used. Evidence from seven trials was available for preparations based on the aerial parts of Echinacea purpurea. Ten trials were considered to have a low risk of bias, six to have an unclear risk of bias and eight to have a high risk of bias. Ten trials with 13 comparisons investigated prevention and 15 trials with 20 comparisons investigated treatment of colds (one trial addressed both prevention and treatment). Due to the strong clinical heterogeneity of the studies we refrained from pooling for the main analysis. None of the 12 prevention comparisons reporting the number of patients with at least one cold episode found a statistically significant difference. However a post hoc pooling of their results, suggests a relative risk reduction of 10% to 20%. Of the seven treatment trials reporting data on the duration of colds, only one showed a significant effect of Echinacea over placebo. The number of patients dropping out or reporting adverse effects did not differ significantly between treatment and control groups in prevention and treatment trials. However, in prevention trials there was a trend towards a larger number of patients dropping out due to adverse events in the treatment groups. Authors’ conclusions Echinacea products have not here been shown to provide benefits for treating colds, although, it is possible there is a weak benefit from some Echinacea products: the results of individual prophylaxis trials consistently show positive (if non-significant) trends, although potential effects are of questionable clinical relevance. PMID:24554461

Local Knowledge and Experiences of Vaccination: Implications for HIV-Preventive Vaccine Trials in South Africa

ERIC Educational Resources Information Center

Lindegger, Graham; Quayle, Michael; Ndlovu, Moses

2007-01-01

This study forms part of the preparation of communities for HIV-preventive vaccine trials in South Africa. On the basis of the assumption that attitudes to any HIV vaccine or vaccine trials will partly be influenced by experiences of vaccination in general, this study aimed to investigate knowledge of, attitudes to, and experiences of vaccination…

An Effectiveness Trial of a Selected Dissonance-Based Eating Disorder Prevention Program for Female High School Students: Long-Term Effects

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Shaw, Heather; Gau, Jeff

2011-01-01

Objective: Efficacy trials found that a dissonance-based eating disorder prevention program in which female high school and college students with body image concerns critique the thin ideal reduced eating disorder risk factors, eating disorder symptoms, and future eating disorder onset. The present effectiveness trial tested whether this program…

Estimates of Intraclass Correlation Coefficients from Longitudinal Group-Randomized Trials of Adolescent HIV/STI/Pregnancy Prevention Programs

ERIC Educational Resources Information Center

Glassman, Jill R.; Potter, Susan C.; Baumler, Elizabeth R.; Coyle, Karin K.

2015-01-01

Introduction: Group-randomized trials (GRTs) are one of the most rigorous methods for evaluating the effectiveness of group-based health risk prevention programs. Efficiently designing GRTs with a sample size that is sufficient for meeting the trial's power and precision goals while not wasting resources exceeding them requires estimates of the…

Survival of Patients Receiving a Primary Prevention Implantable Cardioverter-Defibrillator in Clinical Practice vs Clinical Trials

PubMed Central

Al-Khatib, Sana M.; Hellkamp, Anne; Bardy, Gust H.; Hammill, Stephen; Jackson Hall, W.; Mark, Daniel B.; Anstrom, Kevin J.; Curtis, Jeptha; Al-Khalidi, Hussein; Curtis, Lesley H.; Heidenreich, Paul; Peterson, Eric D.; Sanders, Gillian; Clapp-Channing, Nancy; Lee, Kerry L.; Moss, Arthur J.

2013-01-01

Importance Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown. Objective To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n=742) and SCD-HeFT (n=829). Design, Setting, and Patients Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score–matched patients) or the SCD-HeFT criteria (3352 propensity score–matched patients). Mortality data for the registry patients were collected through December 31, 2009. Main Outcome Measures Cox proportional hazards models were used to compare mortality from any cause. Results The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II–like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85–1.31; P=.62). Likewise, the survival among SCD-HeFT–like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry vs trial hazard ratio, 1.16; 95% CI, 0.97–1.38; P=.11). Conclusions and Relevance There was no significant difference in survival between clinical trial patients randomized to receive an ICD and a similar group of clinical registry patients who received a primary prevention ICD. Our findings support the continued use of primary prevention ICDs in similar patients seen in clinical practice. Trial Registration clinicaltrials.gov Identifier: NCT00000609 PMID:23280225

Exploring barriers and facilitators to participation of male-to-female transgender persons in preventive HIV vaccine clinical trials.

PubMed

Andrasik, Michele Peake; Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet

2014-06-01

Observed seroincidence and prevalence rates in male-to-female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group's participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia, and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (a) transgender cultural competency training, (b) creating trans-friendly environments, (c) true partnerships with local trans-friendly organizations and health care providers, (d) protocols that focus on transgender specific issues, and (e) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general.

Meta-analysis of randomized controlled trials comparing 17α-hydroxyprogesterone caproate and vaginal progesterone for the prevention of recurrent spontaneous preterm delivery.

PubMed

Oler, Elizabeth; Eke, Ahizechukwu C; Hesson, Ashley

2017-07-01

Vaginal progesterone and 17α-hydroxyprogesterone (17α-OHP) are both used to prevent preterm delivery in women who have experienced spontaneous preterm delivery (SPTD) previously. Randomized trial data of the comparative effectiveness of these interventions have been mixed. To compare the efficacy of intramuscular 17α-OHP and vaginal progesterone in the prevention of recurrent SPTD. Cochrane Central Register of Controlled Trials, African Journals Online, Embase, Google Scholar, ISI Web of Science, LILACS, CINAHL, PubMed, and registers of ongoing trials were searched using keywords related to 17α-OHP, vaginal progesterone, and preterm delivery. Randomized controlled trials published between January 1, 1966, and November 30, 2016, comparing 17α-OHP and vaginal progesterone for the prevention of recurrent SPTD during singleton pregnancies were included. Study data were extracted and meta-analyses were performed when outcomes were comparable. The meta-analyses included data from three randomized trials. Lower rates of SPTD before 34 weeks (relative risk 0.71, 95% confidence interval 0.53-0.95) and before 32 weeks (relative risk 0.62, 95% confidence interval 0.40-0.94) of pregnancy were observed among patients treated with vaginal progesterone. Vaginal progesterone and 17α-OHP were comparable for the prevention of recurrent SPTD in singleton pregnancies; vaginal progesterone could be superior. © 2017 International Federation of Gynecology and Obstetrics.

POLLUTION PREVENTION TECHNOLOGY DIFFUSION INITIATIVE (TDI)

EPA Science Inventory

Although pollution prevention (P2) technologies save money and help prevent the release of toxic and hazardous wastes into the environment, many companies are reluctant to install new equipment or change the current processes. Some of the reluctance is initiated by lack of time a...

Appraising the uptake and use of recommendations for a common outcome data set for clinical trials: a case study in fall injury prevention.

PubMed

Copsey, Bethan; Hopewell, Sally; Becker, Clemens; Cameron, Ian D; Lamb, Sarah E

2016-03-10

Many researchers and professional bodies are seeking consensus for core outcomes for clinical trials. The Prevention of Falls Network Europe (ProFaNE) developed a common outcome data set for fall injury prevention trials 10 years ago. This study assesses the impact of these recommendations. A systematic search (up to 16 January 2015) was performed using Web of Science, Scopus and PubMed for articles citing the ProFaNE recommendations. Randomised trials on fall prevention in older people were selected for further analysis. Data were extracted on study characteristics and adherence to the key domains recommended by the ProFaNE consensus: falls, fall injury, physical activity, psychological consequences and health-related quality of life. Details of non-recommended outcome measures used were also recorded. The ProFaNE recommendations were cited in a total of 464 published articles, of which 34 were randomised trials on fall prevention in older people. Only one study (3 %) reported on all core domains. Most of the trials reported on falls (n = 32/34, 94 %) as a core outcome measure. Most of the recommendations within the falls domain were well-followed. Around half of the trials reported on fall-related injury (n = 16/34, 47 %). However, none reported the number of radiologically confirmed peripheral fracture events, which is the recommended outcome measure for injury. The other key domains (quality of life, physical activity and psychological consequences) were less frequently reported on, with a lack of consistency in the outcome measures used. The ProFaNE recommendations had a limited effect on standardising the reporting of outcomes in randomised trials on fall injury prevention in older people during the search period. Authors of consensus guidelines should consider maximising buy-in by including a diversity of geographic areas and academic disciplines at the development stage and using a solid dissemination strategy.

Cotrimoxazole prophylaxis versus mefloquine intermittent preventive treatment to prevent malaria in HIV-infected pregnant women: two randomized controlled trials.

PubMed

Denoeud-Ndam, Lise; Zannou, Djimon-Marcel; Fourcade, Camille; Taron-Brocard, Clément; Porcher, Raphaël; Atadokpede, Felix; Komongui, Didier G; Dossou-Gbete, Lucien; Afangnihoun, Aldric; Ndam, Nicaise T; Girard, Pierre-Marie; Cot, Michel

2014-02-01

Malaria during pregnancy has serious consequences that are worsened by HIV infection. Malaria preventive measures for HIV-infected pregnant women include cotrimoxazole (CTX) prophylaxis given to prevent HIV-related opportunistic infections and also protective against malaria, or intermittent preventive treatment (IPTp) with an antimalarial drug. Here, we present the first study evaluating CTX efficacy versus mefloquine (MQ)-IPTp, alone and in combination, in HIV-infected pregnant women. We conducted 2 randomized, open-label, noninferiority trials in Benin. In the CTX-mandatory trial, HIV-infected women with CD4 counts of <350 per cubic millimeter received CTX either alone or with MQ-IPTp (N = 292). In the CTX-not-mandatory trial (CD4 count >350/mm), CTX was compared with MQ-IPTp (N = 140). In both the trials, the primary end point was microscopic placental parasitemia. At delivery, 1 woman in each CTX-alone treatment group exhibited placental parasitemia, versus no women in the groups receiving MQ. CTX alone demonstrated noninferiority in the CTX-mandatory trial. However, polymerase chain reaction-detected placental parasitemia was markedly reduced in the CTX + MQ group compared with CTX alone (0/105 vs. 5/103, P = 0.03). Because of insufficient recruitment in the CTX-not-mandatory trial, noninferiority could not be conclusively assessed. Dizziness and vomiting of moderate intensity were reported by 34%-37% of women receiving MQ in both the trials, versus 0%-3% in CTX groups (P < 0.0001). No serious adverse events related to these drugs were found. CTX alone provided adequate protection against malaria in HIV-infected pregnant women, although MQ-IPTp showed higher efficacy against placental infection. Although more frequently associated with dizziness and vomiting, MQ-IPTp may be an effective alternative given concerns about parasite resistance to CTX.

Multi-site Study of Diffusion Metric Variability: Characterizing the Effects of Site, Vendor, Field Strength, and Echo Time using the Histogram Distance

PubMed Central

Helmer, K. G.; Chou, M-C.; Preciado, R. I.; Gimi, B.; Rollins, N. K.; Song, A.; Turner, J.; Mori, S.

2016-01-01

MRI-based multi-site trials now routinely include some form of diffusion-weighted imaging (DWI) in their protocol. These studies can include data originating from scanners built by different vendors, each with their own set of unique protocol restrictions, including restrictions on the number of available gradient directions, whether an externally-generated list of gradient directions can be used, and restrictions on the echo time (TE). One challenge of multi-site studies is to create a common imaging protocol that will result in a reliable and accurate set of diffusion metrics. The present study describes the effect of site, scanner vendor, field strength, and TE on two common metrics: the first moment of the diffusion tensor field (mean diffusivity, MD), and the fractional anisotropy (FA). We have shown in earlier work that ROI metrics and the mean of MD and FA histograms are not sufficiently sensitive for use in site characterization. Here we use the distance between whole brain histograms of FA and MD to investigate within- and between-site effects. We concluded that the variability of DTI metrics due to site, vendor, field strength, and echo time could influence the results in multi-center trials and that histogram distance is sensitive metrics for each of these variables. PMID:27350723

Design of trials for interrupting the transmission of endemic pathogens.

PubMed

Silkey, Mariabeth; Homan, Tobias; Maire, Nicolas; Hiscox, Alexandra; Mukabana, Richard; Takken, Willem; Smith, Thomas A

2016-06-06

Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs for providing generalizable causal inferences about the impact of such interventions, including measurements of the contamination effects. The simulations were applied to the geography of Rusinga Island, Lake Victoria, Kenya, the site of the SolarMal trial on the use of odor-baited mosquito traps to eliminate Plasmodium falciparum malaria. These were used to compare variants in the proposed SWCRT designs for the SolarMal trial. Measures of contamination effects were found that could be assessed in the simulated trials. Inspired by analyses of trials of insecticide-treated nets against malaria when applied to the geography of the SolarMal trial, these measures were found to be robust to different variants of SWCRT design. Analyses of the likely extent of contamination effects supported the choice of cluster size for the trial. The SWCRT is an appropriate design for trials that assess the feasibility of local elimination of a pathogen. The effects of incomplete coverage can be estimated by analyzing the extent of contamination between arms in such trials, and the estimates also support inferences about causality. The SolarMal example illustrates how generic transmission models incorporating spatial smoothing can be used to simulate such trials for a power calculation and optimization of cluster size and randomization strategies. The approach is applicable to a range of infectious diseases transmitted via environmental reservoirs or via arthropod vectors.

FUEL ELEMENT CONSTRUCTION

DOEpatents

Simnad, M.T.

1961-08-15

A method of preventing diffusible and volatile fission products from diffusing through a fuel element container and contaminating reactor coolant is described. More specifically, relatively volatile and diffusible fission products either are adsorbed by or react with magnesium fluoride or difluoride to form stable, less volatile, less diffusible forms. The magnesium fluoride or difluoride is disposed anywhere inwardly from the outer surface of the fuel element container in order to be contacted by the fission products before they reach and contaminate the reactor coolant. (AEC)

Survival in prostate cancer prevention trial detailed

Cancer.gov

In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

Effective behaviour change techniques in the prevention and management of childhood obesity.

PubMed

Martin, J; Chater, A; Lorencatto, F

2013-10-01

Rates of childhood obesity are increasing, and it is essential to identify the active components of interventions aiming to prevent and manage obesity in children. A systematic review of behaviour change interventions was conducted to find evidence of behaviour change techniques (BCTs) that are most effective in changing physical activity and/or eating behaviour for the prevention or management of childhood obesity. An electronic search was conducted for randomised controlled trials published between January 1990 and December 2009. Of 4309 titles and abstracts screened, full texts of 135 articles were assessed, of which 17 published articles were included in this review. Intervention descriptions were coded according to the behaviour-specific CALO-RE taxonomy of BCTs. BCTs were identified and compared across obesity management (n=9) vs prevention (n=8) trials. To assess the effectiveness of individual BCTs, trials were further divided into those that were effective (defined as either a group reduction of at least 0.13 body mass index (BMI) units or a significant difference in BMI between intervention and control groups at follow-up) vs non-effective (reported no significant differences between groups). We reliably identified BCTs utilised in effective and non-effective prevention and management trials. To illustrate the relative effectiveness of each BCT, effectiveness ratios were calculated as the ratio of the number of times each BCT was a component of an intervention in an effective trial divided by the number of times they were a component of all trials. Results indicated six BCTs that may be effective components of future management interventions (provide information on the consequences of behaviour to the individual, environmental restructuring, prompt practice, prompt identification as role model/position advocate, stress management/emotional control training and general communication skills training), and one that may be effective in prevention interventions (prompting generalisation of a target behaviour). We identified that for management trials, providing information on the consequences of behaviour in general was a feature of non-effective interventions and for prevention trials, providing information on the consequences of behaviour in general, providing rewards contingent on successful behaviour and facilitating social comparison were non-effective. To design effective behaviour change programmes for the prevention and management of childhood obesity, we would recommend utilising the BCTs identified as effective in this review. The impact on intervention effectiveness of combining BCTs should be the topic of further research.

Drugs for preventing malaria in pregnant women in endemic areas: any drug regimen versus placebo or no treatment.

PubMed

Radeva-Petrova, Denitsa; Kayentao, Kassoum; ter Kuile, Feiko O; Sinclair, David; Garner, Paul

2014-10-10

Pregnancy increases the risk of malaria and this is associated with poor health outcomes for both the mother and the infant, especially during the first or second pregnancy. To reduce these effects, the World Health Organization recommends that pregnant women living in malaria endemic areas sleep under insecticide-treated bednets, are treated for malaria illness and anaemia, and receive chemoprevention with an effective antimalarial drug during the second and third trimesters. To assess the effects of malaria chemoprevention given to pregnant women living in malaria endemic areas on substantive maternal and infant health outcomes. We also summarised the effects of intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) alone, and preventive regimens for Plasmodium vivax. We searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and reference lists up to 1 June 2014. Randomized controlled trials (RCTs) and quasi-RCTs of any antimalarial drug regimen for preventing malaria in pregnant women living in malaria-endemic areas compared to placebo or no intervention. In the mother, we sought outcomes that included mortality, severe anaemia, and severe malaria; anaemia, haemoglobin values, and malaria episodes; indicators of malaria infection, and adverse events. In the baby, we sought foetal loss, perinatal, neonatal and infant mortality; preterm birth and birthweight measures; and indicators of malaria infection. We included regimens that were known to be effective against the malaria parasite at the time but may no longer be used because of parasite drug resistance. Two review authors applied inclusion criteria, assessed risk of bias and extracted data. Dichotomous outcomes were compared using risk ratios (RR), and continuous outcomes using mean differences (MD); both are presented with 95% confidence intervals (CI). We assessed the quality of evidence using the GRADE approach. Seventeen trials enrolling 14,481 pregnant women met our inclusion criteria. These trials were conducted between 1957 and 2008, in Nigeria (three trials), The Gambia (three trials), Kenya (three trials), Mozambique (two trials), Uganda (two trials), Cameroon (one trial), Burkina Faso (one trial), and Thailand (two trials). Six different antimalarials were evaluated against placebo or no intervention; chloroquine (given weekly), pyrimethamine (weekly or monthly), proguanil (daily), pyrimethamine-dapsone (weekly or fortnightly), and mefloquine (weekly), or intermittent preventive therapy with SP (given twice, three times or monthly). Trials recruited women in their first or second pregnancy (eight trials); only multigravid women (one trial); or all women (eight trials). Only six trials had adequate allocation concealment.For women in their first or second pregnancy, malaria chemoprevention reduces the risk of moderate to severe anaemia by around 40% (RR 0.60, 95% CI 0.47 to 0.75; three trials, 2503 participants, high quality evidence), and the risk of any anaemia by around 17% (RR 0.83, 95% CI 0.74 to 0.93; five trials,, 3662 participants, high quality evidence). Malaria chemoprevention reduces the risk of antenatal parasitaemia by around 61% (RR 0.39, 95% CI 0.26 to 0.58; seven trials, 3663 participants, high quality evidence), and two trials reported a reduction in febrile illness (low quality evidence). There were only 16 maternal deaths and these trials were underpowered to detect an effect on maternal mortality (very low quality evidence).For infants of women in their first and second pregnancies, malaria chemoprevention probably increases mean birthweight by around 93 g (MD 92.72 g, 95% CI 62.05 to 123.39; nine trials, 3936 participants, moderate quality evidence), reduces low birthweight by around 27% (RR 0.73, 95% CI 0.61 to 0.87; eight trials, 3619 participants, moderate quality evidence), and reduces placental parasitaemia by around 46% (RR 0.54, 95% CI 0.43 to 0.69; seven trials, 2830 participants, high quality evidence). Fewer trials evaluated spontaneous abortions, still births, perinatal deaths, or neonatal deaths, and these analyses were underpowered to detect clinically important differences.In multigravid women, chemoprevention has similar effects on antenatal parasitaemia (RR 0.38, 95% CI 0.28 to 0.50; three trials, 977 participants, high quality evidence)but there are too few trials to evaluate effects on other outcomes.In trials giving chemoprevention to all pregnant women irrespective of parity, the average effects of chemoprevention measured in all women indicated it may prevent severe anaemia (defined by authors, but at least < 8 g/L: RR 0.19, 95% CI 0.05 to 0.75; two trials, 1327 participants, low quality evidence), but consistent benefits have not been shown for other outcomes.In an analysis confined only to intermittent preventive therapy with SP, the estimates of effect and the quality of the evidence were similar.A summary of a single trial in Thailand of prophylaxis against P. vivax showed chloroquine prevented vivax infection (RR 0.01, 95% CI 0.00 to 0.20; one trial, 942 participants). Routine chemoprevention to prevent malaria and its consequences has been extensively tested in RCTs, with clinically important benefits on anaemia and parasitaemia in the mother, and on birthweight in infants.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

PubMed

Vedel, Anne G; Holmgaard, Frederik; Rasmussen, Lars S; Langkilde, Annika; Paulson, Olaf B; Lange, Theis; Thomsen, Carsten; Olsen, Peter Skov; Ravn, Hanne Berg; Nilsson, Jens C

2018-04-24

Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min -1 ·m -2 . The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group ( P =0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm 3 (interquartile range, 0-118 mm 3 ; range, 0-25 261 mm 3 ) in the low-target group versus 29 mm 3 (interquartile range, 0-143 mm 3 ; range, 0-22 116 mm 3 ) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P =0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P =0.71). No significant difference was observed in frequency of severe adverse events. Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885. © 2018 American Heart Association, Inc.

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

PubMed

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

Cancer prevention clinical trials.

PubMed

Nixon, D W

1994-01-01

Many kinds of cancer are preventable. Avoidance of tobacco would essentially eliminate lung cancer and most head and neck cancers as well. Other common cancers (breast, colon, prostate) are related to diet and therefore may also be preventable, at least in part. Abundant epidemiologic and laboratory data link specific nutrients including fat, fiber and vitamins to cancer so that appropriate manipulation of these constituents might reduce cancer risk. Determination of appropriate manipulations requires prospective clinical trials in humans. Approximately 40 such trials are in progress. Some have been completed with encouraging results. Future large scale trials will require designs that overcome the barriers of cost, large subject numbers and long study duration. The use of "intermediate markers" rather than cancer end points is a strategy that will help overcome these barriers.

Does perioperative ketamine have a role in the prevention of chronic postsurgical pain: the ROCKet trial.

PubMed

Schug, Stephan A; Peyton, Philip

2017-11-01

Identifying operations and individuals with an increased risk of chronic postsurgical pain (CPSP) has led to significant interest in interventions with the potential to achieve primary prevention of this condition. Pharmacological prevention remains controversial with a Cochrane review identifying perioperative ketamine administration as the only intervention with possible benefit although, with only small, heterogeneous studies, the authors called for a large randomised controlled trial (RCT) to confirm the validity of this result. In response to these data, a group of researchers from Australia and Hong Kong designed the ROCKet trial - Reduction Of Chronic Post-surgical Pain with Ketamine, endorsed by the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical Trials Network (CTN).

Moving from Efficacy to Effectiveness Trials in Prevention Research

PubMed Central

Marchand, Erica; Stice, Eric; Rohde, Paul; Becker, Carolyn Black

2013-01-01

Efficacy trials test whether interventions work under optimal, highly controlled conditions whereas effectiveness trials test whether interventions work with typical clients and providers in real-world settings. Researchers, providers, and funding bodies have called for more effectiveness trials to understand whether interventions produce effects under ecologically valid conditions, which factors predict program effectiveness, and what strategies are needed to successfully implement programs in practice settings. The transition from efficacy to effectiveness with preventive interventions involves unique considerations, some of which are not shared by treatment research. The purpose of this article is to discuss conceptual and methodological issues that arise when making the transition from efficacy to effectiveness research in primary, secondary, and tertiary prevention, drawing on the experiences of two complimentary research groups as well as the existing literature. We address (a) program of research, (b) intervention design and conceptualization, (c) participant selection and characteristics, (d) providers, (e) context, (f) measurement and methodology, (g) outcomes, (h) cost, and (i) sustainability. We present examples of research in eating disorder prevention that demonstrate the progression from efficacy to effectiveness trials. PMID:21092935

Improving immunogenicity and efficacy of vaccines for genital herpes containing herpes simplex virus glycoprotein D.

PubMed

Awasthi, Sita; Shaw, Carolyn; Friedman, Harvey

2014-12-01

No vaccines are approved for prevention or treatment of genital herpes. The focus of genital herpes vaccine trials has been on prevention using herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) alone or combined with glycoprotein B. These prevention trials did not achieve their primary end points. However, subset analyses reported some positive outcomes in each study. The most recent trial was the Herpevac Trial for Women that used gD2 with monophosphoryl lipid A and alum as adjuvants in herpes simplex virus type 1 (HSV-1) and HSV-2 seronegative women. Unexpectedly, the vaccine prevented genital disease by HSV-1 but not HSV-2. Currently, HSV-1 causes more first episodes of genital herpes than HSV-2, highlighting the importance of protecting against HSV-1. The scientific community is conflicted between abandoning vaccine efforts that include gD2 and building upon the partial successes of previous trials. We favor building upon success and present approaches to improve outcomes of gD2-based subunit antigen vaccines.

Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials.

PubMed

Pasquini, Marcelo C; Logan, Brent; Jones, Richard J; Alousi, Amin M; Appelbaum, Frederick R; Bolaños-Meade, Javier; Flowers, Mary E D; Giralt, Sergio; Horowitz, Mary M; Jacobsohn, David; Koreth, John; Levine, John E; Luznik, Leo; Maziarz, Richard; Mendizabal, Adam; Pavletic, Steven; Perales, Miguel-Angel; Porter, David; Reshef, Ran; Weisdorf, Daniel; Antin, Joseph H

2018-06-01

Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Community engagement in diverse populations for Alzheimer disease prevention trials.

PubMed

Romero, Heather R; Welsh-Bohmer, Kathleen A; Gwyther, Lisa P; Edmonds, Henry L; Plassman, Brenda L; Germain, Cassandra M; McCart, Michelle; Hayden, Kathleen M; Pieper, Carl; Roses, Allen D

2014-01-01

The recruitment of asymptomatic volunteers has been identified as a critical factor that is delaying the development and validation of preventive therapies for Alzheimer disease (AD). Typical recruitment strategies involve the use of convenience samples or soliciting participation of older adults with a family history of AD from clinics and outreach efforts. However, high-risk groups, such as ethnic/racial minorities, are traditionally less likely to be recruited for AD prevention studies, thus limiting the ability to generalize findings for a significant proportion of the aging population. A community-engagement approach was used to create a registry of 2311 research-ready, healthy adult volunteers who reflect the ethnically diverse local community. Furthermore, the registry's actual commitment to research was examined, through demonstrated participation rates in a clinical study. The approach had varying levels of success in establishing a large, diverse pool of individuals who are interested in participating in pharmacological prevention trials and meet the criteria for primary prevention research trials designed to delay the onset of AD. Our efforts suggest that entry criteria for the clinical trials need to be carefully considered to be inclusive of African Americans, and that sustained effort is needed to engage African Americans in pharmacological prevention approaches.

The Prevention Program for Externalizing Problem Behavior (PEP) Improves Child Behavior by Reducing Negative Parenting: Analysis of Mediating Processes in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Hanisch, Charlotte; Hautmann, Christopher; Plück, Julia; Eichelberger, Ilka; Döpfner, Manfred

2014-01-01

Background: Our indicated Prevention program for preschool children with Externalizing Problem behavior (PEP) demonstrated improved parenting and child problem behavior in a randomized controlled efficacy trial and in a study with an effectiveness design. The aim of the present analysis of data from the randomized controlled trial was to identify…

A community intervention trial of multimodal suicide prevention program in Japan: a novel multimodal community intervention program to prevent suicide and suicide attempt in Japan, NOCOMIT-J.

PubMed

Ono, Yutaka; Awata, Shuichi; Iida, Hideharu; Ishida, Yasushi; Ishizuka, Naoki; Iwasa, Hiroto; Kamei, Yuichi; Motohashi, Yutaka; Nakagawa, Atsuo; Nakamura, Jun; Nishi, Nobuyuki; Otsuka, Kotaro; Oyama, Hirofumi; Sakai, Akio; Sakai, Hironori; Suzuki, Yuriko; Tajima, Miyuki; Tanaka, Eriko; Uda, Hidenori; Yonemoto, Naohiro; Yotsumoto, Toshihiko; Watanabe, Naoki

2008-09-15

To respond to the rapid surge in the incidence of suicide in Japan, which appears to be an ongoing trend, the Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) have launched a multimodal community-based suicide prevention program, NOCOMIT-J. The primary aim of this study is to examine whether NOCOMIT-J is effective in reducing suicidal behavior in the community. This study is a community intervention trial involving seven intervention regions with accompanying control regions, all with populations of statistically sufficient size. The program focuses on building social support networks in the public health system for suicide prevention and mental health promotion, intending to reinforce human relationships in the community. The intervention program components includes a primary prevention measures of awareness campaign for the public and key personnel, secondary prevention measures for screening of, and assisting, high-risk individuals, after-care for individuals bereaved by suicide, and other measures. The intervention started in July 2006, and will continue for 3.5 years. Participants are Japanese and foreign residents living in the intervention and control regions (a total of population of 2,120,000 individuals). The present study is designed to evaluate the effectiveness of the community-based suicide prevention program in the seven participating areas. UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000460.

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT)

PubMed Central

Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-01

Introduction Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. Methods and analysis A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver ‘active’ interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to ‘active’ intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. Ethics and dissemination The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. Trial registration number ISRCTN 71002650; Pre-results. PMID:26781504

Some design issues in trials of microbicides for the prevention of HIV infection.

PubMed

Fleming, Thomas R; Richardson, Barbra A

2004-08-15

Trials for the prevention of human immunodeficiency virus (HIV) infection that evaluate microbicides provide significant design challenges. Three of these design issues deserve more careful consideration. The first issue relates to the benefits of using both blinded and unblinded control groups when the placebo regimen may not be inert and when the effectiveness of an intervention heavily depends on behavioral, as well as biological, factors. The second issue relates to the strength of evidence required for regulatory approval for the marketing of drugs and biologics when only a single pivotal phase 3 clinical trial has provided such evidence. The third issue relates to the appropriate next step after the completion of phase 1 trials, as well as the specific merits of conducting phase 2b screening trials that assess the effects on the same clinical efficacy end point that will be the primary end point in a phase 3 trial. The issues considered in microbicide trials for the prevention of HIV infection are also of importance in many other clinical scenarios.

Defining, Designing, Implementing, and Evaluating Phase 4 HIV Prevention Effectiveness Trials for Vulnerable Populations

PubMed Central

Kelly, Jeffrey A.; Spielberg, Freya; McAuliffe, Timothy L.

2008-01-01

Summary The efficacy of behavioral HIV prevention interventions has been convincingly demonstrated in a large number of randomized controlled phase 3 research outcome trials. Little research attention has been directed toward studying the effectiveness of the same interventions when delivered by providers to their own clients or community members, however. This article argues for the need to conduct phase 4 effectiveness trials of HIV prevention interventions that have been found efficacious in the research arena. Such trials can provide important information concerning the impact of interventions when applied in heterogeneous “real-world” circumstances. This article raises design issues and methodologic questions that need to be addressed in the conduct of phase 4 trials of behavioral interventions. These issues include the selection and training of service providers engaged in such trials, maintenance of fidelity to intervention protocol in provider-delivered interventions, determination of intervention core elements versus aspects that require tailoring, selection of relevant phase 4 study outcomes, interpretation of findings indicative of field effectiveness, sustainability, and other aspects of phase 4 trial design. PMID:18301131

Post-licence driver education for the prevention of road traffic crashes: a systematic review of randomised controlled trials.

PubMed

Ker, Katharine; Roberts, Ian; Collier, Timothy; Beyer, Fiona; Bunn, Frances; Frost, Chris

2005-03-01

The effectiveness of post-licence driver education for preventing road traffic crashes was quantified using a systematic review and meta-analyses of randomised controlled trials. Searches of appropriate electronic databases, the Internet and reference lists of relevant papers were conducted. The searches were not restricted by language or publication status. Data were pooled from 21 randomised controlled trials, including over 300,000 full licence-holding drivers of all ages. Nineteen trials reported subsequent traffic offences, with a pooled relative risk of 0.96 (95% confidence interval 0.94, 0.98). Fifteen trials reported traffic crashes with a pooled relative risk of 0.98 (0.96, 1.01). Four trials reported injury crashes with a pooled relative risk of 1.12 (0.88, 1.41). The results provide no evidence that post-licence driver education is effective in preventing road injuries or crashes. Although the results are compatible with a small reduction in the occurrence of traffic crashes, this may be due to selection biases or bias in the included trials.

Application of TRIZ Methodology in Diffusion Welding System Optimization

NASA Astrophysics Data System (ADS)

Ravinder Reddy, N.; Satyanarayana, V. V.; Prashanthi, M.; Suguna, N.

2017-12-01

Welding is tremendously used in metal joining processes in the manufacturing process. In recent years, diffusion welding method has significantly increased the quality of a weld. Nevertheless, diffusion welding has some extent short research and application progress. Therefore, diffusion welding has a lack of relevant information, concerned with the joining of thick and thin materials with or without interlayers, on welding design such as fixture, parameters selection and integrated design. This article intends to combine innovative methods in the application of diffusion welding design. This will help to decrease trial and error or failure risks in the welding process being guided by the theory of inventive problem solving (TRIZ) design method. This article hopes to provide welding design personnel with innovative design ideas under research and for practical application.

Worta McCaskill-Stevens, MD, MS | Division of Cancer Prevention

Cancer.gov

Dr. Worta McCaskill-Stevens is a medical oncologist and Chief of the Community Oncology and Prevention Trials Research Group, which houses the NCI Community Oncology Research Program (NCORP), a community-based clinical trials network launched in 2014. |

Retaining Hard-to-Reach Women in HIV Prevention and Vaccine Trials: Project ACHIEVE

PubMed Central

Brown-Peterside, Pamela; Rivera, Evelyn; Lucy, Debbie; Slaughter, Izzie; Ren, Leigh; Chiasson, Mary Ann; Koblin, Beryl A.

2001-01-01

Project ACHIEVE, which conducts HIV prevention research studies, maintains a women's site in the South Bronx in New York City. Owing to a focused retention effort at the South Bronx site, high retention rates were achieved in a vaccine preparedness study for women at high risk of HIV infection. Comparable retention rates have been achieved in HIV vaccine trials with similar cohorts of women at this site. These results suggest that concerns about retaining hard-to-reach populations should not cause these populations to be excluded from HIV vaccine and prevention trials. PMID:11527761

Zusanli (ST36) acupoint injection for preventing postoperative ileus: A systematic review and meta-analysis of randomized clinical trials.

PubMed

Wang, Mei; Gao, Yun-Hai; Xu, Jie; Chi, Yuan; Wei, Xiao-Bing; Lewith, George; Liu, Jian-Ping

2015-06-01

To evaluate the preventive effect of Zusanli (ST36) acupoint injections with various agents, for postoperative ileus (POI). We searched electronic databases for randomized controlled trials from inception to 1st February 2015 evaluating ST36 acupoint injection for preventing POI. Revman 5.2.0 was used for data analysis with effect estimates presented as mean difference (MD) with 95% confidence interval (CI). Statistical heterogeneity was tested using I(2) (defined as significant if I(2)>75%). We used a random effects model (REM) for pooling data with significant heterogeneity. Thirty trials involving 2967 participants were included. All trials were assessed as high risk of bias (poor methodological quality). For time to first flatus, meta-analysis favored ST36 acupoint injection of neostigmine (MD -20.70h, 95% CI -25.53 to -15.87, 15 trials, I(2)=98%, REM), vitamin B1 (MD -11.22h, 95% CI -17.01 to -5.43, 5 trials, I(2)=98%, REM), and metoclopramide (MD -15.65h, 95% CI -24.77 to -6.53, 3 trials, I(2)=94%, REM) compared to usual care alone. Meta-analysis of vitamin B1 favored ST36 acupoint injection compared to intra-muscular injection (MD -17.21h, 95% CI -21.05 to -13.36, 4 trials, I(2)=89%, REM). Similarly, for time to bowel sounds recovery and first defecation, ST36 acupoint injection also showed positive effects. ST36 acupoint injections with various agents may have a preventive effect for POI. Safety is inconclusive as few of included trials reported adverse events. Due to the poor methodological quality and likely publication bias further robust clinical trials are required to arrive at a definitive conclusion. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Commentary on "A roadmap for the prevention of dementia II. Leon Thal Symposium 2008." The Multidomain Alzheimer Preventive Trial (MAPT): a new approach to the prevention of Alzheimer's disease.

PubMed

Gillette-Guyonnet, Sophie; Andrieu, Sandrine; Dantoine, Thierry; Dartigues, Jean-François; Touchon, Jacques; Vellas, B

2009-03-01

Because no effective curative approaches are available, preventive approaches in the field of Alzheimer's disease (AD) are needed. We present the design of the ongoing Multidomain Alzheimer Preventive Trial (MAPT) Study. Several previous studies suggested that many factors may be involved in the occurrence of AD at late ages. Because of the probable multifactorial nature of AD, it seems logical to initiate multidomain interventions to examine their potential synergistic effects. The MAPT Study aims to evaluate the efficacy of a multidomain intervention (nutritional, physical, and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. The study also collects imaging and biological data that could be used in future AD prevention and treatment trials. The MAPT Study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in four French cities (Bordeaux, Limoges, Montpellier, and Toulouse). The study plans to enroll 1200 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 300 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test. The MAPT Study is the first preventive trial involving multidomain interventions. Final results should be available in 2013.

Antibiotics for preventing suppurative complications from undifferentiated acute respiratory infections in children under five years of age.

PubMed

Alves Galvão, Márcia G; Rocha Crispino Santos, Marilene Augusta; Alves da Cunha, Antonio J L

2016-02-29

Undifferentiated acute respiratory infections (ARIs) are a large and heterogeneous group of infections not clearly restricted to one specific part of the upper respiratory tract, which last for up to seven days. They are more common in pre-school children in low-income countries and are responsible for 75% of the total amount of prescribed antibiotics in high-income countries. One possible rationale for prescribing antibiotics is the wish to prevent bacterial complications. To assess the effectiveness and safety of antibiotics in preventing bacterial complications in children aged two months to 59 months with undifferentiated ARIs. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to August week 1, 2015) and EMBASE (1974 to August 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing antibiotic prescriptions with placebo or no treatment in children aged two months to 59 months with an undifferentiated ARI for up to seven days. Two review authors independently assessed trial quality and extracted and analysed data using the standard Cochrane methodological procedures. We identified four trials involving 1314 children. Three trials investigated the use of amoxicillin/clavulanic acid to prevent otitis and one investigated ampicillin to prevent pneumonia.The use of amoxicillin/clavulanic acid compared to placebo to prevent otitis showed a risk ratio (RR) of 0.70 (95% confidence interval (CI) 0.45 to 1.11, three trials, 414 selected children, moderate-quality evidence). Methods of random sequence generation and allocation concealment were not clearly stated in two trials. Performance, detection and reporting bias could not be ruled out in three trials.Ampicillin compared to supportive care (continuation of breastfeeding, clearing of the nose and paracetamol for fever control) to prevent pneumonia showed a RR of 1.05 (95% CI 0.74 to 1.49, one trial, 889 selected children, moderate-quality evidence). The trial was non-blinded. Random sequence generation and allocation concealment methods were not clearly stated, so the possibility of reporting bias could not be ruled out.Harm outcomes could not be analysed as they were expressed only in percentages.We found no studies assessing mastoiditis, quinsy, abscess, meningitis, hospital admission or death. There is insufficient evidence for antibiotic use as a means of reducing the risk of otitis or pneumonia in children up to five years of age with undifferentiated ARIs. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.

Biomarkers and biometric measures of adherence to use of ARV-based vaginal rings.

PubMed

Stalter, Randy M; Moench, Thomas R; MacQueen, Kathleen M; Tolley, Elizabeth E; Owen, Derek H

2016-01-01

Poor adherence to product use has been observed in recent trials of antiretroviral (ARV)-based oral and vaginal gel HIV prevention products, resulting in an inability to determine product efficacy. The delivery of microbicides through vaginal rings is widely perceived as a way to achieve better adherence but vaginal rings do not eliminate the adherence challenges exhibited in clinical trials. Improved objective measures of adherence are needed as new ARV-based vaginal ring products enter the clinical trial stage. To identify technologies that have potential future application for vaginal ring adherence measurement, a comprehensive literature search was conducted that covered a number of biomedical and public health databases, including PubMed, Embase, POPLINE and the Web of Science. Published patents and patent applications were also searched. Technical experts were also consulted to gather more information and help evaluate identified technologies. Approaches were evaluated as to feasibility of development and clinical trial implementation, cost and technical strength. Numerous approaches were identified through our landscape analysis and classified as either point measures or cumulative measures of vaginal ring adherence. Point measurements are those that give a measure of adherence at a particular point in time. Cumulative measures attempt to measure ring adherence over a period of time. Approaches that require modifications to an existing ring product are at a significant disadvantage, as this will likely introduce additional regulatory barriers to the development process and increase manufacturing costs. From the point of view of clinical trial implementation, desirable attributes would be high acceptance by trial participants, and little or no additional time or training requirements on the part of participants or clinic staff. We have identified four promising approaches as being high priority for further development based on the following measurements: intracellular drug levels, drug levels in hair, the accumulation of a vaginal analyte that diffuses into the ring, and the depletion of an intrinsic ring constituent. While some approaches show significant promise over others, it is recommended that a strategy of using complementary biometric and behavioural approaches be adopted to best understand participants' adherence to ARV-based ring products in clinical trials.

Exercise programs may be effective in preventing a new episode of neck pain: a systematic review and meta-analysis.

PubMed

de Campos, Tarcisio F; Maher, Chris G; Steffens, Daniel; Fuller, Joel T; Hancock, Mark J

2018-06-13

What is the effectiveness of interventions that aim to prevent a new episode of neck pain? Systematic review and meta-analysis of randomised, controlled trials. People without neck pain at study entry. Any intervention aiming to prevent a future episode of neck pain. New episode of neck pain. Five trials including a total of 3852 individuals met the inclusion criteria. The pooled results from two randomised, controlled trials (500 participants) found moderate-quality evidence that exercise reduces the risk of a new episode of neck pain (OR 0.32, 95% CI 0.12 to 0.86). One of the meta-analysed trials included some co-interventions with the exercise. There was low-quality evidence from three randomised, controlled trials (3352 participants) that ergonomic programs do not reduce the risk of a new neck pain episode (OR 1.00, 95% CI 0.74 to 1.35). This review found moderate-quality evidence supporting the effectiveness of an exercise program for reducing the risk of a new episode of neck pain. There is a need for high-quality randomised, controlled trials evaluating interventions to prevent new episodes of neck pain. PROSPERO CRD42017055174. [de Campos TF, Maher CG, Steffens D, Fuller JT, Hancock MJ (2018) Exercise programs may be effective in preventing a new episode of neck pain: a systematic review. Journal of Physiotherapy XX: XX-XX]. Copyright © 2018 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Glyburide is associated with attenuated vasogenic edema in stroke patients.

PubMed

Kimberly, W Taylor; Battey, Thomas W K; Pham, Ly; Wu, Ona; Yoo, Albert J; Furie, Karen L; Singhal, Aneesh B; Elm, Jordan J; Stern, Barney J; Sheth, Kevin N

2014-04-01

Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Using a case-control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the glyburide advantage in malignant edema and stroke-pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 (MMP-9) plasma level in large hemispheric stroke. We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial.

Efficacy Trial of a Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents: Effects at 1- and 2-Year Follow-Up

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Gau, Jeff M.; Wade, Emily

2010-01-01

Objective: To evaluate the effects of a brief group cognitive-behavioral (CB) depression prevention program for high-risk adolescents with elevated depressive symptoms at 1- and 2-year follow-up. Method: In this indicated prevention trial, 341 at-risk youths were randomized to a group CB intervention, group supportive expressive intervention, CB…

A Pilot Randomised Controlled Trial of a School-Based Resilience Intervention to Prevent Depressive Symptoms for Young Adolescents with Autism Spectrum Disorder: A Mixed Methods Analysis

ERIC Educational Resources Information Center

Mackay, Bethany A.; Shochet, Ian M.; Orr, Jayne A.

2017-01-01

Despite increased depression in adolescents with Autism Spectrum Disorder (ASD), effective prevention approaches for this population are limited. A mixed methods pilot randomised controlled trial (N = 29) of the evidence-based Resourceful Adolescent Program-Autism Spectrum Disorder (RAP-A-ASD) designed to prevent depression was conducted in…

Dietary supplements and risk of cause-specific death, cardiovascular disease, and cancer: a protocol for a systematic review and network meta-analysis of primary prevention trials.

PubMed

Schwingshackl, Lukas; Hoffmann, Georg; Buijsse, Brian; Mittag, Tamara; Stelmach-Mardas, Marta; Boeing, Heiner; Gottschald, Marion; Dietrich, Stefan; Arregui, Maria; Dias, Sofia

2015-03-26

In the Western world, dietary supplements are commonly used to prevent chronic diseases, mainly cardiovascular disease and cancer. However, there is inconsistent evidence on which dietary supplements actually lower risk of chronic disease, and some may even increase risk. We aim to evaluate the comparative safety and/or effectiveness of dietary supplements for the prevention of mortality (all-cause, cardiovascular, and cancer) and cardiovascular and cancer incidence in primary prevention trials. We will search PubMed, EMBASE, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, clinical trials.gov, and the World Health Organization International Trial Registry Platform. Randomized controlled trials will be included if they meet the following criteria: (1) minimum intervention period of 12 months; (2) primary prevention of chronic disease (is concerned with preventing the onset of diseases and conditions); (3) minimum mean age ≥18 years (maximum mean age 70 years); (4) intervention(s) include vitamins (beta-carotene, vitamin A, B vitamins, Vitamin C, Vitamin D, Vitamin E, and multivitamin supplements); fatty acids (omega-3 fatty acids, omega-6 fatty acids, monounsaturated fat); minerals (magnesium, calcium, selenium, potassium, iron, zinc, copper, iodine; multiminerals); supplements containing combinations of both vitamins and minerals; protein (amino acids); fiber; prebiotics; probiotics; synbiotics; (5) supplements are orally administered as liquids, pills, capsules, tablets, drops, ampoules, or powder; (6) report results on all-cause mortality (primary outcome) and/or mortality from cardiovascular disease or cancer, cardiovascular and/or cancer incidence (secondary outcomes). Pooled effects across studies will be calculated using Bayesian random effects network meta-analysis. Sensitivity analysis will be performed for trials lasting ≥5 years, trials with low risk of bias, trials in elderly people (≥65 years), ethnicity, geographical region, and trials in men and women. The results of the corresponding fixed effects models will also be compared in sensitivity analyses. This is a presentation of the study protocol only. Results and conclusions are pending completion of this study. Our systematic review will be of great value to consumers of supplements, healthcare providers, and policy-makers, regarding the use of dietary supplements. CRD42014014801 .

Antibiotics or probiotics as preventive measures against ventilator-associated pneumonia: a literature review

PubMed Central

2011-01-01

Introduction Mechanically ventilated critically ill patients frequently develop ventilator-associated pneumonia (VAP), a life-threatening complication. Proposed preventive measures against VAP include, but are not restricted to, selective decontamination of the digestive tract (SDD), selective oropharyngeal decontamination (SOD) and the use of probiotics. Probiotics are live bacteria that could have beneficial effects on the host by altering gastrointestinal flora. Similar to SDD and SOD, a prescription of probiotics aims at the prevention of secondary colonization of the upper and/or lower digestive tract. Methods We performed a literature review to describe the differences and similarities between SDD/SOD and probiotic preventive strategies, focusing on (a) efficacy, (b) risks, and (c) the routing of these strategies. Results Reductions in the incidence of VAP have been achieved with SDD and SOD. Two large randomized controlled trials even showed reduced mortality with these preventive strategies. Randomized controlled trials of probiotic strategies also showed a reduction of the incidence of VAP, but trials were too small to draw firm conclusions. Preventive strategies with antibiotics and probiotics may be limited due to the risk of emerging resistance to the locally applied antibiotics and the risk of probiotic-related infections, respectively. The majority of trials of SDD and SOD did not exhaustively address the issue of emerging resistance. Likewise, trials of probiotic strategies did not adequately address the risk of colonization with probiotics and probiotic-related infection. In studies of SDD and SOD the preventive strategy aimed at decontamination of the oral cavity, throat, stomach and intestines, and the oral cavity and throat, respectively. In the vast majority of studies of probiotic therapy the preventive strategy aimed at decontamination of the stomach and intestines. Conclusions Prophylactic use of antibiotics in critically ill patients is effective in reducing the incidence of VAP. Probiotic strategies deserve consideration in future well-powered trials. Future studies are needed to determine if preventive antibiotic and probiotic strategies are safe with regard to development of antibiotic resistance and probiotic infections. It should be determined whether the efficacy of probiotics improves when these agents are provided to the mouth and the intestines simultaneously. PMID:21232110

SOME DESIGN ISSUES IN PHASE 2B VERSUS PHASE 3 PREVENTION TRIALS FOR TESTING EFFICACY OF PRODUCTS OR CONCEPTS

PubMed Central

Gilbert, Peter B.

2009-01-01

SUMMARY After one or more Phase 2 trials show that a candidate preventive vaccine induces immune responses that putatively protect against an infectious disease for which there is no licensed vaccine, the next step is to evaluate the efficacy of the candidate. The trial-designer faces the question of what is the optimal size of the initial efficacy trial? Part of the answer will entail deciding between a large Phase 3 licensure trial or an intermediate-sized Phase 2b screening trial, the latter of which may be designed to directly contribute to the evidence-base for licensing the candidate, or, to test a scientific concept for moving the vaccine field forward, acknowledging that the particular candidate will never be licensable. Using the HIV vaccine field as a case study, we describe distinguishing marks of Phase 2b and Phase 3 prevention efficacy trials, and compare the expected utility of these trial types using Pascal’s decision-theoretic framework. By integrating values/utilities on (1) Correct or incorrect conclusions resulting from the trial; (2) Timeliness of obtaining the trial results; (3) Precision for estimating the intervention effect; and (4) Resources expended; this decision framework provides a more complete approach to selecting the optimal efficacy trial size than a traditional approach that is based primarily on power calculations. Our objective is to help inform the decision-process for planning an initial efficacy trial design. PMID:20419758

"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial.

PubMed

Cortellini, Mauro; Berrino, Franco; Pasanisi, Patrizia

2017-01-01

Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test ( P =0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single answer to sort out the short blanket syndrome.

Rationale and baseline characteristics of PREVENT: a second-generation intervention trial in subjects at-risk (prodromal) of developing first-episode psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for the prevention of psychosis.

PubMed

Bechdolf, Andreas; Müller, Hendrik; Stützer, Hartmut; Wagner, Michael; Maier, Wolfgang; Lautenschlager, Marion; Heinz, Andreas; de Millas, Walter; Janssen, Birgit; Gaebel, Wolfgang; Michel, Tanja Maria; Schneider, Frank; Lambert, Martin; Naber, Dieter; Brüne, Martin; Krüger-Özgürdal, Seza; Wobrock, Thomas; Riedel, Michael; Klosterkötter, Joachim

2011-09-01

Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as well as placebo and CM for the prevention of psychosis in a randomized, double-blind, placebo-controlled trial with regard to the antipsychotic intervention and a randomized controlled trial with regard to the CBT intervention with blinded ratings. The hypotheses are first that CBT and aripiprazole and CM are superior to placebo and CM and second that CBT is not inferior to aripiprazole and CM combined. The primary outcome is transition to psychosis. By November 2010, 156 patients were recruited into the trial. The subjects were substantially functionally compromised (Social and Occupational Functioning Assessment Scale mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to randomization, 51.5% of the participants preferred to be randomized into the CBT arm, whereas only 12.9% preferred pharmacological treatment. First, assessments of audiotaped treatment sessions confirmed the application of CBT-specific skills in the CBT condition and the absence of those in CM. The overall quality rating of the CBT techniques applied in the CBT condition was good. When the final results of the trial are available, PREVENT will substantially expand the current limited evidence base for best clinical practice in people at-risk (prodromal) of first-episode psychosis.

Pressure ulcer risk assessment and prevention: a systematic comparative effectiveness review.

PubMed

Chou, Roger; Dana, Tracy; Bougatsos, Christina; Blazina, Ian; Starmer, Amy J; Reitel, Katie; Buckley, David I

2013-07-02

Pressure ulcers are associated with substantial health burdens but may be preventable. To review the clinical utility of pressure ulcer risk assessment instruments and the comparative effectiveness of preventive interventions in persons at higher risk. MEDLINE (1946 through November 2012), CINAHL, the Cochrane Library, grant databases, clinical trial registries, and reference lists. Randomized trials and observational studies on effects of using risk assessment on clinical outcomes and randomized trials of preventive interventions on clinical outcomes. Multiple investigators abstracted and checked study details and quality using predefined criteria. One good-quality trial found no evidence that use of a pressure ulcer risk assessment instrument, with or without a protocolized intervention strategy based on assessed risk, reduces risk for incident pressure ulcers compared with less standardized risk assessment based on nurses' clinical judgment. In higher-risk populations, 1 good-quality and 4 fair-quality randomized trials found that more advanced static support surfaces were associated with lower risk for pressure ulcers compared with standard mattresses (relative risk range, 0.20 to 0.60). Evidence on the effectiveness of low-air-loss and alternating-air mattresses was limited, with some trials showing no clear differences from advanced static support surfaces. Evidence on the effectiveness of nutritional supplementation, repositioning, and skin care interventions versus usual care was limited and had methodological shortcomings, precluding strong conclusions. Only English-language articles were included, publication bias could not be formally assessed, and most studies had methodological shortcomings. More advanced static support surfaces are more effective than standard mattresses for preventing ulcers in higher-risk populations. The effectiveness of formal risk assessment instruments and associated intervention protocols compared with less standardized assessment methods and the effectiveness of other preventive interventions compared with usual care have not been clearly established.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention.

PubMed

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.

Characteristics of Women Enrolled into a Randomized Clinical Trial of Dapivirine Vaginal Ring for HIV-1 Prevention

PubMed Central

Palanee-Phillips, Thesla; Schwartz, Katie; Brown, Elizabeth R.; Govender, Vaneshree; Mgodi, Nyaradzo; Kiweewa, Flavia Matovu; Nair, Gonasagrie; Mhlanga, Felix; Siva, Samantha; Bekker, Linda-Gail; Jeenarain, Nitesha; Gaffoor, Zakir; Martinson, Francis; Makanani, Bonus; Naidoo, Sarita; Pather, Arendevi; Phillip, Jessica; Husnik, Marla J.; van der Straten, Ariane; Soto-Torres, Lydia; Baeten, Jared

2015-01-01

Introduction Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges. Methods ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial. Results Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18–45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22–31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis. Conclusions African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention. PMID:26061040

Mind the gap: An empirical study of post-trial access in HIV biomedical prevention trials.

PubMed

Haire, Bridget; Jordens, Christopher

2015-08-01

The principle of providing post-trial access for research participants to successful products of that research is widely accepted and has been enshrined in various declarations and guidelines. While recent ethical guidelines recognise that the responsibility to provide post-trial access extends to sponsors, regulators and government bodies as well as to researchers, it is the researchers who have the direct duty of care to participants. Researchers may thus need to act as advocates for trial participants, especially where government bodies, sponsors, and regulatory bodies have complex interests vested in decisions about whether or not new interventions are made available, how, and to whom. This paper provides an empirical account of post-trial access in the context of HIV prevention research. It describes both access to the successful products of research and the provision antiretroviral drugs for trial participants who acquire HIV. First, we provide evidence that, in the current system, there is considerable variation in the duration and timeliness of access. We then argue that by analysing the difficulties faced by researchers to this point, and their efforts to meet this obligation, much can be learned about how to secure post-trial access in HIV biomedical preventions trials. While researchers alone have a limited obligation, their advocacy on behalf of trial participants may be necessary to call the other parties to account. © 2013 John Wiley & Sons Ltd.

[How to prevent hazards and to reduce risk in clinical trials?].

PubMed

Czarkowski, Marek

2008-12-01

Different stakeholders involved in clinical trials are exposed to hazards related with this biomedical research. Beside clinical trials participants other important stakeholders are: investigators, sponsors, centers and clinical research organizations. Hazard prevention needs effective methods of hazard disclosure and analysis. A reduction of risks related with clinical trials is possible due to education, training, inspections, research discipline and penalties. Effective ways of hazard elimination or hazard reduction should be developed as well. Education and training should be offered to all stakeholders but their forms and contents should be adapted to different types of stakeholders. Direct control of the clinical trials should be held by stakeholders conducting clinical trials and outside inspections should be done by other institutions like clinical research organizations, research ethics committees and The Office for Registration of Medicinal Products, Medical Devices and Biocidal Products. Serious oversight is an absence of any independent inspection during a phase of publication of clinical trial results. We should not accept any exception from the golden rule that results of all clinical trials must be published. Indemnity for damages is a popular way of compensation for clinical trials participants. Investigators, sponsors and centers should have valid liability insurance. Drastic measures for reduction of risks in clinical trials are different kinds of penalties. They should prevent participation of unreliable stakeholders and promote those who respect regulations and high ethical standards.

Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease.

PubMed

Wang, Winfred C; Dwan, Kerry

2013-11-14

In sickle cell disease, a common inherited haemoglobin disorder, abnormal haemoglobin distorts red blood cells, causing anaemia, vaso-occlusion and dysfunction in most body organs. Without intervention, stroke affects around 10% of children with sickle cell anaemia (HbSS) and recurrence is likely. Chronic blood transfusion dilutes the sickled red blood cells, reducing the risk of vaso-occlusion and stroke. However, side effects can be severe. To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease to prevent first stroke or recurrences. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and conference proceedings.Date of the latest search of the Group's Haemoglobinopathies Trials Register: 28 January 2013. Randomised and quasi-randomised controlled trials comparing blood transfusion as prophylaxis for stroke in people with sickle cell disease to alternative or no treatment. Both authors independently assessed the risk of bias of the included trials and extracted data. Searches identified three eligible randomised trials (n = 342). The first two trials addressed the use of chronic transfusion to prevent primary stroke; the third utilized the drug hydroxycarbamide (hydroxyurea) and phlebotomy to prevent both recurrent (secondary) stroke and iron overload in patients who had already experienced an initial stroke. In the first trial (STOP) a chronic transfusion regimen for maintaining sickle haemoglobin lower than 30% was compared with standard care in 130 children with sickle cell disease judged (through transcranial Doppler ultrasonography) as high-risk for first stroke. During the trial, 11 children in the standard care group suffered a stroke compared to one in the transfusion group, odds ratio 0.08 (95% confidence interval 0.01 to 0.66). This meant the trial was terminated early. The transfusion group had a high complications rate, including iron overload, alloimmunisation, and transfusion reactions. The second trial (STOP II) investigated risk of stroke when transfusion was stopped after at least 30 months in this population. The trial closed early due to a significant difference in risk of stroke between participants who stopped transfusion and those who continued as measured by reoccurrence of abnormal velocities on Doppler examination or the occurrence of overt stroke in the group that stopped transfusion. The third trial (SWiTCH) was a non-inferiority trial comparing transfusion and iron chelation (standard management) with hydroxyurea and phlebotomy (alternative treatment) with the combination endpoint of prevention of stroke recurrence and reduction of iron overload. This trial was stopped early after enrolment and follow up of 133 children because of analysis showing futility in reaching the composite primary endpoint. The stroke rate (seven strokes on hydroxyurea and phlebotomy, none on transfusion and chelation, odds ratio 16.49 (95% confidence interval 0.92 to 294.84)) was within the non-inferiority margin, but the liver iron content was not better in the alternative arm. The STOP trial demonstrated a significantly reduced risk of stroke in participants with abnormal transcranial Doppler ultrasonography velocities receiving regular blood transfusions. The follow-up trial (STOP 2) indicated that individuals may revert to former risk status if transfusion is discontinued. The degree of risk must be balanced against the burden of chronic transfusions. The combination of hydroxyurea and phlebotomy is not as effective as "standard" transfusion and chelation in preventing secondary stroke and iron overload. Ongoing multicentre trials are investigating the use of chronic transfusion to prevent silent infarcts, the use of hydroxyurea as an alternative to transfusion in children with abnormal transcranial Doppler ultrasonography velocities, and the use of hydroxyurea to prevent conversion of transcranial Doppler ultrasonography velocities from conditional (borderline) to abnormal values.

Efficacy of homocysteine lowering therapy with folic acid in stroke prevention: a meta-analysis

PubMed Central

Lee, Meng; Hong, Keun-Sik; Chang, Shen-Chih; Saver, Jeffrey L.

2010-01-01

Background and Purpose Although lower serum homocysteine concentration is associated with a reduced risk of stroke in epidemiologic studies, randomized controlled trials (RCTs) have yielded mixed findings regarding the effect of therapeutic homocysteine lowering on stroke prevention. We performed a meta-analysis of RCTs to assess the efficacy of folic acid supplementation in the prevention of stroke. Methods Salient trials were identified by formal literature search. Relative risk (RR) with 95% confidence interval (CI) was used as a measure of the association between folic acid supplementation and risk of stroke, pooling data across trials using a fixed-effects model. Results The search identified 13 RCTs of folic acid therapy to reduce homocysteine, enrolling 39,005 participants, in which stroke was reported as an outcome measure. Across all trials, folic acid supplementation was associated with a trend toward mild benefit that did not reach statistical significance in reducing the risk of stroke (RR 0.93, 95% CI 0.85-1.03; p=0.16). The RR for non-secondary prevention trials was 0.89 (95% CI 0.79-0.99; p=0.03). In stratified analyses, a greater beneficial effect was seen in the trials testing combination therapy of folic acid plus vitamins B6 and B12 (RR 0.83, 0.71-0.97; p=0.02) and in the trials which disproportionately enrolled male patients (men/women > 2, RR 0.84, 0.74-0.94; p=0.003). Conclusions Folic acid supplementation did not demonstrate a major effect in averting stroke. However, potential mild benefits in primary stroke prevention, especially when folate is combined with B vitamins and in male patients, merit further investigation. PMID:20413740

Undercoat prevents blistering of silver plating at elevated temperatures

NASA Technical Reports Server (NTRS)

Kuster, C. A.

1967-01-01

Gold undercoat prevents blistering in the silver plating of Inconel 718 seals from steam at high temperatures. The undercoat is diffused into the surface of the parent metal by baking prior to silver plating.

Primary prevention of gestational diabetes mellitus through nutritional factors: a systematic review.

PubMed

Donazar-Ezcurra, Mikel; López-Del Burgo, Cristina; Bes-Rastrollo, Maira

2017-01-13

Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with onset during pregnancy, is increasing worldwide, mostly because obesity among women of reproductive age is continuously escalating. GDM is associated with adverse maternal and fetal outcomes. The aim of this article was to systematically review literature on the effectiveness of nutritional factors before or during pregnancy to prevent GDM. We assessed the primary prevention of GDM through nutritional factors, as diet and supplements. We searched on PubMed, Cochrane Databases and ClinicalTrials.gov from inception to June 2016. Clinical trials and adjusted prospective cohort studies were included. Eight clinical trials and twenty observational studies assessing the association between dietary factors and primary prevention of GDM were included. Furthermore, six clinical trials and two observational studies related to supplements were also added. Only two nutritional interventions were found to significantly reduce the incidence of GDM, besides the supplements. However, the observational studies showed that a higher adherence to a healthier dietary pattern can prevent the incidence of GDM, especially in high risk population before getting pregnant. The results indicate that there may be some benefits of some nutritional factors to prevent GDM. However, better-designed studies are required to generate higher quality evidence. At the moment, no strong conclusions can be drawn with regard to the best intervention for the prevention of GDM.

Interventions for preventing lower limb soft-tissue running injuries.

PubMed

Yeung, Simon S; Yeung, Ella W; Gillespie, Lesley D

2011-07-06

Overuse soft-tissue injuries occur frequently in runners. Stretching exercises, modification of training schedules, and the use of protective devices such as braces and insoles are often advocated for prevention. This is an update of a review first published in 2001. To assess the effects of interventions for preventing lower limb soft-tissue running injuries. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2011); The Cochrane Library 2010, Issue 4; MEDLINE (1966 to January 2011); EMBASE (1980 to January 2011); and international trial registries (17 January 2011). Randomised or quasi-randomised trials evaluating interventions to prevent lower limb soft-tissue running injuries. Two authors independently assessed risk of bias (relating to sequence generation, allocation concealment, blinding, incomplete outcome data) and extracted data. Data were adjusted for clustering if necessary and pooled using the fixed-effect model when appropriate. We included 25 trials (30,252 participants). Participants were military recruits (19 trials), runners from the general population (three trials), soccer referees (one trial), and prisoners (two trials). The interventions tested in the included trials fell into four main preventive strategies: exercises, modification of training schedules, use of orthoses, and footwear and socks. All 25 included trials were judged as 'unclear' or 'high' risk of bias for at least one of the four domains listed above.We found no evidence that stretching reduces lower limb soft-tissue injuries (6 trials; 5130 participants; risk ratio [RR] 0.85, 95% confidence interval [95% CI] 0.65 to 1.12). As with all non-significant results, this is compatible with either a reduction or an increase in soft-tissue injuries. We found no evidence to support a training regimen of conditioning exercises to improve strength, flexibility and coordination (one trial; 1020 participants; RR 1.20, 95% CI 0.77 to 1.87).We found no evidence that a longer, more gradual increase in training reduces injuries in novice runners (one trial; 486 participants; RR 1.02, 95% CI 0.72 to 1.45). There was some evidence from a poor quality trial that additional training resulted in a significant increase in the number of naval recruits with shin splints (one trial; 1670 participants; RR 2.02, 95% CI 1.11 to 3.70). There was limited evidence that injuries were less frequent in prisoners when running duration (one trial; 69 participants; RR 0.41, 95% CI 0.21 to 0.79) or frequency (one trial; 58 participants; RR 0.19, 95% CI 0.06 to 0.66) were reduced.Patellofemoral braces appear to be effective for preventing anterior knee pain (two trials; 227 participants; RR 0.41, 95% CI 0.24 to 0.67).Custom-made biomechanical insoles may be more effective than no insoles for reducing shin splints (medial tibial stress syndrome) in military recruits (one trial; 146 participants; RR 0.24, 95% CI 0.08 to 0.69).We found no evidence in military recruits that wearing running shoes based on foot shape, rather than standard running shoes, significantly reduced rate of running injuries (2 trials; 5795 participants; Rate Ratio 1.03, 95% CI 0.93 to 1.14). Overall, the evidence base for the effectiveness of interventions to reduce soft-tissue injury after intensive running is very weak, with few trials at low risk of bias. More well-designed and reported RCTs are needed that test interventions in recreational and competitive runners.

Support surfaces for pressure ulcer prevention.

PubMed

McInnes, Elizabeth; Jammali-Blasi, Asmara; Bell-Syer, Sally E M; Dumville, Jo C; Middleton, Victoria; Cullum, Nicky

2015-09-03

Pressure ulcers (i.e. bedsores, pressure sores, pressure injuries, decubitus ulcers) are areas of localised damage to the skin and underlying tissue. They are common in the elderly and immobile, and costly in financial and human terms. Pressure-relieving support surfaces (i.e. beds, mattresses, seat cushions etc) are used to help prevent ulcer development. This systematic review seeks to establish:(1) the extent to which pressure-relieving support surfaces reduce the incidence of pressure ulcers compared with standard support surfaces, and,(2) their comparative effectiveness in ulcer prevention. In April 2015, for this fourth update we searched The Cochrane Wounds Group Specialised Register (searched 15 April 2015) which includes the results of regular searches of MEDLINE, EMBASE and CINAHL and The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 3). Randomised controlled trials (RCTs) and quasi-randomised trials, published or unpublished, that assessed the effects of any support surface for prevention of pressure ulcers, in any patient group or setting which measured pressure ulcer incidence. Trials reporting only proxy outcomes (e.g. interface pressure) were excluded. Two review authors independently selected trials. Data were extracted by one review author and checked by another. Where appropriate, estimates from similar trials were pooled for meta-analysis. For this fourth update six new trials were included, bringing the total of included trials to 59.Foam alternatives to standard hospital foam mattresses reduce the incidence of pressure ulcers in people at risk (RR 0.40 95% CI 0.21 to 0.74). The relative merits of alternating- and constant low-pressure devices are unclear. One high-quality trial suggested that alternating-pressure mattresses may be more cost effective than alternating-pressure overlays in a UK context.Pressure-relieving overlays on the operating table reduce postoperative pressure ulcer incidence, although two trials indicated that foam overlays caused adverse skin changes. Meta-analysis of three trials suggest that Australian standard medical sheepskins prevent pressure ulcers (RR 0.56 95% CI 0.32 to 0.97).  People at high risk of developing pressure ulcers should use higher-specification foam mattresses rather than standard hospital foam mattresses. The relative merits of higher-specification constant low-pressure and alternating-pressure support surfaces for preventing pressure ulcers are unclear, but alternating-pressure mattresses may be more cost effective than alternating-pressure overlays in a UK context. Medical grade sheepskins are associated with a decrease in pressure ulcer development. Organisations might consider the use of some forms of pressure relief for high risk patients in the operating theatre.

Immunotherapy trials for type 1 diabetes: the contribution of George Eisenbarth.

PubMed

Skyler, Jay S; Pugliese, Alberto

2013-06-01

Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic β-cells, and as such it should respond to immunotherapy. George Eisenbarth gave many significant contributions to this field. He has been involved at some level in most immunotherapy trials during the past three decades. He was among the pioneers who attempted immunotherapy approaches in patients with recent-onset T1D. In the early 1980s he began studying relatives of those with the disease, leading to the concept that T1D was a chronic autoimmune disease, in which islet autoimmune responses would silently destroy β-cells and cause progressive impairment of insulin secretion, years to months before a diagnosis was made. Consequently, he was one of the first to attempt immune intervention in people at high risk of T1D. Throughout his career he developed autoantibody assays and predictive models (which included metabolic testing and later genetics) to identify individuals at risk of T1D. He provided seminal intellectual contributions and critical tools for prevention trials. His focus on insulin as a critical autoantigen led to multiple prevention trials, including the Diabetes Prevention Trial-Type 1 (DPT-1), which studied both parenteral and oral insulin. In the DPT-1 Oral Insulin Trial, a cohort with higher levels of insulin autoantibodies was identified that appeared to have delayed disease progression. Type 1 Diabetes TrialNet is conducting a new trial to verify or refute this observation. Moreover, George identified and tested in the mouse small molecules that block or modulate presentation of a key insulin peptide and in turn prevent the activation of insulin-specific T-lymphocytes. Thus, we believe his greatest contribution is yet to come, as in the near future we should see this most recent work translate into clinical trials.

Effects of folic acid on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

PubMed Central

Vollset, Stein Emil; Clarke, Robert; Lewington, Sarah; Ebbing, Marta; Halsey, Jim; Lonn, Eva; Armitage, Jane; Manson, JoAnn E; Hankey, Graeme J; Spence, J David; Galan, Pilar; Bønaa, Kaare H; Jamison, Rex; Gaziano, J Michael; Guarino, Peter; Baron, John A; Logan, Richard FA; Giovannucci, Edward L; den Heijer, Martin; Ueland, Per M; Bennett, Derrick; Collins, Rory; Peto, Richard

2013-01-01

Summary Background Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials. Methods Meta-analyses of data on each individual in all placebo-controlled trials of folic acid for prevention of cardiovascular disease (10 trials, n=46,969) or colorectal adenoma (3 trials, n=2652) that recorded cancer incidence and recruited >500 participants. All trials were evenly randomised. Risk ratios (RRs) compare those allocated folic acid vs those allocated placebo, giving cancer incidence rate ratios (among those still free of cancer) during, but not after the scheduled treatment period. Findings During a weighted mean follow-up duration of 5.5 years, allocation to folic acid quadrupled plasma folate, but had no statistically significant effect on overall cancer incidence (1904 vs 1809 cancers, RR=1.06 [95%CI 0.99–1.13], p=0.10; trend with duration of treatment p=0.46). There was no significant heterogeneity between the results of individual trials (p=0.23), or between the cadiovascular prevention trials and the adenoma prevention trials (p=0.13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast or any other specific site. Interpretation Folic acid supplementation does not substantially increase or decrease site-specific cancer incidence during the first 5 years of treatment. Funding British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency. PMID:23352552

Pressure ulcer prevention in patients with advanced illness.

PubMed

White-Chu, E Foy; Reddy, Madhuri

2013-03-01

Pressure ulcers can be challenging to prevent, particularly in patients with advanced illnesses. This review summarizes the relevant literature since 2011. Through a MEDLINE and CINAHL database search from January 1, 2011 to June 1, 2012, a total of 14 abstracts were found addressing the prevention of pressure ulcers in persons with advanced illness. Search terms included pressure ulcer, prevention, and control. Advanced illness was defined as patients transitioning from curative to supportive and palliative care. Ten original studies and four review articles specifically addressed pressure ulcer prevention. There were four articles that specifically addressed patients with advanced illness. The studies varied in quality. One systematic review, one randomized controlled trial, three prospective trials, two retrospective trials, one cost-effectiveness analysis, one quality improvement project, one comparative descriptive design, and four review articles were found. The interventions for pressure ulcer prevention were risk assessment, repositioning, surface selection, nutritional support and maintenance of skin integrity with or without incontinence. The quality of pressure ulcer prevention studies in persons with advanced illness is poor. Increased number and higher quality studies are needed to further investigate this important topic for these fragile patients.

Alzheimer's Prevention Education: If We Build It, Will They Come? www.AlzU.org.

PubMed

Isaacson, R S; Haynes, N; Seifan, A; Larsen, D; Christiansen, S; Berger, J C; Safdieh, J E; Lunde, A M; Luo, A; Kramps, M; McInnis, M; Ochner, C N

2014-01-01

Internet-based educational interventions may be useful for impacting knowledge and behavioral change. However, in AD prevention, little data exists about which educational tools work best in terms of learning and interest in participating in clinical trials. Primary: Assess effectiveness of interactive webinars vs. written blog-posts on AD prevention learning. Secondary: Evaluate the effect of AD prevention education on interest in participating in clinical trials; Assess usability of, and user perceptions about, an online AD education research platform; Classify target populations (demographics, learning needs, interests). Observational. Online. Men/Women, aged 25+, recruited via facebook.com. Alzheimer's Universe (www.AlzU.org) education research platform. Pre/post-test performance, self-reported Likert-scale ratings, completion rates. Over two-weeks, 4268 visits were generated. 503 signed-up for a user account (11.8% join rate), 196 participated in the lessons (39.0%) and 100 completed all beta-testing steps (19.9%). Users randomized to webinar instruction about AD prevention and the stages of AD demonstrated significant increases (p=0.01) in pre vs. post-testing scores compared to blog-post intervention. Upon joining, 42% were interested in participating in a clinical trial in AD prevention. After completing all beta-test activities, interest increased to 86%. Users were primarily women and the largest category was children of AD patients. 66.3% joined to learn more about AD prevention, 65.3% to learn more about AD treatment. Webinar-based education led to significant improvements in learning about AD prevention and the stages of AD. AlzU.org participation more than doubled interest in AD prevention clinical trial participation. Subjects were quickly and cost-effectively recruited, and highly satisfied with the AD education research platform. Based on these data, we will further refine AlzU.org prior to public launch and aim to study the effectiveness of 25 interactive webinar-based vs. blog-post style lessons on learning and patient outcomes, in a randomized, within-subjects design trial.

Recent development of a jet-diffuser ejector

NASA Technical Reports Server (NTRS)

Alperin, M.; Wu, J. J.

1980-01-01

The paper considers thrust augmenting ejectors in which the processes of mixing and diffusion are partly carried out downstream of the ejector solid surfaces. A jet sheet surrounding the periphery of a widely diverging diffuser prevents separation and forms a gaseous, curved surface to provide effective diffuser ratio and additional length for mixing of primary and induced flows. Three-dimensional potential flow methods achieved a large reduction in the length of the associated solid surface; primary nozzle design further reduced the volume required by the jet-diffuser ejectors, resulting in thrust augmentation in excess of two, and an overall length of about 2 1/2 times the throat width.

Adaptation and dissemination of an evidence-based obesity prevention intervention: design of a comparative effectiveness trial.

PubMed

Buscemi, Joanna; Odoms-Young, Angela; Stolley, Melinda L; Blumstein, Lara; Schiffer, Linda; Berbaum, Michael L; McCaffrey, Jennifer; Montoya, Anastasia McGee; Braunschweig, Carol; Fitzgibbon, Marian L

2014-07-01

Low-income youth are at increased risk for excess weight gain. Although evidence-based prevention programs exist, successful adaptation to provide wide dissemination presents a challenge. Hip-Hop to Health (HH) is a school-based obesity prevention intervention that targets primarily preschool children of low-income families. In a large randomized controlled trial, HH was found to be efficacious for prevention of excessive weight gain. The Expanded Food and Nutrition Education Program (EFNEP) and the Supplemental Nutrition Assistance Program-Education (SNAP-Ed) are USDA-funded nutrition education programs offered to low-income families, and may provide an ideal platform for the wide dissemination of evidence-based obesity prevention programs. A research-practice partnership was established in order to conduct formative research to guide the adaptation and implementation of HH through EFNEP and SNAP-Ed. We present the design and method of a comparative effectiveness trial that will determine the efficacy of HH when delivered by peer educators through these programs compared to the standard EFNEP and SNAP-Ed nutrition education (NE) curriculum. Results from this trial will inform larger scale dissemination. The dissemination of HH through government programs has the potential to increase the reach of efficacious obesity prevention programs that target low-income children and families. Copyright © 2014 Elsevier Inc. All rights reserved.

Adaptation and Dissemination of an Evidence-Based Obesity Prevention Intervention: Design of a Comparative Effectiveness Trial

PubMed Central

Buscemi, Joanna; Odoms-Young, Angela; Stolley, Melinda L.; Blumstein, Lara; Schiffer, Linda; Berbaum, Michael L.; McCaffrey, Jennifer; Montoya, Anastasia McGee; Braunschweig, Carol; Fitzgibbon, Marian L.

2014-01-01

Low-income youth are at increased risk for excess weight gain. Although evidence-based prevention programs exist, successful adaptation to provide wide dissemination presents a challenge. Hip-Hop to Health (HH) is a school-based obesity prevention intervention that targets primarily preschool children of low-income families. In a large randomized controlled trial, HH was found to be efficacious for prevention of excessive weight gain. The Expanded Food and Nutrition Education Program (EFNEP) and the Supplemental Nutrition Assistance Program--Education (SNAP-Ed) are USDA-funded nutrition education programs offered to low-income families, and may provide an ideal platform for the wide dissemination of evidence-based obesity prevention programs. A research-practice partnership was established in order to conduct formative research to guide the adaptation and implementation of HH through EFNEP and SNAP-Ed. We present the design and method of a comparative effectiveness trial that will determine the efficacy of HH when delivered by peer educators through these programs compared to the standard EFNEP and SNAP-Ed nutrition education (NE) curriculum. Results from this trial will inform larger scale dissemination. The dissemination of HH through government programs has the potential to increase the reach of efficacious obesity prevention programs that target low-income children and families. PMID:24952282

Ongoing Use of Data and Specimens from NCI Sponsored Cancer Prevention Clinical Trials in the Community Clinical Oncology Program

PubMed Central

Minasian, Lori; Tangen, Catherine M.; Wickerham, D. Lawrence

2015-01-01

Large cancer prevention trials provide opportunities to collect a wide array of data and biospecimens at study entry and longitudinally, for a healthy, aging population without cancer. This provides an opportunity to use pre-diagnostic data and specimens to evaluate hypotheses about the initial development of cancer. This paper reports on strides made by, and future possibilities for, the use of accessible biorepositories developed from precisely annotated samples obtained through large-scale National Cancer Institute (NCI)-sponsored cancer prevention clinical trials conducted by the NCI Cooperative Groups. These large cancer prevention studies, which have enrolled over 80,000 volunteers, continue to contribute to our understanding of cancer development more than 10 years after they were closed. PMID:26433556

Early amniotomy and early oxytocin for prevention of, or therapy for, delay in first stage spontaneous labour compared with routine care

PubMed Central

Wei, Shuqin; Wo, Bi Lan; Qi, Hui-Ping; Xu, Hairong; Luo, Zhong-Cheng; Roy, Chantal; Fraser, William D

2014-01-01

Background Caesarean section rates are over 20% in many developed countries. The main diagnosis contributing to the high rate in nulliparae is dystocia or prolonged labour. The present review assesses the effects of a policy of early amniotomy with early oxytocin administration for the prevention of, or the therapy for, delay in labour progress. Objectives To estimate the effects of early augmentation with amniotomy and oxytocin for prevention of, or therapy for, delay in labour progress on the caesarean birth rate and on indicators of maternal and neonatal morbidity. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (15 February 2012), MEDLINE (1966 to 15 February 2012), EMBASE (1980 to 15 February 2012), CINAHL (1982 to 15 February 2012), MIDIRS (1985 to February 2012) and contacted authors for data from unpublished trials. Selection criteria Randomized and quasi-randomized controlled trials that compared oxytocin and amniotomy with expectant management. Data collection and analysis Three review authors extracted data independently. We stratified the analyses into ’Prevention Trials’ and ’Therapy Trials’ according to the status of the woman at the time of randomization. Participants in the ’Prevention Trials’ were unselected women, without slow progress in labour, who were randomized to a policy of early augmentation or to routine care. In ’Treatment Trials’ women were eligible if they had an established delay in labour progress. Main results For this update, we have included a further two new clinical trials. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) −1.28 hours; 95% CI −1.97 to −0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. Authors’ conclusions In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care. PMID:22972098

Effectiveness of an implementation optimisation intervention aimed at increasing parent engagement in HENRY, a childhood obesity prevention programme - the Optimising Family Engagement in HENRY (OFTEN) trial: study protocol for a randomised controlled trial.

PubMed

Bryant, Maria; Burton, Wendy; Cundill, Bonnie; Farrin, Amanda J; Nixon, Jane; Stevens, June; Roberts, Kim; Foy, Robbie; Rutter, Harry; Hartley, Suzanne; Tubeuf, Sandy; Collinson, Michelle; Brown, Julia

2017-01-24

Family-based interventions to prevent childhood obesity depend upon parents' taking action to improve diet and other lifestyle behaviours in their families. Programmes that attract and retain high numbers of parents provide an enhanced opportunity to improve public health and are also likely to be more cost-effective than those that do not. We have developed a theory-informed optimisation intervention to promote parent engagement within an existing childhood obesity prevention group programme, HENRY (Health Exercise Nutrition for the Really Young). Here, we describe a proposal to evaluate the effectiveness of this optimisation intervention in regard to the engagement of parents and cost-effectiveness. The Optimising Family Engagement in HENRY (OFTEN) trial is a cluster randomised controlled trial being conducted across 24 local authorities (approximately 144 children's centres) which currently deliver HENRY programmes. The primary outcome will be parental enrolment and attendance at the HENRY programme, assessed using routinely collected process data. Cost-effectiveness will be presented in terms of primary outcomes using acceptability curves and through eliciting the willingness to pay for the optimisation from HENRY commissioners. Secondary outcomes include the longitudinal impact of the optimisation, parent-reported infant intake of fruits and vegetables (as a proxy to compliance) and other parent-reported family habits and lifestyle. This innovative trial will provide evidence on the implementation of a theory-informed optimisation intervention to promote parent engagement in HENRY, a community-based childhood obesity prevention programme. The findings will be generalisable to other interventions delivered to parents in other community-based environments. This research meets the expressed needs of commissioners, children's centres and parents to optimise the potential impact that HENRY has on obesity prevention. A subsequent cluster randomised controlled pilot trial is planned to determine the practicality of undertaking a definitive trial to robustly evaluate the effectiveness and cost-effectiveness of the optimised intervention on childhood obesity prevention. ClinicalTrials.gov identifier: NCT02675699 . Registered on 4 February 2016.

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

PubMed

Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-18

Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. ISRCTN 71002650; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Inclusion of adolescents in preventive HIV vaccine trials: public health policy and research design at a crossroads.

PubMed

Jaspan, Heather B; Cunningham, Coleen K; Tucker, Tim J P; Wright, Peter F; Self, Steve G; Sheets, Rebecca L; Rogers, Audrey S; Bekker, Linda-Gail; Wilson, Craig M; Duerr, Ann; Wasserheit, Judith N

2008-01-01

The search for a safe effective HIV vaccine has been a centerpiece of HIV research for almost 2 decades. More than 60 clinical HIV vaccine trials have been conducted to date. Several promising candidate HIV vaccines are in advanced clinical development. To date, however, no trial has included adolescents, one of the most important target groups for any preventive HIV vaccine. To license a vaccine for use in this age group, efficacy data or, at a minimum, bridging safety and immunogenicity data in this population are needed. To accomplish this, several critical issues and special challenges in the development and implementation of HIV vaccine trials in adolescents must be addressed, including regulatory considerations, potential differentials in safety and immunogenicity, alternative trial design strategies, recruitment and retention challenges, community involvement models, and approaches to informed consent/assent. This article examines these issues and proposes specific next steps to facilitate the routine inclusion of this high-priority population in preventive HIV vaccine trials as early and seamlessly as possible.

[Selenium supplementation trials for cancer prevention and the subsequent risk of type 2 diabetes mellitus: selenium and vitamin E cancer prevention trial and after].

PubMed

Koyama, Hiroshi; Mutakin; Abdulah, Rizky; Yamazaki, Chiho; Kameo, Satomi

2013-01-01

The essential trace element selenium has long been considered to exhibit cancer-preventive, antidiabetic and insulin-mimetic properties. However, recent epidemiological studies have indicated that supranutritional selenium intake and high plasma selenium levels are not necessarily preventive against cancer, and are possible risk factors for developing type 2 diabetes mellitus. The results of the SELECT, Selenium and Vitamin E Cancer Prevention Trial, in which it is hypothesized that the supplementations with selenium and/or vitamin E decrease the prostate cancer incidence among healthy men in the U.S., showed that the supplementation did not prevent the development of prostate cancer and that the incidence of newly diagnosed type 2 diabetes mellitus increased among the selenium-supplemented participants. The Nutritional Prevention of Cancer (NPC) trial showed a decreased risk of prostate cancer among participants taking 200 μg of selenium daily for 7.7 years. However, the results of the NPC trial also showed an increased risk of type 2 diabetes mellitus in the participants with plasma selenium levels in the top tertile at the start of the study. Recently, the association of serum selenium with adipocytokines, such as TNF-α, VCAM-1, leptin, FABP-4, and MCP-1, has been observed. Selenoprotein P has been reported to associated with adiponectin, which suggests new roles of selenoprotein P in cellular energy metabolism, possibly leading to the increased risk of type 2 diabetes mellitus and also the development of cancer. Further studies are required to elucidate the relationship between selenium and adipocytokines and the role of selenoprotein P in the development of type 2 diabetes mellitus and cancer at high levels of selenium.

Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents.

PubMed

Cox, Georgina R; Fisher, Caroline A; De Silva, Stefanie; Phelan, Mark; Akinwale, Olaoluwa P; Simmons, Magenta B; Hetrick, Sarah E

2012-11-14

Depressive disorders often begin during childhood or adolescence. There is a growing body of evidence supporting effective treatments during the acute phase of a depressive disorder. However, little is known about treatments for preventing relapse or recurrence of depression once an individual has achieved remission or recovery from their symptoms. To determine the efficacy of early interventions, including psychological and pharmacological interventions, to prevent relapse or recurrence of depressive disorders in children and adolescents. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 1 June 2011). The CCDANCTR contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition we handsearched the references of all included studies and review articles. Randomised controlled trials using a psychological or pharmacological intervention, with the aim of preventing relapse or recurrence from an episode of major depressive disorder (MDD) or dysthymic disorder (DD) in children and adolescents were included. Participants were required to have been diagnosed with MDD or DD according to DSM or ICD criteria, using a standardised and validated assessment tool. Two review authors independently assessed all trials for inclusion in the review, extracted trial and outcome data, and assessed trial quality. Results for dichotomous outcomes are expressed as odds ratio and continuous measures as mean difference or standardised mean difference. We combined results using random-effects meta-analyses, with 95% confidence intervals. We contacted lead authors of included trials and requested additional data where possible. Nine trials with 882 participants were included in the review. In five trials the outcome assessors were blind to the participants' intervention condition and in the remainder of trials it was unclear. In the majority of trials, participants were either not blind to their intervention condition, or it was unclear whether they were or not. Allocation concealment was also unclear in the majority of trials. Although all trials treated participants in an outpatient setting, the designs implemented in trials was diverse, which limits the generalisability of the results. Three trials indicated participants treated with antidepressant medication had lower relapse-recurrence rates (40.9%) compared to those treated with placebo (66.6%) during a relapse prevention phase (odds ratio (OR) 0.34; 95% confidence interval (CI) 0.18 to 0.64, P = 0.02). One trial that compared a combination of psychological therapy and medication to medication alone favoured a combination approach over medication alone, however this result did not reach statistical significance (OR 0.26; 95% CI 0.06 to 1.15). The majority of trials that involved antidepressant medication reported adverse events including suicide-related behaviours. However, there were not enough data to show which treatment approach results in the most favourable adverse event profile. Currently, there is little evidence to conclude which type of treatment approach is most effective in preventing relapse or recurrence of depressive episodes in children and adolescents. Limited trials found that antidepressant medication reduces the chance of relapse-recurrence in the future, however, there is considerable diversity in the design of trials, making it difficult to compare outcomes across studies. Some of the research involving psychological therapies is encouraging, however at present more trials with larger sample sizes need to be conducted in order to explore this treatment approach further.

Diffusion and dissemination of evidence-based dietary srategies for the prevention of cancer

PubMed Central

Ciliska, Donna; Robinson, Paula; Armour, Tanya; Ellis, Peter; Brouwers, Melissa; Gauld, Mary; Baldassarre, Fulvia; Raina, Parminder

2005-01-01

Objective The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? Methods A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. Results One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. Conclusions and Implications Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences. PMID:15819991

Diffusion and dissemination of evidence-based dietary strategies for the prevention of cancer.

PubMed

Ciliska, Donna; Robinson, Paula; Armour, Tanya; Ellis, Peter; Brouwers, Melissa; Gauld, Mary; Baldassarre, Fulvia; Raina, Parminder

2005-04-08

The purpose was to determine what strategies have been evaluated to disseminate cancer control interventions that promote the uptake of adult healthy diet? A systematic review was conducted. Studies were identified by searching MEDLINE, PREMEDLINE, Cancer LIT, EMBASE/Excerpta Medica, PsycINFO, CINAHL, the Cochrane Database of Systematic Reviews, and reference lists and by contacting technical experts. English-language primary studies were selected if they evaluated the dissemination of healthy diet interventions in individuals, healthcare providers, or institutions. Studies of children or adolescents only were excluded. One hundred one articles were retrieved for full text screening. Nine reports of seven distinct studies were included; four were randomized trials, one was a cohort design and three were descriptive studies. Six studies were rated as methodologically weak, and one was rated as moderate. Studies were not meta-analyzed because of heterogeneity, low methodological quality, and incomplete data reporting. No beneficial dissemination strategies were found except one that looks promising, the use of peer educators in the worksite, which led to a short-term increase in fruit and vegetable intake. Overall, the quality of the evidence is not strong and is primarily descriptive rather than evaluative. No clear conclusions can be drawn from these data. Controlled studies are needed to evaluate dissemination strategies, and to compare dissemination and diffusion strategies with different messages and different target audiences.

Medial tibial stress syndrome: evidence-based prevention.

PubMed

Craig, Debbie I

2008-01-01

Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32-40. Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Studies were identified by searching MEDLINE (1966-2000), Current Contents (1996-2000), Biomedical Collection (1993-1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury.

Preventing Depression in Final Year Secondary Students: School-Based Randomized Controlled Trial

PubMed Central

Perry, Yael; Werner-Seidler, Aliza; Calear, Alison; Mackinnon, Andrew; King, Catherine; Scott, Jan; Merry, Sally; Fleming, Theresa; Stasiak, Karolina; Batterham, Philip J

2017-01-01

Background Depression often emerges for the first time during adolescence. There is accumulating evidence that universal depression prevention programs may have the capacity to reduce the impact of depression when delivered in the school environment. Objective This trial investigated the effectiveness of SPARX-R, a gamified online cognitive behavior therapy intervention for the prevention of depression relative to an attention-matched control intervention delivered to students prior to facing a significant stressor—final secondary school exams. It was hypothesized that delivering a prevention intervention in advance of a stressor would reduce depressive symptoms relative to the control group. Methods A cluster randomized controlled trial was conducted in 10 government schools in Sydney, Australia. Participants were 540 final year secondary students (mean 16.7 [SD 0.51] years), and clusters at the school level were randomly allocated to SPARX-R or the control intervention. Interventions were delivered weekly in 7 modules, each taking approximately 20 to 30 minutes to complete. The primary outcome was symptoms of depression as measured by the Major Depression Inventory. Intention-to-treat analyses were performed. Results Compared to controls, participants in the SPARX-R condition (n=242) showed significantly reduced depression symptoms relative to the control (n=298) at post-intervention (Cohen d=0.29) and 6 months post-baseline (d=0.21) but not at 18 months post-baseline (d=0.33). Conclusions This is the first trial to demonstrate a preventive effect on depressive symptoms prior to a significant and universal stressor in adolescents. It demonstrates that an online intervention delivered in advance of a stressful experience can reduce the impact of such an event on the potential development or exacerbation of depression. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12614000316606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365986 (Archived by WebCite at http://www.webcitation.org/ 6u7ou1aI9) PMID:29097357

Tachikawa project for prevention of posttraumatic stress disorder with polyunsaturated fatty acid (TPOP): study protocol for a randomized controlled trial.

PubMed

Matsuoka, Yutaka; Nishi, Daisuke; Yonemoto, Naohiro; Hamazaki, Kei; Matsumura, Kenta; Noguchi, Hiroko; Hashimoto, Kenji; Hamazaki, Tomohito

2013-01-05

Preclinical and clinical studies suggest that supplementation with omega-3 fatty acids after trauma might reduce subsequent posttraumatic stress disorder (PTSD). To date, we have shown in an open trial that PTSD symptoms in critically injured patients can be reduced by taking omega-3 fatty acids, hypothesized to stimulate hippocampal neurogenesis. The primary aim of the present randomized controlled trial is to examine the efficacy of omega-3 fatty acid supplementation in the secondary prevention of PTSD following accidental injury, as compared with placebo. This paper describes the rationale and protocol of this trial. The Tachikawa Project for Prevention of Posttraumatic Stress Disorder with Polyunsaturated Fatty Acid (TPOP) is a double-blinded, parallel group, randomized controlled trial to assess whether omega-3 fatty acid supplementation can prevent PTSD symptoms among accident-injured patients consecutively admitted to an intensive care unit. We plan to recruit accident-injured patients and follow them prospectively for 12 weeks. Enrolled patients will be randomized to either the omega-3 fatty acid supplement group (1,470 mg docosahexaenoic acid and 147 mg eicosapentaenoic acid daily) or placebo group. Primary outcome is score on the Clinician-Administered PTSD Scale (CAPS). We will need to randomize 140 injured patients to have 90% power to detect a 10-point difference in mean CAPS scores with omega-3 fatty acid supplementation compared with placebo. Secondary measures are diagnosis of PTSD and major depressive disorder, depressive symptoms, physiologic response in the experiment using script-driven imagery and acoustic stimulation, serum brain-derived neurotrophic factor, health-related quality of life, resilience, and aggression. Analyses will be by intent to treat. The trial was initiated on December 13 2008, with 104 subjects randomized by November 30 2012. This study promises to be the first trial to provide a novel prevention strategy for PTSD among traumatized people. ClinicalTrials.gov Identifier NCT00671099.

The exploitation of "Exploitation" in the tenofovir prep trial in Cameroon: Lessons learned from media coverage of an HIV prevention trial.

PubMed

Mack, Natasha; Robinson, Elizabeth T; MacQueen, Kathleen M; Moffett, Jill; Johnson, Laura M

2010-06-01

media coverage influences how clinical trials are perceived internationally and in communities where trials occur, affecting recruitment, retention, and political support for research. We conducted a discourse analysis of news coverage from 2004-2005 of a trial in Cameroon on oral PrEP for HIV prevention, to identify messages, communication techniques, and sources of messages that were amplified via media. We identified two parallel discourses: one on ethical concerns about the Cameroon trial, and a second, more general "science exploitation" discourse concerned with the potential for trials with vulnerable participant populations to be conducted unethically, benefiting only wealthy populations. Researchers should overtly address exploitation as an integral, ongoing component of research, particularly where historical or cultural conditions set the stage for controversy to emerge.

Complementary and alternative medicine for prevention and treatment of the common cold

PubMed Central

Nahas, Richard; Balla, Agneta

2011-01-01

Abstract Objective To review the evidence supporting complementary and alternative medicine approaches to treatment and prevention of the common cold in adults. Quality of Evidence MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched from January 1966 to September 2009 combining the key words common cold or influenza with echinacea, garlic, ginseng, probiotics, vitamin C, and zinc. Clinical trials and prospective studies were included. Main Message For prevention, vitamin C demonstrated benefit in a large meta-analysis, with possibly increased benefit in patients subjected to cold stress. There is inconsistent evidence for Asian ginseng (Panax ginseng) and North American ginseng (Panax quinquefolius). Allicin was highly effective in 1 small trial. For treatment, Echinacea purpurea is the most consistently useful variety; it was effective in 5 of 6 trials. Zinc lozenges were effective in 5 of 9 trials, likely owing to dose and formulation issues. Overall, the evidence suggests no benefit from probiotics for prevention or treatment of the common cold. Conclusion Vitamin C can be recommended to Canadian patients for prevention of the common cold. There is moderate evidence supporting the use of Echinacea purpurea and zinc lozenges for treatment. Ginseng and allicin warrant further research. PMID:21322286

Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation.

PubMed

Nelson, Heidi D; Fu, Rochelle; Cantor, Amy; Pappas, Miranda; Daeges, Monica; Humphrey, Linda

2016-02-16

In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years. To review studies of the effectiveness of breast cancer screening in average-risk women. MEDLINE and Cochrane databases to 4 June 2015. English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes. Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus. Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10,000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10,000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10,000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10,000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome. Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited. Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older. Agency for Healthcare Research and Quality.

Evaluation of two supplements for the prevention of alfalfa bloat.

PubMed Central

Hall, J W; Walker, I; Majak, W

1994-01-01

Poloxalene and a mineral mixture feed supplement patented for the treatment of emphysema, polyarthritis, and other pectin related diseases were tested in two trials for their ability to prevent bloat in cattle fed fresh alfalfa. Each trial had a crossover design using three Jersey steers with rumen fistulas per group. Each trial period continued until the total number of cases of bloat reached > or = 24. Treatments were given at 0800 each day. The mineral mixture was given at 100 g/d and 190 mg/kg body weight per day in the first and second trials, respectively. Poloxalene, which was tested only in the second trial, was given at 23 mg/kg body weight per day. Each group of steers was then fed 200 kg of freshly harvested alfalfa in the vegetative to early bloom stages of growth at 0830. In the first trial, only 69% as many cases of bloat occurred on the mineral mixture as on the control treatment, but no significant difference was detected in the second trial. The potency of the alfalfa may have been higher in the second trial, when forage dry matter was lower, magnesium and soluble nitrogen were higher, and bloat occasionally occurred twice a day. Bloat did not occur when the steers were treated with poloxalene. In these trials, poloxalene was completely effective in preventing bloat, but the mineral mixture was only partially so. PMID:7866960

Evaluation of two supplements for the prevention of alfalfa bloat.

PubMed

Hall, J W; Walker, I; Majak, W

1994-11-01

Poloxalene and a mineral mixture feed supplement patented for the treatment of emphysema, polyarthritis, and other pectin related diseases were tested in two trials for their ability to prevent bloat in cattle fed fresh alfalfa. Each trial had a crossover design using three Jersey steers with rumen fistulas per group. Each trial period continued until the total number of cases of bloat reached > or = 24. Treatments were given at 0800 each day. The mineral mixture was given at 100 g/d and 190 mg/kg body weight per day in the first and second trials, respectively. Poloxalene, which was tested only in the second trial, was given at 23 mg/kg body weight per day. Each group of steers was then fed 200 kg of freshly harvested alfalfa in the vegetative to early bloom stages of growth at 0830. In the first trial, only 69% as many cases of bloat occurred on the mineral mixture as on the control treatment, but no significant difference was detected in the second trial. The potency of the alfalfa may have been higher in the second trial, when forage dry matter was lower, magnesium and soluble nitrogen were higher, and bloat occasionally occurred twice a day. Bloat did not occur when the steers were treated with poloxalene. In these trials, poloxalene was completely effective in preventing bloat, but the mineral mixture was only partially so.

Research participants' skills development as HIV prevention peer educators in their communities.

PubMed

Morar, Neetha Shagan; Naidoo, Sarita; Goolam, Ahmed; Ramjee, Gita

2016-06-01

This article describes the influence of a peer education programme on skills development among 22 women participating in HIV prevention trials. Interviews were used to collect data on peer educator experiences and their opinions of the trainings. The training enhanced their agency and confidence to engage their family and community on health promotion, including HIV prevention research procedures, thus improving their self-esteem and communication skills. Training and partnering with clinical trial participants as peer educators is an effective and sustainable community-based approach for HIV prevention.

Providers' Perceptions of and Receptivity toward Evidence-Based HIV Prevention Interventions

ERIC Educational Resources Information Center

Owczarzak, Jill; Dickson-Gomez, Julia

2011-01-01

Since 1999, the Centers for Disease Control and Prevention have trained over 10,000 service providers from more than 5,000 agencies to implement evidence-based HIV prevention interventions through its Diffusion of Effective Behavioral Interventions DEBI) program. Based on in-depth, semistructured interviews with a convenience sample of 22 HIV…

Diffusion chamber system for testing of collagen-based cell migration barriers for separation of ligament enthesis zones in tissue-engineered ACL constructs.

PubMed

Hahner, J; Hoyer, M; Hillig, S; Schulze-Tanzil, G; Meyer, M; Schröpfer, M; Lohan, A; Garbe, L-A; Heinrich, G; Breier, A

2015-01-01

A temporary barrier separating scaffold zones seeded with different cell types prevents faster growing cells from overgrowing co-cultured cells within the same construct. This barrier should allow sufficient nutrient diffusion through the scaffold. The aim of this study was to test the effect of two variants of collagen-based barriers on macromolecule diffusion, viability, and the spreading efficiency of primary ligament cells on embroidered scaffolds. Two collagen barriers, a thread consisting of a twisted film tape and a sponge, were integrated into embroidered poly(lactic-co-caprolactone) and polypropylene scaffolds, which had the dimension of lapine anterior cruciate ligaments (ACL). A diffusion chamber system was designed and established to monitor nutrient diffusion using fluorescein isothiocyanate-labeled dextran of different molecular weights (20, 40, 150, 500 kDa). Vitality of primary lapine ACL cells was tested at days 7 and 14 after seeding using fluorescein diacetate and ethidium bromide staining. Cell spreading on the scaffold surface was measured using histomorphometry. Nuclei staining of the cross-sectioned scaffolds revealed the penetration of ligament cells through both barrier types. The diffusion chamber was suitable to characterize the diffusivity of dextran molecules through embroidered scaffolds with or without integrated collagen barriers. The diffusion coefficients were generally significantly lower in scaffolds with barriers compared to those without barriers. No significant differences between diffusion coefficients of both barrier types were detected. Both barriers were cyto-compatible and prevented most of the ACL cells from crossing the barrier, whereby the collagen thread was easier to handle and allowed a higher rate of cell spreading.

Improved Cardiovascular Prevention Using Best CME Practices: A Randomized Trial

ERIC Educational Resources Information Center

Laprise, Rejean; Thivierge, Robert; Gosselin, Gilbert; Bujas-Bobanovic, Maja; Vandal, Sylvie; Paquette, Daniel; Luneau, Micheline; Julien, Pierre; Goulet, Serge; Desaulniers, Jean; Maltais, Paule

2009-01-01

Introduction: It was hypothesized that after a continuing medical education (CME) event, practice enablers and reinforcers addressing main clinical barriers to preventive care would be more effective in improving general practitioners' (GPs) adherence to cardiovascular guidelines than a CME event only. Methods: A cluster-randomized trial was…

New clinical trial aims to prevent breast cancer from recurring in the brain | Center for Cancer Research

Cancer.gov

In some types of breast cancer, the tumor cells spread more frequently to the brain. A new clinical trial run by CCR investigators will test whether a drug called temozolomide can prevent these deadly lesions from recurring. Read more... 

Keeping the Spirit of Community Partnerships Alive in the Scale Up of HIV/AIDS Prevention: Critical Reflections on the Roll Out of DEBI (Diffusion of Effective Behavioral Interventions)

PubMed Central

Pinto, Rogério M.; Hunter, Joyce; Rapkin, Bruce; Remien, Robert H.

2009-01-01

DEBI, or the Diffusion of Effective Behavioral Interventions is the largest centralized effort to diffuse evidence-based prevention science to fight HIV/AIDS in the United States. DEBI seeks to ensure that the most effective science-based prevention interventions are widely implemented across the country in community-based organizations. Thus, this is a particularly timely juncture in which to critically reflect on the extent to which known principles of community collaboration have guided key processes associated with the DEBI rollout. We review the available evidence on how the dissemination of packaged interventions is necessary but not sufficient for ensuring the success of technology transfer. We consider additional principles that are vital for successful technology transfer, which were not central considerations in the rollout of the DEBI initiative. These issues are: (1) community perceptions of a top-down mode of dissemination; (2) the extent to which local innovations are being embraced, bolstered, or eliminated; and (3) contextual and methodological considerations that shape community preparedness. Consideration of these additional factors is necessary in order to effectively document, manage, and advance the science of dissemination and technology transfer in centralized prevention efforts within and outside of HIV/AIDS. PMID:18612809

Biorepositories for the Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Raloxifene (STAR) | Division of Cancer Prevention

Cancer.gov

The National Surgical Adjuvant Breast and Bowel Project (NSABP) has a serum and lymphocyte bank with specimens on more than 90% of the 33,000 women in the Breast Cancer Prevention Trial (BCPT) and Study of Tamoxifen and Raloxifene (STAR). They also have tumor blocks on the majority of the breast cancers that have occurred in women on these studies. |

Unity in Diversity: Results of a Randomized Clinical Culturally Tailored Pilot HIV Prevention Intervention Trial in Baltimore, Maryland, for African American Men Who Have Sex with Men

ERIC Educational Resources Information Center

Tobin, Karin; Kuramoto, Satoko J.; German, Danielle; Fields, Errol; Spikes, Pilgrim S.; Patterson, Jocelyn; Latkin, Carl

2013-01-01

Unity in Diversity was a randomized controlled trial of a culturally tailored HIV prevention intervention for African American men who have sex with men. The intervention condition was six group-based sessions and one individual session. The control condition was a single-session HIV prevention review. Participants were aged 18 years or older,…

Strength in Numbers: Opportunities for Enhancing the Development of Effective Treatments for Type 1 Diabetes-The TrialNet Experience.

PubMed

Greenbaum, Carla J; Speake, Cate; Krischer, Jeffrey; Buckner, Jane; Gottlieb, Peter A; Schatz, Desmond A; Herold, Kevan C; Atkinson, Mark A

2018-07-01

The early to mid-1980s were an inflection point in the history of type 1 diabetes research. Two landmark events occurred: the initiation of immune-based interventions seeking to prevent type 1 diabetes and the presentation of an innovative model describing the disorder's natural history. Both formed the basis for hundreds of subsequent studies designed to achieve a dramatic therapeutic goal-a means to prevent and/or reverse type 1 diabetes. However, the need to screen large numbers of individuals and prospectively monitor them using immunologic and metabolic tests for extended periods of time suggested such efforts would require a large collaborative network. Hence, the National Institutes of Health formed the landmark Diabetes Prevention Trial-Type 1 (DPT-1) in the mid-1990s, an effort that led to Type 1 Diabetes TrialNet. TrialNet studies have helped identify novel biomarkers; delineate type 1 diabetes progression, resulting in identification of highly predictable stages defined by the accumulation of autoantibodies (stage 1), dysglycemia (stage 2), and disease meeting clinical criteria for diagnosis (stage 3); and oversee numerous clinical trials aimed at preventing disease progression. Such efforts pave the way for stage-specific intervention trials with improved hope that a means to effectively disrupt the disorder's development will be identified. © 2018 by the American Diabetes Association.

Prostate cancer chemoprevention agent development: the National Cancer Institute, Division of Cancer Prevention portfolio.

PubMed

Parnes, Howard L; House, Margaret G; Kagan, Jacob; Kausal, David J; Lieberman, Ronald

2004-02-01

We describe the current National Cancer Institute chemoprevention agent development program and provide a summary of the intermediate end points used. The National Cancer Institute is currently sponsoring a wide range of studies of promising chemoprevention agents in a variety of informative cohorts, eg high grade prostatic intraepithelial neoplasia, positive family history of cancer, increased prostate specific antigen with negative biopsies, prostate cancer followed expectantly, prostate cancer awaiting definitive therapy and the general population. The rationale for each agent under investigation is derived from epidemiological observations, prostate cancer treatment trials, secondary analyses of large cancer prevention studies, an understanding of cancer biology and prostate carcinogenesis, and/or experimental animal models. Carcinogenesis is a multistep process occurring over decades which is characterized by disruption of the normal regulatory pathways controlling cellular proliferation, programmed cell death and differentiation. Administration of agents to reverse, inhibit or slow this process of malignant transformation is known as chemoprevention. Chemoprevention represents a promising approach to reducing the morbidity and mortality of prostate cancer. A variety of agents are currently being studied in phase 2 clinical trials, some of which may warrant subsequent evaluation in phase 3 trials with definitive cancer end points. Two large phase 3 trials, the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, which are ongoing, are also sponsored by the National Cancer Institute.

Antifungal Prevention of Systemic Candidiasis in Immunocompetent ICU Adults: Systematic Review and Meta-Analysis of Clinical Trials.

PubMed

Dupont, Hervé; Mahjoub, Yazine; Chouaki, Taieb; Lorne, Emmanuel; Zogheib, Elie

2017-11-01

The aim of this study was to identify the impact of antifungal prevention in critically ill immunocompetent adult patients on mortality and subsequent infection. A systematic review and meta-analysis of randomized controlled trials comparing any antifungal use versus placebo to prevent candidiasis in ICU patients were performed. Searches were performed on PubMed, Embase, Scopus, main conference proceedings, and ClinicalTrials.gov, as well as reference lists. The primary outcomes were mortality and invasive candidiasis. The secondary outcome was the rate of Candida albicans and nonalbicans strains after treatment. A random effect model was used, and sensitivity analysis was performed for both outcomes. Results are expressed as risk ratios and their 95% CIs. Nineteen trials (10 with fluconazole, four with ketoconazole, one with itraconazole, three with micafungin, and one with caspofungin) including 2,792 patients were identified. No individual trial showed a decreased mortality rate. Combined analysis showed that preventive antifungal did not decrease mortality (risk ratio, 0.88; 95% CI, 0.74-1.04; p = 0.14) but significantly decreased secondary fungal infections by 50% (risk ratio, 0.49; 95% CI, 0.35-0.68; p = 0.0001). No shift across nonalbicans strains was observed during treatment (risk ratio, 0.62; 95% CI, 0.19-1.97; p = 0.42). However, publication biases preclude any definite conclusions for prevention of infection. Antifungal prevention of systemic candidiasis in immunocompetent critically ill adults did not reduce mortality and may have decreased secondary fungal infection rates. However, significant publication bias was present.

Implementing a stigma reduction intervention in healthcare settings

PubMed Central

Li, Li; Lin, Chunqing; Guan, Jihui; Wu, Zunyou

2013-01-01

Introduction Globally, HIV-related stigma is prevalent in healthcare settings and is a major barrier to HIV prevention and treatment adherence. Some intervention studies have showed encouraging outcomes, but a gap continues to exist between what is known and what is actually delivered in medical settings to reduce HIV-related stigma. Methods This article describes the process of implementing a stigma reduction intervention trial that involved 1760 service providers in 40 hospitals in China. Guided by Diffusion of Innovation theory, the intervention identified and trained about 15–20% providers as popular opinion leaders (POLs) to disseminate stigma reduction messages in each intervention hospital. The intervention also engaged governmental support in the provision of universal precaution supplies to all participating hospitals in the trial. The frequency of message diffusion and reception, perceived improvement in universal precaution practices and reduction in the level of stigma in hospitals were measured at 6- and 12-month follow-up assessments. Results Within the intervention hospitals, POL providers reported more frequent discussions with their co-workers regarding universal precaution principles, equal treatment of patients, provider-patient relationships and reducing HIV-related stigma. Service providers in the intervention hospitals reported more desirable intervention outcomes than providers in the control hospitals. Our evaluation revealed that the POL model is compatible with the target population, and that the unique intervention entry point of enhancing universal precaution and occupational safety was the key to improved acceptance by service providers. The involvement of health authorities in supporting occupational safety was an important element for sustainability. Conclusions This report focuses on explaining the elements of our intervention rather than its outcomes. Lessons learned from the intervention implementation will enrich the development of future programs that integrate this or other intervention models into routine medical practice, with the aim of reducing HIV-related stigma and improving HIV testing, treatment and care in medical settings. PMID:24242261

Neuroimaging basis in the conversion of aMCI patients with APOE-ε4 to AD: study protocol of a prospective diagnostic trial.

PubMed

Chen, Guan-Qun; Sheng, Can; Li, Yu-Xia; Yu, Yang; Wang, Xiao-Ni; Sun, Yu; Li, Hong-Yan; Li, Xuan-Yu; Xie, Yun-Yan; Han, Ying

2016-05-12

The ε4 allele of the Apolipoprotein E gene (APOE-ε4) is a potent genetic risk factor for sporadic Alzheimer's disease (AD). Amnestic mild cognitive impairment (aMCI) is an intermediate state between normal cognitive aging and dementia, which is easy to convert to AD dementia. It is an urgent problem in the field of cognitive neuroscience to reveal the conversion of aMCI-ε4 to AD. Based on our preliminary work, we will study the neuroimaging features in the special group of aMCI-ε4 with multi-modality magnetic resonance imaging (structural MRI, resting state-fMRI and diffusion tensor imaging) longitudinally. In this study, 200 right-handed subjects who are diagnosed as aMCI with APOE-ε4 will be recruited at the memory clinic of the Neurology Department, XuanWu Hospital, Capital Medical University, Beijing, China. All subjects will undergo the neuroimaging and neuropsychological evaluation at a 1 year-interval for 3 years. The primary outcome measures are 1) Microstructural alterations revealed with multimodal MRI scans including structure MRI (sMRI), resting state functional MRI (rs-fMRI), diffusion tensor imaging (DTI); 2) neuropsychological evaluation, including the World Health Organization-University of California-LosAngeles Auditory Verbal Learning Test (WHO-UCLA AVLT), Addenbrook's cognitive examination-revised (ACE-R), mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating scale (CDR). This study is to find out the neuroimaging biomarker and the changing laws of the marker during the progress of aMCI-ε4 to AD, and the final purpose is to provide scientific evidence for new prevention, diagnosis and treatment of AD. This study has been registered to ClinicalTrials.gov (NCT02225964, https://www.clinicaltrials.gov/ ) in August 24, 2014.

A tale of three labels: translating the JUPITER trial data into regulatory claims.

PubMed

Ridker, Paul M

2011-08-01

Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C <130 mg/dL and hsCRP ≥ 2 mg/L, provides the only available data on rosuvastatin for primary prevention of cardiovascular disease. Thus, the JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p < 0.000001) in the trial pre-specified primary endpoint (nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, coronary revascularization, or cardiovascular death) with no evidence of heterogeneity across geographic regions. In response to these data, the US Food and Drug Administration label for rosuvastatin in primary prevention came closest to the actual JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk' that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. The JUPITER experience represents a case study and is not a systematic review of the regulatory decision process. Labeling indications can vary widely in different regulatory environments even when based on the same trial data.

Clinical Trials

MedlinePlus

Clinical trials are research studies that test how well new medical approaches work in people. Each study ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to ...

Health, human rights, and the conduct of clinical research within oppressed populations

PubMed Central

Mills, Edward J; Singh, Sonal

2007-01-01

Background Clinical trials evaluating interventions for infectious diseases require enrolling participants that are vulnerable to infection. As clinical trials are conducted in increasingly vulnerable populations, issues of protection of these populations become challenging. In settings where populations are forseeably oppressed, the conduct of research requires considerations that go beyond common ethical concerns and into issues of international human rights law. Discussion Using examples of HIV prevention trials in Thailand, hepatitis-E prevention trials in Nepal and malaria therapeutic trials in Burma (Myanmar), we address the inadequacies of current ethical guidelines when conducting research within oppressed populations. We review existing legislature in the United States and United Kingdom that may be used against foreign investigators if trial hardships exist. We conclude by making considerations for research conducted within oppressed populations. PMID:17996056

Perioperative Aspirin for Prevention of Venous Thromboembolism: The PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials.

PubMed

Eikelboom, John W; Kearon, Clive; Guyatt, Gordon; Sessler, Daniel I; Yusuf, Salim; Cook, Deborah; Douketis, James; Patel, Ameen; Kurz, Andrea; Allard, Rene; Jones, Philip M; Dennis, Rodolfo J; Painter, Thomas W; Bergese, Sergio D; Leslie, Kate; Wijeysundera, Duminda N; Balasubramanian, Kumar; Duceppe, Emmanuelle; Miller, Scott; Diedericks, Johan; Devereaux, P J

2016-12-01

The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.

The LIPPSMAck POP (Lung Infection Prevention Post Surgery - Major Abdominal - with Pre-Operative Physiotherapy) trial: study protocol for a multi-centre randomised controlled trial.

PubMed

Boden, Ianthe; Browning, Laura; Skinner, Elizabeth H; Reeve, Julie; El-Ansary, Doa; Robertson, Iain K; Denehy, Linda

2015-12-15

Post-operative pulmonary complications are a significant problem following open upper abdominal surgery. Preliminary evidence suggests that a single pre-operative physiotherapy education and preparatory lung expansion training session alone may prevent respiratory complications more effectively than supervised post-operative breathing and coughing exercises. However, the evidence is inconclusive due to methodological limitations. No well-designed, adequately powered, randomised controlled trial has investigated the effect of pre-operative education and training on post-operative respiratory complications, hospital length of stay, and health-related quality of life following upper abdominal surgery. The Lung Infection Prevention Post Surgery - Major Abdominal- with Pre-Operative Physiotherapy (LIPPSMAck POP) trial is a pragmatic, investigator-initiated, bi-national, multi-centre, patient- and assessor-blinded, parallel group, randomised controlled trial, powered for superiority. Four hundred and forty-one patients scheduled for elective open upper abdominal surgery at two Australian and one New Zealand hospital will be randomised using concealed allocation to receive either i) an information booklet or ii) an information booklet, plus one additional pre-operative physiotherapy education and training session. The primary outcome is respiratory complication incidence using standardised diagnostic criteria. Secondary outcomes include hospital length of stay and costs, pneumonia diagnosis, intensive care unit readmission and length of stay, days/h to mobilise >1 min and >10 min, and, at 6 weeks post-surgery, patient reported complications, health-related quality of life, and physical capacity. The LIPPSMAck POP trial is a multi-centre randomised controlled trial powered and designed to investigate whether a single pre-operative physiotherapy session prevents post-operative respiratory complications. This trial standardises post-operative assisted ambulation and physiotherapy, measures many known confounders, and includes a post-discharge follow-up of complication rates, functional capacity, and health-related quality of life. This trial is currently recruiting. Australian New Zealand Clinical Trials Registry number: ACTRN12613000664741 , 19 June 2013.

Is there a role for modified probiotics as beneficial microbes: a systematic review of the literature.

PubMed

Zorzela, L; Ardestani, S K; McFarland, L V; Vohra, S

2017-10-13

Our objective was to conduct a systematic review and meta-analysis for the use of modified (heat-killed or sonicated) probiotics for the efficacy and safety to prevent and treat various diseases. Recent clinical research has focused on living strains of probiotics, but use in high-risk patients and potential adverse reactions including bacteremia has focused interest on alternatives to the use of live probiotics. We searched MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials, CINAHL, Alt Health Watch, Web of Science, Scopus, PubMed, from inception to February 14, 2017 for randomised controlled trials involving modified probiotic strains. The primary outcome was efficacy to prevent or treat disease and the secondary outcome was incidence of adverse events. A total of 40 trials were included (n=3,913): 14 trials (15 arms with modified probiotics and 20 control arms) for the prevention of diseases and 26 trials (29 arms with modified probiotics and 32 control arms) for treatment of various diseases. Modified microbes were compared to either placebo (44%), or the same living probiotic strain (39%) or to only standard therapies (17%). Modified microbes were not significantly more or less effective than the living probiotic in 86% of the preventive trials and 69% of the treatment trials. Modified probiotic strains were significantly more effective in 15% of the treatment trials. Incidence rates of adverse events were similar for modified and living probiotics and other control groups, but many trials did not collect adequate safety data. Although several types of modified probiotics showed significant efficacy over living strains of probiotics, firm conclusions could not be reached due to the limited number of trials using the same type of modified microbe (strain, daily dose and duration) for a specific disease indication. Further research may illuminate other strains of modified probiotics that may have potential as clinical biotherapeutics.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two review authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

Recruitment strategies for a possible tamoxifen trial.

PubMed

Kuller, L H

1991-01-01

Participants in a primary prevention trial using tamoxifen to prevent breast cancer should comprise a sample of (a) age-eligible women from the "general population," (b) higher risk sisters of breast cancer patients, (c) women participating in mammography screening programs, or (d) patients of (or other users of) primary care physicians' offices. The recruitment should consider the risk of breast cancer among eligible women, likelihood of adherence to protocol, and unbiased and accurate measurement of endpoints. The Risks for coronary heart disease, hypertension, diabetes, osteoporosis, and other cancers, especially uterine cancer, must also be evaluated. Recruitment is feasible and should not be the limiting factor in the decision to undertake a primary prevention trial.

Primary Prevention With Statins: ACC/AHA Risk-Based Approach Versus Trial-Based Approaches to Guide Statin Therapy.

PubMed

Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G; Falk, Erling

2015-12-22

Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. This study compared these approaches in a direct head-to-head fashion in a contemporary population. The study used the CGPS (Copenhagen General Population Study) with 37,892 subjects aged 40 to 75 years recruited in 2003 to 2008, all free of ASCVD, diabetes, and statin use at baseline. Among the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC/AHA risk-based approach, the net reclassification index for eligibility for statin therapy among 40- to 75-year-old subjects from the CGPS was -0.21 for the trial-based approach and -0.13 for the hybrid approach. The clinical performance of the ACC/AHA risk-based approach for primary prevention of ASCVD with statins was superior to the trial-based and hybrid approaches. Our results indicate that the ACC/AHA guidelines will prevent more ASCVD events than the trial-based and hybrid approaches, while treating fewer people compared with the trial-based approach. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research

PubMed Central

Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F.; Baumeister, Harald

2017-01-01

Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive–compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD. PMID:28848454

Prevention of Mental Health Disorders Using Internet- and Mobile-Based Interventions: A Narrative Review and Recommendations for Future Research.

PubMed

Ebert, David Daniel; Cuijpers, Pim; Muñoz, Ricardo F; Baumeister, Harald

2017-01-01

Although psychological interventions might have a tremendous potential for the prevention of mental health disorders (MHD), their current impact on the reduction of disease burden is questionable. Possible reasons include that it is not practical to deliver those interventions to the community en masse due to limited health care resources and the limited availability of evidence-based interventions and clinicians in routine practice, especially in rural areas. Therefore, new approaches are needed to maximize the impact of psychological preventive interventions. Limitations of traditional prevention programs could potentially be overcome by providing Internet- and mobile-based interventions (IMIs). This relatively new medium for promoting mental health and preventing MHD introduces a fresh array of possibilities, including the provision of evidence-based psychological interventions that are free from the restraints of travel and time and allow reaching participants for whom traditional opportunities are not an option. This article provides an introduction to the subject and narratively reviews the available evidence for the effectiveness of IMIs with regard to the prevention of MHD onsets. The number of randomized controlled trials that have been conducted to date is very limited and so far it is not possible to draw definite conclusions about the potential of IMIs for the prevention of MHD for specific disorders. Only for the indicated prevention of depression there is consistent evidence across four different randomized trial trials. The only trial on the prevention of general anxiety did not result in positive findings in terms of eating disorders (EDs), effects were only found in post hoc subgroup analyses, indicating that it might be possible to prevent ED onset for subpopulations of people at risk of developing EDs. Future studies need to identify those subpopulations likely to profit from preventive. Disorders not examined so far include substance use disorders, bipolar disorders, stress-related disorders, phobic disorders and panic disorder, obsessive-compulsive disorder, impulse-control disorders, somatic symptom disorder, and insomnia. In summary, there is a need for more rigorously conducted large scale randomized controlled trials using standard clinical diagnostic instruments for the selection of participants without MHD at baseline and the assessment of MHD onset. Subsequently, we discuss future directions for the field in order to fully exploit the potential of IMI for the prevention of MHD.

Do prophylactic antibiotics in gynecologic surgery prevent postoperative inflammatory complications? A systematic review.

PubMed

Boesch, Cedric Emanuel; Pronk, Roderick Franziskus; Medved, Fabian; Hentschel, Pascal; Schaller, Hans-Eberhard; Umek, Wolfgang

2017-06-01

The aim of this study was to systematically review the literature on antibiotic prophylaxis in gynaecologic surgeries to prevent inflammatory complications after gynaecological operations. The study was carried out as a systematic review. Only randomised controlled trials of women undergoing gynaecological surgery were included. The Medline and the Cochrane library databases were searched from 1966 to 2016. The trials must have investigated an antibiotic intervention to prevent an inflammatory complication after gynaecological surgery. Trials were excluded if they were not randomised, uncontrolled or included obstetrical surgery. Prophylactic antibiotics prevent inflammatory complications after gynaecological surgery. Prophylactic antibiotics are more effective in surgery requiring access to the peritoneal cavity or the vagina. Cefotetan appears to be more capable in preventing the overall inflammatory complication rate than cefoxitin or cefazolin. No benefit has been shown for the combination of antibiotics as prophylaxis. No difference has been shown between the long-term and short-term use of antibiotics. There is no need for the primary use of an anaerobic antibacterial agent. Antibiotics help to prevent postoperative inflammatory complications after major gynecologic surgeries.

Fluoride gel effective at reducing caries in children.

PubMed

Richards, Derek

2015-12-01

Data Cochrane Oral Health Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline , Embase, CINAHL, LILACS, ProQuest Dissertations and Theses, the Web of Science Conference Proceedings, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Randomised or quasi-randomised controlled trials comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years were considered. Studies had to be at least one year in duration with a frequency of application of at least once a year with blind outcome assessment. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). At least two reviewers extracted data and assessed risk of bias. The primary measure of effect was the prevented fraction (PF). Where data could be pooled random-effects meta-analyses were conducted. Potential sources of heterogeneity were examined in random-effects meta-regression analyses. Twenty-eight trials involving 9140 children and adolescents were included. Most of the studies (20) were at high risk of bias, with eight at unclear risk of bias. Twenty-five trials (8479 participants) provided data for meta-analysis on permanent teeth, with a D(M)FS pooled prevented fraction (PF) estimate of 28% (95% CI; 19-36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the ten trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials.A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.For primary teeth the d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) = 20% (95%CI; 1% - 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

[Kagocel in the therapy of influenza and acute respiratory viral infections: Data analysis and systematization from the results of preclinical and clinical trials].

PubMed

Sologub, T V; Tsvetkov, V V

The article provides the summarized data of clinical trials evaluating the efficacy and safety of kagocel used to prevent and treat influenza and acute respiratory viral infections of different etiologies. The results of numerous preclinical and clinical trials suggest that the kagocel substance is highly safe and that it is appropriate to use the drug for the treatment and prevention of influenza and acute respiratory viral infections of another etiology.

Randomized Controlled Trial of a Preventive Intervention for Perinatal Depression in High-Risk Latinas

ERIC Educational Resources Information Center

Le, Huynh-Nhu; Perry, Deborah F.; Stuart, Elizabeth A.

2011-01-01

Objective: A randomized controlled trial was conducted to evaluate the efficacy of a cognitive-behavioral (CBT) intervention to prevent perinatal depression in high-risk Latinas. Method: A sample of 217 participants, predominantly low-income Central American immigrants who met demographic and depression risk criteria, were randomized into usual…

Preventing Childhood Bullying: Findings and Lessons from the Denver Public Schools Trial

ERIC Educational Resources Information Center

Jenson, Jeffrey M.; Dieterich, William A.; Brisson, Daniel; Bender, Kimberly A.; Powell, Anne

2010-01-01

Twelve-month follow-up outcomes from a group-randomized trial (GRT) of a classroom curriculum aimed at preventing bullying and victimization among elementary students in the Denver, Colorado, public school system are presented. Twenty-eight elementary schools were randomly assigned to receive selected modules of "Youth Matters" (YM), a…

A Meta-Analysis of Trials Evaluating Patient Education and Counseling for Three Groups of Preventive Health Behaviors.

ERIC Educational Resources Information Center

Mullen, Patricia Dolan; Simons-Morton, Denise G.; Ramirez, Gilbert; Frankowski, Ralph F.; Green, Lawrence W.; Mains, Douglas A.

1997-01-01

The overall effectiveness of patient education and counseling on preventive health behaviors was examined across published clinical trials, 1971-1994. The effectiveness of various approaches for modifying specific types of behaviors among patients without diagnosed disease was assessed. Multiple regression models indicated differences among…

Outcomes from a School-Randomized Controlled Trial of Steps to Respect: A Bullying Prevention Program

ERIC Educational Resources Information Center

Brown, Eric C.; Low, Sabina; Smith, Brian H.; Haggerty, Kevin P.

2011-01-01

This study reports the outcomes of a randomized controlled trial of Steps to Respect: A Bullying Prevention Program conducted in 33 California elementary schools. Schools were matched on school demographic characteristics and assigned randomly to intervention or waitlisted control conditions. Outcome measures were obtained from (a) all school…

Protocol Information Office (PIO) | Division of Cancer Prevention

Cancer.gov

PIO Instructions and Tools Find instructions, forms, and templates for the management of all types of Division of Cancer Prevention clinical trials.Read more about PIO Instructions and Tools Clinical Trials Reference Materials Model clinical agreements, human subject protection and informed consent models, gender and minority inclusion information, and monitoring policy and

The Lifestyle Interventions and Independence for Elders (LIFE) study, randomized trial of physical activity: Effect on the prevention of major mobility disability

USDA-ARS?s Scientific Manuscript database

In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining if physical activi...

Interventions for preventing silent cerebral infarcts in people with sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Doree, Carolyn; Abboud, Miguel R

2017-01-01

Background Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient. Objectives To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD. Search methods We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016. Selection criteria Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis We used standard Cochrane methodological procedures. Main results We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention. Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents). The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence). No deaths were reported in either trial. Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence). Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial) Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence). We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence). The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial) We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95% CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence). Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence). Neither trial reported on quality of life or cognitive function. Authors’ conclusions We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD. Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises). In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions. Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention. All other evidence in this review is of very low-quality. PMID:28500860

Adolescents and HIV clinical trials

PubMed Central

MacQueen, Kathleen M.; Karim, Quarraisha Abdool

2007-01-01

One quarter of HIV infections globally occur among young people 15-24 years of age and more than half of all new infections are to people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical and several promising methods are in development, including microbicides, vaccines, and pre-exposure prophylaxis (PREP) or the daily use of antiretrovirals to prevent the acquisition of HIV. There is widespread reluctance to enroll minors in such biomedical prevention trials due to concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted via the example of one rural South African community that has been particularly devastated by the HIV epidemic. PMID:17403499

Practice brief: adolescents and HIV clinical trials: ethics, culture, and context.

PubMed

MacQueen, Kathleen M; Karim, Quarraisha Abdool

2007-01-01

One quarter of HIV infections globally occur among young people 15 to 24 years of age, and more than half of all new infections are in people younger than 25 years. Clearly, there is a need to identify and implement effective HIV prevention strategies among at-risk teens. Some of the most effective options for slowing the epidemic are biomedical, and several promising methods are in development, including microbicides, vaccines, and preexposure prophylaxis (PREP, or the daily use of antiretrovirals to prevent the acquisition of HIV). There is widespread reluctance to enroll minors in such biomedical prevention trials because of concerns about vulnerability related to physical maturity, experiential maturity, and diminished autonomy as well as legal and social challenges that vary across and within nations. However, excluding minors from trials misses an important opportunity to evaluate the effectiveness, acceptability, and safety of innovative interventions under the best conditions for identifying and resolving potential problems. The challenges of including minors in HIV prevention trials are highlighted through the example of one rural South African community that has been particularly devastated by the HIV epidemic.

Natural Products for Cancer Prevention: Clinical Update 2016.

PubMed

Sanders, Kathleen; Moran, Zelda; Shi, Zaixing; Paul, Rachel; Greenlee, Heather

2016-08-01

To present a clinical update of natural products for cancer prevention and provide oncology nurses with an evidence-based review of natural products for patient counseling and education. Clinical trials published in PubMed. In the past 4 years since the publication of the original review there have been minimal changes in the conclusions of the published literature on the use of natural products for cancer prevention. To date, clinical trials have not demonstrated conclusive benefit of using natural products for cancer prevention, and current guidelines do not recommend their use. This review provides an update on published and ongoing trials and can serve as an updated resource for nurses. Evidence-based natural products databases can help nurses stay current with the scientific literature and be effective educators and health coaches for their patients, who can be influenced by marketing of unregulated products. Patients often discuss the use of natural products with nurses. Nurses have an opportunity to educate and coach patients in effective preventive lifestyle practices. Copyright © 2016 Elsevier Inc. All rights reserved.

The Alzheimer's Disease Cooperative Study Prevention Instrument Project: Longitudinal Outcome of Behavioral Measures as Predictors of Cognitive Decline

PubMed Central

Banks, Sarah Jane; Raman, Rema; He, Feng; Salmon, David P.; Ferris, Steven; Aisen, Paul; Cummings, Jeffrey

2014-01-01

Background/Methods The Alzheimer's Disease Cooperative Study Prevention Instrument Project is a longitudinal study that recruited 644 cognitively healthy older subjects (aged between 75 and 93 years, 58% women) at baseline and evaluated their cognitive change over 4 years. The study was structured like a clinical trial to anticipate a prevention trial and to determine the performance of novel trial instruments in a longitudinal non-interventional trial framework. Behavioral symptoms were assessed at baseline. Results The existence of participant-reported behavioral symptoms at baseline predicted conversion to Clinical Dementia Rating scale score ≥0.5 over the 4-year period. Conclusions The results imply that early anxiety and depression may be harbingers of future cognitive decline, and that patients exhibiting such symptoms, even in the absence of co-occurring cognitive symptoms, should be closely followed over time. PMID:25685141

Antiviral agents and HIV prevention: controversies, conflicts, and consensus

PubMed Central

Cohen, Myron S.; Muessig, Kathryn E.; Smith, M. Kumi; Powers, Kimberly A.; Kashuba, Angela D.M.

2013-01-01

Antiviral agents can be used to prevent HIV transmission before exposure as preexpo-sure prophylaxis (PrEP), after exposure as postexposure prophylaxis, and as treatment of infected people for secondary prevention. Considerable research has shed new light on antiviral agents for PrEP and for prevention of secondary HIV transmission. While promising results have emerged from several PrEP trials, the challenges of poor adherence among HIV-negative clients and possible increase in sexual risk behaviors remain a concern. In addition, a broader pipeline of antiviral agents for PrEP that focuses on genital tract pharmacology and safety and resistance issues must be developed. Antiretroviral drugs have also been used to prevent HIV transmission from HIV-infected patients to their HIV-discordant sexual partners. The HIV Prevention Trials Network 052 trial demonstrated nearly complete prevention of HIV transmission by early treatment of infection, but the generalizability of the results to other risk groups – including intravenous drug users and MSM – has not been determined. Most importantly, the best strategy for use of antiretroviral agents to reduce the spread of HIV at either the individual level or the population level has not been developed, and remains the ultimate goal of this area of investigation. PMID:22507927

An Interdisciplinary Approach for the Integration and Diffusion of Substance Abuse Prevention Programs

ERIC Educational Resources Information Center

Bechtel, Lori J.; Vicary, Judith; Swisher, John; Smith, Edward; Hopkins, Abigail; Henry, Kimberly; Minner, Daphne

2006-01-01

Effective substance abuse prevention programs help students develop knowledge as well as psychosocial competencies that can help them resist or delay the initiation of alcohol, tobacco and other drug (ATOD) use. This paper describes the integration process used in a five-year project, Adoption of Drug Abuse Prevention Training (ADAPT), to study…

Dietary intervention for preventing food allergy in children.

PubMed

Wang, Yichao; Allen, Katrina J; Koplin, Jennifer J

2017-12-01

In the past decade, food allergy has been increasingly recognized as an important public health issue. The role of maternal and infant diet in the development of food allergy has been a major focus of research throughout this period. Recently, research in this area has moved from observational studies to intervention trials, and the findings from these trials have started to influence infant feeding guidelines. In this article, we review recent studies of dietary interventions for preventing food allergy, summarize current knowledge and discuss future research directions. The latest result from an intervention trial shows that introduction of peanut in the first year of life reduces the risk of peanut allergy in high-risk infants. A systematic review and meta-analysis of intervention trials also suggests a protective effect of egg introduction from around 4 to 6 months of age for reducing the risk of egg allergy, with most studies conducted in high-risk infants. Despite several intervention trials involving modifications to the maternal diet, the effect of maternal diet during pregnancy and lactation in preventing food allergy remains unclear. Earlier introduction of allergenic foods is a promising intervention to reduce the risk of some food allergies in high-risk infants. Further work is needed to improve knowledge of how to prevent food allergy in the general population.

Water vapor diffusion membranes, 2

NASA Technical Reports Server (NTRS)

Holland, F. F.; Klein, E.; Smith, J. K.; Eyer, C.

1976-01-01

Transport mechanisms were investigated for the three different types of water vapor diffusion membranes. Membranes representing porous wetting and porous nonwetting structures as well as dense diffusive membrane structures were investigated for water permeation rate as a function of: (1) temperature, (2) solids composition in solution, and (3) such hydrodynamic parameters as sweep gas flow rate, solution flow rate and cell geometry. These properties were measured using nitrogen sweep gas to collect the effluent. In addition, the chemical stability to chromic acid-stabilized urine was measured for several of each type of membrane. A technology based on the mechanism of vapor transport was developed, whereby the vapor diffusion rates and relative susceptibility of membranes to fouling and failure could be projected for long-term vapor recovery trials using natural chromic acid-stabilized urine.

Establishing HIV treatment as prevention in the HIV Prevention Trials Network 052 randomized trial: an ethical odyssey.

PubMed

Cohen, Myron S; McCauley, Marybeth; Sugarman, Jeremy

2012-06-01

Obtaining the definitive data necessary to determine the safety and efficacy of using antiretroviral treatment (ART) to reduce the sexual transmission of HIV in heterosexual couples encountered an array of ethical challenges that threatened to compromise HIV Prevention Trials Network (HPTN) 052, the multinational clinical trial addressing this issue that has profound public health implications. To describe and analyze the major ethical challenges faced in HPTN 052. The ethical issues and modifications of HPTN 052 in response to these issues were cataloged by the principal investigator, the lead coordinator, and the ethicist working on the trial. The major ethical issues that were unique to the trial were then described and analyzed in light of the published literature as well as guidances and policies. The ethical challenges that must be addressed in many clinical trials, such as those related to obtaining informed consent and making provisions for ancillary care, are not described. When HPTN 052 was being designed, ethical questions emerged related to the relevance of the research question itself given data from observational research and a range of beliefs about the appropriate means of preventing and treating HIV infection and AIDS. Furthermore, ethical challenges were faced regarding site selection since there was a scientific need to conduct the research in settings where HIV incidence was high, but alternatives to study participation should be available. As in most HIV-prevention research, ethical questions surrounded the determination of the appropriate prevention package for all of those enrolled. During the course of the trial, guidance documents and policies emerged that were of direct relevance to the research questions, calling for a balancing of concerns for the research subjects and trial integrity. When the study results were made public, there was a need to ensure access to the treatment shown to be effective that in some cases differed from the guidelines used at the sites where the research was being conducted. In addition, questions were raised about whether there was an obligation to notify subjects about 'unlinked' transmissions of HIV, that is, infections acquired from someone other than the designated sexual partner enrolled in the study. The ethical issues described are limited to those discerned by the authors and not those of other stakeholders who may have identified additional issues or had a different perspective in analyzing them. Understanding the ethical challenges faced in HPTN 052 promises to inform the design and conduct of future complex, long-term clinical trials aimed at addressing critical scientific and public health questions, where data and practice patterns emerge over the course of the trial.

Motivation, recruitment, and screening of volunteers for a phase I/II HIV preventive vaccine trial in Thailand.

PubMed

Jenkins, R A; Chinaworapong, S; Morgan, P A; Ruangyuttikarn, C; Sontirat, A; Chiu, J; Michael, R A; Nitayaphan, S; Khamboonruang, C

1998-06-01

Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thailand were evaluated with respect to correlates of participation at each phase. Correlates included demographic variables, motivation for interest in the trial, and factors related to communication and contact. Participants were recruited at two sites through varied methods. The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic. Findings indicated site differences in attrition during recruitment and screening, but not in enrollment into the vaccine trial. Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments.

Substance abuse prevention in American Indian and Alaska Native communities.

PubMed

Whitbeck, Les B; Walls, Melissa L; Welch, Melissa L

2012-09-01

In this article we review three categories of American Indian/Alaska Native (AIAN) substance abuse prevention programs: (1) published empirical trials; (2) promising programs published and unpublished that are in the process of development and that have the potential for empirical trials; and (3) examples of innovative grassroots programs that originate at the local level and may have promise for further development. AIAN communities are taking more and more independent control of substance abuse prevention. We point out that European American prevention scientists are largely unaware of the numerous grassroots prevention work going on in AIAN communities and urge a paradigm shift from adapting European American prevention science "best practices" to creating cultural "best practices" by working from inside AIAN communities.

Drugs for preventing malaria in pregnant women.

PubMed

Garner, P; Gülmezoglu, A M

2006-10-18

Malaria contributes to maternal illness and anaemia in pregnancy, especially in first-time mothers, and can harm the mother and the baby. Drugs given routinely to prevent or mitigate the effects of malaria during pregnancy are often recommended. To assess drugs given to prevent malaria infection and its consequences in pregnant women living in malarial areas. This includes prophylaxis and intermittent preventive treatment (IPT). We searched the Cochrane Infectious Diseases Group Specialized Register (March 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1974 to March 2006), LILACS (1982 to March 2006), and reference lists. We also contacted researchers working in the field. Randomized and quasi-randomized controlled trials comparing antimalarial drugs given regularly with no antimalarial drugs for preventing malaria in pregnant women living in malaria-endemic areas. Both authors extracted data and assessed methodological quality. Dichotomous variables were combined using relative risks (RR) and weighted mean differences (WMD) for mean values, both with 95% confidence intervals (CI). Sixteen trials (12,638 participants) met the inclusion criteria; two used adequate methods to conceal allocation. Antimalarials reduced antenatal parasitaemia when given to all pregnant women (RR 0.53, 95% CI 0.33 to 0.86; 328 participants, 2 trials), placental malaria (RR 0.34, 95% CI 0.26 to 0.45; 1236 participants, 3 trials), but no effect was detected with perinatal deaths (2890 participants, 4 trials). In women in their first or second pregnancy, antimalarial drugs reduced severe antenatal anaemia (RR 0.62, 95% CI 0.50 to 0.78; 2809 participants, 1 prophylaxis and 2 IPT trials), antenatal parasitaemia (RR 0.27, 95% CI 0.17 to 0.44, random-effects model; 2906 participants, 6 trials), and perinatal deaths (RR 0.73, 95% CI 0.53 to 0.99; 1986 participants, 2 prophylaxis and 1 IPT trial; mean birthweight was higher (WMD 126.70 g, 95% CI 88.64 to 164.75 g; 2648 participants, 8 trials), and low birthweight less frequent (RR 0.57, 95% CI 0.46 to 0.72; 2350 participants, 6 trials). Proguanil performed better than chloroquine in one trial of women of all parities in relation to maternal fever episodes. Sulfadoxine-pyrimethamine performed better than chloroquine in two trials of low-parity women. Chemoprophylaxis or IPT reduces antenatal parasite prevalence and placental malaria when given to women in all parity groups. They also have positive effects on birthweight and possibly on perinatal death in low-parity women.

Alzheimer’s Prevention Initiative: A Plan to Accelerate the Evaluation of Presymptomatic Treatments

PubMed Central

Reiman, Eric M.; Langbaum, Jessica B.S.; Fleisher, Adam S.; Caselli, Richard J.; Chen, Kewei; Ayutyanont, Napatkamon; Quiroz, Yakeel T.; Kosik, Kenneth S.; Lopera, Francisco; Tariot, Pierre N.

2012-01-01

There is an urgent need to find effective presymptomatic Alzheimer’s disease (AD) treatments that reduce the risk of AD symptoms or prevent them completely. It currently takes too many healthy people, too much money and too many years to evaluate the range of promising presymptomatic treatments using clinical endpoints. We have used brain imaging and other measurements to track some of the earliest changes associated with the predisposition to AD. We have proposed the Alzheimer’s Prevention Initiative (API) to evaluate investigational amyloid-modifying treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD using brain imaging, cerebrospinal fluid (CSF), and cognitive endpoints. In one trial, we propose to study AD-causing presenilin 1 [PS1] mutation carriers from the world’s largest early-onset AD kindred in Antioquia, Colombia, close to their estimated average age at clinical onset. In another trial, we propose to study apolipoprotein E (APOE)ε4 homozygotes (and possibly heterozygotes) close to their estimated average age at clinical onset. The API has several goals: 1) to evaluate investigational AD-modifying treatments sooner than otherwise possible; 2) to determine the extent to which the treatment’s brain imaging and other biomarker effects predict a clinical benefit—information needed to help qualify biomarker endpoints for use in pivotal prevention trials; 3) to provide a better test of the amyloid hypothesis than clinical trials in symptomatic patients, when these treatments may be too little too late to exert their most profound effect; 4) to establish AD prevention registries needed to support these and other presymptomatic AD trials; and 5) to give those individuals at highest imminent risk of AD symptoms access to the most promising investigational treatments in clinical trials. PMID:21971471

Prevention of Chronic Kidney Disease and Subsequent Effect on Mortality: A Systematic Review and Meta-Analysis

PubMed Central

Khan, Usman A.; Garg, Amit X.; Parikh, Chirag R.; Coca, Steven G.

2013-01-01

Objectives To perform a systematic review of randomized controlled trials to determine whether prevention or slowing of progression of chronic kidney disease would translate into improved mortality, and if so, the attributable risk due to CKD itself on mortality. Background CKD is associated with increased mortality. This association is largely based on evidence from the observational studies and evidence from randomized controlled trials is lacking. Methods We searched Ovid, Medline and Embase for RCTs in which an intervention was given to prevent or slow the progression of CKD and mortality was reported as primary, secondary or adverse outcomes were eligible and selected. For the first phase, pooled relative risks for renal endpoints were assessed. For the second phase, we assessed the effect on mortality in trials of interventions that definitively reduced CKD endpoints. Results Among 52 studies selected in first phase, only renin-angiotensin-aldosterone-system blockade vs. placebo (n = 18 trials, 32,557 participants) met the efficacy criteria for further analysis in the second phase by reducing renal endpoints 15 to 27% compared to placebo. There was no difference in all-cause mortality (RR 0.99, 95% CI 0.92 to 1.08) or CV death (RR 0.97, 95% CI 0.78 to 1.21) between the treatment and control groups in these trials. There was sufficient statistical power to detect a 9% relative risk reduction in all-cause mortality and a 14% relative risk reduction in cardiovascular mortality. Conclusions Firm evidence is lacking that prevention of CKD translates into reductions in mortality. Larger trials with longer follow-up time are needed to determine the benefit of CKD prevention on survival. PMID:24009665

Preventing lower extremity injury in elite orienteerers: study protocol for a randomised controlled trial

PubMed Central

Halvarsson, Bodil

2018-01-01

Background The high physical load associated with running through uneven terrain contributes toorienteerers being exposed to high injury risk, where the majority of injuries are located in the lower extremities. Specific training programmes have been effective at reducing injury risk in sports. Yet no trial has been conducted in elite orienteering. The aim of this study is to investigate the effectiveness of a specific training programme in preventing lower extremity injury in adult elite orienteerers. Study design Randomised controlled trial (RCT). Methods Seventy-two Swedish elite orienteerers, aged 18–40 years, are allocated to an intervention or control group. The intervention group performs four specific exercises, with three difficult levels intensified every second week over the first 4 weeks, targeting strength, flexibility and coordination of the lower extremity. The exercises are completed four times a week (10 min per session) in conjunction with normal training over 14 weeks. Injury data are collected every second week using a valid injury questionnaire distributed by text messages over 14 weeks. The primary outcome is number of substantial injuries in the lower extremity. The secondary outcomes are incidence of ankle sprains and the average substantial injury prevalence across 14 weeks. Discussion Due to high injury risk and lack of injury prevention trials in orienteering, an RCT investigating the effect of a specific exercise programme in preventing lower extremity injury is warranted. The results of this trial will be beneficial to orienteerers, clubs and federations, and increase our understanding on how lower extremity injuries can be prevented in a physically challenging sport. Trial registration number NCT03408925. PMID:29707231

Treatment of diverticular disease of the colon and prevention of acute diverticulitis: a systematic review.

PubMed

Maconi, Giovanni; Barbara, Giovanni; Bosetti, Cristina; Cuomo, Rosario; Annibale, Bruno

2011-10-01

Diverticular disease of the colon is a common disorder, characterized by recurrent symptoms and complications such as diverticulitis, requiring hospital admissions and surgery. This study aimed to systematically review the evidence for medical therapy of diverticular disease in reducing symptoms and preventing acute diverticulitis. MEDLINE and Embase databases (1966 to February 2010). The studies selected were prospective clinical trials on uncomplicated diverticular disease of the colon. Four investigators independently reviewed articles, extracted data, and assessed study quality according to standardized criteria. The main outcomes measured were improvement in symptoms, complete remission of symptoms, and prevention of acute diverticulitis. We identified 31 studies, including 6 placebo-controlled trials. The methodological quality of these studies was suboptimal. Only 10 trials provided a detailed description of the patient history, 8 assessed symptoms by the use of a validated questionnaire, and 14 appropriately defined inclusion and exclusion criteria. Only one long-term double-blind placebo-controlled study was identified. This reported a significant improvement in symptoms and greater prevalence of symptom-free patients at 1 year with fiber plus rifaximin in comparison with fiber alone. The efficacy of treatment in preventing acute diverticulitis was evaluated in 11 randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and failed to show a significant difference between treatments. However, cumulative data from these trials revealed a significant benefit following rifaximin and fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P = .012), but with a number needed to treat of 57, to prevent an attack of acute diverticulitis. : Heterogeneity of the study design, patients' characteristics, regimens and combination of studied treatment, and outcome reporting precluded the pooling of results and limited interpretation. The treatment for diverticular disease relies mainly on data from uncontrolled studies. Treatment showed some evidence of improvement in symptoms, but its role in the prevention of acute diverticulitis remains to be defined.

Fixed-node diffusion Monte Carlo potential energy curve of the fluorine molecule F{sub 2} using selected configuration interaction trial wavefunctions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giner, Emmanuel; Scemama, Anthony; Caffarel, Michel

2015-01-28

The potential energy curve of the F{sub 2} molecule is calculated with Fixed-Node Diffusion Monte Carlo (FN-DMC) using Configuration Interaction (CI)-type trial wavefunctions. To keep the number of determinants reasonable and thus make FN-DMC calculations feasible in practice, the CI expansion is restricted to those determinants that contribute the most to the total energy. The selection of the determinants is made using the CIPSI approach (Configuration Interaction using a Perturbative Selection made Iteratively). The trial wavefunction used in FN-DMC is directly issued from the deterministic CI program; no Jastrow factor is used and no preliminary multi-parameter stochastic optimization of themore » trial wavefunction is performed. The nodes of CIPSI wavefunctions are found to reduce significantly the fixed-node error and to be systematically improved upon increasing the number of selected determinants. To reduce the non-parallelism error of the potential energy curve, a scheme based on the use of a R-dependent number of determinants is introduced. Using Dunning’s cc-pVDZ basis set, the FN-DMC energy curve of F{sub 2} is found to be of a quality similar to that obtained with full configuration interaction/cc-pVQZ.« less

Recruitment barriers for prophylactic vaccine trials: A study in Belgium.

PubMed

Harrington, Lauriane; Van Damme, Pierre; Vandermeulen, Corinne; Mali, Stéphanie

2017-12-04

Recruitment of volunteers is one of the main challenges in clinical trial management, and there is little information about recruitment barriers for preventative vaccine trials. We investigated both the recruitment barriers and recruitment strategies for preventive vaccine trials in Belgium. A 10 min survey was used as well as interviews of staff at all clinical trial sites in Belgium that regularly perform vaccine trials. We observed that there are successful recruitment strategies and few recruitment issues for trials involving healthy adults and those over 65 years old. However, challenges face the recruitment of paediatric populations, pregnant women, patients and the very elderly (over 85 years old). From these results, we identified three priority areas to increase recruitment for prophylactic vaccine trials in Belgium. These are: the lack of public knowledge about infectious diseases; the lack of resources of healthcare professionals to take part in clinical trials; and the burden to potential volunteers to take part in a trial. These were discussed with stakeholders and solutions were proposed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The diffusion of a community-level HIV intervention for women: lessons learned and best practices.

PubMed

King, Winifred; Nu'Man, Jeanette; Fuller, Talleria R; Brown, Mari; Smith, Shuenae; Howell, A Vyann; Little, Stacey; Patrick, Patricia; Glover, LaShon

2008-09-01

Abstract Early in the HIV/AIDS epidemic in the United States, relatively few women were diagnosed with HIV infection and AIDS. Today, the epidemic represents a growing and persistent health threat to women in the United States, especially young women and women of color. In 2005, the leading cause of HIV infection among African American women and Latinas was heterosexual contact. In addressing HIV prevention needs among women, community-level strategies are needed to increase consistent condom use by women and their partners and to change community norms to support safer sex behaviors. The Real AIDS Prevention Project (RAPP) is a community-based HIV prevention intervention for women and their partners. RAPP is based on a community mobilization model that involves a combination of activities, including street outreach, one-on-one discussions called stage-based encounters, role model stories, community networks, and small group activities. The objectives of RAPP are to increase consistent condom use by women and their partners and change community norms associated with perceptions of condom use and high-risk behaviors in an effort to make safer sex practice more acceptable. This paper describes the Centers for Disease Control and Prevention (CDC) Division of HIV/AIDS Prevention (DHAP) effort to nationally diffuse RAPP from March 2003 through May 2007 and lessons learned from that diffusion experience. The paper specifically discusses (1) collaborating and planning with researchers, (2) a diffusion needs assessment that was designed to assess prior implementation experiences among select agencies, (3) developing the intervention package, (4) developing and piloting training for community-based organizations (CBOs), (5) a rollout of national trainings for health departments and community-based organizations interested in implementing RAPP, and (6) ongoing quality assurance activities and the provision of technical assistance and support. RAPP has been proven effective in reducing HIV transmission risk behaviors and improving communication and negotiation skills necessary for African American women and Latinas to reduce their risk for HIV infection and improve their overall health status.

Effectiveness of the population-based Check your health preventive programme conducted in primary care with 4 years follow-up [the CORE trial]: study protocol for a randomised controlled trial.

PubMed

Maindal, Helle Terkildsen; Støvring, Henrik; Sandbaek, Annelli

2014-08-29

The periodic health check-up has been a fundamental part of routine medical practice for decades, despite a lack of consensus regarding its value in health promotion and disease prevention. A large-scale Danish population-based preventive programme 'Check your health' was developed based on available evidence of screening and successive accepted treatment, prevention for diseases and health promotion, and is closely aligned with the current health care system.The objective of the 'Check your health' [CORE] trial is to investigate effectiveness on health outcomes of a preventive health check offered at a population-level to all individuals aged 30-49 years, and to establish the cost-effectiveness. The trial will be conducted as a pragmatic household-cluster randomised controlled trial involving 10,505 individuals. All individuals within a well-defined geographical area in the Central Denmark Region, Denmark (DK) were randomised to be offered a preventive health check (Intervention group, n = 5250) or to maintain routine access to healthcare until a delayed intervention (Comparison group, n = 5255). The programme consists of a health examination which yields an individual risk profile, and according to this participants are assigned to one of the following interventions: (a) referral to a health promoting consultation in general practice, (b) behavioural programmes at the local Health Centre, or (c) no need for follow-up.The primary outcomes at 4 years follow-up are: ten-year-risk of fatal cardiovascular event (Heart-SCORE model), physical activity level (self-report and cardiorespiratory fitness), quality of life (SF12), sick leave and labour market attachment. Cost-effectiveness will be evaluated according to life years gained, direct costs and total health costs. Intention to treat analysis will be performed. Results from the largest Danish health check programme conducted within the current healthcare system, spanning the sectors which share responsibility for the individual, will provide a scientific basis to be used in the development of systems to optimise population health in the 21st century. The trial has registered at ClinicalTrials.gov with an ID: NCT02028195 (7. March 2014).

The effect of fall prevention exercise programmes on fall induced injuries in community dwelling older adults: systematic review and meta-analysis of randomised controlled trials.

PubMed

El-Khoury, Fabienne; Cassou, Bernard; Charles, Marie-Aline; Dargent-Molina, Patricia

2013-10-29

To determine whether, and to what extent, fall prevention exercise interventions for older community dwelling people are effective in preventing different types of fall related injuries. Electronic databases (PubMed, the Cochrane Library, Embase, and CINAHL) and reference lists of included studies and relevant reviews from inception to July 2013. Randomised controlled trials of fall prevention exercise interventions, targeting older (>60 years) community dwelling people and providing quantitative data on injurious falls, serious falls, or fall related fractures. Based on a systematic review of the case definitions used in the selected studies, we grouped the definitions of injurious falls into more homogeneous categories to allow comparisons of results across studies and the pooling of data. For each study we extracted or calculated the rate ratio of injurious falls. Depending on the available data, a given study could contribute data relevant to one or more categories of injurious falls. A pooled rate ratio was estimated for each category of injurious falls based on random effects models. 17 trials involving 4305 participants were eligible for meta-analysis. Four categories of falls were identified: all injurious falls, falls resulting in medical care, severe injurious falls, and falls resulting in fractures. Exercise had a significant effect in all categories, with pooled estimates of the rate ratios of 0.63 (95% confidence interval 0.51 to 0.77, 10 trials) for all injurious falls, 0.70 (0.54 to 0.92, 8 trials) for falls resulting in medical care, 0.57 (0.36 to 0.90, 7 trials) for severe injurious falls, and 0.39 (0.22 to 0.66, 6 trials) for falls resulting in fractures, but significant heterogeneity was observed between studies of all injurious falls (I(2)=50%, P=0.04). Exercise programmes designed to prevent falls in older adults also seem to prevent injuries caused by falls, including the most severe ones. Such programmes also reduce the rate of falls leading to medical care.

Latino recruitment to cancer prevention/screening trials in the Southwest: setting a research agenda.

PubMed

Larkey, Linda K; Ogden, Sheryl L; Tenorio, Sally; Ewell, Teresa

2008-02-01

Examples of cancer prevention and screening trials in the Southwest are reviewed as a platform for highlighting gaps in research on Latino recruitment. Three trials are described, using "message/source/channel" categories as a framework. Each trial engaged community members to facilitate recruitment and developed tailored strategies to meet challenges emerging after recruitment began. Although we affirm that culturally relevant messages, community member referral networks, and adjustment to community realities seem important to Latino recruitment, current anecdotal and research findings do not allow evidence-based recommendations to be made. We suggest a research agenda to further illuminate critical factors for successful Latino recruitment.

Hand washing promotion for preventing diarrhoea

PubMed Central

Ejemot-Nwadiaro, Regina I; Ehiri, John E; Arikpo, Dachi; Meremikwu, Martin M; Critchley, Julia A

2015-01-01

Background Diarrhoea accounts for 1.8 million deaths in children in low- and middle-income countries (LMICs). One of the identified strategies to prevent diarrhoea is hand washing. Objectives To assess the effects of hand washing promotion interventions on diarrhoeal episodes in children and adults. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (27 May 2015); CENTRAL (published in the Cochrane Library 2015, Issue 5); MEDLINE (1966 to 27 May 2015); EMBASE (1974 to 27 May 2015); LILACS (1982 to 27 May 2015); PsycINFO (1967 to 27 May 2015); Science Citation Index and Social Science Citation Index (1981 to 27 May 2015); ERIC (1966 to 27 May 2015); SPECTR (2000 to 27 May 2015); Bibliomap (1990 to 27 May 2015); RoRe, The Grey Literature (2002 to 27 May 2015); World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP), metaRegister of Controlled Trials (mRCT), and reference lists of articles up to 27 May 2015. We also contacted researchers and organizations in the field. Selection criteria Individually randomized controlled trials (RCTs) and cluster-RCTs that compared the effects of hand washing interventions on diarrhoea episodes in children and adults with no intervention. Data collection and analysis Three review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. We stratified the analyses for child day-care centres or schools, community, and hospital-based settings. Where appropriate, incidence rate ratios (IRR) were pooled using the generic inverse variance method and random-effects model with 95% confidence intervals (CIs). We used the GRADE approach to assess the quality of evidence. Main results We included 22 RCTs: 12 trials from child day-care centres or schools in mainly high-income countries (54,006 participants), nine community-based trials in LMICs (15,303 participants), and one hospital-based trial among people with acquired immune deficiency syndrome (AIDS) (148 participants). Hand washing promotion (education activities, sometimes with provision of soap) at child day-care facilities or schools prevents around one-third of diarrhoea episodes in high income countries (rate ratio 0.70; 95% CI 0.58 to 0.85; nine trials, 4664 participants, high quality evidence), and may prevent a similar proportion in LMICs but only two trials from urban Egypt and Kenya have evaluated this (rate ratio 0.66, 95% CI 0.43 to 0.99; two trials, 45,380 participants, low quality evidence). Only three trials reported measures of behaviour change and the methods of data collection were susceptible to bias. In one trial from the USA hand washing behaviour was reported to improve; and in the trial from Kenya that provided free soap, hand washing did not increase, but soap use did (data not pooled; three trials, 1845 participants, low quality evidence). Hand washing promotion among communities in LMICs probably prevents around one-quarter of diarrhoea episodes (rate ratio 0.72, 95% CI 0.62 to 0.83; eight trials, 14,726 participants, moderate quality evidence). However, six of these eight trials were from Asian settings, with only single trials from South America and sub-Saharan Africa. In six trials, soap was provided free alongside hand washing education, and the overall average effect size was larger than in the two trials which did not provide soap (soap provided: rate ratio 0.66, 95% CI 0.56 to 0.78; six trials, 11,422 participants; education only: rate ratio: 0.84, 95% CI 0.67 to 1.05; two trials, 3304 participants). There was increased hand washing at major prompts (before eating/cooking, after visiting the toilet or cleaning the baby's bottom), and increased compliance to hand hygiene procedure (behavioural outcome) in the intervention groups than the control in community trials (data not pooled: three trials, 3490 participants, high quality evidence). Hand washing promotion for the one trial conducted in a hospital among high-risk population showed significant reduction in mean episodes of diarrhoea (1.68 fewer) in the intervention group (Mean difference 1.68, 95% CI 1.93 to 1.43; one trial, 148 participants, moderate quality evidence). There was increase in hand washing frequency, seven times per day in the intervention group versus three times in the control in this hospital trial (one trial, 148 participants, moderate quality evidence). We found no trials evaluating or reporting the effects of hand washing promotions on diarrhoea-related deaths, all-cause-under five mortality, or costs. Authors' conclusions Hand washing promotion probably reduces diarrhoea episodes in both child day-care centres in high-income countries and among communities living in LMICs by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term. PLAIN LANGUAGE SUMMARY Hand washing promotion for preventing diarrhoea Review question This Cochrane Review summarises trials evaluating the effects of promoting hand washing on the incidence of diarrhoea among children and adults in day-care centres, schools, communities, or hospitals. After searching for relevant trials up to 27 May 2015, we included 22 randomized controlled trials conducted in both high-income countries (HICs) and low- and middle-income countries (LMICs). These trials enrolled 69,309 children and 148 adults. How does hand washing prevent diarrhoea and how might hand washing be promoted Diarrhoea causes many deaths in children below five years of age, mostly in LMICs. The organisms causing diarrhoea are transmitted from person to person through food and water contaminated with faeces, or through person-to-person contact. Hand washing after defecation, or after cleaning a baby's bottom, and before preparing and eating food, can therefore reduce the risk of diarrhoea. Hand washing can be promoted through group or individual training on hygiene education, germ-health awareness, use of posters, leaflets, comic books, songs, and drama. What this review says Hand washing promotion at child day-care facilities or schools in HICs probably prevents around 30% of diarrhoea episodes (high quality evidence), and may prevent a similar proportion in schools in LMICs (low quality evidence). Among communities in LMICs hand washing promotion prevents around 28% of diarrhoea episodes (moderate quality evidence). In the only hospital-based trial included in this review, hand washing promotion also had important reduction in the mean episodes of diarrhoea (moderate quality evidence). This is based on only a single trial with few participants and thus there is need for more trials to confirm this. Effects of hand washing promotion on related hand hygiene behaviour changes improved more in the intervention groups than in the control in all the settings (low to high quality evidence). None of the included trials assessed the effect of handwashing promotion on diarrhoeal-related deaths, all-cause under-five mortality, or the cost-effectiveness of hand washing promotions. Conclusion Hand washing promotion in HICs and LMICs settings may reduce incidence of diarrhoea by about 30%. However, less is known about how to help people maintain hand washing habits in the longer term. PMID:26346329

Ionising radiation-free whole-body MRI versus (18)F-fluorodeoxyglucose PET/CT scans for children and young adults with cancer: a prospective, non-randomised, single-centre study.

PubMed

Klenk, Christopher; Gawande, Rakhee; Uslu, Lebriz; Khurana, Aman; Qiu, Deqiang; Quon, Andrew; Donig, Jessica; Rosenberg, Jarrett; Luna-Fineman, Sandra; Moseley, Michael; Daldrup-Link, Heike E

2014-03-01

Imaging tests are essential for staging of children with cancer. However, CT and radiotracer-based imaging procedures are associated with substantial exposure to ionising radiation and risk of secondary cancer development later in life. Our aim was to create a highly effective, clinically feasible, ionising radiation-free staging method based on whole-body diffusion-weighted MRI and the iron supplement ferumoxytol, used off-label as a contrast agent. We compared whole-body diffusion-weighted MRI with standard clinical (18)F-fluorodeoxyglucose ((18)F-FDG) PET/CT scans in children and young adults with malignant lymphomas and sarcomas. Whole-body diffusion-weighted magnetic resonance images were generated by coregistration of colour-encoded ferumoxytol-enhanced whole-body diffusion-weighted MRI scans for tumour detection with ferumoxytol-enhanced T1-weighted MRI scans for anatomical orientation, similar to the concept of integrated (18)F-FDG PET/CT scans. Tumour staging results were compared using Cohen's κ statistics. Histopathology and follow-up imaging served as the standard of reference. Data was assessed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01542879. 22 of 23 recruited patients were analysed because one patient discontinued before completion of the whole-body scan. Mean exposure to ionising radiation was 12·5 mSv (SD 4·1) for (18)F-FDG PET/CT compared with zero for whole-body diffusion-weighted MRI. (18)F-FDG PET/CT detected 163 of 174 malignant lesions at 1325 anatomical regions and whole-body diffusion-weighted MRI detected 158. Comparing (18)F-FDG PET/CT to whole-body diffusion-weighted MRI, sensitivities were 93·7% (95% CI 89·0-96·8) versus 90·8% (85·5-94·7); specificities 97·7% (95% CI 96·7-98·5) versus 99·5% (98·9-99·8); and diagnostic accuracies 97·2% (93·6-99·4) versus 98·3% (97·4-99·2). Tumour staging results showed very good agreement between both imaging modalities with a κ of 0·93 (0·81-1·00). No adverse events after administration of ferumoxytol were recorded. Ferumoxytol-enhanced whole-body diffusion-weighted MRI could be an alternative to (18)F-FDG PET/CT for staging of children and young adults with cancer that is free of ionising radiation. This new imaging test might help to prevent long-term side-effects from radiographic staging procedures. Thrasher Research Fund and Clinical Health Research Institute at Stanford University. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prevention of recurrent urinary tract infection in children.

PubMed

Williams, Gabrielle; Craig, Jonathan C

2009-02-01

Urinary tract infection (UTI) in children is common (5-10%) and recurs in 10-30%. UTI causes an unpleasant, usually febrile illness in children. This review focuses on studies evaluating interventions to prevent UTI in children and published between January 2007 and June 2008. Three relevant updated Cochrane reviews, six randomized trials and an evidence-based guideline were published in the study period. Five of the six trials and one of the three Cochrane updates included data on the effects of relevant interventions in children. Three of the six trials investigated the efficacy of long-term, low-dose antibiotics as prophylaxis, and the other trials and both Cochrane updates evaluated complementary therapies such as vitamin A, probiotics and herbal supplements. The benefit of prophylactic antibiotics for the prevention of recurrent UTI in children remains unclear because of underpowered and suboptimally designed trials, but these studies suggest that any benefit is likely to be small, and clinical significance may be limited. The trials of complementary interventions (vitamin A, probiotics, cranberry, nasturtium and horseradish) generally gave favourable results but were not conclusive. Children and families who use these products should be aware that further infections are possible despite their use.

HIV vaccine trials: will intravenous drug users enroll?

PubMed Central

Meyers, K; Metzger, D S; Navaline, H; Woody, G E; McLellan, A T

1994-01-01

OBJECTIVES. The purpose of this study was to assess the willingness of intravenous drug users to participate in a preventive human immunodeficiency virus (HIV) vaccine efficacy trial. METHODS. Of the 347 intravenous drug users in methadone treatment who were approached for participation, 257 completed a battery of self-administered questionnaires assessing risk behaviors, interest in vaccine trials, and other vaccine-related information. Data from 16 known seropositives and 1 inconsistent responder were dropped from analyses (n = 240). RESULTS. Fifty-two percent of the subjects expressed a willingness to be one of the first individuals to participate in a preventive HIV vaccine efficacy trial. Subjects who had recently shared needles or works and subjects who trusted the government to ensure vaccine safety were both twice as likely to report interest in participation. Twenty-two percent of subjects reported that they would increase needle sharing if vaccinated. Thirty percent did not know what a vaccine was. CONCLUSIONS. These findings suggest that some in-treatment intravenous drug users would volunteer for a preventive HIV vaccine efficacy trial. Education and counseling will be required to ensure that subjects fully understand the trial's purposes, methods, risks and benefits. PMID:8179045

What's new in stroke? The top 10 studies of 2009-2011: part II.

PubMed

Hart, Robert G; Oczkowski, Wiesław J

2011-06-01

Five studies published between 2009 and 2011 are reviewed that importantly inform stroke prevention for patients with atrial fibrillation (AF) or with cervical carotid artery stenosis. Two large, phase III randomized trials tested novel oral anticoagulants for stroke prevention in patients with AF: the direct thrombin inhibitor dabigatran 150 mg twice daily was superior to adjusted-dose warfarin (RE-LY trial) and the direct factor Xa inhibitor apixaban was far superior to aspirin in patients deemed unsuitable for warfarin (AVERROES trial). For both novel anticoagulants, major bleeding rates were similar to the comparator treatment. Clopidogrel plus aspirin was more efficacious than aspirin alone for prevention of stroke in patients with AF deemed unsuitable for warfarin, but major bleeding was significantly increased with dual antiplatelet therapy (ACTIVE A trial). Two large randomized trials (CREST, ICSS) provide the best available data on the short-term risks of carotid artery stenting vs. endarterectomy. In both trials, periprocedural stroke was more frequent with stenting than with endarterectomy, but the increased risk was largely confined to patients >70 years old. For younger patients, periprocedural risks were comparable with stenting or endarterectomy, but long-term outcomes are required to assess the relative merits of the two procedures.

The Value of Pre-Screening in the Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease Trial.

PubMed

Rios-Romenets, S; Giraldo-Chica, M; López, H; Piedrahita, F; Ramos, C; Acosta-Baena, N; Muñoz, C; Ospina, P; Tobón, C; Cho, W; Ward, M; Langbaum, J B; Tariot, P N; Reiman, E M; Lopera, F

2018-01-01

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD.

HDDM: Hierarchical Bayesian estimation of the Drift-Diffusion Model in Python.

PubMed

Wiecki, Thomas V; Sofer, Imri; Frank, Michael J

2013-01-01

The diffusion model is a commonly used tool to infer latent psychological processes underlying decision-making, and to link them to neural mechanisms based on response times. Although efficient open source software has been made available to quantitatively fit the model to data, current estimation methods require an abundance of response time measurements to recover meaningful parameters, and only provide point estimates of each parameter. In contrast, hierarchical Bayesian parameter estimation methods are useful for enhancing statistical power, allowing for simultaneous estimation of individual subject parameters and the group distribution that they are drawn from, while also providing measures of uncertainty in these parameters in the posterior distribution. Here, we present a novel Python-based toolbox called HDDM (hierarchical drift diffusion model), which allows fast and flexible estimation of the the drift-diffusion model and the related linear ballistic accumulator model. HDDM requires fewer data per subject/condition than non-hierarchical methods, allows for full Bayesian data analysis, and can handle outliers in the data. Finally, HDDM supports the estimation of how trial-by-trial measurements (e.g., fMRI) influence decision-making parameters. This paper will first describe the theoretical background of the drift diffusion model and Bayesian inference. We then illustrate usage of the toolbox on a real-world data set from our lab. Finally, parameter recovery studies show that HDDM beats alternative fitting methods like the χ(2)-quantile method as well as maximum likelihood estimation. The software and documentation can be downloaded at: http://ski.clps.brown.edu/hddm_docs/

Intervening with practitioners to improve the quality of prevention: One year findings from a randomized trial of Assets-Getting To Outcomes

PubMed Central

Chinman, Matthew; Acosta, Joie; Ebener, Patricia; Burkhart, Q; Malone, Patrick; Paddock, Susan M.; Clifford, Michael; Corsello, Maryann; Duffy, Tim; Hunter, Sarah; Jones, Margaret; Lahti, Michel; Phillips, Andrea; Savell, Susan; Scales, Peter C.; Tellett-Royce, Nancy

2013-01-01

There continues to be a gap in prevention outcomes achieved in research trials vs. “real world” practice. This article summarizes interim findings from a randomized trial testing Assets-Getting To Outcomes (AGTO), a two-year intervention to build prevention practitioners’ capacity to implement positive youth development-oriented prevention practices in 12 prevention coalitions in Maine. A survey of coalition members was used to assess change on individual practitioners’ prevention capacity between Baseline and one year later. Structured interviews with 32 program leaders (16 intervention, 16 control) were used to assess changes in prevention practices during the same time period. Change in prevention capacity over time between intervention and control did not differ, however in secondary analyses of only those assigned to the AGTO condition, AGTO users had evidenced greater improvement in their self-efficacy to conduct Assets-based programming and the frequency with which they engaged in AGTO behaviors. Non-users’ self-efficacy of AGTO declined. Interview ratings showed improvement in several key areas of performance among intervention programs. Improvement was associated with the number of technical assistance hours received. These results suggest that, after one year, AGTO is beginning to improve the capacity of community practitioners who make use of it. PMID:23605473

Interventions for preventing recurrent urinary tract infection during pregnancy.

PubMed

Schneeberger, Caroline; Geerlings, Suzanne E; Middleton, Philippa; Crowther, Caroline A

2012-11-14

Recurrent urinary tract infections (RUTI) are common in women who are pregnant and may cause serious adverse pregnancy outcomes for both mother and child including preterm birth and small-for-gestational-age babies. Interventions used to prevent RUTI in women who are pregnant can be pharmacological (antibiotics) or non-pharmacological (cranberry products, acupuncture, probiotics and behavioural modifications). So far little is known about the best way to prevent RUTI in pregnant women. To assess the effects of interventions for preventing recurrent urinary tract infections in pregnant women.The primary maternal outcomes were RUTI before birth (variously defined) and preterm birth (before 37 weeks). The primary infant outcomes were small-for-gestational age and total mortality. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (8 June 2012) and reference lists of retrieved articles. Published, unpublished and ongoing randomised controlled trials (RCTs), quasi-RCTs, clustered-randomised trials and abstracts of any intervention (pharmacological and non-pharmacological) for preventing RUTI during pregnancy (compared with another intervention, placebo or with usual care). Two review authors independently evaluated the one identified trial for inclusion and assessed trial quality. Two review authors extracted data. Data were checked for accuracy. The review included one trial involving 200 women. The trial compared a daily dose of nitrofurantoin and close surveillance (regular clinic visit, urine cultures and antibiotics when a positive culture was found) with close surveillance only. No significant differences were found for the primary outcomes: recurrent pyelonephritis (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.31 to 2.53, one study, 167 women), recurrent urinary tract infection before birth (RR 0.30, 95% CI 0.06 to 1.38; one study 167 women) and preterm birth (before 37 weeks) (RR 1.18, 95% CI 0.42 to 3.35; one study 147 women). The incidence of asymptomatic bacteriuria (ASB) (at least 10(3) colonies per mL) (secondary outcome), only reported in women with a clinic attendance rate of more than 90% (RR 0.55, 95% CI 0.34 to 0.89; one study, 102 women), was significantly reduced in women who received nitrofurantoin and close surveillance. A daily dose of nitrofurantoin and close surveillance has not been shown to prevent RUTI compared with close surveillance alone. A significant reduction of ASB was found in women with a high clinic attendance rate and who received nitrofurantoin and close surveillance. There was limited reporting of both primary and secondary outcomes for both women and infants. No conclusions can be drawn regarding the optimal intervention to prevent RUTI in women who are pregnant. Randomised controlled trials comparing different pharmacological and non-pharmacological interventions are necessary to investigate potentially effective interventions to prevent RUTI in women who are pregnant.

Integrating Models of Diffusion and Behavior to Predict Innovation Adoption, Maintenance, and Social Diffusion.

PubMed

Smith, Rachel A; Kim, Youllee; Zhu, Xun; Doudou, Dimi Théodore; Sternberg, Eleanore D; Thomas, Matthew B

2018-01-01

This study documents an investigation into the adoption and diffusion of eave tubes, a novel mosquito vector control, during a large-scale scientific field trial in West Africa. The diffusion of innovations (DOI) and the integrated model of behavior (IMB) were integrated (i.e., innovation attributes with attitudes and social pressures with norms) to predict participants' (N = 329) diffusion intentions. The findings showed that positive attitudes about the innovation's attributes were a consistent positive predictor of diffusion intentions: adopting it, maintaining it, and talking with others about it. As expected by the DOI and the IMB, the social pressure created by a descriptive norm positively predicted intentions to adopt and maintain the innovation. Drawing upon sharing research, we argued that the descriptive norm may dampen future talk about the innovation, because it may no longer be seen as a novel, useful topic to discuss. As predicted, the results showed that as the descriptive norm increased, the intention to talk about the innovation decreased. These results provide broad support for integrating the DOI and the IMB to predict diffusion and for efforts to draw on other research to understand motivations for social diffusion.

Sharing the trousers: gender roles and relationships in an HIV-prevention trial in Zimbabwe.

PubMed

Montgomery, Elizabeth T; Chidanyika, Agnes; Chipato, Tsungai; van der Straten, Ariane

2012-01-01

Male and female gender roles and inequalities are important in contributing to the disproportionate burden of HIV experienced by women in sub-Saharan Africa. Within the context of an HIV prevention trial, we aimed to describe and understand male partner influence on women's use of HIV-prevention methods. Our presumption was not that regressive gender norms prevailed - rather, that a wide range of gendered attitudes and dynamics would be expressed among couples. Data from 16 focus groups with Zimbabwean female trial participants and their male partners and 4 in-depth couples interviews were collected, and form the basis of the analysis. Findings offer descriptions of how couples have adapted techniques for negotiating modern household economies and sexual decision-making in a manner that both preserves traditional gender roles, while accommodating women's entrance into new domains such as the workforce or an HIV-prevention trial. Women's agency to introduce novel female-initiated-method use into her intimate relationships is described. Men and women's accounts of method introduction and use suggest different perceptions about the locus of sexual decision making. The study provides unique insight into a gendered context that is dynamic yet sensitive to change, which in turn can provide useful information to more appropriately guide HIV-prevention activities in this setting.

European Prevention of Alzheimer's Dementia Registry: Recruitment and prescreening approach for a longitudinal cohort and prevention trials.

PubMed

Vermunt, Lisa; Veal, Colin D; Ter Meulen, Lea; Chrysostomou, Charalambos; van der Flier, Wiesje; Frisoni, Giovanni B; Guessous, Idris; Kivipelto, Miia; Marizzoni, Moira; Martinez-Lage, Pablo; Molinuevo, José Luis; Porteous, David; Ritchie, Karen; Scheltens, Philip; Ousset, Pierre-Jean; Ritchie, Craig W; Luscan, Gerald; Brookes, Anthony J; Visser, Pieter Jelle

2018-06-01

It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach. A virtual registry, with access to risk factors and biomarkers for AD through minimal data sets of ongoing cohort studies, was set up. To date, ten cohorts have been included in the EPAD. Around 2500 participants have been selected, using variables associated with the risk for AD. Of these, 15% were already recruited in the EPAD longitudinal cohort study, which serves as a trial readiness cohort. This study demonstrates that a virtual registry can be used for the preselection of participants for AD studies. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

PubMed Central

Pandit, Anil; Aryal, Madan Raj; Aryal Pandit, Aashrayata; Hakim, Fayaz Ahmad; Giri, Smith; Mainali, Naba Raj; Sharma, Prashant; Lee, Howard R; Fortuin, F David; Mookadam, Farouk

2014-01-01

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials. PMID:25332779

Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.

PubMed

Schrijver, E J M; de Graaf, K; de Vries, O J; Maier, A B; Nanayakkara, P W B

2016-01-01

Haloperidol is generally considered the drug of choice for in-hospital delirium management. We conducted a systematic review to evaluate the evidence for the efficacy and safety of haloperidol for the prevention and treatment of delirium in hospitalized patients. PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO, and the Cochrane Library were systematically searched up to April 21, 2015. We included English full-text randomized controlled trials using haloperidol for the prevention or treatment of delirium in adult hospitalized patients reporting on delirium incidence, duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis was not conducted because of between-study heterogeneity. Twelve studies met our inclusion criteria, four prevention and eight treatment trials. Methodological limitations decreased the graded quality of included studies. Results from placebo-controlled prevention studies suggest a haloperidol-induced protective effect for delirium in older patients scheduled for surgery: two studies reported a significant reduction in ICU delirium incidence and one study found a significant reduction in delirium severity and duration. Although placebo-controlled trials are missing, pharmacological treatment of established delirium reduced symptom severity. Haloperidol administration was not associated with treatment-limiting side-effects, but few studies used a systematic approach to identify adverse events. Although results on haloperidol for delirium management seem promising, current prevention trials lack external validity and treatment trials did not include a placebo arm on top of standard nonpharmacological care. We therefore conclude that the current use of haloperidol for in-hospital delirium is not based on robust and generalizable evidence. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Efficacy of smoking prevention program 'Smoke-free Kids': study protocol of a randomized controlled trial

PubMed Central

2009-01-01

Background A strong increase in smoking is noted especially among adolescents. In the Netherlands, about 5% of all 10-year olds, 25% of all 13-year olds and 62% of all 17-year olds report ever smoking. In the U.S., an intervention program called 'Smoke-free Kids' was developed to prevent children from smoking. The present study aims to assess the effects of this home-based smoking prevention program in the Netherlands. Methods/Design A randomized controlled trial is conducted among 9 to 11-year old children of primary schools. Participants are randomly assigned to the intervention and control conditions. The intervention program consists of five printed activity modules designed to improve parenting skills specific to smoking prevention and parent-child communication regarding smoking. These modules will include additional sheets with communication tips. The modules for the control condition will include solely information on smoking and tobacco use. Initiation of cigarette smoking (first instance of puffing on a lighted cigarette), susceptibility to cigarette smoking, smoking-related cognitions, and anti-smoking socialization will be the outcome measures. To collect the data, telephone interviews with mothers as well as with their child will be conducted at baseline. Only the children will be examined at post-intervention follow-ups (6, 12, 24, and 36 months after the baseline). Discussion This study protocol describes the design of a randomized controlled trial that will evaluate the effectiveness of a home-based smoking prevention program. We expect that a significantly lower number of children will start smoking in the intervention condition compared to control condition as a direct result of this intervention. If the program is effective, it is applicable in daily live, which will facilitate implementation of the prevention protocol. Trial registration Netherlands Trial Register NTR1465 PMID:20025727

Intravenous N-Acetylcysteine for Prevention of Contrast-Induced Nephropathy: A Meta-Analysis of Randomized, Controlled Trials

PubMed Central

Sun, Zikai; Fu, Qiang; Cao, Longxing; Jin, Wen; Cheng, LingLing; Li, Zhiliang

2013-01-01

Background Contrast-induced nephropathy (CIN) is one of the common causes of acute renal insufficiency after contrast procedures. Whether intravenous N-acetylcysteine (NAC) is beneficial for the prevention of contrast-induced nephropathy is uncertain. In this meta-analysis of randomized controlled trials, we aimed to assess the efficacy of intravenous NAC for preventing CIN after administration of intravenous contrast media. Study Design Relevant studies published up to September 2012 that investigated the efficacy of intravenous N-acetylcysteine for preventing CIN were collected from MEDLINE, OVID, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and the conference proceedings from major cardiology and nephrology meetings. The primary outcome was CIN. Secondary outcomes included renal failure requiring dialysis, mortality, and length of hospitalization. Data were combined using random-effects models with the performance of standard tests to assess for heterogeneity and publication bias. Meta-regression analyses were also performed. Results Ten trials involving 1916 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-induced nephropathy was 0.68 (95% CI, 0.46 to 1.02), a nonsignificant trend towards benefit in patients treated with intravenous NAC. There was evidence of significant heterogeneity in NAC effect across studies (Q = 17.42, P = 0.04; I2 = 48%). Meta-regression revealed no significant relation between the relative risk of CIN and identified differences in participant or study characteristics. Conclusion This meta-analysis showed that research on intravenous N-acetylcysteine and the incidence of CIN is too inconsistent at present to warrant a conclusion on efficacy. A large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for intravenous NAC in CIN prevention. PMID:23383076

Prevention of low back pain and its consequences among nurses’ aides in elderly care: a stepped-wedge multi-faceted cluster-randomized controlled trial

PubMed Central

2013-01-01

Background A high prevalence of low back pain has persisted over the years despite extensive primary prevention initiatives among nurses’ aides. Many single-faceted interventions addressing just one aspect of low back pain have been carried out at workplaces, but with low success rate. This may be due to the multi-factorial origin of low back pain. Participatory ergonomics, cognitive behavioral training and physical training have previously shown promising effects on prevention and rehabilitation of low back pain. Therefore, the main aim of this study is to examine whether a multi-faceted workplace intervention consisting of participatory ergonomics, physical training and cognitive behavioral training can prevent low back pain and its consequences among nurses’ aides. External resources for the participating workplace and a strong commitment from the management and the organization support the intervention. Methods/design To overcome implementation barriers within usual randomized controlled trial designed workplace interventions, this study uses a stepped-wedge cluster-randomized controlled trial design with 4 groups. The intervention is delivered to the groups at random along four successive time periods three months apart. The intervention lasts three months and integrates participatory ergonomics, physical training and cognitive behavioral training tailored to the target group. Local physiotherapists and occupational therapists conduct the intervention after having received standardized training. Primary outcomes are low back pain and its consequences measured monthly by text messages up to three months after initiation of the intervention. Discussion Intervention effectiveness trials for preventing low back pain and its consequences in workplaces with physically demanding work are few, primarily single-faceted, with strict adherence to a traditional randomized controlled trial design that may hamper implementation and compliance, and have mostly been unsuccessful. By using a stepped wedge design, and obtain high management commitment and support we intend to improve implementation and aim to establish the effectiveness of a multi-faceted intervention to prevent low back pain. This study will potentially provide knowledge of prevention of low back pain and its consequences among nurses’ aides. Results are expected to be published in 2015–2016. Trial registration The study is registered as ISRCTN78113519. PMID:24261985

Refining the definition of mandibular osteoradionecrosis in clinical trials: The cancer research UK HOPON trial (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis).

PubMed

Shaw, Richard; Tesfaye, Binyam; Bickerstaff, Matt; Silcocks, Paul; Butterworth, Christopher

2017-01-01

Mandibular osteoradionecrosis (ORN) is a common and serious complication of head and neck radiotherapy for which there is little reliable evidence for prevention or treatment. The diagnosis and classification of ORN have been inconsistently and imprecisely defined, even in clinical trials. A systematic review of diagnosis and classifications of ORN with specific focus on clinical trials is presented. The most suitable classification was evaluated for consistency using blinded independent review of outcome data (clinical photographs and radiographs) in the HOPON trial. Of 16 ORN classifications found, only one (Notani) appeared suitable as an endpoint in clinical trials. Clinical records of 217 timepoints were analysed amongst 94 randomised patients in the HOPON trial. The only inconsistency in classification arose where minor bone spicules (MBS) were apparent, which occurred in 19% of patients. Some trial investigators judged MBS as clinically unimportant and not reflecting ORN, others classified as ORN based on rigid definitions in common clinical use. When MBS was added as a distinct category to the Notani classification this ambiguity was resolved and agreement between observers was achieved. Most definitions and clinical classifications are based on retrospective case series and may be unsuitable for prospective interventional trials of ORN prevention or treatment. When ORN is used as a primary or secondary outcome in prospective clinical trials, the use of Notani classification with the additional category of MBS is recommended as it avoids subjectivity and enhances reliability and consistency of reporting. Copyright © 2016 Elsevier Ltd. All rights reserved.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for primary prevention of osteoarthritis by joint injury prevention in sport and recreation.

PubMed

Emery, C A; Roos, E M; Verhagen, E; Finch, C F; Bennell, K L; Story, B; Spindler, K; Kemp, J; Lohmander, L S

2015-05-01

The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers internationally with expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input and resultant consensus was established through teleconference, face to face and email correspondence over a 1 year period. Recommendations for injury prevention RCTs include context specific considerations regarding the research question, research design, study participants, randomization, baseline characteristics, intervention, outcome measurement, analysis, implementation, cost evaluation, reporting and future considerations including the impact on development of PTOA. Methodological recommendations for injury prevention RCTs are critical to informing evidence-based practice and policy decisions in health care, public health and the community. Recommendations regarding the interpretation and conduct of injury prevention RCTs will inform the highest level of evidence in the field. These recommendations will facilitate between study comparisons to inform best practice in injury prevention that will have the greatest public health impact. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression: A systematic review of systematic reviews and meta-analyses.

PubMed

Bellón, Juan Ángel; Moreno-Peral, Patricia; Motrico, Emma; Rodríguez-Morejón, Alberto; Fernández, Ana; Serrano-Blanco, Antoni; Zabaleta-del-Olmo, Edurne; Conejo-Cerón, Sonia

2015-07-01

To determine the effectiveness of psychological and/or educational interventions to prevent the onset of episodes of depression. Systematic review of systematic reviews and meta-analyses (SR/MA). We searched PubMed, PsycINFO, Cochrane Database of Systematic Reviews, OpenGrey, and PROSPERO from their inception until February 2014. Two reviewers independently evaluated the eligibility criteria of all SR/MA, abstracted data, and determined bias risk (AMSTAR). Twelve SR/MA (156 non-repeated trials and 56,158 participants) were included. Of these, 142 (91%) were randomized-controlled, 13 (8.3%) controlled trials, and 1 (0.6%) had no control group. Five SR/MA focused on children and adolescents, four on specific populations (women after childbirth, of low socioeconomic status, or unfavorable circumstances; patients with severe traumatic physical injuries or stroke) and three addressed the general population. Nine (75%) SR/MA concluded that interventions to prevent depression were effective. Of the 156 trials, 137 (87.8%) reported some kind of effect size calculation. Effect sizes were small in 45 (32.8%), medium in 26 (19.1%), and large in 25 (18.2%) trials; 41 (29.9%) trials were not effective. Of the 141 trials for which follow-up periods were available, only 34 (24.1%) exceeded 12 months. Psychological and/or educational interventions to prevent onset of episodes of depression were effective, although most had small or medium effect sizes. Copyright © 2014. Published by Elsevier Inc.

Implementing post-trial access plans for HIV prevention research.

PubMed

Paul, Amy; Merritt, Maria W; Sugarman, Jeremy

2018-05-01

Ethics guidance increasingly recognises that researchers and sponsors have obligations to consider provisions for post-trial access (PTA) to interventions that are found to be beneficial in research. Yet, there is little information regarding whether and how such plans can actually be implemented. Understanding practical experiences of developing and implementing these plans is critical to both optimising their implementation and informing conceptual work related to PTA. This viewpoint is informed by experiences with developing and implementing PTA plans for six large-scale multicentre HIV prevention trials supported by the HIV Prevention Trials Network. These experiences suggest that planning and implementing PTA often involve challenges of planning under uncertainty and confronting practical barriers to accessing healthcare systems. Even in relatively favourable circumstances where a tested intervention medication is approved and available in the local healthcare system, system-level barriers can threaten the viability of PTA plans. The aggregate experience across these HIV prevention trials suggests that simply referring participants to local healthcare systems for PTA will not necessarily result in continued access to beneficial interventions for trial participants. Serious commitments to PTA will require additional efforts to learn from future approaches, measuring the success of PTA plans with dedicated follow-up and further developing normative guidance to help research stakeholders navigate the complex practical challenges of realising PTA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Treating people with intercurrent infection in HIV prevention trials. Report from a WHO/UNAIDS consultation, Geneva 17-18th July 2003.

PubMed

2004-10-21

While broad agreement now exists among sponsors of HIV prevention trials that antiretroviral therapy (ART) and a clinical care package should be provided to those who become infected during the conduct of a trial, certain practical issues remain unresolved, including Who should pay for ART? How long should ART be provided for? Does treatment extend outside of ART? What else should be included in the standard of care package and who should pay for it? Who should provide treatment and care? This report summarizes the discussions from a consultation held in Geneva (17-18 July 2003) organized by the World Health Organization (WHO) and the joint United Nations Programme on HIV/AIDS (UNAIDS). The group discussed issues related to the various types of HIV prevention trials covered - vaccines, microbicides, behavioural - the ethics and legal rational for providing treatment and care as well as relevant economic issues and developments around scale-up of treatment and care in middle- and lower-income countries. Also discussed were policies of certain research agencies, countries and international funding agencies. The implementation of the conclusions which came out of these discussions on the treatment and care for people who become infected during HIV prevention trials requires the active participation of members of the research community, funders of research, local and national governments and industry as well as the individuals or communities participating in the trials.

The use of intermediate endpoints in the design of type 1 diabetes prevention trials.

PubMed

Krischer, Jeffrey P

2013-09-01

This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials.

The use of intermediate endpoints in the design of type 1 diabetes prevention trials

PubMed Central

Krischer, Jeffrey P.

2013-01-01

Aims/hypothesis This paper presents a rationale for the selection of intermediate endpoints to be used in the design of type 1 diabetes prevention clinical trials. Methods Relatives of individuals diagnosed with type 1 diabetes were enrolled on the TrialNet Natural History Study and screened for diabetes-related autoantibodies. Those with two or more such autoantibodies were analysed with respect to increased HbA1c, decreased C-peptide following an OGTT, or abnormal OGTT values as intermediate markers of disease progression. Results Over 2 years, a 10% increase in HbA1c, and a 20% or 30% decrease in C-peptide from baseline, or progression to abnormal OGTT, occurred with a frequency between 20% and 41%. The 3- to 5-year risk of type 1 diabetes following each intermediate endpoint was high, namely 47% to 84%. The lower the incidence of the endpoint being reached, the higher the risk of diabetes. A diabetes prevention trial using these intermediate endpoints would require a 30% to 50% smaller sample size than one using type 1 diabetes as the endpoint. Conclusions/interpretation The use of an intermediate endpoint in diabetes prevention is based on the generally held view of disease progression from initial occurrence of autoantibodies through successive immunological and metabolic changes to manifest type 1 diabetes. Thus, these markers are suitable for randomised phase 2 trials, which can more rapidly screen promising new therapies, allowing them to be subsequently confirmed in definitive phase 3 trials. PMID:23744306

Extreme all-cause mortality in JUPITER requires reexamination of vital records.

PubMed

Serebruany, Victor L

2011-01-01

To compare all-cause mortality in JUPITER with other statin trials at 21 months of follow-up. Outcome advantages including all-cause mortality reduction yielded from the JUPITER trial support aggressive use of rosuvastatin and, perhaps by extension, other statins for primary prevention. Despite enrolling apparently healthy subjects and early trial termination at 21 months of mean follow-up, JUPITER revealed very high all-cause mortality in both the placebo (2.8%) and rosuvastatin (2.2%) arms. Comparison of all-cause mortality prorated for 21 months in 10 primary prevention studies and 1 acute coronary syndromes statin trial. The all-cause mortality in JUPITER was more than twice that of the average of primary prevention studies, matching well only with specific trials designed in diabetics (ASPEN or CARDS), early hypertension studies (ALLHAT-LLT) or a trial in patients with acute coronary syndromes (PROVE IT). Since the 'play of chance' is unlikely to explain these discrepancies due to excellent baseline match, excess death rates and all-cause mortality rates in both JUPITER arms must be questioned. It may be important that the study sponsor self-monitored sites. Excess all-cause mortality rates in the apparently relatively healthy JUPITER population are alarming and require independent verification. If, indeed, the surprising outcomes in JUPITER are successfully challenged, and considering established harm of statins with regard to rhabdomyolysis as well as, potentially, diabetes, millions of patients may find better and safer options for primary prevention of vascular events. Copyright © 2011 S. Karger AG, Basel.

Best practices for health and safety technology transfer in construction.

PubMed

Welch, Laura S; Russell, Dustin; Weinstock, Deborah; Betit, Eileen

2015-08-01

Construction continues to be a dangerous industry, yet solutions that would prevent injury and illness do exist. Prevention of injury and illness among construction workers requires dissemination, adoption, and implementation of these effective interventions, or "research to practice" (r2p). CPWR recruited participants with experience and insight into effective methods for diffusion of health and safety technologies in this industry for a symposium with 3 group sessions and 3 breakout groups. The organizers reviewed session notes and identified 141 recommendations, which were then assigned to 13 over-arching themes. Recommendations included a guide for researchers on patenting and licensing, a business case model, and in-depth case studies including development, testing, manufacturing, marketing, and diffusion. A more comprehensive understanding of the health and safety technology transfer landscape, the various actors, and their motivators and goals will help to foster the successful commercialization and diffusion of health and safety innovations. © 2015 Wiley Periodicals, Inc.

Best practices for preventing musculoskeletal disorders in masonry: stakeholder perspectives.

PubMed

Entzel, Pamela; Albers, Jim; Welch, Laura

2007-09-01

Brick masons and mason tenders report a high prevalence of work-related musculoskeletal disorders (WMSDs), many of which can be prevented with changes in materials, work equipment or work practices. To explore the use of "best practices" in the masonry industry, NIOSH organized a 2-day meeting of masonry stakeholders. Attendees included 30 industry representatives, 5 health and safety researchers, 4 health/safety specialists, 2 ergonomic consultants, and 2 representatives of state workers' compensation programs. Small groups discussed ergonomic interventions currently utilized in the masonry industry, including factors affecting intervention implementation and ways to promote diffusion of interventions. Meeting participants also identified various barriers to intervention implementation, including business considerations, quality concerns, design issues, supply problems, jobsite conditions and management practices that can slow or limit intervention diffusion. To be successful, future diffusion efforts must not only raise awareness of available solutions but also address these practical concerns.

Garlic for the common cold.

PubMed

Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

2012-03-14

Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four. To determine whether garlic (allium sativum) is effective for either the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, OLDMEDLINE (1950 to 1965), MEDLINE (January 1966 to November week 3, 2011), EMBASE (1974 to December 2011) and AMED (1985 to December 2011). Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment. Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data. Of the six trials identified as potentially relevant from our searches, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily) for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

Dressings and topical agents for preventing pressure ulcers.

PubMed

Moore, Zena E H; Webster, Joan

2013-08-18

Pressure ulcers, which are localised injury to the skin, or underlying tissue or both, occur when people are unable to reposition themselves to relieve pressure on bony prominences. Pressure ulcers are often difficult to heal, painful and impact negatively on the individual's quality of life. The cost implications of pressure ulcer treatment are considerable, compounding the challenges in providing cost effective, efficient health services. Efforts to prevent the development of pressure ulcers have focused on nutritional support, pressure redistributing devices, turning regimes and the application of various topical agents and dressings designed to maintain healthy skin, relieve pressure and prevent shearing forces. Although products aimed at preventing pressure ulcers are widely used, it remains unclear which, if any, of these approaches are effective in preventing the development of pressure ulcers. To evaluate the effects of dressings and topical agents on the prevention of pressure ulcers, in people of any age without existing pressure ulcers, but considered to be at risk of developing a pressure ulcer, in any healthcare setting. In February 2013 we searched the following electronic databases to identify reports of relevant randomised clinical trials (RCTs): the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Database of Abstracts of Reviews of Effects (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. We included RCTs evaluating the use of dressings, topical agents, or topical agents with dressings, compared with a different dressing, topical agent, or combined topical agent and dressing, or no intervention or standard care, with the aim of preventing the development of a pressure ulcer. We assessed trials for their appropriateness for inclusion and for their risk of bias. This was done by two review authors working independently, using pre-determined inclusion and quality criteria. Five trials (940 participants) of unclear or high risk of bias compared a topical agent with a placebo. Four of these trials randomised by individual and one by cluster. When results from the five trials were combined, the risk ratio (RR) was 0.78 (95% CI 0.47 to 1.31; P value 0.35) indicating no overall beneficial effect of the topical agents. When the cluster randomised trial was omitted from the analysis, use of topical agents reduced the pressure ulcer incidence by 36%; RR 0.64 (95% CI 0.49 to 0.83; P value 0.0008).Four trials (561 participants), all of which were of high or unclear risk of bias, showed that dressings applied over bony prominences reduced pressure ulcer incidence; RR 0.21 (95% CI 0.09 to 0.51; P value 0.0006). There is insufficient evidence from RCTs to support or refute the use of topical agents applied over bony prominences to prevent pressure ulcers. Although the incidence of pressure ulcers was reduced when dressings were used to protect the skin, results were compromised by the low quality of the included trials. These trials contained substantial risk of bias and clinical heterogeneity (variations in populations and interventions); consequently, results should be interpreted as inconclusive. Further well designed trials addressing important clinical, quality of life and economic outcomes are justified, based on the incidence of the problem and the high costs associated with pressure ulcer management.

Using a drug facts box to communicate drug benefits and harms: two randomized trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Welch, H Gilbert

2009-04-21

Direct-to-consumer prescription drug ads typically fail to provide fundamental information that consumers need to make informed decisions: data on how well the drug works. To see whether providing consumers with a drug facts box-a table quantifying outcomes with and without the drug-improves knowledge and affects judgments about prescription medications. Two randomized, controlled trials conducted between October 2006 and April 2007: a symptom drug box trial using direct-to-consumer ads for a histamine-2 blocker and a proton-pump inhibitor to treat heartburn, and a prevention drug box trial using direct-to-consumer ads for a statin and clopidogrel to prevent cardiovascular events. National sample of U.S. adults identified by random-digit dialing. Adults age 35 to 70 years who completed a mailed survey; the final samples comprised 231 participants with completed surveys in the symptom drug box trial (49% response rate) and 219 in the prevention drug box trial (46% response rate). In both trials, the control group received 2 actual drug ads (including both the front page and brief summary). The drug box group received the same ads, except that the brief summary was replaced by a drug facts box. Choice between drugs (primary outcome of the symptom drug box trial) and accurate perceptions of drug benefits and side effects (primary outcome of the prevention drug box trial). In the symptom drug box trial, 70% of the drug box group and 8% of the control group correctly identified the PPI as being "a lot more effective" than the histamine-2 blocker (P < 0.001), and 80% and 38% correctly recognized that the side effects of the 2 drugs were similar (P < 0.001). When asked what they would do if they had bothersome heartburn and could have either drug for free, 68% of the drug box group and 31% of the control group chose the proton-pump inhibitor, the superior drug (P < 0.001). In the prevention drug box trial, the drug box improved consumers' knowledge of the benefits and side effects of a statin and clopidogrel. For example, 72% of the drug box group and 9% of the control group correctly quantified the benefit (absolute risk reduction) of the statin (P < 0.001). Most of the control participants overestimated this benefit, and 65% did so by a factor of 10 or more. The trials tested drug boxes in only 4 direct-to-consumer ads. If other direct-to-consumer ads were to communicate outcome data better, the effect of the drug box would be reduced. A drug facts box improved U.S. consumers' knowledge of prescription drug benefits and side effects. It resulted in better choices between drugs for current symptoms and corrected the overestimation of benefit in the setting of prevention. National Cancer Institute and Attorney General Consumer and Prescriber Education Program.

Testing a Violence-Prevention Intervention for Incarcerated Women Using a Randomized Control Trial

ERIC Educational Resources Information Center

Kubiak, Sheryl Pimlott; Kim, Woo Jong; Fedock, Gina; Bybee, Deborah

2015-01-01

Objective: Beyond Violence (BV), a new prevention program for women with assaultive offenses, demonstrated feasibility in previous studies. This study's purpose is to assess the efficacy of BV using a randomized control trial. Method: Eligible women were randomly assigned to treatment as usual (TAU) and the experimental condition (BV). Measures of…

Effect of a Universal Anxiety Prevention Programme (FRIENDS) on Children's Academic Performance: Results from a Randomised Controlled Trial

ERIC Educational Resources Information Center

Skryabina, Elena; Taylor, Gordon; Stallard, Paul

2016-01-01

Background: Evaluations of school-based anxiety prevention programmes have reported improvements in psychological functioning although little is known about their effect upon educational outcomes. Methods: One thousand three hundred and sixty-two children from 40 primary schools in England took part in the randomised controlled trial, Preventing…

Puerto Rico NCI Community Oncology Research Program Minority/Underserved | Division of Cancer Prevention

Cancer.gov

The Puerto Rico NCI Community Oncology Research Program (PRNCORP) will be the principal organization in the island that promotes cancer prevention, control and screening/post-treatment surveillance clinical trials. It will conduct cancer care delivery research and will provide access to treatment and imaging clinical trials conducted under the reorganization of the National

Brief Cognitive-Behavioral Depression Prevention Program for High-Risk Adolescents Outperforms Two Alternative Interventions: A Randomized Efficacy Trial

ERIC Educational Resources Information Center

Stice, Eric; Rohde, Paul; Seeley, John R.; Gau, Jeff M.

2008-01-01

In this depression prevention trial, 341 high-risk adolescents (mean age = 15.6 years, SD = 1.2) with elevated depressive symptoms were randomized to a brief group cognitive-behavioral (CB) intervention, group supportive-expressive intervention, bibliotherapy, or assessment-only control condition. CB participants showed significantly greater…

Randomized Trials on Consider This, a Tailored, Internet-Delivered Smoking Prevention Program for Adolescents

ERIC Educational Resources Information Center

Buller, David B.; Borland, Ron; Woodall, W. Gill; Hall, John R.; Hines, Joan M.; Burris-Woodall, Patricia; Cutter, Gary R.; Miller, Caroline; Balmford, James; Starling, Randall; Ax, Bryan; Saba, Laura

2008-01-01

The Internet may be an effective medium for delivering smoking prevention to children. Consider This, an Internet-based program, was hypothesized to reduce expectations concerning smoking and smoking prevalence. Group-randomized pretest-posttest controlled trials were conducted in Australia (n = 2,077) and the United States (n = 1,234) in schools…

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2010-09-01

determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 2 of the award, we were approved by the...Trial (PCPT), a randomized placebo‐ controlled clinical trial to determine if  finasteride  (an inhibitor of androgen bioactivation) could  prevent

Interventions for preventing and treating incontinence-associated dermatitis in adults.

PubMed

Beeckman, Dimitri; Van Damme, Nele; Schoonhoven, Lisette; Van Lancker, Aurélie; Kottner, Jan; Beele, Hilde; Gray, Mikel; Woodward, Sue; Fader, Mandy; Van den Bussche, Karen; Van Hecke, Ann; De Meyer, Dorien; Verhaeghe, Sofie

2016-11-10

Incontinence-associated dermatitis (IAD) is one of the most common skin problems in adults who are incontinent for urine, stool, or both. In practice, products and procedures are the same for both prevention and treatment of IAD. The objective of this review was to assess the effectiveness of various products and procedures to preventand treat incontinence-associated dermatitis in adults. We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 28 September 2016). Additionally we searched other electronic databases: CENTRAL(2015, Issue 4), MEDLINE (January 1946 to May Week 3 2015), MEDLINE In-Process (inception to 26 May 2015), CINAHL(December 1981 to 28 May 2015), Web of Science (WoS; inception to 28 May 2015) and handsearched conference proceedings (to June 2015) and the reference lists of relevant articles, and contacted authors and experts in the field. We selected randomised controlled trials (RCTs) and quasi-RCTs, performed in any healthcare setting, with included participants over 18 years of age, with or without IAD. We included trials comparing the (cost) effectiveness of topical skin care products such as skin cleansers, moisturisers, and skin protectants of different compositions and skin care procedures aiming to prevent and treat IAD. Two review authors independently screened titles, abstracts and full-texts, extracted data, and assessed the risk of bias of the included trials. We included 13 trials with 1295 participants in a qualitative synthesis. Participants were incontinent for urine, stool, or both, and were residents in a nursing home or were hospitalised.Eleven trials had a small sample size and short follow-up periods. .The overall risk of bias in the included studies was high. The data were not suitable for meta-analysis due to heterogeneity in participant population, skin care products, skin care procedures, outcomes, and measurement tools.Nine trials compared different topical skin care products, including a combination of products. Two trials tested a structured skin care procedure. One trial compared topical skin care products alongside frequencies of application. One trial compared frequencies of application of topical skin care products.We found evidence in two trials, being of low and moderate quality, that soap and water performed poorly in the prevention and treatment of IAD (primary outcomes of this review). The first trial indicated that the use of a skin cleanser might be more effective than the use of soap and water (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.17 to 0.87; low quality evidence). The second trial indicated that a structured skin care procedure, being a washcloth with cleansing, moisturising, and protecting properties, might be more effective than soap and water (RR 0.31, 95% CI 0.12 to 0.79; moderate quality evidence). Findings from the other trials, all being of low to very low quality, suggest that applying a leave-on product (moisturiser, skin protectant, or a combination) might be more effective than not applying a leave-on product. No trial reported on the third primary outcome 'number of participants not satisfied with treatment' or on adverse effects. Little evidence, of very low to moderate quality, exists on the effects of interventions for preventing and treating IAD in adults. Soap and water performed poorly in the prevention and treatment of IAD. Application of leave-on products (moisturisers, skin protectants, or a combination) and avoiding soap seems to be more effective than withholding these products. The performance of leave-on products depends on the combination of ingredients, the overall formulation and the usage (e.g. amount applied). High quality confirmatory trials using standardised, and comparable prevention and treatment regimens in different settings/regions are required. Furthermore, to increase the comparability of trial results, we recommend the development of a core outcome set, including validated measurement tools. The evidence in this review is current up to 28 September 2016.

Preventing invasive breast cancer using endocrine therapy.

PubMed

Thorat, Mangesh A; Cuzick, Jack

2017-08-01

Developments in breast cancer treatment have resulted in reduction in breast cancer mortality in the developed world. However incidence continues to rise and greater use of preventive interventions including the use of therapeutic agents is needed to control this burden. High quality evidence from 9 major trials involving more than 83000 participants shows that selective oestrogen receptor modulators (SERMs) reduce breast cancer incidence by 38%. Combined results from 2 large trials with 8424 participants show that aromatase inhibitors (AIs) reduce breast cancer incidence by 53%. These benefits are restricted to prevention of ER positive breast cancers. Restricting preventive therapy to high-risk women improves the benefit-harm balance and many guidelines now encourage healthcare professionals to discuss preventive therapy in these women. Further research is needed to improve our risk-prediction models for the identification of high risk women for preventive therapy with greater accuracy and to develop surrogate biomarkers of response. Long-term follow-up of the IBIS-I trial has provided valuable insights into the durability of benefits from preventive therapy, and underscores the need for such follow up to fully evaluate other agents. Full utilisation of preventive therapy also requires greater knowledge and awareness among both doctors and patients about benefits, harms and risk factors. Healthcare professionals should routinely discuss preventive therapy with women at high-risk of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Validation of the Diabetes Prevention Trial-Type 1 Risk Score in the TrialNet Natural History Study.

PubMed

Sosenko, Jay M; Skyler, Jay S; Mahon, Jeffrey; Krischer, Jeffrey P; Beam, Craig A; Boulware, David C; Greenbaum, Carla J; Rafkin, Lisa E; Cowie, Catherine; Cuthbertson, David; Palmer, Jerry P

2011-08-01

We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS). Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS intervals was compared between the TNNHS and DPT-1 cohorts. Receiver-operating characteristic curve areas for the DPTRS were substantial in the TNNHS (P < 0.001 at both 2 and 3 years). The type 1 diabetes cumulative incidence did not differ significantly between the TNNHS and DPT-1 cohorts within DPTRS intervals. In the TNNHS, 2-year and 3-year risks were low for DPTRS intervals <6.50 (<0.10 and <0.20, respectively). Thresholds ≥7.50 were indicative of high risk in both cohorts (2-year risks: 0.49 in the TNNHS and 0.51 in DPT-1). The DPTRS is an accurate and robust predictor of type 1 diabetes in autoantibody-positive populations.

Prevention of Malaria during Pregnancy: Assessing the Effect of the Distribution of IPTp Through the National Policy in Benin

PubMed Central

Port, Agnès Le; Cottrell, Gilles; Dechavanne, Célia; Briand, Valérie; Bouraima, Aziz; Guerra, José; Choudat, Isabelle; Massougbodji, Achille; Fayomi, Benjamin; Migot-Nabias, Florence; Garcia, André; Cot, Michel

2011-01-01

The efficiency of malaria prevention during pregnancy was compared between three studies in Benin for malaria infection of the placenta (MIP) and low birth weight (LBW). The first was carried out when chloroquine prophylaxis was still recommended, the second was an intermittent preventive treatment in pregnancy (IPTp) clinical trial comparing sulfadoxine pyrimetamine (SP) versus mefloquine, and the third was an observational study after SP-IPTp national implementation. We showed an association between the use of IPTp and the reduction of LBW (10% with national IPTp and 8.7% in IPTp trial versus 15.7% in pre-trial study). The effect on MIP was better in the trial (2.9% versus 11.2% and 16.7% for national IPTp and pre-trial studies, respectively). In spite of a good overall compliance with the national IPTp (with 84% of women taking at least one dose of SP), there are still failures in adherence to the directly observed therapy (DOT) scheme and needs for better training of health staff. PMID:21292898

SR-90107 (Sanofi-Synthélabo).

PubMed

Liu, F; Bagley, W P; Carroll, R C

2000-09-01

SR-90107 is a synthetic pentasaccharide heparinoid Factor Xa antagonist and thrombokinase inhibitor in joint development by Sanofi-Synthelabo (formerly Sanofi) and Organon as a potential treatment and prophylaxis for deep vein thrombosis (DVT) and symptomatic pulmonary embolism following hip or knee surgery and as a potential treatment for coronary artery diseases [330073,359231]. The compound is in phase III clinical trials for the prevention of DVT and pulmonary embolism; phase III trials for the treatment of DVT and pulmonary embolism were expected to start in the first quarter of 2000 and phase IIb trials in cardiology indications are also underway. NDAs are planned to be submitted in Europe and the US in the third quarter of 2000 for the prevention of DVT and symptomatic pulmonary embolism, in 2002 for the treatment of DVT and pulmonary embolism and in 2004 for the treatment of coronary artery diseases [359231]. DVT AND PULMONARY EMBOLISM: The compound had entered phase III clinical trials by December 1998 for the prevention of thrombosis [320585]. By February 2000, four phase III trials in the prevention of DVT and pulmonary embolism following orthopaedic surgery were underway: the European PENTHIFRA trial, which involves 1707 patients with hip fracture; the US PENTATHLON trial, which involves 2200 patients undergoing hip replacements; the European EPHESUS trial, which involves 2200 patients undergoing hip replacements; and the US PENTAMAKS trial, which involves 1000 patients undergoing major knee surgery [359231]. Clinical data from these trials are expected to be available by June 2000 [359793]. By February 2000, preparations were also being made for two phase III trials of SR-90107 for the treatment of DVT and pulmonary embolism, both expected to be initiated in the first quarter of 2000; the MATISSE DVT trial, a double-blind trial of SR-90107 versus enoxaparin sodium in 2200 patients; and the MATISSE PE trial, an open study of SR-90107 versus unfractionated heparin in 2200 patients [359231]. CORONARY ARTERY DISEASES: By February 2000, SR-90107 was also under development for unstable angina, percutaneous transluminal coronary angioplasty, and acute myocardial infarction. At this time, the phase IIb PENTALYSE trial in thrombolyzed acute myocardial infarction patients had been completed, demonstrating a good safety/efficacy ratio, and the phase IIb PENTUA trial in unstable angina was ongoing [359231]. In October 1999, Merrill Lynch forecast sales of EUR 180 million in 2003, planning a review of this figure once clinical data were available [346209]. Also in October 1999, Lehman Brothers predicted that the product had a 70% chance of reaching the market with potential peak sales of US 700 million dollars in 2008 [346267].

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, Peter; Stead, Lindsay F; West, Robert; Jarvis, Martin; Hartmann-Boyce, Jamie; Lancaster, Tim

2013-08-20

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions have been proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register in May 2013 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow-up of six months. We included smokers who quit on their own, were undergoing enforced abstinence, or were participating in treatment programmes. We included trials that compared relapse prevention interventions with a no intervention control, or that compared a cessation programme with additional relapse prevention components with a cessation programme alone. Studies were screened and data extracted by one review author, and checked by a second. Disagreements were resolved by discussion or by referral to a third review author. Sixty-three studies met inclusion criteria but were heterogeneous in terms of populations and interventions. We considered 41 studies that randomly assigned abstainers separately from studies that randomly assigned participants before their quit date.Upon looking at studies of behavioural interventions that randomly assigned abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking because of pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or through a formal programme. Amongst trials randomly assigning smokers before their quit date and evaluating the effects of additional relapse prevention components, we found no evidence of benefit of behavioural interventions or combined behavioural and pharmacotherapeutic interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio (RR) 1.18, 95% confidence interval (CI) 1.03 to 1.36). Pooling of six studies of extended treatment with bupropion failed to detect a significant effect (RR 1.15, 95% CI 0.98 to 1.35). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect, but treatment compliance was low, and in two other trials of oral NRT in which short-term abstainers were randomly assigned, a significant effect of intervention was noted. At the moment, there is insufficient evidence to support the use of any specific behavioural intervention to help smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focused on identifying and resolving tempting situations, as most studies were concerned with these. Little research is available regarding other behavioural approaches.Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, Peter; Stead, Lindsay F; West, Robert; Jarvis, Martin; Lancaster, Tim

2009-01-21

A number of treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. Several interventions were proposed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction Group trials register in August 2008 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow up of six months. We included smokers who quit on their own, or were undergoing enforced abstinence, or who were participating in treatment programmes. We included trials that compared relapse prevention interventions to a no intervention control, or that compared a cessation programme with additional relapse prevention components to a cessation programme alone. Studies were screened and data extracted by one author and checked by a second. Disagreements were resolved by discussion or referral to a third author. Fifty-four studies met inclusion criteria, but were heterogeneous in terms of populations and interventions. We considered 36 studies that randomized abstainers separately from studies that randomized participants prior to their quit date.Looking at studies of behavioural interventions which randomised abstainers, we detected no benefit of brief and 'skills-based' relapse prevention methods for women who had quit smoking due to pregnancy, or for smokers undergoing a period of enforced abstinence during hospitalisation or military training. We also failed to detect significant effects of behavioural interventions in trials in unselected groups of smokers who had quit on their own or with a formal programme. Amongst trials randomising smokers prior to their quit date and evaluating the effect of additional relapse prevention components we also found no evidence of benefit of behavioural interventions in any subgroup. Overall, providing training in skills thought to be needed for relapse avoidance did not reduce relapse, but most studies did not use experimental designs best suited to the task, and had limited power to detect expected small differences between interventions. For pharmacological interventions, extended treatment with varenicline significantly reduced relapse in one trial (risk ratio 1.18, 95% confidence interval 1.03 to 1.36). Pooling of five studies of extended treatment with bupropion failed to detect a significant effect (risk ratio 1.17; 95% confidence interval 0.99 to 1.39). Two small trials of oral nicotine replacement treatment (NRT) failed to detect an effect but treatment compliance was low and in two other trials of oral NRT randomizing short-term abstainers there was a significant effect of intervention. At the moment there is insufficient evidence to support the use of any specific behavioural intervention for helping smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focusing on identifying and resolving tempting situations, as most studies were concerned with these. There is little research available regarding other behavioural approaches. Extended treatment with varenicline may prevent relapse. Extended treatment with bupropion is unlikely to have a clinically important effect. Studies of extended treatment with nicotine replacement are needed.

Treating High-grade Lesions to Prevent Anal Cancer in HIV-infected People

Cancer.gov

This study, called the ANCHOR trial, will investigate whether screening and prevention methods similar to those used to prevent cervical cancer can help prevent anal cancer in HIV-infected men and women.

Fluoride gels for preventing dental caries in children and adolescents.

PubMed

Marinho, Valeria C C; Worthington, Helen V; Walsh, Tanya; Chong, Lee Yee

2015-06-15

Topically applied fluoride gels have been widely used as a caries-preventive intervention in dental surgeries and school-based programmes for over three decades. This updates the Cochrane review of fluoride gels for preventing dental caries in children and adolescents that was first published in 2002. The primary objective is to determine the effectiveness and safety of fluoride gels in preventing dental caries in the child and adolescent population.The secondary objectives are to examine whether the effect of fluoride gels is influenced by the following: initial level of caries severity; background exposure to fluoride in water (or salt), toothpastes, or reported fluoride sources other than the study option(s); mode of use (self applied under supervision or operator-applied), and whether there is a differential effect between the tray and toothbrush methods of application; frequency of use (times per year) or fluoride concentration (ppm F). We searched the Cochrane Oral Health Group Trials Register (to 5 November 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2014, Issue 11), MEDLINE via OVID (1946 to 5 November 2014), EMBASE via OVID (1980 to 5 November 2014), CINAHL via EBSCO (1980 to 5 November 2014), LILACS and BBO via the BIREME Virtual Health Library (1980 to 5 November 2014), ProQuest Dissertations and Theses (1861 to 5 November 2014) and Web of Science Conference Proceedings (1945 to 5 November 2014). We undertook a search for ongoing trials on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform on 5 November 2014. We placed no restrictions on language or date of publication in the search of the electronic databases. We also searched reference lists of articles and contacted selected authors and manufacturers. Randomised or quasi-randomised controlled trials where blind outcome assessment was stated or indicated, comparing topically applied fluoride gel with placebo or no treatment in children up to 16 years. The frequency of application had to be at least once a year, and study duration at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces in both permanent and primary teeth (D(M)FS and d(e/m)fs). At least two review authors independently performed study selection, data extraction and 'Risk of bias' assessment. We contacted study authors for additional information where required. The primary measure of effect was the prevented fraction (PF), that is, the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. We performed random-effects meta-analyses where we could pool data. We examined potential sources of heterogeneity in random-effects metaregression analyses. We collected adverse effects information from the included trials. We included 28 trials (3 of which are new trials since the original review), involving 9140 children and adolescents. Most of these trials recruited participants from schools. Most of the studies (20) were at high risk of bias, with 8 at unclear risk of bias.Twenty-five trials (8479 participants) contributed data for meta-analysis on permanent tooth surfaces: the D(M)FS pooled prevented fraction (PF) estimate was 28% (95% confidence intervals (CI) 19% to 36%; P < 0.0001; with substantial heterogeneity (P < 0.0001; I(2) = 82%); moderate quality evidence). Subgroup and metaregression analyses suggested no significant association between estimates of D(M)FS prevented fractions and the prespecified trial characteristics. However, the effect of fluoride gel varied according to the type of control group used, with D(M)FS PF on average being 17% (95% CI 3% to 31%; P = 0.018) higher in non-placebo-controlled trials (the reduction in caries was 38% (95% CI 24% to 52%; P < 0.0001, 2808 participants) for the 10 trials with no treatment as control group, and 21% (95% CI 15% to 28%; P < 0.0001, 5671 participants) for the 15 placebo-controlled trials. A funnel plot of the 25 trials in the D(M)FS PF meta-analysis indicated a relationship between prevented fraction and study precision, with an apparent lack of small studies with statistically significant large effects.The d(e/m)fs pooled prevented fraction estimate for the three trials (1254 participants) that contributed data for the meta-analysis on primary teeth surfaces was 20% (95% CI 1% to 38%; P = 0.04; with no heterogeneity (P = 0.54; I(2) = 0%); low quality evidence).There was limited reporting of adverse events. Only two trials reported information on acute toxicity signs and symptoms during the application of the gel (risk difference 0.01, 95% CI -0.01 to 0.02; P = 0.36; with no heterogeneity (P = 36; I(2) = 0%); 490 participants; very low quality evidence). None of the trials reported information on tooth staining, mucosal irritation or allergic reaction. The conclusions of this updated review remain the same as those when it was first published. There is moderate quality evidence of a large caries-inhibiting effect of fluoride gel in the permanent dentition. Information concerning the caries-preventive effect of fluoride gel on the primary dentition, which also shows a large effect, is based on low quality evidence from only three placebo-controlled trials. There is little information on adverse effects or on acceptability of treatment. Future trials should include assessment of potential adverse effects.

ADCS Prevention Instrument Project: assessment of instrumental activities of daily living for community-dwelling elderly individuals in dementia prevention clinical trials.

PubMed

Galasko, Douglas; Bennett, David A; Sano, Mary; Marson, Daniel; Kaye, Jeff; Edland, Steven D

2006-01-01

In primary prevention trials for Alzheimer disease, the inception cohort typically has normal or minimally impaired complex activities of daily living (ADL). ADL change during a trial could trigger detailed evaluation or serve as an outcome measure. A brief, easily administered, and reliable ADL rating scale would assist prevention studies. To develop an ADL scale for prevention trials that allows self-rating or completion by informants. The Activities of Daily Living-Prevention Instrument (ADL-PI) was developed, comprising 15 ADL and 5 physical function questions. Six hundred forty-four elderly subjects participating in the Prevention Instrument Project completed a self-rated version of the ADL-PI, and informants for 632 subjects completed an informant version. Informants also completed a Mild Cognitive Impairment (MCI) ADL questionnaire to allow comparisons. Subjects performed well on all ADL scales at baseline. Completion of the ADL-PI questionnaires at home or in-clinic yielded comparable information. Scores from baseline to 3 months had good reliability. The ADL-PI, obtained from either self-report or informants, discriminated between subjects rated as CDR 0 and CDR 0.5. Subjects with worse baseline cognitive performance also had slightly worse ADL-PI scores. Preliminary analysis indicates that subjects who triggered cognitive evaluations had slightly lower baseline ADL-PI scores by both self and informant reports. The ADL-PI can be completed at home or in clinic, and has adequate reliability. The utility of self-administered and informant versions and predictive value of reported deficits requires further follow-up.

Glyburide is associated with attenuated vasogenic edema in stroke patients

PubMed Central

Kimberly, W. Taylor; Battey, Thomas W. K.; Pham, Ly; Wu, Ona; Yoo, Albert J.; Furie, Karen L.; Singhal, Aneesh B.; Elm, Jordan J.; Stern, Barney J.; Sheth, Kevin N.

2016-01-01

Background and Purpose Brain edema is a serious complication of ischemic stroke that can lead to secondary neurological deterioration and death. Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 (SUR1) and transient receptor potential cation channel subfamily M member 4 (TRPM4). However, the relevance of this pathway to the development of cerebral edema in stroke patients is not known. Methods Using a case control design, we retrospectively assessed neuroimaging and blood markers of cytotoxic and vasogenic edema in subjects who were enrolled in the Glyburide Advantage in Malignant Edema and Stroke-Pilot (GAMES-Pilot) trial. We compared serial brain magnetic resonance images (MRIs) to a cohort with similar large volume infarctions. We also compared matrix metalloproteinase-9 plasma level in large hemispheric stroke. Results We report that IV glyburide was associated with attenuated T2 fluid attenuated inversion recovery (FLAIR) signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood matrix metalloproteinase-9 (MMP-9) level. Conclusions Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. Verification of these potential imaging and blood biomarkers is warranted in the context of a randomized, placebo-controlled trial. PMID:24072459

Water footbath, automatic flushing, and disinfection to improve the health of bovine feet.

PubMed

Fjeldaas, T; Knappe-Poindecker, M; Bøe, K E; Larssen, R B

2014-05-01

Disinfecting footbaths are used to treat and prevent interdigital dermatitis (ID) and heel horn erosion (HHE). However, many disinfectants are disadvantageous for the environment and, as an alternative, washing of the feet has been introduced. Our aim was to investigate the effect of water footbaths (trial 1), footbaths with CuSO4 (trial 2), automatic water flushing (trial 3), and water flushing followed by disinfection with a glutaraldehyde-based compound (trial 4) in 4 randomized controlled clinical trials performed in a freestall dairy herd of approximately 45 Norwegian Red cows. At trimming before and after each trial, hind foot diseases, hardness of the claw horn (in D-units), locomotion, and cleanliness of the claws were recorded. Before each trial, the cows were divided in comparable study and control groups, based on prevalence of ID and HHE, parity, and days in milk. Using a transponder-regulated gate, the study groups were led through a footbath (trials 1 and 2) or an automatic washer (trials 3 and 4), whereas the control groups were left untreated. Each trial lasted 3 mo and the curative effect in diseased cows and the preventive effect in cows with healthy feet on ID, HHE, and ID + HHE were analyzed. In trial 2, a preventive effect of CuSO4 on HHE compared with the untreated cows was observed. During trial 1, 100% (11/11) of the treated cows with ID got better and 22% (2/9) without ID became diseased, whereas 92% (11/12) of the treated cows with ID + HHE got better and 38% (3/8) without ID + HHE became diseased. During trial 2, 69% (9/13) of the treated cows with ID got better and 11% (1/9) without ID became diseased. During trial 4, 19% (3/16) of the untreated cows with ID + HHE got better and 71% (5/7) without ID + HHE became diseased. In trial 3, no significant effects on ID, HHE, or ID + HHE were revealed. In trial 2 (CuSO4), the treated cows' claw horn was harder after the trial compared with the controls (D-unit difference: 13.25). In trial 3 (stationary water flushing) the treated cows' claw horn was softer after the trial when compared with the controls (D-unit difference: -15.66). The CuSO4 footbaths were useful to prevent HHE and indicate that automatic stationary flushing with only water had no beneficial effect on ID or HHE. The claw horn of cows walking through CuSO4 became harder and the claw horn of cows that had their hind feet flushed with water became softer compared with the controls. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Study Identifies New Lymphoma Treatment Target

Cancer.gov

NCI researchers have identified new therapeutic targets for diffuse large B-cell lymphoma. Drugs that hit these targets are under clinical development and the researchers hope to begin testing them in clinical trials of patients with DLBCL.

Medial Tibial Stress Syndrome: Evidence-Based Prevention

PubMed Central

Craig, Debbie I

2008-01-01

Reference: Thacker SB, Gilchrist J, Stroup DF, Kimsey CD. The prevention of shin splints in sports: a systematic review of literature. Med Sci Sports Exerc. 2002;34(1):32–40. Clinical Question: Among physically active individuals, which medial tibial stress syndrome (MTSS) prevention methods are most effective to decrease injury rates? Data Sources: Studies were identified by searching MEDLINE (1966–2000), Current Contents (1996–2000), Biomedical Collection (1993–1999), and Dissertation Abstracts. Reference lists of identified studies were searched manually until no further studies were identified. Experts in the field were contacted, including first authors of randomized controlled trials addressing prevention of MTSS. The Cochrane Collaboration (early stage of Cochrane Database of Systematic Reviews) was contacted. Study Selection: Inclusion criteria included randomized controlled trials or clinical trials comparing different MTSS prevention methods with control groups. Excluded were studies that did not provide primary research data or that addressed treatment and rehabilitation rather than prevention of incident MTSS. Data Extraction: A total of 199 citations were identified. Of these, 4 studies compared prevention methods for MTSS. Three reviewers independently scored the 4 studies. Reviewers were blinded to the authors' names and affiliations but not the results. Each study was evaluated independently for methodologic quality using a 100-point checklist. Final scores were averages of the 3 reviewers' scores. Main Results: Prevention methods studied were shock-absorbent insoles, foam heel pads, Achilles tendon stretching, footwear, and graduated running programs. No statistically significant results were noted for any of the prevention methods. Median quality scores ranged from 29 to 47, revealing flaws in design, control for bias, and statistical methods. Conclusions: No current evidence supports any single prevention method for MTSS. The most promising outcomes support the use of shock-absorbing insoles. Well-designed and controlled trials are critically needed to decrease the incidence of this common injury. PMID:18523568

Mesalamine did not prevent recurrent diverticulitis in phase 3 controlled trials.

PubMed

Raskin, Jeffrey B; Kamm, Michael A; Jamal, M Mazen; Márquez, Juan; Melzer, Ehud; Schoen, Robert E; Szalóki, Tibor; Barrett, Karen; Streck, Paul

2014-10-01

No therapy has been proven to prevent the recurrence of diverticulitis. Mesalamine has shown efficacy in preventing relapse in inflammatory bowel disease, and there is preliminary evidence that it might be effective for diverticular disease. We investigated the efficacy of mesalamine in preventing recurrence of diverticulitis in 2 identical but separate phase 3, randomized, double-blind, placebo-controlled, multicenter trials (identical confirmatory trials were conducted for regulatory reasons). We evaluated the efficacy and safety of multimatrix mesalamine vs placebo in the prevention of recurrent diverticulitis in 590 (PREVENT1) and 592 (PREVENT2) adult patients with ≥1 episodes of acute diverticulitis in the previous 24 months that resolved without surgery. Patients received mesalamine (1.2 g, 2.4 g, or 4.8 g) or placebo once daily for 104 weeks. The primary end point was the proportion of recurrence-free patients at week 104. Diverticulitis recurrence was defined as surgical intervention at any time for diverticular disease or presence of computed tomography scan results demonstrating bowel wall thickening (>5 mm) and/or fat stranding consistent with diverticulitis. For a portion of the study, recurrence also required the presence of abdominal pain and an increase in white blood cells. Mesalamine did not reduce the rate of diverticulitis recurrence at week 104. Among patients in PREVENT1, 53%-63% did not have disease recurrence, compared with 65% of those given placebo. Among patients in PREVENT2, 59%-69% of patients did not have disease recurrence, compared with 68% of those given placebo. Mesalamine did not reduce time to recurrence, and the proportions of patients requiring surgery were comparable among treatment groups. No new adverse events were identified with mesalamine administration. Mesalamine was not superior to placebo in preventing recurrent diverticulitis. Mesalamine is not recommended for this indication. ClinicalTrials.gov ID: NCT00545740 and NCT00545103. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Optimizing the Primary Prevention of Type-2 Diabetes in Primary Health Care

ClinicalTrials.gov

2017-08-18

Interprofessional Relations; Primary Health Care/Organization & Administration; Diabetes Mellitus, Type 2/Prevention & Control; Primary Prevention/Methods; Risk Reduction Behavior; Randomized Controlled Trial; Life Style

Enhancing the effectiveness of HIV/AIDS prevention programs targeted to unique population groups in Thailand: lessons learned from applying concepts of diffusion of innovation and social marketing.

PubMed

Svenkerud, P J; Singhal, A

1998-01-01

Diffusion of innovations theory and social marketing theory have been criticized for their limited applicability in influencing unique population groups (e.g., female commercial sex workers (CSWs) working in low-class brothels). This study investigated the applicability of these two theoretical frameworks in outreach efforts directed to unique populations at high risk for HIV/AIDS in Bangkok, Thailand. Further, this study examined Thai cultural characteristics that influence communication about HIV/AIDS prevention. The results suggest that certain concepts and strategies drawn from the two frameworks were used more or less by effective outreach programs, providing several policy-relevant lessons. Cultural constraints, such as the lack of visibility of the disease and traditional sexual practices, influenced communication about HIV/AIDS prevention.

The baby or the bath water? Lessons learned from the National Action Alliance for Suicide Prevention Research Prioritization Task Force literature review.

PubMed

Davis Molock, Sherry; Heekin, Janet M; Matlin, Samantha G; Barksdale, Crystal L; Gray, Ekwenzi; Booth, Chelsea L

2014-09-01

The Research Prioritization Task Force of the National Action Alliance for Suicide Prevention conducted a comprehensive literature review of suicide prevention/intervention trials to assess the quality of the scientific evidence. A literature "review of reviews" was conducted by searching the most widely used databases for mental health and public health research. The quality of the reviews was evaluated using the Revised Assessment of Multiple Systematic Reviews system; the quality of the scientific evidence for the suicide preventions/interventions was assessed using U.S. Preventive Services Task Force criteria. The reviews were limited to peer-reviewed publications with human subjects published in English. Ninety-eight systematic reviews and 45 primary sources on suicide prevention/interventions published between January 2000 and September 2012 were evaluated. The results suggest that the quality of both the systematic reviews and the scientific evidence for suicide preventions/interventions were mixed. The majority of the systematic reviews and prevention/interventions were evaluated as fair to poor in quality. There are many promising suicide prevention/intervention trials, but research findings are often inconclusive because of methodologic problems. Methodologic problems across systematic reviews include not conducting hand searches, not surveying gray literature, and being unable to aggregate data across studies. Methodologic problems with the scientific quality of the prevention/intervention trials include paucity of information on sample demographic characteristics, poorly defined outcomes, and excluding actively suicidal participants. Suggestions for ways to improve the quality of the systematic reviews and suicide preventions/interventions are provided. Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions

PubMed Central

McNicholl, Janet M.

2016-01-01

ABSTRACT Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention. PMID:27679928

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

PubMed

McNicholl, Janet M

2016-12-01

Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

Fibrates for secondary prevention of cardiovascular disease and stroke.

PubMed

Wang, Deren; Liu, Bian; Tao, Wendan; Hao, Zilong; Liu, Ming

2015-10-25

Fibrates are a class of drugs characterised by mainly lowering high triglyceride, raising high-density lipoprotein (HDL) cholesterol, and lowering the small dense fraction of low-density lipoprotein (LDL) cholesterol. Their efficacy for secondary prevention of serious vascular events is unclear, and to date no systematic review focusing on secondary prevention has been undertaken. To assess the efficacy and safety of fibrates for the prevention of serious vascular events in people with previous cardiovascular disease (CVD), including coronary heart disease and stroke. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2014) on the Cochrane Library, MEDLINE (OVID, 1946 to October week 1 2014), EMBASE (OVID, 1980 to 2014 week 41), the China Biological Medicine Database (CBM) (1978 to 2014), the Chinese National Knowledge Infrastructure (CNKI) (1979 to 2014), Chinese Science and Technique Journals Database (VIP) (1989 to 2014). We also searched other resources, such as ongoing trials registers and databases of conference abstracts, to identify further published, unpublished, and ongoing studies. We included randomised controlled trials (RCTs) in which a fibrate (for example gemfibrozil, fenofibrate) was compared with placebo or no treatment. We excluded RCTs with only laboratory outcomes. We also excluded trials comparing two different fibrates without a placebo or no-treatment control. Two review authors independently selected trials for inclusion, assessed risk of bias, and extracted the data. We contacted authors of trials for missing data. We included 13 trials involving a total of 16,112 participants. Eleven trials recruited participants with history of coronary heart disease, two trials recruited participants with history of stroke, and one trial recruited participants with a mix of people with CVD. We judged overall risk of bias to be moderate. The meta-analysis (including all fibrate trials) showed evidence for a protective effect of fibrates primarily compared to placebo for the primary composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI), and vascular death (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.94; participants = 16,064; studies = 12; I(2) = 45%, fixed effect). Fibrates were moderately effective for preventing MI occurrence (RR 0.86, 95% CI 0.80 to 0.93; participants = 13,942; studies = 10; I(2) = 24%, fixed effect). Fibrates were not effective against all-cause mortality (RR 0.98, 95% CI 0.91 to 1.06; participants = 13,653; studies = 10; I(2) = 23%), death from vascular causes (RR 0.95, 95% CI 0.86 to 1.05; participants = 13,653; studies = 10; I(2) = 11%, fixed effect), and stroke events (RR 1.03, 95% CI 0.91 to 1.16; participants = 11,719; studies = 6; I(2) = 11%, fixed effect). Excluding clofibrate trials, as the use of clofibrate was discontinued in 2012 due to safety concerns, the remaining class of fibrates were no longer effective in preventing the primary composite outcome (RR 0.90, 95% CI 0.79 to 1.03; participants = 10,320; studies = 7; I(2) = 50%, random effects). However, without clofibrate data, fibrates remained effective in preventing MI (RR 0.85, 95% CI 0.76 to 0.94; participants = 8304; studies = 6; I(2) = 47%, fixed effect). There was no increase in adverse events with fibrates compared to control. Subgroup analyses showed the benefit of fibrates on the primary composite outcome to be consistent irrespective of age, gender, and diabetes mellitus. Moderate evidence showed that the fibrate class can be effective in the secondary prevention of composite outcome of non-fatal stroke, non-fatal MI, and vascular death. However, this beneficial effect relies on the inclusion of clofibrate data, a drug that was discontinued in 2002 due to its unacceptably large adverse effects. Further trials of the use of fibrates in populations with previous stroke and also against a background treatment with statins (standard of care) are required.

From Controlled Trial to Community Adoption: The Multisite Translational Community Trial

PubMed Central

Murimi, Mary; Gonzalez, Anjelica; Njike, Valentine; Green, Lawrence W.

2011-01-01

Methods for translating the findings of controlled trials, such as the Diabetes Prevention Program, into real-world community application have not been clearly defined. A standardized research methodology for making and evaluating such a transition is needed. We introduce the multisite translational community trial (mTCT) as the research analog to the multisite randomized controlled trial. The mTCT is adapted to incorporate the principles and practices of community-based participatory research and the increased relevance and generalizability gained from diverse community settings. The mTCT is a tool designed to bridge the gap between what a clinical trial demonstrates can work in principle and what is needed to make it workable and effective in real-world settings. Its utility could be put to the test, in particular with practice-based research networks such as the Prevention Research Centers. PMID:21680935

Adherence and the Lie in a HIV Prevention Clinical Trial

PubMed Central

Stadler, Jonathan; Scorgie, Fiona; van der Straten, Ariane; Saethre, Eirik

2016-01-01

The lie has been presented as a performance that protects identities against moral judgment in the context of power imbalances. We explore this assertion from the perspective of a pre-exposure prophylaxis trial to prevent HIV for African women in South Africa, in which context biological evidence of widespread lying about product adherence was produced, resulting in a moral discourse that opposed altruistic and selfish motivations. In this article, we seek to understand the meaning of the lie from the perspective of women trial participants. Seeing the trial as representing a hopeful future, and perfect adherence as sustaining their investment in this, participants recited scripted accounts of adherence and performed the role of the perfect adherer, while identifying other participants as dishonest. Given that clinical trials create moral orders and adherence is key to this, we argue that women embraced the apparatus of the clinical trial to assert their moral subjectivities. PMID:26575611

Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses

PubMed Central

Hernán, Miguel A.; Sauer, Brian C.; Hernández-Díaz, Sonia; Platt, Robert; Shrier, Ian

2016-01-01

Many analyses of observational data are attempts to emulate a target trial. The emulation of the target trial may fail when researchers deviate from simple principles that guide the design and analysis of randomized experiments. We review a framework to describe and prevent biases, including immortal time bias, that result from a failure to align start of follow-up, specification of eligibility, and treatment assignment. We review some analytic approaches to avoid these problems in comparative effectiveness or safety research. PMID:27237061

Microbicides and their potential as a catalyst for multipurpose sexual reproductive health technologies

PubMed Central

Karim, Quarraisha Abdool; Baxter, Cheryl; Karim, Salim Abdool

2014-01-01

There is an urgent need for technologies to prevent sexual acquisition of HIV infection in young women in sub-Saharan Africa. After two decades of eleven pivotal trials of seven products, antiretroviral-based topical microbicides are showing promise. Building on the CAPRISA 004 trial findings, several trials of new antiviral agents, novel delivery mechanisms and combination/multi-purpose products that address challenges of adherence and meet the sexual and reproductive health needs of men and women, including preventing HIV infection, are underway. PMID:25335841

A systematic review and meta-analysis of exercise-based falls prevention strategies in adults aged 50+ years with visual impairment.

PubMed

Dillon, Lisa; Clemson, Lindy; Ramulu, Pradeep; Sherrington, Catherine; Keay, Lisa

2018-05-06

To determine the impact of exercise or physical training on falls or physical function in people aged 50+ years with visual impairment, compared with control (no intervention or usual care). An updated systematic review of randomised controlled trials, investigating the effect of exercise or physical activity on falls prevention or physical function in adults aged 50+ with visual impairment. Searches of CINAHL, the Cochrane Register of Controlled Trials (CENTRAL), Embase, and Medline were undertaken. Three trials were identified for the period February 2013 to July 2017 and added to the four in the original review. New trials evaluated yoga, the Otago Exercise Programme in combination with a home safety programme and the Alexander Technique. Meta-analysis of data from two trials (n = 163) indicated a non-statistically significant positive impact of exercise on the Chair Stand Test (WMD -1.85 s, 95% CI -4.65 to 0.96, p = 0.20, I 2 22%). In this update, two new trials measured falls so meta-analysis was possible for three trials (n = 539) and revealed no impact on falls (RR 1.05, 95% CI 0.73 to 1.50, p = 0.81, I 2 30%). Although exercise or physical training can improve physical function in older adults with visual impairment, and diverse strategies are being evaluated, there are no proven falls prevention strategies. In the few studies available, falls are not consistently reported and more work is required to investigate falls prevention in older adults with visual impairment. © 2018 The Authors Ophthalmic & Physiological Optics © 2018 The College of Optometrists.

Future directions in treatment of brain metastases

PubMed Central

Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

2013-01-01

Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID:23717793

Future directions in treatment of brain metastases.

PubMed

Barani, Igor J; Larson, David A; Berger, Mitchel S

2013-01-01

Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT.

Guideline harmonization and implementation plan for the BETTER trial: Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice

PubMed Central

Rogers, Jess; Manca, Donna; Lang-Robertson, Kelly; Bell, Stephanie; Salvalaggio, Ginetta; Greiver, Michelle; Korownyk, Christina; Klein, Doug; Carroll, June C.; Kahan, Mel; Meuser, Jamie; Buchman, Sandy; Barrett, Rebekah M.; Grunfeld, Eva

2014-01-01

Background The aim of the Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Family Practice (BETTER) randomized controlled trial is to improve the primary prevention of and screening for multiple conditions (diabetes, cardiovascular disease, cancer) and some of the associated lifestyle factors (tobacco use, alcohol overuse, poor nutrition, physical inactivity). In this article, we describe how we harmonized the evidence-based clinical practice guideline recommendations and patient tools to determine the content for the BETTER trial. Methods We identified clinical practice guidelines and tools through a structured literature search; we included both indexed and grey literature. From these guidelines, recommendations were extracted and integrated into knowledge products and outcome measures for use in the BETTER trial. End-users (family physicians, nurse practitioners, nurses and dieticians) were engaged in reviewing the recommendations and tools, as well as tailoring the content to the needs of the BETTER trial and family practice. Results In total, 3–5 high-quality guidelines were identified for each condition; from these, we identified high-grade recommendations for the prevention of and screening for chronic disease. The guideline recommendations were limited by conflicting recommendations, vague wording and different taxonomies for strength of recommendation. There was a lack of quality evidence for manoeuvres to improve the uptake of guidelines among patients with depression. We developed the BETTER clinical algorithms for the implementation plan. Although it was difficult to identify high-quality tools, 180 tools of interest were identified. Interpretation The intervention for the BETTER trial was built by integrating existing guidelines and tools, and working with end-users throughout the process to increase the intervention’s utility for practice. Trial registration: ISRCTN07170460 PMID:25077119

Dietary Flavonoids and Colorectal Adenoma Recurrence in the Polyp Prevention Trial

PubMed Central

Bobe, Gerd; Sansbury, Leah B.; Albert, Paul S.; Cross, Amanda J.; Kahle, Lisa; Ashby, Jason; Slattery, Martha L.; Caan, Bette; Paskett, Electra; Iber, Frank; Kikendall, James Walter; Lance, Peter; Daston, Cassandra; Marshall, James R.; Schatzkin, Arthur; Lanza, Elaine

2008-01-01

Two recent case-control studies suggested that some flavonoid subgroups may play a role in preventing colorectal cancer. Previous prospective cohort studies generally reported no association; however, only a small subset of flavonoids was evaluated and partial flavonoid databases were used. We used the newly constructed U.S. Department of Agriculture flavonoid database to examine the association between consumption of total flavonoids, 6 flavonoid subgroups, and 29 individual flavonoids with adenomatous polyp recurrence in the Polyp Prevention Trial. The Polyp Prevention Trial was a randomized dietary intervention trial, which examined the effectiveness of a low-fat, high-fiber, high-fruit, and high-vegetable diet on adenoma recurrence. Intakes of flavonoids were estimated from a food frequency questionnaire. Multivariate logistic regression models (adjusted for age, body mass index, sex, regular non–steroidal anti-inflammatory use, and dietary fiber intake) were used to estimate odds ratios and 95% confidence intervals for both any and advanced adenoma recurrence within quartiles of energy-adjusted flavonoid intake (baseline, during the trial, and change during the trial). Total flavonoid intake was not associated with any or advanced adenoma recurrence. However, high intake of flavonols, which are at greater concentrations in beans, onions, apples, and tea, was associated with decreased risk of advanced adenoma recurrence (4th versus 1st quartile during the trial; odds ratio, 0.24; 95% confidence interval, 0.11, 0.53; Ptrend = 0.0006). Similar inverse associations were observed to a smaller extent for isoflavonoids, the flavonol kaempferol, and the isoflavonoids genistein and formononetin. Our data suggest that a flavonol-rich diet may decrease the risk of advanced adenoma recurrence. PMID:18559549

Information diffusion, Facebook clusters, and the simplicial model of social aggregation: a computational simulation of simplicial diffusers for community health interventions.

PubMed

Kee, Kerk F; Sparks, Lisa; Struppa, Daniele C; Mannucci, Mirco A; Damiano, Alberto

2016-01-01

By integrating the simplicial model of social aggregation with existing research on opinion leadership and diffusion networks, this article introduces the constructs of simplicial diffusers (mathematically defined as nodes embedded in simplexes; a simplex is a socially bonded cluster) and simplicial diffusing sets (mathematically defined as minimal covers of a simplicial complex; a simplicial complex is a social aggregation in which socially bonded clusters are embedded) to propose a strategic approach for information diffusion of cancer screenings as a health intervention on Facebook for community cancer prevention and control. This approach is novel in its incorporation of interpersonally bonded clusters, culturally distinct subgroups, and different united social entities that coexist within a larger community into a computational simulation to select sets of simplicial diffusers with the highest degree of information diffusion for health intervention dissemination. The unique contributions of the article also include seven propositions and five algorithmic steps for computationally modeling the simplicial model with Facebook data.

Molecular Cancer Prevention: Current Status & Future Directions

PubMed Central

Maresso, Karen Colbert; Tsai, Kenneth Y.; Brown, Powel H.; Szabo, Eva; Lippman, Scott; Hawk, Ernest

2016-01-01

The heterogeneity and complexity of advanced cancers strongly supports the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (e.g., aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the FDA for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, a number of challenges to the field must be addressed. Here we provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results of major randomized controlled trials. PMID:26284997

Nanolaminates with Novel Properties Fabricated Using Atomic Layer Deposition Techniques

DTIC Science & Technology

2006-07-01

Enhance X-Ray Reflectivity of Polysilicon Micro-Mirrors at 1.54 A Wavelength", Proceedings of SPIE 5720, 241-251 (2005). 20. D.C. Miller, C.F...diodes ( OLEDs ). This project has demonstrated that the A120 3 ALD gas diffusion barrier helps to prevent H20 and 02 gases from diffusing through the

CAR T-Cell therapy can lead to long-lasting remissions in patients with lymphoma | Center for Cancer Research

Cancer.gov

More than three years after treatment, some clinical trial participants who received CAR T-cell therapy for diffuse large B-cell lymphoma remain in remission. These results are reported in a paper in Molecular Therapy by James Kochenderfer, M.D., of CCR's Experimental Transplantation and Immunology Branch. “This raises the possibility that CAR T cells can be curative for diffuse large B cell lymphoma,” Kochenderfer says.

Trials in the prevention of type 1 diabetes: current and future.

PubMed

Wherrett, Diane K

2014-08-01

A major thrust in type 1 diabetes research is stopping the destruction of beta cells that leads to type 1 diabetes. Research over the past 30 years has defined genetic factors and evidence of autoimmunity that have led to the development of robust prediction models in those at high risk for type 1 diabetes. The ability to identify those at risk and the development of new agents and of collaborative research networks has led to multiple trials aimed at preventing beta cell loss. Trials at all stages of beta cell loss have been conducted: primary prevention (prior to the development of autoimmunity); secondary prevention (after autoantibodies are found) and tertiary prevention (intervening after diagnosis to maintain remaining beta cells). Studies have shown mixed results; evidence of maintained insulin secretion after the time of diagnosis has been described in a number of studies, and primary and secondary prevention is proving to be elusive. Much has been learned from the increasing number of studies in the field in terms of network creation, study design and choice of intervention that will facilitate new avenues of investigation. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Relapse prevention interventions for smoking cessation.

PubMed

Hajek, P; Stead, L F; West, R; Jarvis, M

2005-01-25

Several treatments can help smokers make a successful quit attempt, but many initially successful quitters relapse over time. There are interventions designed to help prevent relapse. To assess whether specific interventions for relapse prevention reduce the proportion of recent quitters who return to smoking. We searched the Cochrane Tobacco Addiction group trials register in September 2004 for studies mentioning relapse prevention or maintenance in title, abstracts or keywords. Randomized or quasi-randomized controlled trials of relapse prevention interventions with a minimum follow up of six months. We included smokers who quit on their own, or were undergoing enforced abstinence, or who were participating in treatment programmes. We included trials that compared relapse prevention interventions to a no intervention control, or that compared a cessation programme with additional relapse prevention components to a cessation programme alone. Studies were screened and data extracted by one author and checked by a second. Disagreements were resolved by discussion or referral to a third author. Forty studies met inclusion criteria, but were heterogeneous in terms of populations and interventions. We considered studies that randomized abstainers separately from studies that randomized participants prior to their quit date. We detected no benefit of brief and 'skills-based' relapse prevention interventions for women who had quit smoking due to pregnancy, or for smokers undergoing a period of enforced abstinence. We also failed to detect significant effects in trials in other smokers who had quit on their own or with a formal programme. Amongst trials recruiting smokers and evaluating the effect of additional relapse prevention components we also found no evidence of benefit in any subgroup. We did not find that providing training in skills thought to be needed for relapse avoidance reduced relapse, but most studies did not use experimental designs best suited to the task, and had limited power to detect expected small differences between interventions. At the moment there is insufficient evidence to support the use of any specific intervention for helping smokers who have successfully quit for a short time to avoid relapse. The verdict is strongest for interventions focusing on identifying and resolving tempting situations, as most studies were concerned with these. There is very little research available regarding other approaches. Until more evidence becomes available it may be more efficient to focus resources on supporting the initial cessation attempt rather than on additional relapse prevention efforts.

Diffusion of school-based prevention programs in two urban districts: adaptations, rationales, and suggestions for change.

PubMed

Ozer, Emily J; Wanis, Maggie G; Bazell, Nickie

2010-03-01

The diffusion of school-based preventive interventions involves the balancing of high-fidelity implementation of empirically-supported programs with flexibility to permit local stakeholders to target the specific needs of their youth. There has been little systematic research that directly seeks to integrate research- and community-driven approaches to diffusion. The present study provides a primarily qualitative investigation of the initial roll-out of two empirically-supported substance and violence prevention programs in two urban school districts that serve a high proportion of low-income, ethnic minority youth. The predominant ethnic group in most of our study schools was Asian American, followed by smaller numbers of Latinos, African Americans, and European Americans. We examined the adaptations made by experienced health teachers as they implemented the programs, the elicitation of suggested adaptations to the curricula from student and teacher stakeholders, and the evaluation of the consistency of these suggested adaptations with the core components of the programs. Data sources include extensive classroom observations of curricula delivery and interviews with students, teachers, and program developers. All health teachers made adaptations, primarily with respect to instructional format, integration of real-life experiences into the curriculum, and supplementation with additional resources; pedagogical and class management issues were cited as the rationale for these changes. Students and teachers were equally likely to propose adaptations that met with the program developers' approval with respect to program theory and implementation logistics. Tensions between teaching practice and prevention science-as well as implications for future research and practice in school-based prevention-are considered.

Epidural blood patching for preventing and treating post-dural puncture headache.

PubMed

Sudlow, C; Warlow, C

2002-01-01

Dural puncture is a common procedure, but leakage of CSF from the resulting dural defect may cause postural headache after the procedure, and this can be disabling. Injecting an epidural blood patch around the site of the defect may stop this leakage, and so may have a role in preventing or treating post dural puncture headache. To assess the possible benefits and harms of epidural blood patching in both the prevention and the treatment of post-dural puncture headache. We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 4, 2000), MEDLINE (January 1994 to December 1998), and EMBASE (January 1980 to December 1998). We also searched the reference lists of relevant articles identified electronically, and asked both the authors of all included trials and colleagues with an interest in this area to let us know of any other potentially relevant studies not already identified. Date of last search: December 2000. We sought all properly randomised, unconfounded trials that compared epidural blood patch versus no epidural blood patch in the prevention or treatment of post-dural puncture headache among all types of patients undergoing dural puncture for any reason. The primary outcome of effectiveness was postural headache. One reviewer extracted details of trial methodology and outcome data from the reports of all trials considered eligible for inclusion. We invited the authors of all such trials both to check the information extracted and to provide any details that were unavailable in the published reports. Intention-to-treat analyses were performed using the Peto O-E method. Information about adverse effects (post-dural puncture backache, epidural infection and lower limb paraesthesia) was also extracted. Three trials (77 patients) were eligible for inclusion. Methodological details were generally incomplete. Although the results of our analyses suggested that both prophylactic and therapeutic epidural blood patching may be of benefit, the very small numbers of patients and outcome events, as well as uncertainties about trial methodology, precluded reliable assessments of the potential benefits and harms of this intervention. Further, adequately powered, randomised trials (including at least a few hundred patients) are required before reliable conclusions can be drawn about the role of epidural blood patching in the prevention and treatment of post-dural puncture headache.

Long-term follow-up of moderately hypercholesterolemic hypertensive patients following randomization to pravastatin vs. usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)

PubMed Central

Margolis, Karen L.; Davis, Barry R.; Baimbridge, Charles; Ciocon, Jerry O.; Cuyjet, Aloysius B.; Dart, Richard A.; Einhorn, Paula T.; Ford, Charles E.; Gordon, David; Hartney, Thomas J; Haywood, L. Julian; Holtzman, Jordan; Mathis, David E.; Oparil, Suzanne; Probstfield, Jeffrey L.; Simpson, Lara M.; Stokes, John D.; Wiegmann, Thomas B.; Williamson, Jeff D.

2015-01-01

A randomized, controlled, multicenter trial assigned well-controlled hypertensive participants ≥55 years, with moderate hypercholesterolemia to receive pravastatin (n=5170) or usual care (n=5185) for 4-8 years, when trial therapy was discontinued. Passive surveillance using national databases to ascertain deaths and hospitalizations continued for total follow-up of 8-13 years to assess whether mortality and morbidity differences persisted or new differences developed. During the post-trial period, fatal and nonfatal outcomes were available for 98% and 64% of participants, respectively. Primary outcome was all-cause mortality; secondary outcomes included cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, cardiovascular disease, and end-stage renal disease. No significant differences appeared in mortality for pravastatin versus usual care (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.89-1.03), or other secondary outcomes. Similar to the previously reported in-trial result, there was a significant treatment effect for CHD in Blacks (HR, 0.79; 95% CI, 0.64-0.98). However, the in-trial result showing a significant treatment by race effect did not remain significant over the entire follow-up (P=.08). These findings are consistent with evidence from other large trials that show statins prevent CHD and add evidence that they are effective for CHD prevention in Blacks. PMID:23889716

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alsolamy, Sami; Al-Dawood, Abdulaziz; Al-Omari, Awad; Al-Hameed, Fahad; Burns, Karen E A; Almaani, Mohammed; Lababidi, Hani; Al Bshabshe, Ali; Mehta, Sangeeta; Al-Aithan, Abdulsalam M; Mandourah, Yasser; Almekhlafi, Ghaleb; Finfer, Simon; Abdukahil, Sheryl Ann I; Afesh, Lara Y; Dbsawy, Maamoun; Sadat, Musharaf

2016-08-03

Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).

Diffusion MRI: Pitfalls, literature review and future directions of research in mild traumatic brain injury.

PubMed

Delouche, Aurélie; Attyé, Arnaud; Heck, Olivier; Grand, Sylvie; Kastler, Adrian; Lamalle, Laurent; Renard, Felix; Krainik, Alexandre

2016-01-01

Mild traumatic brain injury (mTBI) is a leading cause of disability in adults, many of whom report a distressing combination of physical, emotional and cognitive symptoms, collectively known as post-concussion syndrome, that persist after the injury. Significant developments in magnetic resonance diffusion imaging, involving voxel-based quantitative analysis through the measurement of fractional anisotropy or mean diffusivity, have enhanced our knowledge on the different stages of mTBI pathophysiology. Other diffusion imaging-derived techniques, including diffusion kurtosis imaging with multi-shell diffusion and high-order tractography models, have recently demonstrated their usefulness in mTBI. Our review starts by briefly outlining the physical basis of diffusion tensor imaging including the pitfalls for use in brain trauma, before discussing findings from diagnostic trials testing its usefulness in assessing brain structural changes in patients with mTBI. Use of different post-processing techniques for the diffusion imaging data, identified the corpus callosum as the most frequently injured structure in mTBI, particularly at sub-acute and chronic stages, and a crucial location for evaluating functional outcome. However, structural changes appear too subtle for identification using traditional diffusion biomarkers, thus disallowing expansion of these techniques into clinical practice. In this regard, more advanced diffusion techniques are promising in the assessment of this complex disease. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Selective decontamination of the digestive tract reduces pneumonia and mortality.

PubMed

Haas, Lenneke E M; Schultz, Marcus J

2010-01-01

Selective decontamination of the digestive tract (SDD) has been subject of numerous randomized controlled trials in critically ill patients. Almost all clinical trials showed SDD to prevent pneumonia. Nevertheless, SDD has remained a controversial strategy. One reason for why clinicians remained reluctant to implement SDD into daily practice could be that mortality was reduced in only 2 trials. Another reason could be the heterogeneity of trials of SDD. Indeed, many different prophylactic antimicrobial regimes were tested, and dissimilar diagnostic criteria for pneumonia were applied amongst the trials. This heterogeneity impeded interpretation and comparison of trial results. Two other hampering factors for implementation of SDD have been concerns over the risk of antimicrobial resistance and fear for escalation of costs associated with the use of prophylactic antimicrobials. This paper describes the concept of SDD, summarizes the results of published trials of SDD in mixed medical-surgical intensive care units, and rationalizes the risk of antimicrobial resistance and rise of costs associated with this potentially life-saving preventive strategy.

Alcohol-Specific Parenting within a Cluster-Randomized Effectiveness Trial of a Swedish Primary Prevention Program

ERIC Educational Resources Information Center

Strandberg, Anna K.; Bodin, Maria C.

2011-01-01

Purpose: Within the framework of an ongoing cluster-randomized effectiveness trial of a parental prevention program, the aim of the present study is to investigate attitudes towards under-age drinking and use of program components, i.e. alcohol-specific parenting behaviors, in parents who did and did not take part in the programme.…

Installing the Communities that Care Prevention System: Implementation Progress and Fidelity in a Randomized Controlled Trial

ERIC Educational Resources Information Center

Quinby, Rose K.; Hanson, Koren; Brooke-Weiss, Blair; Arthur, Michael W.; Hawkins, J. David; Fagan, Abigail A.

2008-01-01

This article describes the degree to which high fidelity implementation of the Communities That Care (CTC) prevention operating system was reached during the first 18 months of intervention in 12 communities in the Community Youth Development Study, a 5-year group randomized controlled trial designed to test the efficacy of the CTC system. CTC…

A Controlled Trial of a Novel Primary Prevention Program for Lyme Disease and Other Tick-Borne Illnesses

ERIC Educational Resources Information Center

Daltroy, Lawren H.; Phillips, Charlotte; Lew, Robert; Wright, Elizabeth; Shadick, Nancy A.; Liang, Matthew H.

2007-01-01

To evaluate a theory-based educational program to prevent Lyme disease and other tick-borne illnesses (TBI), a randomized controlled trial of an educational program was delivered to ferry passengers traveling to an endemic area in southeastern Massachusetts. Rates of TBI and precautionary and tick check behaviors were measured over three summers…

Correlates of Adherence to a Telephone-Based Multiple Health Behavior Change Cancer Preventive Intervention for Teens: The Healthy for Life Program (HELP)

ERIC Educational Resources Information Center

Mays, Darren; Peshkin, Beth N.; Sharff, McKane E.; Walker, Leslie R.; Abraham, Anisha A.; Hawkins, Kirsten B.; Tercyak, Kenneth P.

2012-01-01

This study examined factors associated with teens' adherence to a multiple health behavior cancer preventive intervention. Analyses identified predictors of trial enrollment, run-in completion, and adherence (intervention initiation, number of sessions completed). Of 104 teens screened, 73% (n = 76) were trial eligible. White teens were more…

A Quasi-Randomized Trial of a School-Wide Universal Prevention Program: Results and Lessons Learned

ERIC Educational Resources Information Center

Bodin, Maria C.; South, Sandra H.; Ingemarson, Maria

2016-01-01

Prevention in School (PS) is a comprehensive program which aims to improve the learning climate and reduce problem behavior in elementary schools. Core components are teaching of school rules, praise and rewards to support prosocial behavior, and a forum involving parents. This trial investigated the effects of PS on its intended outcomes, and…

Relapse prevention after index electroconvulsive therapy in treatment-resistant depression

PubMed Central

Youssef, Nagy A.; McCall, W. Vaughn

2015-01-01

Background One-third of patients who suffer from depression are resistant to conventional treatments. An acute course of electroconvulsive therapy (ECT) can lead to remission of depressive symptoms in a substantial portion of the treatment-resistant patients. However, prevention of relapse with depressive symptoms after the index course of ECT can be challenging. We review pertinent studies on the topic and analyze the best strategies to avoid relapse and recurrence of depressive symptoms. Methods We performed a systematic literature review of PubMed through April 2014 for clinical trials published in English to determine if continuation ECT, continuation medication, continuation psychotherapy, or combinations of these are the best strategy to avoid relapse and recurrence of depressive symptoms after an acute course of ECT. Clinical trials comparing ≥2 of the above strategies were included in the review. Results Although there are few rigorous randomized clinical trials in this area, most studies suggest that combined continuation ECT (C-ECT) and continuation pharmacotherapy are the most effective strategy in relapse prevention. Conclusions C-ECT and continuation pharmacotherapy may be more effective than either alone for preventing relapse. However, more definitive randomized clinical trials are needed. PMID:25401716

'I heard about this study on the radio': using community radio to strengthen Good Participatory Practice in HIV prevention trials.

PubMed

Medeossi, Bonnie-Jeanne; Stadler, Jonathan; Delany-Moretlwe, Sinead

2014-08-26

During the Microbicides Development Program (MDP) 301, a clinical trial of a candidate microbicide amongst women in Johannesburg, South Africa, we used community radio to promote awareness of the trial, to inform community members about specific medical research procedures and terminologies, and to stimulate dialogue between researchers and local citizens. We used mixed methods to undertake a retrospective analysis of the social responses to the radio shows, focusing specifically on recruitment and participation in the MDP301 trial. We collected quantitative data that describes the themes and listener responses, the costs per broadcast, and the impact of the radio broadcasts on trial recruitment. Qualitative data on local reactions to the shows was gleaned from in-depth interviews with trial participants. Over a seven-year period, 205 individual broadcasts were made on two separate community radio stations. Show themes were either specifically related to medical research issues (36%), or focused on general health issues (46%), and sexual and reproductive health, including HIV prevention (18%). 403 listeners made telephone calls to the radio station, and 12% of women enrolled as participants in MDP301 (n = 9, 385) reported that they had first heard about the trial from the radio. Qualitative interviews (n = 401) with female MDP301 participants highlighted the effects of the radio shows in making women aware of the trial, impressing them with the importance of health screening and knowledge, legitimizing trial participation, and stimulating dialogue between trial participants and their male partners. Community radio is a potent tool for raising awareness and local knowledge about medical research and, in addition to other methodologies, can be used to promote recruitment into clinical trials. We suggest that future HIV prevention trials consider an investment in community radio beyond recruitment advertisements that incorporates this into the broader community engagement plan as a key element of Good Participatory Practice in clinical trial settings.

Garlic for the common cold.

PubMed

Lissiman, Elizabeth; Bhasale, Alice L; Cohen, Marc

2014-11-11

Background Garlic is alleged to have antimicrobial and antiviral properties that relieve the common cold, among other beneficial effects. There is widespread usage of garlic supplements. The common cold is associated with significant morbidity and economic consequences. On average, children have six to eight colds per year and adults have two to four.Objectives To determine whether garlic (Allium sativum) is effective for the prevention or treatment of the common cold, when compared to placebo, no treatment or other treatments.Search methods We searched CENTRAL (2014, Issue 7),OLDMEDLINE (1950 to 1965),MEDLINE (January 1966 to July week 5, 2014), EMBASE(1974 to August 2014) and AMED (1985 to August 2014).Selection criteria Randomised controlled trials of common cold prevention and treatment comparing garlic with placebo, no treatment or standard treatment.Data collection and analysis Two review authors independently reviewed and selected trials from searches, assessed and rated study quality and extracted relevant data.Main results In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria.This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily)for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. Authors' conclusions There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

“If It’s Not Working, Why Would They Be Testing It?”: mental models of HIV vaccine trials and preventive misconception among men who have sex with men in India

PubMed Central

2013-01-01

Background Informed consent based on comprehension of potential risks and benefits is fundamental to the ethical conduct of clinical research. We explored mental models of candidate HIV vaccines and clinical trials that may impact on the feasibility and ethics of biomedical HIV prevention trials among men who have sex with men (MSM) in India. Methods A community-based research project was designed and implemented in partnership with community-based organizations serving MSM in Chennai and Mumbai. We conducted 12 focus groups (n = 68) with diverse MSM and 14 key informant interviews with MSM community leaders/service providers using a semi-structured interview guide to explore knowledge and beliefs about HIV vaccines and clinical trials. Focus groups (60–90 minutes) and interviews (45–60 minutes) were conducted in participants’ native language (Tamil in Chennai; Marathi or Hindi in Mumbai), audio-taped, transcribed and translated into English. We explored focus group and interview data using thematic analysis and a constant comparative method, with a focus on mental models of HIV vaccines and clinical trials. Results A mental model of HIV vaccine-induced seropositivity as “having HIV” resulted in fears of vaccine-induced infection and HIV stigma. Some participants feared inactivated vaccines might “drink blood” and “come alive”. Pervasive preventive misconception was based on a mental model of prevention trials as interventions, overestimation of likely efficacy of candidate vaccines and likelihood of being assigned to the experimental group, with expectations of protective benefits and decreased condom use. Widespread misunderstanding and lack of acceptance of placebo and random assignment supported perceptions of clinical trials as “cheating”. Key informants expressed concerns that volunteers from vulnerable Indian communities were being used as “experimental rats” to benefit high-income countries. Conclusions Evidence-informed interventions that engage with shared mental models among potential trial volunteers, along with policies and funding mechanisms that ensure local access to products that demonstrate efficacy in trials, may support the safe and ethical implementation of HIV vaccine trials in India. PMID:23919283

Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials

PubMed Central

Ju, Woong; Oh, Seung-Won; Park, Sang Min; Koo, Bon-Kwon; Park, Byung-Joo

2013-01-01

Objective To assess the efficacy of vitamin and antioxidant supplements in the prevention of cardiovascular diseases. Design Meta-analysis of randomised controlled trials. Data sources and study selection PubMed, EMBASE, the Cochrane Library, Scopus, CINAHL, and ClinicalTrials.gov searched in June and November 2012. Two authors independently reviewed and selected eligible randomised controlled trials, based on predetermined selection criteria. Results Out of 2240 articles retrieved from databases and relevant bibliographies, 50 randomised controlled trials with 294 478 participants (156 663 in intervention groups and 137 815 in control groups) were included in the final analyses. In a fixed effect meta-analysis of the 50 trials, supplementation with vitamins and antioxidants was not associated with reductions in the risk of major cardiovascular events (relative risk 1.00, 95% confidence interval 0.98 to 1.02; I2=42%). Overall, there was no beneficial effect of these supplements in the subgroup meta-analyses by type of prevention, type of vitamins and antioxidants, type of cardiovascular outcomes, study design, methodological quality, duration of treatment, funding source, provider of supplements, type of control, number of participants in each trial, and supplements given singly or in combination with other supplements. Among the subgroup meta-analyses by type of cardiovascular outcomes, vitamin and antioxidant supplementation was associated with a marginally increased risk of angina pectoris, while low dose vitamin B6 supplementation was associated with a slightly decreased risk of major cardiovascular events. Those beneficial or harmful effects disappeared in subgroup meta-analysis of high quality randomised controlled trials within each category. Also, even though supplementation with vitamin B6 was associated with a decreased risk of cardiovascular death in high quality trials, and vitamin E supplementation with a decreased risk of myocardial infarction, those beneficial effects were seen only in randomised controlled trials in which the supplements were supplied by the pharmaceutical industry. Conclusion There is no evidence to support the use of vitamin and antioxidant supplements for prevention of cardiovascular diseases. PMID:23335472

Pharmacological interventions for preventing post-traumatic stress disorder (PTSD).

PubMed

Amos, Taryn; Stein, Dan J; Ipser, Jonathan C

2014-07-08

Post-traumatic stress disorder (PTSD) is a debilitating disorder which, after a sufficient delay, may be diagnosed amongst individuals who respond with intense fear, helplessness or horror to traumatic events. There is some evidence that the use of pharmacological interventions immediately after exposure to trauma may reduce the risk of developing of PTSD. To assess the effects of pharmacological interventions for the prevention of PTSD in adults following exposure to a traumatic event. We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) (to 14 February 2014). This register contains relevant reports of randomised controlled trials from the following bibliographic databases: CENTRAL (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). We identified unpublished trials by searching the National Institute of Health (NIH) Reporter, the metaRegister of Controlled Trials database (mRCT) and the WHO International Clinical Trials Registry Platform (to December 2013). We scanned the reference lists of articles for additional studies. We placed no constraints on language and setting. We restricted studies to randomised controlled trials (RCTs) of pharmacological interventions compared with placebo for the prevention of PTSD in adults. Two authors (TA and JI) independently assessed trials for eligibility and inclusion based on the review selection criteria. We independently extracted sample, methodological, outcome and 'Risk of bias' data, as well as the number of side effects, from each trial and entered these into a customised data extraction form. We contacted investigators for missing information. We calculated summary statistics for continuous and dichotomous variables (if provided). We did not undertake subgroup analyses due to the small number of included studies. We included nine short-term RCTs (duration 12 weeks or less) in the analysis (345 participants; age range 18 to 76 years). Participants were exposed to a variety of traumas, ranging from assault, traffic accidents and work accidents to cardiac surgery and septic shock. Seven studies were conducted at single centres. The seven RCTs included four hydrocortisone studies, three propranolol studies (of which one study had a third arm investigating gabapentin), and single trials of escitalopram and temazepam. Outcome assessment measures included the Clinician-Administered PTSD Scale (CAPS), the 36-Item Short-Form Health Survey (SF-36) and the Center for Epidemiological Studies - Depression Scale (CES-D).In four trials with 165 participants there was moderate quality evidence for the efficacy of hydrocortisone in preventing the onset of PTSD (risk ratio (RR) 0.17; 95% confidence interval (CI) 0.05 to 0.56; P value = 0.004), indicating that between seven and 13 patients would need to be treated with this agent in order to prevent the onset of PTSD in one patient. There was low quality evidence for preventing the onset of PTSD in three trials with 118 participants treated with propranolol (RR 0.62; 95% CI 0.24 to 1.59; P value = 0.32). Drop-outs due to treatment-emergent side effects, where reported, were low for all of the agents tested. Three of the four RCTs of hydrocortisone reported that medication was more effective than placebo in reducing PTSD symptoms after a median of 4.5 months after the event. None of the single trials of escitalopram, temazepam and gabapentin demonstrated evidence that medication was superior to placebo in preventing the onset of PTSD.Seven of the included RCTs were at a high risk of bias. Differential drop-outs between groups undermined the results of three studies, while one study failed to describe how the allocation of medication was concealed. Other forms of bias that might have influenced study results included possible confounding through group differences in concurrent medication and termination of the study based on treatment response. There is moderate quality evidence for the efficacy of hydrocortisone for the prevention of PTSD development in adults. We found no evidence to support the efficacy of propranolol, escitalopram, temazepam and gabapentin in preventing PTSD onset. The findings, however, are based on a few small studies with multiple limitations. Further research is necessary in order to determine the efficacy of pharmacotherapy in preventing PTSD and to identify potential moderators of treatment effect.

The Road Ahead to Cure Alzheimer’s Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations

PubMed Central

Cavedo, E.; Lista, S.; Khachaturian, Z.; Aisen, P.; Amouyel, P.; Herholz, K.; Jack, C.R.; Sperling, R.; Cummings, J.; Blennow, K.; O’Bryant, S.; Frisoni, G.B.; Khachaturian, A.; Kivipelto, M.; Klunk, W.; Broich, K.; Andrieu, S.; de Schotten, M. Thiebaut; Mangin, J.-F.; Lammertsma, A.A.; Johnson, K.; Teipel, S.; Drzezga, A.; Bokde, A.; Colliot, O.; Bakardjian, H.; Zetterberg, H.; Dubois, B.; Vellas, B.; Schneider, L.S.; Hampel, H.

2015-01-01

Alzheimer’s disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group’s revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard (“core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for “prodromal AD” and “mild cognitive impairment due to AD” include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication. PMID:26478889

Diffusion of an evidence-based smoking cessation intervention through Facebook: a randomised controlled trial study protocol

PubMed Central

Cobb, Nathan K; Jacobs, Megan A; Saul, Jessie; Wileyto, E Paul; Graham, Amanda L

2014-01-01

Introduction Online social networks represent a potential mechanism for the dissemination of health interventions including smoking cessation; however, which elements of an intervention determine diffusion between participants is unclear. Diffusion is frequently measured using R, the reproductive rate, which is determined by the duration of use (t), the ‘contagiousness’ of an intervention (β) and a participant's total contacts (z). We have developed a Facebook ‘app’ that allows us to enable or disable various components designed to impact the duration of use (expanded content, proactive contact), contagiousness (active and passive sharing) and number of contacts (use by non-smoker supporters). We hypothesised that these elements would be synergistic in their impact on R, while including non-smokers would induce a ‘carrier’ state allowing the app to bridge clusters of smokers. Methods and analysis This study is a fractional factorial, randomised control trial of the diffusion of a Facebook application for smoking cessation. Participants recruited through online advertising are randomised to 1 of 12 cells and serve as ‘seed’ users. All user interactions are tracked, including social interactions with friends. Individuals installing the application that can be traced back to a seed participant are deemed ‘descendants’ and form the outcome of interest. Analysis will be conducted using Poisson regression, with event count as the outcome and the number of seeds in the cell as the exposure. Results The results will be reported as a baseline R0 for the reference group, and incidence rate ratio for the remainder of predictors. Ethics and Dissemination This study uses an abbreviated consent process designed to minimise barriers to adoption and was deemed to be minimal risk by the Institutional Review Board (IRB). Results will be disseminated through traditional academic literature as well as social media. If feasible, anonymised data and underlying source code are intended to be made available under an open source license. ClinicalTrials.gov registration number NCT01746472. PMID:24448847

Theory-based interventions for contraception.

PubMed

Lopez, Laureen M; Tolley, Elizabeth E; Grimes, David A; Chen-Mok, Mario

2009-01-21

The explicit use of theory in research helps expand the knowledge base. Theories and models have been used extensively in HIV-prevention research and in interventions for preventing sexually transmitted infections (STIs). The health behavior field uses many theories or models of change. However, educational interventions addressing contraception often have no stated theoretical base. Review randomized controlled trials that tested a theoretical approach to inform contraceptive choice; encourage contraceptive use; or promote adherence to, or continuation of, a contraceptive regimen. We searched computerized databases for trials that tested a theory-based intervention for improving contraceptive use (MEDLINE, POPLINE, CENTRAL, PsycINFO, EMBASE, ClinicalTrials.gov, and ICTRP). We also wrote to researchers to find other trials. Trials tested a theory-based intervention for improving contraceptive use. We excluded trials focused on high-risk groups. Interventions addressed the use of one or more contraceptive methods. The reports provided evidence that the intervention was based on a specific theory or model. The primary outcomes were pregnancy, contraceptive choice, initiating or changing contraceptive use, contraceptive regimen adherence, and contraception continuation. The primary author evaluated abstracts for eligibility. Two authors extracted data from included studies. We calculated the odds ratio for dichotomous outcomes and the mean difference for continuous data. No meta-analysis was conducted due to intervention differences. Of 26 trials, 12 interventions addressed contraception (other than condoms), while 14 focused on condom use for preventing HIV or STIs. In 2 of 10 trials with pregnancy or birth data, a theory-based group showed better results. Four of nine trials with contraceptive use (other than condoms) showed better outcomes in an experimental group. For condom use, a theory-based group had favorable results in 14 of 20 trials, but the number was halved in a subgroup analysis. Social Cognitive Theory was the main theoretical basis for 12 trials, and 10 showed positive results. Of the other 14 trials, favorable results were shown for other social cognition models (N=2), motivational interviewing (N=5), and the AIDS Risk Reduction Model (N=2). No major patterns were detected by type of theory, intervention, or target population. Family planning researchers and practitioners could apply the relevant theories and effective interventions from HIV and STI prevention. More thorough use of single theories would help inform the field about what works. Better reporting is needed on research design and intervention implementation.

Promise of precision medicine for common type of lymphoma

Cancer.gov

A clinical trial has shown that patients with a specific molecular subtype of diffuse large B-cell lymphoma are more likely to respond to the drug ibrutinib than patients with another molecular subtype of the disease

Efficacy of falls prevention interventions: protocol for a systematic review and network meta-analysis

PubMed Central

2013-01-01

Background Falls are a leading cause of morbidity and mortality in older adults. Although numerous trials of falls prevention interventions have been completed, there is extensive variation in their intervention components and clinical context, such that the key elements of an effective falls prevention program remain unclear to patients, clinicians, and policy-makers. Our objective is to identify the most effective interventions and combinations of interventions that prevent falls though a systematic review and meta-analysis, including a network meta-analysis. Methods/Design We will search for published (e.g., MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Ageline) and unpublished (e.g., trial registries, dissertations) randomised clinical trials (RCTs) in all languages examining interventions to prevent falls compared to usual care or other falls prevention interventions among adults aged ≥65 years from all settings (e.g., community, acute care, long-term care, and rehabilitation). The primary outcomes are number of injurious falls and number of hospitalizations due to falls. Secondary outcomes include falls rate, number of fallers, number of emergency room visits due to falls, number of physician visits due to falls, number of fractures, costs, and number of intervention-related harms (e.g., muscle soreness related to exercise). We will calibrate our eligibility criteria amongst the team and two independent team members will screen the literature search results in duplicate. Conflicts will be resolved through team discussion. A similar process will be used for data abstraction and quality appraisal with the Cochrane risk of bias tool. Our results will be synthesized descriptively and a random effects meta-analysis will be conducted if the studies are deemed methodologically, clinically, and statistically (e.g., I2<60%) similar. If appropriate, a network meta-analysis will be conducted, which will allow the comparison of interventions that have not been compared in head-to-head RCTs, as well as the effectiveness of interventions. Discussion We will identify the most effective interventions and combinations of interventions that prevent falls in older people. Our results will be used to optimize falls prevention strategies, and our goal is to ultimately improve the health of seniors internationally. Trial registration PROSPERO registry number: CRD42013004151 PMID:23738619

Mapping the evidence for the prevention and treatment of eating disorders in young people

PubMed Central

2014-01-01

Abstract Eating disorders often develop during adolescence and young adulthood, and are associated with significant psychological and physical burden. Identifying evidence-based interventions is critical and there is need to take stock of the extant literature, to inform clinical practice regarding well-researched interventions and to direct future research agendas by identifying gaps in the evidence base. Aim To investigate and quantify the nature and distribution of existing high-quality research on the prevention and treatment of eating disorders in young people using evidence mapping methodology. Method A systematic search for prevention and treatment intervention studies in adolescents and young adults (12–25 years) was conducted using EMBASE, PSYCINFO and MEDLINE. Studies were screened and mapped according to disorder, intervention modality, stage of eating disorder and study design. Included studies were restricted to controlled trials and systematic reviews published since 1980. Results The eating disorders evidence map included 197 trials and 22 systematic reviews. Prevention research was dominated by trials of psychoeducation (PE). Bulimia nervosa (BN) received the most attention in the treatment literature, with cognitive behavioural therapy (CBT) and antidepressants the most common interventions. For anorexia nervosa (AN), family based therapy (FBT) was the most studied. Lacking were trials exploring treatments for binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS). Relapse prevention strategies were notably absent across the eating disorders. Conclusions Despite substantial literature devoted to the prevention and treatment of eating disorders in young people, the evidence base is not well established and significant gaps remain. For those identified as being at-risk, there is need for prevention research exploring strategies other than passive PE. Treatment interventions targeting BED and EDNOS are required, as are systematic reviews synthesising BN treatment trials (e.g., CBT, antidepressants). FBTs for AN require investigation against other validated psychological interventions, and the development of relapse prevention strategies is urgently required. By systematically identifying existing interventions for young people with eating disorders and exposing gaps in the current literature, the evidence map can inform researchers, funding bodies and policy makers as to the opportunities for future research. PMID:24999427

Mapping the evidence for the prevention and treatment of eating disorders in young people.

PubMed

Bailey, Alan P; Parker, Alexandra G; Colautti, Lauren A; Hart, Laura M; Liu, Ping; Hetrick, Sarah E

2014-01-01

Eating disorders often develop during adolescence and young adulthood, and are associated with significant psychological and physical burden. Identifying evidence-based interventions is critical and there is need to take stock of the extant literature, to inform clinical practice regarding well-researched interventions and to direct future research agendas by identifying gaps in the evidence base. To investigate and quantify the nature and distribution of existing high-quality research on the prevention and treatment of eating disorders in young people using evidence mapping methodology. A systematic search for prevention and treatment intervention studies in adolescents and young adults (12-25 years) was conducted using EMBASE, PSYCINFO and MEDLINE. Studies were screened and mapped according to disorder, intervention modality, stage of eating disorder and study design. Included studies were restricted to controlled trials and systematic reviews published since 1980. The eating disorders evidence map included 197 trials and 22 systematic reviews. Prevention research was dominated by trials of psychoeducation (PE). Bulimia nervosa (BN) received the most attention in the treatment literature, with cognitive behavioural therapy (CBT) and antidepressants the most common interventions. For anorexia nervosa (AN), family based therapy (FBT) was the most studied. Lacking were trials exploring treatments for binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS). Relapse prevention strategies were notably absent across the eating disorders. Despite substantial literature devoted to the prevention and treatment of eating disorders in young people, the evidence base is not well established and significant gaps remain. For those identified as being at-risk, there is need for prevention research exploring strategies other than passive PE. Treatment interventions targeting BED and EDNOS are required, as are systematic reviews synthesising BN treatment trials (e.g., CBT, antidepressants). FBTs for AN require investigation against other validated psychological interventions, and the development of relapse prevention strategies is urgently required. By systematically identifying existing interventions for young people with eating disorders and exposing gaps in the current literature, the evidence map can inform researchers, funding bodies and policy makers as to the opportunities for future research.

Action seniors! - secondary falls prevention in community-dwelling senior fallers: study protocol for a randomized controlled trial.

PubMed

Liu-Ambrose, Teresa; Davis, Jennifer C; Hsu, Chun Liang; Gomez, Caitlin; Vertes, Kelly; Marra, Carlo; Brasher, Penelope M; Dao, Elizabeth; Khan, Karim M; Cook, Wendy; Donaldson, Meghan G; Rhodes, Ryan; Dian, Larry

2015-04-10

Falls are a 'geriatric giant' and are the third leading cause of chronic disability worldwide. About 30% of community-dwellers over the age of 65 experience one or more falls every year leading to significant risk for hospitalization, institutionalization, and even death. As the proportion of older adults increases, falls will place an increasing demand and cost on the health care system. Exercise can effectively and efficiently reduce falls. Specifically, the Otago Exercise Program has demonstrated benefit and cost-effectiveness for the primary prevention of falls in four randomized trials of community-dwelling seniors. Although evidence is mounting, few studies have evaluated exercise for secondary falls prevention (that is, preventing falls among those with a significant history of falls). Hence, we propose a randomized controlled trial powered for falls that will, for the first time, assess the efficacy and efficiency of the Otago Exercise Program for secondary falls prevention. A randomized controlled trial among 344 community-dwelling seniors aged 70 years and older who attend a falls prevention clinic to assess the efficacy and the cost-effectiveness of a 12-month Otago Exercise Program intervention as a secondary falls prevention strategy. Participants randomized to the control group will continue to behave as they did prior to study enrolment. The economic evaluation will examine the incremental costs and benefits generated by using the Otago Exercise Program intervention versus the control. The burden of falls is significant. The challenge is to make a difference - to discover effective, ideally cost-effective, interventions that prevent injurious falls that can be readily translated to the population. Our proposal is very practical - the exercise program requires minimal equipment, the physical therapist expertise is widely available, and seniors in Canada and elsewhere have adopted the program and complied with it. Our innovation includes applying the intervention to a targeted high-risk population, aiming to provide the best value for money. Given society's limited financial resources and the known and increasing burden of falls, there is an urgent need to test this feasible intervention which would be eminently ready for roll out. ClinicalTrials.gov Protocol Registration System: NCT01029171; registered 7 December 2009.

The Value of Pre-Screening in the Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease Trial

PubMed Central

Rios-Romenets, S.; Giraldo-Chica, M.; López, H.; Piedrahita, F.; Ramos, C.; Acosta-Baena, N.; Muñoz, C.; Ospina, P.; Tobón, C.; Cho, W.; Ward, M.; Langbaum, J.B.; Tariot, P.N.; Reiman, E.M.; Lopera, F.

2018-01-01

The Alzheimer’s Prevention Initiative (API) Autosomal Dominant Alzheimer’s Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30–60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD. PMID:29405233

Alzheimer's disease prevention: from risk factors to early intervention.

PubMed

Crous-Bou, Marta; Minguillón, Carolina; Gramunt, Nina; Molinuevo, José Luis

2017-09-12

Due to the progressive aging of the population, Alzheimer's disease (AD) is becoming a healthcare burden of epidemic proportions for which there is currently no cure. Disappointing results from clinical trials performed in mild-moderate AD dementia combined with clear epidemiological evidence on AD risk factors are contributing to the development of primary prevention initiatives. In addition, the characterization of the long asymptomatic stage of AD is allowing the development of intervention studies and secondary prevention programmes on asymptomatic at-risk individuals, before substantial irreversible neuronal dysfunction and loss have occurred, an approach that emerges as highly relevant.In this manuscript, we review current strategies for AD prevention, from primary prevention strategies based on identifying risk factors and risk reduction, to secondary prevention initiatives based on the early detection of the pathophysiological hallmarks and intervention at the preclinical stage of the disease. Firstly, we summarize the evidence on several AD risk factors, which are the rationale for the establishment of primary prevention programmes as well as revising current primary prevention strategies. Secondly, we review the development of public-private partnerships for disease prevention that aim to characterize the AD continuum as well as serving as platforms for secondary prevention trials. Finally, we summarize currently ongoing clinical trials recruiting participants with preclinical AD or a higher risk for the onset of AD-related cognitive impairment.The growing body of research on the risk factors for AD and its preclinical stage is favouring the development of AD prevention programmes that, by delaying the onset of Alzheimer's dementia for only a few years, would have a huge impact on public health.

Role of supplemental calcium in the recurrence of colorectal adenomas: a metaanalysis of randomized controlled trials.

PubMed

Shaukat, Aasma; Scouras, Nicole; Schünemann, Holger J

2005-02-01

Colorectal adenomas are neoplastic growths that are important targets for chemoprevention. Dietary calcium is thought to play an important role in chemoprevention. However, the role of calcium supplementation for preventing recurrence of adenomas is controversial. We performed a systematic review and meta-analysis to study the role of calcium supplementation in preventing recurrence of adenomas. We searched electronic bibliographic databases (Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, CINAHL, EMBASE, and MEDLINE) and contacted authors to identify potentially eligible studies. We identified three trials including 1,485 subjects with previously removed adenomas who were randomized to calcium versus placebo supplementation. The study endpoint was recurrence of adenomas at the end of 3-4 yr in 1,279 patients who completed the trials. We found that the recurrence of adenomas was significantly lower in subjects randomized to calcium supplementation (RR: 0.80, CI: 0.68, 0.93; p-value = 0.004). This systematic review and meta-analysis suggest that calcium supplementation prevents recurrent colorectal adenomas.

Strategies to retain participants in a long-term HIV prevention randomized controlled trial: Lessons from the MINTS-II study

PubMed Central

Horvath, Keith J.; Nygaard, Kate; Danilenko, Gene P.; Goknur, Sinan; Oakes, J. Michael; Rosser, B.R. Simon

2012-01-01

Achieving satisfactory retention in online HIV prevention trials typically have proved difficult, particularly over extended timeframes. The overall aim of this study was to assess factors associated with retention in the Men’s INTernet Study II (MINTS-II), a randomized controlled trial of a sexual risk reduction intervention for men who have sex with men. Participants were recruited via e-mails and banner advertisements in December, 2007 to participate in the MINTS-II Sexpulse intervention and followed over a 12-month period. Retention across the treatment and control arms was 85.2% at 12 months. Factors associated with higher retention included: randomization to the control arm, previous participation in a study by the research team, e-mail and telephone reminders to complete a survey once it was available to take, and fewer e-mail contacts between surveys. The results provide evidence that achieving satisfactory retention is possible in online HIV prevention trials, and suggest best practices for maximizing retention. PMID:21538084

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

PubMed

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Immigrant family skills-building to prevent tobacco use in Latino youth: study protocol for a community-based participatory randomized controlled trial

PubMed Central

2012-01-01

Background Despite declines over recent years, youth tobacco and other substance use rates remain high. Latino youth are at equal or increased risk for lifetime tobacco, alcohol, marijuana, and other illicit drug use compared with their white peers. Family plays an important and influential role in the lives of youth, and longitudinal research suggests that improving parenting skills may reduce youth substance use. However, few interventions are oriented towards immigrant Latino families, and none have been developed and evaluated using a community-based participatory research (CBPR) process that may increase the effectiveness and sustainability of such projects. Therefore, using CBPR principles, we developed a randomized clinical trial to assess the efficacy of a family-skills training intervention to prevent tobacco and other substance use intentions in Latino youth. Methods/Design In collaboration with seven Latino community-serving agencies, we will recruit and randomize 336 immigrant families, into intervention or delayed treatment conditions. The primary outcome is youth intention to smoke 6 months post intervention. The intervention consists of eight parent and four youth sessions targeting parenting skills and parent–youth relational factors associated with lower smoking and other substance use in youth. Discussion We present the study protocol for a family intervention using a CBPR randomized clinical trial to prevent smoking among Latino youth. The results of this trial will contribute to the limited information on effective and sustainable primary prevention programs for tobacco and other substance use directed at the growing US Latino communities. Trial registration ClinicalTrials.gov: NCT01442753 PMID:23253201

Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials

PubMed Central

Pittler, Max H; Verster, Joris C; Ernst, Edzard

2005-01-01

Objective To assess the clinical evidence on the effectiveness of any medical intervention for preventing or treating alcohol hangover. Data sources Systematic searches on Medline, Embase, Amed, Cochrane Central, the National Research Register (UK), and ClincalTrials.gov (USA); hand searches of conference proceedings and bibliographies; contact with experts and manufacturers of commercial preparations. Language of publication was not restricted. Study selection and data extraction All randomised controlled trials of any medical intervention for preventing or treating alcohol hangover were included. Trials were considered if they were placebo controlled or controlled against a comparator intervention. Titles and abstracts of identified articles were read and hard copies were obtained. The selection of studies, data extraction, and validation were done independently by two reviewers. The Jadad score was used to evaluate methodological quality. Results Fifteen potentially relevant trials were identified. Seven publications failed to meet all inclusion criteria. Eight randomised controlled trials assessing eight different interventions were reviewed. The agents tested were propranolol, tropisetron, tolfenamic acid, fructose or glucose, and the dietary supplements Borago officinalis (borage), Cynara scolymus (artichoke), Opuntia ficus-indica (prickly pear), and a yeast based preparation. All studies were double blind. Significant intergroup differences for overall symptom scores and individual symptoms were reported only for tolfenamic acid, γ linolenic acid from B officinalis, and a yeast based preparation. Conclusion No compelling evidence exists to suggest that any conventional or complementary intervention is effective for preventing or treating alcohol hangover. The most effective way to avoid the symptoms of alcohol induced hangover is to practise abstinence or moderation. PMID:16373736

Did 20 years of technological innovations in hemodialysis contribute to better patient outcomes?

PubMed

Lameire, Norbert; Van Biesen, Wim; Vanholder, Raymond

2009-12-01

During the past two decades, impressive technological innovations have been introduced in the field of hemodialysis. This review analyzes whether these have been translated into better patient survival. The potential impacts of an increase in dialysis dosage, the preference of high-flux versus low-flux membranes, the choice between convection and diffusion as dialysis strategy, the chemical composition and biologic purity of dialysate, the effect of sodium, potassium, volume profiling, and the intradialytic volume monitoring aiming at improving hemodynamic stability are explored. Studies in which the dialysis dosage was increased were not associated with increased patient survival, whereas the superiority of high-flux over low-flux membranes is not convincingly demonstrated. Although strict evidence is lacking, observational data suggest an advantage of convective over pure diffusive strategies. Longer duration of the dialysis sessions and/or higher frequency of dialysis is probably beneficial, but the results of powerful randomized, controlled trials should be awaited. Sodium profiling has more disadvantages than advantages, whereas potassium profiling mainly in arrhythmia-prone patients with ventricular hypertrophy should be considered. Intradialytic blood volume monitoring has reduced intradialytic hypotension episodes, but hard evidence for improving patient survival is lacking. Overall, the major technological advances in dialysis have not yet been translated into longer patient survival. Optimal predialysis care in preventing the cardiovascular damage that accumulates before the start of dialysis and timely creation of an arteriovenous fistula as vascular access is a more effective and more economic strategy in the long-term outcome of the dialysis patient.

Exploring Implementation and Fidelity of Evidence-Based Behavioral Interventions for HIV Prevention: Lessons Learned from the Focus on Kids Diffusion Case Study

ERIC Educational Resources Information Center

Galbraith, Jennifer S.; Stanton, Bonita; Boekeloo, Bradley; King, Winifred; Desmond, Sharon; Howard, Donna; Black, Maureen M.; Carey, James W.

2009-01-01

Evidence-based interventions (EBIs) are used in public health to prevent HIV infection among youth and other groups. EBIs include core elements, features that are thought to be responsible for the efficacy of interventions. The authors evaluate experiences of organizations that adopted an HIV-prevention EBI, Focus on Kids (FOK), and their fidelity…

Tuberculosis Control in South African Gold Mines: Mathematical Modeling of a Trial of Community-Wide Isoniazid Preventive Therapy

PubMed Central

Vynnycky, Emilia; Sumner, Tom; Fielding, Katherine L.; Lewis, James J.; Cox, Andrew P.; Hayes, Richard J.; Corbett, Elizabeth L.; Churchyard, Gavin J.; Grant, Alison D.; White, Richard G.

2015-01-01

A recent major cluster randomized trial of screening, active disease treatment, and mass isoniazid preventive therapy for 9 months during 2006–2011 among South African gold miners showed reduced individual-level tuberculosis incidence but no detectable population-level impact. We fitted a dynamic mathematical model to trial data and explored 1) factors contributing to the lack of population-level impact, 2) the best-achievable impact if all implementation characteristics were increased to the highest level achieved during the trial (“optimized intervention”), and 3) how tuberculosis might be better controlled with additional interventions (improving diagnostics, reducing treatment delay, providing isoniazid preventive therapy continuously to human immunodeficiency virus–positive people, or scaling up antiretroviral treatment coverage) individually and in combination. We found the following: 1) The model suggests that a small proportion of latent infections among human immunodeficiency virus–positive people were cured, which could have been a key factor explaining the lack of detectable population-level impact. 2) The optimized implementation increased impact by only 10%. 3) Implementing additional interventions individually and in combination led to up to 30% and 75% reductions, respectively, in tuberculosis incidence after 10 years. Tuberculosis control requires a combination prevention approach, including health systems strengthening to minimize treatment delay, improving diagnostics, increased antiretroviral treatment coverage, and effective preventive treatment regimens. PMID:25792607

The history of hormone therapy use and recent controversy related to heart disease and breast cancer arising from prevention trial outcomes.

PubMed

Alexander, Ivy M

2012-01-01

The reasons for hormone therapy use have changed dramatically over time from being very popular for the purpose of preserving youth in women to menopause-related symptom management, disease prevention, and now back to menopause-related symptom management. Over time, several important risks associated with the use of hormone therapy have become evident, causing dramatic reductions in the use of hormone therapy for periods of time following identification of these risks. Most recently, randomized controlled prevention trials that evaluated hormone therapy for the purpose of reducing or preventing coronary heart disease among women have found that hormone therapy is associated with increased rather than decreased risks for coronary heart disease. The most recent of these trials again identified increased risks for breast cancer associated with estrogen plus progestogen therapy. The evolving evidence base from these randomized controlled prevention trials is complicated and in some cases contradictory. Specifically, the data suggest that the timing of when hormone therapy is initiated once a woman is postmenopausal may influence her risk for developing heart disease and breast cancer. In this article, contradictory evidence is carefully sifted so risks and benefits can be weighed by clinicians when partnering with women to individualize decisions about using hormone therapy. © 2012 by the American College of Nurse-Midwives.

Effective prevention programs for tobacco use.

PubMed

Pentz, M A

1999-01-01

Several types of prevention programs have shown effects on delaying or reducing youth tobacco use for periods of 1-5 years or more. These are referred to as evidence-based programs. However, they are not widely used. At the same time, with few exceptions, adolescent tobacco use rates have been stable or have increased in the 1990s. The challenge for prevention is to identify critical components shared by effective prevention programs--that is, components most associated with effect, and then to evaluate factors that are most likely to promote adoption, implementation, and diffusion of effective programs across schools and communities in the United States. Effective tobacco prevention programs focus on counteracting social influences on tobacco use, include either direct training of youth in resistance and assertiveness skills or, for policy and community organization interventions, direct or indirect (through adults) training in community activism, and are mainly theory-based, with an emphasis on three levels of theory: (a) personal (attitudes, normative expectations, and beliefs); (b) social (social or group behavior); and/or (c) environmental (communications and diffusion). Program effects increase with the use of booster sessions, standardized implementor training and support, multiple program components, and multiple levels of theory. Overall, multi-component community programs that have a school program as a basis, with supportive parent, media, and community organization components, have shown the most sustained effects on tobacco use. Positive program adoption by the school or community, extent and quality of program implementation, and existence of credible networks of leaders to promote the program are critical for any effect. Research on predictors of adoption, implementation, and diffusion of evidence-based programs is scanty relative to outcome research. In addition, more research is needed on why multi-component programs appear to be most effective, whether effect is related to existing tobacco policies, whether prevention programs have differential effects on youth with different natural trajectories of tobacco use, and whether prevention programs can be used to recruit smokers into cessation programs.

Community health workers for non-communicable diseases prevention and control in developing countries: Evidence and implications

PubMed Central

Jeet, Gursimer; Thakur, J. S.; Prinja, Shankar; Singh, Meenu

2017-01-01

Background National programs for non-communicable diseases (NCD) prevention and control in different low middle income countries have a strong community component. A community health worker (CHW) delivers NCD preventive services using informational as well as behavioural approaches. Community education and interpersonal communication on lifestyle modifications is imparted with focus on primordial prevention of NCDs and screening is conducted as part of early diagnosis and management. However, the effectiveness of health promotion and screening interventions delivered through community health workers needs to be established. Objective This review synthesised evidence on effectiveness of CHW delivered NCD primary prevention interventions in low and middle-income countries (LMICs). Methods A systematic review of trials that utilised community health workers for primary prevention/ early detection strategy in the management of NCDs (Diabetes, cardiovascular diseases (CVD), cancers, stroke, Chronic Obstructive Pulmonary Diseases (COPD)) in LMICs was conducted. Digital databases like PubMed, EMBASE, OVID, Cochrane library, dissertation abstracts, clinical trials registry web sites of different LMIC were searched for such publications between years 2000 and 2015. We focussed on community based randomised controlled trial and cluster randomised trials without any publication language limitation. The primary outcome of review was percentage change in population with different behavioural risk factors. Additionally, mean overall changes in levels of several physical or biochemical parameters were studied as secondary outcomes. Subgroup analyses was performed by the age and sex of participants, and sensitivity analyses was conducted to assess the robustness of the findings. Results Sixteen trials meeting the inclusion criteria were included in the review. Duration, study populations and content of interventions varied across trials. The duration of the studies ranged from mean follow up of 4 months for some risk factors to 19 months, and primary responsibilities of health workers included health promotion, treatment adherence and follow ups. Only a single trial reported all-cause mortality. The pooled effect computed indicated an increase in tobacco cessation (RR: 2.0, 95%CI: 1.11, 3.58, moderate-quality evidence) and a decrease in systolic blood pressure ((MD: -4.80, 95% CI: -8.12, -1.49, I2 = 93%, very low-quality evidence), diastolic blood pressure ((MD: -2.88, 95% CI: -5.65, -0.10, I2 = 96%, very low-quality evidence)) and blood sugar levels (glycated haemoglobin MD: -0.83%, 95%CI: -1.25,-0.41). None of the included trials reported on adverse events. Conclusions Evidence on the implementation of primary prevention strategies using community health workers is still developing. Existing evidence suggests that, compared with standard care, using CHWs in health programmes have the potential to be effective in LMICs, particularly for tobacco cessation, blood pressure and diabetes control. PMID:28704405

Community health workers for non-communicable diseases prevention and control in developing countries: Evidence and implications.

PubMed

Jeet, Gursimer; Thakur, J S; Prinja, Shankar; Singh, Meenu

2017-01-01

National programs for non-communicable diseases (NCD) prevention and control in different low middle income countries have a strong community component. A community health worker (CHW) delivers NCD preventive services using informational as well as behavioural approaches. Community education and interpersonal communication on lifestyle modifications is imparted with focus on primordial prevention of NCDs and screening is conducted as part of early diagnosis and management. However, the effectiveness of health promotion and screening interventions delivered through community health workers needs to be established. This review synthesised evidence on effectiveness of CHW delivered NCD primary prevention interventions in low and middle-income countries (LMICs). A systematic review of trials that utilised community health workers for primary prevention/ early detection strategy in the management of NCDs (Diabetes, cardiovascular diseases (CVD), cancers, stroke, Chronic Obstructive Pulmonary Diseases (COPD)) in LMICs was conducted. Digital databases like PubMed, EMBASE, OVID, Cochrane library, dissertation abstracts, clinical trials registry web sites of different LMIC were searched for such publications between years 2000 and 2015. We focussed on community based randomised controlled trial and cluster randomised trials without any publication language limitation. The primary outcome of review was percentage change in population with different behavioural risk factors. Additionally, mean overall changes in levels of several physical or biochemical parameters were studied as secondary outcomes. Subgroup analyses was performed by the age and sex of participants, and sensitivity analyses was conducted to assess the robustness of the findings. Sixteen trials meeting the inclusion criteria were included in the review. Duration, study populations and content of interventions varied across trials. The duration of the studies ranged from mean follow up of 4 months for some risk factors to 19 months, and primary responsibilities of health workers included health promotion, treatment adherence and follow ups. Only a single trial reported all-cause mortality. The pooled effect computed indicated an increase in tobacco cessation (RR: 2.0, 95%CI: 1.11, 3.58, moderate-quality evidence) and a decrease in systolic blood pressure ((MD: -4.80, 95% CI: -8.12, -1.49, I2 = 93%, very low-quality evidence), diastolic blood pressure ((MD: -2.88, 95% CI: -5.65, -0.10, I2 = 96%, very low-quality evidence)) and blood sugar levels (glycated haemoglobin MD: -0.83%, 95%CI: -1.25,-0.41). None of the included trials reported on adverse events. Evidence on the implementation of primary prevention strategies using community health workers is still developing. Existing evidence suggests that, compared with standard care, using CHWs in health programmes have the potential to be effective in LMICs, particularly for tobacco cessation, blood pressure and diabetes control.

Have clinical studies demonstrated diabetes prevention or delay of diabetes through early treatment?

PubMed

Southwood, Robin L

2010-01-01

The incidence of type 2 diabetes continues to increase at alarming rates. Prediabetes is a state of abnormal glycemic values that are not abnormal enough to result in the diagnosis of type 2 diabetes. Significant interest in the prevention of diabetes has resulted in trials evaluating pharmacologic intervention and lifestyle intervention to prevent the development of diabetes. Controversy exists over the exact definition of diabetes prevention. Agents might possibly delay diagnosis of diabetes via pharmacologic lowering of blood glucose. Goals of diabetes prevention include decreased cardiovascular disease. Trials assessing diabetes prevention should assess 1) Impact of the study drug upon the incidence of diabetes, 2) Impact of the study drug upon diagnosis of diabetes after post-treatment washout phase, 3) Assessment of insulin sensitivity/@-cell function/insulin secretion and blood glucose, 4) Assessment of confounding factors, 5) Impact of the study drug on the occurrence of cardiovascular disease. The published studies were reviewed using these criteria. Six studies evaluating seven agents have been were reviewed. Six of the seven agents reduced diagnosis of diabetes during use, but only two demonstrated effect after washout phase. One of the two agents has been withdrawn from the market. The second agent had a short follow-up period making the results difficult to interpret. Assessment of insulin secretion at entry to trial was common, however ongoing reassessment was uncommon. All studies attempted to assess confounding factors, however stratification of drug benefit relative to amount of lifestyle modification benefit was not reported in trials. Cardiovascular benefit in the form of reduced hypertension was documented with three agents. Pharmacologic prevention of type 2 diabetes remains unproven, due in part to the difficulty distinguishing between prevention and delay. Reduction in cardiovascular benefit is unproven with most agents studied. Larger studies powered to detect cardiovascular endpoints are necessary to determine benefit of diabetes prevention.

Integrating spatial and temporal oxygen data to improve the quantification of in situ petroleum biodegradation rates.

PubMed

Davis, Gregory B; Laslett, Dean; Patterson, Bradley M; Johnston, Colin D

2013-03-15

Accurate estimation of biodegradation rates during remediation of petroleum impacted soil and groundwater is critical to avoid excessive costs and to ensure remedial effectiveness. Oxygen depth profiles or oxygen consumption over time are often used separately to estimate the magnitude and timeframe for biodegradation of petroleum hydrocarbons in soil and subsurface environments. Each method has limitations. Here we integrate spatial and temporal oxygen concentration data from a field experiment to develop better estimates and more reliably quantify biodegradation rates. During a nine-month bioremediation trial, 84 sets of respiration rate data (where aeration was halted and oxygen consumption was measured over time) were collected from in situ oxygen sensors at multiple locations and depths across a diesel non-aqueous phase liquid (NAPL) contaminated subsurface. Additionally, detailed vertical soil moisture (air-filled porosity) and NAPL content profiles were determined. The spatial and temporal oxygen concentration (respiration) data were modeled assuming one-dimensional diffusion of oxygen through the soil profile which was open to the atmosphere. Point and vertically averaged biodegradation rates were determined, and compared to modeled data from a previous field trial. Point estimates of biodegradation rates assuming no diffusion ranged up to 58 mg kg(-1) day(-1) while rates accounting for diffusion ranged up to 87 mg kg(-1) day(-1). Typically, accounting for diffusion increased point biodegradation rate estimates by 15-75% and vertically averaged rates by 60-80% depending on the averaging method adopted. Importantly, ignoring diffusion led to overestimation of biodegradation rates where the location of measurement was outside the zone of NAPL contamination. Over or underestimation of biodegradation rate estimates leads to cost implications for successful remediation of petroleum impacted sites. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Analysis of head impact exposure and brain microstructure response in a season-long application of a jugular vein compression collar: a prospective, neuroimaging investigation in American football

PubMed Central

Myer, Gregory D; Yuan, Weihong; Barber Foss, Kim D; Thomas, Staci; Smith, David; Leach, James; Kiefer, Adam W; Dicesare, Chris; Adams, Janet; Gubanich, Paul J; Kitchen, Katie; Schneider, Daniel K; Braswell, Daniel; Krueger, Darcy; Altaye, Mekibib

2016-01-01

Background Historical approaches to protect the brain from outside the skull (eg, helmets and mouthpieces) have been ineffective in reducing internal injury to the brain that arises from energy absorption during sports-related collisions. We aimed to evaluate the effects of a neck collar, which applies gentle bilateral jugular vein compression, resulting in cerebral venous engorgement to reduce head impact energy absorption during collision. Specifically, we investigated the effect of collar wearing during head impact exposure on brain microstructure integrity following a competitive high school American football season. Methods A prospective longitudinal controlled trial was employed to evaluate the effects of collar wearing (n=32) relative to controls (CTRL; n=30) during one competitive football season (age: 17.04±0.67 years). Impact exposure was collected using helmet sensors and white matter (WM) integrity was quantified based on diffusion tensor imaging (DTI) serving as the primary outcome. Results With similar overall g-forces and total head impact exposure experienced in the two study groups during the season (p>0.05), significant preseason to postseason changes in mean diffusivity, axial diffusivity and radial diffusivity in the WM integrity were noted in the CTRL group (corrected p<0.05) but not in the collar group (p>0.05). The CTRL group demonstrated significantly larger preseason to postseason DTI change in multiple WM regions compared with the collar group (corrected p<0.05). Discussion Reduced WM diffusivity alteration was noted in participants wearing a neck collar after a season of competitive football. Collar wearing may have provided a protective effect against brain microstructural changes after repetitive head impacts. Trial registration number NCT02696200. PMID:27307271

Association of Antioxidant Supplement Use and Dementia in the Prevention of Alzheimer's Disease by Vitamin E and Selenium Trial (PREADViSE).

PubMed

Kryscio, Richard J; Abner, Erin L; Caban-Holt, Allison; Lovell, Mark; Goodman, Phyllis; Darke, Amy K; Yee, Monica; Crowley, John; Schmitt, Frederick A

2017-05-01

Oxidative stress is an established dementia pathway, but it is unknown if the use of antioxidant supplements can prevent dementia. To determine if antioxidant supplements (vitamin E or selenium) used alone or in combination can prevent dementia in asymptomatic older men. The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADViSE) trial began as a double-blind randomized clinical trial in May 2002, which transformed into a cohort study from September 2009 to May 2015. The PREADViSE trial was ancillary to the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized clinical trial of the same antioxidant supplements for preventing prostate cancer, which closed in 2009 owing to findings from a futility analysis. The PREADViSE trial recruited 7540 men, of whom 3786 continued into the cohort study. Participants were at least 60 years old at study entry and were enrolled at 130 SELECT sites, and Cox proportional hazards models were used in a modified intent-to-treat analysis to compare hazard rates among the study arms. Participants were randomized to vitamin E, selenium, vitamin E and selenium, or placebo. While taking study supplements, enrolled men visited their SELECT site and were evaluated for dementia using a 2-stage screen. During the cohort study, men were contacted by telephone and assessed using an enhanced 2-stage cognitive screen. In both phases, men were encouraged to visit their physician if the screen results indicated possible cognitive impairment. Dementia case ascertainment relied on a consensus review of the cognitive screens and medical records for men with suspected dementia who visited their physician for an evaluation or by review of all available information, including a functional assessment screen. The mean (SD) baseline age of the 7540 participants was 67.5 (5.3) years, with 3936 (52.2%) reporting a college education or better, 754 (10.0%) reporting black race, and 505 (6.7%) reporting Hispanic ethnicity. Dementia incidence (325 of 7338 men [4.4%]) was not different among the 4 study arms. A Cox model, which adjusted incidence for participant demographic information and baseline self-reported comorbidities, yielded hazard ratios of 0.88 (95% CI, 0.64-1.20) for vitamin E, 0.83 (0.60-1.13) for selenium, and 1.00 (0.75-1.35) for the combination compared with placebo. Neither supplement prevented dementia. To our knowledge, this is the first study to investigate the long-term association of antioxidant supplement use and dementia incidence among asymptomatic men.

HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa.

PubMed

Hargreaves, James R; Stangl, Anne; Bond, Virginia; Hoddinott, Graeme; Krishnaratne, Shari; Mathema, Hlengani; Moyo, Maureen; Viljoen, Lario; Brady, Laura; Sievwright, Kirsty; Horn, Lyn; Sabapathy, Kalpana; Ayles, Helen; Beyers, Nulda; Bock, Peter; Fidler, Sarah; Griffith, Sam; Seeley, Janet; Hayes, Richard

2016-12-01

Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. HIV-related stigma may impede the successful implementation of HIV prevention and treatment programmes. Using a novel study-design nested within a large, community randomized trial we will evaluate the extent to which HIV-related stigma affects and is affected by the implementation of a comprehensive combination HIV prevention intervention including a universal test and treatment approach. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

An assessment of the cost-effectiveness of magnetic resonance, including diffusion-weighted imaging, in patients with transient ischaemic attack and minor stroke: a systematic review, meta-analysis and economic evaluation.

PubMed

Wardlaw, Joanna; Brazzelli, Miriam; Miranda, Hector; Chappell, Francesca; McNamee, Paul; Scotland, Graham; Quayyum, Zahid; Martin, Duncan; Shuler, Kirsten; Sandercock, Peter; Dennis, Martin

2014-04-01

Patients with transient ischaemic attack (TIA) or minor stroke need rapid treatment of risk factors to prevent recurrent stroke. ABCD2 score or magnetic resonance diffusion-weighted brain imaging (MR DWI) may help assessment and treatment. Is MR with DWI cost-effective in stroke prevention compared with computed tomography (CT) brain scanning in all patients, in specific subgroups or as 'one-stop' brain-carotid imaging? What is the current UK availability of services for stroke prevention? Published literature; stroke registries, audit and randomised clinical trials; national databases; survey of UK clinical and imaging services for stroke; expert opinion. Systematic reviews and meta-analyses of published/unpublished data. Decision-analytic model of stroke prevention including on a 20-year time horizon including nine representative imaging scenarios. The pooled recurrent stroke rate after TIA (53 studies, 30,558 patients) is 5.2% [95% confidence interval (CI) 3.9% to 5.9%] by 7 days, and 6.7% (5.2% to 8.7%) at 90 days. ABCD2 score does not identify patients with key stroke causes or identify mimics: 66% of specialist-diagnosed true TIAs and 35-41% of mimics had an ABCD2 score of ≥ 4; 20% of true TIAs with ABCD2 score of < 4 had key risk factors. MR DWI (45 studies, 9078 patients) showed an acute ischaemic lesion in 34.3% (95% CI 30.5% to 38.4%) of TIA, 69% of minor stroke patients, i.e. two-thirds of TIA patients are DWI negative. TIA mimics (16 studies, 14,542 patients) make up 40-45% of patients attending clinics. UK survey (45% response) showed most secondary prevention started prior to clinic, 85% of primary brain imaging was same-day CT; 51-54% of patients had MR, mostly additional to CT, on average 1 week later; 55% omitted blood-sensitive MR sequences. Compared with 'CT scan all patients' MR was more expensive and no more cost-effective, except for patients presenting at > 1 week after symptoms to diagnose haemorrhage; strategies that triaged patients with low ABCD2 scores for slow investigation or treated DWI-negative patients as non-TIA/minor stroke prevented fewer strokes and increased costs. 'One-stop' CT/MR angiographic-plus-brain imaging was not cost-effective. Data on sensitivity/specificity of MR in TIA/minor stroke, stroke costs, prognosis of TIA mimics and accuracy of ABCD2 score by non-specialists are sparse or absent; all analysis had substantial heterogeneity. Magnetic resonance with DWI is not cost-effective for secondary stroke prevention. MR was most helpful in patients presenting at > 1 week after symptoms if blood-sensitive sequences were used. ABCD2 score is unlikely to facilitate patient triage by non-stroke specialists. Rapid specialist assessment, CT brain scanning and identification of serious underlying stroke causes is the most cost-effective stroke prevention strategy. The National Institute for Health Research Health Technology Assessment programme.

Effect of screens in wide-angle diffusers

NASA Technical Reports Server (NTRS)

Schubauer, G B; Spangenberg, W G

1949-01-01

An experimental investigation at low airspeeds was made of the filling effect observed when a screen or similar resistance is placed across a diffuser. The filling effect is found to be real in that screens can prevent separation or restore separated flow in diffusers even of extreme divergence and to depend principally on screen location and pressure-drop coefficient of the screen. Results are given for three different diffusers of circular cross section with a variety of screen arrangements. Effects of single screens and multiple screens are shown. The mechanics of the filling effect is explained, and possible efficiencies are discussed. Results of arrangements of multiple screens in wide-angle diffusers are given to show a possible application to damping screens as used in wind tunnels to reduce turbulence. (author)

In vivo soft tissue differentiation by diffuse reflectance spectroscopy: preliminary results

NASA Astrophysics Data System (ADS)

Zam, Azhar; Stelzle, Florian; Tangermann-Gerk, Katja; Adler, Werner; Nkenke, Emeka; Neukam, Friedrich Wilhelm; Schmidt, Michael; Douplik, Alexandre

Remote laser surgery does not provide haptic feedback to operate layer by layer and preserve vulnerable anatomical structures like nerve tissue or blood vessels. The aim of this study is identification of soft tissue in vivo by diffuse reflectance spectroscopy to set the base for a feedback control system to enhance nerve preservation in oral and maxillofacial laser surgery. Various soft tissues can be identified by diffuse reflectance spectroscopy in vivo. The results may set the base for a feedback system to prevent nerve damage during oral and maxillofacial laser surgery.

Inositol for prevention of neural tube defects: a pilot randomised controlled trial - CORRIGENDUM

PubMed Central

Greene, Nicholas D. E.; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S.; Copp, Andrew J.

2016-01-01

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTDs), there is increasing evidence that many NTDs are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTDs. Inositol prevented NTDs in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-four further pregnancies were documented. Two NTDs recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised. PMID:26917444

Inositol for the prevention of neural tube defects: a pilot randomised controlled trial.

PubMed

Greene, Nicholas D E; Leung, Kit-Yi; Gay, Victoria; Burren, Katie; Mills, Kevin; Chitty, Lyn S; Copp, Andrew J

2016-03-28

Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised.

QIN DAWG Validation of Gradient Nonlinearity Bias Correction Workflow for Quantitative Diffusion-Weighted Imaging in Multicenter Trials.

PubMed

Malyarenko, Dariya I; Wilmes, Lisa J; Arlinghaus, Lori R; Jacobs, Michael A; Huang, Wei; Helmer, Karl G; Taouli, Bachir; Yankeelov, Thomas E; Newitt, David; Chenevert, Thomas L

2016-12-01

Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, -35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI.

QIN DAWG Validation of Gradient Nonlinearity Bias Correction Workflow for Quantitative Diffusion-Weighted Imaging in Multicenter Trials

PubMed Central

Malyarenko, Dariya I.; Wilmes, Lisa J.; Arlinghaus, Lori R.; Jacobs, Michael A.; Huang, Wei; Helmer, Karl G.; Taouli, Bachir; Yankeelov, Thomas E.; Newitt, David; Chenevert, Thomas L.

2017-01-01

Previous research has shown that system-dependent gradient nonlinearity (GNL) introduces a significant spatial bias (nonuniformity) in apparent diffusion coefficient (ADC) maps. Here, the feasibility of centralized retrospective system-specific correction of GNL bias for quantitative diffusion-weighted imaging (DWI) in multisite clinical trials is demonstrated across diverse scanners independent of the scanned object. Using corrector maps generated from system characterization by ice-water phantom measurement completed in the previous project phase, GNL bias correction was performed for test ADC measurements from an independent DWI phantom (room temperature agar) at two offset locations in the bore. The precomputed three-dimensional GNL correctors were retrospectively applied to test DWI scans by the central analysis site. The correction was blinded to reference DWI of the agar phantom at magnet isocenter where the GNL bias is negligible. The performance was evaluated from changes in ADC region of interest histogram statistics before and after correction with respect to the unbiased reference ADC values provided by sites. Both absolute error and nonuniformity of the ADC map induced by GNL (median, 12%; range, −35% to +10%) were substantially reduced by correction (7-fold in median and 3-fold in range). The residual ADC nonuniformity errors were attributed to measurement noise and other non-GNL sources. Correction of systematic GNL bias resulted in a 2-fold decrease in technical variability across scanners (down to site temperature range). The described validation of GNL bias correction marks progress toward implementation of this technology in multicenter trials that utilize quantitative DWI. PMID:28105469

Interventions for the prevention of nutritional rickets in term born children.

PubMed

Lerch, C; Meissner, T

2007-10-17

Nutritional rickets is a disease of growing children leading to bone deformities, bone pain, convulsions or delayed motor development. Today, high-incidence of nutritional rickets is mainly found in low-income countries. To assess the effects of various interventions on the prevention of nutritional rickets in term born children. Studies were obtained from computerised searches of The Cochrane Library, MEDLINE, EMBASE, LILACS and reference lists of relevant articles. We contacted authors of studies or reviews to obtain further studies. Studies were included if they were randomised controlled clinical trials, controlled clinical trials or prospective cohort studies comparing any intervention for the prevention of nutritional rickets in term born children with placebo or no intervention. Minimum duration of the intervention was three months for children under 12 months or six months for children over 12 months. Two authors independently extracted data and assessed study quality. Authors of studies were contacted to obtain missing information. Four studies enrolled approximately 1700 participants. Trials lasted between nine months to two years. Three studies were randomised controlled trials, two of which showed a cluster randomised design; one trial probably was a controlled trial with researcher controlled group assignment. In children up to three years of age in Turkey, Vitamin D compared to no intervention showed a relative risk of 0.04 (95% confidence interval (CI) 0 to 0.71). Despite a marked non-compliance, a Chinese trial in children up to three years of age comparing a combined intervention of supplementation of vitamin D, calcium and nutritional counseling showed a relative risk of 0.76 (95% CI 0.61 to 0.95) compared to no intervention. In two studies conducted in older children in China and in France no rickets occurred in both the intervention and control group. There a only few studies on the prevention of nutritional rickets in term born children. Until new data become available, it appears sound to offer preventive measures (vitamin D or calcium) to groups of high risk, like infants and toddlers; children living in Africa, Asia or the Middle East or migrated children from these regions into areas where rickets is not frequent. Due to a marked clinical heterogeneity and the scarcity of data, the main and adverse effects of preventive measures against nutritional rickets should be investigated in different countries, different age groups and in children of different ethnic origin.

Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting.

PubMed

Natarajan, Pradeep; Young, Robin; Stitziel, Nathan O; Padmanabhan, Sandosh; Baber, Usman; Mehran, Roxana; Sartori, Samantha; Fuster, Valentin; Reilly, Dermot F; Butterworth, Adam; Rader, Daniel J; Ford, Ian; Sattar, Naveed; Kathiresan, Sekar

2017-05-30

Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis. We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage). Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22-60; P <0.001), whereas in all others, the relative risk reduction was 24% (95% CI, 8-37; P =0.004) despite similar low-density lipoprotein cholesterol lowering. In a study-level meta-analysis across the WOSCOPS, ASCOT, and JUPITER primary prevention, relative risk reduction in those at high genetic risk was 46% versus 26% in all others ( P for heterogeneity=0.05). Across all 3 studies, the absolute risk reduction with statin therapy was 3.6% (95% CI, 2.0-5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6-1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque. Those at high genetic risk have a greater burden of subclinical atherosclerosis and derive greater relative and absolute benefit from statin therapy to prevent a first coronary heart disease event. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00738725 (BioImage) and NCT00005130 (CARDIA). WOSCOPS was carried out and completed before the requirement for clinical trial registration. © 2017 American Heart Association, Inc.

Brief psychosocial education, not core stabilization, reduced incidence of low back pain: results from the Prevention of Low Back Pain in the Military (POLM) cluster randomized trial

PubMed Central

2011-01-01

Background Effective strategies for the primary prevention of low back pain (LBP) remain elusive with few large-scale clinical trials investigating exercise and education approaches. The purpose of this trial was to determine whether core stabilization alone or in combination with psychosocial education prevented incidence of low back pain in comparison to traditional lumbar exercise. Methods The Prevention of Low Back Pain in the Military study was a cluster randomized clinical study with four intervention arms and a two-year follow-up. Participants were recruited from a military training setting from 2007 to 2008. Soldiers in 20 consecutive companies were considered for eligibility (n = 7,616). Of those, 1,741 were ineligible and 1,550 were eligible but refused participation. For the 4,325 Soldiers enrolled with no previous history of LBP average age was 22.0 years (SD = 4.2) and there were 3,082 males (71.3%). Companies were randomly assigned to receive traditional lumbar exercise, traditional lumbar exercise with psychosocial education, core stabilization exercise, or core stabilization with psychosocial education, The psychosocial education session occurred during one session and the exercise programs were done daily for 5 minutes over 12 weeks. The primary outcome for this trial was incidence of low back pain resulting in the seeking of health care. Results There were no adverse events reported. Evaluable patient analysis (4,147/4,325 provided data) indicated no differences in low back incidence resulting in the seeking of health care between those receiving the traditional exercise and core stabilization exercise programs. However, brief psychosocial education prevented low back pain episodes regardless of the assigned exercise approach, resulting in a 3.3% (95% CI: 1.1 to 5.5%) decrease over two years (numbers needed to treat (NNT) = 30.3, 95% CI = 18.2 to 90.9). Conclusions Core stabilization has been advocated as preventative, but offered no such benefit when compared to traditional lumbar exercise in this trial. Instead, a brief psychosocial education program that reduced fear and threat of low back pain decreased incidence of low back pain resulting in the seeking of health care. Since this trial was conducted in a military setting, future studies are necessary to determine if these findings can be translated into civilian populations. Trial Registration NCT00373009 at ClinicalTrials.gov - http://clinicaltrials.gov/ PMID:22126534

The Influence of Feedback on Task-Switching Performance: A Drift Diffusion Modeling Account.

PubMed

Cohen Hoffing, Russell; Karvelis, Povilas; Rupprechter, Samuel; Seriès, Peggy; Seitz, Aaron R

2018-01-01

Task-switching is an important cognitive skill that facilitates our ability to choose appropriate behavior in a varied and changing environment. Task-switching training studies have sought to improve this ability by practicing switching between multiple tasks. However, an efficacious training paradigm has been difficult to develop in part due to findings that small differences in task parameters influence switching behavior in a non-trivial manner. Here, for the first time we employ the Drift Diffusion Model (DDM) to understand the influence of feedback on task-switching and investigate how drift diffusion parameters change over the course of task switch training. We trained 316 participants on a simple task where they alternated sorting stimuli by color or by shape. Feedback differed in six different ways between subjects groups, ranging from No Feedback (NFB) to a variety of manipulations addressing trial-wise vs. Block Feedback (BFB), rewards vs. punishments, payment bonuses and different payouts depending upon the trial type (switch/non-switch). While overall performance was found to be affected by feedback, no effect of feedback was found on task-switching learning. Drift Diffusion Modeling revealed that the reductions in reaction time (RT) switch cost over the course of training were driven by a continually decreasing decision boundary. Furthermore, feedback effects on RT switch cost were also driven by differences in decision boundary, but not in drift rate. These results reveal that participants systematically modified their task-switching performance without yielding an overall gain in performance.

Ginkgo biloba for prevention of dementia: a systematic review and meta-analysis.

PubMed

Charemboon, Thammanard; Jaisin, Kankamol

2015-05-01

To determine the efficacy of Ginkgo biloba for the prevention of dementia in individuals without dementia. English databases including Medline, Embase, Cochrane Library and PsycINFO, were searched, and randomized double-blind controlled studies comparing Ginkgo biloba with placebo in prevention of dementia were considered. Two trials met inclusion criteria. Methodological quality was assessed using the Jadad criteria. Meta-analysis of the two trials involving 5,889 participants indicated no significant difference in dementia rate between Ginkgo biloba and the placebo (347/2,951 vs. 330/2,938, odds ratio = 1.05, 95% CI 0.89-1.23) and there was no considerable heterogeneity between the trials. The two studies revealed no statistically significant differences in the rate of serious adverse effect between Ginko biloba and the placebo. There is no convincing evidence from this review that demonstrated Ginkgo biloba in late-life can prevent the development of dementia. Using it for this indication is not suggested at present.

Selenium and Prostate Cancer Prevention: Insights from the Selenium and Vitamin E Cancer Prevention Trial (SELECT)

PubMed Central

Nicastro, Holly L.; Dunn, Barbara K.

2013-01-01

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was conducted to assess the efficacy of selenium and vitamin E alone, and in combination, on the incidence of prostate cancer. This randomized, double-blind, placebo-controlled, 2 × 2 factorial design clinical trial found that neither selenium nor vitamin E reduced the incidence of prostate cancer after seven years and that vitamin E was associated with a 17% increased risk of prostate cancer compared to placebo. The null result was surprising given the strong preclinical and clinical evidence suggesting chemopreventive activity of selenium. Potential explanations for the null findings include the agent formulation and dose, the characteristics of the cohort, and the study design. It is likely that only specific subpopulations may benefit from selenium supplementation; therefore, future studies should consider the baseline selenium status of the participants, age of the cohort, and genotype of specific selenoproteins, among other characteristics, in order to determine the activity of selenium in cancer prevention. PMID:23552052

The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

ERIC Educational Resources Information Center

Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

2016-01-01

Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

One-Year Efficacy Testing of Enabling Mothers to Prevent Pediatric Obesity through Web-Based Education and Reciprocal Determinism (EMPOWER) Randomized Control Trial

ERIC Educational Resources Information Center

Knowlden, Adam; Sharma, Manoj

2016-01-01

Background: The purpose of this study was to evaluate the efficacy of the Enabling Mothers to Prevent Pediatric Obesity through Web-Based Education and Reciprocal Determinism (EMPOWER) intervention at 1-year, postintervention follow-up. Method: A mixed between-within subjects design was used to evaluate the trial. Independent variables included a…

Internet-Based Personalized Feedback to Reduce 21st-Birthday Drinking: A Randomized Controlled Trial of an Event-Specific Prevention Intervention

ERIC Educational Resources Information Center

Neighbors, Clayton; Lee, Christine M.; Lewis, Melissa A.; Fossos, Nicole; Walter, Theresa

2009-01-01

This article presents an initial randomized controlled trial of an event-specific prevention intervention. Participants included 295 college students (41.69% male, 58.31% female) who intended to consume 2 or more drinks on their 21st birthday. Participants completed a screening/baseline assessment approximately 1 week before they turned 21 and…

Indicated Prevention and Early Intervention for Childhood Anxiety: A Randomized Trial with Caucasian and Hispanic/Latino Youth

ERIC Educational Resources Information Center

Pina, Armando A.; Zerr, Argero A.; Villalta, Ian K.; Gonzales, Nancy A.

2012-01-01

Objective: This trial of a randomized indicated anxiety prevention and early intervention explored initial program effects as well as the role of ethnicity and language on measured outcomes. Method: A total of 88 youth (M = 10.36 years; 45 girls, 52 Latino) received 1 of 2 protocols with varying degrees of parent involvement, and response was…

Process evaluation of a cluster-randomised trial testing a pressure ulcer prevention care bundle: a mixed-methods study.

PubMed

Roberts, Shelley; McInnes, Elizabeth; Bucknall, Tracey; Wallis, Marianne; Banks, Merrilyn; Chaboyer, Wendy

2017-02-13

As pressure ulcers contribute to significant patient burden and increased health care costs, their prevention is a clinical priority. Our team developed and tested a complex intervention, a pressure ulcer prevention care bundle promoting patient participation in care, in a cluster-randomised trial. The UK Medical Research Council recommends process evaluation of complex interventions to provide insight into why they work or fail and how they might be improved. This study aimed to evaluate processes underpinning implementation of the intervention and explore end-users' perceptions of it, in order to give a deeper understanding of its effects. A pre-specified, mixed-methods process evaluation was conducted as an adjunct to the main trial, guided by a framework for process evaluation of cluster-randomised trials. Data was collected across eight Australian hospitals but mainly focused on the four intervention hospitals. Quantitative and qualitative data were collected across the evaluation domains: recruitment, reach, intervention delivery and response to intervention, at both cluster and individual patient level. Quantitative data were analysed using descriptive and inferential statistics. Qualitative data were analysed using thematic analysis. In the context of the main trial, which found a 42% reduction in risk of pressure ulcer with the intervention that was not significant after adjusting for clustering and covariates, this process evaluation provides important insights. Recruitment and reach among clusters and individuals was high, indicating that patients, nurses and hospitals are willing to engage with a pressure ulcer prevention care bundle. Of 799 intervention patients in the trial, 96.7% received the intervention, which took under 10 min to deliver. Patients and nurses accepted the care bundle, recognising benefits to it and describing how it enabled participation in pressure ulcer prevention (PUP) care. This process evaluation found no major failures relating to implementation of the intervention. The care bundle was found to be easy to understand and deliver, and it reached a large proportion of the target population and was found to be acceptable to patients and nurses; therefore, it may be an effective way of engaging patients in their pressure ulcer prevention care and promoting evidence-based practise.

Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men.

PubMed

Avenell, Alison; Mak, Jenson C S; O'Connell, Dianne

2014-04-14

Vitamin D and related compounds have been used to prevent osteoporotic fractures in older people. This is the third update of a Cochrane review first published in 1996. To determine the effects of vitamin D or related compounds, with or without calcium, for preventing fractures in post-menopausal women and older men. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (to December 2012), the Cochrane Central Register of Controlled Trials (2012, Issue 12), MEDLINE (1966 to November Week 3 2012), EMBASE (1980 to 2012 Week 50), CINAHL (1982 to December 2012), BIOSIS (1985 to 3 January 2013), Current Controlled Trials (December 2012) and reference lists of articles. Randomised or quasi-randomised trials that compared vitamin D or related compounds, alone or with calcium, against placebo, no intervention or calcium alone, and that reported fracture outcomes in older people. The primary outcome was hip fracture. Two authors independently assessed trial risk of selection bias and aspects of methodological quality, and extracted data. Data were pooled, where possible, using the fixed-effect model, or the random-effects model when heterogeneity between studies appeared substantial. We included 53 trials with a total of 91,791 participants. Thirty-one trials, with sample sizes ranging from 70 to 36,282 participants, examined vitamin D (including 25-hydroxy vitamin D) with or without calcium in the prevention of fractures in community, nursing home or hospital inpatient populations. Twelve of these 31 trials had participants with a mean or median age of 80 years or over.Another group of 22 smaller trials examined calcitriol or alfacalcidol (1-alphahydroxyvitamin D3), mostly with participants who had established osteoporosis. These trials were carried out in the setting of institutional referral clinics or hospitals.In the assessment of risk of bias for random sequence generation, 21 trials (40%) were deemed to be at low risk, 28 trials (53%) at unclear risk and four trials at high risk (8%). For allocation concealment, 22 trials were at low risk (42%), 29 trials were at unclear risk (55%) and two trials were at high risk (4%).There is high quality evidence that vitamin D alone, in the formats and doses tested, is unlikely to be effective in preventing hip fracture (11 trials, 27,693 participants; risk ratio (RR) 1.12, 95% confidence intervals (CI) 0.98 to 1.29) or any new fracture (15 trials, 28,271 participants; RR 1.03, 95% CI 0.96 to 1.11).There is high quality evidence that vitamin D plus calcium results in a small reduction in hip fracture risk (nine trials, 49,853 participants; RR 0.84, 95% confidence interval (CI) 0.74 to 0.96; P value 0.01). In low-risk populations (residents in the community: with an estimated eight hip fractures per 1000 per year), this equates to one fewer hip fracture per 1000 older adults per year (95% CI 0 to 2). In high risk populations (residents in institutions: with an estimated 54 hip fractures per 1000 per year), this equates to nine fewer hip fractures per 1000 older adults per year (95% CI 2 to 14). There is high quality evidence that vitamin D plus calcium is associated with a statistically significant reduction in incidence of new non-vertebral fractures. However, there is only moderate quality evidence of an absence of a statistically significant preventive effect on clinical vertebral fractures. There is high quality evidence that vitamin D plus calcium reduces the risk of any type of fracture (10 trials, 49,976 participants; RR 0.95, 95% CI 0.90 to 0.99).In terms of the results for adverse effects: mortality was not adversely affected by either vitamin D or vitamin D plus calcium supplementation (29 trials, 71,032 participants, RR 0.97, 95% CI 0.93 to 1.01). Hypercalcaemia, which was usually mild (2.6 to 2.8 mmol/L), was more common in people receiving vitamin D or an analogue, with or without calcium (21 trials, 17,124 participants, RR 2.28, 95% CI 1.57 to 3.31), especially for calcitriol (four trials, 988 participants, RR 4.41, 95% CI 2.14 to 9.09), than in people receiving placebo or control. There was also a small increased risk of gastrointestinal symptoms (15 trials, 47,761 participants, RR 1.04, 95% CI 1.00 to 1.08), especially for calcium plus vitamin D (four trials, 40,524 participants, RR 1.05, 95% CI 1.01 to 1.09), and a significant increase in renal disease (11 trials, 46,548 participants, RR 1.16, 95% CI 1.02 to 1.33). Other systematic reviews have found an increased association of myocardial infarction with supplemental calcium; and evidence of increased myocardial infarction and stroke, but decreased cancer, with supplemental calcium plus vitamin D, without an overall effect on mortality. Vitamin D alone is unlikely to prevent fractures in the doses and formulations tested so far in older people. Supplements of vitamin D and calcium may prevent hip or any type of fracture. There was a small but significant increase in gastrointestinal symptoms and renal disease associated with vitamin D and calcium. This review found that there was no increased risk of death from taking calcium and vitamin D.

Lenalidomide and Radiation for Children with Brain Cancers

Cancer.gov

n this trial, patients up to age 18 who are newly diagnosed with diffuse intrinsic pontine gliomas (DIPG) or who have other incompletely resected high-grade gliomas will undergo radiation therapy and receive oral lenalidomide, followed by lenalidomide.

Intensive glycemic control and cardiovascular disease: an update.

PubMed

Brown, Aparna; Reynolds, L Raymond; Bruemmer, Dennis

2010-07-01

Cardiovascular complications constitute the major cause of morbidity and mortality in patients with diabetes. The Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) provided consistent evidence that intensive glycemic control prevents the development and progression of microvascular complications in patients with type 1 or type 2 diabetes. However, whether intensive glucose lowering also prevents macrovascular disease and major cardiovascular events remains unclear. Extended follow-up of participants in these studies demonstrated that intensive glycemic control reduced the long-term incidence of myocardial infarction and death from cardiovascular disease. By contrast, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, and Veterans Affairs Diabetes Trial (VADT) results suggested that intensive glycemic control to near normoglycemia had either no, or potentially even a detrimental, effect on cardiovascular outcomes. This article discusses the effects of intensive glycemic control on cardiovascular disease, and examines key differences in the design of these trials that might have contributed to their disparate findings. Recommendations from the current joint ADA, AHA, and ACCF position statement on intensive glycemic control and prevention of cardiovascular disease are highlighted.

The implementation effectiveness of the ‘Strengthen your ankle’ smartphone application for the prevention of ankle sprains: design of a randomized controlled trial

PubMed Central

2014-01-01

Background Ankle sprains continue to pose a significant burden to the individual athlete, as well as to society as a whole. However, despite ankle sprains being the single most common sports injury and despite an active approach by various Dutch organisations in implementing preventive measures, large-scale community uptake of these preventive measures, and thus actual prevention of ankle sprains, is lagging well behind. In an attempt to bridge this implementation gap, the Dutch Consumer Safety Institute VeiligheidNL developed a freely available interactive App (‘Strenghten your ankle’ translated in Dutch as: ‘Versterk je enkel; available for iOS and Android) that contains - next to general advice on bracing and taping - a proven cost-effective neuromuscular program. The ‘Strengthen your ankle’ App has not been evaluated against the ‘regular’ prevention approach in which the neuromuscular program is advocated through written material. The aim of the current project is to evaluate the implementation value of the ‘Strengthen your ankle’ App as compared to the usual practice of providing injured athletes with written materials. In addition, as a secondary outcome measure, the cost-effectiveness will be assessed against usual practice. Methods/Design The proposed study will be a randomised controlled trial. After stratification for medical caregiver, athletes will be randomised to two study groups. One group will receive a standardized eight-week proprioceptive training program that has proven to be cost-effective to prevent recurrent ankle injuries, consisting of a balance board (machU/ MSG Europe BVBA), and a traditional instructional booklet. The other group will receive the same exercise program and balance board. However, for this group the instructional booklet is exchanged by the interactive ‘Strengthen your ankle’ App. Discussion This trial is the first randomized controlled trial to study the implementation effectiveness of an App for proprioceptive balance board training program in comparison to a traditional printed instruction booklet, with the recurrence of ankle sprains among athletes as study outcome. Results of this study could possibly lead to changes in practical guidelines on the treatment of ankle sprains and in the use of mobile applications for injury prevention. Results will become available in 2014. Trial registration The Netherlands National Trial Register NTR4027. The NTR is part of the WHO Primary Registries. PMID:24393146

Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses.

PubMed

Hernán, Miguel A; Sauer, Brian C; Hernández-Díaz, Sonia; Platt, Robert; Shrier, Ian

2016-11-01

Many analyses of observational data are attempts to emulate a target trial. The emulation of the target trial may fail when researchers deviate from simple principles that guide the design and analysis of randomized experiments. We review a framework to describe and prevent biases, including immortal time bias, that result from a failure to align start of follow-up, specification of eligibility, and treatment assignment. We review some analytic approaches to avoid these problems in comparative effectiveness or safety research. Copyright © 2016 Elsevier Inc. All rights reserved.

Microbicides and their potential as a catalyst for multipurpose sexual and reproductive health technologies.

PubMed

Karim, Q Abdool; Baxter, C; Karim, S Abdool

2014-10-01

There is an urgent need for technologies to prevent sexual acquisition of HIV infection in young women in sub-Saharan Africa. After two decades of 11 pivotal trials of seven products, anti-retroviral-based topical microbicides are showing promise. Building on the CAPRISA 004 trial findings, several trials of new anti-viral agents, novel delivery mechanisms and combination/multipurpose products that address challenges of adherence and meet the sexual and reproductive health needs of men and women, including preventing HIV infection, are underway. © 2014 Royal College of Obstetricians and Gynaecologists.

Multicentre cluster randomised controlled trial evaluating implementation of a fire prevention Injury Prevention Briefing in children’s centres: study protocol

PubMed Central

2014-01-01

Background The UK has one of the highest fatality rates for deaths from fire-related injuries in children aged 0–14 years; these injuries have the steepest social gradient of all injuries in the UK. Children’s centres provide children under five years old and their families with a range of services and information, including home safety, but their effectiveness in promoting injury prevention has yet to be evaluated. We developed a fire prevention intervention for use in children’s centres comprising an Injury Prevention Briefing (IPB) which provides evidence on what works and best practice from those running injury prevention programmes, and a facilitation package to support implementation of the IPB. This protocol describes the design and methods of a trial evaluating the effectiveness and cost-effectiveness of the IPB and facilitation package in promoting fire prevention. Methods/Design Pragmatic, multicentre cluster randomised controlled trial, with a nested qualitative study, in four study centres in England. Children’s centres in the most disadvantaged areas will be eligible to participate and will be randomised to one of three treatment arms comprising: IPB with facilitation package; IPB with no facilitation package; usual care (control). The primary outcome measure will be the proportion of families who have a fire escape plan at follow-up. Eleven children’s centres per arm are required to detect an absolute difference in the percentage of families with a fire escape plan of 20% in either of the two intervention arms compared with the control arm, with 80% power and a 5% significance level (2-sided), an intraclass correlation coefficient of 0.05 and assuming outcomes are assessed on 20 families per children’s centre. Secondary outcomes include the assessment of the cost-effectiveness of the intervention, other fire safety behaviours and factors associated with degree of implementation of the IPB. Discussion This will be the first trial to develop and evaluate a fire prevention intervention for use in children’s centres in the UK. Its findings will be generalisable to children’s centres in the most disadvantaged areas of the UK and may also be generalisable to similar interventions to prevent other types of injury. Trial registration http://NCT01452191 (date of registration: 13/10/2011). PMID:24450931

Low-molecular-weight heparin for prevention of placenta-mediated pregnancy complications: protocol for a systematic review and individual patient data meta-analysis (AFFIRM)

PubMed Central

2014-01-01

Background Placenta-mediated pregnancy complications include pre-eclampsia, late pregnancy loss, placental abruption, and the small-for-gestational age newborn. They are leading causes of maternal, fetal, and neonatal morbidity and mortality in developed nations. Women who have experienced these complications are at an elevated risk of recurrence in subsequent pregnancies. However, despite decades of research no effective strategies to prevent recurrence have been identified, until recently. We completed a pooled summary-based meta-analysis that strongly suggests that low-molecular-weight heparin reduces the risk of recurrent placenta-mediated complications. The proposed individual patient data meta-analysis builds on this successful collaboration. The project is called AFFIRM, An individual patient data meta-analysis oF low-molecular-weight heparin For prevention of placenta-medIated pRegnancy coMplications. Methods/Design We conducted a systematic review to identify randomized controlled trials with a low-molecular-weight heparin intervention for the prevention of recurrent placenta-mediated pregnancy complications. Investigators and statisticians representing eight trials met to discuss the outcomes and analysis plan for an individual patient data meta-analysis. An additional trial has since been added for a total of nine eligible trials. The primary analyses from the original trials will be replicated for quality assurance prior to recoding the data from each trial and combining it into a common dataset for analysis. Using the anonymized combined data we will conduct logistic regression and subgroup analyses aimed at identifying which women with previous pregnancy complications benefit most from treatment with low-molecular-weight heparin during pregnancy. Discussion The goal of the proposed individual patient data meta-analysis is a thorough estimation of treatment effects in patients with prior individual placenta-mediated pregnancy complications and exploration of which complications are specifically prevented by low-molecular-weight heparin. Systematic review registration PROSPERO (International Prospective Registry of Systematic Reviews) 23 December 2013, CRD42013006249 PMID:24969227

Undisclosed antiretroviral drug use in a multinational clinical trial (HIV Prevention Trials Network 052).

PubMed

Fogel, Jessica M; Wang, Lei; Parsons, Teresa L; Ou, San-San; Piwowar-Manning, Estelle; Chen, Ying; Mudhune, Victor O; Hosseinipour, Mina C; Kumwenda, Johnstone; Hakim, James G; Chariyalertsak, Suwat; Panchia, Ravindre; Sanne, Ian; Kumarasamy, Nagalingeswaran; Grinsztejn, Beatriz; Makhema, Joseph; Pilotto, Jose; Santos, Breno R; Mayer, Kenneth H; McCauley, Marybeth; Gamble, Theresa; Bumpus, Namandjé N; Hendrix, Craig W; Cohen, Myron S; Eshleman, Susan H

2013-11-15

The HIV Prevention Trials Network 052 study enrolled serodiscordant couples. Index participants infected with human immunodeficiency virus reported no prior antiretroviral (ARV) treatment at enrollment. ARV drug testing was performed retrospectively using enrollment samples from a subset of index participants. ARV drugs were detected in 45 of 96 participants (46.9%) with an undetectable viral load, 2 of 48 (4.2%) with a low viral load, and 1 of 65 (1.5%) with a high viral load (P < .0001); they were also detected in follow-up samples from participants who were not receiving study-administered treatment. ARV drug testing may be useful in addition to self-report of ARV drug use in some clinical trial settings.

Optimizing adherence in HIV prevention product trials: Development and psychometric evaluation of simple tools for screening and adherence counseling.

PubMed

Tolley, Elizabeth E; Guthrie, Kate Morrow; Zissette, Seth; Fava, Joseph L; Gill, Katherine; Louw, Cheryl E; Kotze, Philip; Reddy, Krishnaveni; MacQueen, Kathleen

2018-01-01

Low adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants' adherence to HIV prevention products within the context of clinical trial research. Based on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4 Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring Benefits, Ring Removal, and Side Effects with good to very good internal reliability (α = .71-.82). Evidence of content and construct validity was found; relationship to social desirability bias was examined. These scales are easy and inexpensive to administer, available in several languages, and are applicable regardless of randomization. Once validated prospectively, they could (1) screen for propensity to adhere, (2) target adherence support/counselling, and (3) complement biomarker measures in determining true efficacy of the experimental product.

Strategies for Effective Eating Development-SEEDS: Design of an Obesity Prevention Program to Promote Healthy Food Preferences and Eating Self-Regulation in Children From Low-Income Families.

PubMed

Hughes, Sheryl O; Power, Thomas G; Beck, Ashley; Betz, Drew; Calodich, Shirley; Goodell, L Suzanne; Hill, Laura G; Hill, Rachael; Jaramillo, J Andrea; Johnson, Susan L; Lanigan, Jane; Lawrence, Adair; Martinez, AnaMaria Diaz; Nesbitt, Merrianneeta; Overath, Irene; Parker, Louise; Ullrich-French, Sarah

2016-06-01

To develop a scientifically based childhood obesity prevention program supporting child eating self-regulation and taste preferences. This article describes the research methods for the Strategies for Effective Eating Development program. A logic model is provided that depicts a visual presentation of the activities that will be used to guide the development of the prevention program. Randomized, controlled prevention program, pretest, posttest, 6 months, and 12 months. Two sites: Houston, TX and Pasco, WA. Each trial will last 7 weeks with 8-10 mother-child dyads in each arm (prevention and control). Recruitment at Head Start districts (Texas; n = 160) and Inspire Child Development Center including Early Childhood Education and Head Start (Washington; n = 160). Sixteen trials with 16-20 parent-child dyads per trial will provide adequate power to detect moderate effects. Multicomponent family-based prevention program incorporating a dialogue approach to adult learning and self-determination theory. Child assessments will include observed taste preferences, caloric compensation, and eating in the absence of hunger. Parent assessments will include parent-reported feeding, feeding emotions, acculturation, child eating behaviors, child food preferences, and child dietary intake. Heights and weights will be measured for parent and child. A multilevel growth modeling analysis will be employed to consider the nested nature of the data: time points (level 1) within families (level 2) within trials (level 3). Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Modeling of tritium transport in a fusion reactor pin-type solid breeder blanket using the diffuse code

NASA Astrophysics Data System (ADS)

Martin, Rodger; Ghoniem, Nasr M.

1986-11-01

A pin-type fusion reactor blanket is designed using γ-LiAlO 2 solid tritium breeder. Tritium transport and diffusive inventory are modeled using the DIFFUSE code. Two approaches are used to obtain characteristic LiAlO 2 grain temperatures. DIFFUSE provides intragranular diffusive inventories which scale up to blanket size. These results compare well with a numerical analysis, giving a steady-state blanket tritium inventory of 13 g. Start-up transient inventories are modeled using DIFFUSE for both full and restricted coolant flow. Full flow gives rapid inventory buildup while restricted flow prevents this buildup. Inventories after shutdown are modeled: reduced cooling is found to have little effect on removing tritium, but preheating rapidly purges inventory. DIFFUSE provides parametric modeling of solid breeder density, radiation, and surface effects. 100% dense pins are found to give massive inventory and marginal tritium release. Only large trapping energies and concentrations significantly increase inventory. Diatomic surface recombination is only significant at high temperatures.

A Model Designed to Enhance Informed Consent: Experiences From the HIV Prevention Trials Network

PubMed Central

Woodsong, Cynthia; Karim, Quarraisha Abdool

2005-01-01

HIV prevention research in developing countries has resulted in increased attention to and discussion of ethical issues, particularly the issue of the quality of informed consent. We present a conceptual framework for an enhanced informed consent process, drawing on experiences garnered from domestic and international studies conducted by the HIV Prevention Trials Network, funded by the National Institutes of Health. This framework guides the development of an informed consent process designed to help ensure initial and continued comprehension of research participation, with an emphasis on HIV prevention research. Attention is focused at the individual and community levels and on 3 study phases: preenrollment, enrollment, and postenrollment. PMID:15727968

Statistical Considerations of Food Allergy Prevention Studies.

PubMed

Bahnson, Henry T; du Toit, George; Lack, Gideon

Clinical studies to prevent the development of food allergy have recently helped reshape public policy recommendations on the early introduction of allergenic foods. These trials are also prompting new research, and it is therefore important to address the unique design and analysis challenges of prevention trials. We highlight statistical concepts and give recommendations that clinical researchers may wish to adopt when designing future study protocols and analysis plans for prevention studies. Topics include selecting a study sample, addressing internal and external validity, improving statistical power, choosing alpha and beta, analysis innovations to address dilution effects, and analysis methods to deal with poor compliance, dropout, and missing data. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions

PubMed Central

Cheong, Chang Heon; Lee, Seonhye

2018-01-01

The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system’s inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens. PMID:29534043

Case Study of Airborne Pathogen Dispersion Patterns in Emergency Departments with Different Ventilation and Partition Conditions.

PubMed

Cheong, Chang Heon; Lee, Seonhye

2018-03-13

The prevention of airborne infections in emergency departments is a very important issue. This study investigated the effects of architectural features on airborne pathogen dispersion in emergency departments by using a CFD (computational fluid dynamics) simulation tool. The study included three architectural features as the major variables: increased ventilation rate, inlet and outlet diffuser positions, and partitions between beds. The most effective method for preventing pathogen dispersion and reducing the pathogen concentration was found to be increasing the ventilation rate. Installing partitions between the beds and changing the ventilation system's inlet and outlet diffuser positions contributed only minimally to reducing the concentration of airborne pathogens.

Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101--Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI.

PubMed

Pituskin, Edith; Haykowsky, Mark; Mackey, John R; Thompson, Richard B; Ezekowitz, Justin; Koshman, Sheri; Oudit, Gavin; Chow, Kelvin; Pagano, Joseph J; Paterson, Ian

2011-07-27

MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in the prevention of trastuzumab-mediated cardiotoxicity. We expect the findings of this trial to provide important evidence in the development of guidelines for preventive therapy. ClinicalTrials.gov: NCT01016886.

PCSK9 inhibitors may improve cardiovascular outcomes-Can we afford them?

PubMed

Arbel, Ronen; Hammerman, Ariel; Triki, Noa; Greenberg, Dan

2016-10-01

Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) can significantly lower low-density lipoprotein (LDL) cholesterol levels. Early evidence suggests that use of PCSK9i also reduces the incidence of major adverse cardiovascular events (MACE). Our objective was to determine preliminary economic implications of PCSK9i use to avoid MACE, based on the current data from major phase III clinical trials. Outcome data of the 4529 patients treated with PCSK9i in the OSLER and ODYSSEY LONG TERM trials were collected from the published reports. Cost of preventing MACE was evaluated based on the existing outcome data and current US prices of PCSK9i. The pooled results were compared to the cost of curing Hepatitis C Virus (HCV) patients with novel HCV drugs. PCSK9i treatment in the OSLER and ODYSSEY LONG TERM trials resulted in prevention of 35 MACE in a total of 4903 patient-years: 8 cardiovascular deaths, 22 myocardial infarctions, 0 strokes and 5 unstable anginas. The cost of PCSK9i drugs consumed during the trial's current follow-up period, could have reached $70,172,141. Therefore, the cost of preventing any MACE would be $2,004,918 and the cost of preventing one death would be $8,777,518. These figures are one hundred fold higher than the cost of curing one HCV patient (~$84,000). According to the current published data, using PCSK9i to prevent MACE seems to be a very expensive strategy. If upcoming outcome trials will demonstrate similar results, it seems that at current prices, using these drugs would not be affordable for most healthcare systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Beyond Stroke Prevention in Atrial Fibrillation: Exploring Further Unmet Needs with Rivaroxaban.

PubMed

Gibson, C M; Hankey, G J; Nafee, T; Welsh, R C

2018-03-22

With improved life expectancy and the aging population, the global burden of atrial fibrillation (AF) continues to increase, and with AF comes an estimated fivefold increased risk of ischaemic stroke. Prophylactic anticoagulant therapy is more effective in reducing the risk of ischaemic stroke in AF patients than acetylsalicylic acid or dual-antiplatelet therapy combining ASA with clopidogrel. Non-vitamin K antagonist oral anticoagulants are the standard of care for stroke prevention in patients with non-valvular AF. The optimal anticoagulant strategy to prevent thromboembolism in AF patients who are undergoing percutaneous coronary intervention and stenting, those who have undergone successful transcatheter aortic valve replacement and those with embolic stroke of undetermined source are areas of ongoing research. This article provides an update on three randomized controlled trials of rivaroxaban, a direct, oral factor Xa inhibitor, that are complete or are ongoing, in these unmet areas of stroke prevention: oPen-label, randomized, controlled, multicentre study explorIng twO treatmeNt stratEgiEs of Rivaroxaban and a dose-adjusted oral vitamin K antagonist treatment strategy in patients with Atrial Fibrillation who undergo Percutaneous Coronary Intervention (PIONEER AF-PCI) trial; the New Approach riVaroxaban Inhibition of factor Xa in a Global trial vs Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial and the Global study comparing a rivAroxaban-based antithrombotic strategy to an antipLatelet-based strategy after transcatheter aortIc vaLve rEplacement to Optimize clinical outcomes (GALILEO) trial. The data from these studies are anticipated to help address continuing challenges for a range of patients at risk of stroke. Schattauer.

Disk diffusion quality control guidelines for NVP-PDF 713: a novel peptide deformylase inhibitor.

PubMed

Anderegg, Tamara R; Jones, Ronald N

2004-01-01

NVP-PDF713 is a peptide deformylase inhibitor that has emerged as a candidate for treating Gram-positive infections and selected Gram-negative species that commonly cause community-acquired respiratory tract infections. This report summarizes the results of a multi-center (seven participants) disk diffusion quality control (QC) investigation for NVP PDF-713 using guidelines of the National Committee for Clinical Laboratory Standards and the standardized disk diffusion method. A total of 420 NVP-PDF 713 zone diameter values were generated for each QC organism. The proposed zone diameter ranges contained 97.6-99.8% of the reported participant results and were: Staphylococcus aureus ATCC 25923 (25-35 mm), Streptococcus pneumoniae ATCC 49619 (30-37 mm), and Haemophilus influenzae ATCC 49247 (24-32 mm). These QC criteria for the disk diffusion method should be applied during the NVP-PDF 713 clinical trials to maximize test accuracy.

Molecular modeling of polymers 16. Gaseous diffusion in polymers: a quantitative structure-property relationship (QSPR) analysis.

PubMed

Patel, H C; Tokarski, J S; Hopfinger, A J

1997-10-01

The purpose of this study was to identify the key physicochemical molecular properties of polymeric materials responsible for gaseous diffusion in the polymers. Quantitative structure-property relationships, QSPRs were constructed using a genetic algorithm on a training set of 16 polymers for which CO2, N2, O2 diffusion constants were measured. Nine physicochemical properties of each of the polymers were used in the trial basis set for QSPR model construction. The linear cross-correlation matrices were constructed and investigated for colinearity among the members of the training sets. Common water diffusion measures for a limited training set of six polymers was used to construct a "semi-QSPR" model. The bulk modulus of the polymer was overwhelmingly found to be the dominant physicochemical polymer property that governs CO2, N2 and O2 diffusion. Some secondary physicochemical properties controlling diffusion, including conformational entropy, were also identified as correlation descriptors. Very significant QSPR diffusion models were constructed for all three gases. Cohesive energy was identified as the main correlation physicochemical property with aqueous diffusion measures. The dominant role of polymer bulk modulus on gaseous diffusion makes it difficult to develop criteria for selective transport of gases through polymers. Moreover, high bulk moduli are predicted to be necessary for effective gas barrier materials. This property requirement may limit the processing and packaging features of the material. Aqueous diffusion in polymers may occur by a different mechanism than gaseous diffusion since bulk modulus does not correlate with aqueous diffusion, but rather cohesive energy of the polymer.

Evidence for sample selection effect and Hawthorne effect in behavioural HIV prevention trial among young women in a rural South African community

PubMed Central

Pettifor, Audrey; Twine, Rhian; Hughes, James P; Gomez-Olive, F Xavier; Wagner, Ryan G; Sulaimon, Afolabi; Tollman, Stephen; Selin, Amanda; MacPhail, Catherine; Kahn, Kathleen

2018-01-01

Objectives We examined the potential influence of both sample selection effects and Hawthorne effects in the behavioural HIV Prevention Trial Network 068 study, designed to examine whether cash transfers conditional on school attendance reduce HIV acquisition in young South African women. We explored whether school enrolment among study participants differed from the underlying population, and whether differences existed at baseline (sample selection effect) or arose during study participation (Hawthorne effect). Methods We constructed a cohort of 3889 young women aged 11–20 years using data from the Agincourt Health and socio-Demographic Surveillance System. We compared school enrolment in 2011 (trial start) and 2015 (trial end) between those who did (n=1720) and did not (n=2169) enrol in the trial. To isolate the Hawthorne effect, we restricted the cohort to those enrolled in school in 2011. Results In 2011, trial participants were already more likely to be enrolled in school (99%) compared with non-participants (93%). However, this association was attenuated with covariate adjustment (adjusted risk difference (aRD) (95% CI): 2.9 (− 0.7 to 6.5)). Restricting to those enrolled in school in 2011, trial participants were also more likely to be enrolled in school in 2015 (aRD (95% CI): 4.9 (1.5 to 8.3)). The strength of associations increased with age. Conclusions Trial participants across both study arms were more likely to be enrolled in school than non-participants. Our findings suggest that both sample selection and Hawthorne effects may have diminished the differences in school enrolment between study arms, a plausible explanation for the null trial findings. The Hawthorne-specific findings generate hypotheses for how to structure school retention interventions to prevent HIV. PMID:29326192

The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial.

PubMed

Ford, Andrew H; Flicker, Leon; Passage, Jurgen; Wibrow, Bradley; Anstey, Matthew; Edwards, Mark; Almeida, Osvaldo P

2016-01-28

Delirium is a common occurrence in patients undergoing major cardiac surgery and is associated with a number of adverse consequences for the individual, their family and the health system. Current approaches to the prevention of delirium include identifying those at risk together with various non-pharmacological and pharmacological strategies, although the efficacy of these is often modest. Emerging evidence suggests that melatonin may be biologically implicated in the development of delirium and that melatonin supplementation may be beneficial in reducing the incidence of delirium in medical and surgical patients. We designed this trial to determine whether melatonin reduces the incidence of delirium following cardiac surgery compared with placebo. The Healthy Heart-Mind trial is a randomized, double-blind, placebo-controlled clinical trial of 3 mg melatonin or matching placebo administered on seven consecutive days for the prevention of delirium following cardiac surgery. We will recruit 210 adult participants, aged 50 and older, undergoing elective or semi-elective cardiac surgery with the primary outcome of interest for this study being the difference in the incidence of delirium between the groups within 7 days of surgery. Secondary outcomes of interest include the difference between groups in the severity and duration of delirious episodes, hospital length of stay and referrals to mental health services during admission. In addition, we will assess differences in depressive and anxiety symptoms, as well as cognitive performance, at discharge and 3 months after surgery. The results of this trial will clarify whether melatonin reduces the incidence of delirium following cardiac surgery. The trial is registered with the Australian Clinical Trials Registry, trial number ACTRN12615000819527 (10 August 2015).

Open-tube diffusion techniques for InP/LnGaAs heterojunctior bipolar transistors

NASA Astrophysics Data System (ADS)

Schuitemaker, P.; Houston, P. A.

1986-11-01

Open-tube diffusion techniques used between 450 and 600° C are described which involve the supply of diffusant from a vapour source (via a solution) and a solid evaporated metal source. Investigations of Zn into InP and InGaAs(P) have been undertaken using both sources. SIMS profile analyses show that in the case of the vapour source the profiles indicate a concentration-dependent diffusion coefficient while the solid source diffusions can be well described by a Gaussian-type profile. The usefulness of the vapour source method has been demonstrated in the fabrication of bipolar transistors which exhibit good d.c. characteristics. The solid source method is limited by the slow diffusion velocity and more gradual profile. The InGaAs(P)/InP materials system has important applications in optical communications and future high speed microwave and switching devices. Useful technologies allied to the introduction of impurities into Si by diffusion, have gradually been emerging for use in the III-V semiconductor family. Closed tube systems1 have been used in order to contain the volatile group V species and prevent surface erosion. In addition, simpler open tube systems2,3 have been developed that maintain a sufficient overpressure of the group V element. Zn and Cd p-dopants have been studied extensively because of the volatility and relatively large diffusion rates in III-V semiconductors. Opentube diffusion into both InP and InGaAs2-6 has been studied but little detail has appeared concerning InGaAs and InGaAsP. In this paper we describe a comprehensive study of the diffusion of Zn into InP and InGaAs(P) using both open-tube vapour source and a Au/Zn/Au evaporated solid source with SiNx acting both as a mask and also an encapsulant to prevent loss of Zn and decomposition of the substrate material. The techniques have been successfully applied to the fabrication of InP/lnGaAs heterojunction bipolar transistors which show good dc characteristics. Reference to InGaAs in the text implies the InP lattice-matched composition In0.53Ga0.47As.

Community-led trials: Intervention co-design in a cluster randomised controlled trial.

PubMed

Andersson, Neil

2017-05-30

In conventional randomised controlled trials (RCTs), researchers design the interventions. In the Camino Verde trial, each intervention community designed its own programmes to prevent dengue. Instead of fixed actions or menus of activities to choose from, the trial randomised clusters to a participatory research protocol that began with sharing and discussing evidence from a local survey, going on to local authorship of the action plan for vector control.Adding equitable stakeholder engagement to RCT infrastructure anchors the research culturally, making it more meaningful to stakeholders. Replicability in other conditions is straightforward, since all intervention clusters used the same engagement protocol to discuss and to mobilize for dengue prevention. The ethical codes associated with RCTs play out differently in community-led pragmatic trials, where communities essentially choose what they want to do. Several discussion groups in each intervention community produced multiple plans for prevention, recognising different time lines. Some chose fast turnarounds, like elimination of breeding sites, and some chose longer term actions like garbage disposal and improving water supplies.A big part of the skill set for community-led trials is being able to stand back and simply support communities in what they want to do and how they want to do it, something that does not come naturally to many vector control programs or to RCT researchers. Unexpected negative outcomes can come from the turbulence implicit in participatory research. One example was the gender dynamic in the Mexican arm of the Camino Verde trial. Strong involvement of women in dengue control activities seems to have discouraged men in settings where activity in public spaces or outside of the home would ordinarily be considered a "male competence".Community-led trials address the tension between one-size-fits-all programme interventions and local needs. Whatever the conventional wisdom about how prevention works at a system level, programmes have to be perceived as locally relevant and they must engage stakeholders who make them work. Locally, each participating community has to know the intervention is relevant to them; they have to want to do it. That happens much more easily if they design the programme themselves.

INTroducing A Care bundle To prevent pressure injury (INTACT) in at-risk patients: A protocol for a cluster randomised trial.

PubMed

Chaboyer, Wendy; Bucknall, Tracey; Webster, Joan; McInnes, Elizabeth; Banks, Merrilyn; Wallis, Marianne; Gillespie, Brigid M; Whitty, Jennifer A; Thalib, Lukman; Roberts, Shelley; Cullum, Nicky

2015-11-01

Pressure injuries are a significant clinical and economic issue, affecting both patients and the health care system. Many pressure injuries in hospitals are facility acquired, and are largely preventable. Despite growing evidence and directives for pressure injury prevention, implementation of preventative strategies is suboptimal, and pressure injuries remain a serious problem in hospitals. This study will test the effectiveness and cost-effectiveness of a patient-centred pressure injury prevention care bundle on the development of hospital acquired pressure injury in at-risk patients. This is a multi-site, parallel group cluster randomised trial. The hospital is the unit of randomisation. Adult medical and surgical patients admitted to the study wards of eight hospitals who are (a) deemed to be at risk of pressure injury (i.e. have reduced mobility), (b) expected to stay in hospital for ≥48h, (c) admitted to hospital in the past 36h; and (d) able to provide informed consent will be eligible to participate. Consenting patients will receive either the pressure injury prevention care bundle or standard care. The care bundle contains three main messages: (1) keep moving; (2) look after your skin; and (3) eat a healthy diet. Nurses will receive education about the intervention. Patients will exit the study upon development of a pressure injury, hospital discharge or 28 days, whichever comes first; transfer to another hospital or transfer to critical care and mechanically ventilated. The primary outcome is incidence of hospital acquired pressure injury. Secondary outcomes are pressure injury stage, patient participation in care and health care costs. A health economic sub-study and a process evaluation will be undertaken alongside the trial. Data will be analysed at the cluster (hospital) and patient level. Estimates of hospital acquired pressure injury incidence in each group, group differences and 95% confidence interval and p values will be reported. To our knowledge, this is the first trial of an intervention to incorporate a number of pressure injury prevention strategies into a care bundle focusing on patient participation and nurse-patient partnership. The results of this study will provide important information on the effectiveness and cost-effectiveness of this intervention in preventing pressure injuries in at-risk patients. If the results confirm the utility of the developed care bundle, it could have a significant impact on clinical practice worldwide. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613001343796. Copyright © 2015 Elsevier Ltd. All rights reserved.

Healthy eating and obesity prevention for preschoolers: a randomised controlled trial

PubMed Central

2010-01-01

Background Developing effective prevention and intervention programs for the formative preschool years is seen as an essential step in combating the obesity epidemic across the lifespan. The overall goal of the current project is to measure the effectiveness of a healthy eating and childhood obesity prevention intervention, the MEND (Mind Exercise Nutrition Do It!) program that is delivered to parents of children aged 2-4 years. Methods/Design This randomised controlled trial will be conducted with 200 parents and their 2-4 year old children who attend the MEND 2-4 program in metropolitan and regional Victoria. Parent-child dyads will attend ten 90-minute group workshops. These workshops focus on general nutrition, as well as physical activity and behaviours. They are typically held at community or maternal and child health centres and run by a MEND 2-4 trained program leader. Child eating habits, physical activity levels and parental behaviours and cognitions pertaining to nutrition and physical activity will be assessed at baseline, the end of the intervention, and at 6 and 12 months post the intervention. Informed consent will be obtained from all parents, who will then be randomly allocated to the intervention or wait-list control group. Discussion Our study is the first RCT of a healthy eating and childhood obesity prevention intervention targeted specifically to Australian parents and their preschool children aged 2-4 years. It responds to the call by experts in the area of childhood obesity and child health that prevention of overweight in the formative preschool years should focus on parents, given that parental beliefs, attitudes, perceptions and behaviours appear to impact significantly on the development of early overweight. This is 'solution-oriented' rather than 'problem-oriented' research, with its focus being on prevention rather than intervention. If this is a positive trial, the MEND2-4 program can be implemented as a national program. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12610000200088 PMID:20426840

The rationale, design, and baseline characteristics of PREVENT-DM: A community-based comparative effectiveness trial of lifestyle intervention and metformin among Latinas with prediabetes.

PubMed

Perez, Alberly; Alos, Victor A; Scanlan, Adam; Maia, Catarina M; Davey, Adam; Whitaker, Robert C; Foster, Gary D; Ackermann, Ronald T; O'Brien, Matthew J

2015-11-01

Promotora Effectiveness Versus Metformin Trial (PREVENT-DM) is a randomized comparative effectiveness trial of a lifestyle intervention based on the Diabetes Prevention Program delivered by community health workers (or promotoras), metformin, and standard care. Eligibility criteria are Hispanic ethnicity, female sex, age ≥ 20 years, fluent Spanish-speaking status, BMI ≥ 23 kg/m(2), and prediabetes. We enrolled 92 participants and randomized them to one of the following three groups: standard care, DPP-based lifestyle intervention, or metformin. The primary outcome of the trial is the 12-month difference in weight between groups. Secondary outcomes include the following cardiometabolic markers: BMI, waist circumference, blood pressure, and fasting plasma glucose, hemoglobin A1C (HbA1c), total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and insulin. PREVENT-DM participants are socioeconomically disadvantaged Latinas with a mean annual household income of $15,527 ± 9922 and educational attainment of 9.7 ± 3.6 years. Eighty-six percent of participants are foreign born, 20% have a prior history of gestational diabetes, and 71% have a first-degree relative with diagnosed diabetes. At baseline, PREVENT-DM participants had a mean age of 45.1 ± 12.5 years, weight of 178.8 ± 39.3 lbs, BMI of 33.3 ± 6.5 kg/m(2), HbA1c of 5.9 ± 0.2%, and waist circumference of 97.4 ± 11.1cm. Mean baseline levels of other cardiometabolic markers were normal. The PREVENT-DM study successfully recruited and randomized an understudied population of Latinas with prediabetes. This trial will be the first U.S. study to test the comparative effectiveness of metformin and lifestyle intervention versus standard care among prediabetic adults in a "real-world" setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Pre-exposure prophylaxis of HIV

PubMed Central

Naswa, Smriti; Marfatia, Y. S.

2011-01-01

Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568

Vaccines for preventing typhoid fever.

PubMed

Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J; Paul, Mical; Leibovici, Leonard

2014-01-02

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the study authors did not adjust for clustering.Compared with placebo, this vaccine was not associated with more participants with vomiting, diarrhoea, nausea or abdominal pain (four trials, 2066 participants; moderate quality evidence) headache, or rash (two trials, 1190 participants; moderate quality evidence); however, fever (four trials, 2066 participants; moderate quality evidence) was more common in the vaccine group. Vi polysaccharide vaccine (injection, one dose) A single dose of Vi polysaccharide vaccine prevents around two-thirds of typhoid cases in the first year after vaccination (Year 1: 69%, 95% CI 63% to 74%; three trials, 99,979 participants; high quality evidence). In Year 2, the trial results were more variable, with the vaccine preventing between 45% and 69% of typhoid cases (Year 2: 59%, 95% CI 45% to 69%; four trials, 194,969 participants; moderate quality evidence). The three-year cumulative efficacy of the vaccine is around 55% (95% CI 30% to 70%; 11,384 participants, one trial; moderate quality evidence). These data are taken from a single trial in South Africa in the 1980s.Compared with placebo, this vaccine was not associated with more participants with fever (four trials, 133,038 participants; moderate quality evidence) or erythema (three trials, 132,261 participants; low quality evidence); however, swelling (three trials, 1767 participants; moderate quality evidence) and pain at the injection site (one trial, 667 participants; moderate quality evidence) were more common in the vaccine group. Vi-rEPA vaccine (two doses) Administration of two doses of the Vi-rEPA vaccine prevents between 50% and 96% of typhoid cases during the first two years after vaccination (Year 1: 94%, 95% CI 75% to 99%; Year 2: 87%, 95% CI 56% to 96%; one trial, 12,008 participants; moderate quality evidence). These data are taken from a single trial with children 2 to 5 years of age conducted in Vietnam.Compared with placebo, the first and second doses of this vaccine were not associated with increased risk of adverse events. The first dose of this vaccine was not associated with fever (2 studies, 12,209 participants; low quality evidence), erythema (two trials, 12,209 participants; moderate quality evidence) or swelling at the injection site (two trials, 12,209 participants; moderate quality evidence). The second dose of this vaccine was not associated with fever (two trials, 11,286 participants; low quality evidence), erythema (two trials, 11,286 participants; moderate quality evidence) and swelling at the injection site (two trials, 11,286 participants; moderate quality evidence). The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.

Effectiveness trial of a selective dissonance-based eating disorder prevention program with female college students: Effects at 2- and 3-year follow-up.

PubMed

Stice, Eric; Rohde, Paul; Butryn, Meghan L; Shaw, Heather; Marti, C Nathan

2015-08-01

An efficacy trial found that a dissonance-based prevention program reduced risk factors, eating disorder symptoms, and future eating disorder onset, but smaller effects emerged when high school clinicians recruited students and delivered the program under real-world conditions in an effectiveness trial. The current report describes results at 2- and 3-year follow-up from an effectiveness trial that tested whether a new enhanced dissonance version of this program produced larger effects when college clinicians recruit students and deliver the intervention using improved train and supervision procedures. Young women from eight universities (N = 408, M age = 21.6, SD = 5.64) were randomized to the prevention program or an educational brochure control condition. Dissonance participants showed greater decreases in risk factors, eating disorder symptoms, and psychosocial impairment by 3-year follow-up than controls, but not healthcare utilization, BMI, or eating disorder onset. This novel multisite effectiveness trial found that the enhanced dissonance intervention and improved training and supervision procedures produced an average effect size at 3-year follow-up that was 290% and 160% larger than effects observed in the high school effectiveness trial and efficacy trial respectively. Yet, the lack of eating disorder onset effects may imply that factors beyond pursuit of the thin ideal now contribute to eating disorder onset. Copyright © 2015 Elsevier Ltd. All rights reserved.

Apixaban to prevent stroke in patients with atrial fibrillation: a review

PubMed Central

Peterson, Benjamin E.; Al-Khatib, Sana M.; Granger, Christopher B.

2016-01-01

Atrial fibrillation is a common, costly and morbid cardiovascular arrhythmia. Stroke prevention remains the mainstay of treatment for atrial fibrillation, and the recent advent of novel oral anticoagulants with direct factor IIa or factor Xa inhibition has significantly revolutionized this aspect of treatment for atrial fibrillation patients. This review focuses on the tolerability and efficacy of apixaban and tackles the generalizability of the findings with apixaban to broader patient populations than those primarily enrolled in the clinical trials, drawing from the AVERROES and ARISTOTLE trials and their subsequent secondary analyses. Taken together, findings from these trials show that apixaban is superior to warfarin in preventing stroke with a lower risk of major bleeding in the general population of patients with atrial fibrillation as well as in several key high-risk patient subgroups. PMID:27342651

Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model

PubMed Central

Coley, Rebecca Yates; Browna, Elizabeth R.

2016-01-01

Inconsistent results in recent HIV prevention trials of pre-exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population-level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood-based Bayesian hierarchical model that estimates the individual-level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson-distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. PMID:26869051

Principles for designing randomized preventive trials in mental health: an emerging developmental epidemiology paradigm.

PubMed

Brown, C H; Liao, J

1999-10-01

An emerging population-based paradigm is now being used to guide the design of preventive trials used to test developmental models. We discuss elements of the designs of several ongoing randomized preventive trials involving reduction of risk for children of divorce, for children who exhibit behavioral or learning problems, and for children whose parents are being treated for depression. To test developmental models using this paradigm, we introduce three classes of design issues: design for prerandomization, design for intervention, and design for postintervention. For each of these areas, we present quantitative results from power calculations. Both scientific and cost implications of these power calculations are discussed in terms of variation among subjects on preintervention measures, unit of intervention, assignment, balancing, number of pretest and posttest measures, and the examination of moderation effects.

An empirical assessment of implementation, adaptation, and tailoring: the evaluation of CDC's National Diffusion of VOICES/VOCES.

PubMed

Harshbarger, Camilla; Simmons, Gretchen; Coelho, Helen; Sloop, Kira; Collins, Charles

2006-08-01

The Centers for Disease Control and Prevention (CDC), through its Diffusion of Effective Behavioral Interventions (DEBI) program, trained over 260 agencies on VOICES/VOCES between August 2003 and April 2005. ORC Macro conducted interviews with agency staff 3 months after receiving VOICES/VOCES training. This article discusses the diffusion of VOICES/VOCES; agencies' adoption, adaptation, and implementation of this intervention; and needs for ongoing proactive technical assistance (TA) for agencies to successfully integrate behavioral interventions into their programs. The vastmajority of agencies implemented VOICES/VOCES with fidelity to the core elements, and agencies successfully adapted the intervention to make it more appealing to target populations. TA is needed for interventions to be successfully adapted and implemented with fidelity to the core elements, and to ensure program sustainability. More effective interventions of short duration and minimum complexity to easily match with existing resources and conditions of agency capacity among HIV prevention providers in the community are needed.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients.

PubMed

McFarland, Lynne V

2010-05-14

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler's diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn's disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea.

Systematic review and meta-analysis of Saccharomyces boulardii in adult patients

PubMed Central

McFarland, Lynne V

2010-01-01

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009. For meta-analysis, only randomized, blinded controlled trials unrestricted by language were included. Pre-clinical studies, volunteer studies and uncontrolled studies were excluded from the review of efficacy and meta-analysis, but included in the systematic review. Of 31 randomized, placebo-controlled treatment arms in 27 trials (encompassing 5029 study patients), S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the traveler’s diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Heliobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn’s disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea. PMID:20458757

Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial.

PubMed

Karim, Quarraisha Abdool; Kharsany, Ayesha Bm; Frohlich, Janet A; Baxter, Cheryl; Yende, Nonhlanhla; Mansoor, Leila E; Mlisana, Koleka P; Maarschalk, Silvia; Arulappan, Natasha; Grobler, Anneke; Sibeko, Sengeziwe; Omar, Zaheen; Gengiah, Tanuja N; Mlotshwa, Mukelisiwe; Samsunder, Natasha; Karim, Salim S Abdool

2011-03-07

Young women in sub-Saharan Africa bear a disproportionate burden of HIV infection compared to men but have limited options to reduce their HIV risk. Microbicides could fill an important HIV prevention gap for sexually active women who are unable to successfully negotiate mutual monogamy or condom use. This paper describes the baseline sample characteristics in the CAPRISA 004 trial which assessed the safety and effectiveness of the vaginal microbicide, 1% tenofovir gel for HIV prevention in South Africa. This analysis assessed the baseline demographic, clinical and sexual behavior data of women screened and enrolled into the trial. The characteristics were summarized using descriptive summary measures; expressed as means and percent for categorical variables. HIV prevalence at screening was 25.8% [95% Confidence Interval (CI):23.9-27.7). Of the 889 eligibly enrolled women who contributed follow-up data, rural participants recruited from a family planning (FP) clinic were younger, more likely to be living apart from their regular partner, reported lower coital frequency, had lower condom use (p < 0.001). In contrast, urban participants recruited from a sexually transmitted disease (STD) clinic reported higher numbers of lifetime sexual partners, new partners in the last 30 days and receiving money in exchange for sex (p < 0.001). The populations selected provide suitable diverse target groups for HIV prevention intervention studies. ClinicalTrials.gov: NCT 00441298.

Randomised controlled trial of the clinical and cost-effectiveness of a peer-delivered self-management intervention to prevent relapse in crisis resolution team users: study protocol

PubMed Central

Mason, Oliver; Osborn, David; Henderson, Claire; Marston, Louise; Ambler, Gareth; Pilling, Stephen; Morant, Nicola; Gray, Richard; Weaver, Tim; Nolan, Fiona; Lloyd-Evans, Brynmor

2017-01-01

Introduction Crisis resolution teams (CRTs) provide assessment and intensive home treatment in a crisis, aiming to offer an alternative for people who would otherwise require a psychiatric inpatient admission. They are available in most areas in England. Despite some evidence for their clinical and cost-effectiveness, recurrent concerns are expressed regarding discontinuity with other services and lack of focus on preventing future relapse and readmission to acute care. Currently evidence on how to prevent readmissions to acute care is limited. Self-management interventions, involving supporting service users in recognising and managing signs of their own illness and in actively planning their recovery, have some supporting evidence, but have not been tested as a means of preventing readmission to acute care in people leaving community crisis care. We thus proposed the current study to test the effectiveness of such an intervention. We selected peer support workers as the preferred staff to deliver such an intervention, as they are well-placed to model and encourage active and autonomous recovery from mental health problems. Methods and analysis The CORE (CRT Optimisation and Relapse Prevention) self-management trial compares the effectiveness of a peer-provided self-management intervention for people leaving CRT care, with treatment as usual supplemented by a booklet on self-management. The planned sample is 440 participants, including 40 participants in an internal pilot. The primary outcome measure is whether participants are readmitted to acute care over 1 year of follow-up following entry to the trial. Secondary outcomes include self-rated recovery at 4 and at 18 months following trial entry, measured using the Questionnaire on the Process of Recovery. Analysis will follow an intention to treatment principle. Random effects logistic regression modelling with adjustment for clustering by peer support worker will be used to test the primary hypothesis. Ethics and dissemination The CORE self-management trial was approved by the London Camden and Islington Research Ethics Committee (REC ref: 12/LO/0988). A Trial Steering Committee and Data Monitoring Committee oversee the progress of the study. We will report on the results of the clinical trial, as well as on the characteristics of the participants and their associations with relapse. Trial registration number ISRCTN 01027104;pre-results stage. PMID:29079602

Design of the Prevention of Adult Caries Study (PACS): A randomized clinical trial assessing the effect of a chlorhexidine dental coating for the prevention of adult caries

PubMed Central

2010-01-01

Background Dental caries is one of the primary causes of tooth loss among adults. It is estimated to affect a majority of Americans aged 55 and older, with a disproportionately higher burden in disadvantaged populations. Although a number of treatments are currently in use for caries prevention in adults, evidence for their efficacy and effectiveness is limited. Methods/Design The Prevention of Adult Caries Study (PACS) is a multicenter, placebo-controlled, double-blind, randomized clinical trial of the efficacy of a chlorhexidine (10% w/v) dental coating in preventing adult caries. Participants (n = 983) were recruited from four different dental delivery systems serving four diverse communities, including one American Indian population, and were randomized to receive either chlorhexidine or a placebo treatment. The primary outcome is the net caries increment (including non-cavitated lesions) from baseline to 13 months of follow-up. A cost-effectiveness analysis also will be considered. Discussion This new dental treatment, if efficacious and approved for use by the Food and Drug Administration (FDA), would become a new in-office, anti-microbial agent for the prevention of adult caries in the United States. Trial Registration Number NCT00357877 PMID:20923557

Prophylactic antibiotics for manual removal of retained placenta in vaginal birth.

PubMed

Chongsomchai, Chompilas; Lumbiganon, Pisake; Laopaiboon, Malinee

2014-10-20

Retained placenta is a potentially life-threatening condition because of its association with postpartum hemorrhage. Manual removal of placenta increases the likelihood of bacterial contamination in the uterine cavity. To compare the effectiveness and side-effects of routine antibiotic use for manual removal of placenta in vaginal birth in women who received antibiotic prophylaxis and those who did not and to identify the appropriate regimen of antibiotic prophylaxis for this procedure. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2014). All randomized controlled trials comparing antibiotic prophylaxis and placebo or non antibiotic use to prevent endometritis after manual removal of placenta in vaginal birth. There are no included trials. In future updates, if we identify eligible trials, two review authors will independently assess trial quality and extract data No studies that met the inclusion criteria were identified. There are no randomized controlled trials to evaluate the effectiveness of antibiotic prophylaxis to prevent endometritis after manual removal of placenta in vaginal birth.

Design of control-group conditions in clinical trials of behavioral interventions.

PubMed

Lindquist, Ruth; Wyman, Jean F; Talley, Kristine M C; Findorff, Mary J; Gross, Cynthia R

2007-01-01

To review considerations in the design of placebo (attention) control conditions for community-based clinical trials of health behavior change interventions and to provide practical strategies for the design of control conditions. A well-designed control condition is an essential component of a clinical trial to foster the unambiguous interpretation of study findings. Pitfalls in the design of control conditions in clinical trials of behavioral interventions are identified and strategies to address them are offered. Types of control conditions that have been used in fall prevention trials are described, along with their strengths and weaknesses. The control condition used in the recent fall evaluation and prevention program (FEPP) was designed to overcome limitations of previous trial designs; it is provided to illustrate how to apply specific design principles. Pitfalls in the design of behavioral intervention studies may be avoided with the application of sound design principles. The FEPP active control condition can be used as a model in the design of future studies.

New Cancer Prevention and Control Central Institutional Review Board Established | Division of Cancer Prevention

Cancer.gov

The NCI Central Institutional Review Board (CIRB) Initiative announced the establishment of the Cancer Prevention and Control (CPC) CIRB January 14, extending the benefits of centralized review to investigators participating in clinical trials sponsored by the Division of Cancer Prevention (DCP). |

Vikrant Sahasrabuddhe, MBBS, MPH, DrPH | Division of Cancer Prevention

Cancer.gov

Dr. Vikrant Sahasrabuddhe is Program Director in the Division of Cancer Prevention at the National Cancer Institute overseeing clinical trials focused on prevention of cervical cancer and other human papillomavirus (HPV)-related cancers. Dr. |

Dietary supplements for preventing postnatal depression.

PubMed

Miller, Brendan J; Murray, Linda; Beckmann, Michael M; Kent, Terrence; Macfarlane, Bonnie

2013-10-24

Postnatal depression is a medical condition that affects many women and the development of their infants. There is a lack of evidence for treatment and prevention strategies that are safe for mothers and infants. Certain dietary deficiencies in a pregnant or postnatal woman's diet may cause postnatal depression. By correcting these deficiencies postnatal depression could be prevented in some women. Specific examples of dietary supplements aimed at preventing postnatal depression include: omega-3 fatty acids, iron, folate, s-adenosyl-L-methionine, cobalamin, pyridoxine, riboflavin, vitamin D and calcium. To assess the benefits of dietary supplements for preventing postnatal depression either in the antenatal period, postnatal period, or both. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). Randomised controlled trials, involving women who were pregnant or who had given birth in the previous six weeks, who were not depressed or taking antidepressants at the commencement of the trials. The trials could use as intervention any dietary supplementation alone or in combination with another treatment compared with any other preventive treatment, or placebo, or standard clinical care. Two review authors independently assessed trials for inclusion and assessed the risk of bias for the two included studies. Two review authors extracted data and the data were checked for accuracy. We included two randomised controlled trials.One trial compared oral 100 microgram (µg) selenium yeast tablets with placebo, taken from the first trimester until birth. The trial randomised 179 women but outcome data were only provided for 85 women. Eighty-three women were randomised to each arm of the trial. Sixty-one women completed the selenium arm, 44 of whom completed an Edinburgh Postnatal Depression Scale (EPDS). In the placebo arm, 64 women completed the trial, 41 of whom completed an EPDS. This included study (n = 85) found selenium had an effect on EPDS scores but did not reach statistical significance (P = 0.07). There was a mean difference (MD) of -1.90 (95% confidence interval (CI) -3.92 to 0.12) of the self-reported EPDS completed by participants within eight weeks of delivery. There was a high risk of attrition bias due to a large proportion of women withdrawing from the study or not completing an EPDS. This included study did not report on any of the secondary outcomes of this review.The other trial compared docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA) with placebo. The trial randomised 126 women at risk of postpartum depression to three arms: 42 were allocated to EPA, 42 to DHA, and 42 to placebo. Three women in the EPA arm, four in the DHA arm, and one woman in the placebo arm were lost to follow-up. Women who were found to have major depressive disorder, bipolar disorder, current substance abuse or dependence, suicidal ideation or schizophrenia at recruitment were excluded from the study. The women who discontinued the intervention (five in the EPA arm, four in the DHA arm and seven in the placebo arm) were included in the intention-to-treat analysis, while those who were lost to follow-up were not. Women received supplements or placebo from recruitment at a gestational age of 12 to 20 weeks until their final review visit six to eight weeks postpartum. The primary outcome measure was the Beck Depression Inventory (BDI) score at the fifth visit (six to eight weeks postpartum). No benefit was found for EPA-rich fish oil (MD 0.70, 95% CI -1.78 to 3.18) or DHA-rich fish oil supplementation (MD 0.90, 95% CI -1.33 to 3.13) in preventing postpartum depression. No difference was found in the effect on postnatal depression comparing EPA with DHA (MD -0.20, 95% CI -2.61 to 2.21). No benefit or significant effect was found in terms of the secondary outcomes of the presence of major depressive disorder at six to eight weeks postpartum, the number of women who commenced antidepressants, maternal estimated blood loss at delivery or admission of neonates to the neonatal intensive care unit. There is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.

A method for optimizing the cosine response of solar UV diffusers

NASA Astrophysics Data System (ADS)

Pulli, Tomi; Kärhä, Petri; Ikonen, Erkki

2013-07-01

Instruments measuring global solar ultraviolet (UV) irradiance at the surface of the Earth need to collect radiation from the entire hemisphere. Entrance optics with angular response as close as possible to the ideal cosine response are necessary to perform these measurements accurately. Typically, the cosine response is obtained using a transmitting diffuser. We have developed an efficient method based on a Monte Carlo algorithm to simulate radiation transport in the solar UV diffuser assembly. The algorithm takes into account propagation, absorption, and scattering of the radiation inside the diffuser material. The effects of the inner sidewalls of the diffuser housing, the shadow ring, and the protective weather dome are also accounted for. The software implementation of the algorithm is highly optimized: a simulation of 109 photons takes approximately 10 to 15 min to complete on a typical high-end PC. The results of the simulations agree well with the measured angular responses, indicating that the algorithm can be used to guide the diffuser design process. Cost savings can be obtained when simulations are carried out before diffuser fabrication as compared to a purely trial-and-error-based diffuser optimization. The algorithm was used to optimize two types of detectors, one with a planar diffuser and the other with a spherically shaped diffuser. The integrated cosine errors—which indicate the relative measurement error caused by the nonideal angular response under isotropic sky radiance—of these two detectors were calculated to be f2=1.4% and 0.66%, respectively.

Development of pre-consultation prevention summary and reminder sheets for patients: preliminary study of acceptability and sustainability.

PubMed

Frank, Oliver; Aylward, Paul; Stocks, Nigel

2014-05-01

Patients attending general practices receive about 60% of indicated preventive services. Patients do not know which preventive services are indicated for them and want their GPs to offer those services. Patients arriving for consultations in three general practices received individualised prevention summary sheets. Acceptability was assessed by patient survey. Sustainability was assessed by the number of sheets printed over time. Seventy-two percent of patients discussed the advice on their sheet in the consultation, and 89% wanted to receive the sheets in the future. Practices printed 8882 sheets in the 52 weeks from the start of the trial. This new intervention seems to be acceptable and sustainable in the Australian setting. It has the potential, therefore, to increase the delivery of preventive care in general practice. A larger trial is needed to demonstrate its effect on performance of preventive activities and on patient outcomes.

Episodic migraines in children: limited evidence on preventive pharmacological treatments.

PubMed

Shamliyan, Tatyana A; Kane, Robert L; Ramakrishnan, Rema; Taylor, Frederick R

2013-10-01

The authors conducted a systematic literature review of preventive pharmacological treatments for episodic childhood migraines searching several databases through May 20, 2012. Episodic migraine prevention was examined in 24 publications of randomized controlled trials that enrolled 1578 children in 16 nonrandomized studies. Single randomized controlled trials provided low-strength evidence that propranolol would result in complete cessation of migraine attacks in 713 per 1000 children treated (95% confidence interval, 452-974); trazodone and nimodipine decreased migraine days, while topiramate, divalproex, and clonidine were no more effective than placebo in preventing migraines. Migraine prevention with multidisciplinary drug management was not sustained at 6 months. Divalproex resulted in treatment discontinuation due to adverse effects, and topiramate increased the risk of paresthesia, upper respiratory tract infection, and weight loss. Long-term preventive benefits and improvement in disability and quality of life are unknown. No studies examined quality of life or provided evidence for individualized treatment decisions.

Venom immunotherapy for preventing allergic reactions to insect stings.

PubMed

Boyle, Robert J; Elremeli, Mariam; Hockenhull, Juliet; Cherry, Mary Gemma; Bulsara, Max K; Daniels, Michael; Oude Elberink, J N G

2012-10-17

Venom immunotherapy (VIT) is commonly used for preventing further allergic reactions to insect stings in people who have had a sting reaction. The efficacy and safety of this treatment has not previously been assessed by a high-quality systematic review. To assess the effects of immunotherapy using extracted insect venom for preventing further allergic reactions to insect stings in people who have had an allergic reaction to a sting. We searched the following databases up to February 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), the Armed Forces Pest Management Board Literature Retrieval System, and OpenGrey. There were no language or publication status restrictions to our searches. We searched trials databases, abstracts from recent European and North American allergy meetings, and the references of identified review articles in order to identify further relevant trials. Randomised controlled trials of venom immunotherapy using standardised venom extract in insect sting allergy. Two authors independently undertook study selection, data extraction, and assessment of risk of bias. We identified adverse events from included controlled trials and from a separate analysis of observational studies identified as part of a National Institute for Health and Clinical Excellence Health Technology Assessment. We identified 6 randomised controlled trials and 1 quasi-randomised controlled trial for inclusion in the review; the total number of participants was 392. The trials had some risk of bias because five of the trials did not blind outcome assessors to treatment allocation. The interventions included ant, bee, and wasp immunotherapy in children or adults with previous systemic or large local reactions to a sting, using sublingual (one trial) or subcutaneous (six trials) VIT. We found that VIT is effective for preventing systemic allergic reaction to an insect sting, which was our primary outcome measure. This applies whether the sting occurs accidentally or is given intentionally as part of a trial procedure.In the trials, 3/113 (2.7%) participants treated with VIT had a subsequent systemic allergic reaction to a sting, compared with 37/93 (39.8%) untreated participants (risk ratio [RR] 0.10, 95% confidence interval [CI] 0.03 to 0.28). The efficacy of VIT was similar across studies; we were unable to identify a patient group or mode of treatment with different efficacy, although these analyses were limited by small numbers. We were unable to confirm whether VIT prevents fatal reactions to insect stings, because of the rarity of this outcome.Venom immunotherapy was also effective for preventing large local reactions to a sting (5 studies; 112 follow-up stings; RR 0.41, 95% CI 0.24 to 0.69) and for improving quality of life (mean difference [MD] in favour of VIT 1.21 points on a 7-point scale, 95% CI 0.75 to 1.67).We found a significant risk of systemic adverse reaction to VIT treatment: 6 trials reported this outcome, in which 14 of 150 (9.3%) participants treated with VIT and 1 of 135 (0.7%) participants treated with placebo or no treatment suffered a systemic reaction to treatment (RR 8.16, 95% CI 1.53 to 43.46; 2 studies contributed to the effect estimate). Our analysis of 11 observational studies found systemic adverse reactions occurred in 131/921 (14.2%) participants treated with bee venom VIT and 8/289 (2.8%) treated with wasp venom VIT. We found venom immunotherapy using extracted insect venom to be an effective therapy for preventing further allergic reactions to insect stings, which can improve quality of life. The treatment carries a small but significant risk of systemic adverse reaction.

Denitrifying bioreactor clogging potential during wastewater treatment

USDA-ARS?s Scientific Manuscript database

Chemoheterotrophic denitrification technologies using woodchips as a solid carbon source (i.e., woodchip bioreactors) have been widely trialed for treatment of diffuse-source agricultural nitrogen pollution. There is growing interest in the use of this simple, relatively low-cost biological wastewat...

Healthy Homes/Healthy Kids: A Randomized Trial of a Pediatric Primary Care Based Obesity Prevention Intervention for At-Risk 5-10 Year Olds

PubMed Central

Sherwood, Nancy E.; Levy, Rona L.; Langer, Shelby L.; Senso, Meghan M.; Crain, A. Lauren; Hayes, Marcia G.; Anderson, Julie D.; Seburg, Elisabeth M.; Jeffery, Robert W.

2014-01-01

Pediatric primary care is an important setting in which to address obesity prevention, yet relatively few interventions have been evaluated and even fewer have been shown to be effective. The development and evaluation of cost-effective approaches to obesity prevention that leverage opportunities of direct access to families in the pediatric primary care setting, overcome barriers to implementation in busy practice settings, and facilitate sustained involvement of parents is an important public health priority. The goal of the Healthy Homes/Healthy Kids (HHHK 5-10) randomized controlled trial is to evaluate the efficacy of a relatively low-cost primary care-based obesity prevention intervention aimed at 5 to 10 year old children who are at risk for obesity. Four hundred twenty one parent/child dyads were recruited and randomized to either the obesity prevention arm or a contact control condition that focuses on safety and injury prevention. The HHHK 5-10 obesity prevention intervention combines brief counseling with a pediatric primary care provider during routine well-child visits and follow-up telephone coaching that supports parents in making home environmental changes to support healthful eating, activity patterns, and body weight. The contact control condition combines the same provider counseling with telephone coaching focused on safety and injury prevention messages. This manuscript describes the study design and baseline characteristics of participants enrolled in the HHHK 5-10 trial. PMID:23816490

New Strategy for Prostate Cancer Prevention Based on Selenium Suppression of Androgen Receptor Signaling

DTIC Science & Technology

2006-10-01

dihydrotestosterone in the prostate by the enzyme 5α-reductase. The Prostate Cancer Prevention Trial (PCPT) demonstrated that treatment with finasteride , an...demand. Finasteride , despite being an older drug, has several advantages over dutasteride. First, its efficacy has been proven by a phase III trial... finasteride treatment. No such information is available with dutasteride. Third, finasteride is available commercially from Steraloids (Newport, RI

Gemcitabine-oxaliplatin plus rituximab (R-GemOx) as first-line treatment in elderly patients with diffuse large B-cell lymphoma: a single-arm, open-label, phase 2 trial.

PubMed

Shen, Qiu-Dan; Zhu, Hua-Yuan; Wang, Li; Fan, Lei; Liang, Jin-Hua; Cao, Lei; Wu, Wei; Xia, Yi; Li, Jian-Yong; Xu, Wei

2018-06-01

The combination of rituximab, gemcitabine, and oxaliplatin (R-GemOx) has shown high efficacy with a low toxicity profile in elderly patients with relapsed and refractory diffuse large B-cell lymphoma. We aimed to evaluate the efficacy, safety, and feasibility of the R-GemOx regimen as a first-line treatment in elderly patients with diffuse large B-cell lymphoma. In this single-arm, open-label, phase 2 clinical trial, we enrolled patients with previously untreated, histologically confirmed, CD20-positive diffuse large B-cell lymphoma, aged 70 years or older, or aged 60-69 years with an Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or greater. Patients were recruited from Jiangsu Province Hospital (Jiangsu Sheng, China). The R-GemOx regimen was administered intravenously: rituximab 375 mg/m 2 on day 0; gemcitabine 1 g/m 2 on day 1; and oxaliplatin 100 mg/m 2 on day 1. The cycle was repeated every 14 days. Six cycles were planned if the patient achieved at least partial remission after the interim assessment. The primary endpoint was the proportion of patients who achieved an overall response at the end of treatment (defined as complete response plus partial response). Analyses were done by intention to treat. The trial is ongoing but no longer recruiting patients. This study is registered with ClinicalTrials.gov, number NCT01670370. Between Aug 22, 2012, and Dec 31, 2015, 60 patients were enrolled and included in the study. The median age of the patients was 75 years (IQR 70-80) and 27 (45%) patients had a poor performance status with an ECOG score of 2 or greater. 45 (75%) patients achieved an overall response at the end of the treatment, with 28 (47%) achieving a complete response. Common grade 3-4 adverse events were haematological toxicities (thrombocytopenia in five [8%] patients, anaemia in four [7%], and neutropenia in nine [15%]) and gastrointestinal complications (nausea in five [8%] patients, vomiting in three [5%], and diarrhoea in one [2%]). No treatment-related deaths were reported. The R-GemOx regimen shows high efficacy and safety as a front-line treatment in an elderly patient subpopulation and might be a therapeutic option for management of diffuse large B-cell lymphoma in elderly patients. National Natural Science Foundation of China, Jiangsu Province's Medical Elite Programme, Project of National Key Clinical Specialty, National Science & Technology Pillar Program, Jiangsu Provincial Special Program of Medical, and National Science and Technology Major Project. Copyright © 2018 Elsevier Ltd. All rights reserved.

Educational interventions in childhood obesity: a systematic review with meta-analysis of randomized clinical trials.

PubMed

Sbruzzi, Graciele; Eibel, Bruna; Barbiero, Sandra M; Petkowicz, Rosemary O; Ribeiro, Rodrigo A; Cesa, Claudia C; Martins, Carla C; Marobin, Roberta; Schaan, Camila W; Souza, Willian B; Schaan, Beatriz D; Pellanda, Lucia C

2013-05-01

To assess the effectiveness of educational interventions including behavioral modification, nutrition and physical activity to prevent or treat childhood obesity through a systematic review and meta-analysis of randomized trials. A search of databases (PubMed, EMBASE and Cochrane CENTRAL) and references of published studies (from inception until May 2012) was conducted. Eligible studies were randomized trials enrolling children 6 to 12 years old and assessing the impact of educational interventions during 6 months or longer on waist circumference, body mass index (BMI), blood pressure and lipid profile to prevent or treat childhood obesity. Calculations were performed using a random effects method and pooled-effect estimates were obtained using the final values. Of 22.852 articles retrieved, 26 trials (23.617 participants) were included. There were no differences in outcomes assessed in prevention studies. However, in treatment studies, educational interventions were associated with a significant reduction in waist circumference [-3.21 cm (95%CI -6.34, -0.07)], BMI [-0.86 kg/m(2) (95%CI -1.59, -0.14)] and diastolic blood pressure [-3.68 mmHg (95%CI -5.48, -1.88)]. Educational interventions are effective in treatment, but not prevention, of childhood obesity and its consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

Caring letters for suicide prevention: implementation of a multi-site randomized clinical trial in the U.S. military and Veteran Affairs healthcare systems.

PubMed

Luxton, David D; Thomas, Elissa K; Chipps, Joan; Relova, Rona M; Brown, Daphne; McLay, Robert; Lee, Tina T; Nakama, Helenna; Smolenski, Derek J

2014-03-01

Caring letters is a suicide prevention intervention that entails the sending of brief messages that espouse caring concern to patients following discharge from treatment. First tested more than four decades ago, this intervention is one of the only interventions shown in a randomized controlled trial to reduce suicide mortality rates. Due to elevated suicide risk among patients following psychiatric hospitalization and the steady increase in suicide rates among the U.S. military personnel, it is imperative to test interventions that may help prevent suicide among high-risk military personnel and veterans. This paper describes the design, methods, study protocol, and regulatory implementation processes for a multi-site randomized controlled trial that aims to evaluate the effectiveness of a caring emails intervention for suicide prevention in the military and VA healthcare systems. The primary outcome is suicide mortality rates to be determined 24 months post-discharge from index hospital stay. Healthcare re-utilization rates will also be evaluated and comprehensive data will be collected regarding suicide risk factors. Recommendations for navigating the military and VA research regulatory processes and implementing a multi-site clinical trial at military and VA hospitals are discussed. Published by Elsevier Inc.

The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large Randomized Controlled Trial of Vitamin D and Marine Omega-3 Fatty Acid Supplements for the Primary Prevention of Cancer and Cardiovascular Disease

PubMed Central

Manson, JoAnn E.; Bassuk, Shari S.; Lee, I-Min; Cook, Nancy R.; Albert, Michelle A.; Gordon, David; Zaharris, Elaine; MacFadyen, Jean G.; Danielson, Eleanor; Lin, Jennifer; Zhang, Shumin M.; Buring, Julie E.

2011-01-01

Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2×2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty acid (Omacor® fish oil, eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1 g/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥50 and women aged ≥55. The mean treatment period will be 5 years. Baseline blood samples will be collected in at least 16,000 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurence of endpoints, and cancer and vascular risk factors. Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment, and deaths will be ascertained through national registries and other sources. Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance; hypertension; cognitive decline; depression; osteoporosis and fracture; physical disability and falls; asthma and other respiratory diseases; infections; rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and other autoimmune disorders. PMID:21986389

Bisphosphonates for prevention of osteopenia in kidney-transplant recipients: a systematic review of randomized controlled trials.

PubMed

Wang, J; Yao, M; Xu, J-h; Shu, B; Wang, Y-j; Cui, X-j

2016-05-01

We conducted a systematic review of randomized controlled trials (RCTs) of bisphosphonates for the prevention of osteopenia in kidney-transplant recipients. Bisphosphonates improved bone mineral density at the lumbar spine and femoral neck after 12 months. However, additional well-designed RCTs are required to determine the optimal treatment strategy. Osteopenic-osteoporotic syndrome is a bone complication of renal transplantation. Bisphosphonates, calcitonin, and vitamin D analogs may be used to prevent or treat osteoporosis or bone loss after renal transplantation. However, there is currently no widely recognized strategy for the prevention of corticosteroid-induced osteoporosis. This study aims to assess the available evidence to guide the targeted use of bisphosphonates for reducing osteoporosis and bone loss in renal-transplant recipients. We searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE for randomized controlled trials of bisphosphonates for osteoporosis or bone loss after renal transplantation. A total of 352 abstracts were identified, of which 55 were considered for evaluation and 9 were included in the final analysis. The primary outcome measure was change in the bone mineral density (BMD) of the lumbar spine and femoral neck after 12 months. Data extraction was performed independently by two investigators. BMD at the lumbar spine was improved after treatment with bisphosphonates [9 trials; 418 patients; weighted mean difference (WMD), 0.61; 95 % confidence interval (CI), 0.16-1.06]. Eight trials (406 patients) that reported changes in BMD at the femoral neck also showed improved outcomes after treatment with bisphosphonates (WMD, 0.06; 95 % CI, 0.03-0.09). Bisphosphonates improve BMD at the lumbar spine and femoral neck after 12 months in renal-transplant recipients.

A Comparison of the Baseline Metabolic Profiles between Diabetes Prevention Trial-Type 1 and TrialNet Natural History Study Participants

PubMed Central

Sosenko, Jay M.; Mahon, Jeffrey; Rafkin, Lisa; Lachin, John M.; Krause-Steinrauf, Heidi; Krischer, Jeffrey P.; Cuthbertson, David; Palmer, Jerry P.; Thompson, Clinton; Greenbaum, Carla J.; Skyler, Jay S.

2010-01-01

Objective We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive. Methods Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies (ICA), whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured. Results The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p<0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p<0.01). Among those in the non-diabetic range (n=860 for DPT-1 and n=604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p<0.001). There was a higher percentage of impaired fasting glucose in the TNNHS participants (10.9% vs. 6.7%, p<0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with IGT. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p<0.001 for all). Discussion Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials. PMID:20522170

A comparison of the baseline metabolic profiles between Diabetes Prevention Trial-Type 1 and TrialNet Natural History Study participants.

PubMed

Sosenko, Jay M; Mahon, Jeffrey; Rafkin, Lisa; Lachin, John M; Krause-Steinrauf, Heidi; Krischer, Jeffrey P; Cuthbertson, David; Palmer, Jerry P; Thompson, Clinton; Greenbaum, Carla J; Skyler, Jay S

2011-03-01

We assessed whether differing autoantibody screening criteria for type 1 diabetes (T1D) prevention trials result in different baseline metabolic profiles of those who screen positive. Diabetes Prevention Trial-Type 1 (DPT-1) participants were screened for islet cell autoantibodies, whereas TrialNet Natural History Study (TNNHS) participants were screened for biochemical autoantibodies. In both studies, those determined to be autoantibody positive underwent baseline oral glucose tolerance tests (OGTTs) in which glucose and C-peptide were measured. The percentage of those with an OGTT in the diabetic range was higher among the DPT-1 participants (10.0% of 956 vs. 6.4% of 645, p < 0.01). In a logistic regression analysis with adjustments for age and gender, the difference persisted (p < 0.01). Among those in the non-diabetic range (n = 860 for DPT-1 and n = 604 for the TNNHS), glucose levels were similar at all time points, except for higher fasting glucose levels in the TNNHS participants (p < 0.001). There was a higher percentage of impaired fasting glucose (IFG) in the TNNHS participants (10.9 vs. 6.7%, p < 0.01); however, with adjustments for age and gender, there was no longer a significant difference. There was no significant difference in the percentages with impaired glucose tolerance. C-peptide levels were much lower in the DPT-1 cohort at all OGTT time points (p < 0.001 for all). Differing criteria for autoantibody screening can result in marked differences in the baseline metabolic profiles of prospective participants of T1D prevention trials. © 2010 John Wiley & Sons A/S.

A core outcome set for clinical trials in acute diarrhoea.

PubMed

Karas, Jacek; Ashkenazi, Shai; Guarino, Alfredo; Lo Vecchio, Andrea; Shamir, Raanan; Vandenplas, Yvan; Szajewska, Hania

2015-04-01

Core outcome sets are the baseline for what should be measured in clinical research and, thus, should serve as a guide for what should be collected and reported. The Consensus Group on Outcome Measures Made in Pediatric Enteral Nutrition Clinical Trials, established in 2012, agreed that consensus on a core set of outcomes with agreed-upon definitions that should be measured and reported in clinical trials was needed. To achieve this goal, six working groups (WGs) were setup, including WG on acute diarrhoea, whose main goal was to develop a core outcome set for trials in acute diarrhoea. The first step identified how published outcomes related to acute diarrhoea were reported. The second focused on the methodology for determining which outcomes to measure in clinical trials. The third employed a two-phase questionnaire study using the Delphi technique to define clinically important outcomes to clinicians and parents. For therapeutic studies, the five most important outcome measures were diarrhoea duration, degree of dehydration, need for hospitalisation (or duration of hospitalisation for inpatients), the proportion of patients recovered by 48 h and adverse effects. The prophylactic core outcome set included prevention of diarrhoea, prevention of dehydration, prevention of hospitalisation and adverse effects. The outcome sets for therapy and prevention can be recommended for use in future trials of patients with gastroenteritis. Their envisioned goal is to decrease study heterogeneity and to ease the comparability of studies. WG's next step is to determine how to measure the outcomes included in the core set. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Secondary Prevention of Cardiovascular Disease in Patients With Type 2 Diabetes Mellitus: International Insights From the TECOS Trial (Trial Evaluating Cardiovascular Outcomes With Sitagliptin).

PubMed

Pagidipati, Neha J; Navar, Ann Marie; Pieper, Karen S; Green, Jennifer B; Bethel, M Angelyn; Armstrong, Paul W; Josse, Robert G; McGuire, Darren K; Lokhnygina, Yuliya; Cornel, Jan H; Halvorsen, Sigrun; Strandberg, Timo E; Delibasi, Tuncay; Holman, Rury R; Peterson, Eric D

2017-09-26

Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown. Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol <70 mg/dL or statin therapy), blood pressure control (<140 mm Hg systolic, <90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke. Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2). In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205. © 2017 American Heart Association, Inc.

Influences of geo-spatial location on pre-exposure prophylaxis use in South Africa: positioning microbicides for better product uptake.

PubMed

Govender, Eliza M; Mansoor, Leila E; Abdool Karim, Quarraisha

2017-06-01

Young women bear a disproportionately high burden of HIV infection in sub-Saharan Africa, prioritising pre-exposure prophylaxis (PrEP) can be an integral part of HIV prevention combination strategies. Women initiated HIV prevention technology options will require consistent adherence, an imperative for product effectiveness. With several PrEP clinical trials underway; exploring women's acceptability to advances in HIV prevention technologies can better facilitate demand creation for future PrEP roll out. This study utilised the opportunity of post-trial access to CAPRISA 008 women (trial) and non-trial women from three geo-spatial settings (urban, rural and peri-urban) to identify microbicide acceptability and how product associations of microbicides can influence future HIV prevention choices. Six participatory workshops using participatory action research with art-based activities and discussion groups were conducted in KwaZulu-Natal with 104 women from various geo-spatial locations and social status to understand microbicide acceptability and product associations. The data were analysed using thematic analysis. The study found that women's acceptability and product association of the tenofovir gel microbicide differed according to rural and urban areas. Most urban women identified confidence, sexiness and classiness as key associations that will encourage microbicide acceptability and use, while rural women identified respect, responsibility and confidence as the key product associations, with increased focus on the individual and collective family/community benefits of product acceptance and use. Urban-rural differences suggest a market segmentation that is contextualised to be locally responsive to promote HIV prevention technologies. Various sexual encounters further determined the types of HIV prevention technologies women would consider. In line with WHO's recommendation that PrEP should be an additional prevention choice for people at risk of HIV, this study underscores the importance of user engagement, understanding product associations and how this can influence product acceptability and promotion of HIV prevention technologies.

Designing behavioral self-regulation application for preventive personal mental healthcare

PubMed Central

Hirano, Mari; Ogura, Kanako; Kitahara, Mizuho; Sakamoto, Daisuke; Shimoyama, Haruhiko

2017-01-01

Most of computerized cognitive behavioral therapy targeted restoration and few have targeted primary prevention. The purpose of this study is to obtain the knowledge for further development on preventive mental healthcare application. We developed a personal mental healthcare application which aimed to give users the chance to manage their mental health by self-monitoring and regulating their behavior. Through the 30-day field trial, the results showed improvement of mood score through conducting of suggested action, and the depressive mood of the participants was significantly decreased after the trial. The possibility of application and further problem was confirmed. PMID:28567301

Prevention of depression through nutritional strategies in high-risk persons: rationale and design of the MooDFOOD prevention trial.

PubMed

Roca, Miquel; Kohls, Elisabeth; Gili, Margalida; Watkins, Ed; Owens, Matthew; Hegerl, Ulrich; van Grootheest, Gerard; Bot, Mariska; Cabout, Mieke; Brouwer, Ingeborg A; Visser, Marjolein; Penninx, Brenda W

2016-06-08

Obesity and depression are two prevalent conditions that are costly to individuals and society. The bidirectional association of obesity with depression, in which unhealthy dietary patterns may play an important role, has been well established. Few experimental studies have been conducted to investigate whether supplementing specific nutrients or improving diet and food-related behaviors can prevent depression in overweight persons. The MooDFOOD prevention trial examines the feasibility and effectiveness of two different nutritional strategies [multi-nutrient supplementation and food-related behavioral change therapy (FBC)] to prevent depression in individuals who are overweight and have elevated depressive symptoms but who are not currently or in the last 6 months meeting criteria for an episode of major depressive disorder (MDD). The randomized controlled prevention trial has a two-by-two factorial design: participants are randomized to daily multi-nutrient supplement (omega-3 fatty acids, calcium, selenium, B-11 vitamin and D-3 vitamin) versus placebo, and/or FBC therapy sessions versus usual care. Interventions last 12 months. In total 1000 participants aged 18-75 years with body mass index between 25-40 kg/m(2) and with a Patient Health Questionnaire-9 score ≥ 5 will be recruited at four study sites in four European countries. Baseline and follow-up assessments take place at 0, 3, 6, and 12 months. Primary endpoint is the onset of an episode of MDD, assessed according to DSM-IV based criteria using the MINI 5.0 interview. Depressive symptoms, anxiety, food and eating behavior, physical activity and health related quality of life are secondary outcomes. During the intervention, compliance, adverse events and potentially mediating variables are carefully monitored. The trial aims to provide a better understanding of the causal role of specific nutrients, overall diet, and food-related behavior change with respect to the incidence of MDD episodes. This knowledge will be used to develop and disseminate innovative evidence-based, feasible, and effective nutritional public health strategies for the prevention of clinical depression. ClinicalTrials.gov. Number of identification: NCT02529423 . August 2015.

Inert-Gas Diffuser For Plasma Or Arc Welding

NASA Technical Reports Server (NTRS)

Gilbert, Jeffrey L.; Spencer, Carl N.; Hosking, Timothy J.

1994-01-01

Inert-gas diffuser provides protective gas cover for weld bead as it cools. Follows welding torch, maintaining continuous flow of argon over newly formed joint and prevents it from oxidizing. Helps to ensure welds of consistently high quality. Devised for plasma arc keyhole welding of plates of 0.25-in. or greater thickness, also used in tungsten/inert-gas and other plasma or arc welding processes.

Vacancy Transport and Interactions on Metal Surfaces

DTIC Science & Technology

2014-03-06

prevent obtaining systematical pictures with atomic scale resolution. Thus the experiments on adatom and mono -vacancy surface diffusion on Ag(110) were...vacuum conditions with atomic scale resolution with Scanning Tunneling Microscope (STM) and Field Ion Microscope (FIM). For each investigated material...experimental conditions for creation of surface vacancies on Au(100) has been determined and observations of surface diffusion of mono vacancies has been

Integrated Protection Against Lyctid Beetle Infestations Part II. - Laboratory Dip-Diffusion Treatment of Unseasoned Banak (Virola spp.) Lumber with Boron Compounds

Treesearch

Lonnie H. Williams; Joe K. Mauldin

1985-01-01

A manufacturer of conventional moulding wanted a method that would prevent lyctid beetle damage to banak (Virola spp.) wood throughout the period from initial cutting in Brazil until final mouldings were in use. Because complete penetration of wood may be obtained, unseasoned banak wood was treated by dip-diffusion with disodium octaborate...

Cranberry

MedlinePlus

... protect against bacteria, as 20 ounces of cranberry juice. A 2012 research review of 13 clinical trials ... review of 24 clinical trials concluded that cranberry juice and supplements don’t prevent UTIs but many ...

Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence.

PubMed

Hall, Wayne; Gartner, Coral

2011-05-01

To describe the rationale of vaccines against cocaine and nicotine, to review progress in developing and trialing vaccines to treat dependence on these drugs and to discuss some of the ethical issues that may arise from their use in legally coerced addiction treatment or for prevention of addiction in adolescents. Several randomized controlled trials of cocaine and nicotine vaccines for relapse prevention have produced mixed results. The studies demonstrate that it is possible to raise antibodies to cocaine and nicotine in humans. In abstinent patients who show high levels of drug antibodies, the rewarding effects of these drugs are attenuated. Phase 2 trials have not found nicotine vaccines to be superior to placebo because only a third of those vaccinated develop sufficient levels of antibody to block the effects of nicotine. Vaccines are a novel approach to relapse prevention that need to more reliably induce immunity in a larger proportion of vaccinated patients if they are to protect against relapse after achieving abstinence. Vaccines are unlikely to prevent addiction in adolescents. Their use under legal coercion should only be considered after considerable experience with their use in voluntary patients.

[Survey of recent clinical trials of the prevention and immunointervention of type 1 diabetes mellitus].

PubMed

Boerschmann, H; Walter, M; Achenbach, P; Ziegler, A-G

2010-02-01

Immunomodulatory strategies in the management of type 1 diabetes mellitus (T1DM) have as their primary target the prevention of initiating islet autoimmunity (primary-), the secondary one is the progression to diabetes (secondary-) in non-diabetic persons at risk, and the decline of beta-cell function in new-onset patients (tertiary-prevention). This article reviews four recent immunointervention trials in patients with T1DM. (1) The Pre-POINT study is a primary prevention trial that will test whether vaccination with oral or nasal insulin can prevent the progression of islet autoimmunity and of T1DM in autoantibody-negative children who are genetically at high diabetes risk. (2) The Cord Blood study is a tertiary immunointervention trial that will test whether administration of autologous umbilical cord blood to children with T1DM can lead to regeneration of pancreatic islet insulin-producing beta-cells and improved blood glucose control. (3) The GAD Vaccination study will test whether vaccination with alum-formulated rhGAD65 (recombinant human glutamic acid decarboxylate) can preserve beta-cell function in 320 children with newly diagnosed T1DM, as has been suggested in a recent phase II study. (4) The AIDA study will test the beta-cell protective effect of interleukin-1-receptor antagonist Anakinra in 80 patients with T1DM, which has recently been shown to improve beta-cell function in patients with type 2 diabetes. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Knowledge and acceptability of alternative HIV prevention bio-medical products among MSM who bareback.

PubMed

Nodin, N; Carballo-Diéguez, A; Ventuneac, A M; Balan, I C; Remien, R

2008-01-01

Condom use is the best available strategy to prevent HIV infection during sexual intercourse. However, since many people choose not to use condoms in circumstances in which HIV risk exists, alternatives to condom use for HIV prevention are needed. Currently there are several alternative bio-medical HIV-prevention products in different stages of development: microbicides, vaccines, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP). Seventy-two men who have sex with men (MSM) who took part in a study on Internet use and intentional condomless anal intercourse were asked about these four products during a semi-structured interview. The questions explored knowledge and acceptability of all the products and willingness to participate in microbicide and vaccine trials. Qualitative analysis of the data suggests that these men had virtually no knowledge of PrEP, very limited knowledge of microbicides, some information about PEP and considerably more knowledge about vaccines. Reactions towards the products were generally positive except for PrEP, for which reactions were polarized as either enthusiastic or negative. With the exception of PrEP, many men expressed willingness to use the products in the future. Most men would be willing to participate in trials for microbicides and vaccines if given basic reassurances. Concerns over negative side effects and preoccupation with possible infection were some of the motives given for non-willingness to participate in a vaccine trial. These results should inform the development of future trials of biomedical prevention products.

Diffusion of Innovations Theory: A Unifying Framework for HIV Peer Education

ERIC Educational Resources Information Center

Ramseyer Winter, Virginia

2013-01-01

Peer education programs are a popular approach to preventing HIV infection among adolescents. While the programs show promise for effectively preventing HIV among the peers who are provided education, little evaluation research has been conducted to determine if the peer educators themselves experience knowledge, attitude, and behavior changes. A…

A method for polycrystalline silicon delineation applicable to a double-diffused MOS transistor

NASA Technical Reports Server (NTRS)

Halsor, J. L.; Lin, H. C.

1974-01-01

Method is simple and eliminates requirement for unreliable special etchants. Structure is graded in resistivity to prevent punch-through and has very narrow channel length to increase frequency response. Contacts are on top to permit planar integrated circuit structure. Polycrystalline shield will prevent creation of inversion layer in isolated region.

Mammograms

MedlinePlus

... gov/widgets/fahc.html" width="243" height="179" title="Find a Health Center Widget" ... M.D., Community Oncology and Prevention Trials Research Group, Division of Cancer Prevention, National Cancer Institute, ...

Comparative Effectiveness of Web-Based vs. Educator-Delivered HIV Prevention for Adolescent Substance Users: A Randomized, Controlled Trial.

PubMed

Marsch, Lisa A; Guarino, Honoria; Grabinski, Michael J; Syckes, Cassandra; Dillingham, Elaine T; Xie, Haiyi; Crosier, Benjamin S

2015-12-01

Young people who engage in substance use are at risk for becoming infected with HIV and diseases with similar transmission dynamics. Effective disease prevention programs delivered by prevention specialists exist but are rarely provided in systems of care due to staffing/resource constraints and operational barriers-and are thus of limited reach. Web-based prevention interventions could possibly offer an effective alternative to prevention specialist-delivered interventions and may enable widespread, cost-effective access to evidence-based prevention programming. Previous research has shown the HIV/disease prevention program within the Web-based therapeutic education system (TES) to be an effective adjunct to a prevention specialist-delivered intervention. The present study was the first randomized, clinical trial to evaluate the comparative effectiveness of this Web-based intervention as a standalone intervention relative to a traditional, prevention specialist-delivered intervention. Adolescents entering outpatient treatment for substance use participated in this multi-site trial. Participants were randomly assigned to either a traditional intervention delivered by a prevention specialist (n=72) or the Web-delivered TES intervention (n=69). Intervention effectiveness was assessed by evaluating changes in participants' knowledge about HIV, hepatitis, and sexually transmitted infections, intentions to engage in safer sex, sex-related risk behavior, self-efficacy to use condoms, and condom use skills. Participants in the TES intervention achieved significant and comparable increases in HIV/disease-related knowledge, condom use self-efficacy, and condom use skills and comparable decreases in HIV risk behavior relative to participants who received the intervention delivered by a prevention specialist. Participants rated TES as easier to understand. This study indicates that TES is as effective as HIV/disease prevention delivered by a prevention specialist. Because technology-based interventions such as TES have high fidelity, are inexpensive and scalable, and can be implemented in a wide variety of settings, they have the potential to greatly increase access to effective prevention programming. Copyright © 2015 Elsevier Inc. All rights reserved.

DIABETES PREVENTION PROGRAM

EPA Science Inventory

The Diabetes Prevention Program (DPP) was a major clinical trial, or research study, aimed at discovering whether either diet and exercise or the oral diabetes drug metformin (Glucophage) could prevent or delay the onset of type 2 diabetes in people with impaired glucose toleranc...

Clinical Trials in Benign Prostatic Hyperplasia: A Moving Target of Success.

PubMed

Thomas, Dominique; Chung, Caroline; Zhang, Yiye; Te, Alexis; Gratzke, Christian; Woo, Henry; Chughtai, Bilal

2018-05-24

Benign prostatic hyperplasia (BPH) affects over 50% of men above the age of 50 yr. With half of these men having bothersome lower urinary tract symptoms, this area represents a hot bed of novel treatments. Many BPH therapies have favorable short-term outcomes but lack durability or well-defined adverse events (AEs). Clinical trials are a gold standard for comparing treatments. We characterized all BPH clinical trials registered worldwide from inception to 2017. A total of 251 clinical trials were included. Of the studies, 30.1% used patient-reported outcomes such as the American Urological Association Symptom Score. Approximately 70% of clinical trials studied medical interventions, while the remaining trials investigated surgical approaches. Seventy-nine percent of trials were industry sponsored, while a minority were funded without commercial interest. Only 42% of trials had 12-mo follow-up, with the majority with <3 mo of follow-up. No trials evaluated prevention, diet, behavior, or alternative methods Overall, only 23% of trials reported results. Management options for BPH need unified benchmarks of success, AEs, durability, and standard reporting for all clinical trials, regardless of outcomes. We found that the majority of clinical trials were medical intervention, with very few trials evaluating prevention, diet, behavior, or alternative methods Furthermore, a few trials reported results in peer-reviewed journals. All clinical trials need to report results regardless of outcome, and in conclusion, standardized methods are needed in order to document the successes, adverse events, and durability for all clinical trials. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.