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Adherence to lifestyle changes is a major challenge for healthcare professionals. The transtheoretical model (TTM) was proposed to promote behavioral changes, used in different health conditions (smoking, alcoholism, drug addiction, and obesity) and age groups. However, the effectiveness of the model in older persons is not yet known. This systematic review protocol follows the PRISMA‐P guidance. The question the review will address is, Are interventions based on the TTM, compared with conventional interventions, associated with lifestyle changes in older adults? Databases MEDLINE/PubMed, EMBASE, LILACS, CENTRAL, WoS, and PsycINFO will be searched. Randomized clinical controlled trials and quasi‐experimental studies describing the effectiveness of TTM‐based interventions in changing the lifestyle of individuals aged 65 and over, compared with conventional interventions for lifestyle changes, will be included. Studies that do not address the stages of change characteristic of TTM or that use pharmacological interventions as a comparator will be excluded. Reviewers independently will screen papers for eligibility criteria, and, extracting data, assess the risk of bias for included studies and will evaluate the overall quality of evidence (GRADE system). If possible, a meta‐analysis will be conducted. Otherwise, a narrative synthesis will be prepared according to the SWiM guideline. [ABSTRACT FROM AUTHOR]

Randomized controlled trials can benefit from proactive assessment of how well their participant selection strategies during the design of eligibility criteria can influence the study generalizability. In this paper, we present a quantitative metric called generalizability index for study traits 2.0 (GIST 2.0) to assess the a priori generalizability (based on population representativeness) of a clinical trial by accounting for the dependencies among multiple eligibility criteria. The metric was evaluated on 16 sepsis trials identified from ClinicalTrials.gov, with their adverse event reports extracted from the trial results sections. The correlation between GIST scores and adverse events was analyzed. We found that the GIST 2.0 score was significantly correlated with total adverse events and serious adverse events (weighted correlation coefficients of 0.825 and 0.709, respectively, with P < 0.01). This study exemplifies the promising use of Big Data in electronic health records and ClinicalTrials.gov for optimizing eligibility criteria design for clinical studies. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]

Resveratrol is a naturally occurring polyphenol found in the skin of red grapes, peanuts, and red wine that has been shown to modify many cardiovascular risk factors. Small animal models have been extensively used to investigate cardiovascular disease, but the results often fail to translate in clinical trials. Disease-specific pig models are emerging as clinically useful tools that may offer insight into cardiovascular disease and the effect of drugs such as resveratrol on cardiovascular health. In this paper, we discuss the advantage of using clinically relevant pig models of diabetes, hypercholesterolemia, and myocardial ischemia to investigate the role of resveratrol in cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

Numerous scientific papers have suggested health-promoting effects of resveratrol, including claims in the prevention of diseases such as coronary heart disease, diabetes, and cancer. Therefore, it was proposed that the scientific community needed to express recommendations on the human use of resveratrol. Such recommendations were formulated after the first international resveratrol conference in Denmark, Resveratrol2010. The working group stated that the evidence was 'not sufficiently strong to justify recommendation for the chronic administration of resveratrol to human beings, beyond the dose which can be obtained from dietary sources.' It was a disappointing conclusion relative to the positive claims about the therapeutic potential of resveratrol made by the media. However, since 2010, results from the first clinical trials on resveratrol have been made available. Because of these emerging results, it is necessary to formulate updated versions of the recommendations. [ABSTRACT FROM AUTHOR]

Thymosin β4 (Tβ4) is a peptide known for its abilities to protect and facilitate regeneration in a number of tissues following injury. Its cardioprotective effects have been evaluated in different animal models and, currently, a clinical trial is being planned in patients suffering from acute myocardial infarction. This paper focuses on the effects of Tβ4 on cardiac function in animal studies utilizing different imaging modalities for outcome measurements. [ABSTRACT FROM AUTHOR]

The antibiotic telithromycin (Ketek, Sanofi-aventis) had two of three treatment indications withdrawn after postmarketing reports of serious and fatal adverse events. The rationale for the withdrawal of specific indications (acute bacterial sinusitis and acute exacerbations of chronic bronchitis), while permitting the drug to remain available for the treatment of community-acquired pneumonia, focused on the lack of demonstrated efficacy from clinical trials that included an active control to which the investigational drug, telethromycin, was determined to be statistically noninferior. This action regarding telithromycin represents a reversal of previous FDA guidelines for the conduct of clinical trials for antibacterial treatment indications and has increased the regulatory risk for future drug development. New clinical trial guidelines have been published that will increase the time and resources required to achieve regulatory marketing approval. This paper reviews recent regulatory actions and discusses the impact these new guidelines will have on future antibacterial clinical trial designs and challenges. [ABSTRACT FROM AUTHOR]

Rotavirus gastroenteritis (RVGE) is the leading cause of severe diarrhea in children worldwide. This paper provides an overview of the development, clinical evaluation, and postlicensure impact of RotaTeq™(Rotavirus Vaccine, Live, Oral, Pentavalent, Merck & Co., Inc.). RotaTeq, an oral vaccine, is uniquely designed to contain five human-bovine reassortant rotavirus strains expressing the human serotypes G1, G2, G3, G4, and P1A[8], which represent the most common human rotavirus serotypes responsible for ∼85% of RVGE worldwide. The development required novel solutions for manufacturing, testing, and formulation for each of the reassortants. In one of the largest vaccine clinical trials conducted, the vaccine was shown to be well tolerated and highly efficacious against severe RVGE. Efficacy has also been demonstrated in lower-income countries. In large U.S. postlicensure studies, there have been no safety signals identified, and RotaTeq has had a significant impact on reducing RVGE and its associated medical costs since licensure in 2006. [ABSTRACT FROM AUTHOR]

Effective gene therapy for hemoglobinopathies will require high numbers of autologous gene-engineered hematopoetic stem cells to be reintroduced into the patients. Stem cell mobilization using G-CSF is the most convenient and effective approach to achieve this goal, but it can have severe side effects in sickle cell anemia and be potentially harmful in the case of severe thalassemia. Hence, the optimal way of collection of hematopoetic stem cells from patients with thalassemia and sickle cell disease needs to be determined. In this paper, we review the possible risks of G-CSF mobilization in hemoglobinopathies and we outline the approaches used in an on-going clinical trial in which pretreatment with hydroxyurea is used to reduce potential risks of G-CSF administration to patients with severe beta thalassemia. [ABSTRACT FROM AUTHOR]

Studies in various animal models of disease and repair with thymosin β4 (Tβ4), the major actin-sequestering molecule in mammalian cells, have provided the scientific foundation for the ongoing dermal, corneal, and cardiac wound repair multicenter clinical trials. Tβ4 has of multiple biological activities, which include down-regulation of inflammatory chemokines and cytokines, and promotion of cell migration, blood vessel formation, cell survival, and stem cell maturation. All of these activities contribute to the multiple wound healing properties that have been observed in animal studies. This paper reviews and discusses the topical and systemic uses of Tβ4 in various animal models that demonstrate its potential for clinical use. [ABSTRACT FROM AUTHOR]

This paper reviews worldwide efforts to interdict the type 1 diabetes (T1D) disease process, during the stage of evolution of the disease prior to the time of disease onset. The goal of intervention before disease onset is to arrest immune destruction and thus prevent or delay clinical disease. In this regard, there have been several large-scale multicenter randomized controlled clinical trials designed to prevent T1D. These have tested nicotinamide, parenteral insulin, oral insulin, nasal insulin, and the elimination of cow's milk from infant feeding. [ABSTRACT FROM AUTHOR]

Breast conservation by wide local excision for early breast cancer is now considered safe and should be considered default therapy wherever possible. Unfortunately, this requires access to costly radiotherapy centers. Many women in the developing world or for that matter in wealthy countries with large land masses and small populations do not have access to radiotherapy and are therefore denied the option of breast-conserving surgery. Whole-breast radiation by external beam after tumorectomy is predicated on the belief that latent foci of subclinical cancer outside the index quadrant are responsible for local recurrence. We do not think this is the case, as over 90% of these recurrences occur in the index quadrant. In this paper we describe a novel system for intra-operative radiotherapy using a mobile unit that should, in theory, be able to replace 6 weeks of external beam from a linear accelerator. The technique, TARGIT, is currently undergoing a multinational clinical trial in comparison with conventional external beam. If we can prove at least equivalence in outcome, then breast-conserving surgery might become available to all women in the developing world and to those living long distances from the nearest radiotherapy center. [ABSTRACT FROM AUTHOR]

Acquired myasthenia gravis (MG) is an autoimmune disorder treated with cholinesterase inhibitors and a number of immunotherapies. Intravenous immunoglobulin (IVIG) is an expensive and commonly used immunotherapy for patients with an exacerbation of MG, but its effectiveness has only recently been demonstrated in a randomized clinical trial. This paper describes the study design, results, and limitations of a double-blind, randomized, placebo-controlled trial designed to definitively determine if IVIG benefits patients with MG who present with worsening weakness. Fifty-one patients with worsening weakness due to MG were randomized to receive either 2 g/kg of IVIG over 2 days or an equivalent volume of placebo (5% dextrose in water). The Quantitative MG Score (QMG Score) for Disease Severity, a validated clinical composite scale and the primary outcome measure in the study, was calculated by a masked observer 14 and 28 days after treatment. Patients treated with IVIG demonstrated a significant improvement in QMG Score for Disease Severity at day 14 and the response persisted at day 28. The largest clinical improvement occurred in patients with more severe disease. IVIG was well tolerated with no significant side effects observed. Given the observed efficacy and safety of IVIG demonstrated in this trial, future studies are necessary to determine if there is a role for interval IVIG treatments in chronic MG. [ABSTRACT FROM AUTHOR]

The potential of a transdisciplinary research method—Quali-Quantitative Analysis (QQA)—for delivering better evidence for healthy aging is explored. Illustrative reviews from the literature on healthy aging are summarized, as are papers on methodology by Charles Ragin and colleagues. The evidence needs for healthy aging are explored, particularly in relation to the ability of randomized controlled trials (RCTs) to deliver rich, diversity-oriented evidence. The techniques of QQA, which involves treating cases as configurations, are described. The QQA method has potential value for healthy aging research in that: ( a) it could provide evidence in combinatorial forms useful to holistic practice; ( b) it could enrich the evidence for practice by providing more rigorous information from small- N groups, within RCTs and where RCTs cannot be used; and ( c) it could add to the ability of RCTs to generate theoretical advances. [ABSTRACT FROM AUTHOR]

There has been an upsurge of multidisciplinary research since the adoption of a standardized definition of osteonecrosis of the jaw (ONJ) and the first bisphosphenate-related ONJ conference in 2007 held at the New York Academy of Sciences. This series of papers revisits topics presented at the conference in addition to covering recent advances in the history, mechanisms, clinical management, and prevention of bisphosphonate-related ONJ. [ABSTRACT FROM AUTHOR]