Area covered: In this article, current strategies including pharmacological and nonpharmacological approaches for improving the diseased host milieu are reviewed. Specifically, the authors provide focus on: i) the mechanism of ED in patients with cardiovascular diseases, ii) the current results of ED improving strategies in pre-clinical and clinical studies, and iii) the use of biomaterials as a novel modulator in damaged post-MI environment.
Expert opinion: Adjunct therapies which improve host endothelial function have demonstrated promising outcomes, potentially overcoming disappointing results of cell therapy in human studies. In the future, elucidation of the interactions between the host tissue and therapeutic agents, as well as downstream signaling pathways, will be the next challenges in enhancing regenerative therapy. More careful investigations are also required to establish these agents’ safety and efficacy for wide usage in humans. 相似文献
Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans.
Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics. 相似文献
Areas covered: In this review, the authors summarize the clinical results achieved with two specific strategies in hematological malignancies: chimeric antigen receptor (CAR) and T cell receptor (transgenic TCR) redirected T cells. Moreover, they discuss the recent pre-clinical studies aimed at increasing the feasibility, safety and efficacy of ACT.
Expert opinion: ACT can promote cancer regression in patients with leukemia, lymphoma and multiple myeloma. Nevertheless, more precise targeting of tumor cells and containment of side effects are needed. Overcoming tumor-associated immunosuppressive mechanisms and preventing tumor escape are also emerging as critical barriers. Finally, simplification in the manufacturing procedures should promote wider application of these technologies outside academic centers. Although the enthusiasm for ACT-based therapies is high, comprehensive and systematic clinical studies are required to advance the field. 相似文献
Objectives: To examine the effect of external application in pain compared to traditional method.
Design: A double-blind placebo-controlled clinical investigation.
Setting: A public hospital.
Participants: 168 LBP subjects.
Interventions: Assignment: (1) external IFT, (2) placebo external IFT, (3) traditional IFT and (4) placebo traditional IFT. Groups 1 and 3 received 20 min of IFT at 100 Hz and groups 2 and 4 received sham IFT.
Main outcome measures: Before and after IFT session, pain severity (VAS), pressure threshold (PPT), pain distribution and ROM were assessed.
Results: IFT changed all outcomes similarly. VAS and ROM improved statistically, P < 0.03. A trend of better VAS reduced with active IFTs.
Conclusions: No therapeutic difference between the two methods. 相似文献
Areas covered: This review discusses the epidemiology of CLI, revascularization options, and drug-elution therapies.
Expert commentary: Drug-eluting stents (DES) and drug-coated balloons (DCB) improve patency rates in the femoropopliteal segment, and are generally used as first-line therapies. For below-knee disease, angioplasty is the default strategy unless lesions are focal whereby DES can be used to reduce restenosis risk. 相似文献
Objective: This systematic review aimed to synthesize and interpret the findings of qualitative studies designed to examine factors that are inherent in physical therapists’ clinical reasoning with respect to their knowledge, experiences, and practices.
Methods: Searches of studies were carried out in four databases, gray literature, and reference lists. Two reviewers independently assessed methodological quality of the studies using the Critical Appraisal Skills Program (CASP) and performed the analysis: extraction and comparative appraisal of findings, identification of themes, reciprocal translation synthesis, and identification of categories and subcategories.
Results: Ten studies were included. Four themes of factors influencing physical therapists’ clinical reasoning emerged, namely, Physical therapist as a source, Patient as a source, Elements of the reasoning process, and Context.
Conclusions: The identified themes validated some constructs underlying existing clinical reasoning frameworks. Most influencing factors were related to the physical therapist, which highlights opportunities to improve effective reasoning at this level. The notion that this process is recurrent, multifaceted, and contextual lends itself to changing in accordance with the needs of the patient, consistent with a biopsychosocial perspective. How clinicians weigh biomedical and psychosocial elements in their reasoning however warrants further study. 相似文献
Areas covered: Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy.
Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns. 相似文献
Areas covered: Key metabolic features of stem cells are reviewed and unique stem cell metabolic characteristics are discussed. Metabolic changes altering stem cell fate are considered from quiescence and self-renewal to lineage commitment. Key metabolic concepts are applied toward examining cardiac regeneration through stem cell-based approaches, and clinical implications of current cell therapies are evaluated to identify potential areas of improvement.
Expert commentary: The metabolism and biology of stem cells used for cardiac therapy remain poorly characterized. A growing appreciation for the fundamental relationship between stem cell functionality and metabolic phenotype is developing. Future studies unraveling links between cardiac stem cell metabolism and regenerative potential may considerably improve treatment strategies and therapeutic outcomes. 相似文献
Areas covered: Composition, in vitro and in vivo differentiation of hUCB cells, and the advantages of cord blood as a source of transplant cells are discussed. A brief history of hUCB in treatment of an ALS animal model and the feasibility of these cells in therapy for ALS patients is provided. Current ALS clinical trials are also deliberated.
Expert opinion: Among multiple advantages, hUCB cells’ production of various anti-inflammatory/growth/trophic factors makes them an attractive cell source for ALS therapy. Biodistribution and optimal hUCB cell dose for transplantation have been determined in preclinical studies. Repeated intravenous cell doses during disease progression may be the best approach for cell-based ALS treatment. Accumulated evidence shows the efficacy of naïve or genetically modified MNC hUCB cells in the treatment of ALS and provide a superior basis for the development of clinical trials in the near future. 相似文献
Areas covered: In this review, we specifically focus on biology and imaging markers. We detail the innovative field of ‘omics’ approach and imaging and explain their limits to be useful in routine practice. We describe the most relevant biomarkers and suggest some perspectives for biomarker research.
Expert commentary: The successive failures of clinical trials in ALS underline the need for new strategy based on innovative tools to stratify patients and to evaluate their responses to treatment. Biomarker data may be useful to improve the designs of clinical trials. Biomarkers are also needed to better investigate disease pathophysiology, to identify new therapeutic targets, and to improve the performance of clinical assessments for diagnosis and prognosis in the clinical setting. A consensus on the best management of neuroimaging and ‘omics’ methods is necessary and a systematic independent validation of findings may add robustness to future studies. 相似文献
Objective: The purpose of this review was to address two questions: (1) is there a difference in clinical outcomes between different exercise programmes; and (2) what is the optimal dosage of exercises for people with knee osteoarthritis.
Methods: A systematic review was conducted. A study of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, and the Cochrane Library) and unpublished literature (WHO International Clinical Trials Registry Platform, current controlled trials and the United States National Institute of Health Trials Registry, and Open Grey) was undertaken in January 2013. Studies assessing the clinical outcomes of different types and dosages of exercise for people with osteoarthritis of the knee were included. Methodological quality was assessed using the critical appraisal skills programme (CASP) randomized controlled trial (RCT) appraisal tool.
Results: Ten studies assessing 958 knees from 916 participants were included. Exercise significantly improved pain and function for people with knee osteoarthritis. There was no significant difference in outcomes for different types of exercise i.e., aerobic versus resistance, weight bearing versus non-weight bearing. There was no significant difference in respect to the intensity of exercise i.e., high- versus lower-intensity resistance or aerobic exercises. The quality of the literature was moderate to high.
Conclusions: While exercise appears to improve symptoms and optimize function for people with knee osteoarthritis, the optimal form and dosage of exercise remains unknown.
Funding: None.
PROSPERO Registration Number: CRD42012002811. 相似文献
Objectives: The review presents in a series of questions-answers and under a clinical point of view the current data regarding the use of osmolal gap.
Discussion: The definition and the best formula used for the calculation of osmolal gap, the main causes of increased osmolal gap with or without increased anion gap metabolic acidosis, as well as the role of concurrent lactic acidosis or ketoacidosis are presented under a clinical point of view.
Conclusions: The calculation of osmolal gap is crucial in the differential diagnosis of many patients presenting in emergency departments with possible drug or substance overdose as well as in comatose hospitalized patients. 相似文献
Areas covered: This review focuses on cell-based LSCD treatment approaches ranging from current available clinical therapies to preclinical studies of novel promising applications.
Expert opinion: Improved understanding of LSC identity and development of LSC expansion methods will influence the evolution of successful LSCD therapies. Ultimately, future controlled clinical studies enabling direct comparison of the diverse employed approaches will help to identify the most effective treatment strategies. 相似文献
Objective: To examine the associations between patients’ self-rated health and their sleep problems, somatic health complaints, and unmet needs in interpersonal relationships.
Design: We collected data via questionnaires for this cross-sectional study from general practice.
Setting: Primary health care in Norway.
Subjects: 1302 consecutive patients participated.
Main outcome measures: The questionnaire included a single question about SRH, the Bergen Insomnia Scale (BIS), five questions on somatic health complaints, and three questions from the Basic Psychological Needs Scale (BPNS) pertaining to the relationships domain. We analyzed our data using ordinal logistic regression models.
Results: Our response rate was 74%. The prevalence of fair/poor SRH was 26%, with no gender differences. We revealed a significant association between increasing age and reduced SRH. The study showed that sleep problems and somatic health complaints were strongly associated with SRH, and unmet needs in relationships were also significantly and independently associated with reduced SRH in a full model analysis.
Conclusion: Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH. These factors are all modifiable and could be managed both within and outside a primary care setting in order to improve SRH.
- Key Points
There was a high prevalence of reduced SRH in clinical general practice
Sleep problems, somatic health complaints, and unmet needs in interpersonal relationships were all associated with reduced SRH
These predictors are all modifiable with a potential to improve SRH
Areas covered: In this review, the authors summarize the most relevant knowledge related to TILs. This includes their prognostic and predictive significance in various types of tumour and the recent findings about their potential role in the cancer immunotherapy.
Expert opinion: TILs evaluation could lead to a predictive biomarker for immunotherapy effectiveness in several cancer types. Furthermore, typing of TILs subpopulation could have clinical relevance in patient selection for treatment with immune checkpoint inhibitors. However further studies are still needed. 相似文献
Design: A RAND/UCLA Appropriateness Method was used.
Setting: General practice.
Subjects: A panel of nine experts, mainly general practitioners, was asked to rate the relevance of 64 quality indicators for the diagnosis and antibiotic treatment of acute respiratory tract infections based on guidelines. Subsequently, a face-to-face meeting was held to resolve misinterpretations and to achieve consensus.
Main outcome measures: The experts were asked to rate the indicators on a nine-point Likert scale. Consensus of appropriateness for a quality indicator was reached if the overall panel median rating was 7–9 with agreement.
Results: A total of 50 of the 64 proposed quality indicators attained consensus. Consensus was achieved for 12 indicators focusing on the diagnostic process and 19 indicators focusing on the decision about antibiotic treatment and choice of antibiotics, respectively.
Conclusion: These newly developed quality indicators may be used to strengthen Danish general practitioners’ focus on their management of patients with acute respiratory tract infections and to identify where there is a need for future quality improvements. 相似文献
Design: An observational study.
Setting: Register-based retrospective quasi-experimental longitudinal follow-up study based on a before–after setting in a Finnish city.
Subjects: Patients who consulted different doctors in a local health care unit.
Main outcome measures: Numbers of monthly visits to different doctor groups in public and private primary care, and numbers of monthly referrals to secondary care ED from different sources of primary care were recorded before and after abrupt implementation of the reverse triage.
Results: The beginning of reverse triage decreased the number of patient visits to a primary ED doctor without increasing mortality. Simultaneously, there was an increase in doctor visits in the adjacent secondary care ED and local private sector. The number of patients who came to secondary care ED without a referral or with a referral from the private sector increased.
Conclusions: The data suggested that the reverse triage causes redistribution of the use of doctors’ services rather than a true decrease in the use of these services. 相似文献