Area covered: This review highlights the results of recent clinical studies of single or combination checkpoint inhibitor immunotherapy in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). The authors discuss pembrolizumab and pembrolizumab plus ipilimumab, durvalumab and durvalumab plus tremelimumab, nivolumab and nivolumab plus ipilimumab for NSCLC as well as nivolumab and nivolumab plus ipilimumab for SCLC.
Expert opinion: Available data suggest that, in both metastatic NSCLC and SCLC, combined PD-1 and CTLA-4 blockade may produce a higher tumor response rate than PD-1 blockade alone. Nevertheless, combination therapy is associated with an increased toxicity. Several larger-scale studies are currently ongoing. For checkpoint inhibitor immunotherapy in SCLC and NSCLC, combination therapy is associated with a higher incidence of toxicities than single therapy; however, it appears to help increase tumor response rate. The increased response rate, if confirmed in larger scale studies, will likely make combination therapy another useful therapeutic approach for lung cancer. 相似文献
Areas covered: The pharmacodynamics and pharmacokinetics of nivolumab and ipilimumab are reviewed. Clinical safety and efficacy results from pivotal phase I and III trials of the combination of nivolumab plus ipilimumab in mRCC are summarized, and the combination is reviewed in the context of other available systemic therapies for RCC. Ongoing clinical studies involving the combination of nivolumab plus ipilimumab in RCC are discussed.
Expert opinion: The combination of nivolumab and ipilimumab has demonstrated superior efficacy for treatment-naïve patients with intermediate- and poor-risk mRCC with clear cell histology and is likely to replace anti-angiogenic therapies as the treatment-of-choice in this patient population in the United States. Development of additional combination strategies, novel trial designs, and predictive biomarkers of response will be important to further optimize therapeutic selection and clinical outcomes. 相似文献
Areas covered: The authors review the preclinical and clinical data supporting nivolumab employment in mRCC. Discussion of the underlying mechanisms of immunotherapy, data on objective responses, safety and tolerability, regulatory affairs, and future directions of nivolumab therapy are highlighted.
Expert opinion: Nivolumab serves as a proof-of-principle of the efficacy of immunotherapy with checkpoint inhibition in mRCC. Nivolumab may be considered the leading monotherapy in the second-line setting for patients with low tumor volume considering its risks and benefits. Nivolumab was recently approved in the first-line setting as part of combination therapy with another immune modulator. Moreover, nivolumab use may offer clinicians the option for treatment beyond progression as emerging data has indicated possible overall survival benefits in this setting. Ongoing clinical studies may result in nivolumab use in the first-line setting, as monotherapy or in combination therapy with antiangiogenesis agents. 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 covers recent clinical data on systemic agents and ongoing trials in patients with advanced HCC focusing on immunotherapy.
Expert opinion: In unselected patients with advanced HCC immunotherapeutics, namely the programmed cell death-1 (PD-1) antibodies, nivolumab and pembrolizumab have shown promising efficacy in therapy-naïve, as well as pre-treated patients with advanced HCC. However, only 10–20 percent of treated patients show an objective and durable response to the indicated therapeutics. Therefore, combination therapies including different immunotherapeutics, e.g. PD-1/programmed cell death 1 ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies, or combinations of immunotherapeutics and small molecules, or bifunctional antibodies will be needed to improve response rates.
Abbreviations: HCC: hepatocellular carcinoma; TKI: tyrosine-kinase inhibitors; PD-1: programmed death receptor-1; PD-L1: programmed cell death 1 ligand 1; CTLA-4: cytotoxic T-lymphocyte-associated Protein 4; CAR-T: chimeric T cell receptors; TACE: transarterial chemoembolization; SIRT: selective internal radiation therapy; SBRT: stereotactic body radiation therapy; VEGF: vascular endothelial growth factor; MEK: mitogen-activated protein kinase kinase; NK cell: natural killer cell; TGFβ: transforming growth factor-β; OV: Oncolytic viruses; PFU: plaque-forming unit 相似文献
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: 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
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
Areas covered: This review provides an overview and the status of immunotherapy in EC. Clinical significance of molecules related immune checkpoints, especially PD-1 and PD-L1 is presented and the designs, results and future directions of clinical trials using immunotherapy in EC are provided.
Expert opinion: To bring immunotherapy to the forefront of treatment for EC, it is necessary to select patients who can obtain a high efficacy of immunotherapy and to also elucidate the correct timing for administration. Moreover, combination therapies of immunotherapy with existing chemotherapy or radiation or other immunotherapy with different mechanisms of action must be evaluated to achieve excellent outcomes in patients with EC. 相似文献
Objectives: To review age-related changes in pharmacokinetics and pharmacodynamics, and to put these changes in the context of providing palliative care to geriatric patients.
Method: Review of literature relevant to age-related changes in physiology, pharmacokinetics, and pharmacodynamics; and the practice of palliative care for geriatric patients.
Results: Multiple age related changes occur which affect the choice and dosing of medications, including those used for pain and symptom management.
Conclusion: The safe and effective management of symptoms in advanced illness for older adults depends on having a clear understanding of physical and metabolic changes and their impact of selection of drug therapy. 相似文献
Areas covered: This is a comprehensive review of the literature on the role of pembrolizumab in melanoma. Pembrolizumab is a Programmed Death Receptor 1 (PD-1) directed monoclonal antibody which is approved by FDA and EMA for the treatment of patients with metastatic melanoma.
Expert opinion: Phase II and III trials demonstrated that pembrolizumab is superior to ipilimumab in previously untreated patients and to chemotherapy in ipilimumab pre-treated patients. Unfortunately, prospectively validated predictive markers are lacking. Immune-related adverse events are particularly interesting and should be managed per the published guidelines. There are still many issues that remain unresolved including: when to stop treatment, biomarkers for choosing a single agent or combination therapy, the optimal schedule of ipilimumab in combination with anti-PD1 monoclonal antibodies, optimal management of adverse events, the role of immunotherapy in specific populations, the optimal sequence of immunotherapy and the BRAF/MEK inhibitor combination in patients. 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: To date, the efficacy and toxicity of immune checkpoint inhibitors in the elderly is unclear because available studies involved mainly a low number of elderly patients. In this paper, the authors discuss the frailty of the elderly patient and the challenges of choosing the best therapeutic strategy, focusing on the role of immune checkpoint inhibitors.
Expert opinion: There are several outstanding goals that need to be met for the proper and safe use of immunotherapeutic drugs. In terms of the elderly, it is true that age-tailored clinical trials are needed to confirm the real impact of immunotherapy and harmonize the standard of care in this specific demographic. 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
Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences. Ongoing clinical trials were also reviewed.
Expert opinion: Early phase trials of durvalumab monotherapy (and in combination) have demonstrated activity in advanced NSCLC patients and it has demonstrated a good safety profile. The authors believe that durvalumab will likely play an important role in future treatment strategies for NSCLC. The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care. 相似文献
Design: A qualitative interview study using thematic analysis.
Setting: Norway.
Participants: Fifteen Thai and 15 Filipino immigrant women over the age of 18 who had been living in Norway at least one year.
Results: The women took time to understand the role of the general practitioner and some were unaware of their right to an interpreter during consultations. In addition to reliance on family members and friends in their social networks, voluntary and cultural organisations provided valuable tips and advice on how to navigate the Norwegian health system. While some women actively engaged in learning more about the system, they noted a lack of information available in multiple languages.
Conclusions: Informal sources play an important role in learning about the health care system. Formal information should be available in different languages in order to better empower immigrant women. 相似文献
Purpose: We describe a series of thirteen cases of suspected cannabis hyperemesis syndrome treated with capsaicin in the emergency departments of two academic medical centers.
Methods: A query of the electronic health record at both centers identified thirteen patients with documented daily cannabis use and symptoms consistent with CHS who were administered topical capsaicin cream for symptom management.
Results: All 13 patients experienced symptom relief after administration of capsaicin cream.
Conclusion: Topical capsaicin was associated with improvement in symptoms of CHS after other treatments failed. 相似文献
The effective management of lateral canal benign paroxysmal positional vertigo (LC-BPPV) is dependent upon the accurate identification of the affected ear. The supine roll test is the gold standard for diagnosing LC-BPPV. However, in some cases, the elicited nystagmus has a similar intensity when the head is rolled to the right or to the left.
Objectives:
The purpose of this systematic review was to determine the effectiveness of accessory diagnostic procedures, used in conjunction with the supine roll test, at accurately identifying the affected ear in individuals with LC-BPPV.
Methods:
The following databases were searched: (1) CINAHL Plus with Full Text, (2) ProQuest Medical Library, and (3) MEDLINE. The following search terms were used: (1) ‘lateral canal’ OR ‘horizontal canal’ AND (2) ‘positional vertigo’ OR ‘positioning vertigo’ OR ‘positional nystagmus’ OR ‘positioning nystagmus’. Evidence level was examined with the Oxford Centre for Evidence-Based Medicine 2011 levels of evidence method, and methodological rigour was examined with the QUADAS method.
Results:
A database search originally identified 1348 records, and nine studies were ultimately included in the qualitative synthesis. This systematic review revealed four index tests that, when used in conjunction with the supine roll test, were able to accurately identify the affected ear in a majority of individuals with LC-BPPV.
Conclusions:
The pseudo-spontaneous test was found to be slightly superior to the other three index tests in terms of eliciting nystagmus during its administration and identifying the same affected ear as the supine roll test. 相似文献
Yoga is a popular complementary and alternative medicine (CAM) therapy among people with rheumatoid arthritis (RA), perceived as offering self-management options for physical and psychosocial symptoms associated with RA.
Objectives:
The primary aims of the current pilot study are (1) to assess the feasibility and safety of a relaxation-focused yoga intervention tailored for people with RA and (2) to estimate the effect of yoga on RA-related pain, sleep quality, functional disability, disease activity, quality of life, anxiety, depression, and fatigue.
Method:
Twenty-eight participants with at least minimum levels of RA-related pain and sleep disturbance will be recruited from a local public hospital database. Participants meeting inclusion criteria will be randomized into either a yoga group (receiving an 8-week program of once-weekly 75-minute relaxation-based yoga classes and thrice-weekly home practice), or a usual care control group. Outcomes will be assessed at baseline, 9, and 12 weeks. Feasibility is operationalized as acceptability (recruitment, adherence, participant retention, and participant satisfaction) and safety of the yoga intervention. Effect sizes for changes in pain, sleep quality, functional disability, disease activity, quality of life, mental health, and fatigue will be estimated.
Discussion:
Results of this pilot study will provide empirical data to determine if a larger, statistically powered main trial is feasible and safe in a national RA population. Additionally, participant feedback will provide information regarding further adaption and tailoring of the study protocol to a clinical RA population.
Trial registration:
Australian New Zealand Clinical Trials Registry ACTRN12612001019897 (registered 20/09/2012). 相似文献