Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. CONCLUSIONS: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.

Comparison of multimedia and printed patient education tools for patients with osteoporosis: a 6-month randomized controlled trial.

We conducted a randomized controlled trial to compare the efficacy of adding a video tool to a printed booklet on osteoporosis. Both strategies were effective in increasing knowledge and decreasing decisional conflict. There was no difference in the measured outcomes between the intervention and control groups. Patient preferences and learning styles are key factors in deciding a presentation format when educating patients with osteoporosis. INTRODUCTION: Innovative approaches to patient education about self-management in osteoporosis may improve outcomes. METHODS: We conducted a randomized controlled trial to compare the efficacy of adding a multimedia patient education tool involving video modeling to a printed educational booklet on osteoporosis. Participants were post-menopausal women with osteoporosis. We assessed osteoporosis knowledge, decisional conflict, self-efficacy, and effectiveness in disease management at baseline, immediately post-intervention, and at 3 and 6 months. Linear regression models were used to explore changes in outcomes at 6 months with respect to baseline characteristics. RESULTS: Two hundred and twenty-five women were randomized, 111 to receive the multimedia tool in addition to the booklet and 114 to receive the booklet alone. Knowledge and decisional conflict scores significantly improved in both groups at all post-intervention assessment points, but with no significant differences in score changes between the groups. Self-efficacy and disease management effectiveness showed no significant changes from baseline. In the entire cohort, younger age was associated with better effectiveness in disease management and Hispanic women had greater gains in knowledge at 6 months compared to White women. Women with limited health literacy who had received the multimedia tool in addition to the printed materials had higher decisional conflict than those who received printed materials alone. CONCLUSION: Both multimedia and printed tools increased knowledge and decreased decisional conflict to the same extent, neither of the educational materials proved to be better than the other. For women with limited health literacy, receiving the booklet alone was more effective in reducing decisional conflict after 6 months, than adding the multimedia tool.

Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis.

Objective The objective of this paper is to conduct a systematic review and meta-analysis on the risk of developing elevated antiphospholipid (aPL) antibodies and related thromboembolic and/or pregnancy events following a viral infection. Method We searched Medline, EMBASE, Web of Science, PubMed ePubs, and Cochrane Central Register of Controlled Trials through June 2016. Independent observational studies of elevated aPL antibodies in patients with a viral infection compared with controls or patients with lupus were included. Results We analyzed 73 publications for 60 studies. Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) were most commonly reported. Compared with healthy controls, patients with HIV were more likely to develop elevated anticardiolipin (aCL) antibodies (risk ratio (RR) 10.5, 95% confidence interval (CI) 5.6-19.4), as were those with HCV (RR 6.3, 95% CI 3.9-10.1), hepatitis B virus (HBV) (RR 4.2, 95% CI 1.8-9.5), and Epstein-Barr virus (EBV) (RR 10.9 95% CI 5.4-22.2). The only statistically significant increased risk for anti-ß2-glycoprotein I (anti-ß2-GPI) antibodies was observed in patients with HCV (RR 4.8 95% CI 1.0-22.3). Compared with patients with lupus, patients with HIV were more likely to develop elevated aCL antibodies (RR 1.8, 95% CI 1.3-2.6), and those with EBV, elevated anti-ß2-GPI antibodies (RR 2.2, 95% CI 1.3-3.9). Thromboembolic events were most prevalent in patients with elevated aPL antibodies who had HCV (9.1%, 95% CI 3.0-18.1), and HBV (5.9%, 95% CI 2.0-11.9) infections, and pregnancy events were most prevalent in those with parvovirus B19 (16.3%, 95% CI 0.78-45.7). However, compared to virus-infected patients with negative aPL antibodies, the only statistically significant increased risk was observed in those with HCV and positive aPL. Conclusions Viral infection can increase the risk of developing elevated aPL antibodies and associated thromboembolic events. Results are contingent on the reported information.

Effect of beta-blockers on cancer recurrence and survival: a meta-analysis of epidemiological and perioperative studies.

BACKGROUND: The biological perturbation associated with psychological and surgical stress is implicated in cancer recurrence. Preclinical evidence suggests that beta-blockers can be protective against cancer progression. We undertook a meta-analysis of epidemiological and perioperative clinical studies to investigate the association between beta-blocker use and cancer recurrence (CR), disease-free survival (DFS), and overall survival (OS). METHODS: Databases were searched until September 2017, reported hazard ratios (HRs) pooled, and 95% confidence intervals (CIs) calculated. Comparative studies examining the effect of beta-blockers (selective and non-selective) on cancer outcomes were included. The Newcastle Ottawa Scale was used to assess methodological quality and bias. RESULTS: Of the 27 included studies, nine evaluated the incidental use of non-selective beta-blockers, and ten were perioperative studies. Beta-blocker use had no effect on CR. Within subgroups of cancer, melanoma was associated with improved DFS (HR 0.03, 95% CI 0.01-0.17) and OS (HR 0.04, 95% CI 0.00-0.38), while endometrial cancer had an associated reduction in DFS (HR 1.40, 95% CI 1.10-1.80) and OS (HR 1.50, 95% CI 1.12-2.00). There was also reduced OS seen with head and neck and prostate cancer. Non-selective beta-blocker use was associated with improved DFS and OS in ovarian cancer, improved DFS in melanoma, but reduced OS in lung cancer. Perioperative studies showed similar variable effects across cancer types, albeit from a limited data pool. CONCLUSION: Beta-blocker use had no evident effect on CR. The beneficial effect of beta-blockers on DFS and OS in the epidemiological or perioperative setting remains variable, tumour-specific, and of low-level evidence at present.

Do Spanish Medical Students Understand the Concept of Brain Death?

OBJECTIVE: To analyze the level of understanding of the brain death concept among medical students in universities in Spain. METHODS: This cross-sectional sociological, interdisciplinary, and multicenter study was performed on 9598 medical students in Spain. The sample was stratified by geographical area and academic year. A previously validated self-reported measure of brain death knowledge (questionnaire Proyecto Colaborativo Internacional Donante sobre la Donación y Transplante de Organos) was completed anonymously by students. RESULTS: Respondents completed 9275 surveys for a completion rate of 95.7%. Of those, 67% (n = 6190) of the respondents understood the brain death concept. Of the rest, 28% (n = 2652) did not know what it meant, and the remaining 5% (n = 433) believed that it did not mean that the patient was dead. The variables related to a correct understanding of the concept were: (1) being older ( P < .001), (2) studying at a public university ( P < .001), (3) year of medical school ( P < .001), (4) studying at one of the universities in the south of Spain ( P = .003), (5) having discussed donation and transplantation with the family ( P < .001), (6) having spoken to friends about the matter ( P < .001), (7) a partner's favorable attitude toward donation and transplantation ( P < .001), and (8) religious beliefs ( P < .001). CONCLUSIONS: Sixty-seven percent of medical students know the concept of brain death, and knowledge improved as they advanced in their degree.

A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer.

BACKGROUND: Eribulin is a microtubule dynamics inhibitor with a novel mechanism of action. This phase 3 study aimed to compare overall survival (OS) in patients with heavily pretreated non-small cell lung cancer (NSCLC) receiving eribulin to treatment of physician's choice (TPC). PATIENTS AND METHODS: Patients with advanced NSCLC who had received ≥2 prior therapies, including platinum-based doublet and epidermal growth factor receptor tyrosine kinase inhibitor, were randomly assigned to receive eribulin or TPC (gemcitabine, pemetrexed, vinorelbine, docetaxel). The primary endpoint was OS. Secondary endpoints were progression-free survival and objective response rate. RESULTS: Five hundred and forty patients were randomized to either eribulin (n = 270) or TPC (n = 270). Median OS for eribulin and TPC was the same: 9.5 months [hazard ratio (HR): 1.16; 95% confidence interval: 0.95-1.41; P = 0.13]. Progression-free survival for eribulin and TPC was 3.0 and 2.8 months, respectively (HR: 1.09; 95% confidence interval: 0.90-1.32; P = 0.39). The objective response rate was 12% for eribulin and 15% for TPC. Clinical benefit rate (eribulin, 57%; TPC, 55%) and disease control rate (eribulin, 63%; TPC, 58%) were similar between treatment arms. The most common adverse event was neutropenia, which occurred in 57% of eribulin patients and 49% of TPC patients at all grades. Other non-hematologic side-effects were manageable and similar in both groups except for peripheral sensory neuropathy (all grades; eribulin, 16%; TPC, 9%). CONCLUSION: This phase 3 study did not demonstrate superiority of eribulin over TPC with regard to overall survival. However, eribulin does show activity in the third-line setting for NSCLC. TRIAL REGISTRATION ID: www.ClinicalTrials.gov; NCT01454934.

Structural and functional 3D mapping of skin tumours with non-invasive multispectral optoacoustic tomography.

BACKGROUND: Recent advances in technology have enabled the development of various non-invasive skin imaging tools to aid real-time diagnosis of both benign and malignant skin tumours, minimizing the need for invasive skin biopsy. Multispectral optoacoustic tomography (MSOT) is a recently developed non-invasive imaging tool, which offers the unique capacity for high resolution three dimensional (3D) optical mapping of tissue by further delivering highly specific optical contrast from a depth of several millimetres to centimetres in living tissues. MSOT enables volumetric, spectroscopic differentiation of tissue, both in vivo and in real time, with and without the application of biomarker-specific probes, and is further able of providing spatial maps of skin chromophores, as well as underlying blood vasculature. METHODS: Three patients with suspicious skin tumours consented to have their lesions imaged with MSOT prior to excision. The histological findings and measurements were compared. RESULTS: We demonstrated the first in vivo clinical use of MSOT for 3D reconstruction of skin tumours in three patients with good histological correlation. CONCLUSION: Our findings confirm the potential benefit of the new imaging method in guiding surgical intervention to achieve a more precise excision with better clearance and lower relapse rates. It can also potentially help to shorten the duration of Mohs' micrographic surgery. Further large-scale studies are necessary to ensure correlation between MSOT and histology.

Systematic review of case reports of antiphospholipid syndrome following infection.

OBJECTIVE: The objective of this study was to conduct a systematic review of case reports documenting the development of antiphospholipid syndrome or antiphospholipid syndrome-related features after an infection. METHODS: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and The Cochrane Library - CENTRAL through March 2015 without restrictions. Studies reporting cases of antiphospholipid syndrome or antiphospholipid syndrome-related features following an infection were included. RESULTS: Two hundred and fifty-nine publications met inclusion criteria, reporting on 293 cases. Three different groups of patients were identified; group 1 included patients who fulfilled the criteria for definitive antiphospholipid syndrome (24.6%), group 2 included patients who developed transient antiphospholipid antibodies with thromboembolic phenomena (43.7%), and group 3 included patients who developed transient antiphospholipid antibodies without thromboembolic events (31.7%). The most common preceding infection was viral (55.6%). In cases that developed thromboembolic events Human immunodeficiency and Hepatitis C viruses were the most frequently reported. Parvovirus B19 was the most common in cases that developed antibodies without thromboembolic events. Hematological manifestations and peripheral thrombosis were the most common clinical manifestations. Positive anticardiolipin antibodies were the most frequent antibodies reported, primarily coexisting IgG and IgM isotypes. Few patients in groups 1 and 2 had persistent antiphospholipid antibodies for more than 6 months. Outcome was variable with some cases reporting persistent antiphospholipid syndrome features and others achieving complete resolution of clinical events. CONCLUSIONS: Development of antiphospholipid antibodies with all traditional manifestations of antiphospholipid syndrome were observed after variety of infections, most frequently after chronic viral infections with Human immunodeficiency and Hepatitis C. The causal relationship between infection and antiphospholipid syndrome cannot be established, but the possible contribution of various infections in the pathogenesis of antiphospholipid syndrome need further longitudinal and controlled studies to establish the incidence, and better quantify the risk and the outcomes of antiphospholipid-related events after infection.

Medical students faced with related and unrelated living kidney donation: a stratified and multicentre study in Spain.

INTRODUCTION: The attitude of medical students towards living kidney donation (LKD) is of great interest given that they will become promoters of this technique in the near future. OBJECTIVE: To analyse the attitude of Spanish medical students towards related and unrelated LKD and to determine the factors affecting this attitude. MATERIALS AND METHODS: Type of study: A sociological, interdisciplinary, multicentre, and observational study. STUDY POPULATION: Medical students enrolled in Spain (n = 34.000). SAMPLE SIZE: A sample of 9598 students (99 % confidence and precision of ±1 %), stratified by geographical area and academic year. Measurement instrument: A validated questionnaire (PCID-DVR RIOS) was administered and completed anonymously. RESULTS: There was a completion rate of 95.7 % (n = 9275); 93 % (n = 8630) were in favour of related LKD, and 30 % (n = 2784) were in favour of unrelated LKD. The following factors were associated with this attitude: (1) age (p = 0.008); (2) sex (p < 0.001); (3) year of university degree (p < 0.001); (4) a belief that a transplant might be necessary in the future (p < 0.001); (5) attitude towards deceased organ donation (p < 0.001); (6) a willingness to accept a kidney from a living donor (p < 0.001); (7) attitude towards living liver donation (p < 0.001); (8) a partner's attitude towards donation (p < 0.001); (9) having spoken about the subject with one's family (p < 0.001), or friends (p < 0.001); (10) pro-social behaviour (p < 0.001); (11) the respondent's religious attitude (p < 0.001); and (12) fear of possible mutilation of the body after donation (p < 0.001). CONCLUSIONS: The attitude of medical students towards LKD is very favourable when it is the related kind of donation, and it is associated with factors of general knowledge about organ donation and transplantation and social interaction and religion.

Point of care optical diagnostic technologies for the detection of oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: Despite significant advances in treatment modalities, the 5 year survival rate in oral and oropharyngeal squamous cell carcinoma (SCC) is less than 60%. Clinical examination, white light endoscopy followed by blind biopsies and histopathological analysis remains the gold standard for diagnosis and surveillance. These modalities continue to have a limited diagnostic accuracy of less than 55%. METHODS: Novel optical-based diagnostic methods are promising new technologies for improving both screening and detection of cancer. This review will discuss their role in oral and oropharyngeal cancer detection with particular emphasis on optical imaging in oral and oropharyngeal cancer diagnosis, including the use of surface enhanced Raman spectroscopy, optical coherence tomography, fluorescence diagnosis, confocal laser endomicroscopy, confocal reflectance microscopy and narrow band imaging. RESULTS: Aided by the use of differing wavelengths of light, these methods are capable of detecting physical and biochemical changes that precede and mirror malignant change within tissue. CONCLUSION: Our review of the currently utilized optical diagnostic modalities suggests the possibility of a cost effective, point of care diagnosis that could facilitate early detection, reduce healthcare costs and improve patient survival and quality of life.

Factors Associated With Obtaining Lung Cancer Screening Among Persons Who Smoke.

Background. Screening with low-dose computed tomography scans can reduce lung cancer deaths but uptake remains low. This study examines psychosocial factors associated with obtaining lung cancer screening (LCS) among individuals. Methods. This is a secondary analysis of a randomized clinical trial conducted with 13 state quitlines' clients. Participants who met age and smoking history criteria were enrolled and followed-up for 6 months. Only participants randomized to the intervention group (a patient decision aid) were included in this analysis. A logistic regression was performed to identify determinants of obtaining LCS 6 months after the intervention. Results. There were 204 participants included in this study. Regarding individual attitudes, high and moderate levels of concern about overdiagnosis were associated with a decreased likelihood of obtaining LCS compared with lower levels of concern (high levels of concern, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04-0.65; moderate levels of concern, OR 0.15, 95% CI 0.05-0.53). In contrast, higher levels of anticipated regret about not obtaining LCS and later being diagnosed with lung cancer were associated with an increased likelihood of being screened compared with lower levels of anticipated regret (OR 5.59, 95% CI 1.72-18.10). Other potential harms related to LCS were not significant. Limitations. Follow-up may not have been long enough for all individuals who wished to be screened to complete the scan. Additionally, participants may have been more health motivated due to recruitment via tobacco quitlines. Conclusions. Anticipated regret about not obtaining screening is associated with screening behavior, whereas concern about overdiagnosis is associated with decreased likelihood of LCS. Implications. Decision support research may benefit from further examining anticipated regret in screening decisions. Additional training and information may be helpful to address concerns regarding overdiagnosis.

Clinical application of fluorescence endoscopic imaging using hypericin for the diagnosis of human oral cavity lesions.

BACKGROUND: Diagnosis of oral cancer is conventionally carried out using white light endoscopy and histopathology of biopsy samples. However, oral tumours are mostly superficial and the lesion and its margins can be difficult to visualise under white light. We present clinical data on fluorescence diagnostic imaging of oral lesions using hypericin, a plant-based photosensitiser. METHODS: Fluorescence images of lesions and normal tissue were captured using an endoscope after hypericin administration. The images were analysed to extract their colour parameters, which, along with the red-to-blue intensity ratios, were analysed and used to discriminate between tissue types. The results were correlated with those from histopathology. RESULTS: The red-to-blue intensity ratio increased from normal to hyperplastic to cancerous tissue and was a good parameter to discriminate between these tissue types, with sensitivity and specificity levels of 90% and above. CONCLUSION: Our results show that hypericin fluorescence imaging has the potential to be used for the clinical diagnosis of oral cancer. Further study to enhance the clinical potential of this technique includes the development of a real-time image processing and analysis system interfaced to the endoscope to enable same-day cancer diagnosis and demarcation of lesion margins in a clinical setting.

Multi-language translation and cross-cultural adaptation of the OARSI/OMERACT measure of intermittent and constant osteoarthritis pain (ICOAP).

AIM: To conduct a multi-language translation and cross-cultural adaptation of the Intermittent and Constant OsteoArthritis Pain (ICOAP) questionnaire for hip and knee osteoarthritis (OA). METHODS: The questionnaires were translated and cross-culturally adapted in parallel, using a common protocol, into the following languages: Czech, Dutch, French (France), German, Italian, Norwegian, Spanish (Castillan), North and Central American Spanish, Swedish. The process was conducted following five steps: (1)--independent translation into the target language by two or three persons; (2)--consensus meeting to obtain a single preliminary translated version; (3)--backward translation by an independent bilingual native English speaker, blinded to the English original version; (4)--final version produced by a multidisciplinary consensus committee; (5)--pre-testing of the final version with 10-20 target-language-native hip and knee OA patients. RESULTS: The process could be followed and completed in all countries. Only slight differences were identified in the structure of the sentences between the original and the translated versions. A large majority of the patients felt that the questionnaire was easy to understand and complete. Only a few minor criticisms were expressed. Moreover, a majority of patients found the concepts of constant pain and pain that comes and goes to be of a great pertinence and were very happy with the distinction. CONCLUSION: The ICOAP questionnaire is now available for multi-center international studies.

[Importance of the time for stopping the combined use of aspirin and clopidogrel in patients undergoing coronary artery by-pass graft surgery]. / Importancia del tiempo de suspensión del uso combinado de aspirina y clopidogrel en pacientes sometidos a cirugía de revascularización coronaria.

The combined use of aspirin and clopidogrel is the standard of care for patients with acute coronary syndromes. The risk for perioperative bleeding is considerably increased after coronary artery by-pass graft surgery (CABG). This study was designed to evaluate the effect of antiplatelet therapy on perioperative CABG outcome. We studied 49 consecutive patients undergoing first time CABG, and compared two groups: Group A, patients who stopped antiplatelet treatment at least 6 days before surgery, and group B, those who received antiplatelet therapy within 5 days before surgery or did not suspended therapy. The groups were comparable in their demographic characteristics, manifestations of disease, perioperative medication use and the characteristics of surgery. There was a non significant tendency for more cardiovascular complications (primary cardiovascular endpoint) in the group that stopped antiplatelet therapy 6 or more days before surgery (Group A 12%, group B 8%; p = 0.923). The bleeding endpoint was significantly higher in group B, that remained on antiplatelet therapy within 5 days before surgery (Group A 4%, group B 29%; p = 0.023), as well as the need for transfusion. We concluded that the combined use of aspirin and clopidogrel before CABG increases postoperative bleeding and morbidity; there was no definitive difference in the cardiovascular outcome.

Developing guidelines in musculoskeletal disorders.

Clinical practice guidelines (CPGs) are systematically developed statements to assist practitioners and patients on healthcare decisions. They provide recommendations for the average patient, which should take into account individual clinical judgment and the patient's values and expectations. Quality benchmarks differ from CPGs in that they are best practices that are medically necessary under almost all circumstances, and constitute a standard by which quality of care can be measured. Scientifically rigorous CPGs should be evidence-based and evolve from multidisciplinary and systematic development processes. To maximize their validity, the available evidence must be graded according to its methodological quality and the strength of the recommendations should be based on these ratings. We conducted a systematic review of the literature and relevant websites, which identified 276 CPGs for the diagnosis and/or treatment of musculoskeletal disorders. Of these, 61 were retrieved from 3 sources: 1) the American College of Rheumatology (ACR); 2) the European League against Rheumatism (EULAR); and 3) musculoskeletal CPGs retrieved from the National Guideline Clearinghouse. While use of scientific evidence was commonly cited in the discussion, methodological information was often lacking, without specification as to whether the evidence had been systematically reviewed and graded. We also observed substantial overlap between organizations in the development of CPGs for a given disease.CPGs can improve quality of care by providing evidence-based recommendations. However, it is imperative that they be developed with the utmost transparency, and using a careful and systematic appraisal of the totality of evidence, with recommendations graded according a systematic approach to avoid bias. While many CPGs exist in the rheumatology field, the consensus processes followed in their development is not always explicit, leading to limitations in their interpretations that can hamper broader acceptance and adoption.

Systematic review: cost-effectiveness of direct-acting antivirals for treatment of hepatitis C genotypes 2-6.

BACKGROUND: The availability of direct-acting antivirals (DAAs) has dramatically changed the landscape of hepatitis C virus (HCV) therapy; however, the cost and budget requirements for DAA treatment have been widely debated. AIMS: To systematically review published studies evaluating the cost-effectiveness of DAAs for HCV genotype 2-6 infections, and synthesise and re-evaluate results with updated drug prices. METHODS: We conducted a systematic search of various electronic databases, including Medline, EMBASE, Cochrane library and EconLit for cost-effectiveness studies published from 2011 to 2016. Studies evaluating DAAs for genotypes 2-6 were included. Reported costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were abstracted. We re-estimated ICERs by varying the price of DAAs from $20 000 to $100 000, and estimated the threshold price at which DAA regimens would be deemed cost-effective (ICER≤$100 000/QALY). RESULTS: A total of 92 ICERs for 7 different DAA regimens from 10 published articles were included. Among the abstracted 92 ICERs, 20 were for genotype 2, 40 for genotype 3, 30 for genotype 4, 2 for genotype 5 and none for genotype 6; therefore, only genotypes 2-5 were analysed. At the discounted price of $40 000, 87.0% analyses found DAA regiments to be cost-effective, and 7.6% found to be cost-saving. The median threshold price below which DAAs would be deemed cost-effective was between $144 400 and $225 000, and cost-saving between $17 300 and $25 400. CONCLUSIONS: HCV treatment with DAAs is highly cost-effective in patients with HCV genotypes 2-5 at a $100 000/QALY threshold. Timely HCV treatment would be an optimal strategy from both a public health and economic perspective.

Prevention and treatment of bone loss and fractures in patients undergoing a hematopoietic stem cell transplant: a systematic review and meta-analysis.

The most effective method to prevent and treat bone loss following hematopoietic stem cell transplantation (HSCT) remains uncertain. We conducted a comprehensive search in four electronic databases until August 2015. We retrieved articles describing patients with bone loss or fractures who received HSCT. Controlled trials, with a follow-up period of at least 12 months, were included. Twelve studies (19 publications) met our inclusion criteria. A total of 643 participants underwent HSCT (85.7% allogeneic HSCT). There was a statistically significant lower mean bone mineral density (g/cm2) percentage change of the lumbar spine (mean difference (MD) 7.8, 95% confidence interval (CI) 5.6-10.0) and femoral neck (MD 6.7, 95% CI 5.6-7.9) in the bisphosphonate therapy group compared with the control group with no bisphosphonate therapy at 12 months. In a subgroup analysis, seven different comparison groups were evaluated. The rate of fractures or X-ray findings of subclinical vertebral fractures was similar between groups. Bisphosphonates are promising in the prevention and treatment of bone loss following HSCT. Additional research is required to determine whether they reduce long-term fracture risk.

Photoactivation of hypericin down-regulates glutathione S-transferase activity in nasopharyngeal cancer cells.

Photodynamic therapy (PDT) is a new modality of treatment for cancer. Hypericin is a photosensitizer, which is known to generate reactive oxygen species upon activation with light. We observed that photoactivated hypericin induces the generation of reactive oxygen intermediates in nasopharyngeal cancer (NPC) cells in vitro. There was also significant reduction of Glutathione S-transferase (GST) activity in HK1 and CNE-2 NPC cells and in tumor tissues from the NPC/HK1 murine tumor model by hypericin-mediated PDT. As antioxidants protect cells against phototoxicity, down-regulation of GST activity would potentiate the efficacy of hypericin-PDT treatment.