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 ed. 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 ed 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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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-β2-glycoprotein I (anti-β2-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-β2-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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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 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.
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.
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.
•The majority of patients (80%) with mTNBC in the ASCENT study with available data had high/medium tumor Trop-2 expression.•Survival outcomes and ORRs were numerically higher in SG- versus TPC-treated patients with high/medium Trop-2 expression.•Benefit of SG in patients with high/medium Trop-2 expression was similar to that of overall primary efficacy population.•The small number of patients with low Trop-2 expression prevents definitive conclusions on benefit of SG in this subgroup.•Benefit of SG over TPC was also similar regardless of germline BRCA1/2 mutation status.
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).
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.
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.
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.
Summary
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.
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/cm
) 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.
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.
In this paper we explore some properties of the well known root-finding Chebyshev’s method applied to polynomials defined on the real field. In particular we are interested in showing the existence ...of extraneous fixed points, that is fixed points of the iteration map that are not root of the considered polynomial. The existence of such extraneous fixed points is a specific property in the dynamical study of Chebyshev’s method that does not happen in other known iterative methods as Newton’s or Halley’s methods. In addition, in this work we consider other dynamical aspects of the method as, for instance, the Feigenbaum bifurcation diagrams or the parameter plane.
High extrusion temperatures may compromise the functionality of probiotics in dry food. This study aimed to (i) evaluate the effects of two types of microencapsulation techniques, different ...encapsulating agents, and 120 days of storage on the viability of a commercial probiotic product and (ii) investigate fecal microbiota populations and fecal characteristics of adult cats fed with diets supplemented with probiotics. Three experimental treatments were evaluated: T1, commercial feed (control); T2, commercial kibbles coated with probiotics; and T3, commercial feed supplemented with freeze-dried probiotics and fructooligosaccharides. Fructooligosaccharides and gum arabic were used as encapsulating agents for freeze drying and spray drying and a pool containing Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus lactis, Bifidobacterium bifidum, Enterococcus faecium, and Saccharomyces cerevisiae as a probiotic. Diets were provided to 18 adult cats for 20 days. Feed samples were evaluated microbiologically, and feces were characterized according to their microbial content, pH, and fecal score. Freeze drying was more effective in maintaining microbial viability. Microcapsules prepared using fructooligosaccharides as encapsulants had the highest bacterial count: 8.74 log CFU/g of lactic acid bacteria and 8.75 log CFU/g of enterococci. Probiotics and synbiotics positively modulated (P<0.05) the fecal microbiota of cats, increasing the lactic acid bacteria counts from 3.65 to 4.87 and 5.07 log CFU/g, respectively. Microbial viability decreased significantly (P<0.05) after storage, demonstrating the need for effective protection mechanisms against extrinsic agents. In conclusion, the supplementation of cat diets with probiotics positively affected the gut microbiota. However, the results reinforce that probiotic microorganisms must be incorporated into the animal feed via effective mechanisms to withstand harsh processing conditions and storage.
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