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1.
Introduction
Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias.Methods
A MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison.Results
Our results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22–1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44–1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10–1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02–0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04–1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01–8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths.Conclusion
Our analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events.Funding
Janssen-Cilag Ltd.2.
Junlong Li Medha Sasane Jing Zhao Viviana Garcia Horton Pingkuan Zhang Marie Louise Ricculli Zheng-Yi Zhou James Signorovitch 《Advances in therapy》2018,35(7):1035-1048
Introduction
Due to the rarity of BRAF V600E mutation, no randomized study has compared the combination targeted therapy dabrafenib?+?trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative efficacy of treatments among patients with previously treated advanced or metastatic NSCLC.Methods
Randomized trials of dabrafenib?+?trametinib, docetaxel, erlotinib, nintedanib?+?docetaxel, nivolumab, pemetrexed, pembrolizumab, and best supportive care as second-line or above treatments for advanced or metastatic NSCLC identified in a systematic literature review were included in the NMA. Overall response rates (ORRs) and disease control rates (DCRs) were compared using logit models; progression-free survival (PFS) and overall survival (OS) were compared using fractional polynomial hazards models. Dabrafenib?+?trametinib was linked into the evidence network through a matching-adjusted indirect comparison versus nivolumab.Results
Ten trials met the inclusion criteria and were included in the NMA. Dabrafenib?+?trametinib, pembrolizumab, and nivolumab were associated with the highest odds of achieving overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with docetaxel). Estimated DCR was higher for dabrafenib?+?trametinib, nintedanib?+?docetaxel, and pemetrexed compared with other treatments. Patients treated with dabrafenib?+?trametinib, nivolumab, and pembrolizumab had the lowest hazards of disease progression or death during follow-up (72, 61, and 29% lower hazard of progression at 6 months; 61, 48, and 46% lower hazard of death at 1 year, respectively, compared with docetaxel).Conclusion
Dabrafenib?+?trametinib, pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS and OS compared with chemotherapy in previously treated advanced or metastatic NSCLC.Funding
Novartis Pharmaceuticals Corporation.3.
Se-Il?Go Mi?Jung?Park Haa-Na?Song Myoung?Hee?Kang Hee?Jung?Park Kyung?Nyeo?Jeon Seok-Hyun?Kim Moon?Jin?Kim Jung-Hun?Kang Gyeong-Won?Lee
Purpose
Sarcopenia is suggested to be associated with cancer-related inflammation. We assessed the clinical outcome of small cell lung cancer (SCLC) patients according to sarcopenia and the neutrophil-to-lymphocyte ratio (NLR).Methods
A total of 117 male SCLC patients treated with first-line chemo- or chemoradiotherapy were assessed based on a retrospective chart review. The mass of the pectoralis muscle was measured by computed tomography and normalized to height. Patients with the lowest quartile of muscle mass were considered to have sarcopenia. Patients were classified into four groups according to their sarcopenia and NLR statuses: sarcopenia/high NLR, sarcopenia/low NLR, non-sarcopenia/high NLR, and non-sarcopenia/low NLR.Results
Sarcopenic patients had lower progression-free survival (PFS) than did non-sarcopenic patients (median 6.0 vs. 7.5 months, p?=?0.009), but the difference in overall survival (OS) was not statistically significant (median 10.5 vs. 13.5 months, p?=?0.052). However, the OS of sarcopenic patients with high NLR was significantly lower than that in all other groups (median 3.2 vs. 16.0 vs. 12.5 vs. 13.7 months, respectively, p?<?0.001), as was PFS (median 3.2 vs. 7.7 vs. 7.6 vs. 7.1 months, respectively, p?<?0.001). On multivariate analysis, sarcopenia with high NLR was an independent prognostic factor for shorter PFS and OS. Early discontinuation of treatment (20.0 vs. 10.3 %) and treatment-related mortality (50.0 vs. 8.4 %) occurred more frequently in these patients than in the other groups (p?<?0.001).Conclusions
In SCLC, sarcopenic male patients with high NLR have a poor prognosis and do not tolerate standard treatment. Intensive supportive care is needed in these patients.4.
Arun Azad Fiona Chionh Andrew M. Scott Szeting T. Lee Sam U. Berlangieri Shane White Paul L. Mitchell 《Molecular imaging and biology》2010,12(4):443-451
Purpose
We evaluated whether 18F-FDG-PET altered stage classification, management, and prognostic stratification of newly diagnosed small cell lung cancer (SCLC).Procedures
We identified 46 consecutive patients undergoing staging positron emission tomography for SCLC from 1993–2008 inclusive. Updated survival data from the state Cancer Registry was available on 42 of 46 patients.Results
PET altered stage classification in 12 of 46 (26%) patients. PET altered treatment modality in nine patients, and the target mediastinal radiation field in another three patients. Therefore, PET altered management in 12 of 46 (26%) patients. Patients with limited disease (LD) on pre-PET staging had significantly longer overall survival (OS) than those upstaged to extensive disease (ED; median 18.6 months versus 5.7 months; log-rank p?0.0001). In patients with ED on pre-PET staging, those downstaged to LD by PET had significantly longer OS than those with ED on PET (median 10.9 months versus 5.9 months; log-rank p?=?0.037).Conclusion
PET had a major impact on stage classification, management, and prognostic stratification of newly diagnosed SCLC.5.
Background
Migraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans.Methods
We conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions.Results
Eletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan.Conclusion
This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.6.
Laura Pietiläinen Johanna Hästbacka Minna Bäcklund Ilkka Parviainen Ville Pettilä Matti Reinikainen 《Intensive care medicine》2018,44(8):1221-1229
Purpose
We assessed the association between the premorbid functional status (PFS) and 1-year mortality and functional status of very old intensive care patients.Methods
Using a nationwide quality registry, we retrieved data on patients treated in Finnish intensive care units (ICUs) during the period May 2012?April 2013. Of 16,389 patients, 1827 (11.1%) were very old (aged 80 years or older). We defined a person with good functional status as someone independent in activities of daily living (ADL) and able to climb stairs without assistance; a person with poor functional status was defined as needing assistance for ADL or being unable to climb stairs. We adjusted for severity of illness and calculated the impact of PFS.Results
Overall, hospital mortality was 21.3% and 1-year mortality was 38.2%. For emergency patients (73.5% of all), hospital mortality was 28% and 1-year mortality was 48%. The functional status at 1 year was comparable to the PFS in 78% of the survivors. PFS was poor for 43.3% of the patients. A poor PFS predicted an increased risk of in-hospital death, adjusted odds ratio (OR) 1.50 (95% confidence interval, 1.07–2.10), and of 1-year mortality, OR 2.18 (1.67–2.85). PFS data significantly improved the prediction of 1-year mortality.Conclusions
Of very old ICU patients, 62% were alive 1 year after ICU admission and 78% of the survivors had a functional status comparable to the premorbid situation. A poor PFS doubled the odds of death within a year. Knowledge of PFS improved the prediction of 1-year mortality.7.
Mustapha Tehfe Scot Dowden Hagen Kennecke Robert El-Maraghi Bernard Lesperance Felix Couture Richard Letourneau Helen Liu Alfredo Romano 《Advances in therapy》2016,33(5):747-759
Introduction
The phase III MPACT trial in patients with metastatic pancreatic cancer (MPC) demonstrated superior efficacy of nab-paclitaxel (nab-P) plus gemcitabine (Gem) compared with Gem monotherapy, including the primary endpoint of overall survival (OS; median 8.7 vs. 6.6 months; hazard ratio [HR] 0.72; P < 0.001). A significant treatment difference favoring nab-P + Gem over Gem was observed for OS in patients treated in North America. The majority of patients were from the US (88%) with only 12% from Canada. Healthcare systems and treatment patterns are different between the 2 countries, and there is limited published information on outcomes of Canadian patients treated with first-line nab-P + Gem. This analysis evaluated efficacy and safety outcomes in Canadian patients in the MPACT trial.Methods
Treatment-naive patients with MPC (N = 861) received either nab-P 125 mg/m2 + Gem 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or Gem 1000 mg/m2 weekly for the first 7 of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle ≥2).Results
The MPACT trial enrolled 63 patients in Canada. Baseline characteristics were well balanced and comparable with those of the intent-to-treat population. Both OS (median 11.9 vs. 7.1 months; HR 0.76; P = 0.373) and progression-free survival (median 7.2 vs. 5.2 months; HR 0.65; P = 0.224) were numerically longer and overall response rate (27% vs. 17%; P = 0.312) was numerically higher with nab-P + Gem vs. Gem. The most common grade ≥3 adverse events with nab-P + Gem vs. Gem were neutropenia (22% vs. 10%), fatigue (34% vs. 33%), and neuropathy (25% vs. 0%).Conclusion
This subanalysis confirmed that nab-P + Gem is an efficacious treatment option and has a manageable safety profile in patients with MPC treated in Canada.Trial registration
ClinicalTrials.gov identifier, NCT00844649.Funding
Celgene Corporation, Summit, NJ, USA.8.
Nicholas J. Vogelzang Sumanta K. Pal Sameer R. Ghate Elyse Swallow Nanxin Li Miranda Peeples Miriam L. Zichlin Mark K. Meiselbach Jose Ricardo Perez Neeraj Agarwal 《Advances in therapy》2017,34(11):2452-2465
Introduction
Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment.Methods
Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014). Patients were stratified by index drug and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death and compared by Kaplan–Meier analyses and univariable Cox models; patients were censored at the end of eligibility/data. Monthly HRU and costs from an intent-to-treat perspective were compared by Wilcoxon signed-rank tests.Results
Baseline characteristics were balanced after matching (both N = 522). Treatment with pazopanib was associated with significantly longer median OS compared with treatment with sunitinib (18.2 months vs 14.6 months, respectively; log-rank p = 0.015). Pazopanib was associated with significantly lower monthly all-cause costs compared with sunitinib ($8845 vs $10,416, respectively), as well as lower inpatient costs associated with RCC diagnosis ($1542 vs $2522), fewer monthly inpatient admissions (0.179 vs 0.262), and shorter length of inpatient stay (1.375 days vs 1.883 days; all p ≤ 0.004).Conclusions
Among elderly Medicare patients with advanced RCC, first-line pazopanib tretament was associated with significantly longer OS, as well as lower healthcare costs and HRU, compared with first-line sunitinib treatment.9.
Casey Quinn Qiufei Ma Amber Kudlac Stephen Palmer Beth Barber Zhongyun Zhao 《Advances in therapy》2017,34(2):495-512
Introduction
Advances in the treatment of metastatic melanoma have been achieved in recent years: immunotherapies and targeted therapies have demonstrated survival benefits over older agents such as granulocyte-macrophage colony-stimulating factor (GM-CSF), dacarbazine, and glycoprotein peptide vaccine (gp100) in pivotal phase 3 trials. It is important to compare therapies to guide the treatment decision-making process, and establishing the relationship between older agents can strengthen the networks of evidence for newer therapies. We report the outcome of an indirect comparison of GM-CSF, dacarbazine, and gp100 in metastatic melanoma through meta-analysis of absolute treatment effect.Methods
A systematic literature review identified trials for inclusion in the meta-analysis. A valid network meta-analysis was not feasible: treatment-specific meta-analysis was conducted. A published algorithm was used to adjust overall survival estimates from trials of GM-CSF, dacarbazine, and gp100 for heterogeneity in baseline prognostic factors. Survival estimates were compared in three patient groups: stage IIIB–IV M1c, stage IIIB–IV M1a, and stage IV M1b/c.Results
One trial of GM-CSF, four of dacarbazine, and one of gp100 were included in the analysis. After adjusting for differences in baseline prognostic factors, median overall survival (OS) in all patient groups was longer for those receiving GM-CSF than for those receiving dacarbazine or gp100. The observed survival over time for GM-CSF was similar to the adjusted survival for dacarbazine and greater than for gp100 in all patient groups.Conclusion
The relative treatment effect of GM-CSF, dacarbazine, and gp100 has been reliably estimated by adjusting for differences in baseline prognostic factors. Results suggest that OS with GM-CSF is at least as good as with dacarbazine and greater than with gp100. Given the role of these agents as controls in phase 3 trials of new immunotherapies and targeted agents, these results can be used to contextualize the efficacy of newer therapies.Funding
Amgen Inc.10.
Objective
To compare the safety and estimate the response profile of olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of delirium in the critical care setting.Design
Prospective randomized trialSetting
Tertiary care university affiliated critical care unit.Patients
All admissions to a medical and surgical intensive care unit with a diagnosis of delirium.Interventions
Patients were randomized to receive either enteral olanzapine or haloperidol.Measurements
Patient’s delirium severity and benzodiazepine use were monitored over 5 days after the diagnosis of delirium.Main results
Delirium Index decreased over time in both groups, as did the administered dose of benzodiazepines. Clinical improvement was similar in both treatment arms. No side effects were noted in the olanzapine group, whereas the use of haloperidol was associated with extrapyramidal side effects.Conclusions
Olanzapine is a safe alternative to haloperidol in delirious critical care patients, and may be of particular interest in patients in whom haloperidol is contraindicated.11.
Andriy Danyliv Julie Glanville Rachael McCool Alberto Ferreira Adrian Skelly Ruth Pulikottil Jacob 《Advances in therapy》2017,34(3):611-619
Introduction
Neovascular age-related macular degeneration (nAMD) is a chronic eye condition that causes severe deterioration of vision and ultimately blindness. Two vascular endothelial growth factor inhibitors are approved for nAMD treatment in Europe: ranibizumab and aflibercept. The European license for ranibizumab was updated with an individualized “treat and extend” (T&E) regimen, which involves more proactive treatment based on changes in best corrected visual acuity (BCVA) and/or anatomical outcomes. The aim of this publication is to compare the efficacy of the ranibizumab T&E regimen with other approved dosing regimens for nAMD on the basis of outcomes identified from a systematic review and subsequent NMA.Methods
Following a systematic search of publications, to identify relevant studies, a repeated-measures network meta-analysis (NMA) was performed to estimate the relative effectiveness of ranibizumab T&E versus approved dosing regimens of ranibizumab and aflibercept. The analysis focused on licensed treatment regimens for nAMD. We examined mean change from baseline in BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.Results
The systematic literature review identified 22,949 records, of which 23 studies were included in the NMA. At 12 months, the ranibizumab T&E dosing regimen vs ranibizumab pro re nata (PRN) was associated with small differences in change in BCVA, between 1.86 letter gain at 12 months and 2.35 letter gain at 24 months. A similar difference was observed in the aflibercept dosing regimen versus ranibizumab T&E ; 1.94 letter gain at 12 months and 3.31 letter gain at 24 months. All doses of ranibizumab and aflibercept showed similar effectiveness, and the differences between treatment options were not significant.Conclusion
This study used novel repeated-measures NMA to synthesize efficacy results when treatment effects were reported at multiple follow-up times. This repeated-measures NMA suggests that treating patients with the ranibizumab T&E regimen yields similar effectiveness compared to other approved ranibizumab and aflibercept dosing regimens for nAMD treatment. Funding: Novartis Pharmaceuticals UK Ltd, Surrey, UK.12.
13.
Jin Cheng Jing Wu Yingjiang Ye Chunfang Zhang Yinli Zhang Yi Wang 《Abdominal imaging》2016,41(7):1219-1226
Purpose
To determine the 1-year progression-free survival (PFS) of extramural venous invasion (EMVI), detected with contrast-enhanced multiple-row detector computed tomography (ceMDCT), in patients with stage III gastric cancer.Methods
Between January 2009 and December 2013, 117 patients with pathological-proved stage III gastric cancer based on the criteria of the AJCC 7th were included in this retrospective study. All patients underwent adjuvant chemotherapy postoperatively and had been monitored with the follow-up chest/abdomen/pelvis ceMDCT on 3, 6, and 12 months post-operation. Two radiologists reviewed preoperative images regarding the presence of EMVI, categories of tumor and categories of lymph node. Conventional prognostic histological factors including pathological T/N status, tumor location/growth pattern, histological type/tumor differentiation, and tumor size were also recorded. Disease progression was defined as the presence of radiological or/and pathology-confirmed metachronous metastases, local recurrence, or gastric cancer-related death. The 1-year PFS for both EMVI-positive and EMVI-negative was calculated using the Kaplan–Meier product limit. Hazard ratios for 1-year PFS were generated using a Cox proportional hazard regression on ceMDCT tumor characteristics.Results
The prevalence of EMVI detected with ceMDCT was 43.6% (51/117) in patients with stage III gastric cancer. The EMVI-positive patients had significantly lower 1-year PFS rates (45.1%), than the EMVI-negative patients (75.8%), (Log-rank test, P = 0.0008). In a Cox proportional hazards regression analysis, EMVI and tumor location/growth pattern were identified as independent prognostic factors of 1-year PFS with hazard ratio of 2.272 (95% CI 1.133–4.556, P = 0.021) and 1.982 (95% CI 1.040–3.780, P = 0.039), respectively.Conclusion
EMVI status, detected with ceMDCT, could be used to counsel patients regarding ongoing risks of metastatic disease, implications for surveillance, and systemic chemotherapy.14.
Takamasa Ohki Mayuko Kondo Yuki Karasawa Satoshi Kawamura Shuuya Maeshima Kentaro Kojima Michiharu Seki Nobuo Toda Yoshinobu Shioda Kazumi Tagawa 《Advances in therapy》2017,34(5):1097-1108
Introduction
Transcatheter arterial chemoembolization (TACE) is the first-line treatment for intermediate stage hepatocellular carcinoma (HCC) and prolongs survival in HCC patients. However, repeated TACE results in diminished therapeutic response. In addition, the superiority of sorafenib to TACE monotherapy or combined therapy in patients with HCC is still controversial. The prognosis of HCC has many variables and, thus, the effect of a specific treatment is difficult to evaluate. The frequency of treatments per year (FT rate) used in this study was obtained by dividing the total number of radiofrequency ablations and TACE or transcatheter arterial infusion treatments by the years of survival. The aim of this study was to evaluate the overall survival (OS) of TACE versus sorafenib using the FT rate.Methods
We compared the OS of patients with recurrence of HCC receiving repeated TACE monotherapy (CON) with those receiving therapy switched from TACE to sorafenib (SOR). In addition, a one-to-one FT rate matching cohort consisting of matched SOR (mSOR) and matched CON (mCON) was determined using the propensity score matching method, and OS in the cohort was evaluated. Factors influencing survival were evaluated using Cox proportional hazard regression analysis in all patients and the FT rate matched cohort.Results
In the FT rate matched cohort, the cumulative survival rate was significantly higher in the mSOR group compared with the mCON group. Multivariate regression analysis of the FT rate matched cohort showed the FT rate and sorafenib to be significant variables for survival with a hazard ratio (HR) of 2.86 (p < 0.001) and 0.42 (p = 0.008), respectively.Conclusion
Early switching from TACE to sorafenib therapy may prolong OS in HCC patients unresponsive to TACE. The present study indicates that the FT rate is potentially a useful index in evaluating the outcome for patients at various stages and treatment regimens.Funding
Bayer Yakuhin, Ltd.15.
Casey Quinn Qiufei Ma Amber Kudlac Stephen Palmer Beth Barber Zhongyun Zhao 《Advances in therapy》2016,33(4):643-657
Introduction
Few randomized controlled trials have compared new treatments for metastatic melanoma. We sought to examine the relative treatment effect of talimogene laherparepvec compared with ipilimumab and vemurafenib.Methods
A systematic literature review of treatments for metastatic melanoma was undertaken but a valid network of evidence could not be established because of a lack of comparative data or studies with sufficient common comparators. A conventional adjusted indirect treatment comparison via network meta-analysis was, therefore, not feasible. Instead, a meta-analysis of absolute efficacy was undertaken, adjusting overall survival (OS) data for differences in prognostic factors between studies using a published algorithm.Results
Four trials were included in the final indirect treatment comparison: two of ipilimumab, one of vemurafenib, and one of talimogene laherparepvec. Median OS for ipilimumab and vemurafenib increased significantly when adjustment was applied, demonstrating that variation in disease and patient characteristics was biasing OS estimates; adjusting for this made the survival data more comparable. For both ipilimumab and vemurafenib, the adjustments improved Kaplan–Meier OS curves; the observed talimogene laherparepvec OS curve remained above the adjusted OS curves for ipilimumab and vemurafenib, showing that long-term survival could differ from the observed medians.Conclusion
Even with limited data, talimogene laherparepvec, ipilimumab, and vemurafenib could be compared following adjustments, thereby providing a more reliable understanding of the relative effect of treatment on survival in a more comparable patient population. The results of this analysis suggest that OS with talimogene laherparepvec is at least as good as with ipilimumab and vemurafenib and improvement was more pronounced in patients with no bone, brain, lung or other visceral metastases.Funding
Amgen Inc.16.
David J. W. Knight Dale Gardiner Amanda Banks Susan E. Snape Vivienne C. Weston Stig Bengmark Keith J. Girling 《Intensive care medicine》2009,35(5):854-861
Objective
To investigate the effect of enteral Synbiotic 2000 FORTE® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.Design
Prospective, randomised, double blind, placebo controlled trial.Setting
Tertiary referral centre, general Adult Intensive Care Unit (ICU).Patients and participants
259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.Intervention
All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE® (twice a day) or a cellulose-based placebo for a maximum of 28 days.Measurements and results
Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.Conclusions
Enteral administration of Synbiotic 2000 FORTE® has no statistically significant impact on the incidence of VAP in critically ill patients.17.
Introduction
A comprehensive and up-to-date network meta-analysis (NMA) helps to determine the comparative efficacies of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B (CHB). The aim of this NMA was to assess the efficacy of telbivudine versus adefovir, entecavir, lamivudine, and tenofovir in nucleos(t)ide-naïve hepatitis B e antigen (HBeAg)-positive patients with CHB.Methods
A systematic review was conducted to search Medline, Medline-In Process, EMBASE, and the Cochrane Central Register of Controlled Trials databases for publications of randomized controlled trials (RCTs). NMA was performed to compare the efficacy outcomes of telbivudine versus other approved NAs at 1- and 2-year time points.Results
A total of 75 RCTs were included in the systematic review. At the 1-year time point, telbivudine was associated with significantly higher rates of: (1) HBeAg seroconversion than adefovir [odds ratio (OR) 1.99 (95% credible interval (CrI): 1.05, 3.45)], entecavir [OR 2.00 (95% CrI: 1.44, 2.82)] and lamivudine [OR 1.49 (95% CrI: 1.10, 2.03)]; (2) HBeAg loss than entecavir [OR 1.85 (95% CrI: 1.28, 2.76)] and lamivudine [OR 1.62 (95% CrI: 1.20, 2.24)]; (3) alanine aminotransferase (ALT) normalization than lamivudine [OR 1.50 (95% CrI: 1.05, 2.21)]; and (4) hepatitis B virus (HBV) DNA suppression than adefovir [OR 2.77 (95% CrI: 1.28, 5.45)] and lamivudine [OR 2.97 (95% CrI: 1.99, 4.53)]. At the 2-year time point, the relative efficacy outcomes were not statistically significant.Conclusion
At 1 year, telbivudine was superior to adefovir, entecavir and lamivudine in HBeAg seroconversion, and to entecavir and lamivudine in HBeAg loss. Telbivudine was also superior to lamivudine in ALT normalization and to adefovir and lamivudine in suppressing HBV DNA levels.Funding
Novartis Pharma AG.18.
Background
Owing to a rise of psychosomatic comorbidities, the treatment of psychological disorders, which may negatively impact prognosis and therapy, is increasingly becoming a focus of attention for pain outpatient clinics.Aim
This study investigates and discusses the advantages of liaison psychiatric care in a university pain clinic.Methods
In this retrospective study, we investigated all patients who presented to an anaesthesiologically led pain clinic between January and June 2014. The psychiatric history was taken by the liaison psychiatrist of the pain clinic.Results
In the period investigated, 485 patients were treated as outpatients. A psychiatric diagnosis was present 351 patients (72.4%). The distribution of the diagnoses was comparable with that of a consultation service. Adaptation and affective disorders dominated. The patients were preferentially treated with new generation antidepressants.Conclusion
The constant presence of a liaison psychiatrist allows for timely, specialised care of pain patients in terms of a multimodal therapeutic approach.19.
Arie Barlev Vincent W. Lin Aaron Katz Kuolung Hu Ze Cong Beth Barber 《Advances in therapy》2017,34(1):148-155
Introduction
Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(?) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.Methods
The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.Results
At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.Conclusions
These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(?) B-precursor ALL compared with salvage chemotherapy.Funding
Amgen.Trial Registration
ClinicalTrials.gov identifier NCT01466179 and NCT02003612.20.