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1.
François Lamontagne Maureen O. Meade Paul C. Hébert Pierre Asfar François Lauzier Andrew J.E. Seely Andrew G. Day Sangeeta Mehta John Muscedere Sean M. Bagshaw Niall D. Ferguson Deborah J. Cook Salmaan Kanji Alexis F. Turgeon Margaret S. Herridge Sanjay Subramanian Jacques Lacroix Neill K.J. Adhikari Damon C. Scales Alison Fox-Robichaud Yoanna Skrobik Richard P. Whitlock Robert S. Green Karen K.Y. Koo Teddie Tanguay Sheldon Magder Daren K. Heyland for the Canadian Critical Care Trials Group. 《Intensive care medicine》2016,42(4):542-550
Purpose
In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.Methods
We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60–65 mmHg) versus a higher (75–80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.Results
A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7–11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (p = 0.059). Risks of cardiac arrhythmias (20 versus 36 %, p = 0.07) and hospital mortality (30 versus 33 %, p = 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %, p = 0.03) but not in younger patients.Conclusions
This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.2.
Harm-Jan de Grooth Jonne Postema Stephan A. Loer Jean-Jacques Parienti Heleen M. Oudemans-van Straaten Armand R. Girbes 《Intensive care medicine》2018,44(3):311-322
Purpose
Although the definition of septic shock has been standardized, some variation in mortality rates among clinical trials is expected. Insights into the sources of heterogeneity may influence the design and interpretation of septic shock studies. We set out to identify inclusion criteria and baseline characteristics associated with between-trial differences in control group mortality rates.Methods
We conducted a systematic review of RCTs published between 2006 and 2018 that included patients with septic shock. The percentage of variance in control-group mortality attributable to study heterogeneity rather than chance was measured by I2. The association between control-group mortality and population characteristics was estimated using linear mixed models and a recursive partitioning algorithm.Results
Sixty-five septic shock RCTs were included. Overall control-group mortality was 38.6%, with significant heterogeneity (I2 = 93%, P < 0.0001) and a 95% prediction interval of 13.5–71.7%. The mean mortality rate did not differ between trials with different definitions of hypotension, infection or vasopressor or mechanical ventilation inclusion criteria. Population characteristics univariately associated with mortality rates were mean Sequential Organ Failure Assessment score (standardized regression coefficient (β) = 0.57, P = 0.007), mean serum creatinine (β = 0.48, P = 0.007), the proportion of patients on mechanical ventilation (β = 0.61, P < 0.001), and the proportion with vasopressors (β = 0.57, P = 0.002). Combinations of population characteristics selected with a linear model and recursive partitioning explained 41 and 42%, respectively, of the heterogeneity in mortality rates.Conclusions
Among 65 septic shock trials, there was a clinically relevant amount of heterogeneity in control group mortality rates which was explained only partly by differences in inclusion criteria and reported baseline characteristics.3.
Ville Pettilä Peter Buhl Hjortrup Stephan M. Jakob Erika Wilkman Anders Perner Jukka Takala 《Intensive care medicine》2016,42(12):1912-1921
Purpose
The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials.Methods
We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting.Results
A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8–32). Of 18 predefined control group characteristics, a mean of 8 (range 2–17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care.Conclusions
Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.4.
Pekka Jakkula Ville Pettilä Markus B. Skrifvars Johanna Hästbacka Pekka Loisa Marjaana Tiainen Erika Wilkman Jussi Toppila Talvikki Koskue Stepani Bendel Thomas Birkelund Raili Laru-Sompa Miia Valkonen Matti Reinikainen COMACARE study group 《Intensive care medicine》2018,44(12):2091-2101
Purpose
We aimed to determine the feasibility of targeting low-normal or high-normal mean arterial pressure (MAP) after out-of-hospital cardiac arrest (OHCA) and its effect on markers of neurological injury.Methods
In the Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial, we used a 23 factorial design to randomly assign patients after OHCA and resuscitation to low-normal or high-normal levels of arterial carbon dioxide tension, to normoxia or moderate hyperoxia, and to low-normal or high-normal MAP. In this paper we report the results of the low-normal (65–75 mmHg) vs. high-normal (80–100 mmHg) MAP comparison. The primary outcome was the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The feasibility outcome was the difference in MAP between the groups. Secondary outcomes included S100B protein and cardiac troponin (TnT) concentrations, electroencephalography (EEG) findings, cerebral oxygenation and neurological outcome at 6 months after cardiac arrest.Results
We recruited 123 patients and included 120 in the final analysis. We found a clear separation in MAP between the groups (p?<?0.001). The median (interquartile range) NSE concentration at 48 h was 20.6 µg/L (15.2–34.9 µg/L) in the low-normal MAP group and 22.0 µg/L (13.6–30.9 µg/L) in the high-normal MAP group, p?=?0.522. We found no differences in the secondary outcomes.Conclusions
Targeting a specific range of MAP was feasible during post-resuscitation intensive care. However, the blood pressure level did not affect the NSE concentration at 48 h after cardiac arrest, nor any secondary outcomes.5.
M. Joannidis W. Druml L. G. Forni A. B. J. Groeneveld P. M. Honore E. Hoste M. Ostermann H. M. Oudemans-van Straaten M. Schetz 《Intensive care medicine》2017,43(6):730-749
Background
Acute kidney injury (AKI) in the intensive care unit is associated with significant mortality and morbidity.Objectives
To determine and update previous recommendations for the prevention of AKI, specifically the role of fluids, diuretics, inotropes, vasopressors/vasodilators, hormonal and nutritional interventions, sedatives, statins, remote ischaemic preconditioning and care bundles.Method
A systematic search of the literature was performed for studies published between 1966 and March 2017 using these potential protective strategies in adult patients at risk of AKI. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, exposure to potentially nephrotoxic drugs and radiocontrast. Clinical endpoints included incidence or grade of AKI, the need for renal replacement therapy and mortality. Studies were graded according to the international GRADE system.Results
We formulated 12 recommendations, 13 suggestions and seven best practice statements. The few strong recommendations with high-level evidence are mostly against the intervention in question (starches, low-dose dopamine, statins in cardiac surgery). Strong recommendations with lower-level evidence include controlled fluid resuscitation with crystalloids, avoiding fluid overload, titration of norepinephrine to a target MAP of 65–70 mmHg (unless chronic hypertension) and not using diuretics or levosimendan for kidney protection solely.Conclusion
The results of recent randomised controlled trials have allowed the formulation of new recommendations and/or increase the strength of previous recommendations. On the other hand, in many domains the available evidence remains insufficient, resulting from the limited quality of the clinical trials and the poor reporting of kidney outcomes.6.
Stephen P. J. Macdonald Gerben Keijzers David McD Taylor Frances Kinnear Glenn Arendts Daniel M. Fatovich Rinaldo Bellomo David McCutcheon Juan-Carlos Ascencio-Lane Sally Burrows Edward Litton Amanda Harley Matthew Anstey Ashes Mukherjee for the REFRESH trial investigators 《Intensive care medicine》2018,44(12):2070-2078
Purpose
To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis.Methods
A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6 h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100 mmHg, after minimum 1000 ml of IV fluid. Primary outcome was total fluid administered within 6 h post randomisation.Results
There were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6 h in the restricted volume group was 2387 ml [first to third quartile (Q1–Q3) 1750–2750 ml]; 30 ml/kg (Q1–Q3 32–39 ml/kg) vs. 3000 ml (Q1–Q3 2250–3900 ml); 43 ml/kg (Q1–Q3 35–50 ml/kg) in the usual care group (p?<?0.001). Median duration of vasopressor support was 21 h (Q1–Q3 9–42 h) vs. 33 h (Q1–Q3 15–50 h), (p?=?0.13) in the restricted volume and usual care groups, respectively. At 90-days, 4 of 48 (8%) in the restricted volume group and 3 of 47 (6%) in the usual care group had died. Protocol deviations occurred in 6/50 (12%) in restricted group and 11/49 (22%) in the usual care group, and serious adverse events in four cases (8%) in each group.Conclusions
A regimen of restricted fluids and early vasopressor in ED patients with suspected sepsis and hypotension appears feasible. Illness severity was moderate and mortality rates low. A future trial is necessary with recruitment of high-risk patients to determine effects on clinical outcomes in this setting.7.
Sobha Sivaprasad Stephane A. Regnier Franck Fajnkuchen Jonathan Wright Alan R. Berger Paul Mitchell Michael Larsen 《Advances in therapy》2016,33(4):597-609
Introduction
The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations.Methods
A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.5 mg pro re nata or laser photocoagulation monotherapy were predicted, assuming baseline characteristics equivalent to those in the VIVID-DME/VISTA-DME trials. These results were compared with the gain with aflibercept 2.0 mg every 8 weeks in VIVID-DME/VISTA-DME. Sensitivity analyses assessed outcome robustness.Results
Baseline BCVA and central retinal thickness differed significantly between trials. In unadjusted data, patients in RESPOND/RESTORE receiving ranibizumab gained an additional 6.6 letters [95% confidence interval (CI): 4.5–8.7] compared with patients receiving laser monotherapy. After adjusting data to assume baseline characteristics equivalent to VIVID-DME/VISTA-DME, patients receiving ranibizumab were predicted to gain an additional 9.9 letters (95% CI: 7.3–12.4) compared with those receiving laser monotherapy. These results were similar (0.1-letter difference in favor of aflibercept; 95% CI: ?2.9 to 3.2; P = 0.94) to the gain in BCVA in patients receiving aflibercept in VIVID-DME/VISTA-DME compared with those receiving laser monotherapy (10.0 letters, 95% CI: 8.3–11.7).Conclusion
After adjusting for baseline characteristics, the difference in letters gained between patients receiving ranibizumab versus aflibercept was non-significant across trials, highlighting the importance of adjusting for baseline characteristics in future comparisons.Funding
Novartis Pharma AG.8.
Keisuke Imade Takashi Kageyama Daisuke Koyama Yoshiaki Watanabe Kentaro Nakamura Iwaki Akiyama 《Journal of Medical Ultrasonics》2016,43(4):473-479
Purpose
The experimental investigation of an optical fiber Bragg grating (FBG) sensor for biomedical application is described. The FBG sensor can be used to measure sound pressure and temperature rise simultaneously in biological tissues exposed to ultrasound. The theoretical maximum values that can be measured with the FBG sensor are 73.0 MPa and 30 °C.Methods
In this study, measurement of sound pressure up to 5 MPa was performed at an ultrasound frequency of 2 MHz. A maximum temperature change of 6 °C was measured in a tissue-mimicking material.Results
Values yielded by the FBG sensor agreed with those measured using a thermocouple and a hydrophone.Conclusion
Since this sensor is used to monitor the sound pressure and temperature simultaneously, it can also be used for industrial applications, such as ultrasonic cleaning of semiconductors under controlled temperatures.9.
Maria?Glezer 《Advances in therapy》2018,35(7):1103-1113
Introduction
Trimetazidine (TMZ) has been shown to reduce angina symptoms and to increase exercise capacity in randomized clinical trials, but more extensive data would be useful to assess its effects in real-world clinical practice and in patients with different durations of disease.Methods
CHOICE-2 was a Russian, multicenter, 6-month, open-label, prospective observational study that assessed the effect of adding TMZ modified release 35 mg bid to antianginal treatment in a real-world setting. The present analysis of CHOICE-2 results explored the effects of adding TMZ to background antianginal therapies with regard to the duration of stable angina.Results
A total of 741 patients with known durations of disease were divided into four groups according to stable angina pectoris (AP) duration, ranging from less than 1 year to more than 9 years. Addition of TMZ led to a significant decrease in the frequency of angina attacks and in the use of short-acting nitrates in all groups. In patients with recently diagnosed angina (AP duration < 1 year), the average number of angina attacks per week decreased significantly from 3.75 ± 4.63 to 0.67 ± 1.51 and in those with advanced disease (AP duration > 9 years) from 5.63 ± 5.24 to 1.32 ± 2.07. Angina-free walking distance also improved significantly. Addition of TMZ also improved patient well-being. Results were achieved rapidly (within 2 weeks), were maintained over 6 months, and were obtained in all patient groups regardless of angina duration.Conclusion
TMZ added to other antianginal therapies proved to be effective for reducing angina attacks and short-acting nitrate use, increasing angina-free walking distance, and improving patient well-being in a real-life setting, irrespective of angina duration, including patients with recently diagnosed angina. This provides an opportunity for intensification of treatment early on in the disease process, with the aim of decreasing angina burden and improving patient quality of life.Funding
Servier.Trial Registration
ISRCTN identifier ISRCTN65209863.Plain Language Summary
Plain language summary available for this article.10.
Automatic adjustment of pressure support by a computer-driven knowledge-based system during noninvasive ventilation: a feasibility study 总被引:1,自引:1,他引:0
Objective
To evaluate the feasibility of using a knowledge-based system designed to automatically titrate pressure support (PS) to maintain the patient in a “respiratory comfort zone” during noninvasive ventilation (NIV) in patients with acute respiratory failure.Design and setting
Prospective crossover interventional study in an intensive care unit of a university hospital.Patients
Twenty patients.Interventions
After initial NIV setting and startup in conventional PS by the chest physiotherapist NIV was continued for 45?min with the automated PS activated.Measurements and results
During automated PS minute-volume was maintained constant while respiratory rate decreased significantly from its pre-NIV value (20?±?3 vs. 25?±?3?bpm). There was a trend towards a progressive lowering of dyspnea. In hypercapnic patients PaCO2 decreased significantly from 61?±?9 to 51?±?2?mmHg, and pH increased significantly from 7.31?±?0.05 to 7.35?±?0.03. Automated PS was well tolerated. Two system malfunctions occurred prompting physiotherapist intervention.Conclusions
The results of this feasibility study suggest that the system can be used during NIV in patients with acute respiratory failure. Further studies should now determine whether it can improve patient-ventilator interaction and reduce caregiver workload.11.
Ary Serpa Neto Matthieu Schmidt Luciano C. P. Azevedo Thomas Bein Laurent Brochard Gernot Beutel Alain Combes Eduardo L. V. Costa Carol Hodgson Christian Lindskov Matthias Lubnow Catherina Lueck Andrew J. Michaels Jose-Artur Paiva Marcelo Park Antonio Pesenti Tài Pham Michael Quintel V. Marco Ranieri Michael Ried Roberto Roncon-AlbuquerqueJr Arthur S. Slutsky Shinhiro Takeda Pier Paolo Terragni Marie Vejen Steffen Weber-Carstens Tobias Welte Marcelo Gama de Abreu Paolo Pelosi Marcus J. Schultz The ReVA Research Network the PROVE Network Investigators 《Intensive care medicine》2016,42(11):1672-1684
Purpose
Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients.Methods
In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality.Results
Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure ? PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO2/FiO2, higher arterial pH and lower PaCO2 levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03–1.10)].Conclusion
In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.12.
Peter M. A. Calverley Michael Könen-Bergmann Frank Richard Susan Bell Jens M. Hohlfeld 《Advances in therapy》2016,33(5):786-793
Introduction
The long-acting muscarinic antagonist tiotropium bromide is approved in many countries as maintenance therapy for chronic obstructive pulmonary disease (COPD). Tiotropium is available as a dry-powder formulation delivered via HandiHaler® (18 μg once daily) and is now also approved as an aqueous solution delivered via the Respimat® Soft Mist? Inhaler (5 μg once daily, 2 puffs of 2.5 µg). Several studies have compared the efficacy of tiotropium HandiHaler (18 μg once daily) with different doses of Respimat. We aimed to compare available bronchodilator efficacy data of once-daily Respimat 1.25, 2.5, 5, 10, 20 µg, and HandiHaler 18 µg to investigate which dose of tiotropium delivered by Respimat is the closest match to tiotropium HandiHaler.Methods
Evaluation of six clinical trials (duration from 3 weeks to 2–3 years) that included lung function measures (trough forced expiratory volume in 1 s and trough forced vital capacity) as key outcomes.Results
In the six trials, bronchodilator efficacy of Respimat 5 μg and HandiHaler 18 μg was similar; however, reduced bronchodilator efficacy was observed with lower doses of Respimat (1.25 and 2.5 μg).Conclusion
These findings support the use of the marketed once-daily dose of Respimat 5 μg for the maintenance treatment of patients with COPD.Funding
Boehringer Ingelheim.13.
Introduction
To present short-term safety and efficacy data of men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) treated with Aquablation.Methods
Men with LUTs secondary to BPH (60–150 cc) underwent Aquablation treatment from February 2016 to December 2017 across 17 investigational sites in the USA from two contemporary investigational device exemption (IDE) studies called WATER (NCT02505919) and WATER II (NCT03123250).Results
One hundred seven males with mean age of 67.3?±?6.5 years were treated with Aquablation; mean prostate volume was 99.4?±?24.1 cc. The pooled results show that large prostates have an average procedure time of less than 36 min and discharge on average 1.6?±?1 days. The IPSS decreased by 16.7?±?8.1 points at 3 months and Qmax increased by 11.2?±?12.4 ml/s. The Clavien-Dindo (CD) grade 2 or higher event rate at 3 months was 29%. A non-hierarchical breakdown for CD events yielded 18% grade 2 and 19% grade 3 or higher.Conclusion
Men with LUTS secondary to BPH (60–150 cc) in a pooled analysis were treated safely and effectively with Aquablation up to 3 months postoperatively.Trial Registration
ClinicalTrials.gov identifiers, NCT02505919 and NCT03123250.Funding
PROCEPT BioRobotics.14.
Nicolas Nin Alfonso Muriel Oscar Peñuelas Laurent Brochard José Angel Lorente Niall D. Ferguson Konstantinos Raymondos Fernando Ríos Damian A. Violi Arnaud W. Thille Marco González Asisclo J. Villagomez Javier Hurtado Andrew R. Davies Bin Du Salvatore M. Maggiore Luis Soto Gabriel D’Empaire Dimitrios Matamis Fekri Abroug Rui P. Moreno Marco Antonio Soares Yaseen Arabi Freddy Sandi Manuel Jibaja Pravin Amin Younsuck Koh Michael A. Kuiper Hans-Henrik Bülow Amine Ali Zeggwagh Antonio Anzueto Jacob I. Sznajder Andres Esteban for the VENTILA Group 《Intensive care medicine》2017,43(2):200-208
Purpose
To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS).Patients and methods
We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality.Main outcomes
We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04–2.41; p = 0.032).Conclusions
Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.Trial registration
Clinicaltrials.gov identifier, NCT01093482.15.
Annunziata?Lapolla Cesare?Berra Massimo?Boemi Antonio?Carlo?Bossi Riccardo?Candido Graziano?Di?Cianni Simona?Frontoni Stefano?Genovese Paola?Ponzani Vincenzo?Provenzano Giuseppina?T.?Russo Luigi?Sciangula Natalino?Simioni Cristiano?Bette Antonio?Nicolucci On behalf of the NN- Study Group 《Advances in therapy》2018,35(2):243-253
16.
Zi-Meng Liu Juan Chen Qiuye Kou Qinhan Lin Xiaobo Huang Zhanhong Tang Yan Kang Ke Li Lixin Zhou Qing Song Tongwen Sun Ling Zhao Xue Wang Xiandi He Chunting Wang Benquan Wu Jiandong Lin Shiying Yuan Qin Gu Kejian Qian Xianqing Shi Yongwen Feng Aihua Lin Xiaoshun He Study Group of investigators Xiang-Dong Guan 《Intensive care medicine》2018,44(11):1816-1825
Purpose
Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin’s effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock.Methods
In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20–160 µg/h with maximum infusion rate of 4 mg/day) or NE (4–30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population.Results
Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55–1.56]; p?=?0.80). Change in SOFA score on day 7 was similar between the two groups: ??7 (IQR ??11 to 3) in the terlipressin group and ??6 (IQR ??10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p?<?0.001).Conclusions
In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events.Trial registration
This trial is registered at ClinicalTrials.gov: ID NCT01697410.17.
Claire M. Ervin David S. Reasner Jennifer T. Hanlon Sheri E. Fehnel 《Advances in therapy》2017,34(12):2680-2692
Introduction
To improve understanding of the diabetic gastroparesis (DGP) patient experience and inform the patient-reported outcome measurement strategy for future trials in DGP, qualitative interviews were conducted with participants in a phase 2 clinical trial of a novel DGP treatment.Methods
Trial participants were invited to participate in interviews at both the pretreatment visit (PTV) and the end-of-treatment visit (EOTV). The interviews were conducted by experienced qualitative researchers and followed a semistructured interview guide. The PTV interviews focused on patients’ DGP symptoms and the impact of DGP on their lives, and the EOTV interviews focused on any symptom changes patients experienced during the trial.Results
Of 90 enrolled trial participants, 78 (86.7%) opted to participate in the interview study. Bloating, stomach fullness, upper abdominal pain, vomiting, constipation, and heartburn or reflux were each reported spontaneously by a majority of the 73 PTV interview participants with evaluable data. These patients commonly reported bloating (n = 20), upper abdominal pain (n = 12), and nausea (n = 11) as their most bothersome DGP symptom. Of 51 EOTV interview participants, 44 (86.3%) reported improvement in at least one DGP symptom either spontaneously or when asked about specific symptoms reported during their PTV interview.Conclusion
Bloating, abdominal pain, nausea, constipation, stomach fullness, vomiting, and heartburn were frequently reported by patients as the most bothersome and important-to-treat symptoms. These results support the assessment of these symptoms in future DGP clinical trials, whether for symptom improvement or worsening.Funding
Ironwood Pharmaceuticals.Trial Registration
ClinicalTrials.gov identifier NCT02289846.18.
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.19.
Richard Lindstrom Richard Lewis Dana M. Hornbeak Lilit Voskanyan Jane Ellen Giamporcaro John Hovanesian Steven Sarkisian 《Advances in therapy》2016,33(11):2082-2090
Introduction
The study objective was to evaluate the intraocular pressure (IOP) and medication-lowering effect of 2 second-generation trabecular micro-bypass stents in eyes with open-angle glaucoma (OAG) on one preoperative medication.Methods
Fifty-seven qualified phakic eyes with OAG on 1 medication, preoperative medicated IOP of 18–30 mmHg, and preoperative unmedicated (post-washout) IOP of 22–38 mmHg underwent implantation of 2 second-generation trabecular micro-bypass stents in a standalone procedure. Evaluations included IOP, best-corrected visual acuity, medication use, fundus and slit lamp examinations, visual field, cup to disc ratio, pachymetry, and complications and interventions. Subjects have been followed for 18 months, and follow-up is ongoing.Results
At Month 12 postoperative, 100% of eyes had achieved an IOP reduction ≥20% (100% had IOP ≤18 mmHg and 67% had IOP ≤15 mmHg) without medication versus preoperative unmedicated IOP, and 75% had IOP reduction ≥20% without medication versus preoperative medicated IOP. The Month 12 mean unmedicated IOP had decreased by 42%, to 14.2 ± 1.9 mmHg vs 24.4 ± 1.3 mmHg preoperatively, and this reduction was maintained through 18 months (14.4 ± 2.1 mmHg). A high safety profile was observed.Conclusion
In this prospective, open-label, single-arm study, the standalone implantation of two second-generation trabecular micro-bypass stents in OAG patients on 1 preoperative medication resulted in IOP reduction to ≤15 mmHg and elimination of medication through 18 months, with favorable safety.Trial Registration
ClinicalTrials.gov identifier, NCT02868190.Funding
Glaukos Corporation, San Clemente, CA.20.
Kamal Maheshwari Brian H. Nathanson Sibyl H. Munson Victor Khangulov Mitali Stevens Hussain Badani Ashish K. Khanna Daniel I. Sessler 《Intensive care medicine》2018,44(6):857-867