OBJECTIVES: To assess the efficacy and safety of combined aclidinium bromide and long-acting beta2-agonists in stable COPD.
SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), ClinicalTrials.gov, World Health Organization (WHO) trials portal, United States Food and Drug Administration (FDA) and manufacturers' websites as well as the reference list of published trials up to 12 October 2018.
SELECTION CRITERIA: Parallel-group randomised controlled trials (RCTs) assessing combined aclidinium bromide and LABAs in people with stable COPD.
DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane for data collection and analysis. The primary outcomes were exacerbations requiring a short course of an oral steroid or antibiotic, or both; quality of life measured by a validated scale and non-fatal serious adverse events (SAEs). Where the outcome or study details were not reported, we contacted the study investigators or pharmaceutical company trial co-ordinators (or both) for missing data.
MAIN RESULTS: We identified RCTs comparing aclidinium/formoterol FDC versus aclidinium, formoterol or placebo only. We included seven multicentre trials of four to 52 weeks' duration conducted in outpatient settings. There were 5921 participants, whose mean age ranged from 60.7 to 64.7 years, mostly men with a mean smoking pack-years of 46.4 to 61.3 of which 43.9% to 63.4% were current smokers. They had a moderate-to-severe degree of COPD with a mean postbronchodilator forced expiratory volume in one second (FEV1) between 50.5% and 61% of predicted normal and the baseline mean FEV1 of 1.23 L to 1.43 L. We assessed performance and detection biases as low for all studies whereas selection, attrition and reporting biases were either low or unclear.FDC versus aclidiniumThere was no evidence of a difference between FDC and aclidinium for exacerbations requiring steroids or antibiotics, or both (OR 0.95, 95% CI 0.71 to 1.27; 2 trials, 2156 participants; moderate-certainty evidence); quality of life measured by St George's Respiratory Questionnaire (SGRQ) total score (MD -0.92, 95% CI -2.15 to 0.30); participants with significant improvement in SGRQ score (OR 1.17, 95% CI 0.97 to 1.41; 2 trials, 2002 participants; moderate-certainty evidence); non-fatal SAE (OR 1.19, 95% CI 0.79 to 1.80; 3 trials, 2473 participants; moderate-certainty evidence); hospital admissions due to severe exacerbations (OR 0.62, 95% CI 0.29 to 1.29; 2 trials, 2156 participants; moderate-certainty evidence) or adverse events (OR 0.95, 95% CI 0.76 to 1.18; 3 trials, 2473 participants; moderate-certainty evidence). Compared with aclidinium, FDC improved symptoms (Transitional Dyspnoea Index (TDI) focal score: MD 0.37, 95% CI 0.07 to 0.68; 2 trials, 2013 participants) with a higher chance of achieving a minimal clinically important difference (MCID) of at least one unit improvement (OR 1.34, 95% CI 1.11 to 1.62; high-certainty evidence); the number needed to treat for an additional beneficial outcome (NNTB) being 14 (95% CI 9 to 39).FDC versus formoterolWhen compared to formoterol, combination therapy reduced exacerbations requiring steroids or antibiotics, or both (OR 0.78, 95% CI 0.62 to 0.99; 3 trials, 2694 participants; high-certainty evidence); may decrease SGRQ total score (MD -1.88, 95% CI -3.10 to -0.65; 2 trials, 2002 participants; low-certainty evidence; MCID for SGRQ is 4 units); increased TDI focal score (MD 0.42, 95% CI 0.11 to 0.72; 2 trials, 2010 participants) with more participants attaining an MCID (OR 1.30, 95% CI 1.07 to 1.56; high-certainty evidence) and an NNTB of 16 (95% CI 10 to 60). FDC lowered the risk of adverse events compared to formoterol (OR 0.78, 95% CI 0.65 to 0.93; 5 trials, 3140 participants; high-certainty evidence; NNTB 22). However, there was no difference between FDC and formoterol for hospital admissions, all-cause mortality and non-fatal SAEs.FDC versus placeboCompared with placebo, FDC demonstrated no evidence of a difference in exacerbations requiring steroids or antibiotics, or both (OR 0.82, 95% CI 0.60 to 1.12; 2 trials, 1960 participants; moderate-certainty evidence) or hospital admissions due to severe exacerbations (OR 0.55, 95% CI 0.25 to 1.18; 2 trials, 1960 participants; moderate-certainty evidence), although estimates were uncertain. Quality of life measure by SGRQ total score was significantly better with FDC compared to placebo (MD -2.91, 95% CI -4.33 to -1.50; 2 trials, 1823 participants) resulting in a corresponding increase in SGRQ responders who achieved at least four units decrease in SGRQ total score (OR 1.72, 95% CI 1.39 to 2.13; high-certainty evidence) with an NNTB of 7 (95% CI 5 to 12). FDC also improved symptoms measured by TDI focal score (MD 1.32, 95% CI 0.96 to 1.69; 2 studies, 1832 participants) with more participants attaining at least one unit improvement in TDI focal score (OR 2.51, 95% CI 2.02 to 3.11; high-certainty evidence; NNTB 4). There were no differences in non-fatal SAEs, adverse events and all-cause mortality between FDC and placebo.Combination therapy significantly improved trough FEV1 compared to aclidinium, formoterol or placebo.
AUTHORS' CONCLUSIONS: FDC improved dyspnoea and lung function compared to aclidinium, formoterol or placebo, and this translated into an increase in the number of responders on combination treatment. Quality of life was better with combination compared to formoterol or placebo. There was no evidence of a difference between FDC and monotherapy or placebo for exacerbations, hospital admissions, mortality, non-fatal SAEs or adverse events. Studies reported a lower risk of moderate exacerbations and adverse events with FDC compared to formoterol; however, larger studies would yield a more precise estimate for these outcomes.
METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).
RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).
CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.
TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).
METHODS: We searched PubMed, Embase and the Cochrane Central systematically for the randomised control trials (RCTs) of interventions for preventing OM. Network meta-analysis (NMA) was performed to estimate risk ratios (RR) and 95% confidence intervals (CI) from both direct and indirect evidence. The primary outcome was any grade of OM. Secondary outcomes were mild-moderate OM, severe OM and adverse events, such as taste disturbance and gastrointestinal adverse events. This study was registered with PROSPERO, number CRD42016052489.
RESULTS: A total of 29 RCTs with 2348 patients (median age, 56.1 years; 57.5% male) were included. Cryotherapy was associated with a significantly lower risk of OM than control (RR 0.51, 95% CI 0.38 to 0.68), and zinc sulphate (RR 0.47, 95% CI 0.23 to 0.97), but not significantly lower than sucralfate and palifermin. No significant differences were observed between cryotherapy and control for taste disturbance and gastrointestinal adverse events. Palifermin was associated with the highest risk of taste disturbance.
CONCLUSIONS: This NMA suggests that cryotherapy was the most effective intervention for preventing chemotherapy-induced OM with a safety profile similar to control, but not significantly lower than sucralfate and palifermin. Large RCTs are needed to confirm these findings.
DESIGN: Network meta-analysis.
DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.
RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).
CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.
METHODS: We selected randomized controlled trials, assessing efficacy of antibiotics for the treatment of leptospirosis as a case study. A pairwise meta-analysis was conducted using a random effect model, assuming that different studies assessed different but related treatment effects. The analysis was then extended to a network meta-analysis, which consists of direct and indirect evidence in a network of antibiotics trials, using a suite of multivariate meta-analysis routines of STATA (mvmeta command). We also assessed an assumption of 'consistency' that estimates of treatment effects from direct and indirect evidence are in agreement.
RESULTS: Seven randomised controlled trials were identified for this analysis. These RCTs assessed the efficacy of antibiotics such as penicillin, doxycycline and cephalosporin for the treatment of human leptospirosis. These studies made comparisons between antibiotics (i.e. an antibiotic versus alternative antibiotic) in the primary study and a placebo, except for cephalosporin. These studies were sufficient to allow the creation of a network for the network meta-analysis; a closed loop in which three comparator antibiotics were connected to each other through a polygon. The comparison of penicillin versus the placebo has the largest contribution to the entire network (31.8%). The assessment of rank probabilities indicated that penicillin presented the greatest likelihood of improving efficacy among the evaluated antibiotics for treating leptospirosis.
CONCLUSIONS: Findings suggest that network meta-analysis, a meta-analysis comparing multiple treatments, is feasible and should be considered as better precision of effect estimates for decisions when several antibiotic options are available for the treatment of leptospirosis.
OBJECTIVES: To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non-tertiary hospitals, with the need for sensitivity analysis determined by trial quality.At the 2008 update, the objectives were modified to include preterm infants with respiratory failure.
SEARCH METHODS: We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled-trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO).
SELECTION CRITERIA: All random or quasi-random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary.
DATA COLLECTION AND ANALYSIS: We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author.
MAIN RESULTS: We included six studies involving 355 infants - two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials.Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) -0.20, 95% CI -0.29 to -0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD -0.15, 95% CI -0.26 to -0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD -0.28, 95% CI -0.48 to -0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants).
AUTHORS' CONCLUSIONS: In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration.
OBJECTIVES: In spontaneously breathing preterm infants with RDS, to determine if continuous distending pressure (CDP) reduces the need for IPPV and associated morbidity without adverse effects.
SEARCH STRATEGY: The standard search strategy of the Neonatal Review group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), MEDLINE (1966-January 2002), and EMBASE (1980-January 2002), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language.
SELECTION CRITERIA: All trials using random or quasi-random allocation of preterm infants with RDS were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube, or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and lower body, compared with standard care.
DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group were used, including independent assessment of trial quality and extraction of data by each author.
MAIN RESULTS: CDP is associated with a lower rate of failed treatment (death or use of assisted ventilation) [summary RR 0.70 (0.55, 0.88), RD -0.22 (-0.35, -0.09), NNT 5 (3, 11)], overall mortality [summary RR 0.52 (0.32, 0.87), RD -0.15 (-0.26, -0.04), NNT 7 (4, 25)], and mortality in infants with birthweights above 1500 g [summary RR 0.24 (0.07, 0.84), RD -0.281 (-0.483, -0.078), NNT 4 (2, 13)]. The use of CDP is associated with an increased rate of pneumothorax [summary RR 2.36 (1.25, 5.54), RD 0.14 (0.04, 0.23), NNH 7 (4, 24)].
REVIEWER'S CONCLUSIONS: In preterm infants with RDS the application of CDP either as CPAP or CNP is associated with benefits in terms of reduced respiratory failure and reduced mortality. CDP is associated with an increased rate of pneumothorax. The applicability of these results to current practice is difficult to assess, given the intensive care setting of the 1970s when four out of five of these trials were done. Where resources are limited, such as in developing countries, CPAP for RDS may have a clinical role. Further research is required to determine the best mode of administration and its role in modern intensive care settings
OBJECTIVES: In spontaneously breathing preterm infants with RDS, to determine if continuous distending pressure (CDP) reduces the need for IPPV and associated morbidity without adverse effects.
SEARCH STRATEGY: The standard search strategy of the Neonatal Review group was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE (1966-Jan. 2000), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, journal hand searching mainly in the English language.
SELECTION CRITERIA: All trials using random or quasi-random patient allocation of newborn infants with RDS were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube, or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and lower body, compared with standard care.
DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each author, were used.
MAIN RESULTS: CDP is associated with a lower rate of failed treatment (death or use of assisted ventilation), overall mortality, and mortality in infants with birthweights above 1500 g. The use of CDP is associated with an increased rate of pneumothorax.
REVIEWER'S CONCLUSIONS: In preterm infants with RDS the application of CDP either as CPAP or CNP is associated with some benefits in terms of reduced respiratory failure and reduced mortality. CDP is associated with an increased rate of pneumothorax. The applicability of these results to current practice is difficult to assess, given the outdated methods to administer CDP, low use of antenatal corticosteroids, non-availability of surfactant and the intensive care setting of the 1970s when these trials were done. Where resources are limited, such as in developing countries, CPAP for RDS may have a clinical role. Further research is required to determine the best mode of administration and its role in modern intensive care settings
OBJECTIVES: To determine the effect of continuous distending pressure in the form of CPAP on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress.
SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search CENTRAL (2020, Issue 6); Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions; and CINAHL on 30 June 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA: All randomised or quasi-randomised trials of preterm infants with respiratory distress were eligible. Interventions were CPAP by mask, nasal prong, nasopharyngeal tube or endotracheal tube, compared with spontaneous breathing with supplemental oxygen as necessary.
DATA COLLECTION AND ANALYSIS: We used standard methods of Cochrane and its Neonatal Review Group, including independent assessment of risk of bias and extraction of data by two review authors. We used the GRADE approach to assess the certainty of evidence. Subgroup analyses were planned on the basis of birth weight (greater than or less than 1000 g or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), timing of application (early versus late in the course of respiratory distress), pressure applied (high versus low) and trial setting (tertiary compared with non-tertiary hospitals; high income compared with low income) MAIN RESULTS: We included five studies involving 322 infants; two studies used face mask CPAP, two studies used nasal CPAP and one study used endotracheal CPAP and continuing negative pressure for a small number of less ill babies. For this update, we included one new trial. CPAP was associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.64, 95% confidence interval (CI) 0.50 to 0.82; typical risk difference (RD) -0.19, 95% CI -0.28 to -0.09; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 4 to 11; I2 = 50%; 5 studies, 322 infants; very low-certainty evidence), lower use of ventilatory assistance (typical RR 0.72, 95% CI 0.54 to 0.96; typical RD -0.13, 95% CI -0.25 to -0.02; NNTB 8, 95% CI 4 to 50; I2 = 55%; very low-certainty evidence) and lower overall mortality (typical RR 0.53, 95% CI 0.34 to 0.83; typical RD -0.11, 95% CI -0.18 to -0.04; NNTB 9, 95% CI 2 to 13; I2 = 0%; 5 studies, 322 infants; moderate-certainty evidence). CPAP was associated with increased risk of pneumothorax (typical RR 2.48, 95% CI 1.16 to 5.30; typical RD 0.09, 95% CI 0.02 to 0.16; number needed to treat for an additional harmful outcome (NNTH) 11, 95% CI 7 to 50; I2 = 0%; 4 studies, 274 infants; low-certainty evidence). There was no evidence of a difference in bronchopulmonary dysplasia, defined as oxygen dependency at 28 days (RR 1.04, 95% CI 0.35 to 3.13; I2 = 0%; 2 studies, 209 infants; very low-certainty evidence). The trials did not report use of surfactant, intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis and neurodevelopment outcomes in childhood.
AUTHORS' CONCLUSIONS: In preterm infants with respiratory distress, the application of CPAP is associated with reduced respiratory failure, use of mechanical ventilation and mortality and an increased rate of pneumothorax compared to spontaneous breathing with supplemental oxygen as necessary. Three out of five of these trials were conducted in the 1970s. Therefore, the applicability of these results to current practice is unclear. Further studies in resource-poor settings should be considered and research to determine the most appropriate pressure level needs to be considered.
METHODS: Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified.
RESULTS: Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities.
CONCLUSIONS: A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients.Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, https://clinicaltrials.gov/ct2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597.Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, https://clinicaltrials.gov/ct2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501.Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, https://clinicaltrials.gov/ct2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348.Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), https://clinicaltrials.gov/ct2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.
OBJECTIVES: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.
METHODS: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.
MEASUREMENTS AND MAIN RESULTS: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.
CONCLUSIONS: Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.
METHODS: A systematic review of the literature was performed to identify randomized controlled trials that compared the use of carbetocin to oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was then performed using secondary data from the perspective of a maternity unit within the Malaysian Ministry of Health, over a 24 h time period.
RESULTS: Seven randomized controlled trials with over 2000 patients comparing carbetocin with oxytocin during cesarean section were identified. The use of carbetocin in our center, which has an average of 3000 cesarean deliveries annually, would have prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need for additional uterotonics in 455 patients. The incremental cost effectiveness ratio of carbetocin for averting an episode of PPH was US$278.70.
CONCLUSION: Reduction in retreatment, staffing requirements, transfusion and potential medication errors mitigates the higher index cost of carbetocin. From a pharmacoeconomic perspective, in the context of cesarean section, carbetocin was cost effective as prophylaxis against PPH. Ultimately, the relative value placed on the outcomes above and the individual unit's resources would influence the choice of uterotonic.