Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage.

BACKGROUND: Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES: To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome.  MAIN RESULTS: We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS: We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.

Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care. OBJECTIVES: To assess the effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources. SELECTION CRITERIA: Randomised clinical trials (RCTs) comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity. MAIN RESULTS: In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales. In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured. AUTHORS' CONCLUSIONS: Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.

Statins for aortic valve stenosis.

BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. SELECTION CRITERIA: Randomised controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. DATA COLLECTION AND ANALYSIS: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalisation for any reason, overall mortality, adverse events and patient quality of life.Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0.14; participants = 155; study = 1). Moderate-quality evidence showed no effect on freedom from valve replacement with statins (risk ratio (RR) 0.93, 95% CI 0.81 to 1.06; participants = 2360; studies = 4), and no effect on muscle pain as an adverse event (RR 0.91, 95% CI 0.75 to 1.09; participants = 2204; studies = 3; moderate-quality evidence). Low- and very low-quality evidence showed uncertainty around the effect of statins on death from cardiovascular cause (RR 0.80, 95% CI 0.56 to 1.15; participants = 2297; studies = 3; low-quality evidence) and hospitalisation for any reason (RR 0.84, 95% CI 0.39 to 1.84; participants = 155; study = 1; very low-quality evidence). None of the four included studies reported on overall mortality and patient quality of life. AUTHORS' CONCLUSIONS: Result findings showed uncertainty surrounding the effect of statins for aortic valve stenosis.The quality of evidence from the reported outcomes ranged from moderate to very low. These results give support to European and USA guidelines (2012 and 2014, respectively) that so far there is no clinical treatment option for aortic valve stenosis.