OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults.
SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence.
MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics.
AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.
Methods: A prospective, observational single-centre study was conducted where all 504 cases that were consecutively admitted for pneumonia were enrolled. Blood and sputum samples obtained were used to identify pathogens using standard microbiological culture methods. The urine samples collected were tested using the ImmunocatchTMLegionella immunochromatographic (ICT) urine antigen test.
Results: A microbiological diagnosis was only achieved in 104 cases (20.6%) and a Gram-negative infection predominance was observed. Culture-positive cases required longer hospitalisation (8.46 days versus 5.53 days; P < 0.001) and the higher usage of antipseudomonal antibiotics (23.1% versus 8.3%; P < 0.001). Only 3 cases (0.6%) were diagnosed with Legionella pneumonia.
Conclusion: The local pathogen distribution is diverse compared to other regions. Culture-negative pneumonia is common and significantly differs from culture-positive pneumonia. Legionella pneumophila serotype 1 is not a common cause of pneumonia and LUAT did not help demystify the cause of culture-negative pneumonia.
Methods: A single-centre, retrospective cohort study was conducted. From 2014 to 2018, all patients over 40 years old with COPD who were admitted to the hospital with a case of COPD exacerbation and received systemic corticosteroids at presentation were included. The subjects were divided into two groups according to the duration of systemic corticosteroid therapy. The primary outcome was hospital re-admission within 180 days. The secondary outcomes were 30 days mortality and length of hospitalisation. The two groups were compared using an independent sample t-test, a Chi-square test, and a Mann-Whitney U test, according to the data type.
Results: Eighty patients met the inclusion criteria. A total of 52 (65%) patients completed long-term therapy, while 28 (35%) patients were on short-term treatment. A total of 15 (28.8%) patients reached the primary endpoint in the long-term treatment group versus 19 (67.9%) in the short-term treatment group (P = 0.001). The 30-day mortality was 4 (7.7%) and 0 (0%), respectively, and the median length of hospitalisation was 6.5 and 7.5 days in the long-term group and short-term group, respectively (P = 0.32, P = 0.88).
Conclusion: Long-term corticosteroid use in the management of acute COPD exacerbation was significantly associated with fewer 180 days re-admission. The duration of corticosteroid use remains controversial, and further studies are recommended to assess the relationship between patient profile and adherence to therapy post-discharge with re-exacerbation.
OBJECTIVES: To assess the effect of increased energy intake on mortality and respiratory, growth and neurodevelopmental outcomes for preterm infants with (or developing) CLD/BPD. Secondarily, the review examines any adverse effects associated with increased energy intake.
SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) , MEDLINE (accessed via Ovid), references cited in previous relevant Cochrane reviews and in other relevant studies, review articles, standard textbooks, and manuals of neonatal medicine. Hand search results of the Cochrane Neonatal Review Group were also assessed.
SELECTION CRITERIA: All randomized and quasi-randomized trials comparing the outcomes of preterm infants with (or developing) CLD/BPD who had either increased (> 135 kcal/kg/day) or standard energy intake (98 to 135 kcal/kg/day). Increasing energy intake might be achieved enterally and/or parenterally, enterally by increasing the energy content of the milk, increasing feed volume, or by nutrient supplementation with protein, carbohydrate or fat. The primary outcomes were the development of CLD and neonatal mortality; secondary outcomes included respiratory morbidities, growth, neurodevelopmental status and possible complications with increased energy intake.
DATA COLLECTION AND ANALYSIS: We planned to extract data using the standard methods of the Cochrane Neonatal Review Group. Relevant trials would be scrutinized for methodological quality independently by the reviewers to determine their eligibility for inclusion. Data of the included trials would be expressed as relative risk, risk difference, NNT and weighted mean difference where appropriate, using a fixed effect model.
MAIN RESULTS: No eligible trials were identified. Twelve studies that appeared to be relevant were excluded, as no study directly compared increased versus standard energy intakes in infants with CLD/BPD. However, two excluded trials provided some insights into the topic. One study showed that infants with CLD/BPD who were fed formula enriched with protein and minerals had improved growth parameters up until the cessation of the intervention at three months of corrected age. The other study compared different energy density of formula but identical energy intake by setting different feed volumes for both groups. It showed that both groups were unable to achieve the pre-designated feed volumes, and that there were no differences in growth, respiratory outcomes, oedema and the diuretic requirements.
AUTHORS' CONCLUSIONS: To date, no randomized controlled trials are available that examine the effects of increased versus standard energy intake for preterm infants with (or developing) CLD/BPD. Research should be directed at evaluating the effects of various levels of energy intake on this group of infants on clinically important outcomes like mortality, respiratory status, growth and neurodevelopment. The benefits and harms of various ways of increasing energy intake, including higher energy density of milk feed and/or fluid volume (clinically realistic target volume should be set), parenteral nutrition, and the use of various constituents of energy like carbohydrate, protein and fat for this purpose also need to be assessed.
METHODS: Cross-sectional data from a multicenter cohort of 419 HF outpatients were used. Both direct and indirect mapping approaches were attempted using 5 sets of explanatory variables and 8 models (ordinary least squares, Tobit, censored least absolute deviations, generalized linear model, 2-part model [TPM], beta regression-based model, adjusted limited dependent variable mixture model, and multinomial ordinal regression [MLOGIT]). The models' predictive performance was assessed through 10-fold cross-validated mean absolute error [MAE] and root mean squared error [RMSE]). Potential prediction bias was also examined graphically. The best-performing models, with the lowest RMSE and no bias, were then identified.
RESULTS: Among the models evaluated, TPM, which included age, sex, and 5 AQoL-6D dimension scores as predictors, appears to be the best-performing model for directly predicting EQ-5D-5L HSUVs from AQoL-6D. TPM yielded the lowest MAE (0.0802) and RMSE (0.1116), and demonstrated predictive accuracy for HSUVs >0.2 without significant bias. A MLOGIT model developed for response mapping had suboptimal predictive accuracy.
CONCLUSIONS: This study developed potentially useful mapping algorithms for generating Malaysian EQ-5D-5L HSUVs from AQoL-6D responses among patients with HF when direct EQ-5D-5L data are unavailable.
MATERIALS AND METHODS: 18 patients with histologically confirmed early NSCLC (stage I-IIIA) were recruited from October 2019 to January 2021. The serum CEA was measured pre-operatively, and then at 6, 12, 18 and 24 months post-operatively, in conjunction with routine CT and/or CT-PET surveillance scans.
RESULTS: All patients had a curative R0 anatomical resection (lobectomy) with concurrent systematic mediastinal nodal dissection via a uniportal minimally invasive approach under single lung ventilation general anaesthesia. There was no operative, in-hospital or 30-day mortality. 7 patients (39%) had an elevated pre-operative baseline CEA level > 5.0ng/ml. The mean number of nodes sampled intraoperatively was 15. At median follow-up of 42 months, 11/18 (61.1%) patients were recurrence-free. There were no deaths and two recurrences (18.2%) amongst patients with a CEA < 5 (n=11). In the CEA > 5 subgroup (n=7), there were two deaths (28.5%) and 5/7 (71.4%) patients had a radiological recurrence. There was no difference in overall survival however disease-free survival (DFS) was significantly inferior in patients with a baseline CEA > 5. Median DFS was not reached in patients with CEA < 5 and 18 months in those with an elevated CEA > 5 (p<0.001) Conclusion: Almost 40% of local NSCLC patients had an elevated baseline CEA suggesting this is a useful prognostic and surveillance biomarker to incorporate in the routine work-up for any newly diagnosed NSCLC. Despite curative R0 resection and extensive intra-operative mediastinal lymph node sampling, an elevated pre-operative CEA was associated with a significantly reduced DFS and may be a surrogate for more aggressive tumour biology. Such patients will benefit from meticulous post resection surveillance and adjuvant therapy beyond conventional TNM criteria.
METHODS: The 62-item questionnaire was distributed electronically via email. The questions covered five domains: (1) structure of the IRD service and registry/database; (2) genotyping practices; (3) genetic counselling; (4) deep phenotyping practices; (5) low-vision rehabilitation services.
RESULTS: The survey was completed by 36 of 45 centres in twelve countries and regions in APAC. Among these centres, 42 % reported managing more than 1000 patients. Notably, 39 % of centres lack an IRD database or registry, and 44 % of centres have tested less than one-quarter of their IRD patients. The majority of centres (67 %) do not have genetic counsellors. While there was consistency in the imaging-based investigations, there was marked heterogeneity for functional testing using electrophysiology and formal perimetry. Only 34 % of centres confirmed the availability of access to low-vision assistive devices.
CONCLUSIONS: This study reveals several critical gaps in managing IRDs in the APAC region. These include the lack of IRD database/registry in one-third of centres, a substantial proportion of patients remaining genetically undiagnosed, and limited availability of genetic counsellors. The findings also underscore a need to harmonise investigations for evaluating retinal function and identify areas for improvement in the provision of low-vision rehabilitation services.