ABSTRACT
There are no guidelines for the most effective medication to reduce hepatic encephalopathy (HE) or the associated mortality. The purpose of this study is to determine the most effective possible treatment among the single treatment options or the combined treatment options for decreasing the morbidity and mortality of HE. We evaluated the outcomes by various parameters such as the quality of life, reduction in ammonia, all causes of mortality, adverse events, reversal of minimal HE, and development of overt HE. We systematically searched PubMed, Cochrane, Web of Science, and Scopus till the 19th of January 2023 for studies that assess various treatment options for HE. Data were extracted from eligible studies and pooled in a frequentist network meta-analysis as standardized mean difference (SMD) and their 95% confidence interval (CI) using the MetaInsight web-based tool. The Cochrane Tool was used to assess the randomized controlled trials' quality (RCT), while the NIH tool was used to assess the quality of the included cohort studies. Utilizing the R software, the network meta-analysis was conducted. In addition to a significant variation in cases of (Lactulose and Rifaximin) compared with Rifaximin (RR= 0.39, 95% CI [0.17; 0.89]), the results demonstrated a significantly lower incidence of overt HE in (Lactulose and Rifaximin) compared with placebo (RR=0.19, 95% CI [0.09; 0.40]). Most arms demonstrated a statistically significant reduction in the incidence of overt HE compared to albumin and placebo. The results also demonstrated a significant reduction in ammonia between L-ornithine-L-aspartate (LOLA) and probiotics (MD= -19.17, 95% CI [-38.01; -0.32]), as well as a significant difference in the incidence of LOLA compared to placebo (MD= -22.62, 95% CI [-39.16; -6.07]). This network meta-analysis has significant data for managing subclinical HE in people without a history of overt HE. Our analysis showed that (Lactulose and Rifaximin), followed by (Rifaximin and L-carnitine), followed by (Lactulose and Rifaximin with zinc) were the best combinations regarding overt HE. LOLA reduced ammonia best, followed by Nitazoxanide and finally Lactulose. (Lactulose and Nitazoxanide) have the least adverse effects, followed by (Rifaximin and L-carnitine), then Probiotics. Yet, all mortality outcomes and quality of life changes yielded no useful findings. Future studies like RCTs must be done to compare our therapies directly.
ABSTRACT
Background: More than six million people died due to COVID-19, and 10-15% of infected individuals suffer from post-covid syndrome. Corticosteroids are widely used in the management of severe COVID-19 and post-acute COVID-19 symptoms. This study synthesizes current evidence of the effectiveness of inhaled corticosteroids (ICS) on mortality, hospital length-of-stay (LOS), and improvement of smell scores in patients with COVID-19. Methods: We searched Embase, Web of Science, PubMed, Cochrane Library, and Scopus until Aug 2022. The Cochrane risk of bias tool was used to assess the quality of studies. We evaluated the effectiveness of ICS in COVID-19 patients through measures of mortality, LOS, alleviation of post-acute COVID-19 symptoms, time to sustained self-reported cure, and sense of smell (visual analog scale (VAS)). Results: Ten studies were included in the meta-analysis. Our study showed a significant decrease in the LOS in ICS patients over placebo (MD = -1.52, 95% CI [-2.77 to -0.28], p-value = 0.02). Patients treated with intranasal corticosteroids (INC) showed a significant improvement in VAS smell scores from week three to week four (MD =1.52, 95% CI [0.27 to 2.78], p-value = 0.02), and alleviation of COVID-related symptoms after 14 days (RR = 1.17, 95% CI [1.09 to 1.26], p-value < 0.0001). No significant differences were detected in mortality (RR= 0.69, 95% CI [0.36 to 1.35], p-value = 0.28) and time to sustained self-reported cure (MD = -1.28, 95% CI [-6.77 to 4.20], p-value = 0.65). Conclusion: We concluded that the use of ICS decreased patient LOS and improved COVID-19-related symptoms. INC may have a role in improving the smell score. Therefore, using INC and ICS for two weeks or more may prove beneficial. Current data do not demonstrate an effect on mortality or time to sustained self-reported cure. However, the evidence is inconclusive, and more studies are needed for more precise data.
ABSTRACT
BACKGROUND: Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or precluding chemotherapy entirely. Prior studies have suggested that using common cardioprotective agents may attenuate chemotherapy-induced cardiotoxicity. However, small sample sizes and conflicting outcomes have limited the clinical significance of these results. HYPOTHESIS: A comprehensive network meta-analysis using updated and high-quality data can provide more conclusive information to assess which drug or drug class has the most significant effect in the management of chemotherapy-induced cardiotoxicity. METHODS: We performed a literature search for randomized controlled trials (RCTs) investigating the effects of cardioprotective agents in patients with chemotherapy-induced cardiotoxicity. We used established analytical tools (netmeta package in RStudio) and data extraction formats to analyze the outcome data. To obviate systematic bias in the selection and interpretation of RCTs, we employed the validated Cochrane risk-of-bias tools. Agents included were statins, aldosterone receptor antagonists (MRAs), ACEIs, ARBs, and beta-blockers. Outcomes examined were improvement in clinical and laboratory parameters of cardiac function including a decreased reduction in left ventricular ejection fraction (LVEF), clinical HF, troponin-I, and B-natriuretic peptide levels. RESULTS: Our study included 33 RCTs including a total of 3,285 patients. Compared to control groups, spironolactone therapy was associated with the greatest LVEF improvement (Mean difference (MD) = 12.80, [7.90; 17.70]), followed by enalapril (MD = 7.62, [5.31; 9.94]), nebivolol (MD = 7.30, [2.39; 12.21]), and statins (MD = 6.72, [3.58; 9.85]). Spironolactone was also associated with a significant reduction in troponin elevation (MD = - 0.01, [- 0.02; - 0.01]). Enalapril demonstrated the greatest BNP reduction (MD = - 49.00, [- 68.89; - 29.11]), which was followed by spironolactone (MD = - 16.00, [- 23.9; - 8.10]). Additionally, patients on enalapril had the lowest risk of developing clinical HF compared to the control population (RR = 0.05, [0.00; 0.75]). CONCLUSION: Our analysis reaffirmed that statins, MRAs, ACEIs, and beta-blockers can significantly attenuate chemotherapy-induced cardiotoxicity, while ARBs showed no significant effects. Spironolactone showed the most robust improvement of LVEF, which best supports its use among this population. Our analysis warrants future clinical studies examining the cardioprotective effects of cardiac remodeling therapy in cancer patients treated with chemotherapeutic agents.
