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Pharmaceuticals (Basel, Switzerland) May 2024Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to... (Review)
Review
Comparative Efficacy and Safety of Potassium-Competitive Acid Blockers vs. Proton Pump Inhibitors for Peptic Ulcer with or without Infection: A Systematic Review and Network Meta-Analysis.
Novel potassium-competitive acid blockers (P-CABs) have emerged as effective acid-suppressive drugs in recent years, replacing proton pump inhibitors (PPIs). We aim to compare the efficacy and safety of P-CABs versus PPIs in the treatment of peptic ulcers with or without () infection. We searched in PubMed, Embase, WOS, Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang databases (all years up to January 2024). Efficacy and safety outcomes were evaluated using odds ratio (OR) and 95% confidence intervals (CI). The Surface Under the Cumulative Ranking (SUCRA) probabilities were used to rank each intervention. Among 14,056 studies screened, 56 studies involving 9792 participants were analyzed. Vonoprazan demonstrated the best efficacy in ulcer healing rate and eradication rate (SUCRA = 86.4% and 90.7%, respectively). Keverprazan ranked second in ulcer healing rates (SUCRA = 76.0%) and was more effective in pain remission rates (SUCRA = 91.7%). The risk of adverse events was low for keverprazan (SUCRA = 11.8%) and tegoprazan (SUCRA = 12.9%), and moderate risk for vonoprazan (SUCRA = 44.3%) was demonstrated. Compared to lansoprazole, vonoprazan exhibited a higher risk of drug-related adverse events (OR: 2.15; 95% CI: 1.60-2.89) and serious adverse events (OR: 2.22; 95% CI: 1.11-4.42). Subgroup analysis on patients with -positive peptic ulcers showed that vonoprazan was at the top of the SUCRA rankings, followed by keverprazan. Vonoprazan showed superior performance in peptic ulcers, especially for patients with -positive peptic ulcers. However, the risk of adverse events associated with vonoprazan should be noted. Keverprazan has also shown good therapeutic outcomes and has performed better in terms of safety.
PubMed: 38931366
DOI: 10.3390/ph17060698 -
Therapeutic Advances in Gastroenterology 2024Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it... (Review)
Review
BACKGROUND
Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE.
OBJECTIVES
This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose.
DESIGN
A systematic review and network meta-analysis.
DATA SOURCES AND METHODS
Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted.
RESULTS
In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline.
CONCLUSION
This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients.
TRIAL REGISTRATION
The study protocol was registered with INPLASY (registration number INPLASY2023120053).
PubMed: 38903448
DOI: 10.1177/17562848241251567 -
Helicobacter 2024The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The amoxicillin dose used in dual therapy to eradicate Helicobacter pylori varies across studies and the optimal amoxicillin dose for vonoprazan-based dual therapies remains unclear. We aimed to investigate the efficacy and safety of low- and high-dose amoxicillin in vonoprazan-amoxicillin dual therapy.
MATERIALS AND METHODS
A comprehensive systematic review was conducted by searching databases from inception to October 2023. All trials that evaluated the effectiveness and safety of vonoprazan-amoxicillin dual therapy for eradicating H. pylori were included. Pooled eradication rate, incidence of adverse events, relative risks, and 95% confidence intervals are presented.
RESULTS
Eighteen studies with 12 low-dose amoxicillin (VLA) and 13 high-dose amoxicillin (VHA) arms were included. The pooled eradication rates were 82.4% and 86.8% for VLA therapy, and 86.0% and 90.9% for VHA therapy by the intention-to-treat and per-protocol analyses, respectively. In the subgroup analysis stratified by duration, the eradication rates achieved in 7 days, 10 days, and 14 days treatments with VLA and VHA dual therapies were 80.8%, 84.2%, 83.1%, and 67.3%, 88.8%, 87.5%, respectively. In the four randomized controlled trials that directly compared VLA and VHA dual therapies, the efficacy was not statistically different in the intention-to-treat (76.9% vs 81.4%, p = 0.337) and per-protocol (81.6% vs 84.0%, p = 0.166) analyses. Additionally, the incidence of adverse events (p = 0.965) and compliance (p = 0.994) were similar in both groups.
CONCLUSION
VLA therapy demonstrated comparable efficacy and safety to VHA therapy, along with regional differences. An appropriately extended treatment duration may be critical for therapeutic optimization of vonoprazan-amoxicillin treatment.
Topics: Amoxicillin; Humans; Helicobacter Infections; Sulfonamides; Pyrroles; Helicobacter pylori; Drug Therapy, Combination; Anti-Bacterial Agents; Treatment Outcome; Proton Pump Inhibitors
PubMed: 38900537
DOI: 10.1111/hel.13054 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024To date, treatment of chordomas involves maximal tumor resection followed by proton therapy. Various approaches are used depending on location of tumor (transcranial and...
UNLABELLED
To date, treatment of chordomas involves maximal tumor resection followed by proton therapy. Various approaches are used depending on location of tumor (transcranial and through natural anatomical openings (nose, mouth), as well as their combinations). Although transoral approach has been introduced into neurosurgical practice for a long time, it is routinely used in patients with chordoma only in certain hospitals in the world.
OBJECTIVE
To analyze postoperative outcomes in patients with chordomas of skull base and craniovertebral joint after transoral surgery.
MATERIAL AND METHODS
We analyzed literature data devoted to patients with chordomas of skull base and craniovertebral joint after transoral surgery or another approach combined with transoral access. Among 111 primary articles, we selected 38 manuscripts including description of 109 patients with skull base chordoma who underwent transoral surgery or combination of approaches including transoral one.
RESULTS
Gross total resection was achieved in 45.9% (=50) of cases including 1 patient after en bloc resection. Subtotal resection was carried out in 28.4% of cases, partial - in 24.8%, biopsy - in 0.9% of cases. The complication rate in this group was 30%. The most common events were swelling of the tongue (10%) and diastasis of posterior pharyngeal wall sutures (8.2%) that required redo surgery. CSF leakage and meningitis were rare (1.8% and 3.6%, respectively).
CONCLUSION
Transoral access allows for gross total resection of midline tumors with low incidence of severe complications. Combination of transoral and transcranial approaches is advisable to increase extent of resection.
Topics: Humans; Chordoma; Skull Base Neoplasms; Female; Neurosurgical Procedures; Male
PubMed: 38881024
DOI: 10.17116/neiro202488031111 -
NEJM Evidence Jul 2024The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients.
METHODS
We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses.
RESULTS
Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on infection (low certainty).
CONCLUSIONS
High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).
Topics: Humans; Proton Pump Inhibitors; Gastrointestinal Hemorrhage; Critical Illness; Randomized Controlled Trials as Topic
PubMed: 38874580
DOI: 10.1056/EVIDoa2400134 -
Digestive Diseases and Sciences Jun 2024Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients.
BACKGROUND
Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients.
AIM
This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding.
METHODS
Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included.
RESULTS
The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I = 91.6%], 3% [95% CI - 2 to 8, I = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I = 0%], all-cause mortality rate was 17% [95% CI 12-22, I = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor.
CONCLUSIONS
Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.
PubMed: 38864930
DOI: 10.1007/s10620-024-08482-x -
BMC Primary Care Jun 2024Proton Pump Inhibitors (PPI) are frequently prescribed. Long-term use is associated with side-effects and patients often lack a valid indication. Inappropriate PPI...
BACKGROUND
Proton Pump Inhibitors (PPI) are frequently prescribed. Long-term use is associated with side-effects and patients often lack a valid indication. Inappropriate PPI prescribing thus needs to be addressed. This review aims to scope 1) what determinants are studied as reasons for PPI prescribing, 2) what strategies are used for changing PPI (de)prescribing, and 3) whether important determinants are addressed in these interventions.
METHODS
We searched eight databases for papers on determinants of physician PPI prescribing. Studies were included if they were conducted in a Western country and focused on oral PPIs for an adult population. By following the Behaviour Change Wheel, we extracted information regarding PPI prescribing behavior, behavioral determinants and intervention strategies.
FINDINGS
We included 74 papers. Most focused on the determinants knowledge and beliefs about consequences. The latter was consistently related to PPI prescribing. Results for knowledge were mixed. Most interventions used education or enablement (e.g., algorithms, quality check improvements, involvement of pharmacists) as strategies. Enablement consistently improved PPI prescribing, while results for education were mixed.
INTERPRETATION
There is an overemphasis on reflective processes in studies on PPI prescribing. Future research should comprehensively identify behavioral determinants, focusing on reflective and impulsive processes, such that interventions can address the most important determinants.
Topics: Proton Pump Inhibitors; Humans; Practice Patterns, Physicians'; Inappropriate Prescribing; Health Knowledge, Attitudes, Practice; Drug Prescriptions
PubMed: 38862886
DOI: 10.1186/s12875-024-02459-5 -
Clinical and Molecular Hepatology Jun 2024Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The...
BACKGROUND/AIMS
Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The current systemic review aimed to assess the changes in MRI-determined hepatic proton density fat fraction (MRI-PDFF) and nonalcoholic fatty liver disease activity score (NAS) after bariatric surgery or intragastric balloon/gastric banding in MASLD patients with obesity.
METHODS
We searched various databases including PubMed, OVID Medline, EMBASE, and Cochrane Library. Primary outcomes were the changes in intrahepatic fat on MRI-PDFF and histologic features of metabolic dysfunction-associated steatohepatitis (MASH).
RESULTS
Thirty studies with a total of 3,134 patients were selected for meta-analysis. Bariatric intervention significantly reduced BMI (ratio of means, 0.79) and showed 72% of reduction of intrahepatic fat on MRI-PDFF at 6 months after bariatric intervention (ratio of means, 0.28). Eight studies revealed that NAS was reduced 60% at 3-6 months compared to baseline, 40% at 12-24 months, and 50% at 36-60 months. Nineteen studies revealed that the proportion of patients with steatosis decreased by 44% at 3-6 months, 37% at 12-24 months, and 29% at 36-60 months; lobular inflammation by 36% at 12-24 months and 51% at 36-60 months; ballooning degeneration by 38% at 12-24 months; significant fibrosis (≥F2) by 18% at 12-24 months and by 17% at 36-60 months after intervention.
CONCLUSIONS
Bariatric intervention significantly improved MRI-PDFF and histologic features of MASH in patients with obesity. Bariatric intervention might be the effective alternative treatment option for patients MASLD who do not respond to life style modification or medical treatment.
PubMed: 38830642
DOI: 10.3350/cmh.2023.0384 -
Radiotherapy and Oncology : Journal of... Jun 2024Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of... (Review)
Review
Compared to conventional radiotherapy using X-rays, proton therapy, in principle, allows better conformity of the dose distribution to target volumes, at the cost of greater sensitivity to physical, anatomical, and positioning uncertainties. Robust planning, both in terms of plan optimization and evaluation, has gained high visibility in publications on the subject and is part of clinical practice in many centers. However, there is currently no consensus on the methods and parameters to be used for robust optimization or robustness evaluation. We propose to overcome this deficiency by following the modified Delphi consensus method. This method first requires a systematic review of the literature. We performed this review using the PubMed and Web Of Science databases, via two different experts. Potential conflicts were resolved by a third expert. We then explored the different methods before focusing on clinical studies that evaluate robustness on a significant number of patients. Many robustness assessment methods are proposed in the literature. Some are more successful than others and their implementation varies between centers. Moreover, they are not all statistically or mathematically equivalent. The most sophisticated and rigorous methods have seen more limited application due to the difficulty of their implementation and their lack of widespread availability.
PubMed: 38830538
DOI: 10.1016/j.radonc.2024.110365 -
European Journal of Gastroenterology &... Jul 2024Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump...
Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.
Topics: Humans; Proton Pump Inhibitors; Polyps; Female; Confounding Factors, Epidemiologic; Risk Factors; Male; Stomach Neoplasms
PubMed: 38829941
DOI: 10.1097/MEG.0000000000002788