The introduction of proton pump inhibitors (PPIs) into clinical practice has revolutionized the management of acid-related diseases. Studies in primary care and emergency settings suggest that PPIs ...are frequently prescribed for inappropriate indications or for indications where their use offers little benefit. Inappropriate PPI use is a matter of great concern, especially in the elderly, who are often affected by multiple comorbidities and are taking multiple medications, and are thus at an increased risk of long-term PPI-related adverse outcomes as well as drug-to-drug interactions. Herein, we aim to review the current literature on PPI use and develop a position paper addressing the benefits and potential harms of acid suppression with the purpose of providing evidence-based guidelines on the appropriate use of these medications.
The topics, identified by a Scientific Committee, were assigned to experts selected by three Italian Scientific Societies, who independently performed a systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were distilled, paying more attention to systematic reviews and meta-analyses (where available) representing the best evidence. The draft prepared on each topic was circulated amongst all the members of the Scientific Committee. Each expert then provided her/his input to the writing, suggesting changes and the inclusion of new material and/or additional relevant references. The global recommendations were then thoroughly discussed in a specific meeting, refined with regard to both content and wording, and approved to obtain a summary of current evidence.
Twenty-five years after their introduction into clinical practice, PPIs remain the mainstay of the treatment of acid-related diseases, where their use in gastroesophageal reflux disease, eosinophilic esophagitis, Helicobacter pylori infection, peptic ulcer disease and bleeding as well as, and Zollinger-Ellison syndrome is appropriate. Prevention of gastroduodenal mucosal lesions (and symptoms) in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or antiplatelet therapies and carrying gastrointestinal risk factors also represents an appropriate indication. On the contrary, steroid use does not need any gastroprotection, unless combined with NSAID therapy. In dyspeptic patients with persisting symptoms, despite successful H. pylori eradication, short-term PPI treatment could be attempted. Finally, addition of PPIs to pancreatic enzyme replacement therapy in patients with refractory steatorrhea may be worthwhile.
Overall, PPIs are irreplaceable drugs in the management of acid-related diseases. However, PPI treatment, as any kind of drug therapy, is not without risk of adverse effects. The overall benefits of therapy and improvement in quality of life significantly outweigh potential harms in most patients, but those without clear clinical indication are only exposed to the risks of PPI prescription. Adhering with evidence-based guidelines represents the only rational approach to effective and safe PPI therapy. Please see related Commentary: doi: 10.1186/s12916-016-0724-1 .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the diagnosis and management of nonvariceal upper gastrointestinal hemorrhage ...(NVUGIH).
Main Recommendations
MR1.
ESGE recommends immediate assessment of hemodynamic status in patients who present with acute upper gastrointestinal hemorrhage (UGIH), with prompt intravascular volume replacement initially using crystalloid fluids if hemodynamic instability exists (strong recommendation, moderate quality evidence).
MR2.
ESGE recommends a restrictive red blood cell transfusion strategy that aims for a target hemoglobin between 7 g/dL and 9 g/dL. A higher target hemoglobin should be considered in patients with significant co-morbidity (e. g., ischemic cardiovascular disease) (strong recommendation, moderate quality evidence).
MR3.
ESGE recommends the use of the Glasgow-Blatchford Score (GBS) for pre-endoscopy risk stratification. Outpatients determined to be at very low risk, based upon a GBS score of 0 – 1, do not require early endoscopy nor hospital admission. Discharged patients should be informed of the risk of recurrent bleeding and be advised to maintain contact with the discharging hospital (strong recommendation, moderate quality evidence).
MR4.
ESGE recommends initiating high dose intravenous proton pump inhibitors (PPI), intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour), in patients presenting with acute UGIH awaiting upper endoscopy. However, PPI infusion should not delay the performance of early endoscopy (strong recommendation, high quality evidence).
MR5.
ESGE does not recommend the routine use of nasogastric or orogastric aspiration/lavage in patients presenting with acute UGIH (strong recommendation, moderate quality evidence).
MR6.
ESGE recommends intravenous erythromycin (single dose, 250 mg given 30 – 120 minutes prior to upper gastrointestinal GI endoscopy) in patients with clinically severe or ongoing active UGIH. In selected patients, pre-endoscopic infusion of erythromycin significantly improves endoscopic visualization, reduces the need for second-look endoscopy, decreases the number of units of blood transfused, and reduces duration of hospital stay (strong recommendation, high quality evidence).
MR7.
Following hemodynamic resuscitation, ESGE recommends early (≤ 24 hours) upper GI endoscopy. Very early (< 12 hours) upper GI endoscopy may be considered in patients with high risk clinical features, namely: hemodynamic instability (tachycardia, hypotension) that persists despite ongoing attempts at volume resuscitation; in-hospital bloody emesis/nasogastric aspirate; or contraindication to the interruption of anticoagulation (strong recommendation, moderate quality evidence).
MR8.
ESGE recommends that peptic ulcers with spurting or oozing bleeding (Forrest classification Ia and Ib, respectively) or with a nonbleeding visible vessel (Forrest classification IIa) receive endoscopic hemostasis because these lesions are at high risk for persistent bleeding or rebleeding (strong recommendation, high quality evidence).
MR9.
ESGE recommends that peptic ulcers with an adherent clot (Forrest classification IIb) be considered for endoscopic clot removal. Once the clot is removed, any identified underlying active bleeding (Forrest classification Ia or Ib) or nonbleeding visible vessel (Forrest classification IIa) should receive endoscopic hemostasis (weak recommendation, moderate quality evidence).
MR10.
In patients with peptic ulcers having a flat pigmented spot (Forrest classification IIc) or clean base (Forrest classification III), ESGE does not recommend endoscopic hemostasis as these stigmata present a low risk of recurrent bleeding. In selected clinical settings, these patients may be discharged to home on standard PPI therapy, e. g., oral PPI once-daily (strong recommendation, moderate quality evidence).
MR11.
ESGE recommends that epinephrine injection therapy not be used as endoscopic monotherapy. If used, it should be combined with a second endoscopic hemostasis modality (strong recommendation, high quality evidence).
MR12.
ESGE recommends PPI therapy for patients who receive endoscopic hemostasis and for patients with adherent clot not receiving endoscopic hemostasis. PPI therapy should be high dose and administered as an intravenous bolus followed by continuous infusion (80 mg then 8 mg/hour) for 72 hours post endoscopy (strong recommendation, high quality evidence).
MR13.
ESGE does not recommend routine second-look endoscopy as part of the management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH). However, in patients with clinical evidence of rebleeding following successful initial endoscopic hemostasis, ESGE recommends repeat upper endoscopy with hemostasis if indicated. In the case of failure of this second attempt at hemostasis, transcatheter angiographic embolization (TAE) or surgery should be considered (strong recommendation, high quality evidence).
MR14.
In patients with NVUGIH secondary to peptic ulcer, ESGE recommends investigating for the presence of
Helicobacter pylori
in the acute setting with initiation of appropriate antibiotic therapy when
H. pylori
is detected. Re-testing for
H. pylori
should be performed in those patients with a negative test in the acute setting. Documentation of successful
H. pylori
eradication is recommended (strong recommendation, high quality evidence).
MR15.
In patients receiving low dose aspirin for secondary cardiovascular prophylaxis who develop peptic ulcer bleeding, ESGE recommends aspirin be resumed immediately following index endoscopy if the risk of rebleeding is low (e. g., FIIc, FIII). In patients with high risk peptic ulcer (FIa, FIb, FIIa, FIIb), early reintroduction of aspirin by day 3 after index endoscopy is recommended, provided that adequate hemostasis has been established (strong recommendation, moderate quality evidence).
Naturally fermented black table olives are usually processed in brine with low pH and high NaCl content. Because salt is responsible for several cardiovascular problems, methods are needed to ...decrease the salt (NaCl) content in olive pulp. This study investigated a new natural processing system wherein microorganism growth is inhibited by slight pressure of CO2 (spCO2), in addition to low pH and NaCl, in brine with decreased salt content. The fermentation performed under spCO2 with a low-salt brine with 6% (w v−1) NaCl and 0.5% (w v−1) citric acid, unlike the traditional system, inhibited the growth of bacteria and fungi and decreased the concentration of yeasts. Processing tests with spCO2 in the presence of different salt and citric acid concentrations indicated a slight decrease in yeasts in brines containing 6% (w v−1) NaCl and 0.6% (w v−1) citric acid but not after inoculation of the same brines with Saccharomyces cerevisiae. In contrast, in the presence of 11% (w v−1) NaCl and 0.3% or 0.6% (w v−1) citric acid, the inhibitory effect of brines was greater compared to those with low-salt and it was also confirmed in the same brines inoculated with S. cerevisiae.
This review sought to describe the role played by some components of the microbiota of extra virgin olive oil (EVOO), particularly yeasts, in structuring the physicochemical and sensorial quality of ...freshly produced olive oil. Yeasts can survive during the entire storage period of the product. To date, approximately 25 yeast species isolated from oil produced in more than six countries have been identified, eight of which are classified as new species. Some yeast species improve the health qualities of oil, whereas many others improve the chemical composition and sensory characteristics based on β‐glucosidase and esterase enzymes, which are involved in the hydrolysis of the bitter glucoside known as oleuropein. However, some species, which are typically favoured by the high water content in the oily matrix, such as lipase‐producing yeasts, can worsen the initial chemical characteristics of EVOO oil during storage. Some physical treatments that are compatible with the EVOO production specification affect the biotic component of the oil by reducing the concentration of yeasts. The possibility of minimizing the invasive action on the biotic component of the oil by appropriately selecting the physical treatment for each oil is discussed.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Naturally fermented black table olives are processed at low pH in the presence of high sodium chloride concentrations ranging from 8 to 12% (w v−1). Reducing the salt content of brine has become an ...urgent issue as it is responsible for several health and environmental problems. The study aim was to evaluate slightly pressurized CO2 (spCO2) as a third barrier to microbial growth in naturally processed black table olives with low pH and a reduced NaCl concentration. Based on the assessments performed on a pilot plant scale, an spCO2 of 1 bar completely inhibited the growth of the bacteria and molds in the presence of reduced saline concentrations. Furthermore, the amount of yeast decreased in the brine as a function of the NaCl content. Laboratory tests performed under spCO2 conditions using a single yeast species from the same habitat confirmed the high sensitivity of some oxidizing yeasts and indicated that the fermenting yeast, Saccharomyces cerevisiae, is the most tolerant species. Overall, in the brine of naturally processed olives with a low pH between 4 and 4.2, the antimicrobial properties observed with the high concentrations of NaCl can be achieved with a lower salt dose of 5% (w v−1) when combined with spCO2.
Abstract
Objectives
Antimicrobial resistance to clarithromycin and metronidazole significantly affects the cure rate of standard therapies for Helicobacter pylori infection. We tested whether ...different MIC levels of resistance to these antibiotics play a role in therapeutic efficacy.
Methods
This was a post hoc analysis of data from a therapeutic trial in which patients with antibiotic susceptibility testing (Etest) received first-line sequential therapy. The level of antibiotic resistance was classified according to MIC values into low (MIC from >0.5 to ≤8 for clarithromycin, and from >8 to ≤32 for metronidazole) and high (MIC from >8 to 256 mg/L for clarithromycin, and from >32 to 256 mg/L for metronidazole).
Results
Data from 1006 patients were included. There were 520 (51.7%) patients with susceptible strains, 136 (13.5%) with clarithromycin-resistant strains, 144 (14.3%) with metronidazole-resistant strains and 206 (20.5%) with clarithromycin-resistant and metronidazole-resistant strains. In the presence of double resistance, the cure rate was still high (38/41, 92.7%) when MIC levels were low and it was reduced (94/112, 83.9%) only when MIC levels of both antibiotics were high. The cure rates did not significantly differ between patients with single antibiotic-resistant strains, irrespective of MIC values, and those with susceptible strains.
Conclusions
We found that MIC levels of resistance to either clarithromycin or metronidazole play a role in H. pylori therapy outcome and that bacterial resistance becomes relevant in vivo when clarithromycin-resistant and metronidazole-resistant strains have high MIC values for at least one of these antibiotics.
Coratina monocultivar extra virgin olive oil (EVOO) is known for its level of bitterness, which, if too high, can cause consumer acceptance problems. The aim of this study was to modulate the bitter ...taste of freshly produced olive oil through endogenous enzymatic activity and microbiota during the decantation phase. The opalescent appearance of the newly produced EVOO was substantially reduced during the first three months of decantation due to the deposition of more than 90% of suspended material, consisting of vegetation water and suspended solid particles. The high content of biophenols and the reduction in water concentration in the oil samples negatively affected the survival of yeasts, which were absent in the oil samples at the end of the third month of decantation. The oleuropeinolytic activity was very intense during the first month of decantation, whereas the reduction in the bitter taste associated with the aglycons was consistent only in the second and third months of decantation. At the end of decantation, the sensory notes of bitterness in the Coratina EVOO were reduced by 33%, lowering the position on the value scale without altering the other qualitative parameters whose values fell within the limits of the commercial EVOO class.
Helicobacter pylori eradication remains a challenge for physicians. Sequential, concomitant and the hybrid regimens have been proposed as novel, more effective therapies. We compare the efficacy of ...these therapies. Dyspeptic patients referred for upper endoscopy with H. pylori infection were enrolled. Patients were randomized to receive: (a) sequential therapy - 20 mg omeprazole and 1 g amoxicillin for 5 days, followed by 20 mg omeprazole, 500 mg clarithromycin and 500 mg tinidazole for the successive 5 days; (b) concomitant therapy - 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for either 5 days (5 day concomitant) or 14 days (14 day concomitant); or (c) hybrid therapy - 20 mg omeprazole and 1 g amoxicillin for 7 days, followed by 20 mg omeprazole, 1 g amoxicillin, 500 mg clarithromycin and 500 mg tinidazole for the successive 7 days. All drugs were given twice daily. Bacterial eradication was checked by using a (13)Curea breath test. In 'intention-to-treat' analysis, sequential therapy achieved the highest eradication rate, which was higher than that of 5 day concomitant therapy (90 vs 78.1 %; P = 0.02). The success rate did not statistically differ among the sequential and either 14 day concomitant (90 vs 86.3 %; P = not significant) or hybrid therapies (90 vs 82.7 %; P = not significant). The 10 day sequential, 14 day concomitant and 14 day hybrid therapies, but not the 5 day concomitant regimen, achieved similarly high eradication rates. The lower therapeutic cost coupled with the lower number of tablets needed would favour the sequential therapy as the first-line H. pylori treatment in clinical practice.
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