Helicobacter pylori therapy: a paradigm shift

Helicobacter pylori (H. Pylori) is a leading cause of gastroduodenal disease, including gastric cancer. H. pylori eradication therapies and their efficacy are summarized. A number of current treatment regimens will reliably yield >90% or 95% cure rates with susceptible strains. None has proven to be superior. We show how to predict the efficacy of a regimen in any population provided one knows the prevalence of antibiotic resistance. As with other infectious diseases, therapy should always be susceptibility-based. Susceptibility testing should be demanded. We provide recommendations for empiric therapies when that is the only option and describe how to distinguish studies providing misinformation from those providing reliable and interpretable data. When treated as an infectious disease, high H. pylori cure rates are relatively simple to reliably achieve.     

Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies

Introduction: Recent Helicobacter pylori treatment guidelines recommend the 4-drug combinations bismuth quadruple therapy and concomitant therapy.

Areas covered: We review antimicrobial therapy for H. pylori in the context of antimicrobial therapy in general and specifically in relation to good antimicrobial stewardship (defined as optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance).

Expert commentary: The lack of regional and local H. pylori susceptibility data prevents implementation of susceptibility-based antimicrobial therapy and forces compromises. Bismuth quadruple therapy employing at least 1,500 mg of metronidazole for 14 days is effective despite metronidazole resistance. The main drawback is side effects causing reduced adherence. Versions where amoxicillin replaces metronidazole or tetracycline also appear effective. It is likely that bismuth quadruple therapy can be simplified by giving bismuth and possibly tetracycline b.i.d., possibly with fewer side effects. Concomitant therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is ineffective with dual clarithromycin-metronidazole resistance and all patients receive at least one unnecessary antibiotic thus promoting antimicrobial resistance worldwide. Concomitant therapy should be abandoned when susceptibility testing becomes widespread or an alternate becomes available.     

Changes in 12-Year First-Line Eradication Rate of Helicobacter pylori Based on Triple Therapy with Proton Pump Inhibitor,Amoxicillin and Clarithromycin

A triple therapy based on a proton pump inhibitor (PPI), amoxicillin (AMPC), and clarithromycin (CAM) is recommended as a first-line therapy for Helicobacter pylori (H. pylori) eradication and is widely used in Japan. However, a decline in eradication rate associated with an increase in prevalence of CAM resistance is viewed as a problem. We investigated CAM resistance and eradication rates over time retrospectively in 750 patients who had undergone the triple therapy as first-line eradication therapy at Nagoya City University Hospital from 1995 to 2008, divided into four terms (Term 1: 1997–2000, Term 2: 2001–2003, Term 3: 2004–2006, Term 4: 2007–2008). Primary resistance to CAM rose significantly over time from 8.7% to 23.5%, 26.7% and 34.5% while the eradication rate decreased significantly from 90.6% to 80.2%, 76.0% and 74.8%. Based on the PPI type, significant declines in eradication rates were observed with omeprazole or lansoprazole, but not with rabeprazole. A decrease in the H. pylori eradication rate after triple therapy using a PPI + AMPC + CAM has been acknowledged, and an increase in CAM resistance is considered to be a factor. From now on, a first-line eradication regimen that results in a higher eradication rate ought to be investigated.     

Strategies for peptic ulcer healing after 1 week proton pump inhibitor-based triple Helicobacter pylori eradication therapy in Japanese patients: differences of gastric ulcers and duodenal ulcers

Helicobacter pylori (H. pylori) eradication therapy alone is insufficient to ensure healing of large ulcers with H. pylori-positive gastric ulcer (GU). The question of what is the optimum antiulcer treatment following H. pylori eradication therapy has not been fully elucidated. Furthermore, the ulcer healing effects of eradication therapy itself with H. pylori-positive duodenal ulcer (DU) have not been investigated. In GU study, the eradication therapy + proton pump inhibitor (PPI) group (group A) were administered eradication therapy followed by 7 weeks of a PPI, and the eradication therapy + gastroprotective drug (GP) group (group B) eradication therapy followed by 7 weeks of a GP. In DU study, the eradication therapy + PPI group (group C) were administered eradication therapy followed by 5 weeks of a PPI, and the eradication therapy only group (group D) was eradication therapy alone. In GU study, healing rates for ulcer of ≥15 mm in diameter were significant greater in the group A. In DU study, high healing rates were seen both the group C and D. In conclusion, a PPI could significantly heal GU than a GP after eradication therapy in GU. Meanwhile, the eradication alone is sufficient for DU.     

Upper Gastrointestinal Bleeding: Etiologies and Management

Upper gastrointestinal bleeding is a medical condition routinely encountered in clinical practice. Overt upper gastrointestinal bleeding usually presents as melena or hematemesis but can also present as hematochezia in cases of brisk bleeding. The initial evaluation of a patient with suspected upper gastrointestinal bleeding begins with assessment of hemodynamic status, identification of potential risk factors, and appropriate triage of level of care. After resuscitation measures, endoscopic evaluation can be performed to diagnose and potentially treat the source of bleeding. Risk factors that increase the propensity for recurrent bleeding should be identified and addressed.     

Meta-analysis: Methods, strengths, weaknesses, and political uses

The general methodology, strengths and weaknesses, and political uses of meta-analysis are examined. As a systematic study of all studies that have been conducted to answer a specific question or hypothesis, meta-analysis is strong in revealing structural flaws and sources of bias in primary research and in posing promising research questions for future study. It cannot exceed, however, the limits of what is reported by primary researchers. Meta-analysis is particularly challenged to quantify the size of a common effect of treatment across reported trials because of (1) the clinical diversity of the trials and (2) the myriad of potential differences among patients with varying characteristics within the trials. Without access to the original data of reported trials, meta-analysis cannot overcome the bias of underpowered trials toward overstatement of the size of main treatment effects, nor the tendency for such trials to falsely conclude there were no statistically significant adverse events. Although severely compromised by ghost-written or honorary-authored reports of primary research, meta-analysis can make use of its methods to focus on the conflicts of interest and likely sources of bias of such research and make known what precautions should be taken by would-be consumers. Examples show how meta-analysis has clarified thinking about the off-label use of selective serotonin reuptake inhibitors for treating child and adolescent depression, use of low-tidal volume respirator assistance for acute lung injury and acute respiratory distress syndrome patients, and the long-term use of COX-2 inhibitors for relieving arthritic pain. Recommendations are made for Congressional action.     

Allocation Concealment and Intention-To-Treat Analysis Do Not Influence the Treatment Effects of Physical Therapy Interventions in Low Back Pain Trials: a Meta-epidemiologic Study

ObjectiveTo evaluate if allocation concealment and intention-to-treat (ITT) analysis influence the treatment effects of physical therapy interventions in low back pain (LBP) trials.Data SourcesWe searched on PubMed, Embase, Cochrane Database of Systematic Reviews, Physiotherapy Evidence Database (PEDro), and CINAHL up to February 2017.Study SelectionWe included LBP trials that compared physical therapy interventions to placebo or no intervention or minimal intervention with pain or disability outcomes.Data ExtractionInformation about allocation concealment and ITT analysis was extracted from PEDro and pain and disability outcomes converted to a 0-100 scale. A meta-regression was performed to evaluate the influence of these methodological features of interest on treatment effects. Other covariates included in the meta-regression were sample size and sequence generation.Data SynthesisWe identified 128 eligible trials (pooled N=20,555 participants). A total of 44.5% of the trials achieved allocation concealment, while 32% performed ITT analysis. Meta regression analyses showed no influence of allocation concealment on treatment effects for pain (regression coefficient 0.009; 95% confidence interval [CI] -2.91 to 2.91) and disability (regression coefficient 1.13; 95% CI -1.35 to 3.62), and no influence of ITT analysis for pain (regression coefficient 1.38; 95% CI -1.73 to 4.50) or disability (regression coefficient 1.27; 95% CI -1.39 to 3.64). For the other covariates, there was also no clinically significant influence on the treatment effects.ConclusionThere is no influence of allocation concealment or ITT analysis on treatment effects of physical therapy interventions for pain and disability in LBP trials.     

Effectiveness of Supervised Home-Based Exercise Therapy Compared to a Control Intervention on Functions,Activities, and Participation in Older Patients After Hip Fracture: A Systematic Review and Meta-analysis

Objective

The aim of this review was to investigate whether supervised home-based exercise therapy after hospitalization is more effective on improving functions, activities, and participation in older patients after hip fracture than a control intervention (including usual care). Furthermore, we aimed to account the body of evidence for therapeutic validity.

The efficacy and safety of sitafloxacin and garenoxacin for the treatment of pneumonia in elderly patients: A randomized,multicenter, open-label trial

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3–10 days. The primary efficacy endpoint was the clinical cure rate at 5–10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6–95.6) and 88.9% (95% confidence interval: 77.4–95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.     

The Effectiveness of Instrument-Assisted Soft Tissue Mobilization in Athletes,Participants Without Extremity or Spinal Conditions,and Individuals with Upper Extremity,Lower Extremity,and Spinal Conditions: A Systematic Review

ObjectiveTo assess the effectiveness of instrument-assisted soft tissue mobilization (IASTM) to other treatments or placebo in athletes or participants without extremity or spinal conditions and individuals with upper extremity, lower extremity, and spinal conditions.Data SourcesThe MEDLINE, EMBASE, CINAHL, and PEDro electronic databases were searched from January 1998 to March 2018.Study SelectionRandomized controlled trials of participants without extremity or spinal conditions or athletes and people with upper extremity, lower extremity, or spinal conditions, who revived IASTM vs other active treatment, placebo, or control (no treatment), to improve outcome (function, pain, range of motion).Data ExtractionTwo independent review authors extracted data, assessed the trials for risk of bias using the Cochrane Risk of Bias tool in included studies, and performed the rating of quality of individual trials per outcome across trials was also performed using the Grading of Recommendations, Assessment, Development, and Evaluations guidelines.Data SynthesisNine trials with 43 reported outcomes (function, pain, range of motion, grip strength), compared the addition of IASTM over other treatments vs other treatments. Six trials with 36 outcomes reported no clinically important differences in outcomes between the 2 groups. Two trials with 2 outcomes displayed clinically important differences favoring the other treatment (without IASTM) group. Six trials with 15 reported outcomes (pressure sensitivity, pain, range of motion, muscle performance), compared IASTM vs control (no treatment). Three trials with 5 outcomes reported no clinically important differences in outcomes between the 2 groups. Furthermore, in 1 trial with 5 outcomes, IASTM demonstrated small effects (standard mean difference range 0.03-0.24) in terms of improvement muscle performance in physically active individuals when compared to a no treatment group.ConclusionThe current evidence does not support the use of IASTM to improve pain, function, or range of motion in individuals without extremity or spinal conditions or those with varied pathologies.