Helicobacter pylori Infection: A 40-Year Journey through Shifting the Paradigm to Transforming the Management.

BACKGROUND: Helicobacter pylori (H. pylori) was discovered 40 years ago and has set a milestone in human medicine. The discovery led to rejection of the dogma of the acidic stomach as a sterile organ and requested to rewrite the chapters on gastric pathophysiology and gastroduodenal diseases. SUMMARY: Over a period of 40 years following the discovery, more than 50,000 articles can be retrieved in PubMed as of today and illustrate the amount and the intensity of research around the role of this bacterium. H. pylori emerged as cause of chronic gastritis and principal cause of peptic ulcer disease (PUD). Eradication of H. pylori became standard of care in management in PUD. The importance of this was highlighted in 2005 with the Nobel Prize in Medicine awarded to Barry Marshall and Robin Warren. H. pylori became eventually recognized for its oncogenic potential in the stomach and as the main risk factor for gastric cancer development. KEY MESSAGES: H. pylori gastritis is defined as infectious disease and requires therapy in all infected individuals. Strategies of gastric cancer prevention and development of therapies to overcome the increasing antibiotic resistance are main targets in clinical research of today.

Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments.

PURPOSE OF THE REVIEW: Acid suppression with proton pump inhibitors (PPIs) represents the standard of care in the treatment of acid-related diseases. However, despite their effectiveness, PPIs display some intrinsic limitations, which underlie the unmet clinical needs that have been identified over the past decades. The aims of this review are to summarize the current status and future development of the new class of antisecretory drugs (potassium-competitive acid blockers, P-CABs) that have recently been introduced into medical practice. RECENT FINDINGS: Over the past decades, clinical needs unmet by the current acid suppressants have been recognized, especially in the management of patients with GERD, Helicobacter pylori infection and NSAID-related peptic ulcer. The failure to address these needs is mainly due to their inability to achieve a consistent acid suppression in all patients and, particularly, to control nighttime acidity. It was then realized that an extended duration of acid suppression would exert additional benefits. The available data with P-CABs show that they are able to address these unmet clinical needs. Four different P-CABs (vonoprazan, tegoprazan, fexuprazan and keverprazan) are currently available. However, only two of them are approved outside Asia. Vonoprazan is available in North, Central and South America while tegoprazan is marketed only in Latin American countries. Two other compounds (namely linazapran glurate and zestaprazan) are presently under clinical development. While clinical trials on GERD have been performed with all P-CABs, only vonoprazan and tegoprazan have been investigated as components of Helicobacter pylori eradication regimens. The available data show that-in the above two clinical indications-P-CABs provide similar or better efficacy in comparison with PPIs. Their safety in the short-term overlaps that of PPIs, but data from long-term treatment are needed.

Helicobacter pylori World Gastroenterology Organization Global Guideline.

Helicobacter pylori remains a major health problem worldwide, causing considerable morbidity and mortality due to peptic ulcer disease and gastric cancer. The burden of disease falls disproportionally on less well-resourced populations. As with most infectious diseases, the largest impact on reducing this burden comes from improvement in socioeconomic status, which interrupts transmission. This has been observed in many regions of the world, but the prevalence of infection remains high in many regions where improvements in living standards are slow to occur. Meanwhile, the optimal clinical management and treatment pathways remain unsettled and are evolving with changing antimicrobial resistance patterns. Despite decades of research and clinical practice, major challenges remain. The quest for the most effective, safe, and simple therapy remains the major issue for clinicians. The search for an effective vaccine appears to be elusive still. Clinical guidelines do not infrequently proffer discordant advice. A major challenge for guidelines is for relevance across a variety of populations with a varying spectrum of disease, antimicrobial resistance rates, and vastly different resources. As local factors are central to determining the impact and management strategies for H. pylori infection, it is important that pathways are based on the best available local knowledge rather than solely extrapolating from guidelines formulated in other regions, which may be less applicable. To this end, this revision of the World Gastroenterology Organisation (WGO) H. pylori guideline uses a "Cascades" approach that seeks to summarize the principles of management and offer advice for pragmatic, relevant and achievable diagnostic and treatment pathways based on established key treatment principles and using local knowledge and available resources to guide regional practice.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.

Design details for overdose education and take-home naloxone kits: Codesign with family medicine, emergency department, addictions medicine and community.

INTRODUCTION: Overdose education and naloxone distribution (OEND) programmes equip and train people who are likely to witness an opioid overdose to respond with effective first aid interventions. Despite OEND expansion across North America, overdose rates are increasing, raising questions about how to improve OEND programmes. We conducted an iterative series of codesign stakeholder workshops to develop a prototype for take-home naloxone (THN)-kit (i.e., two doses of intranasal naloxone and training on how to administer it). METHODS: We recruited people who use opioids, frontline healthcare providers and public health representatives to participate in codesign workshops covering questions related to THN-kit prototypes, training on how to use it, and implementation, including refinement of design artefacts using personas and journey maps. Completed over 9 months, the workshops were audio-recorded and transcribed with visible results of the workshops (i.e., sticky notes, sketches) archived. We used thematic analyses of these materials to identify design requirements for THN-kits and training. RESULTS: We facilitated 13 codesign workshops to identify and address gaps in existing opioid overdose education training and THN-kits and emphasize timely response and stigma in future THN-kit design. Using an iterative process, we created 15 prototypes, 3 candidate prototypes and a final prototype THN-kit from the synthesis of the codesign workshops. CONCLUSION: The final prototype is available for a variety of implementation and evaluation processes. The THN-kit offers an integrated solution combining ultra-brief training animation and physical packaging of nasal naloxone to be distributed in family practice clinics, emergency departments, addiction medicine clinics and community settings. PATIENT OR PUBLIC CONTRIBUTION: The codesign process was deliberately structured to involve community members (the public), with multiple opportunities for public contribution. In addition, patient/public participation was a principle for the management and structuring of the research team.

COVID-19 and Gastrointestinal Disease: Implications for the Gastroenterologist.

BACKGROUND: COVID-19 was initially considered a respiratory disease but the SARS-CoV-2 virus can lead to serious systemic consequences affecting major organs including the digestive system. SUMMARY: This review brings new clinically important information for the gastroenterologist. This includes: the mechanisms of tissue damage seen with the SARS-CoV-2 virus; the consequences of immunosuppression in patients with inflammatory bowel disease (IBD) and chronic liver disease with the additional risks of decompensation in patients with cirrhosis; the impact of COVID-19 on gastrointestinal emergencies, on gastrointestinal endoscopy, diagnosis and treatments. These highlight the need to understand the clinical pharmacology, toxicology and therapeutic implications of drugs commonly used by gastroenterologists and their links with COVID-19. Key Messages: Any part of the digestive system may be affected by the SARS-CoV-2 virus, and those with pre-existing disease are at greatest risk of adverse outcomes. The risk for drug-drug interactions is considerable in patients seriously ill with COVID-19 who often require mechanical ventilation and life support. Some repurposed drugs used against SARS-CoV-2 can cause or aggravate some of the COVID-19-related gastrointestinal symptoms and can also induce liver injury. Ongoing clinical studies will hopefully identify effective drugs with a more favourable risk-benefit ratio than many initially tried treatments.

Virtual Peer-to-Peer Learning to Enhance and Accelerate the Health System Response to COVID-19: The HHS ASPR Project ECHO COVID-19 Clinical Rounds Initiative.

Tasked with identifying digital health solutions to support dynamic learning health systems and their response to COVID-19, the US Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response partnered with the University of New Mexico's Project ECHO and more than 2 dozen other organizations and agencies to create a real-time virtual peer-to-peer clinical education opportunity: the COVID-19 Clinical Rounds Initiative. Focused on 3 "pressure points" in the COVID-19 continuum of care-(1) the out-of-hospital and/or emergency medical services setting, (2) emergency departments, and (3) inpatient critical care environments-the initiative has created a massive peer-to-peer learning network for real-time information sharing, engaging participants in all 50 US states and more than 100 countries. One hundred twenty-five learning sessions had been conducted between March 24, 2020 and February 25, 2021, delivering more than 58,000 total learner-hours of contact in the first 11 months of operation.

Helicobacter pylori eradication for the prevention of gastric neoplasia.

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.

Neo-Adjuvant chemotherapy and its affects to the axilla-Can we safely downgrade axillary surgery to mirror the approach in the breast.

The use of neo-adjuvant chemotherapy (NACT) to downgrade surgery in the breast from mastectomy to breast-conserving surgery is well-established. In certain patients, the use of adjuvant axillary radiotherapy can be safe and effective in place of axillary node clearance. What remains less clear are the alternative surgical options to the axilla following NACT. The aim of this study was to examine the effects of NACT in the axilla and whether downgrading axillary node clearance to axillary conserving surgery to mirror the approach in the breast may be a viable and safe practice. Patients undergoing neo-adjuvant chemotherapy were identified over a seven-year period between 2010 and 2017. Surgical plans were compared with pre- and post-chemotherapy. Histological information at the time of diagnosis was compared to surgical excision specimens. 349 patients were included for analysis, and 264 had axillary status documented at diagnosis. The average patient age was 51 years, and Grade 3, ER-positive, and Her2-negative cancers made the biggest histological subgroups. Complete pathological response (CPR) was seen in the breast in 27% of cases. 19% of patients requiring mastectomy had their surgery downgraded. Following NACT, axillary CPR was seen in 42% of patients and residual axillary nodal burden was limited to four nodes in 73% of patients. Axillary conserving surgery may be a safe alternative surgical approach in the downstaged axilla following neo-adjuvant chemotherapy. Advances in perioperative identification of suspicious nodes may be needed to facilitate progress.

The potential role of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.

PURPOSE OF REVIEW: Gastroesophageal reflux disease (GERD) is primarily a motor disorder, but its pathogenesis is multifactorial. Although gastric acid secretion is usually normal in GERD patients, treatment with proton pump inhibitors (PPIs) has become the standard of care, despite increasing awareness of their shortcomings. In this article, a new class of antisecretory drugs (namely potassium-competitive acid blockers, P-CABs), developed to overcome these limitations, is discussed. RECENT FINDINGS: P-CABs block the K exchange channel of the proton pump, resulting in rapid, competitive, reversible inhibition of acid secretion. These drugs offer a more rapid elevation of intragastric pH than PPIs, while maintaining similar antisecretory effect, the duration of which is dependent on half-life and can be prolonged with extended release formulations. Thus, P-CABs offer advances in the treatment of GERD including rapid heartburn relief, faster and more reliable healing of severe grades of erosive esophagitis, as a consequence of better control of nighttime acid secretion than PPIs. SUMMARY: P-CABs overcome many of the drawbacks of PPIs. The unique antisecretory effects of vonoprazan might be especially useful in the long-term treatment of patients with Barrett's esophagus.

Do infants with transposition of the great arteries born outside a specialist centre have different outcomes?

BACKGROUND: Infants born with undiagnosed transposition of the great arteries continue to be born in district general hospitals despite the improvements made in antenatal scanning. Evidence indicates improved outcomes with early definitive treatment after birth, hence the recommendation of delivery in a tertiary centre. The role of specialist paediatric and neonatal transport teams, to advise, stabilise, and transport the infants to a tertiary centre in a timely manner, is critical for those infants born in a district general hospital. This pilot study aims to compare outcomes between infants born in district general hospitals and those who were born in a tertiary maternity unit in South West England and South Wales. METHODS: This was a secondary data analysis of data collected from the local Paediatric Intensive Care Audit Network and the local transport database. Infants born with a confirmed diagnosis of transposition of the great arteries, that required an arterial switch operation as the definitive procedure between April, 2012 and March 2018 were included. RESULTS: Forty-five infants with a confirmed diagnosis of transposition of the great arteries were included. Statistical analysis demonstrated there were no significant differences in the time to balloon atrial septostomy (p = 0.095), time to arterial switch operation (p = 0.461), length of paediatric ICU stay (p = 0.353), and hospital stay (p = 0.095) or mortality between the two groups. CONCLUSIONS: We found no significant differences in outcomes between infants delivered outside the specialist centre, who were transferred in by a specialist team.

Effect of Aspirin and ibuprofen either alone or in combination on gastric mucosa and bleeding time and on serum prostaglandin E2 and thromboxane A2 levels in the anaesthetized rats in vivo.

There is much evidence that a combination of ibuprofen (IBU) and Aspirin (ASA) can antagonize the irreversible inhibition of platelet function. This study was designed to investigate the degree of gastric damage, bleeding time (BT) and fluctuations in the serum levels of prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) after oral administration of ASA (200 mg/kg) and IBU (50 mg/kg) either alone or in combination in rats in vivo. The stomach was assessed for any damage either after 6 h, 18 h or 6 days and carboxymethylcellulose (1% CMC) served as a vehicle and control. ELISA was used to measure TXA2 and PGE2 in serum. Bleeding time was assessed using tail blood. The results show that ASA and IBU either alone or in combination can cause gastric ulceration in 25-100% of the rats at 6 and 18 h. In contrast, gastric ulceration was seen in 50% of rats with a combination of ASA given before IBU only after 6 days of oral administration. BT was unaffected either by ASA or IBU when administered alone except after 18 h for IBU. In contrast, BT was significantly reduced when IBU was administered before ASA after 18 h and 6 days (P < 0.001). Serum PGE2 levels decreased significantly after ASA administered either alone or in combination with IBU for 6 h, 18 h and 6 days (P < 0.05). Serum TXA2 levels were significantly reduced after 6 h, 18 h and 6 days following ASA and IBU administration except for IBU alone which caused a significant increase in serum TXA2 6 days after its administration (P < 0.01). It can be concluded that ASA and IBU administered either alone or in combination can cause gastric ulcers in the rat stomach after 6 h and 18 h, but less severe after 6 days. IBU either alone or in combination with ASA reduced BT only after 18 h and 6 days of administration. Together, the results show that gastric ulceration correlated well with the inhibition of serum PGE2 and TXA2 levels.

The impact of temperature on insecticide toxicity against the malaria vectors Anopheles arabiensis and Anopheles funestus.

BACKGROUND: It is anticipated that malaria elimination efforts in Africa will be hampered by increasing resistance to the limited arsenal of insecticides approved for use in public health. However, insecticide susceptibility status of vector populations evaluated under standard insectary test conditions can give a false picture of the threat, as the thermal environment in which the insect and insecticide interact plays a significant role in insecticide toxicity. METHODS: The effect of temperature on the expression of the standard WHO insecticide resistance phenotype was examined using Anopheles arabiensis and Anopheles funestus strains: a susceptible strain and the derived resistant strain, selected in the laboratory for resistance to DDT or pyrethroids. The susceptibility of mosquitoes to the pyrethroid deltamethrin or the carbamate bendiocarb was assessed at 18, 25 or 30 °C. The ability of the pyrethroid synergist piperonyl-butoxide (PBO) to restore pyrethroid susceptibility was also assessed at these temperatures. RESULTS: Temperature impacted the toxicity of deltamethrin and bendiocarb. Although the resistant An. funestus strain was uniformly resistant to deltamethrin across temperatures, increasing temperature increased the resistance of the susceptible An. arabiensis strain. Against susceptible An. funestus and resistant An. arabiensis females, deltamethrin exposure at temperatures both lower and higher than standard insectary conditions increased mortality. PBO exposure completely restored deltamethrin susceptibility at all temperatures. Bendiocarb displayed a consistently positive temperature coefficient against both susceptible and resistant An. funestus strains, with survival increasing as temperature increased. CONCLUSIONS: Environmental temperature has a marked effect on the efficacy of insecticides used in public health against important African malaria vectors. Caution must be exercised when drawing conclusions about a chemical's efficacy from laboratory assays performed at only one temperature, as phenotypic resistance can vary significantly even over a temperature range that could be experienced by mosquitoes in the field during a single day. Similarly, it might be inappropriate to assume equal efficacy of a control tool over a geographic area where local conditions vary drastically. Additional studies into the effects of temperature on the efficacy of insecticide-based interventions under field conditions are warranted.

Molecular and physiological analysis of Anopheles funestus swarms in Nchelenge, Zambia.

BACKGROUND: Anopheles funestus has been recognized as a major malaria vector in Africa for over 100 years, but knowledge on many aspects of the biology of this species is still lacking. Anopheles funestus, as with most other anophelines, mate through swarming. A key event that is crucial for the An. funestus male to mate is genitalia rotation. This involves the 135° to 180° rotation of claspers, which are tipped with claws. This physical change then enables the male to grasp the female during copulation. The aim of this investigation was to molecularly characterize wild An. funestus swarms from Zambia and examine the degree of genitalia rotation within the swarm. METHODS: Anopheles funestus swarms were collected from Nchelenge, northern Zambia, during dusk periods in May 2016. All the adults from the swarm were analysed morphologically and identified to species level using a multiplex PCR assay. Anopheles funestus s.s. specimens were molecularly characterized by restriction fragment length polymorphism type and Clade type assays. The different stages of genitalia rotation were examined in the adult males. RESULTS: A total of six swarms were observed during the study period and between 6 and 26 mosquitoes were caught from each swarm. Species analysis revealed that 90% of the males from the swarms were An. funestus s.s. MW-type, with 84% belonging to clade I compared to 14% clade II and 2% failed to amplify. Very few specimens (3.4%) were identified as Anopheles gambiae s.s. Eighty percent of the males from the swarm had complete genitalia rotation. CONCLUSIONS: This is the first time that An. funestus swarms have been molecularly identified to species level. Anopheles funestus swarms appear to be species-specific with no evidence of clade-type differentiation within these swarms. The An. funestus swarms consist mainly of males with fully rotated genitalia, which strongly suggests that swarming behaviour is triggered primarily when males have matured.

The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults.

BACKGROUND & AIMS: Helicobacter pylori infection is increasingly difficult to treat. The purpose of these consensus statements is to provide a review of the literature and specific, updated recommendations for eradication therapy in adults. METHODS: A systematic literature search identified studies on H pylori treatment. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an online platform, finalized, and voted on by an international working group of specialists chosen by the Canadian Association of Gastroenterology. RESULTS: Because of increasing failure of therapy, the consensus group strongly recommends that all H pylori eradication regimens now be given for 14 days. Recommended first-line strategies include concomitant nonbismuth quadruple therapy (proton pump inhibitor [PPI] + amoxicillin + metronidazole + clarithromycin [PAMC]) and traditional bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline [PBMT]). PPI triple therapy (PPI + clarithromycin + either amoxicillin or metronidazole) is restricted to areas with known low clarithromycin resistance or high eradication success with these regimens. Recommended rescue therapies include PBMT and levofloxacin-containing therapy (PPI + amoxicillin + levofloxacin). Rifabutin regimens should be restricted to patients who have failed to respond to at least 3 prior options. CONCLUSIONS: Optimal treatment of H pylori infection requires careful attention to local antibiotic resistance and eradication patterns. The quadruple therapies PAMC or PBMT should play a more prominent role in eradication of H pylori infection, and all treatments should be given for 14 days.

Gastric Cancer as Preventable Disease.

Gastric cancer, 1 of the 5 most common causes of cancer death, is associated with a 5-year overall survival rate less than 30%. A minority of cancers occurs as part of syndromic diseases; more than 90% of adenocarcinomas are considered as the ultimate consequence of a longstanding mucosal inflammation. Helicobacter pylori infection is the leading etiology of non-self-limiting gastritis, which may result in atrophy of the gastric mucosa and impaired acid secretion. Gastric atrophy establishes a field of cancerization prone to further molecular and phenotypic changes, possibly resulting in cancer growth. This well-understood natural history provides the clinicopathologic rationale for primary and secondary cancer prevention strategies. A large body of evidence demonstrates that combined primary (H pylori eradication) and secondary (mainly endoscopy) prevention efforts may prevent or limit the progression of gastric oncogenesis. This approach, which is tailored to different country-specific gastric cancer incidence, socioeconomic, and cultural factors, requires that the complementary competences of gastroenterologists, oncologists, and pathologists be amalgamated into a common strategy of health policy.

Malaria vectors in the Democratic Republic of the Congo: the mechanisms that confer insecticide resistance in Anopheles gambiae and Anopheles funestus.

BACKGROUND: The Democratic Republic of the Congo (DRC) is characterized as a holoendemic malaria area with the main vectors being Anopheles funestus and members of the Anopheles gambiae complex. Due to political instability and socio-economic challenges in the region, knowledge of insecticide resistance status and resistance mechanisms in these vectors is limited. Mosquitoes were collected from a mining site in the north-eastern part of the country and, following identification, were subjected to extensive testing for the target-site and biochemical basis of resistance. Quantitative real-time PCR was used to assess a suite of 10 genes frequently involved in pyrethroid and dichlorodiphenyltrichloroethane (DDT) resistance in An. gambiae females and males. In An. funestus, gene expression microarray analysis was carried out on female mosquitoes. RESULTS: In both species, deltamethrin resistance was recorded along with high resistance and suspected resistance to DDT in An. gambiae and An. funestus, respectively. A total of 85% of An. gambiae carried the kdr mutations as either homozygous resistant (RR) (L1014S, L1014F or both) or heterozygous (RS), however only 3% carried the rdl mutant allele (RS) and no ace-1 mutations were recorded. Synergist assays indicated a strong role for P450s in deltamethrin resistance in both species. In An. gambiae, analysis of transcription levels showed that the glutathione-S-transferase, GSTS1-2, produced the highest fold change in expression (7.6-fold in females and 31-fold in males) followed by GSTE2, thioredoxin peroxidase (TPX2), and cytochrome oxidases (CYP6M2 and CYP6P1). All other genes tested produced fold change values below 2. Microarray analysis revealed significant over-transcription of cuticular proteins as well as CYP6M7, CYP6P9a and CYP6P9b in insecticide resistant An. funestus. CONCLUSIONS: These data show that high levels of deltamethrin resistance in the main malaria vector species, conferred by enzymatic detoxification, are present in the DRC.

Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis--an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks.

BACKGROUND: There are several guidelines addressing the issues around the use of NSAIDs. However, none has specifically addressed the upper versus lower gastrointestinal (GI) risk of COX-2 selective and non-selective compounds nor the interaction at both the GI and cardiovascular (CV) level of either class of drugs with low-dose aspirin. This Consensus paper aims to develop statements and guidance devoted to these specific issues through a review of current evidence by a multidisciplinary group of experts. METHODS: A modified Delphi consensus process was adopted to determine the level of agreement with each statement and to determine the level of agreement with the strength of evidence to be assigned to the statement. RESULTS: For patients with both low GI and CV risks, any non-selective NSAID (ns-NSAID) alone may be acceptable. For those with low GI and high CV risk, naproxen may be preferred because of its potential lower CV risk compared with other ns-NSAIDs or COX-2 selective inhibitors, but celecoxib at the lowest approved dose (200 mg once daily) may be acceptable. In patients with high GI risk, if CV risk is low, a COX-2 selective inhibitor alone or ns-NSAID with a proton pump inhibitor appears to offer similar protection from upper GI events. However, only celecoxib will reduce mucosal harm throughout the entire GI tract. When both GI and CV risks are high, the optimal strategy is to avoid NSAID therapy, if at all possible. CONCLUSIONS: Time is now ripe for offering patients with osteoarthritis the safest and most cost-effective therapeutic option, thus preventing serious adverse events which could have important quality of life and resource use implications. Please see related article: http://dx.doi.org/10.1186/s12916-015-0291-x.

Helicobacter pylori eradication for the prevention of gastric neoplasia.

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 11), MEDLINE (1946 to December 2013), and EMBASE (1974 to December 2013). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2013. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data. Three trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Five trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (6 trials, 6497 participants, risk ratio (RR) of developing subsequent gastric cancer 0.66; 95% confidence interval (CI) 0.46 to 0.95; moderate-quality evidence). Only one trial reported effect of eradication of H. pylori on development of subsequent oesophageal cancer (2 (0.2%) among 817 participants assigned to eradication therapy, compared with 1 (0.1%) of 813 participants allocated to placebo; RR 1.99; 95% CI 0.18 to 21.91). The effect of H. pylori eradication on preventing death from gastric cancer compared with placebo or no treatment was uncertain due to wide confidence intervals (3 trials, 4475 participants, RR 0.67; 95% CI 0.40 to 1.11; moderate-quality evidence). There was no evidence of an effect on all-cause mortality (4 trials, 5253 participants, RR 1.09; 95% CI 0.86 to 1.38; moderate-quality evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found limited, moderate-quality evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.