Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori: Current perspectives and implications.

Yu et al's study in the World Journal of Gastroenterology (2023) introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii (S. boulardii) for the rescue therapy against Helicobacter pylori (H. pylori), a pathogen responsible for peptic ulcers and gastric cancer. Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression, which is minimally affected by mealtime. Compared to proton pump inhibitors, which bind irreversibly to cysteine residues in the H+/K+-ATPase pump, Vonoprazan competes with the K+ ions, prevents the ions from binding to the pump and blocks acid secretion. Concerns with increasing antibiotic resistance, effects on the gut microbiota, patient compliance, and side effects have led to the advent of a dual regimen for H. pylori. Previous studies suggested that S. boulardii plays a role in stabilizing the gut barrier which improves H. pylori eradication rate. With an acceptable safety profile, the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile, thereby strengthening the applicability in clinical settings. Nonetheless, S. boulardii comes in various formulations and dosages, warranting further exploration into the optimal dosage for supplementation in rescue therapy. Additionally, larger, randomized, double-blinded controlled trials are warranted to confirm these promising results.

Vonoprazan is superior to lansoprazole for healing of severe but not mild erosive esophagitis: A systematic review with meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Healing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60-70%). Vonoprazan, a potassium-competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta-analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D. METHODS: We searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed-effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location. RESULTS: Four randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169-1.433], Week 4 1.160 [1.059-1.270], and Week 8 1.175 [95% CI 1.107-1.247]), but was similar for mild EE at all weeks (P-interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P-interaction < 0.01). Any, serious, and drug-related treatment-emergent adverse events were comparable between groups. CONCLUSION: Vonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

A systematic review and meta-analysis of the efficacy of vonoprazan for proton pump inhibitor-resistant gastroesophageal reflux disease.

BACKGROUND AND AIM: Up to 40% of gastroesophageal reflux disease (GERD) patients experience inadequate symptom relief with a proton pump inhibitor (PPI), termed PPI-resistant or refractory GERD. Vonoprazan, a potassium-competitive acid blocker, has better efficacy than PPI in suppressing gastric acid secretion. This meta-analysis summarizes the efficacy and safety of vonoprazan for treating PPI-resistant GERD (both erosive esophagitis [EE] and non-erosive reflux disease [NERD]). METHODS: Four electronic databases (Medline, Embase, SCOPUS, and CENTRAL) were searched for studies indexed until August 1, 2023. Both observational studies and clinical trials assessing the efficacy and safety of vonoprazan in PPI-resistant GERD were included. Efficacy outcomes included healing and maintenance rates of EE and improvement of the Frequency Scale for Symptoms of GERD (FSSG) scores. Serious adverse events (SAEs) were considered a safety outcome. The modified Newcastle-Ottawa Scale (NOS) was used to assess study quality. RESULTS: Twelve studies were included in this meta-analysis. Healing rates of PPI-resistant EE with vonoprazan 20 mg were 91.7% (95% CI 86.8-94.8%) and 88.5% (95% CI 69.7-96.2%) at weeks 4 and 8, respectively. For healed PPI-resistant EE, the overall maintenance rates with vonoprazan 10 mg were 82.6% (95% 61.2-95.0%) at week 8, 86.0% (95% CI 72.1-94.7%) at week 24, and 93.8% (95% CI 69.8-99.8%) at week 48. FSSG scores were improved in 74.6% (95% CI 65.8-81.7%) and 51.9% (95% CI 37.8-65.7%) of patients at weeks 4 and 8. Overall, no SAE was reported. CONCLUSION: Vonoprazan demonstrated high efficacy in the healing and maintenance of PPI-resistant EE and moderate efficacy for the improvement of FSSG score. Vonoprazan was well tolerated in PPI-resistant GERD patients.

Antibiotic use reduces the efficacy of immune checkpoint inhibitors in patients with urothelial carcinoma: A systematic review and meta-analysis.

CONTEXT: Antibiotics have been suggested to diminish the efficacy of immune checkpoint inhibitors (ICIs) by alterations of the gut microbiota. OBJECTIVE: To perform a meta-analysis summarizing the effect of antibiotics on the overall survival (OS) and progression-free survival (PFS) of urothelial cancer (UC) patients receiving ICI. EVIDENCE ACQUISITION: PubMed, EMBASE (Ovid), and the Cochrane Library were searched to identify studies published up to July 14, 2023. Studies reporting the associations between antibiotics use and OS and PFS in UC patients treated with ICI were included in this systematic review and meta-analysis. The random-effect model was used to pool the Hazard Ratios (HRs) for OS and PFS with 95% confidence interval (95%CI). The ROBINS-I was used to assess the risk of bias in the included studies, while the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was used to inform the quality of evidence. EVIDENCE SYNTHESIS: Thirteen nonrandomized studies involving a total of 5,095 ICI-treated UC patients were included in this review, of which 1434 (28%) received antibiotics. Overall, compared to patients who did not receive antibiotics, the pooled HRs for OS and PFS in those who received antibiotics were 1.45 [95% CI 1.25-1.68] and 1.40 [95% CI 1.05-1.87], respectively. Subgroup analysis revealed that the types of ICI and timing of antibiotic initiation did not influence the effect of antibiotics on OS and PFS in UC patients (P > 0.05). CONCLUSIONS: Antibiotic use significantly reduced OS and PFS in UC patients receiving ICI. While antibiotics remain crucial for the treatment of infections in UC patients, antibiotics should be prescribed cautiously in UC patients receiving ICI. PATIENT SUMMARY: Antibiotic use is associated with worsened survival in UC patients receiving immune checkpoint inhibitors.

Left lateral decubitus sleeping position is associated with improved gastroesophageal reflux disease symptoms: A systematic review and meta-analysis.

BACKGROUND: A limited number of studies have demonstrated that sleeping in the left lateral decubitus (LLD) decreases nocturnal reflux in patients with gastroesophageal reflux disease (GERD) compared to right lateral decubitus (RLD) and supine. AIM: This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD. METHODS: Studies published up to July 17, 2023, in MEDLINE, EMBASE, and CENTRAL were searched. Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients. Outcomes include the acid exposure time (AET) (% time in pH<4), acid clearance time (ACT) (in sec/episode), number of reflux episodes, and improvement in N-GSSIQ scores. RESULTS: Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD (mean difference [MD] -2.03 [95%CI: -3.62 to -0.45]; -81.84 [95%CI: -127.48 to -36.20], respectively) and supine position (MD -2.71 [95%CI: -4.34 to -1.09]; -74.47 [95%CI: -116.26 to -32.69], respectively). There was no difference in AET and ACT between RLD sleep position and supine. Furthermore, one randomized controlled trial investigating the use of electronic sleep positional therapy, which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham, showed nocturnal symptoms improvement (improved N-GSSIQ score, increased reflux-free nights, and resolution of nocturnal reflux symptoms). CONCLUSION: Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life, therefore warranting interventions that promote LLD sleep position.

Role of endoscopy in gastroesophageal reflux disease.

In general, gastroesophageal reflux disease (GERD) is diagnosed clinically based on typical symptoms and/or response to proton pump inhibitor treatment. Upper gastrointestinal endoscopy is reserved for patients presenting with alarm symptoms, such as dysphagia, odynophagia, significant weight loss, gastrointestinal bleeding, or anorexia; those who meet the criteria for Barrett's esophagus screening; those who report a lack or partial response to proton pump inhibitor treatment; and those with prior endoscopic or surgical anti-reflux interventions. Newer endoscopic techniques are primarily used to increase diagnostic yield and provide an alternative to medical or surgical treatment for GERD. The available endoscopic modalities for the diagnosis of GERD include conventional endoscopy with white-light imaging, high-resolution and high-magnification endoscopy, chromoendoscopy, image-enhanced endoscopy (narrow-band imaging, I- SCAN, flexible spectral imaging color enhancement, blue laser imaging, and linked color imaging), and confocal laser endomicroscopy. Endoscopic techniques for treating GERD include esophageal radiofrequency energy delivery/Stretta procedure, transoral incisionless fundoplication, and endoscopic full-thickness plication. Other novel techniques include anti-reflux mucosectomy, peroral endoscopic cardiac constriction, endoscopic submucosal dissection, and endoscopic band ligation. Currently, many of the new endoscopic techniques are not widely available, and their use is limited to centers of excellence.

The Gut Microbiota Profile in Heart Failure Patients: A Systematic Review.

BACKGROUND AND AIMS: Traditional cardiovascular risk factors are established predictors of heart failure (HF). However, the human gut microbiota is suggested to potentially interact with the cardiovascular system through the "gut-heart axis", which induces inflammation and contributes to HF pathogenesis. This systematic review aims to confirm the interconnection between the gut microbiome in HF patients. METHODS: Peer-reviewed human studies comparing the gut microbiota profile in adult patients with HF and healthy controls (HCs) up to April 18, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, SCOPUS, and the Cochrane Library. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: A total of nine studies, including 317 HF patients and 510 HCs, were included in the review. Decreased gut microbiota richness and similar microbial diversity (alpha diversity), and significantly different gut microbiota composition (beta diversity) were observed between HF patients and HCs. In comparison to HCs, HF patients had a greater abundance of Actinobacteria, Proteobacteria, and Synergistetes phyla; Enterococcus, Escherichia, Klebsiella, Lactobacillus, Streptococcus, and Veilonella genera and Ruminococcus gnavus, Streptococcus sp., and Veilonella sp. species. In contrast, there was decreased abundance of Firmicutes phylum; Blautia, Eubacterium, Faecalibacterium, and Lachnospiraceae FCS020 genera; and Dorea longicatena, Eubacterium rectale, Faecalibacterium prausnitzii, Oscillibacter sp., and Sutterella wadsworthensis species in HF patients. CONCLUSIONS: Gut microbiota diversity, richness, and composition in HF patients differ significantly from the healthy population. Overall, short-chain fatty acid (SCFA)-producing gut microbiota was depleted in HF patients. However, different underlying comorbidities, environments, lifestyles, and dietary choices could affect gut microbiota heterogeneity.

ViSHWaS: Violence Study of Healthcare Workers and Systems-a global survey.

OBJECTIVE: To provide insights into the nature, risk factors, impact and existing measures for reporting and preventing violence in the healthcare system. The under-reporting of violence against healthcare workers (HCWs) globally highlights the need for increased public awareness and education. METHODS: The Violence Study of Healthcare Workers and Systems study used a survey questionnaire created using Research Electronic Data Capture (REDCap) forms and distributed from 6 June to 9 August 2022. Logistic regression analysis evaluated violence predictors, including gender, age, years of experience, institution type, respondent profession and night shift frequency. A χ2 test was performed to determine the association between gender and different violence forms. RESULTS: A total of 5405 responses from 79 countries were analysed. India, the USA and Venezuela were the top three contributors. Female respondents comprised 53%. The majority (45%) fell within the 26-35 age group. Medical students (21%), consultants (20%), residents/fellows (15%) and nurses (10%) constituted highest responders. Nearly 55% HCWs reported firsthand violence experience, and 16% reported violence against their colleagues. Perpetrators were identified as patients or family members in over 50% of cases, while supervisor-incited violence accounted for 16%. Around 80% stated that violence incidence either remained constant or increased during the COVID-19 pandemic. Among HCWs who experienced violence, 55% felt less motivated or more dissatisfied with their jobs afterward, and 25% expressed willingness to quit. Univariate analysis revealed that HCWs aged 26-65 years, nurses, physicians, ancillary staff, those working in public settings, with >1 year of experience, and frequent night shift workers were at significantly higher risk of experiencing violence. These results remained significant in multivariate analysis, except for the 55-65 age group, which lost statistical significance. CONCLUSION: This global cross-sectional study highlights that a majority of HCWs have experienced violence, and the incidence either increased or remained the same during the COVID-19 pandemic. This has resulted in decreased job satisfaction.

Diagnostic accuracy of gastroesophageal reflux disease questionnaire for gastroesophageal reflux disease: A systematic review and meta-analysis.

BACKGROUND: The use of a symptom-based gastroesophageal reflux disease (GERD) questionnaire (GerdQ) for GERD diagnosis has gained interest due to its greater efficacy and ease of use than other available questionnaires. However, different guidelines have given inconsistent recommendations regarding using GerdQ as a diagnostic test. This meta-analysis summarized the diagnostic accuracy of GerdQ for diagnosing GERD. METHODS: Studies published up to April 12, 2023, and indexed in MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library were searched. Diagnostic test accuracy studies comparing GerdQ with upper endoscopy and/or pH-metry for GERD diagnosis in adult patients with symptoms suggestive of GERD were included. The study quality was assessed using the QUADAS-2 tool. Meta-analysis using bivariate (Reitsma) analysis was done to summarize the overall sensitivity, specificity, likelihood ratios (LRs), and diagnostic odds ratio (DOR). The summary receiver operating characteristics (SROC) curve was visualized, and the area under the ROC (AUC) was calculated. KEY RESULTS: A total of 13 studies with 11,166 participants were included in the meta-analysis. The pooled sensitivity, specificity, positive LR, negative LR, and DOR for GerdQ (cut-off value of ≥8) were 66.9% (95% CI 56.4%-73.1%), 65.2% (95% CI 56.4%-73.1%), 1.93 (95% CI 1.55-2.42), 0.51 (95% CI 0.38-0.66), and 3.89 (95% CI 2.44-5.89), respectively. The overall AUC from the SROC was 0.705. The subgroup analysis showed similar pooled sensitivity, specificity, and DOR between Asian and non-Asian studies. CONCLUSIONS & INFERENCES: GerdQ had moderate sensitivity and specificity for GERD diagnosis. GerdQ can still be recommended as a diagnostic tool for GERD, especially when the PPI test is unavailable or contraindicated.

A systematic review of gut microbiota profile in COVID-19 patients and among those who have recovered from COVID-19.

OBJECTIVES: Given the scale and persistence of coronavirus disease 2019 (COVID-19), significant attention has been devoted to understanding the relationship between human gut microbiota and COVID-19. In this systematic review we aimed to comprehensively assess the gut microbiota composition in patients infected with COVID-19 and those recovered from COVID-19 in comparison to healthy controls (HCs). METHODS: Peer-reviewed articles and preprints published up to September 1, 2022, were searched in Ovid MEDLINE, Ovid EMBASE, and SCOPUS. Observational studies reporting the gut microbiota profile in adult (≥18 years) COVID-19 patients or those recovered from COVID-19 compared to HCs were eligible for inclusion in this systematic review. The quality assessment of studies was performed using the Newcastle-Ottawa scale. RESULTS: We identified 27 studies comprising 18 studies that compared COVID-19 patients and six that compared recovered COVID-19 patients to HCs, while the other three studies compared both COVID-19 and recovered COVID-19 patients to HCs. Compared to HCs, decreased gut microbial diversity and richness and a distinctive microbial composition were reported in COVID-19 patients and recovered COVID-19 patients. In COVID-19 patients, Bacteroidetes were found to be enriched, and Firmicutes depleted. Decreased short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium, Ruminococcus, and Bifidobacterium, among others, were also observed in COVID-19 patients, which were not restored to normal levels in those who recovered. CONCLUSION: Gut dysbiosis was evident in COVID-19, and available data suggested that dysbiosis persisted even in recovered COVID-19 patients, with decreased Firmicutes and SCFA-producing bacteria.

Gastrointestinal Symptoms of Monkeypox Infection: A systematic review and meta-analysis.

Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal symptoms and/or liver injury of Mpox are still very limited. This systematic review and meta-analysis is the first to summarize the gastrointestinal symptoms reported by Mpox patients. We searched for Mpox studies published until October 21, 2022, in MEDLINE, EMBASE, SCOPUS, and organization websites. Mpox studies were observational studies that reported at least one of either gastrointestinal symptoms and/or liver injury in Mpox patients. Meta-analysis was done to obtain the pooled prevalence of gastrointestinal symptoms in Mpox patients. Subgroup analyses were done based on the study location, age groups, and Mpox Clades. The quality of included studies was assessed using the NIH Quality Assessment Tool. Overall, 31 studies that reported gastrointestinal symptoms and/or liver injury in Mpox patients were included. The reported gastrointestinal symptoms were abdominal pain, anorexia, diarrhea, nausea, and vomiting. There is a lack of reporting for liver injury. The most prevalent gastrointestinal symptoms in Mpox patients were anorexia (47%; 95% confidence interval [CI] 41%-53%), followed by vomiting (12%; 95% CI 11%-13%), nausea (10%; 95% CI 9%-11%), abdominal pain (9%; 95% CI 8%-10%), and diarrhea (5%; 95% CI 4%-6%). Additionally, the prevalence of proctitis, rectal/anal pain, and rectal bleeding were 11% (95% CI 11%-12%), 25% (95% CI 24%-27%), and 12% (95% CI 11%-13%), respectively. Anorexia was the most frequently reported gastrointestinal symptom in Mpox patients, followed by vomiting, nausea, abdominal pain, and diarrhea. Proctitis is a novel presentation of Mpox in the 2022 outbreak.

Gut microbiota diversity and composition in predicting immunotherapy response and immunotherapy-related colitis in melanoma patients: A systematic review.

BACKGROUND: Gut microbiome (GM) composition and diversity have recently been studied as a biomarker of response to immune checkpoint blockade therapy (ICB) and of ICB-related colitis. AIM: To conduct a systematic review on the role of GM composition and diversity in predicting response and colitis in patients with melanoma treated with ICB. METHODS: The review protocol was registered in PROSPERO: CRD42021228018. From a total of 300 studies, nine studies met inclusion criteria. Two studies were phase I clinical trials, while the remainder were prospective observational studies. All but one study has moderate risk of bias. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). RESULTS: Fecal samples enriched in Firmicutes phylum were associated with good response to ICB, whereas the Bacteroidales family was associated with poor response to ICB. Samples with greater GM diversity were associated with more favorable response to ICB [hazard ratio (HR) = 3.57, 95% confidence interval = 1.02-12.52, P < 0.05]. Fecal samples with a higher abundance in Firmicutes were more susceptible to ICB-related colitis (P < 0.01) whereas samples enriched in Bacteroidetes were more resistant to ICB-related colitis (P < 0.05). Overall, there was limited concordance in the organisms in the GM identified to be associated with response to ICB, and studies evaluating GM diversity showed conflicting results. CONCLUSION: This highlights the need for further prospective studies to confirm whether the GM could be used as a biomarker and potential intervention to modulate ICB response in melanoma patients.

A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases. METHODS: We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings. RESULTS: Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion. CONCLUSION: Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.

Patient-reported Outcomes: the ICHOM Standard Set for Inflammatory Bowel Disease in Real-life Practice Helps Quantify Deficits in Current Care.

BACKGROUND: Patient-reported outcome measures [PROMs] are key to documenting outcomes that matter most to patients and are increasingly important to commissioners of health care seeking value. We report the first series of the ICHOM Standard Set for Inflammatory Bowel Disease [IBD]. METHODS: Patients treated for ulcerative colitis [UC] or Crohn's disease [CD] in our centre were offered enrolment into the web-based TrueColours-IBD programme. Through this programme, e-mail prompts linking to validated questionnaires were sent for symptoms, quality of life, and ICHOM IBD outcomes. RESULTS: The first 1299 consecutive patients enrolled [779 UC, 520 CD] were studied with median 270 days of follow-up (interquartile range [IQR] 116, 504). 671 [52%] were female, mean age 42 years (standard deviation [sd] 16), mean body mass index [BMI] 26 [sd 5.3]. At registration, 483 [37%] were using advanced therapies. Median adherence to fortnightly quality of life reporting and quarterly outcomes was 100% [IQR 48, 100%] and 100% [IQR 75, 100%], respectively. In the previous 12 months, prednisolone use was reported by 229 [29%] patients with UC vs 81 [16%] with CD, p <0.001; 202 [16%] for <3 months; and 108 [8%] for >3 months. An IBD-related intervention was reported by 174 [13%] patients, and 80 [6%] reported an unplanned hospital admission. There were high rates of fatigue [50%] and mood disturbance [23%]. CONCLUSIONS: Outcomes reported by patients illustrate the scale of the therapeutic deficit in current care. Proof of principle is demonstrated that PROM data can be collected continuously with little burden on health care professionals. This may become a metric for quality improvement programmes or to compare outcomes.

Platelet-to-lymphocyte ratio, a novel biomarker to predict the severity of COVID-19 patients: A systematic review and meta-analysis.

Platelet-to-lymphocyte ratio (PLR), a novel inflammatory marker, has been suggested to predict the severity of COVID-19 patients. This systematic review aims to evaluate the association between PLR levels on admission and the severity of COVID-19 patients. A systematic literature search was done on 23 July 2020 to identify peer-reviewed studies, preprints, and grey literatures. Research articles comparing the PLR value on admission in adult patients with COVID-19 with varying degrees of severity were included in the analysis. The following keywords were used for the search: "COVID-19", "PLR", "severity", and "mortality". A total of seven studies were included in the meta-analysis, six of which were conducted in China. From a total of 998 participants included, 316 (31.7%) had severe diseases; and those in the severe group were generally older and had underlying diseases compared to the non-severe group. In comparison to non-severe patients, the meta-analysis showed that severe COVID-19 patients had higher PLR levels on admission (SMD 0.68; 95%CI 0.43-0.93; I2 =58%). High PLR levels on admission were associated with severe COVID-19 cases. Therefore, the on-admission PLR level is a novel, cost-effective, and readily available biomarker with a promising prognostic role for determining the severity of COVID-19 patients.

Alcohol consumption and cause-specific mortality in Cuba: prospective study of 120 623 adults.

BACKGROUND: The associations of cause-specific mortality with alcohol consumption have been studied mainly in higher-income countries. We relate alcohol consumption to mortality in Cuba. METHODS: In 1996-2002, 146 556 adults were recruited into a prospective study from the general population in five areas of Cuba. Participants were interviewed, measured and followed up by electronic linkage to national death registries until January 1, 2017. After excluding all with missing data or chronic disease at recruitment, Cox regression (adjusted for age, sex, province, education, and smoking) was used to relate mortality rate ratios (RRs) at ages 35-79 years to alcohol consumption. RRs were corrected for long-term variability in alcohol consumption using repeat measures among 20 593 participants resurveyed in 2006-08. FINDINGS: After exclusions, there were 120 623 participants aged 35-79 years (mean age 52 [SD 12]; 67 694 [56%] women). At recruitment, 22 670 (43%) men and 9490 (14%) women were current alcohol drinkers, with 15 433 (29%) men and 3054 (5%) women drinking at least weekly; most alcohol consumption was from rum. All-cause mortality was positively and continuously associated with weekly alcohol consumption: each additional 35cl bottle of rum per week (110g of pure alcohol) was associated with ∼10% higher risk of all-cause mortality (RR 1.08 [95%CI 1.05-1.11]). The major causes of excess mortality in weekly drinkers were cancer, vascular disease, and external causes. Non-drinkers had ∼10% higher risk (RR 1.11 [1.09-1.14]) of all-cause mortality than those in the lowest category of weekly alcohol consumption (<1 bottle/week), but this association was almost completely attenuated on exclusion of early follow-up. INTERPRETATION: In this large prospective study in Cuba, weekly alcohol consumption was continuously related to premature mortality. Reverse causality is likely to account for much of the apparent excess risk among non-drinkers. The findings support limits to alcohol consumption that are lower than present recommendations in Cuba. FUNDING: Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients. Here, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients. METHODS: A literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI). RESULTS: A total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72-1.04; I2 = 75.52% and 1.87; 95%CI 1.25-2.49; I2 = 97.81%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.74 (95%CI 0.98-7.66). CONCLUSION: High NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.

D-dimer levels on admission and all-cause mortality risk in COVID-19 patients: a meta-analysis.

D-dimer level on admission is a promising biomarker to predict mortality in patients with COVID-19. In this study, we reviewed the association between on-admission D-dimer levels and all-cause mortality risk in COVID-19 patients. Peer-reviewed studies and preprints reporting categorised D-dimer levels on admission and all-cause mortality until 24 May 2020 were searched for using the following keywords: 'COVID-19', 'D-dimer' and 'Mortality'. A meta-analysis was performed to determine the pooled risk ratio (RR) for all-cause mortality. In total, 2911 COVID-19 patients from nine studies were included in this meta-analysis. Regardless of the different D-dimer cut-off values used, the pooled RR for all-cause mortality in patients with elevated vs. normal on-admission D-dimer level was 4.77 (95% confidence interval (CI) 3.02-7.54). Sensitivity analysis did not significantly affect the overall mortality risk. Analysis restricted to studies with 0.5 µg/ml as the cut-off value resulted in a pooled RR for mortality of 4.60 (95% CI 2.72-7.79). Subgroup analysis showed that the pooled all-cause mortality risk was higher in Chinese vs. non-Chinese studies (RR 5.87; 95% CI 2.67-12.89 and RR 3.35; 95% CI 1.66-6.73; P = 0.29). On-admission D-dimer levels showed a promising prognostic role in predicting all-cause mortality in COVID-19 patients, elevated D-dimer levels were associated with increased risk of mortality.

Mapping global evidence on strategies and interventions in neurotrauma and road traffic collisions prevention: a scoping review.

BACKGROUND: Neurotrauma is an important global health problem. The largest cause of neurotrauma worldwide is road traffic collisions (RTCs), particularly in low- and middle-income countries (LMICs). Neurotrauma and RTCs are preventable, and many preventative interventions have been implemented over the last decades, especially in high-income countries (HICs). However, it is uncertain if these strategies are applicable globally due to variations in environment, resources, population, culture and infrastructure. Given this issue, this scoping review aims to identify, quantify and describe the evidence on approaches in neurotrauma and RTCs prevention, and ascertain contextual factors that influence their implementation in LMICs and HICs. METHODS: A systematic search was conducted using five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health on EBSCO host, Cochrane Database of Systematic Reviews), grey literature databases, government and non-government websites, as well as bibliographic and citation searching of selected articles. The extracted data were presented using figures, tables, and accompanying narrative summaries. The results of this review were reported using the PRISMA Extension for Scoping Reviews (PRISMA-ScR). RESULTS: A total of 411 publications met the inclusion criteria, including 349 primary studies and 62 reviews. More than 80% of the primary studies were from HICs and described all levels of neurotrauma prevention. Only 65 papers came from LMICs, which mostly described primary prevention, focussing on road safety. For the reviews, 41 papers (66.1%) reviewed primary, 18 tertiary (29.1%), and three secondary preventative approaches. Most of the primary papers in the reviews came from HICs (67.7%) with 5 reviews on only LMIC papers. Fifteen reviews (24.1%) included papers from both HICs and LMICs. Intervention settings ranged from nationwide to community-based but were not reported in 44 papers (10.8%), most of which were reviews. Contextual factors were described in 62 papers and varied depending on the interventions. CONCLUSIONS: There is a large quantity of global evidence on strategies and interventions for neurotrauma and RTCs prevention. However, fewer papers were from LMICs, especially on secondary and tertiary prevention. More primary research needs to be done in these countries to determine what strategies and interventions exist and the applicability of HIC interventions in LMICs.

Mapping global evidence on strategies and interventions in neurotrauma and road traffic collisions prevention: a scoping review protocol.

INTRODUCTION: Neurotrauma is an important global health problem. This 'silent epidemic' is a major cause of death and disability in adolescents and young adults, with significant societal and economic impacts. Globally, the largest cause of neurotrauma is road traffic collisions (RTCs). Neurotrauma and RTCs are largely preventable, and many preventative strategies and interventions have been established and implemented over the last decades, particularly in high-income countries. However, these approaches may not be applicable globally, due to variations in environment, resources, population, culture and infrastructure. This paper outlines the protocol for a scoping review, which seeks to map the evidence on strategies and interventions in neurotrauma and RTCs prevention globally, and to ascertain contextual factors that influence their implementation. METHODS AND ANALYSIS: This scoping review will use the established methodology by Arksey and O'Malley. Eligible studies will be identified from five electronic databases (MEDLINE, EMBASE, CINAHL, Global Health/EBSCO and Cochrane Database of Systematic Reviews) and grey literature sources. We will also carry out bibliographical and citation searching of included studies. A two-stage selection process, which involves screening of titles and abstracts, followed by full-text screening, will be used to determine eligible studies which will undergo data abstraction using a customised, piloted data extraction sheet. The extracted data will be presented using evidence mapping and a narrative summary. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review, which is the first step in a multiphase public health research project on the global prevention of neurotrauma. The final review will be submitted for publication to a scientific journal, and results will be presented at appropriate conferences, workshops and meetings. Protocol registered on 5 April 2019 with Open Science Framework (https://osf.io/s4zk3/).