Mechanisms of vascular injury in neurotrauma: A critical review of the literature

One in every two individuals will experience a traumatic brain injury in their lifetime with significant impacts on the global economy and healthcare system each year.Neurovascular injury is a key aspect of neurotrauma to both the brain and the spinal cord and an important avenue of current and future research seeking innovative therapies.In this paper,we discuss primary and secondary neurotrauma,mechanisms of injury,the glymphatic system,repair and recovery.Each of these topics are directly connected to the vasculature of the central ner-vous system,affecting severity of injury and recovery.Consequently,neurova-scular injury in trauma represents a promising target for future therapeutics and innovation.

Exploring influences and risk of bias of studies on return to sport and work after lateral ankle sprain:A systematic review and metaanalysis

BACKGROUND Lateral ankle sprains are the most common traumatic musculoskeletal injuries of the lower extremity,with an incidence rate of 15%-20%.The high incidence and prevalence highlights the economic impact of this injury.Ankle sprains lead to a high socioeconomic burden due to the combination of the high injury incidence and high medical expenses.Up to 40%of patients who suffer from an ankle sprain develop chronic ankle instability.Chronic instability can lead to prolonged periods of pain,immobility and injury recurrence.Identification of factors that influence return to work(RTW)and return to sports(RTS)after a lateral ankle sprain(LAS)may help seriously reduce healthcare costs.AIM To explore which factors may potentially affect RTW and RTS after sustaining an LAS.METHODS EMBASE and PubMed were systematically searched for relevant studies published until June 2023.Inclusion criteria were as follows:(1)Injury including LAS or chronic ankle instability;(2)Described any form of treatment;(3)Assessment of RTW or RTS;(4)Studies published in English;and(5)Study designs including randomized controlled clinical trials,clinical trials or cohort studies.Exclusion criteria were:(1)Studies involving children(age<16 year);or(2)Patients with concomitant ankle injury besides lateral ankle ligament damage.A quality assessment was performed for each of the included studies using established risk of bias tools.Additionally quality of evidence was assessed using the GRADEpro tool in cases where outcomes were included in the quantitative analysis.A best evidence synthesis was performed in cases of qualitative outcome analysis.For all studied outcomes suitable for quantitative analysis a forest plot was created to calculate the effect on RTW and RTS.RESULTS A total of 8904 patients were included in 21 studies,10 randomized controlled trials,7 retrospective cohort studies and 4 prospective cohort studies.Fifteen studies were eligible for meta-analysis.The overall RTS rate ranged were 80%and 83%in the all treatments pool and surgical treatments pool,respectively.The pooled mean days to RTS ranged from 23-93 d.The overall RTW rate was 89%.The pooled mean time to RTW ranged from 5.8-8.1 d.For patients with chronic ankle instability,higher preoperative motivation was the sole factor significantly and independently(P=0.001)associated with the rate of and time to RTS following ligament repair or reconstruction.Higher body mass index was identified as a significant factor(P=0.04)linked to not resuming sports or returning at a lower level(median 24,range 20-37),compared to those who resumed at the same or higher level(median 23,range 17-38).Patients with a history of psychological illness or brain injury,experienced a delay in their rehabilitation process for sprains with fractures and unspecified sprains.The extent of the delayed rehabilitation was directly proportional to the increased likelihood of experiencing a recurrence of the ankle sprain and the number of ankle-related medical visits.We also observed that 10%of athletes who did return to sport after lateral ankle sprain without fractures described non-ankle-related reasons for not returning.CONCLUSION All treatments yielded comparable results,with each treatment potentially offering unique advantages or benefits.Preoperative motivation may influence rehabilitation after LAS.Grading which factor had a greater impact was not possible due to the lack of comparability among the included patients.

Colon capsule endoscopy polyp detection rate vs colonoscopy polyp detection rate:Systematic review and meta-analysis

BACKGROUND Colon capsule endoscopy(CCE)is a modern,non-invasive method for large bowel visualization,offering a less invasive alternative to traditional colonoscopy(TC).While TC remains the gold standard for comprehensive large bowel assessment,including the detection and treatment of various conditions,the effectiveness of CCE in detecting polyps is less established.AIM To systematically review and compare the polyp detection rates(PDR)of CCE and TC.METHODS A systematic literature search was conducted using four scientific databases:CINAHL,MEDLINE via EBSCO,Cochrane Library,and MEDLINE/PubMed.A standardized search command was utilized to ensure consistency.Full papers were retrieved if they compared PDR between CCE and TC and involved patients over 18 years old.A meta-analysis was then conducted using the meta package in R software.RESULTS Initially,339 articles were identified,with 128 duplicates and 15 non-English articles excluded,leaving 196 for screening.After further exclusions,9 articles were included in the review.The meta-analysis revealed minimal differences in PDR between CCE and TC.The pooled PDR for TC was 0.61(95%CI:0.48–0.72),and for CCE,it was 0.61(95%CI:0.48–0.73).The overall comparison of the pooled PDR of both methods was 0.96(95%CI:0.90–1.02),indicating that CCE is noninferior to TC.CONCLUSION CCE has emerged as a modern and safe diagnostic alternative to TC for polyp detection,demonstrating noninferiority when compared to the conventional method.

Is Pilates an effective tool for the management of kinesiophobia in musculoskeletal disorders?

BACKGROUND Kinesiophobia is a common condition often manifested in patients with musculoskeletal disorders within the process of rehabilitation.Recently,the literature has been investigating whether Pilates could contribute to the management of kinesiophobia in various musculoskeletal disorders.However,aggregated data regarding its effectiveness are absent from literature.AIM To evaluate recordings of the Pilates method in kinesiophobia related to musculoskeletal disorders.METHODS PubMed,ScienceDirect,Scopus and Pedro databases were all scrutinized for randomized controlled trials,by two or more intervention groups,where at least one group received a Pilates-based intervention and which had been conducted in patients aged 18-65 years with musculoskeletal disorders,having assessed at least one outcome related to kinesiophobia.The systematic review was based on the PRISMA guidelines.RESULTS We have identified five studies,with a total of 366 patients with musculoskeletal disorders.Three of them showed that a Pilates-based intervention by either mat or equipment can combat kinesiophobia in patients with musculoskeletal conditions,while another showed that Pilates exercises with equipment may have better long-term effects on kinesiophobia compared to Pilates mat.CONCLUSION Overall,a strong level of research evidence has been amassed for the Pilates intervention as well as a moderate level of research evidence for the effectiveness of equipment-based Pilates in reducing kinesiophobia in patients with musculoskeletal disorders.While the underlying mechanisms driving such a result remain unknown,it appears that Pilates can influence both biological and psychological factors in musculoskeletal disorders,thus resulting in the management of kinesiophobic behaviours.

Vascular complications of liver abscess: A literature review

Extensive vascular network and proximity to the gastrointestinal tract make the liver susceptible to abscess formation.While pyogenic liver abscesses account for the majority of liver abscesses in the Western world,amebic liver abscesses are more prevalent in tropical and developing nations.Most liver abscesses heal without complications.However,various vascular complications can occur in these patients,including compression of the inferior vena cava,thrombosis of the portal vein and/or hepatic veins,hepatic artery pseudoaneurysm,direct rupture into major vessels or the pericardium,and biliovascular fistula.These compli-cations can present significant clinical challenges due to the potential for hae-morrhage,ischemia,and systemic embolism,thereby increasing the risk of morbidity and mortality.Mechanical compression,flow stasis,inflammation,endothelial injury,and direct invasion are some of the proposed mechanisms that can cause vascular complications in the setting of a liver abscess.For the diag-nosis,thorough assessment,and therapeutic planning of vascular complications,more sophisticated imaging techniques such as multidetector computed tomo-graphy angiography or magnetic resonance angiography may be necessary.Although most vascular complications resolve with abscess treatment alone,additional interventions may be required based on the nature,severity,and course of the complications.This article aims to provide a systematic update on the spectrum of vascular complications of liver abscesses,offering insights into their pathogenesis,diagnosis,and management strategies.

Role of long non-coding RNAs in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is emerging as a common cause of chronic liver disease in children and adults.NAFLD can progress to steatohepa-titis and potentially even hepatocellular carcinoma.Early identification of pati-ents at risk for progressive disease is crucial for managing NAFLD.Recent studies have identified long noncoding RNAs(lncRNAs),circular RNAs,and microRNAs as playing important roles in the pathogenesis of NAFLD.These noncoding RNAs are involved in modulating several metabolic pathways such as hepatic glucose and lipid metabolism,oxidative stress,and even carcinogenesis.Elevated levels of lncARSR and lncRNA nuclear-enriched abundant transcript 1 have been found in patients with NAFLD.In addition,lncRNAs such as PRYP4-3 and RP11-128N14.5 can distinguish patients with NAFLD from healthy indi-viduals.Increased MEG3 expression has been observed in both NAFLD and non-alcoholic steatohepatitis,suggesting that it may help predict patients at risk for disease progression.With advances in transcriptomics,we may discover additional targets to help in the identification and prognostication of NAFLD.

Role of intestinal ultrasound in ulcerative colitis: A systematic review

BACKGROUND Intestinal ultrasound(IUS)is an emerging,non-invasive,and highly sensitive diagnostic tool in inflammatory bowel disease(IBD),including ulcerative colitis(UC).Despite its potential,its adoption in clinical practice is limited due to a lack of standardization and awareness.AIM To perform a comprehensive scoping review based on a systematic literature review on IUS in UC to inform current practice.METHODS Ninety-nine original articles about ultrasonography in UC were identified among 7608 citations searching PubMed and EMBASE databases for systematic review.RESULTS IUS can be useful as an initial diagnostic strategy in patients with suspected IBD/UC.In UC,IUS can predict endoscopic response,histologic healing,and steroid responsiveness in acute severe cases.IUS can predict response to biologics/small molecules(as early as 2 wk).IUS correlates well with ileocolonoscopy,but IUS could miss rectal,jejunal,and upper GI lesions in suspected IBD and colon polyps or extra-intestinal manifestations in known IBD.IUS is useful in special situations(children,pregnancy,and postoperative Crohn's disease).Inter-observer agreement is acceptable and trained physicians have comparable diagnostic accuracy.Point-of-care ultrasound impacted management in 40%-60%of cases.Hand-held IUS has excellent agreement with conventional IUS.CONCLUSION IUS is a non-invasive,highly sensitive tool in the diagnosis and monitoring of UC,offering excellent patient satisfaction.Point-of-care ultrasound by IBD physicians can significantly impact clinical decision-making.

Blastocystis hominis as a cause of chronic diarrhea in low-resource settings:A systematic review

BACKGROUND Blastocystis hominis(B.hominis),an anaerobic unicellular protist parasite,is known for its diverse clinical manifestations upon infecting the human gastrointestinal tract.Although globally distributed,it is particularly prevalent in developing nations.Examining the symptoms and treatment outcomes of B.hominis infection in low-resource settings holds immense significance,providing healthcare practi-tioners with valuable insights to enhance patient care.AIM To synthesize existing evidence on the symptomatology and treatment outcomes of B.hominis infection in low-resource settings.METHODS Following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines,a systematic review was conducted.The search spanned electronic databases including PubMed,Scopus,and Google Scholar.After a comprehensive screening process,a thorough examination of the papers,adhering to inclusion and exclusion criteria,and data extraction from eligible studies was conducted.The findings underwent summarization through simple descriptive analysis.RESULTS The search yielded 1200 papers,with 17 meeting inclusion criteria.Chronic diarrhea due to B.hominis infection was reported in only two studies,while abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting emerged as the most commonly documented symptoms.Recovery rates after one week of treatment ranged from 71.8%to 100%,and after two weeks,from 60%to 100%.CONCLUSION In low-resource settings,chronic diarrhea resulting from B.hominis infection is infrequent.Common symptoms include abdominal pain,diarrhea,flatulence,constipation,and nausea/vomiting.Post-treatment,clinical outcomes are notably favorable,supporting the recommendation for treatment.Metronidazole is advocated as the first-line agent,with consideration for switching to a second-line option in cases of treatment failure or poor response.

Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

Diabetes distress,the mediator of the poor glycemic control and depression:A meta-analysis

BACKGROUND Diabetes-related distress(DRD)is a common psychological disorder specifically associated with diabetes,its cross-talk with depression,and glycated hemoglobin(HbA1c)was discussed controversially.Interventions addressing DRD were shown to improve HbA1c.However,the primary concern is to investigate the association of DRD with glycemic control.No meta-analyses have compared the effects of depression and diabetes distress on HbA1c.AIM To assess the relationship between DRD,depression,and glycemic control.METHODS We systematically searched PubMed MEDLINE,Google Scholar,and Cochrane Library from inception up to May 2024.The keywords diabetes distress,depression,psychopathology,glycemic control,HbA1c,glycated hemoglobin,fasting,and postprandial blood glucose were used.A datasheet was used to extract the author’s name year and country of publication,diabetes distress,depression,and HbA1c among patients with DRD,depression,and control subjects.RESULTS Out of the 2046 studies retrieved,55 full texts were screened and 22 studies were included in the final meta-analysis.Diabetes distress was associated with poor glycemic control,odd ratio=0.42,95%confidence interval(CI):0.17-0.67,and P value<0.001,and odd ratio=0.52,95%CI:0.38-0.72,and P value<0.001 respectively.No significant difference was observed between depression and DRD regarding the impact on HbA1c,odd ratio=0.13,95%CI:0.15-0.41,P value=0.37,I2 for heterogeneity=76%.However,when heterogeneity was eliminated,diabetes distress influenced the HbA1c more compared to depression,odd ratio=0.29,95%CI:0.17-0.41,and P value<0.001.CONCLUSION DRD negatively influenced the HbA1c and glycemic control more than depression.Further studies using more specific measures(ecological momentary assessment)to assess DRD are recommended.

Incidence and predictors of hypocalcemia in end-stage renal disease patients on denosumab therapy: A systematic review and metaanalysis

BACKGROUND Denosumab inhibits the receptor activator of nuclear factor kappa-ligand.It markedly increases bone mineral density and has been proven to reduce the risk of fractures.However,numerous adverse effects,notably hypocalcemia,are prevalent in patients with end-stage renal disease(ESRD).AIM To analyze the incidence and predictors of hypocalcemia caused by denosumab compared to control in patients with ESRD.METHODS We conducted this study in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.PubMed,Scopus,Cochrane Central,and EMBASE were systematically searched from inception through March 2024.All original studies investigating the effects of denosumab on patients with ESRD compared to control were extracted.The primary outcomes of our study were the incidence of mild,severe,and very severe hypocalcemia.Secondary outcomes included serum levels of intact parathyroid hormone,calcium,and phosphate.The results were pooled and analyzed using a random-effects model.RESULTS Seven articles comprising 3240 patients were included in our study.Patients treated with denosumab had a significantly increased incidence of mild hypocalcemia[risk ratio(RR):2.79;95%confidence interval(CI):0.99-7.91;P=0.05;I^(2)=37%]and of very severe hypocalcemia(RR:9.58;95%CI:1.58-57.98;P=0.01;I^(2)=49%).However,an increase in the occurrence of severe hypocalcemia was non-significant(RR:4.23;95%CI:0.47-38.34;P=0.20;I^(2)=96%).Alternatively,denosumab showed a significant decrease in serum intact parathyroid hormone[mean difference(MD):-433.20,95%CI:-775.12 to-91.28,I2=98%,P=0.01],while there was a non-significant decrease in phosphate(MD:-0.47,95%CI:-1.35 to 0.41,I^(2)=88%,P=0.30)and calcium levels(MD:-0.33,95%CI:-0.95 to 0.29,I^(2)=94%,P=0.29).CONCLUSION Our study demonstrated that denosumab is significantly associated with mild and very severe hypocalcemia in patients with ESRD making it necessary to detect and prevent this side effect of treatment.

Fibroblast activation protein inhibitors positron emission tomography/computed tomography:Review of the literature

Positron emission tomography/computed tomography(PET/CT)with radiolabeled fibroblast activation protein inhibitors(FAPI)is an increasingly relevant molecular diagnostic image in oncology given the high expression of FAP in cancer associated fibroblast,being present in almost 90%of the epithelial carcinomas,which allows imaging with excellent diagnostic performance and can also become a therapeutic strategy.This review summarizes the literature on FAPIPET/CT for the cancer evaluation and compares it in some scenarios with the 18FFluorodeoxyglucose PET/CT.

Different medications for seasonal allergic rhinitis in adults:A systematic review and meta-analysis

BACKGROUND While the efficacy of medications such as fluticasone furoate(FF),fluticasone propionate(FP),and azelastine-fluticasone(AF)has been substantiated in comparison to their respective placebo controls,uncertainties persist regarding the comparative effectiveness of different intranasal agents.AIM To evaluate the efficacy of FP,FF,and AF in the treatment of adult patients with seasonal allergic rhinitis(SAR)using a meta-analytic approach.METHODS A computer search was conducted in Cochrane Library,PubMed,and EMBASE databases to identify randomized controlled trials assessing the effectiveness and safety of FF,FP,and AF in treating SAR.Data on treatment safety and efficacy were extracted and analyzed through meta-analysis.RESULTS A total of 20 studies were included,comprising 10590 participants.The results of the direct meta-analysis indicated that,compared to placebo,both relative Total Nasal Symptom Score(rTNSS)and relative Total Ocular Symptom Score(rTOSS)significantly decreased post-intervention[mean difference(MD)=-1.48,95%confidence interval(CI):-1.73 to-1.22;MD=-0.66,95%CI:-0.82 to-0.49],with similar findings observed across the FF,FP,and AF subgroups.The network meta-analysis results showed that for improving rTNSS and rTOSS,the SUCRA values ranking from highest to lowest were AF,FP,FF,and placebo.Improvements in rTNSS and rTOSS with FP,FF,and AF were all significantly greater than those observed with placebo,with AF demonstrating superior efficacy compared to both FP and FF.No statistically significant difference in rTNSS improvement was found between FP and FF,although FP exhibited significantly greater improvement in rTOSS compared to FF.CONCLUSION In adult patients with SAR,the combination of azelastine and fluticasone shows a significant effect in improving nasal and ocular symptoms,with FP demonstrating marked improvement in ocular symptoms compared to FF.

Epidemiology of carbapenem-resistant Acinetobacter baumannii colonization in neonatal intensive care units:A systematic review and meta-analysis

BACKGROUND The rising prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)in neonatal intensive care units(NICUs)represents an escalating challenge in healthcare settings,particularly in managing hospital-acquired infections(HAIs).Studies across various World Health Organization regions have documented a significant incidence of CRAB-related HAIs,with rates as high as 41.7 cases per 1000 patients in ICUs,accounting for 13.6%of all HAIs.These infections pose a doubled mortality risk compared to infections with carbapenem-susceptible Acinetobacter baumannii.A particularly concerning aspect of CRAB colonization is its asymptomatic nature,enabling its transmission through healthcare workers(HCWs)or the NICU environment to vulnerable neonates with developing immune systems.AIM To explore the prevalence of CRAB colonization in NICUs,focusing on neonates,healthcare workers,and the environmental samples,to enhance epidemiological understanding and inform targeted interventions.METHODS We conducted according to PRISMA 2020 checklist guidelines,a comprehensive literature search across multiple databases including MEDLINE(Ovid),EMBASE(Ovid),Global Health(Ovid),Web of Science,and Global Index Me-dicus.Studies were selected based on predetermined criteria,primarily involving neonates,HCWs,and environmental swabs,using culture or molecular methods to detect CRAB colonization.We excluded studies that did not specifically focus on NICUs,were duplicates,or lacked necessary data.The study selection and quality assessment were conducted independently by two reviewers.Data extraction involved collecting comprehensive details about each study.Our statistical analysis used a random-effects model to calculate the pooled prevalence and confidence intervals,stratifying results by regional location.We assessed study heterogeneity using Cochran's Q statistic and I²statistic,with regression tests employed to evaluate potential publication bias.RESULTS We analyzed 737 records from five databases,ultimately including 13 studies from ten countries.For neonates,the pooled prevalence was 4.8%(95%CI:1.1%to 10.5%)with the highest rates observed in South-East Asia(10.5%;95%CI:2.4%to 23.3%).Among HCWs,a single Indian study reported a 3.3%prevalence.Environmental samples showed a prevalence of 2.3%(95%CI:0%to 9.3%),with the highest rates in South-East Asia(10%;95%CI:4.2%to 17.7%).Significant heterogeneity was found across studies,and no publication bias was detected.CONCLUSION This systematic review highlights a significant prevalence of CRAB colonization in neonates across various regions,particularly in South-East Asia,contrasting with lower rates in high-income countries.The study reveals a gap in research on HCWs colonization,with only a single study from India reporting moderate prevalence.Environmental samples indicate moderate levels of CRAB contamination,again higher in South-East Asia.These findings underscore the need for more extensive and focused research on CRAB colonization in NICUs,including exploring the roles of HCWs and the environment in transmission,understanding antimicrobial resistance patterns,and developing effective prevention measures.

Effectiveness of Pilates exercises in sports

Participation in sports is spreading all around the world in an attempt of the community to stay active,healthy,prevent health issues and conditions and to ensure quality of life while there is life expectancy and population is getting more and more older.Existing protocols in rehabilitation are sometimes demanding and are addressed in athletes and people with good physical condition while population gets involved in recreational sports activities more and more.Sport injuries are very common not only in athletes but in general population as well.Pilates is a very popular type of exercise and industry around it is flourishing.Although there are indications that it could be used as an alternative in rehabilitation,research is limited in certain fields.The aim of this editorial is to motivate researchers to conduct well-designed studies in sports injuries’rehabilitation based on the Pilates method,to explore the efficacy of the method as a complementary approach and the optimal integration strategies in diverse sports rehabilitation settings.Last but not least,it is an attempt for the need of the community to establish certification on Clinical Pilates Physiotherapists based on the principles of rehabilitation.

Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale

One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence in science. Also for this reason, the quality of the studies included should be accurately evaluated by standardized tools. The overall results of the metaanalysis depend indeed also on a rigorous evaluation of the studies quality. Among all the possible tools for this complex evaluation, the Newcastle Ottawa Scale(NOS) is one of the most used worldwide, above all for observational studies. In this review, we will discuss the strengths and limitation of the NOS, also on the basis of the branch of science in which it has been applied.

Meta-analysis of single strain probiotics for the eradication of Helicobacter pylori and prevention of adverse events

AIM:To assess the efficacy and safety of single strain probiotics for the:(1) eradication of Helicobacter pylori(H.pylori);(2) prevention of adverse events;and(3) prevention of antibiotic-associated diarrhea associated with eradication therapy.METHODS:We searched Pub Med(1960-2014),EMBASE(1974-2014),Cochrane Database of Systematic Reviews(1990-2014),and ISI Web of Science(2000-2014).Additionally,we conducted a grey literature search including contact with National Institutes of Health Clinical Trials Registry,abstracts from annual infectious disease and gastroenterology meetings,experts in the field and correspondence with authors.Randomized controlled trials of H.pylori positive adults or children treated with eradication therapy and assessing the adjunctive therapy with a single strain of probiotics were included.The primary outcomes were the rates of eradication of H.pylori and frequency of patients with adverse events or antibiotic-associated diarrhea.Outcomes were pooled using fixed or random-effects models to calculate the relative risk and corresponding 95%CI and weighted on study size.To explore possible explanations for heterogeneity,a priori subgroup analyses were conducted on daily probiotic dose,study population,and quality of the study.The overall quality of the evidence for each probiotic strain was assessed using the GRADE criteria.RESULTS:A total of 25 randomized controlled trials(28 treatment arms,with a total of 3769 participants) assessed one of six single probiotic strains as adjunctive treatments to standard eradication therapy.Only one probiotic strain significantly improved H.pylori eradication rates:Saccharomyces boulardii(S.boulardii) CNCM I-745 [pooled relative risks(p RR) = 1.11,95%CI:1.07-1.16].Only one probiotic strain(S.boulardii CNCM I-745) significantly prevented any adverse events(p RR = 0.42,95%CI:0.28-0.62).Both S.boulardii CNCM I-745 and Lactobacillus rhamnosus GG significantlyreduced antibiotic-associated diarrhea(p RR = 0.47,95%CI:0.37-0.60 and p RR = 0.29,95%CI:0.17-0.48,respectively) associated with H.pylori eradication therapy.Meta-regression of sub-groups did not detect significant differences by dose,adult vs pediatric,symptom status,or study quality,but did find significant differences by the strain of probiotic.Potential mild publication bias was found for antibiotic-associated diarrhea,but not for eradication or adverse event outcomes.Analysis of the study quality illuminated areas for improvement in future studies(use of placebos,study size calculations,attrition reasons and discussion of limitations and generalizability).CONCLUSION:The pooled evidence suggests that the adjunctive use of a few probiotic strains may improve H.pylori eradication rates and prevent the development of adverse events and antibiotic-associated diarrhea in those treated with standard eradication therapies.The type of probiotic strain was the most important factor in predicting efficacy.

Preventing pediatric antibiotic-associated diarrhea and Clostridium difficile infections with probiotics: A metaanalysis

AIM： To assess the effcacy and safety of probiotics for preventing pediatric： （1） antibiotic associated diarrhea and （2） Clostridium diffcile （C. diffcile） infections.METHODS： On June 3, 2013, we searched PubMed （1960-2013）, EMBASE （1974-2013）, Cochrane Da-tabase of Systematic Reviews （1990-2013）, CINAHL （1981-2013）, AMED （1985-2013）, and ISI Web of Science （2000-2013）. Additionally, we conducted an extensive grey literature search including contact with National Institutes of Health Clinical Trials Registry, abstracts from annual infectious disease and gastroen-terology meetings, experts in the feld and correspondence with authors. The primary outcomes were the incidence of antibiotic-associated diarrhea （AAD） and C. difficile infections （CDI）. Dichotomous outcomes （e.g. , incidence of AAD or CDI） were pooled using a random-effects model to calculate the relative risk and corresponding 95% confidence interval （95%CI） and weighted on study quality. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain type, daily dose, quality of study and safety of probiotics. The overall quality of the evidence supporting each outcome was assessed using the grading of recommendations, assessment, development and evaluation criteria.RESULTS： A total of 1329 studies were identifed with 22 trials （23 treatment arms and 4155 participants） meeting eligibility requirements for our review of prevention of AAD and 5 trials （1211 participants） for the prevention of CDI. Trials in adult populations, trials of uncertain antibiotic exposure or studies which did not provide incidence of AAD were excluded. We found 12 trials testing a single strain of probiotic and 10 trials testing a mixture of probiotic strains. Probiotics （all strains combined） signifcantly reduced the incidence of pediatric AAD （pooled RR = 0.42, 95%CI： 0.33-0.53） and significantly reduced pediatric CDI （pooled RR = 0.35, 95%CI： 0.13-0.92）. Of the two strains with multiple trials, both signifcantly reduced pediatric AAD： Sac-charomyces boulardii lyo （pooled RR = 0.43, 95%CI： 0.32-0.60） and Lactobacillus rhamnosus GG （pooled RR = 0.36, 95%CI： 0.19-0.69）. There was no significant effect by type of antibiotic, or by duration or dose of probiotic. No adverse events associated were found in the 22 controlled trials relating to the use of probiotics.CONCLUSION： This meta-analysis found that probiotics signifcantly prevented pediatric antibiotic associated diarrhea and pediatric CDI, but the effcacy varies signifcantly by the strain of the probiotic.

Development of the Documentation and Appraisal Review Tool for systematic reviews

AIM:To develop a tool to more explicitly assess and document the quality of systematic reviews.METHODS:We developed the Documentation and Appraisal Review Tool(DART)using epidemiologic principles of study design and the following resources:the modified Overview Quality Assessment Questionnaire(modified OQAQ),Assessment of Multiple Systematic Reviews(AMSTAR),the Cochrane Handbook,and the standards promoted by the Agency for Healthcare Research and Quality,and the Institutes of Medicine(IOM).We designed the DART tool to include the following:more detail to provide guidance and improve standardization of use,an approach to assess quality of systematic reviews addressing a variety of research designs,and additional space for recording notes to facilitate recall.DART underwent multiple rounds of testing with methodologists of varying levels of training and experience.Based on the results of six phases of pilot testing,we revised DART to improve performance,clarity and consistency.Pilot testing also included comparisons between DART,and the two most commonly used tools to evaluate the quality of systematic reviews,the modified OQAQ and AMSTAR.RESULTS:Compared to AMSTAR and modified OQAQ,DART includes two unique questions and several questions covered by modified OQAQ or AMSTAR but not both.Modified OQAQ and DART had the highest reporting consistency.Four AMSTAR questions were unclear and elicited inconsistent responses.Identifying reviewer rationale was most difficult using the modified OQAQ tool,and easiest using DART.DART allowsfor documentation of reviewer rationale,facilitating reconciliation between reviewers and documentation for future updates.DART also provides a comprehensive,systematic approach for reviewers with limited experience with systematic review methodology,to critically analyze systematic reviews.In addition,DART is the only one of the three tools to explicitly include quality review for biases specific to observational studies.This is now more widely recognized as important for assessing risk in order to generate recommendations that balance benefit to harm.The tool also includes the assessment of standards recommended by the March 2011 IOM Standards for Systematic Review.CONCLUSION:This comprehensive tool improves upon existing tools for assessing the quality of systematic reviews and guides reviewers through critically analyzing a systematic review.

Treatment strategies and preventive methods for drug-resistant Helicobacter pylori infection

The infection and drug resistance rates of Helicobacter pylori(H.pylori)are high and must be prevented and treated by better strategies.Based on recent research advances in this field as well as the results from our team and those on traditional Chinese medicine,we review the causes of drug resistance,and prevention and treatment strategies for drug-resistant H.pylori infection,with an aim to make suggestions for the development of new drugs,such as establishment of new target identification and screening systems,modification of existing drug structures,use of new technologies,application of natural products,and using a commercial compound library.This article may provide reference for eradication of drug-resistant H.pylori.