Systematic review:Laparoscopic fundoplication for gastroesophageal reflux disease in partial responders to proton pump inhibitors

AIM: To assess laparoscopic fundoplication (LF) in partial responders to proton pump inhibitors (PPIs) for gastroesophageal reflux disease (GERD).

Rationally designed mariner vectors for functional genomic analysis of Actinobacillus pleuropneumoniae and other Pasteurellaceae species by transposon-directed insertion-site sequencing (TraDIS)

Comprehensive identification of conditionally essential genes requires efficient tools for generating high-density transposon libraries that, ideally, can be analysed using next-generation sequencing methods such as Transposon Directed Insertion-site Sequencing (TraDIS). The Himar1 (mariner) transposon is ideal for generating near-saturating mutant libraries, especially in AT-rich chromosomes, as the requirement for integration is a TA dinucleotide, and this transposon has been used for mutagenesis of a wide variety of bacteria. However, plasmids for mariner delivery do not necessarily work well in all bacteria. In particular, there are limited tools for functional genomic analysis of Pasteurellaceae species of major veterinary importance, such as swine and cattle pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida, respectively. Here, we developed plasmids, pTsodCPC9 and pTlacPC9 (differing only in the promoter driving expression of the transposase gene), that allow delivery of mariner into both these pathogens, but which should also be applicable to a wider range of bacteria. Using the pTlacPC9 vector, we have generated, for the first time, saturating mariner mutant libraries in both A. pleuropneumoniae and P. multocida that showed a near random distribution of insertions around the respective chromosomes as detected by TraDIS. A preliminary screen of 5000 mutants each identified 8 and 14 genes, respectively, that are required for growth under anaerobic conditions. Future high-throughput screening of the generated libraries will facilitate identification of mutants required for growth under different conditions, including in vivo, highlighting key virulence factors and pathways that can be exploited for development of novel therapeutics and vaccines.

Absolute cardiovascular risk assessment by Australian early-career general practitioners: a cross-sectional study

Objective To determine the prevalence and associations of general practice registrars’performing absolute cardio-vascular risk(ACVR)assessment(ACVRa).Design A cross-sectional study employing data(2017–2018)from the Registrar Clinical Encounters in Training project,an ongoing inception cohort study of Australian GP registrars.The outcome measure was whether an ACVRa was performed.Analyses employed univariable and multivariable regression.Analysis was conducted for all patient problems/diagnoses,then for an‘at-risk’population(specific problems/diagnoses for which ACVRa is indicated).Setting Three GP regional training organisations(RTOs)across three Australian states.Participants GP registrars training within participating RTOs.Results 1003 registrars(response rate 96.8%)recorded details of 69105 problems either with Aboriginal and/or Torres Strait patients aged 35 years and older or with non-Indigenous patients aged 45 years and older.Of these problems/diagnoses,1721(2.5%(95%CI 2.4%to 2.6%))involved an ACVRa.An ACVRa was‘plausibly indicated’in 10384 problems/diagnoses.Of these,1228(11.8%(95%CI 11.2%to 12.4%))involved ACVRa.For‘all problems/diagnoses’,on multivariable analysis female gender was associated with reduced odds of ACVRa(OR 0.61(95%CI 0.54 to 0.68)).There was some evidence for Aboriginal and/or Torres Strait Islander people being more likely to receive ACVRa(OR 1.40(95%CI 0.94 to 2.08),p=0.10).There were associations with variables related to continuity of care,with reduced odds of ACVRa:if the patient was new to the registrar(OR 0.65(95%CI 0.57 to 0.75)),new to the practice(OR 0.24(95%CI 0.15 to 0.38))or the problem was new(OR 0.68(95%CI 0.59 to 0.78));and increased odds if personal follow-up was organised(OR 1.43(95%CI 1.24 to 1.66)).For‘ACVRa indicated’problems/diagnoses,findings were similar to those for‘all problems/diagnoses’.Association with Aboriginal and/or Torres Strait Islander status,however,was significant at p<0.05(OR 1.60(95%CI 1.04 to 2.46))and association with female gender was attenuated(OR 0.88(95%CI 0.77 to 1.01)).Conclusion Continuity of care is associated with registrars assessing ACVR,reinforcing the importance of care continuity in general practice.Registrars’assessment of an individual patient’s ACVR is targeted to patients with individual risk factors,but this may entail ACVRa underutilisation in female patients and younger age groups.

Predictive modeling of COVID-19 death cases in Pakistan

Background:The world is presently facing the challenges posed by COVID-19(2019-nCoV),especially in the public health sector,and these challenges are dangerous to both health and life.The disease results in an acute respiratory infection that may result in pain and death.In Pakistan,the disease curve shows a vertical trend by almost 256K established cases of the diseases and 6035 documented death cases till August 5,2020.Objective:The primary purpose of this study is to provide the statistical model to predict the trend of COVID-19 death cases in Pakistan.The age and gender of COVID-19 victims were represented using a descriptive study.Method:ology:Three regression models,which include Linear,logarithmic,and quadratic,were employed in this study for the modelling of COVID-19 death cases in Pakistan.These three models were compared based on R2,Adjusted R2,AIC,and BIC criterions.The data utilized for the modelling was obtained from the National Institute of Health of Pakistan from February 26,2020 to August 5,2020.Conclusion:The finding deduced after the prediction modelling is that the rate of mortality would decrease by the end of October.The total number of deaths will reach its maximum point;then,it will gradually decrease.This indicates that the curve of total deaths will continue to be flat,i.e.,it will shift to be constant,which is also the upper bound of the underlying function of absolute death.

Specificity of early-career general practitioners’problem formulations in patients presenting with dizziness:a cross-sectional analysis

Objectives Dizziness is a common and challenging clinical presentation in general practice.Failure to determine specific aetiologies can lead to significant morbidity and mortality.We aimed to establish frequency and associations of general practitioner(GP)trainees’(registrars’)specific vertigo provisional diagnoses and their non-specific symptomatic problem formulations.Design A cross-sectional analysis of Registrar Clinical Encounters in Training(ReCEnT)cohort study data between 2010 and 2018.ReCEnT is an ongoing,prospective cohort study of registrars in general practice training in Australia.Data collection occurs once every 6 months midtraining term(for three terms)and entails recording details of 60 consecutive clinical consultations on hardcopy case report forms.The outcome factor was whether dizziness-related or vertigo-related presentations resulted in a specific vertigo provisional diagnosis versus a non-specific symptomatic problem formulation.Associations with patient,practice,registrar and consultation independent variables were assessed by univariate and multivariable logistic regression.Setting Australian general practice training programme.The training is regionalised and delivered by regional training providers(RTPs)(2010-2015)and regional training organisations(RTOs)(2016-2018)across Australia(from five states and one territory).Participants All general practice registrars enrolled with participating RTPs or RTOs undertaking GP training terms.Results 2333 registrars(96%response rate)recorded 1734 new problems related to dizziness or vertigo.Of these,546(31.5%)involved a specific vertigo diagnosis and 1188(68.5%)a non-specific symptom diagnosis.Variables associated with a non-specific symptom diagnosis on multivariable analysis were lower socioeconomic status of the practice location(OR 0.94 for each decile of disadvantage,95%CIs 0.90 to 0.98)and longer consultation duration(OR 1.02,95%CIs 1.00 to 1.04).A specific vertigo diagnosis was associated with performing a procedure(OR 0.52,95%CIs 0.27 to 1.00),with some evidence for seeking information from a supervisor being associated with a non-specific symptom diagnosis(OR 1.39,95%CIs 0.92 to 2.09;p=0.12).Conclusions Australian GP registrars see dizzy patients as frequently as established GPs.The frequency and associations of a non-specific diagnosis are consistent with the acknowledged difficulty of making diagnoses in vertigo/dizziness presentations.Continuing emphasis on this area in GP training and encouragement of supervisor involvement in registrars’diagnostic processes is indicated.