Pandemic lockdowns: who feels coerced and why? - a study on perceived coercion, perceived pressures and procedural justice during the UK COVID-19 lockdowns.

BACKGROUND: This study examined perceptions of coercion, pressures and procedural injustice and how such perceptions influenced psychological well-being in those who experienced a UK COVID-19 lockdown, with a view to preparing for the possibility of future lockdowns. METHODS: 40 individuals categorised as perceiving the lockdown(s) as either highly or lowly coercive took part in one of six asynchronous virtual focus groups (AVFGs). RESULTS: Using thematic analysis, the following key themes were identified in participants' discussions: (1) Choice, control and freedom; (2) threats; (3) fairness; (4) circumstantial factors; and (5) psychological factors. CONCLUSIONS: As the first qualitative study to investigate the psychological construct of perceived coercion in relation to COVID-19 lockdowns, its findings suggest that the extent to which individuals perceived pandemic-related lockdowns as coercive may have been linked to their acceptance of restrictions. Preparing for future pandemics should include consideration of perceptions of coercion and efforts to combat this, particularly in relation to differences in equity, in addition to clarity of public health messaging and public engagement.

SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals.

SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

BACKGROUND: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. METHODS: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. RESULTS: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. CONCLUSIONS: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.

Diagnostic accuracy of reflectance confocal microscopy using VivaScope for detecting and monitoring skin lesions: a systematic review.

BACKGROUND: Skin cancer is one of the most common cancers in the UK. Patients with suspicious skin lesions are assessed clinically with/without dermoscopy, and lesions still considered suspicious are then surgically removed or have the diagnosis confirmed by a punch biopsy. AIM: To evaluate the diagnostic accuracy of the in vivo VivaScope© reflective confocal microscopy (RCM) system, a noninvasive technology designed to provide a more accurate presurgical diagnosis, leading to fewer biopsies of benign lesions, or to provide greater accuracy for lesion margins. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched to identify studies evaluating dermoscopy plus RCM, or RCM alone, with histopathology as the reference test. Clinical experts were also contacted for information on unpublished studies. RESULTS: Eleven studies met the inclusion criteria but were too heterogeneous to be combined by meta-analysis. Results indicated that VivaScope subsequent to dermoscopy may improve diagnostic accuracy of malignant melanomas compared with dermoscopy. For margin delineation, the data suggest that mapping using VivaScope 1500 for lentigo maligna (LM) and LM melanoma may improve accuracy in terms of complete excision of lesions compared with dermoscopically determined margins. For basal cell carcinoma, the limited data show high diagnostic accuracy with both VivaScope 1500 and VivaScope 3000. Evidence on the effectiveness of VivaScope in diagnosing cutaneous squamous cell carcinomas was very limited. CONCLUSION: The use of VivaScope 1500 following dermoscopy may improve patient care and management of suspicious skin lesions, although the generalizability of these results to the UK population remains unclear.

Extreme ultraviolet imaging of three-dimensional magnetic reconnection in a solar eruption.

Magnetic reconnection, a change of magnetic field connectivity, is a fundamental physical process in which magnetic energy is released explosively, and it is responsible for various eruptive phenomena in the universe. However, this process is difficult to observe directly. Here, the magnetic topology associated with a solar reconnection event is studied in three dimensions using the combined perspectives of two spacecraft. The sequence of extreme ultraviolet images clearly shows that two groups of oppositely directed and non-coplanar magnetic loops gradually approach each other, forming a separator or quasi-separator and then reconnecting. The plasma near the reconnection site is subsequently heated from ∼1 to ≥5 MK. Shortly afterwards, warm flare loops (∼3 MK) appear underneath the hot plasma. Other observational signatures of reconnection, including plasma inflows and downflows, are unambiguously revealed and quantitatively measured. These observations provide direct evidence of magnetic reconnection in a three-dimensional configuration and reveal its origin.

Litigation in English rhinology.

OBJECTIVE: Litigation is a rising financial burden on the National Health Service. This study aims to show if litigation is increasing in rhinology and which procedures lead to the most claims. METHODS: Ten years of data were obtained from the National Health Service Litigation Authority. Rhinology claims were examined for cost, injury, diagnosis and operation type. RESULTS: Of the 123 rhinology claims identified, 52 per cent were successful. There was a 56 per cent increase in the average annual number of claims between the first half of the study period and the second (p = 0.0451). The commonest reasons for a claim were poor cosmesis (15.6 per cent) and lack of informed consent (14 per cent). CONCLUSION: The number of claims in rhinology increased over the study period. Most claims resulted from poor cosmetic outcome, lack of consent or recognised complications. It is suggested that enhanced communication and management of patient expectations could reduce litigation and improve patient satisfaction.

Effects of activated carbon on reductive dechlorination of PCBs by organohalide respiring bacteria indigenous to sediments.

Polychlorinated biphenyls (PCBs) have accumulated in aquatic sediments due to their inherent chemical stability and their presence poses a risk due to their potential toxicity in humans and animals. Granular activated carbon (GAC) has been applied to PCB contaminated sediment sites to reduce the aqueous concentration by sequestration thus reducing the PCB exposure and toxicity to both benthic and aquatic organisms. However, it is not known how the reduction of PCB bioavailability by adsorption to GAC affects bacterial transformation of PCBs by indigenous organohalide respiring bacteria. In this study, the impact of GAC on anaerobic dechlorination by putative organohalide respiring bacteria indigenous to sediment from Baltimore Harbor was examined. It was shown that the average Cl/biphenyl after dehalogenation of Aroclor 1260 was similar between treatments with and without GAC amendment. However, GAC caused a substantial shift in the congener distribution whereby a smaller fraction of highly chlorinated congeners was more extensively dechlorinated to mono- through tri-chlorinated congeners compared to the formation of tri- through penta-chlorinated congeners in unamended sediment. The results combined with comparative sequence analysis of 16S rRNA gene sequences suggest that GAC caused a community shift to putative organohalide respiring phylotypes that coincided with more extensive dechlorination of ortho and unflanked chlorines. This shift in activity by GAC shown here for the first time has the potential to promote greater degradation in situ by promoting accumulation of less chlorinated congeners that are generally more susceptible to complete mineralization by aerobic PCB degrading bacteria.

Lithium or an atypical antipsychotic drug in the management of treatment-resistant depression: a systematic review and economic evaluation.

BACKGROUND: Patients with treatment-resistant depression (TRD) are those with major depressive disorder that has not responded adequately to treatment. The causes of depression are not fully understood, although there is evidence to suggest that depression is a complex interaction among biological, genetic, psychosocial and environmental factors. Strategies available for the treatment of patients with TRD include pharmacological, non-pharmacological, and psychological and psychosocial interventions. Pharmacological treatment options include switching to a different antidepressant, the addition of another antidepressant of a different class, or use of an augmenting agent, such as anticonvulsants, lithium or atypical antipsychotics (AAPs). However, there is limited evidence available on the effectiveness of these strategies in the treatment of TRD. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of augmentation of selective serotonin reuptake inhibitor (SSRI) antidepressant therapy with either lithium or an AAP drug in the management of people with treatment-resistant unipolar depression, defined as failure to respond to two or more antidepressant drugs in their current episode of depression. DATA SOURCES: Databases searched were Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, PsycINFO and NHS Economic Evaluation Database (NHS EED). All databases were searched from inception to August 2011. Additional data were obtained from manufacturers. REVIEW METHODS: Systematic reviews of studies evaluating clinical effectiveness, economic analyses and quality of life (QoL) were executed. Quality assessment according to predefined criteria was undertaken independently by two reviewers. Pairwise meta-analyses and mixed-treatment comparisons (MTCs) using both fixed- and random-effects models were undertaken based on intention-to-treat analyses. A probabilistic de novo mathematical model was developed to synthesise the available data on costs and clinical outcomes from the UK NHS perspective over a 1-year time horizon (8 weeks of acute treatment captured by a decision tree and 10 months of maintenance treatment captured by a Markov model). RESULTS: Twelve randomised controlled trials (RCTs) were identified in the review of clinical effectiveness literature; 10 considered SSRI + AAP compared with SSRI + placebo/no treatment, one considered SSRI + AAP compared with SSRI + lithium and one considered SSRI + lithium compared with SSRI + placebo. The RCTs included in the primary analyses used fluoxetine as the background SSRI and olanzapine as the AAP. Results of the MTC showed a non-significant trend in favour of lithium augmentation for response [lithium a priori odds ratio (OR) 1.29; 95% credible interval (CrI) 0.11 to 5.32; lithium post hoc OR 4.15; 95% CrI 0.25 to 20.34 (the trial informing the comparison with lithium reported response using two different definitions)], mean change in Montgomery-Åsberg Depression Rating Scale score from baseline (mean difference - 1.47, 95% CrI - 9.10 to 6.41) and all-cause withdrawals (OR 0.74, 95% CrI 0.10 to 2.66). Four economic evaluations (none directly addressing the review question) and 17 studies that reported on QoL were identified and summarised in narrative reviews. The results of the de novo modelling indicate that augmentation of SSRI with lithium dominates augmentation of an SSRI with AAP (i.e. it resulted in cost savings of £905 per person per year and generated more health benefits, estimated to be 0.03 quality-adjusted life-years). However, sensitivity analyses showed that the model was highly sensitive to changes in acute treatment efficacy (response and remission) or discontinuation. The model was not sensitive to changes in other parameters. LIMITATIONS: In patients with TRD, there is a lack of direct evidence comparing the clinical effectiveness of augmenting an SSRI with an AAP compared with augmenting with lithium. RCTs were identified which facilitated comparison of adding AAP with adding lithium via a MTC. However, variations in the definitions of response implemented in the RCTs, together with differences in patient baseline characteristics across RCTs, introduce bias into the analysis. The direction and extent of the bias is uncertain. CONCLUSIONS: Augmentation of SSRIs with lithium or AAP is likely to be beneficial in people with TRD. Clinical evaluation based on the limited evidence identified in this research indicates no statistically significant difference between the two augmentation strategies. Cost-effectiveness analyses suggest that augmentation with lithium is less expensive and more effective than augmentation with AAP. However, the uncertainty in the clinical estimates of discontinuation and treatment response is reflected in the model results. A RCT comparing the two augmentation strategies, reporting relevant outcomes, including QoL, is needed. STUDY REGISTRATION: PROSPERO CRD42011001464.

Effect of age, weight, and sire on embryo and fetal survival in sheep.

The goal was to estimate the heritabilities and genetic variances for embryo and fetal survival (ES) in sheep along with the effect of premating ewe weight, age, and bilateral or unilateral ovulation on ES. The data consisted of 11,369 records on ovulation rate and litter size. Statistical models for ES included year and ovulation rate as fixed effects, premating ewe weight, and age as covariates, and sire of embryo, maternal grandsire (MGS), and permanent maternal environmental effects of the ewe as random effects. The variance components were estimated using REML. In ewes that survived to yr 6, the mean litter size was 1.87, 2.05, 2.01, 2.07, and 1.91 ± 0.04 in ewes of age 2, 3, 4, 5, and 6 yr, respectively. Litter size was less in ewes of age 2 and 6 yr compared to ewes of age 3, 4, and 5 yr (P < 0.01). Ovulation rate was lower at age 2 yr and increased from age 2 to 6 yr (P < 0.05). Two-year-old ewes had lower ES than 3-yr-old ewes (P < 0.01) and the probability of ES decreased after age 3 yr (P < 0.01). Thus, ES contributes significantly to lower fertility in 2-yr-old ewes. In ewes with high ovulation rates (i.e., 5 corpora lutea, CL), more balanced ovulations (i.e., 2 or 3 CL on each ovary) tended (P = 0.06) to be associated with increased ES. A quadratic relationship was observed between ewe weight and litter size (P < 0.01) and a positive linear relationship between premating ewe weight and ovulation rate (P < 0.01). A quadratic effect of ewe weight on ES was observed, with decreased ES for low and high ewe weights (P < 0.01). The optimal ewe weight for ES increased with ovulation rate, which is consistent with the requirement of greater body reserves for maintaining a larger number of fetuses during gestation. A quadratic relationship between ewe weight and the probability that a ewe is able to maintain a pregnancy was also observed (P < 0.05). Pregnancy loss is due to failure of the embryo or fetus or failure of the dam to maintain the pregnancy. The sire of the embryo only influences the embryo, whereas the MGS influences both the ewe and the embryo. The heritability for the direct additive effect on ES in ewes that lambed was 0.0081 ± 0.0139, and the heritability for the maternal additive effect was 0.0447 ± 0.0242. The permanent maternal environmental variance component was significant and explained 8.5% of the phenotypic variance. Thus, genetically, the dam's ability to maintain a pregnancy has 5.5 times the effect on pregnancy loss than the embryo's ability to survive, and this, in turn, was only half the size of the permanent environmental effect. Therefore, selection among dams based on the mean embryonic survival of their embryos will provide an effective way to improve embryonic survival.

Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials.

AIMS: This analysis was designed to provide a comparison between budesonide/formoterol and salmeterol/fluticasone for the relative incidence of pneumonia adverse events, pneumonia serious adverse events and pneumonia-related mortality in patients being treated for chronic obstructive pulmonary disease. METHODS: An initial literature search revealed no suitable head-to-head trials between budesonide/formoterol and salmeterol/fluticasone and therefore a systematic review was conducted to find randomised controlled trials providing data for input into an adjusted indirect comparison of the two combination treatments using placebo as a common comparator. The Bucher adjusted indirect comparison method was used to calculate odds ratios and 95% confidence intervals. RESULTS: Eight salmeterol/fluticasone trials and four budesonide/formoterol trials were identified as being relevant for the analyses. The proportion of patients experiencing a pneumonia adverse event was significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.47; 95% confidence interval, 0.28-0.80). The proportion of patients experiencing a pneumonia serious adverse event was also significantly lower with budesonide/formoterol than salmeterol/fluticasone (odds ratio, 0.41; 95% confidence interval, 0.19-0.86). However, there were too few events to draw any firm conclusions on pneumonia-related mortality. CONCLUSIONS: The results of the indirect comparison support the hypothesis that budesonide/formoterol is associated with fewer pneumonia events than salmeterol/fluticasone in chronic obstructive pulmonary disease. The limitations of the analysis are that the results from a single study, TORCH, have a large bearing on the overall findings of the analysis, and that there is heterogeneity in the length and the dosing of the included studies, although it does not appear that heterogeneity affected the reported results. Another important limitation is the lack of predefined diagnostic standards for pneumonia in these studies.

A linkage map of sheep chromosome X (OARX) aligned to human chromosome X (HSAX).

We have constructed a genetic linkage map of the sheep X chromosome (OARX) containing 22 new gene loci from across the human X chromosome (HSAX). The female OARX linkage map has a total length of 152.6 cM with average gene spacing of 5.5 cM. Comparison with HSAX confirms one previously reported major breakpoint and inversion, and other minor rearrangements between OARX and HSAX. Comparison of the linkage map with sheep sequence data OAR 1.0 reveals a different arrangement of markers on the q arm, which may more accurately reflect the genuine arrangement of this region.

Budesonide/formoterol for maintenance and reliever therapy of asthma: a meta analysis of randomised controlled trials.

OBJECTIVES: To compare the effectiveness of budesonide/formoterol (Symbicort) for Maintenance and Reliever Therapy (Symbicort SMART) Turbuhaler with twice daily inhaled corticosteroid (ICS) treatment, alone or in combination with a long-acting beta(2)-agonist (LABA). METHODS: Meta analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with budesonide/formoterol for maintenance and relief had the equivalent, or up to fourfold higher, maintenance dose of ICS. The primary outcome was the incidence of severe exacerbation (oral glucocorticosteroid treatment for > or = 3 days, emergency visit and/or hospitalisation). RESULTS: Of the seven RCTs available six met the inclusion criteria. Risk of severe exacerbations was significantly reduced: 41% vs. higher-dose budesonide alone [relative risk (RR) 0.59, 95% confidence interval (95% CI): 0.51-0.68, p < 0.00001]; 43% vs. equivalent dose budesonide/formoterol as maintenance twice daily (RR 0.57, 95% CI: 0.49-0.66, p < 0.00001); 24% vs. higher-dose salmeterol/fluticasone twice daily (RR 0.76, 95% CI: 0.64-0.90, p = 0.002); and 26% vs. higher-dose budesonide/formoterol twice daily (RR 0.74, 95% CI: 0.58-0.96, p = 0.02). Significant heterogeneity was not detected in the primary analyses (p > 0.1). Secondary analyses also demonstrated that budesonide/formoterol for maintenance and relief reduced the most severe exacerbations, resulting in less hospitalisations/accident and emergency visits than higher-dose budesonide, equivalent dose budesonide/formoterol and higher-dose salmeterol/fluticasone twice daily. CONCLUSION: Budesonide/formoterol for maintenance and relief is significantly more effective at reducing severe exacerbations than higher-dose ICS alone, or in combination with a LABA. This has important implications for treating uncontrolled patients at steps 2 and 3 of the joint BTS/SIGN guidelines.

Indirect comparisons of treatments based on systematic reviews of randomised controlled trials.

BACKGROUND: Randomised controlled trials are the most effective way to differentiate between the effects of competing interventions. However, head-to-head studies are unlikely to have been conducted for all competing interventions. AIM: Evaluation of different methodologies used to indirectly compare interventions based on meta analyses of randomised controlled trials. METHODS: Systematic review of Cochrane Database of Systematic Reviews, Cochrane Methodology Register, EMBASE and MEDLINE for reports including meta analyses that contained an indirect comparison. Searching was completed in July 2007. No restriction was placed on language or year of publication. RESULTS: Sixty-two papers identified contained indirect comparisons of treatments. Five different methodologies were employed: comparing point estimates (1/62); comparing 95% confidence intervals (26/62); performing statistical tests on summary estimates (8/62); indirect comparison using a single common comparator (20/62); and mixed treatment comparison (MTC) (7/62). The only methodologies that provide an estimate of the difference between the interventions under consideration and a measure of the uncertainty around that estimate are indirect comparison using a single common comparator and MTC. The MTC might have advantages over other approaches because it is not reliant on a single common comparator and can incorporate the results of direct and indirect comparisons into the analysis. Indirect comparisons require an underlying assumption of consistency of evidence. Utilising any of the methodologies when this assumption is not true can produce misleading results. CONCLUSIONS: Use of either indirect comparison using a common comparator or MTC provides estimates for use in decision making, with the preferred methodology being dependent on the available data.

Systematic review: standard- and double-dose proton pump inhibitors for the healing of severe erosive oesophagitis -- a mixed treatment comparison of randomized controlled trials.

BACKGROUND: No randomized controlled trial (RCT) has compared all European-licensed standard- and double-dose PPIs for the healing of severe erosive oesophagitis. AIM: To compare the effectiveness of licensed doses of PPIs for healing severe erosive oesophagitis (i.e. esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg and 40 mg, pantoprazole 40 mg and rabeprazole 20 mg). METHODS: Systematic review of CENTRAL, EMBASE and MEDLINE for RCTs in patients with erosive oesophagitis (completed October 2008). Endoscopically verified healing rates at 4 and 8 weeks were extracted and re-calculated if not analysed by intention-to-treat. A mixed treatment comparison was used to combine direct treatment comparisons with indirect trial evidence while maintaining randomization. Odds ratios (OR) are reported compared to omeprazole 20 mg. RESULTS: A total of 3021 papers were identified in the literature search; 12 were of sufficient quality to be included in the analysis. Insufficient data were available to included rabeprazole. Esomeprazole 40 mg was found to provide significantly higher healing rates at 4 weeks [OR 1.84, 95% Credible Interval (95% CrI): 1.50 to 2.22] and 8 weeks (OR 1.91, 95% CrI: 1.13 to 2.88). No other PPI investigated had significantly higher healing rates than omeprazole 20 mg. CONCLUSION: Esomeprazole 40 mg consistently demonstrates higher healing rates compared with licensed standard- and double-dose PPIs.

Ethics review of research: in pursuit of proportionality.

The ethics review system of research is now well-established, at least in the developed world, although there are many differences in how countries view it and go about managing it. The UK specifically is now seeking to revise its system by speeding up the process of ethics approval but only for some studies. It is proposed that only those studies which pose "no material ethical issues" should be "fast-tracked". However, it is unclear what this means, who should decide and what should be included in this category. In this paper, we go some way towards answering these questions. While we are certain that the debate is only just beginning, we are equally certain that it will continue to run long after the system has been reformed. To stimulate this conversation and to inform a pilot project of the new system directly, we review two candidates to help give some substance to the notion of "material" ethical issues. Firstly, material could mean a certain type or degree of risk. Second, material could mean how physically invasive the research is. We conclude that there is still much work to be done on making the system of governing health and social care consistent and practicable.

Carbapenems versus other beta-lactams in treating severe infections in intensive care: a systematic review of randomised controlled trials.

Carbapenems have not been comprehensively compared in clinical trials with fourth-generation cephalosporins (4GC) and antipseudomonal penicillins (APP) in the treatment of severe infections (SI) and febrile neutropenia (FN). A systematic review of CENTRAL, EMBASE, MEDLINE and JICST-EPlus for randomised controlled trials was conducted to establish the currently available evidence. Database searching was supplemented by hand searching and contacting conference organisers. Searching was completed in November 2006 and no restriction was placed on the language of publication. Data were extracted on clinical response, bacteriologic response, all-cause mortality and adverse events. Of the 265 papers identified, 12 were appropriate for meta-analysis (four 4GC and eight APP). The results showed that carbapenems are associated with a significant reduction in all-cause mortality (relative risk 0.62, 95% confidence interval: 0.41 to 0.95; p=0.03) compared to APP in the treatment of SI, and withdrawals due to adverse events (RR 0.65, 95% CI: 0.45 to 0.96; p=0.03) are also less common. When compared in the treatment of FN, carbapenems are associated with a significant increase in clinical response during the initial 72 h of treatment (RR 1.37, 95% CI: 1.09 to 1.74; p=0.008) and bacteriologic response (RR 1.73, 95% CI: 1.03 to 2.89; p=0.04). For all other outcomes, including all comparisons with 4GC, there were no significant differences between treatments. The use of carbapenems rather than APP could reduce mortality and, by simplifying treatment decisions, reduce the time before patients receive appropriate antibiotic treatment. The currently available evidence is insufficient for distinguishing between carbapenems and 4GC.

Is exocrine pancreatic insufficiency in adult coeliac disease a cause of persisting symptoms?

BACKGROUND: Patients with coeliac disease may have diarrhoea despite being on a gluten-free diet. AIM: To assess whether exocrine pancreatic insufficiency causes persisting symptoms compared with controls, we determined whether pancreatic enzyme supplementation provided symptomatic benefit in coeliac patients with chronic diarrhoea. METHODS: Patients (n = 259) were subdivided into four groups: (a) new coeliac disease (n = 57), (b) coeliac disease patients on a gluten-free diet without gastrointestinal symptoms (n = 86), (c) coeliac disease patients on a gluten-free diet with chronic diarrhoea (n = 66) and (d) patients with chronic diarrhoea without coeliac disease (n = 50). Stool frequency and weight, before and after treatment with pancreatic enzyme supplementation were recorded. RESULTS: The prevalence of a low faecal elastase-1 within the groups was: group (A) six of 57 (11%), group (B) five of 86 (6%), group (C) 20 of 66 (30%) and group (D) two of 50 (4%). Low faecal elastase-1 was more frequent in coeliac disease patients with chronic diarrhoea vs. other subgroups of coeliac disease (P < or = 0.0001) and controls (P < or = 0.0003). In 18 of 20 stool frequency reduced following pancreatic enzyme supplementation from four per day to one (P < or = 0.001). No weight increase (P = 0.3) was observed. CONCLUSIONS: Low faecal elastase is common in patients with coeliac disease and chronic diarrhoea, suggesting exocrine pancreatic insufficiency. In this group of patients, pancreatic enzyme supplementation may provide symptomatic benefit.

Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs.

BACKGROUND: No randomized controlled trial has compared all the licensed standard dose proton pump inhibitors in the healing of reflux oesophagitis. AIM: To compare the effectiveness of esomeprazole with licensed standard dose proton pump inhibitors for healing of reflux oesophagitis (i.e. lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg and rabeprazole 20 mg). METHODS: Systematic review of CENTRAL, BIOSIS, EMBASE and MEDLINE for randomized controlled trials in patients with reflux oesophagitis. Searching was completed in February 2005. Data on endoscopic healing rates at 4 and 8 weeks were extracted and re-analysed if not analysed by intention-to-treat. Meta-analysis was conducted using a fixed effects model. RESULTS: Of 133 papers identified in the literature search, six were of sufficient quality to be included in the analysis. No studies were identified comparing rabeprazole with esomeprazole. A meta-analysis of healing rates of esomeprazole 40 mg compared with standard dose proton pump inhibitors gave the following results: at 4 weeks [relative risk (RR) 0.92; 95% CI: 0.90, 0.94; P < 0.00001], and 8 weeks (RR 0.95; 95% CI: 0.94, 0.97; P < 0.00001). Publication bias did not have a significant impact on the results. The results were robust to changes in the inclusion/exclusion criteria and using a random effects model. CONCLUSION: Esomeprazole consistently demonstrates higher healing rates when compared with standard dose proton pump inhibitors.