The effectiveness and variation of acute medical units: a systematic review.

PURPOSE: To evaluate the evidence for the effectiveness of acute medical units (AMUs) compared with other models of care and compare the components of AMU models. DATA SOURCES: Six electronic databases and grey literature sources searched between 1990 and 2014. STUDY SELECTION: Studies reporting on AMUs as an intervention for unplanned medical presentations to hospital with the inclusion of all outcome measures/study designs/comparators. DATA EXTRACTION: Data on study characteristics/outcomes/AMU components were extracted by one author and confirmed by a second. DATA SYNTHESIS: Seventeen studies of 12 AMUs across five countries were included. The AMU model was associated with a reduction in-hospital length of stay (LOS) in all analyses ranging from 0.3 to 2.6 days; and a reduction in mortality in 12 of the 14 analyses with the change ranging from a 0.1% increase to a 8.8% reduction. Evidence relating to readmissions and patient/staff satisfaction was less conclusive. There was variation in the following components of AMUs: admission criteria, entry sources, functions and consultant work patterns. CONCLUSION: This review provides evidence that AMUs are associated with reductions in-hospital LOS and, less convincingly, mortality compared with other models of care when implemented in European and Australasian settings. Reported estimates may be affected by residual confounding. This review reports heterogeneity in components of the AMU model. Further work to identify what constitutes the key components of an AMU is needed to improve the quality and effectiveness of acute medical care. This is of particular importance given the escalating demand on acute services.

A randomized trial of a fully covered self-expandable metallic stent versus plastic stents in anastomotic biliary strictures after liver transplantation.

BACKGROUND: Post-liver-transplant biliary anastomotic strictures (ASs) are currently managed with repeated endoscopic retrograde cholangiopancreatographies (ERCPs) inserting multiple plastic stents. Fully covered self-expanding metal stents (FCSEMSs) are being increasingly reported in the management of this condition, however no prospective randomized trials have been performed to date. AIM: The aim of this study was to determine whether FCSEMSs decrease overall numbers of ERCPs needed to achieve stricture resolution and to establish the safety, efficacy and cost-effectiveness in this setting. METHODS: Two tertiary referral centres performed this open-label prospective randomized trial. A total of 32 patients consented and subsequently 20 were randomized with 10 in the FCSEMS arm and 10 in the plastic arm. The FCSEMS arm had the stent in situ for 12 weeks with the plastic stent arm undergoing 3-monthly multiple plastic stenting with or without dilatation over a year. RESULTS: The median number of ERCPs performed per patient in the FCSEMS was 2 versus 4.5 (p = 0.0001) in the plastic stenting arm. Stricture resolution was achieved in all 10 patients with FCSEMSs compared with 8/10 in the plastic arm [p = not significant (NS)]. Complications occurred in 1/10 patients in the FCSEMS arm versus 5/10 in the plastic arm (p = 0.051). Days in hospital for complications was 6 in the FCSEMS versus 56 in the plastic arm (p = 0.11). Cost analysis shows that the FCSEMS arm was more cost effective. No cases of FCSEMS migration were seen. CONCLUSIONS: FCSEMSs reduced the number of ERCPs needed to achieve stricture resolution with similar recurrence rates between arms. The FCSEMSs may do so with fewer complications making it cost effective.

Meta-analysis of narrow-band imaging versus conventional colonoscopy for adenoma detection.

BACKGROUND: At colonoscopy, missed adenomas have been well documented at approximately 22%. The challenge is in reducing this miss rate. Narrow-band imaging (NBI) has been extensively evaluated in prospective, randomized, controlled studies for polyp detection. Sample-size calculations show us that these studies may be underpowered, and hence a meta-analysis is required. OBJECTIVE: Our aim was to determine whether use of NBI enhances the detection of adenomas. DESIGN: Meta-analyses were conducted of 7 studies using NBI for adenoma detection rate. MEDLINE, Embase, PubMed, and Cochrane databases were searched by using a combination of the following terms: "colonoscopy," "NBI," and "electronic chromoendoscopy." PATIENTS: There was a total of 2936 patients in the NBI studies. INTERVENTIONS: Prospective, randomized trials of NBI versus standard white-light colonoscopy (WLC) were conducted. We excluded spray chromoendoscopy studies and studies of inflammatory bowel disease and polyposis syndromes. MAIN OUTCOME MEASUREMENTS: Adenoma and polyp detection rates and the number of polyps and adenomas detected per person. RESULTS: There was no statistically significant difference in the overall adenoma detection rate with the use of NBI or WLC (36% vs 34%; P = .413 [relative risk 1.06; 95% CI, 0.97-1.16]), and there was no statistically significant difference in polyp detection rate by using NBI or WLC (37% vs 35%; P = .289 [relative risk 1.22; 95% CI, 0.85-1.76]). When the number of adenomas and polyps per patient was analyzed, no significant difference was found between NBI and WLC (0.645 vs 0.59; P = .105 and 0.373 vs 0.348; P = .139 [weighted mean difference 0.19; 95% CI, ∞0.06 to 0.44], respectively). LIMITATION: Variability in NBI studies can reduce the accuracy of this analysis. CONCLUSIONS: NBI did not increase adenoma or polyp detection rates.

Managing acute upper gastrointestinal bleeding in the acute assessment unit.

AAUs should develop and review protocols and local guidelines for the multidisciplinary team management of upper GI bleeding, for example with respect to: Early and appropriate resuscitation. Use of the tools for assessing severity. Timing of endoscopy, including recognising low-risk patients who could be discharged for outpatient investigation. Postendoscopy drug treatment, including appropriate and limited use of iv PPIs and Helicobacter pylori eradication therapy. Follow up, including referral for repeat endoscopy and/or urea breath testing. Regular review and audit of local guidance of the management of UGIB should become an integral part of an acute trust's clinical governance programme.

The pattern and outcome of acute severe colitis.

BACKGROUND: The prognosis of acute severe ulcerative colitis (ASC) influences therapeutic decisions, but data on prevalence or long-term outcome are few. METHODS: A systematic review of all patients with UC diagnosed in Oxford was performed to assess the prevalence of ASC defined by Truelove and Witts' (TW) criteria and determine whether outcome is related to disease activity on admission, likelihood of recurrence and long-term prognosis. RESULTS: 750 patients (median follow up 12.7 yr, range 0-648 mo) met inclusion criteria out of a total cohort of 1853 patients. 24.8% (186/750) had at least one admission for ASC (294 admissions in 186 patients). Overall, 12% (93/750) had a colectomy, compared to 39.8% (74/186) of patients with one or more episodes of ASC (p<0.0001) and 3.4% (19/564) in those with no admission. The colectomy rate on first admission (37/186, 19.9%) was lower than on the second or subsequent admissions (OR 2.35, 95% CI 1.33-4.14, p=0.003), being 29.0%, 36.6%, 38.2% after two, three, or subsequent episodes respectively. It was 8.5% (11/129) if patients had one TW criterion in addition to ≥6 bloody bowel motions/day, compared to 31% (29/94) if two additional criteria were present and 48% (34/71) if three or more additional criteria were present (p=1.4 × 10⁻5; OR 4.35, 95% CI 2.20-8.56 one criterion vs two or more). CONCLUSIONS: A quarter of all patients with ulcerative colitis experience at least one episode of ASC; 20% come to colectomy on first admission, but 40% after two admissions. The likelihood of colectomy is related to biological severity on admission.

Complex nature of SNP genotype effects on gene expression in primary human leucocytes.

BACKGROUND: Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown. METHODS: We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110) from individuals with celiac disease - a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90), and performed a meta-analysis to increase power to detect non-tissue specific effects. RESULTS: In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (< 250 kb from SNP, at FDR = 0.05, cis expression quantitative trait loci, eQTLs). 135 of the detected SNP-probe effects (reflecting 51 unique probes) were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed cis-eQTLs. Celiac associated risk variants from two regions, containing genes IL18RAP and CCR3, showed significant cis genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected. CONCLUSION: In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.

Newly identified genetic risk variants for celiac disease related to the immune response.

Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways.

Efficacy of Infliximab treatment in patients with severe Fistulizing Hidradenitis Suppurativa.

BACKGROUND: The association of Crohn's disease with Fistulizing Hidradenitis Suppurativa (FHS) was established in the 90s. FHS is a chronic disease, characterized by the formation of multiple abscesses and sinus tracts in apocrine gland-bearing areas. The aetiology and pathogenesis is unknown. The disease is painful and often socially disabling implying a poor Quality of Life. Treatment of FHS with Infliximab - a chimeric antibody to TNFα - has recently been proposed as alternative to surgery. AIM: To describe efficacy of Infliximab treatment in the first 2 Danish patients with resistant severe FHS. METHODS: Two patients with severe FHS previously unsuccessfully treated with conventional therapies. Infliximab 5 mg/kg was given as induction treatment. Clinical response was measured by MRI and modified Quality of Life scoring before and after the Infliximab. RESULTS: The first patient obtained partial remission after the first infusion, with 2 active sinus tracts of 20 detected by MRI. The patient became INF dependent and continued on maintenance treatment every 8th week. In total 8 infusions. The second patient obtained partial remission after 3 infusions and did not experience relapse after withdrawal of Infliximab. The clinical findings of remission were underscored by showing improvement on MRI. The Quality of Life has been increased in both patients. CONCLUSION: Infliximab treatment seems to be efficacious in patients with severe FHS. Maintenance treatment may be necessary. Infliximab can lead to improvement in Quality of Life, partial remission of disease verified by closure of fistula in MRI and keeping the patients from mutilating surgery.

Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870).

A variety of targets for therapeutic intervention are based upon advances in understanding of the immunopathogenesis of Crohn's disease. Crohn's disease is initiated by an innate immune response, which eventuates in a T-cell driven process, characterized by a T-helper cell 1 type cytokine profile. Several new treatments now focus on suppressing T-cell differentiation or T-cell inflammation. Since inflammatory bowel disease (IBD) represents a state of dysregulated inflammation, drugs that augment the anti-inflammatory response have the potential to downregulate inflammation and thereby hopefully modify the disease. Tumour necrosis factor (TNF) is a major target of research and clinical investigation. TNF has proinflammatory effects in the intestinal mucosa and is a pivotal cytokine in the inflammatory cascade. Certolizumab pegol (CDP870) is a PEGylated, Fab' fragment of a humanized anti-TNF-alpha monoclonal antibody. PEGylation increases the half-life, reduces the requirement for frequent dosing, and possibly reduces antigenicity as well. Certolizumab has been shown in Phase III trials to achieve and maintain clinical response and remission in Crohn's disease patients. It improves the quality of life. Certolizumab pegol will be indicated for moderately to severely active Crohn's disease, but it is not yet licensed in Europe or the US. It is not possible to construct an algorithm for treatment, but when compared with infliximab the two principal advantages are likely to be lower immunogenicity (as shown by anti-drug antibodies, absence of infusion reactions, and low rate of antinuclear antibodies), and a subcutaneous route of administration. These two factors may be sufficient to promote it up the pecking order of anti-TNF agents.

Genetic and environmental factors in monozygotic twins with Crohn's disease and their first-degree relatives: a case report.

BACKGROUND/AIMS: Familial Crohn's disease has shown concordance concerning location and clinical type of the disease especially among monozygotic twins. Susceptibility to Crohn's disease is both based on genetic and environmental factors. We investigated polymorphisms of CARD15, TLR4, and OCTN, and environmental factors in a monozygotic twin pair with Crohn's disease and their first-degree relatives. METHODS: 22-year-old monozygotic female twins with ileocolonic Crohn's disease and their healthy brother and parents were examined. DNA samples from patients and relatives were genotyped for CARD15, TLR4,and OCTN polymorphisms. ASCA and p-ANCA analyses were performed. Additionally, patients and relatives filled out a questionnaire concerning multiple environmental factors. RESULTS: Both twins presented in the same year with identical Vienna Classification phenotypes: stenotic behavior (B2) and localization in terminal ileum and colon (L3). Both carried a CARD15 R702W variant, but had normal alleles in TLR4 and OCTN. They were smokers since the age of 15, used oral contraceptives and had undergone appendectomy. The healthy father and brother were CARD15 R702W positive, were non-smokers and had not undergone appendectomy. CONCLUSION: This case report is the first to describe complete concordance in CARD15 status, phenotypic appearance, and smoking, appendectomy and oral contraceptive use in a pair of monozygotic twins with CD.