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Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

Biologically precise enhancer licensing by lineage-determining transcription factors enables activation of transcripts appropriate to biological demand and prevents deleterious gene activation. This essential process is challenged by the millions of matches to most transcription factor binding motifs present in many eukaryotic genomes, leading to questions about how transcription factors achieve the exquisite specificity required. The importance of chromatin remodeling factors to enhancer activation is highlighted by their frequent mutation in developmental disorders and in cancer. Here we determine the roles of CHD4 to enhancer licensing and maintenance in breast cancer cells and during cellular reprogramming. In unchallenged basal breast cancer cells, CHD4 modulates chromatin accessibility at transcription factor binding sites; its depletion leads to altered motif scanning and redistribution of transcription factors to sites not previously occupied. During GATA3-mediated cellular reprogramming, CHD4 activity is necessary to prevent inappropriate chromatin opening and enhancer licensing. Mechanistically, CHD4 competes with transcription factor-DNA interaction by promoting nucleosome positioning over binding motifs. We propose that CHD4 acts as a chromatin proof-reading enzyme that prevents inappropriate gene expression by editing binding site selection by transcription factors.

Background Tackling antimicrobial resistance by reducing unnecessary or inappropriate prescribing is a key priority. Objectives To review current clinical practice at Guy's and St Thomas’ Hospital around duration of IV antimicrobial therapy framed with Start Smart Then Focus national guidelines. Methods Newly started inpatient prescriptions for IV antimicrobials over three consecutive Mondays were reviewed. Prescriptions not for treatment of acute infections were excluded, as were patients admitted to critical care, obstetrics/gynaecology and paediatric wards. Each patient's record was reviewed at Day 0, 3 and 5. Data were analysed using IBM® SPSS Statistics version 27. Results In total, 80 patients with 89 antibiotic prescriptions (71 = β-lactam, 5 = aminoglycoside, 2 = glycopeptide, 1 = ciprofloxacin, 9 = metronidazole, 1 = linezolid) were included. Median age was 66 (IQR 53–75). Documented indications were for suspected or proven infection of urinary tract (15%), respiratory tract (25%), skin/soft tissue (14%), sepsis (1.25%), intra-abdominal (15%), bacteraemia (7.5%), bone and joint infections (2.5%) or other (20%). Median initial NEWS2 on Day 0 was 3 (IQR 1–4), WCC 11.45 (IQR 8.27–14.15) and CRP 121 (IQR 47–208). Median length of stay was 7.5 days. Median duration of IV antimicrobial was 4 (IQR 2–6) days. By D3, 3 patients had died and 16 had been discharged. Of 61 remaining inpatients on D3, 4 had their antimicrobials switched, 14 had been switched to PO antimicrobials, 43 were continued on IV antibiotics. By D5, 17 further patients had been discharged, 44 remained inpatients. Twenty-two had stopped antimicrobials with 22 continuing IV therapy. A number of patients could have been switched from IV to oral therapy by current guidance but were not (D3 x = 11, D5 n = 8). Higher median D0 CRP was seen in those who continued on IV therapy on D3 (139 versus 79 mg/dL) as was higher D3 WCC (13.9 versus 11.9 × 109/L). There was no significant relationship between a NEWS2 score ≥3 and IV to PO switch at D3 or D5. Thirty-two patients had input from the Infection team within 7 days of first prescription. Fifteen patients (21%) received IV antibiotics for more than 7 days, and 14/15 had Infection team input. Three patients were discharged with OPAT. Conclusions Median duration of IV therapy for suspected/proven infections in our centre is less than 5 days and only 28% of patients were still receiving IV antibiotics by D5. A number of missed opportunities for earlier switch to oral therapy were identified. The potential for earlier safe discontinuation of IV therapy using patient-specific measures should be explored. A minority of patients received IV therapy for >7 days, and this was almost universally associated with specialist Infection involvement in complex infections with a view to optimizing patient management and antimicrobial stewardship.

Objectives Despite the widespread use of vancomycin, optimization of dosing can be difficult. Increased vancomycin concentrations are associated with nephrotoxicity, while subtherapeutic levels may lead to inadequate antibacterial therapy and risk development of antimicrobial resistance. Recent guidelines have recommended the use of loading doses and switching to AUC24 TDM, targeting an AUC24:MIC ratio of 400–600 μg·h/mL to minimize toxicity while maintaining similar effectiveness for the treatment of serious infections. We aimed to review adherence to current local vancomycin dosing and conventional trough monitoring guidelines, as well as record time to, and factors related to, achieving target vancomycin troughs. Methods Fifty consecutive electronic prescriptions were screened for IV vancomycin use in treatment of active infections in a single acute Trust during April/May 2021. These were cross-referenced with microbiological, clinical and biochemical data from patient records. Variables were analysed by parametric or non-parametric methods on the basis of their normality distribution using GraphPad Prism. Results Forty-one patients were included of which 39 had a vancomycin level measured. Mean age was 57 years (range 19–88) and BMI 28 (range 17–44). Nineteen had unstable renal function, including one receiving intermittent haemodialysis. Median CLCR was 95 mL/min (IQR 66–129). Indications were included on the prescription for 26. Median duration of vancomycin was 4 days (range 2–12), and half of patients ultimately switched therapy to an alternate agent . Target troughs were documented in 29 (70%), 9 of which had a target trough ≥15 μg/mL. Twenty-four had positive microbiology samples, 19 of which were organisms against which vancomycin would have expected activity. Five (13%) failed to achieve trough levels >10, 6/39 (15%) achieved troughs of 10–15, 13/39 (33%) 15–20, and 15/39 (38%) had troughs of >20 μg/mL (Figure 1). Where it was achieved, the median time to level ≥10 μg/mL was 46 h (range 11–202) and time to level ≥15 μg/mL was 68 h (range 18–243). Twenty-five (60%) patients required titration above the currently recommended initial dose, and 22 required doses of 1500 mg twice daily or higher. BMI did not correlate with vancomycin level achieved. Conclusions A significant proportion of patients with serious infections fail to achieve or have a considerable delay in achieving therapeutic vancomycin trough. An even greater proportion have troughs above target and are at risk of nephrotoxicity. These findings support a potential switch to more personalized regimens using loading doses and AUC24 monitoring where vancomycin is the drug of choice. This would complement other stewardship measures to limit overall vancomycin use, achieve earlier and more complete source control, and optimize use of alternative antimicrobial therapies with more predictable PK/PD.

Epigenetics is the study of gene expression that does not entail alterations to the actual DNA. Decolonization is a theoretical and political movement that seeks to deconstruct colonial institutions and ideologies and reconstruct new and balanced approaches that accept and respect Indigenous worldviews. This project studies the decolonizing potential of epigenetics. Using genealogy as the method, the study establishes a long history of reductionist and deterministic thought that shaped the study of genetic science. Particular instances like thrift gene theory are explored to highlight how genetic explanations have been detrimental to the health and wellbeing of Indigenous people and illustrate the need for decolonization. The conclusion encourages the use of epigenetics as a decolonizing science that can be applied to Indigenous community-based research projects.

Background Being labelled as “allergic” to an antimicrobial (commonly penicillins) can lead to worse clinical outcomes and increase antimicrobial resistance. Unclear or inappropriate allergy documentation contributes to this issue so clarifying “allergy” status is important to optimise clinical outcomes. Methods The study was conducted at St Thomas’ Hospital, a large teaching hospital in London. An antimicrobial allergy assessment process, consisting of a researcher-developed and administered questionnaire, a review of patient medical records and categorisation of the drug allergy ‘label’, was applied to eligible patients from selected wards. Recommendations for allergy ‘de-labelling’ and referrals were given based on patient categorisation. Results Sixty assessments were completed during the study. Six patients (10%) were identified as unlikely to have a true allergy and could potentially be ‘de-labelled’. A further thirty-seven patients (61.7%) were identified as eligible for allergy referral and testing. The allergy ‘labels’ of twenty-seven patients (45%) led to them receiving second-line antibiotic therapy. Twenty-two patients (34.7%) had inconsistencies in their allergy documentation across the 3 main electronic clinical systems. Conclusion This study demonstrated that the use of a simple, standardized, pharmacy-led approach to antimicrobial allergy assessment could lead to some patients being 'de-labelled' outside of specialist allergy settings. The implementation of this approach could immediately bring about improvements in antimicrobial usage and patient outcome.

Recent exploration into the interactions and relationship between hosts and their microbiota has revealed a connection between many aspects of the host’s biology, health and associated microorganisms. Whereas amplicon sequencing has traditionally been used to characterise the microbiome, the increasing number of published population genomics datasets offer an underexploited opportunity to study microbial profiles from the host shotgun sequencing data. Here, we use sequence data originally generated from killer whale Orcinus orca skin biopsies for population genomics, to characterise the skin microbiome and investigate how host social and geographic factors influence the microbial community composition. Having identified 845 microbial taxa from 2.4 million reads that did not map to the killer whale reference genome, we found that both ecotypic and geographic factors influence community composition of killer whale skin microbiomes. Furthermore, we uncovered key taxa that drive the microbiome community composition and showed that they are embedded in unique networks, one of which is tentatively linked to diatom presence and poor skin condition. Community composition differed between Antarctic killer whales with and without diatom coverage, suggesting that the previously reported episodic migrations of Antarctic killer whales to warmer waters associated with skin turnover may control the effects of potentially pathogenic bacteria such as Tenacibaculum dicentrarchi. Our work demonstrates the feasibility of microbiome studies from host shotgun sequencing data and highlights the importance of metagenomics in understanding the relationship between host and microbial ecology.

Background Strongyloides stercoralis infection presents with varying degrees of severity, but it often primarily involves the small bowel. In severe infection and cases of hyperinfection, ileus and small-bowel obstruction may prevent enteral absorption of anthelminthics such as ivermectin. At present there are no parenteral anthelminthics licensed for use in humans. Methods Here, we describe two cases of severe S. stercoralis infection treated with an unlicensed veterinary preparation of subcutaneous ivermectin, and we discuss the published reports of the use of this treatment elsewhere. Results Both patients were successfully treated with subcutaneous ivermectin, and both recovered completely. Conclusions Despite the limited published experience of parenteral ivermectin use, there is evidence that it may be a safe and effective treatment for severe strongyloidiasis. However, more data are needed to guide dosing schedules and monitoring for toxicity.

Summary Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) ( P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile.

Background Medication incidents (MIs) account for 11.3 % of all reported patient-safety incidents in England and Wales. Approximately one-third of inpatients are prescribed an antibiotic at some point during their hospital stay. The WHO has identified incident reporting as one solution to reduce the recurrence of adverse incidents. Objectives The aim of this study was to determine the number and nature of reported antibiotic-associated MIs occurring in inpatients and to use defined daily doses (DDDs) to calculate the incident rate for the antibiotics most commonly associated with MIs at each hospital. Setting Two UK acute NHS teaching hospitals. Methods Retrospective quantitative analysis was performed on antibiotic-associated MIs reported to the risk management system over a 2-year period. Quality-assurance measures were undertaken before analysis. The study was approved by the clinical audit departments at both hospitals. Drug consumption data from each hospital were used to calculate the DDD for each antibiotic. Main outcome measures The number of antibiotic-related MIs reported and the incident rate for the 10 antibiotics most commonly associated with MIs at each hospital. Results Healthcare staff submitted 6,756 reports, of which 885 (13.1 %) included antibiotics. This resulted in a total of 959 MIs. Most MIs occurred during prescribing (42.4 %, n = 407) and administration (40.0 %, n = 384) stages. Most common types of MIs were omission/delay (26.3 %, n = 252), and dose/frequency (17.9 %, n = 172). Penicillins (34.5 %, n = 331) and aminoglycosides (16.6 %, n = 159) were the most frequently reported groups with co-amoxiclav (16.8 %, n = 161) and gentamicin (14.1 %, n = 135) the most frequently reported drugs. Using DDDs to assess the incident rate showed that cefotaxime (105.4/10,000 DDDs), gentamicin (25.7/10,000 DDDs) and vancomycin (23.7/10,000 DDDs) had the highest rates. Conclusions This study highlights that detailed analysis of data from reports is essential in understanding MIs and developing strategies to prevent their recurrence. Using DDDs in the analysis of MIs allowed determination of an incident rate providing more useful information than the absolute numbers alone. It also highlighted the disproportionate risk associated with less commonly prescribed antibiotics not identified using MI reporting rates alone.

Objectives: To evaluate the impact of an 'intervention' consisting of revised antibiotic guidelines for empirical treatment of common infections and enhanced stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection (CDI). Methods: This was a retrospective, quasi-experimental study using interrupted time series (ITS) over 12 months before and after the intervention. The setting was adult medical and surgical wards in University Hospital Lewisham, an acute general hospital in London. The intervention was introduced in April 2006. Revised guidelines avoided broad-spectrum antibiotics, e.g. fluoroquinolones, cephalosporins, clindamycin, amoxicillin and co-amoxiclav, as they were considered to be 'high risk' for CDI. Instead, 'low risk' antibiotics such as penicillin, clarithromycin, doxycycline, gentamicin, vancomycin, trimethoprim and nitrofurantoin were recommended. Changes in antibiotic usage and incidence of CDI before and after the intervention were compared using segmented regression analysis. The negative binomial model was used to analyse the time series to estimate the CDI incidence rate ratio (IRR) following the intervention. Results: The intervention was associated with a significant reduction in the use of fluoroquinolones by 105.33 defined daily doses (DDDs)/1000 occupied bed-days (OBDs) per month [95% confidence interval (CI) 34.18-176.48, P

The interaction between ecology, culture and genome evolution remains poorly understood. Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and postzygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step toward an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.

To assess the impact of an infection team review of patients receiving antibiotics in six hospitals across the UK and to establish the suitability of these patients for continued care in the community.An evaluation audit tool was used to assess all patients on antibiotic treatment on acute wards on a given day. Clinical and antibiotic use data were collected by an infection team (doctor, nurse and antibiotic pharmacist). Assessments were made of the requirement for continuing antibiotic treatment, route and duration [including intravenous (iv)/oral switch] and of the suitability of the patients for discharge from hospital and their requirement for community support.Of 1356 patients reviewed, 429 (32%) were on systemic antibiotics, comprising 165 (38%) on iv ± oral antibiotics and 264 (62%) on oral antibiotics alone. Ninety-nine (23%) patients (including 26 on iv antibiotics) had their antibiotics stopped immediately on clinical grounds. The other 330 (77%) patients (including 139 on iv antibiotics) needed to continue antibiotics, although 47 (34%) could be switched to oral. Eighty-nine (21%) patients were considered eligible for discharge, comprising 10 who would have required outpatient parenteral antibiotic therapy (OPAT), 55 who were suitable for oral outpatient treatment and 24 who had their antibiotics stopped.Infection team review had a significant impact on antimicrobial use, facilitating iv to oral switch and a reduction in the volume of antibiotic use, possibly reducing the risk of healthcare-associated complications and infections. It identified many patients who could potentially have been managed in the community with appropriate resources, saving 481 bed-days. The health economics are reported in a companion paper.

To describe the methodology in developing an antimicrobial self-assessment toolkit (ASAT).The ASAT was developed through a National Pharmacy Reference Group using an evidence-based approach of published information and national reports to identify criteria for inclusion. These were subdivided into domains that addressed: 1) Antimicrobial management within the Trust-structures and lines of responsibility and accountability-high-level notification to the Board. 2) Operational delivery of an antimicrobial strategy-operational standards of good antimicrobial stewardship. 3) Risk assessment for antimicrobial chemotherapy. 4) Clinical governance assurance. 5) Education and training-training needs and delivery of education and training for all who issue, prescribe and administer antimicrobials. 6) Antimicrobial pharmacist-systems in place for ensuring their optimum use. 7) Patients, Carers and the Public-information needs of patients, carers and the public.A web-based toolkit was developed using information from national reports and guidance on antimicrobial stewardship. The toolkit offers a checklist for hospitals to self-assess their organizations' levels of antimicrobial stewardship.The ASAT offers a web-enabled, version-controlled instrument for the assessment of antimicrobial stewardship in acute hospitals. It may offer a sensitive instrument to assess longitudinal progress on antimicrobial stewardship in an individual institution or act as a benchmark with similar organizations. Further work is ongoing to evaluate and further refine the ASAT.

Study objectives: To determine the magnitude of infection rate and antimicrobial resistance in a pediatric ICU (PICU), and to evaluate the efficacy of using broad-spectrum antibiotics. Design: A 3-month, prospective, observational cohort audit. Setting: A 12-bed tertiary, referral PICU. Patients or participants: All children admitted to the PICU for > 72 h. Interventions: Surveillance cultures of throat and rectum on admission and once weekly thereafter. Measurements and results: Of the 150 admissions during the 3-month period, a total of 52 patients (24 girls and 28 boys) requiring mechanical ventilation for a minimum of 3 days were enrolled in the audit. The median age and interquartile range (IQR) was 17 months (IQR, 5.8 to 63); length of stay, 6.5 days (IQR, 4 to 13); ventilation days, 5 (IQR, 3 to 11); pediatric risk of mortality score, 14 (IQR, 9 to 19); and risk of mortality, 0.03 (IQR, 0.014 to 0.087). Fifteen patients (29%) developed 21 infections, mainly lower-airway infections and septicemias. Of the 52 children, 7 children carried multidrug-resistant bacteria and 3 patients progressed to develop four infections with those resistant bacteria. Of the seven carriers, six patients carried gentamicin-resistant Klebsiella. Methicillinresistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae and gentamicinresistant Pseudomonas aeruginosa each were carried by one child. Six of those nine resistant isolates were present in the admission flora. Despite the potent combination of piperacillin/tazobactam and amikacin, three children acquired the multidrug-resistant Klebsiella while in the PICU and became nosocomial carriers. Conclusions: Only surveillance cultures allow the distinction between import of multidrug-resistance and resistant bacteria acquired while in PICU. In this study, two thirds of the resistant isolates were imported. The introduction of newer potent systemic antibiotic combinations failed to control the endemic reservoir of multidrug-resistant Klebsiella and suggests that such policies have little impact. (CHEST 2001; 119:862‐866)

A 29-year-old lady presented with an increasingly swollen tongue 3 days after commencing oseltamivir (Tamiflu) for flu-like symptoms. Once identified as the cause, her symptoms rapidly improved with antihistamines and discontinuing the Tamiflu. The authors find only one other case in the literature reporting this very rare side effect.

Hospital outbreaks of group A streptococcal (GAS) infection can be devastating and occasionally result in the death of previously well patients. Approximately one in ten cases of severe GAS infection is healthcare-associated. This guidance, produced by a multidisciplinary working group, provides an evidence-based systematic approach to the investigation of single cases or outbreaks of healthcare-associated GAS infection in acute care or maternity settings. The guideline recommends that all cases of GAS infection potentially acquired in hospital or through contact with healthcare or maternity services should be investigated. Healthcare workers, the environment, and other patients are possible sources of transmission. Screening of epidemiologically linked healthcare workers should be considered for healthcare-associated cases of GAS infection where no alternative source is readily identified. Communal facilities, such as baths, bidets and showers, should be cleaned and decontaminated between all patients especially on delivery suites, post-natal wards and other high risk areas. Continuous surveillance is required to identify outbreaks which arise over long periods of time. GAS isolates from in-patients, peri-partum patients, neonates, and post-operative wounds should be saved for six months to facilitate outbreak investigation. These guidelines do not cover diagnosis and treatment of GAS infection which should be discussed with an infection specialist.

We use mitochondrial DNA (mtDNA) (400 bp), six microsatellites and 36 single-nucleotide polymorphisms (SNPs), 20 of which were linked, to investigate population structure of sperm whales (Physeter macrocephalus) in the eastern and central North Pacific. SNP markers, reproducible across technologies and laboratories, are ideal for long-term studies of globally distributed species such as sperm whales, a species of conservation concern because of both historical and contemporary impacts. We estimate genetic differentiation among three strata in the temperate to tropical waters where females are found: California Current, Hawai`i and the eastern tropical Pacific. We then consider how males on sub-Arctic foraging grounds assign to these strata. The California Current stratum was differentiated from both the other strata (P0.05) for mtDNA, microsatellites and SNPs, suggesting that the region supports a demographically independent population and providing the first indication that males may exhibit reproductive philopatry. Comparisons between the Hawai`i stratum and the eastern tropical Pacific stratum are not conclusive at this time. Comparisons with Alaska males were statistically significant, or nearly so, from all three strata and individuals showed mixed assignment to, and few exclusions from, the three potential source strata, suggesting widespread origin of males on sub-Arctic feeding grounds. We show that SNPs have sufficient power to detect population structure even when genetic differentiation is low. There is a need for better analytical methods for SNPs, especially when linked SNPs are used, but SNPs appear to be a valuable marker for long-term studies of globally dispersed and highly mobile species.

Summary Toxin enzyme immunoassays (EIAs) are inadequate for the diagnosis of Clostridium difficile infection (CDI) when used alone. In September 2010 we replaced toxin EIA with a two-step algorithm, testing first with glutamate dehydrogenase and confirming with polymerase chain reaction for toxin B gene. We compared this to the gold standard of toxigenic culture, observing a positive predictive value of 96% (laboratory prevalence of 4.7%). There was no deterioration in turnaround time but there was a decrease of 11% in repeat specimens sent from the same patients. The improved performance of the algorithm increased the laboratory positivity rate from 2.2% to 5.6%. This led to an increase in our Trust CDI rate reported under the Health Protection Agency's mandatory surveillance scheme. We investigated whether the change was due to increasing nosocomial transmission, environmental contamination or consumption of antimicrobials, but found no evidence of this. We conclude that it probably resulted from the change in testing algorithm. Although we have improved testing and enhanced patient safety, we are likely to be unfairly financially penalised because of our apparent (but not real) increase in CDI rates. Assessment of CDI rates should take testing methodology into account and national policies should be revised to reflect this.

Objectives: Gentamicin and vancomycin are narrowtherapeutic-index antibiotics with potential for high toxicity requiring dose individualisation and continuous monitoring. Clinical decision support (CDS) tools have been effective in reducing gentamicin and vancomycin dosing errors. Online dose calculators for these drugs were implemented in a London National Health Service hospital. This study aimed to evaluate the impact of these calculators on the accuracy of gentamicin and vancomycin initial doses. Methods: The study used a pre–postintervention design. Data were collected using electronic patient records and paper notes. Random samples of gentamicin and vancomycin initial doses administered during the 8 months before implementation of the calculators were assessed retrospectively against hospital guidelines. Following implementation of the calculators, doses were assessed prospectively. Any gentamicin dose not within ±10% and any vancomycin dose not within ±20% of the guideline-recommended dose were considered incorrect. Results: The intranet calculator pages were visited 721 times (gentamicin=333; vancomycin=388) during the 2-month period following the calculators’ implementation. Gentamicin dose errors fell from 61.5% (120/195) to 44.2% (95/215), p

The apical junctional complex (AJC) is important in regulating epithelial intercellular adhesion. Disruption of the AJC with the loss of concomitant junctional protein expression is a hallmark of c...