The utility of transbronchial lung biopsies to guide the treatment decision in patients with rheumatic inflammatory diseases: a retrospective cross-sectional study.

The role of transbronchial lung biopsies (TBB) in the diagnostic workup of systemic inflammatory rheumatic disease-associated interstitial lung disease (SIRD-ILD) is unclear and TBB is not generally recommended. The study objective was to examine the utility of TBB to guide treatment in a population of patients with SIRD-ILD. All patients from the Department of Rheumatology, Rigshospitalet, Denmark, who had TBB performed, from 2002 to 2016 were identified. Patient demographics as well as smoking status, previous lung disease, pulmonary function test, SIRD-diagnosis, imaging results and immunomodulatory therapy pre- and post-bronchoscopy were obtained. Histology findings were used to dichotomize patients into a high-inflammatory group or a low-inflammatory group. The high-inflammation group primarily consisted of non-specific interstitial pneumonia, organizing pneumonia, lymphocytic infiltrating pneumonia and granulomatous inflammation whereas the low inflammation group primarily consisted of histological findings of usual interstitial pneumonitis and biopsies describing fibrosis and/or sparse unspecific inflammation. Therapeutic consequence was defined as intensification of therapy. Differences in treatment intensification were calculated using a binominal logistic regression model. Ninety-six patients had TBB performed. Biopsies from 55 patients were categorized as high inflammatory and 41 as low inflammatory, respectively. In the high-inflammatory group, 38 (69%) had their therapy intensified compared to 6 (14%) in the low-inflammatory group (Odds ratio 8.0, 95% confidence limits 3.2-20.0, P < 0.001). No procedure-related complications were registered. TBB findings can guide treatment strategy in SIRD-ILD patients with suspected activity in the pulmonary disease. TBB appears safe and could be considered as part of the diagnostic workup.

Delay from symptom onset to treatment start among tuberculosis patients in England, 2012-2015.

Improving access to tuberculosis (TB) care and ensuring early diagnosis are two major aims of the WHO End TB strategy and the Collaborative TB Strategy for England. This study describes risk factors associated with diagnostic delay among TB cases in England. We conducted a retrospective cohort study of TB cases notified to the Enhanced TB Surveillance System in England between 2012 and 2015. Diagnostic delay was defined as more than 4 months between symptom onset and treatment start date. Multivariable logistic regression was used to identify demographic and clinical factors associated with diagnostic delay. Between 2012 and 2015, 22 422 TB cases were notified in England and included in the study. A third (7612) of TB cases had a diagnostic delay of more than 4 months. Being female, aged 45 years and older, residing outside of London and having extra-pulmonary TB disease were significantly associated with a diagnostic delay in the multivariable model (aOR = 1.2, 1.2, 1.2, 1.3, 1.8, respectively). This study identifies demographic and clinical factors associated with diagnostic delay, which will inform targeted interventions to improve access to care and early diagnosis among these groups, with the ultimate aim of helping reduce transmission and improve treatment outcomes for TB cases in England.

Whole-Genome Sequencing Reveals the Contribution of Long-Term Carriers in Staphylococcus aureus Outbreak Investigation.

Whole-genome sequencing (WGS) makes it possible to determine the relatedness of bacterial isolates at a high resolution, thereby helping to characterize outbreaks. However, for Staphylococcus aureus, the accumulation of within-host diversity during carriage might limit the interpretation of sequencing data. In this study, we hypothesized the converse, namely, that within-host diversity can in fact be exploited to reveal the involvement of long-term carriers (LTCs) in outbreaks. We analyzed WGS data from 20 historical outbreaks and applied phylogenetic methods to assess genetic relatedness and to estimate the time to most recent common ancestor (TMRCA). The findings were compared with the routine investigation results and epidemiological evidence. Outbreaks with epidemiological evidence for an LTC source had a mean estimated TMRCA (adjusted for outbreak duration) of 243 days (95% highest posterior density interval [HPD], 143 to 343 days) compared with 55 days (95% HPD, 28 to 81 days) for outbreaks lacking epidemiological evidence for an LTC (P = 0.004). A threshold of 156 days predicted LTC involvement with a sensitivity of 0.875 and a specificity of 1. We also found 6/20 outbreaks included isolates with differing antimicrobial susceptibility profiles; however, these had only modestly increased pairwise diversity (mean 17.5 single nucleotide variants [SNVs] [95% confidence interval {CI}, 17.3 to 17.8]) compared with isolates with identical antibiograms (12.7 SNVs [95% CI, 12.5 to 12.8]) (P < 0.0001). Additionally, for 2 outbreaks, WGS identified 1 or more isolates that were genetically distinct despite having the outbreak pulsed-field gel electrophoresis (PFGE) pulsotype. The duration-adjusted TMRCA allowed the involvement of LTCs in outbreaks to be identified and could be used to decide whether screening for long-term carriage (e.g., in health care workers) is warranted. Requiring identical antibiograms to trigger investigation could miss important contributors to outbreaks.

An explosive outbreak of Streptococcus pneumoniae serotype-8 infection in a highly vaccinated residential care home, England, summer 2012.

In August 2012, an explosive outbreak of severe lower respiratory tract infection (LRTI) due to Streptococcus pneumoniae serotype-8 occurred in a highly vaccinated elderly institutionalized population in England. Fifteen of 23 residents developed LRTI over 4 days (attack rate 65%); 11 had confirmed S. pneumoniae serotype-8 disease, and two died. Following amoxicillin chemoprophylaxis and pneumococcal polysaccharide vaccine (PPV) re-vaccination no further cases occurred in the following 2 months. No association was found between being an outbreak-associated case and age (P = 0.36), underlying comorbidities [relative risk (RR) 0.84 95% confidence interval (CI) 0.34-2.09], or prior receipt of PPV (RR 1.4, 95% CI 0.60-3.33). However, the median number of years since PPV was significantly higher for cases (n = 15, 10.2 years, range 7.3-17.9 years) than non-cases (n = 8, 7.2 years, range 6.8-12.8 years) (P = 0.045), provided evidence of waning immunity. Alternative vaccination strategies should be considered to prevent future S. pneumoniae outbreaks in institutionalized elderly populations.

Estimating vaccine effectiveness against severe influenza in England and Scotland 2011/2012: applying the screening method to data from intensive care surveillance systems.

Methods for estimating vaccine effectiveness (VE) against severe influenza are not well established. We used the screening method to estimate VE against influenza resulting in intensive care unit (ICU) admission in England and Scotland in 2011/2012. We extracted data on confirmed influenza ICU cases from severe influenza surveillance systems, and obtained their 2011/2012 trivalent influenza vaccine (TIV) status from primary care. We compared case vaccine uptake with population vaccine uptake obtained from routine monitoring systems, adjusting for age group, specific risk group, region and week. Of 60 influenza ICU cases reported, vaccination status was available for 56 (93%). Adjusted VE against ICU admission for those aged ≥ 65 years was -10% [95% confidence interval (CI) -207 to 60], consistent with evidence of poor protection from the 2011/2012 TIV in 2011/2012. Adjusted VE for those aged <65 years in risk groups was -296% (95% CI -930 to -52), suggesting significant residual confounding using the screening method in those subject to selective vaccination.

Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction.

AIMS: In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND. METHODS AND RESULTS: We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics pharmacovigilance data, highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in vivo suppression of galectin-3 in the animal model of heart failure prevented SND. CONCLUSION: Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.

Public health management of Salmonella Typhi/Paratyphi case and contact screening: lessons from North London.

OBJECTIVES: To evaluate the public health management Salmonella enterica serovar Typhi (typhoid) and Salmonella enterica serovar Paratyphi (paratyphoid) cases and their contacts to assess the outcome of screening. STUDY DESIGN: Retrospective case note review. METHODS: 329 cases and 1153 contacts from North London over a four year period were reviewed. Structured questionnaires were developed to capture travel history, relationship between case/contact and the number, timing and documented results of faecal specimens. Evaluation of compliance with the clearance/screening schedule was examined and the positive yield of faecal samples for cases and contacts was calculated. RESULTS: 1% (3/329) of cases had a positive clearance sample; all were identified on their first faecal specimen. Of the 645 contacts who were screened, only 10 (1.5%), all of whom had travelled with the index case, were positive. Person-to-person transmission was only identified for two UK acquired cases, where possible carrier sources were identified outside the screening schedule. CONCLUSION: The lack of evidence of secondary transmission from acute cases, coupled with the low positive yield from clearance samples support the revision of the national guidance for the public health management of cases of enteric fever and their contacts.

The early response to a novel coronavirus in the Middle East.

The detection of a novel coronavirus in patients from the Arabian Peninsula in late 2012 raised serious concerns of a possible international outbreak. Ministries of health of the three affected countries invited missions from the World Health Organization to participate in a review of data and capacity to detect and respond to further cases. Recommendations were made for investigations to answer critical questions about human-to-human transmission and the geographic extent of the virus. Additional recommendations were made to improve surveillance capacity by acquiring the capacity to test for the virus and enhance syndromic surveillance. Available evidence continues to suggest an unknown animal reservoir for the virus with sporadic zoonotic transmission the primary epidemiological pattern of transmission. Human-to-human transmission, while it can occur, does not appear to be sustained in the community.

The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Burden of multidrug-resistant tuberculosis in England: a focus on prevalent cases.

The incidence of multidrug-resistant tuberculosis (MDR-TB) is routinely reported by the Public Health England, UK, but prevalence better represents burden. To estimate MDR-TB prevalence, and identify the factors associated with acquired resistance and unsuccessful outcomes in people managed by the health services. We included notified MDR-TB cases prevalent between 2010 and 2014. Multivariable logistic regression was used to identify the factors associated with acquisition of resistance and unsuccessful outcomes. The social risk factors (SRFs) recorded were alcohol, drug misuse, homelessness and incarceration. Between 2010 and 2014, there were 2.3-3.1 times more prevalent than incident cases each year, with an increasing prevalence-to-incidence ratio over time; 86% of prevalent cases were foreign-born, and 15% had an SRF. Overall, 11% of MDR-TB cases acquired resistance, including 18% of those with SRFs and 22% of UK-born MDR-TB cases acquired resistance. Half of the cases completed treatment by 24 months; those with SRFs, extensive drug resistance or acquired resistance were less likely to complete treatment. The number of prevalent cases is higher than incident cases, and increases over time, so a focus on prevalent cases enables better planning for services to support patients. We recommend that additional support be provided for those at risk of acquiring resistance, including those with SRFs. .

Public health outcome of Tuberculosis Cluster Investigations, England 2010-2013.

OBJECTIVES: Tuberculosis (TB) is a serious re-emergent public health problem in the UK. In response to rising case incidence a National TB Strain-Typing Service based on molecular strain-typing was established. This facilitates early detection and investigation of clusters, targeted public health action, and prevention of further transmission. We review the added public health value of investigating molecular TB strain-typed (ST) clusters. METHODS: A structured questionnaire for each ST cluster investigated in England between 1 January 2010 and 30 June 2013 was completed. Questions related to epidemiological links and public health action and the perceived benefits of ST cluster investigation. RESULTS: There were 278 ST cluster investigations (CIs) involving 1882 TB cases. Cluster size ranged from 2 to 92. CIs identified new epidemiological links in 36% of clusters; in 18% STs were discordant refuting transmission thought to have occurred. Additional public health action was taken following 23% of CI. CONCLUSIONS: We found positive benefits of TB molecular ST and CI, in identifying new epidemiological links between cases and taking public health action and in refuting transmission and saving resources. This needs to be translated to a decrease in transmission to provide evidence of public health value in this low prevalence high resource setting.

The challenge of estimating tuberculosis mortality accurately in England and Wales.

BACKGROUND: Accurate estimates of tuberculosis (TB) mortality are required to monitor progress towards the World Health Organization End TB goal of reducing TB deaths by 95% by 2035. We compared TB death data for England and Wales from the national surveillance system (Enhanced Tuberculosis Surveillance System [ETS]) and the vital registration system from the Office for National Statistics (ONS). METHODS: TB cases notified in ETS were matched to deaths in ONS (dONS) with International Classification of Diseases, Tenth Revision (ICD-10) codes indicating that TB caused/contributed to the death (A15-A19). Deaths captured in one but not both systems were assessed to identify if ONS captured all TB deaths and if there was under-notification of TB in ETS. We stratified deaths into active TB, TB sequelae, incidental deaths and not TB. RESULTS: Between 2005 and 2015, there were fewer deaths in ETS (dETS) than dONS with ICD-10 codes A15-A19 (n = 4207 vs. n = 6560); 57% of dETS were recorded as dONS and 53% of dONS were notified to ETS. A total of 9289 deaths were identified from dETS and dONS: 64% were due to active TB, 23% were TB sequelae, 6% were incidental and 7% were not TB. CONCLUSIONS: TB deaths in ETS and ONS differ substantially. Almost one third of TB deaths recorded by ONS are not due to active TB; this can be amended through coding changes.

Investigating a tuberculosis cluster among Filipino health care workers in a low-incidence country.

SETTING: Nearly 8% of adult tuberculosis (TB) cases in England, Wales and Northern Ireland (EW&NI) occur among health care workers (HCWs), the majority of whom are from high TB incidence countries. OBJECTIVES: To determine if a TB cluster containing multiple HCWs was due to nosocomial transmission. METHODS: A cluster of TB cases notified in EW&NI from 2009 to 2014, with indistinguishable 24-locus mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) profiles, was identified through routine national cluster review. Cases were investigated to identify epidemiological links, and occupational health (OH) information was collected for HCW cases. To further discriminate strains, typing of eight additional loci was conducted. RESULTS: Of the 53 cases identified, 22 were HCWs. The majority (n = 43), including 21 HCWs, were born in the Philippines. Additional typing split the cluster into three subclusters and seven unique strains. No epidemiological links were identified beyond one household and a common residential area. HCWs in this cluster received no or inadequate OH assessment. CONCLUSIONS: The MIRU-VNTR profile of this cluster probably reflects common endemic strains circulating in the Philippines, with reactivation occurring in the UK. Furthermore, 32-locus typing showed that 24-locus MIRU-VNTR failed to distinguish strain diversity. The lack of OH assessment indicates that latent tuberculous infection could have been identified and treated, thereby preventing active cases from occurring.

Retrospective evaluation of equine prepurchase examinations performed 1991-2000.

REASONS FOR PERFORMING STUDY: Prepurchase examinations of horses are used increasingly as a means of evaluating future soundness. Data is lacking in the literature of the radiographic findings and results of the lameness examination of comprehensive prepurchase examinations. OBJECTIVE: To summarise the clinical and radiographic findings of prepurchase examinations and determine if radiographic findings correlated with the lameness examination and sale outcome. METHODS: Records of 510 cases were reviewed, radiographs evaluated and grades assigned the navicular bone, distal phalanx, and tarsus. Follow-up information on the horse status was obtained by telephone interviews for 173 horses. RESULTS: Thoroughbred geldings represented the most common breed and sex, mean age 8 years, mean asking price 12,439.40 dollars, and 52.8% were lame. Radiography was the most common diagnostic procedure performed (61.6%), with views of the front feet requested most often (86.6%) followed by the tarsi (68.1%). Grade 1 was most common for the navicular bone while Grade 2 predominated for the distal phalanx. The number of sound horses decreased as grades became more severe. For the tarsi, Grades 0 and 1 were most common for the proximal intertarsal and distal intertarsal/metatarsal joints, respectively. Horses with significant tarsal changes were still able to compete at their expected level. With respect to the radiographic examination, the mean +/- s.d. grade of the horses which were not lame at follow-up was 1.2 +/- 0.9 for the navicular bone and 15 +/- 0.8 for the third phalanx. The mean +/- s.d. grade of sound horses for the distal intertarsal joint was 0.7 +/- 0.6 and 1.14 +/- 0.8 for the tarsometatarsal joint. Horses for which owner follow-up was available and which had a Grade 3 score were also evaluated. For the navicular bone, 17/31 with a Grade 3 remained in active use at follow-up and for the distal phalanx 21/27 were in active use. For the distal intertarsal and tarsometatarsal joints, 20/21 with a Grade 3 were still in active use. CONCLUSIONS: Prepurchase examinations can have a significant effect on the outcome of the sale. For the navicular bone and distal phalanx, higher grades were associated with lameness. In contrast, higher grades in the tarsus were less likely to be associated with lameness. Warmbloods tended to have more extensive changes in the navicular bone and distal phalanx relative to Thoroughbreds but were not as lame. POTENTIAL RELEVANCE: Radiographic changes detected in the navicular bone, distal phalanx and tarsus should be interpreted with consideration to the clinical examination.

Recent advances in absorbent products for the incontinent patient with burns.

The purpose of this study is to describe the physical configuration of disposable and reusable absorbent products and relate composition and construction to efficacy in the management of urinary incontinence in patients with burn injuries. The basic structure of a wearable absorbent product consists of three layers: a fluid-impermeable backing sheet, a fluid-pervious coverstock on the body-contacting surface, and an interposed absorbent core. The biomechanical performance of these absorbent products was determined by measuring the total absorbent capacity, defined as the maximum amount of liquid held by the product as a whole. On the basis of the results of this study, absorbent products are recommended for the incontinent patient with burns.

Innovations in the design and performance of underpads for patients with burns.

The purpose of this study was to determine the biomechanical performance of commercially available underpads and bed linens to reduce the development of pressure sores in patients with burns who are at high risk. The three biomechanical performance parameters examined were coefficient of friction, absorbent capacity, and rewet. Because wetting either cotton or cotton/polyester bedsheets markedly increases their coefficients of friction, underpads should be used routinely to protect the skin against frictional forces. One disposable underpad is ideally suited to protect the skin of the patient at high risk. It has a polyolefin backing with a low coefficient of friction that serves as an effective barrier to moisture transmission while still shifting easily with the patient's movement. In addition, it is the only underpad studied that contains a superabsorbent polymer that provides a far superior absorbent capacity and minimizes rewet. Wet-back is further inhibited by its thick intermediate tissue layer and its spunbonded polypropylene coverstock.

Radiation exposure to personnel during examination of limbs of horses with a portable hand-held fluoroscopic unit.

OBJECTIVES: To determine radiation exposure to personnel during fluoroscopic imaging of limbs of horses with a portable unit and to determine distance from the c-arm at which radioprotective clothing is not required. DESIGN: Repeated-measures cohort study. SAMPLE POPULATION: Part 1, 1 forelimb and 1 hind limb from each of 5 equine cadavers; parts 2 and 3, personnel involved during imaging of limbs of 5 and 9 horses, respectively. PROCEDURE: Radiation exposure rates were mapped around the suspended c-arm of a portable fluoroscopy unit during imaging of various joints of equine cadaver limbs. During similar examinations in live horses, exposure rates to the fluoroscopist and assistant were measured. Mean duration for fluoroscopy of various joints was determined by observing an experienced fluoroscopist. Exposure to fluoroscopists and assistants per examination and per annum was estimated. RESULTS: Radiation exposure rates were dependent on distance and direction relative to the c-arm and consistently highest on the tube side of the unit. Exposure was significantly greater than background amounts until approximately 4.7 m from the c-arm. During examination of live horses, exposure was highest to the fluoroscopist's hand nearest the tube. Typically, exposure to the fluoroscopist and assistant during carpal examination was 25 to 40 times greater than that for comparable radiographic examination. Annual exposure for fluoroscopists was more than twice the recommended maximum permissible dose. CONCLUSIONS AND CLINICAL RELEVANCE: Fluoroscopic imaging of limbs of horses represents a major source of radiation exposure. Annual maximum permissible doses of radiation will be rapidly exceeded if required radioprotective clothing is not worn.

Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse.

A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during surgical treatment of guttural pouch mycosis. The horse became anemic and a diagnosis of immune-mediated hemolytic anemia was made after other causes of anemia had been ruled out. The anemia resolved after the drugs were withdrawn.

Multiple aneurysmal bone cysts in a foal.

Multiple aneurysmal bone cysts (ABCs) are previously unreported in horses. An ABC was diagnosed in the left 3rd metacarpal of a Thoroughbred foal, which partially resolved following surgical curettage. A 2nd ABC developed in the left tibia, 7 wk postoperatively, and the foal was euthanized.

Postcastration eventration in 18 horses: the prognostic indicators for long-term survival (1985-1995).

Castration of horses is considered a common and routine surgical procedure, but the potential for complications is high. By far the most serious of these is eventration. The objectives of this study were to determine the long-term survival of horses undergoing surgical treatment of indirect (1) inguinal eventration of the small intestine following castration, and to identify prognostic indicators for survival. The case records of 18 horses undergoing surgical treatment of postcastration eventration (PCE) between 1985 and 1995 were reviewed. Follow-up information was obtained by telephone interviews 2 to 13 y postoperatively. A Cox proportional hazard regression model was fitted to determine which clinical features were of significant influence to survival. Clinical features with a significant negative influence on survival were an inguinal surgical approach for correction, an increased length of prolapsed bowel, and performance of bowel resection and anastomosis. Significant postoperative complications developed in 89% of cases; 44% of cases in the "inguinal" surgical approach group developed peritonitis, compared with 10% in the "midline" approach group. Of all horses in this study, 72% were discharged from the hospital; however, only 40% of horses in the inguinal approach group were discharged. The long term survival rate (> 1 y) for all horses in this study was 44%, with a median survival time of 3-1/2 mo.