Xenomake: A pipeline for processing and sorting xenograft reads from spatial transcriptomic experiments.

Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provide a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism specific reads, reduce sparsity of data by increasing gene counts, while maintaining biological relevance for studies. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease.

This evidence-based clinical practice guideline for the prevention, diagnosis, and treatment of Lyme disease was developed by a multidisciplinary panel representing the Infectious Diseases Society of America (IDSA), the American Academy of Neurology (AAN), and the American College of Rheumatology (ACR). The scope of this guideline includes prevention of Lyme disease, and the diagnosis and treatment of Lyme disease presenting as erythema migrans, Lyme disease complicated by neurologic, cardiac, and rheumatologic manifestations, Eurasian manifestations of Lyme disease, and Lyme disease complicated by coinfection with other tick-borne pathogens. This guideline does not include comprehensive recommendations for babesiosis and tick-borne rickettsial infections, which are published in separate guidelines. The target audience for this guideline includes primary care physicians and specialists caring for this condition such as infectious diseases specialists, emergency physicians, internists, pediatricians, family physicians, neurologists, rheumatologists, cardiologists and dermatologists in North America.

Frailty Hinders Recovery From Influenza and Acute Respiratory Illness in Older Adults.

BACKGROUND: We examined frailty as a predictor of recovery in older adults hospitalized with influenza and acute respiratory illness. METHODS: A total of 5011 patients aged ≥65 years were admitted to Canadian Serious Outcomes Surveillance Network hospitals during the 2011/2012, 2012/2013, and 2013/2014 influenza seasons. Frailty was measured using a previously validated frailty index (FI). Poor recovery was defined as death by 30 days postdischarge or an increase of more than 0.06 (≥2 persistent new health deficits) on the FI. Multivariable logistic regression controlled for age, sex, season, influenza diagnosis, and influenza vaccination status. RESULTS: Mean age was 79.4 (standard deviation = 8.4) years; 53.1% were women. At baseline, 15.0% (n = 750) were nonfrail, 39.3% (n = 1971) were prefrail, 39.8% (n = 1995) were frail, and 5.9% (n = 295) were most frail. Poor recovery was experienced by 21.4%, 52.0% of whom had died. Frailty was associated with lower odds of recovery in all 3 seasons: 2011/2012 (odds ratio [OR] = 0.70; 95% confidence interval [CI], 0.59-0.84), 2012/2013 (OR = 0.72; 95% CI, 0.66-0.79), and 2013/2014 (OR = 0.75; 95% CI, 0.69-0.82); results varied by season, influenza status, vaccination status, and age. CONCLUSIONS: Increasing frailty is associated with lower odds of recovery, and persistent worsening frailty is an important adverse outcome of acute illness.

Committee Opinion No. 399: Management of Tick Bites and Lyme Disease During Pregnancy.

OBJECTIVE: Lyme disease is an emerging infection in Canada caused by the bacterium belonging to the Borrelia burgdorferi sensu lato species complex, which is transmitted via the bite of an infected blacklegged tick. Populations of blacklegged ticks continue to expand and are now established in different regions in Canada. It usually takes more than 24 hours of tick attachment to transfer B. burgdorferi to a human. The diagnosis of early localized Lyme disease is made by clinical assessment, as laboratory tests are not reliable at this stage. Most patients with early localized Lyme disease will present with a skin lesion (i.e., erythema migrans) expanding from the tick bite site and/or non-specific "influenza-like" symptoms (e.g., arthralgia, myalgia, and fever). Signs and symptoms may occur from between 3 and 30 days following the tick bite. The care of pregnant patients with a tick bite or suspected Lyme disease should be managed similarly to non-pregnant adults, including the consideration of antibiotics for prophylaxis and treatment. The primary objective of this committee opinion is to inform practitioners about Lyme disease and provide an approach to managing the care of pregnant women who may have been infected via a blacklegged tick bite. INTENDED USERS: Health care providers who care for pregnant women or women of reproductive age. TARGET POPULATION: Women of reproductive age. EVIDENCE: In November 2018, Medline, EMBASE, PubMed, and CENTRAL databases were searched for 2 main categories: (1) Lyme disease and (2) other tick-borne diseases. Because the main focus was Lyme disease, and considering the limited number of the articles, no further filters were applied for publication time or type of study. For other tick-borne diseases, the results were restricted to a publication date within the last 10 years (2008-2018). The search terms were developed using MeSH terms and keywords including Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, and Southern Tick-Associated Rash Illness. All articles on Lyme disease and other tick-borne diseases with a target population of pregnant women were included; other groups and populations were excluded. VALIDATION METHODS: The content and recommendations of this committee opinion were drafted and agreed upon by the authors. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication.

The Importance of Frailty in the Assessment of Influenza Vaccine Effectiveness Against Influenza-Related Hospitalization in Elderly People.

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased. Clinical Trials Registration: NCT01517191.

Influenza vaccine effectiveness against influenza-related hospitalization during a season with mixed outbreaks of four influenza viruses: a test-negative case-control study in adults in Canada.

BACKGROUND: The Serious Outcomes Surveillance (SOS) Network was established to monitor seasonal influenza complications among hospitalized Canadian adults and to assess the effectiveness of influenza vaccination against severe outcomes. Here we report age- and strain-specific vaccine effectiveness (VE) in preventing severe outcomes during a season characterized by mixed outbreaks of four different influenza strains. METHODS: This prospective, multicentre, test-negative case-control study evaluated the VE of trivalent influenza vaccine (TIV) in the prevention of laboratory-confirmed influenza-hospitalization in adults aged ≥16 years (all adults) and adults aged 16-64 years (younger adults). The SOS Network identified hospitalized patients with diagnoses potentially attributable to influenza during the 2011/12 influenza season. Swabs collected at admission were tested by reverse transcriptase polymerase chain reaction (RT PCR) or viral culture to discriminate influenza cases (positive) from controls (negative). VE was calculated as 1-odds ratio (OR) of vaccination in cases versus controls × 100. RESULTS: Overall, in all adults, the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 41.8% (95% Confidence Interval [CI]: 26.0, 54.3), and 42.8% (95% CI: 23.8, 57.0), respectively. In younger adults (16-64 years), the unadjusted and adjusted VEs of TIV against influenza-hospitalization were 35.8% (95% CI: 4.5, 56.8) and 33.2% (95% CI: -6.7, 58.2), respectively. In the all adults group, adjusted VE against influenza A/H1N1 was 72.5% (95% CI: 30.5, 89.1), against A/H3N2 was 86.1% (95% CI: 40.1, 96.8), against B/Victoria was 40.5% (95% CI: -28.9, 72.6), and against B/Yamagata was 32.3% (95% CI: -8.3, 57.7). The adjusted estimate of early season VE (from November 1 to March 11) was 54.4% (95% CI: 29.7-70.4), which was higher than late season (from March 11 to May 25) VE estimate (VE: 29.7%, 95% CI: -5.3, 53.1). CONCLUSIONS: These results suggest that TIV was highly effective against A viruses and moderately effective against B viruses during a mild season characterised by co-circulation of four influenza strains in Canada. Findings underscore the need to provide VE assessment by subtype/lineage as well as the timing of vaccination (early season vs late season) to accurately evaluate vaccine performance and thus guide public health decision-making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01517191. Registration was retrospective and the date of registration was January 17, 2012.

Longitudinal clinical findings and outcome among patients with Cryptococcus gattii infection in British Columbia.

BACKGROUND: Cryptococcus gattii (Cg) infection emerged in British Columbia in 1999. A longitudinal, clinical description of patients has not been reported. METHODS: Medical records were reviewed for Cg patients identified through surveillance (1999-2007). Risk factors for Cg mortality were explored using multivariate Cox regression; longitudinal patterns in serum cryptococcal antigen (SCrAg) titers and the probability of chest cryptococcomas over time were estimated using cubic B-splines in mixed-effects regression models. RESULTS: Among 152 patients, 111 (73.0%) were culture confirmed. Isolated lung infection was present in 105 (69.1%) patients; 47 (30.9%) had central nervous system infection, with or without lung involvement. Malignancy was the provisional diagnosis in 64 (42.1%) patients. Underlying diseases were present in 91 (59.9%) patients; 23 (15.1%) were immunocompromised, and 23 (15.1%) had asymptomatic disease. There were only 2 (1.8%) culture positive relapses, both within 12 months of follow-up. The estimated median time to resolution of lung cryptococcomas and decline in SCrAg titer to <1:8 was 2.8 and 2.9 years, respectively. Cg-related and all-cause mortality among culture-confirmed cases at 12 months' follow-up was 23.3% and 27.2%, respectively. Cg-related mortality was associated with age >50 years (hazard ratio [HR], 15.6; 95% confidence interval [CI], 1.9-130.5) and immunocompromise (HR, 5.8; CI, 1.5-21.6). All Cg-related mortality occurred among culture-positive cases within 1 year of diagnosis. CONCLUSIONS: Cryptococcomas and serum antigenemia were slow to resolve. However, late onset of failed therapy or relapse was uncommon, suggesting that delayed resolution of these findings does not require prolongation of treatment beyond that recommended by guidelines.

Acute Kidney Injury With Tobramycin-Impregnated Bone Cement Spacers in Prosthetic Joint Infections.

BACKGROUND: Antibiotic-impregnated bone cement spacer (ACS) with tobramycin ± vancomycin is commonly used in a 2-stage replacement of infected prosthetic joints. This procedure has been associated with development of acute kidney injury (AKI). OBJECTIVE: To determine the incidence and risk factors for AKI after implantation of tobramycin-impregnated ACS. METHODS: This prospective, observational study evaluated 50 consecutive patients who received tobramycin ACS for first-stage revision of an infected hip or knee arthroplasty from August 2011 to February 2013. AKI was defined as 50% or greater rise in serum creatinine (SCr) from baseline within the first 7 postoperative days (PODs). RESULTS: The incidence of AKI was 20%, with median onset occurring at POD 2 (interquartile range [IQR] = 1-3); patients with AKI had a longer median duration of hospital stay (16 days, IQR = 12-17, vs 10 days, IQR = 8-10; P = 0.03). Serum tobramycin concentrations were significantly higher in the AKI group, peaking on POD 1 (median 1.9 vs 0.9 µg/mL, P = 0.01). Risk factors for nephrotoxicity identified by multivariate analysis were use of bone cement premanufactured with gentamicin (OR = 8.2; 95% CI = 1.1-60; P = 0.04), administration of blood transfusions intraoperatively (OR = 32.5; 95% CI = 2.3-454.3; P = 0.01) and nonsteroidal anti-inflammatory drugs postoperatively (OR = 23.0; 95% CI = 1.3-397.7; P = 0.03). CONCLUSIONS: Tobramycin ACS is associated with a high risk of AKI. Measures to minimize AKI risk in the perioperative period include early detection through close monitoring of SCr, avoiding use of premanufactured bone cement containing gentamicin, and avoiding potential nephrotoxins within the first 72 hours postoperatively.

Opinion du comité No 399 : Prise en charge des morsures de tiques et de la maladie de Lyme pendant la grossesse.

Objectif: La maladie de Lyme est une infection émergente au Canada. Causée par une bactérie appartenant au complexe d'espèces Borrelia burgdorferi sensu lato, elle est transmise par la morsure d'une tique à pattes noires infectée. Les populations de tiques à pattes noires continuent de se propager et sont maintenant établies dans différentes régions du Canada. Il faut habituellement plus de 24 heures de temps d'attachement de la tique pour que la B. burgdorferi soit transmise à l'humain. Le diagnostic de la maladie de Lyme au stade localisé précoce est posé au moyen d'une évaluation clinique, puisque les analyses de laboratoire ne sont pas fiables à ce stade. La plupart des patients atteints de la maladie de Lyme au stade localisé précoce manifestent une lésion cutanée (c.-à-d. érythème migrant) qui s'étend à partir du site de la morsure et/ou des symptômes non spécifiques qui rappellent l'influenza (p. ex. arthralgie, myalgie et fièvre). Les signes et symptômes peuvent se manifester de 3 à 30 jours après la morsure de tique. Il y a lieu de prendre en charge les patientes enceintes qui présentent une morsure de tique ou une maladie de Lyme soupçonnée en leur prodiguant des soins semblables à ceux de la population adulte non enceinte, ce qui implique d'envisager le recours aux antibiotiques pour la prophylaxie et le traitement. L'objectif principal de la présente opinion du comité est de renseigner les praticiens sur la maladie de Lyme et de fournir une façon d'aborder la prise en charge des soins prodigués aux femmes enceintes qui pourraient avoir été infectées par une morsure de tique à pattes noires. Utilisateurs concernés: Les fournisseurs de soins de santé qui prodiguent des soins aux patientes enceintes ou aux femmes en âge de procréer. Population cible: Les femmes en âge de procréer. Données probantes: En novembre 2018, des recherches ont été effectuées dans les bases de données Medline, EMBASE, PubMed et CENTRAL relativement à deux catégories principales : (1) maladie de Lyme, (2) autres maladies transmises par les tiques. Puisque la recherche était principalement axée sur la maladie de Lyme et compte tenu du nombre limité d'articles à ce sujet, aucun filtre supplémentaire n'a été appliqué pour la date de publication ou le type d'étude. Pour ce qui est des autres maladies transmises par les tiques, les résultats ont été restreints à une date de publication qui s'inscrit dans les 10 dernières années (2008­2018). Les termes de recherche ont été déterminés au moyen des termes de recherche MeSH et de mots clés : Lyme Disease, Pregnancy, Pregnant Women, Pregnancy Complications, Ehrlichiosis, Anaplasmosis, Rocky Mountain Spotted Fever, Babesiosis, Tularemia, Powassan Virus, Encephalitis Viruses, Tick-Borne, Tick-Borne Diseases, Colorado Tick Fever, Q Fever, Relapsing Fever, et Southern Tick-Associated Rash Illness. Tous les articles portant sur la maladie de Lyme et autres maladies transmises par les tiques comprenant une population cible de femmes enceintes ont été inclus; les autres groupes et populations ont été exclus. Méthodes de validation: Le contenu et les recommandations de la présente opinion du comité ont été rédigés et acceptés par les auteurs. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication.

Antimicrobial co-resistance patterns of gram-negative bacilli isolated from bloodstream infections: a longitudinal epidemiological study from 2002-2011.

BACKGROUND: Increasing multidrug resistance in gram-negative bacilli (GNB) infections poses a serious threat to public health. Few studies have analyzed co-resistance rates, defined as an antimicrobial susceptibility profile in a subset already resistant to one specific antibiotic. The epidemiologic and clinical utility of determining co-resistance rates are analyzed and discussed. METHODS: A 10-year retrospective study from 2002-2011 of bloodstream infections with GNB were analyzed from three hospitals in Greater Vancouver, BC, Canada. Descriptive statistics were calculated for antimicrobial resistance and co-resistance. Statistical analysis further described temporal trends of antimicrobial resistance, correlations of resistance between combinations of antimicrobials, and temporal trends in co-resistance patterns. RESULTS: The total number of unique blood stream isolates of GNB was 3280. Increasing resistance to individual antimicrobials was observed for E. coli, K. pneumoniae, K. oxytoca, E. cloacae, and P. aeruginosa. Ciprofloxacin resistance in E. coli peaked in 2006 at 40% and subsequently stabilized at 29% in 2011, corresponding to decreasing ciprofloxacin usage after 2007, as assessed by defined daily dose utilization data. High co-resistance rates were observed for ceftriaxone-resistant E. coli with ciprofloxacin (73%), ceftriaxone-resistant K. pneumoniae with trimethoprim-sulfamethoxazole (83%), ciprofloxacin-resistant E. cloacae with ticarcillin-clavulanate (91%), and piperacillin-tazobactam-resistant P. aeruginosa with ceftazidime (83%). CONCLUSIONS: Increasing antimicrobial resistance was demonstrated over the study period, which may partially be associated with antimicrobial consumption. The study of co-resistance rates in multidrug resistant GNB provides insight into the epidemiology of resistance acquisition, and may be used as a clinical tool to aid prescribing empiric antimicrobial therapy.

Increased moxifloxacin utilization associated with an unrestricted addition to a drug reimbursement formulary: A population-based analysis.

OBJECTIVES: To determine whether utilization of moxifloxacin, a broad-spectrum fluoroquinolone antibiotic, has changed since its addition to the British Columbia provincial formulary in 2009 and to determine whether utilization was guideline concordant. METHODS: BC PharmaNet prescriptions for moxifloxacin from 2001 to 2010 were anonymously linked to associated Medical Services Plan fee-for-service practitioner claims for indication-specific analysis. Prescribing trends for adults ≥18 years of age were described using defined daily dose (DDD) per 1000 person-years. Monthly utilization rates were fit to a linear regression model that controlled for seasonal variation to examine the effect of the formulary addition. RESULTS: Utilization rose more than sevenfold throughout the study period, from 21.3 DDD per 1000 person-years in 2001 to 163.3 DDD per 1000 person-years in 2010. Although the formulary addition was not associated with an immediate increase in utilization (7.5% [95% CI -4.4% to 20.9%]; P=0.226), it was associated with an overall increase in utilization of 2.1% (95% CI 1.3% to 3.0%; P<0.001) for every month after 2009. Overall, only 29% of moxifloxacin prescriptions could be linked to a diagnostic code that was considered to be guideline concordant. In more than one-half of moxifloxacin prescriptions, the patient had not used another antibiotic in the previous 90 days. Among moxifloxacin prescriptions in which another antibiotic had been used in the previous 90 days, 41.5% were prescriptions for an alternative fluoroquinolone. CONCLUSIONS: The formulary addition was associated with a sustained increase in moxifloxacin utilization over time. Moxifloxacin is often prescribed to patients for indications that are not guideline concordant or to patients who have not previously received first-line antibiotics.

OBJECTIFS: Déterminer si l'utilisation de moxifloxacine, un antibiotique de la famille des fluoriquonolones à large spectre, a changé depuis son ajout au formulaire provincial de la Colombie-Britannique en 2009 et établir si cette utilisation concorde avec les lignes directrices. MÉTHODOLOGIE: Les chercheurs ont lié de manière anonyme les prescriptions de moxifloxacine figurant dans BC PharmaNet de 2001 à 2010 aux réclamations des médecins rémunérés à l'acte auprès du régime d'assurance-maladie connexe en vue d'une analyse propre aux indications. Ils ont décrit les tendances de prescription aux adultes de 18 ans ou plus au moyen de la dose quotidienne déterminée (DQD) sur 1 000 années-personne. Les taux d'utilisation mensuels respectaient un modèle de régression linéaire de variation saisonnière afin d'examiner l'effet de l'ajout au formulaire. RÉSULTATS: L'utilisation a plus que septuplé pendant la période de l'étude, passant de 21,3 DQD sur 1 000 années-personnes en 2001 à 163,3 DQD sur 1 000 années-personne en 2010. Même si l'ajout au formulaire ne s'associait pas à une augmentation immédiate de l'utilisation (7,5 % [95 % IC −4,4 % à 20,9 %]; P=0,226), il s'associait à une augmentation globale d'utilisation de 2,1 % (95 % IC 1,3 % à 3,0 %; P<0,001) chaque mois après 2009. Dans l'ensemble, seulement 29 % des prescriptions de moxifloxacine pouvaient être liées à un code diagnostique considéré comme correspondant à des lignes directrices. Dans plus de la moitié des prescriptions de moxifloxacine, le patient n'avait pas utilisé d'autre antibiotique au cours des 90 jours précédents. Parmi les prescriptions de moxifloxacine associées à l'utilisation d'un autre antibiotique au cours de 90 jours précédents, 41,5 % étaient des prescriptions pour une autre fluoroquinolone. CONCLUSIONS: L'ajout au formulaire s'est associé à une augmentation soutenue de l'utilisation de moxifloxacine au fil du temps. La moxifloxacine est souvent prescrite aux patients pour des indications qui ne correspondent pas aux lignes directrices ou à des patients qui n'ont pas reçu d'antibiotiques de première ligne auparavant.

A prospective randomized trial of povidone-iodine prophylactic cleansing of the rectum before transrectal ultrasound guided prostate biopsy.

PURPOSE: Transrectal ultrasound guided prostate biopsy can lead to urinary tract infections in 3% to 11% and sepsis in 0.1% to 5% of patients. We investigated the efficacy of rectal cleansing with povidone-iodine before transrectal ultrasound guided prostate biopsy to reduce infectious complications. MATERIALS AND METHODS: Between 2009 and 2011, 865 men were prospectively randomized to rectal cleansing (421) or no cleansing (444) before transrectal ultrasound guided prostate biopsy. Patients received ciprofloxacin prophylaxis and rectal swab cultures were obtained before transrectal ultrasound guided prostate biopsy. Patients completed a telephone interview 7 days after undergoing the biopsy. The primary end point was the rate of infectious complications, a composite end point of 1 or more of 1) fever greater than 38.0C, 2) urinary tract infection or 3) sepsis (standardized definition). Chi-square significance testing was performed for differences between groups and a multivariate analysis was performed to assess risk factors for infectious complications. RESULTS: Infectious complications were observed in 31 (3.5%) patients, including 11 (2.6%) treated and 20 (4.5%) control patients (p = 0.15). Sepsis was observed in 4 (1.0%) treated and 7 (1.6%) control patients (p = 0.55). On multivariate analysis resistance to ciprofloxacin in the rectal swab culture (p = 0.002) and a history of taking ciprofloxacin in the 3 months preceding transrectal ultrasound guided prostate biopsy (p = 0.009) predicted infectious complications. CONCLUSIONS: Rectal cleansing with povidone-iodine before transrectal ultrasound guided prostate biopsy was safe, but the 42% relative risk reduction of infectious complications was not statistically significant. Patients who have received ciprofloxacin within 3 months of transrectal ultrasound guided prostate biopsy should be considered for alternate prophylaxis or possibly a delay of biopsy beyond 3 months.

Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Transrectal ultrasound guided prostate biopsies (TRUSBx) are associated with a spectrum of complications, including most significantly infection, which affects up to 5% of patients. In the most severe cases, infection leads to sepsis, a life-threatening complication. Escherichia coli is the primary responsible pathogen. Although antibiotic prophylaxis with fluoroquinolones is routinely used, there is evidence that the infection rate after TRUSBx is increasing, and this appears to be due to an increasing prevalence of ciprofloxacin-resistant rectal flora. This is the largest prospective clinical trial to date analysing the rectal flora of men undergoing prostate biopsies. We determined the microbial and antibiotic sensitivity profiles from 849 patients. Ciprofloxacin-resistant Gram-negative organisms were identified in the rectal flora of 19.0% of men. Furthermore, fluoroquinolone use within 6 months preceding a TRUSBx and the presence of a prosthetic heart valve were significant predictors of ciprofloxacin resistance on rectal swab. Determining the prevalence of rectal fluoroquinolone resistance has important implications in evaluation of the suitability of prophylactic regimens. Antimicrobial profiles derived from rectal swabs pre-biopsy may prove useful in guiding targeted antibiotic prophylaxis. OBJECTIVES: To establish the prevalence of ciprofloxacin-resistant bacteria in patients undergoing transrectal ultrasound guided prostate biopsies (TRUSBx) and to determine whether this predicts subsequent infectious complications. To identify risk factors for harbouring ciprofloxacin-resistant flora. PATIENTS AND METHODS: Any patient undergoing a TRUSBx from 2009 to 2011 was eligible for enrolment in this prospective study. Pre-biopsy rectal and urine cultures and post-biopsy urine cultures were obtained and antimicrobial susceptibility was determined. Univariate and multivariate analyses were performed to identify independent patient risk factors associated with ciprofloxacin-resistant rectal flora. RESULTS: A total of 865 patients underwent TRUSBx, of whom 19.0% were found to have ciprofloxacin-resistant Gram-negative coliforms. Escherichia coli was the most prevalent Gram-negative rectal isolate (80.9%) and accounted for 90.6% of ciprofloxacin resistance. Patient characteristics that conferred an increased risk of harbouring ciprofloxacin-resistant organisms included a history of a heart valve replacement (P < 0.05) and ciprofloxacin use in the past 3 months (P < 0.05). Infectious complications were observed in 3.6% (n = 31) of the patient population and 48% of these patients grew ciprofloxacin-resistant organisms on the pre-biopsy rectal swab (P < 0.001). CONCLUSIONS: Antimicrobial resistance to ciprofloxacin in the rectal flora was common, particularly in patients with recent ciprofloxacin use and a heart valve replacement. Despite a significant correlation between those patients who developed infections and the detection of ciprofloxacin-resistant organisms, only 9.0% (n = 15) of the total group with ciprofloxacin resistance developed an infectious complication. Future studies will need to evaluate the cost effectiveness and clinical utility of a pre-biopsy rectal culture in targeting antibiotic prophylaxis.

Xenomake: a pipeline for processing and sorting xenograft reads from spatial transcriptomic experiments.

Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provide a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, quantification, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism specific reads, reduce sparsity of data by increasing gene counts, while maintaining biological relevance for studies.

Vaccine Effectiveness of non-adjuvanted and adjuvanted trivalent inactivated influenza vaccines in the prevention of influenza-related hospitalization in older adults: A pooled analysis from the Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN).

BACKGROUND: Influenza vaccines prevent influenza-related morbidity and mortality; however, suboptimal vaccine effectiveness (VE) of non-adjuvanted trivalent inactivated influenza vaccine (naTIV) or quadrivalent formulations in older adults prompted the use of enhanced products such as adjuvanted TIV (aTIV). Here, the VE of aTIV is compared to naTIV for preventing influenza-associated hospitalization among older adults. METHODS: A test-negative design study was used with pooled data from the 2012 to 2015 influenza seasons. An inverse probability of treatment (IPT)-weighted logistic regression estimated the Odds Ratio (OR) for laboratory-confirmed influenza-associated hospitalization. VE was calculated as (1-OR)*100% with accompanying 95% confidence intervals (CI). RESULTS: Of 7,101 adults aged ≥ 65, 3,364 received naTIV and 526 received aTIV. The overall VE against influenza hospitalization was 45.9% (95% CI: 40.2%-51.1%) for naTIV and 53.5% (42.8%-62.3%) for aTIV. No statistically significant differences in VE were found between aTIV and naTIV by age group or influenza season, though a trend favoring aTIV over naTIV was noted. Frailty may have impacted VE in aTIV recipients compared to those receiving naTIV, according to an exploratory analysis; VE adjusted by frailty was 59.1% (49.6%-66.8%) for aTIV and 44.8% (39.1%-50.0%) for naTIV. The overall relative VE of aTIV to naTIV against laboratory-confirmed influenza hospital admission was 25% (OR 0.75; 0.61-0.92), demonstrating statistically significant benefit favoring aTIV. CONCLUSIONS: Adjusting for frailty, aTIV showed statistically significantly better protection than naTIV against influenza-associated hospitalizations in older adults. In future studies, it is important to consider frailty as a significant confounder of VE.

Leveraging Influenza Virus Surveillance From 2012 to 2015 to Characterize the Burden of Respiratory Syncytial Virus Disease in Canadian Adults ≥50 Years of Age Hospitalized With Acute Respiratory Illness.

Background: Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods: Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012-2013, 2013-2014, and 2014-2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results: Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8-12 per 100 000 population in adults aged 50-59 years to 174-487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions: This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza.

Population-based study of the increased incidence of skin and soft tissue infections and associated antimicrobial use.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has spread rapidly throughout the world in the last decade. We sought to demonstrate the impact of the emergence of CA-MRSA in Western Canada on physician visits, incision-and-drainage procedures, and antibiotic prescribing for skin and soft tissue infections (SSTI). We used the provincial physician billing system to determine the rate of physician visits (per 1,000 population per year) of SSTI and incision-and-drainage procedures. A database capturing all outpatient prescriptions in the province was anonymously linked to associated physician billing codes to quantify prescriptions associated with SSTI. Antibiotic prescriptions (overall and class specific) were expressed as their defined daily dose (DDD) per 1,000 inhabitants per day. Between 1996 and 2008, the rate of visits for all SSTI increased by 15%, and the majority of visits did not include an incision-and-drainage procedure. The rate of antibiotic prescribing for SSTI increased by 49%. The majority of this increase was attributable to the higher rates of use of clindamycin (627%), trimethoprim-sulfamethoxazole (380%), cephalosporins (160%), and amoxicillin-clavulanate (627%). Health care utilization and antibiotic prescribing rates for SSTI, but not incision-and-drainage procedures, have increased in association with the CA-MRSA epidemic. While much of the increase in antibiotic use reflects an appropriate change to trimethoprim-sulfamethoxazole, there is room for education regarding the limitations of cephalosporins and clindamycin, given current susceptibility profiles.

Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay.

OBJECTIVE(S): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. METHODS: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. RESULTS: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. CONCLUSION(S): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.

Establishing a community of practice of researchers, practitioners, policy-makers and communities to sustainably manage environmental health risks in Ecuador.

BACKGROUND: The Sustainably Managing Environmental Health Risk in Ecuador project was launched in 2004 as a partnership linking a large Canadian university with leading Cuban and Mexican institutes to strengthen the capacities of four Ecuadorian universities for leading community-based learning and research in areas as diverse as pesticide poisoning, dengue control, water and sanitation, and disaster preparedness. METHODS: In implementing curriculum and complementary innovations through application of an ecosystem approach to health, our interdisciplinary international team focused on the question: "Can strengthening of institutional capacities to support a community of practice of researchers, practitioners, policy-makers and communities produce positive health outcomes and improved capacities to sustainably translate knowledge?" To assess progress in achieving desired outcomes, we review results associated with the logic framework analysis used to guide the project, focusing on how a community of practice network has strengthened implementation, including follow-up tracking of program trainees and presentation of two specific case studies. RESULTS: By 2009, train-the-trainer project initiation involved 27 participatory action research Master's theses in 15 communities where 1200 community learners participated in the implementation of associated interventions. This led to establishment of innovative Ecuadorian-led master's and doctoral programs, and a Population Health Observatory on Collective Health, Environment and Society for the Andean region based at the Universidad Andina Simon Bolivar. Building on this network, numerous initiatives were begun, such as an internationally funded research project to strengthen dengue control in the coastal community of Machala, and establishment of a local community eco-health centre focusing on determinants of health near Cuenca. DISCUSSION: Strengthening capabilities for producing and applying knowledge through direct engagement with affected populations and decision-makers provides a fertile basis for consolidating capacities to act on a larger scale. This can facilitate the capturing of benefits from the "top down" (in consolidating institutional commitments) and the "bottom up" (to achieve local results). CONCLUSIONS: Alliances of academic and non-academic partners from the South and North provide a promising orientation for learning together about ways of addressing negative trends of development. Assessing the impacts and sustainability of such processes, however, requires longer term monitoring of results and related challenges.