Documenting the indication for antimicrobial prescribing: A retrospective observational study of long-term care homes.

BACKGROUND: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting. METHODS: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level. RESULTS: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits. CONCLUSIONS: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications.

Postoperative outcomes for Nunavut Inuit at a Canadian quaternary care centre: a retrospective cohort study.

BACKGROUND: Structural aspects of health care systems, such as limited access to specialized surgical and perioperative care, can negatively affect the outcomes and resource use of patients undergoing elective and emergency surgical procedures. The aim of this study was to compare postoperative outcomes of Nunavut Inuit and non-Inuit patients at a Canadian quaternary care centre. METHODS: We conducted a retrospective cohort study involving adult (age ≥ 18 yr) patients undergoing inpatient surgery from 2011 to 2018 at The Ottawa Hospital, the quaternary referral hospital for the Qikiqtaaluk Region of Nunavut. The study was designed and conducted in collaboration with Nunavut Tunngavik Incorporated. The primary outcome was a composite of in-hospital death or complications.Secondary outcomes included postoperative length of stay in hospital, adverse discharge disposition, readmissions within 30 days and total hospitalization costs. RESULTS: A total of 98 701 episodes of inpatient surgical care occurred among patients aged 18 to 104 years; 928 (0.9%) of these involved Nunavut Inuit, and 97 773 involved non-Inuit patients. Death or postoperative complication occurred more often among Nunavut Inuit than non-Inuit patients (159 [17.2%] v. 15 691 [16.1%]), which was significantly different after adjustment for age, sex, surgical specialty, risk and urgency (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.03-1.51). This association was most pronounced in cases of cancer (OR 1.63, 95% CI 1.03-2.58) and elective surgery (OR 1.58, 95% CI 1.20-2.10). Adjusted rates of readmission, adverse discharge disposition, length of stay and total costs were significantly higher for Nunavut Inuit. INTERPRETATION: Nunavut Inuit had a 25% relative increase in their odds of morbidity and death after surgery at a major quaternary care hospital in Canada compared with non-Inuit patients, while also having higher rates of other adverse outcomes and resource use. An examination of perioperative systems involving patients, Inuit leadership, health care providers and governments is required to address these differences in health outcomes.

Niqivut Silalu Asijjipalliajuq: Building a Community-Led Food Sovereignty and Climate Change Research Program in Nunavut, Canada.

The history of health research in Inuit communities in Canada recounts unethical and colonizing research practices. Recent decades have witnessed profound changes that have advanced ethical and community-driven research, yet much work remains. Inuit have called for research reform in Inuit Nunangat, most recently creating the National Inuit Strategy on Research (NISR) as a framework to support this work. The present study details the process undertaken to create a research program guided by the NISR to address food security, nutrition, and climate change in Inuit Nunangat. Four main elements were identified as critical to supporting the development of a meaningful and authentic community-led program of research: developing Inuit-identified research questions that are relevant and important to Inuit communities; identifying Inuit expertise to answer these questions; re-envisioning and innovating research methodologies that are meaningful to Inuit and reflect Inuit knowledge and societal values; and identifying approaches to mobilizing knowledge that can be applied to support food security and climate change adaptation. We also identify considerations for funding agencies to support the meaningful development of Inuit-led research proposals, including aligning funding with community priorities, reconsidering who the researchers are, and investing in community infrastructure. Our critical reflection on the research program development process provides insight into community-led research that can support Inuit self-determination in research, enhance local ethical conduct of research, privilege Inuit knowledge systems, and align Inuit-identified research priorities with research funding opportunities in health research. While we focus on Inuit-led research in Nunavut, Canada, these insights may be of interest more broadly to Indigenous health research.

Molecular Epidemiology of Mycobacterium tuberculosis To Describe the Transmission Dynamics Among Inuit Residing in Iqaluit Nunavut Using Whole-Genome Sequencing.

BACKGROUND: In the last decade, tuberculosis (TB) incidence among Inuit in the Canadian Arctic has been rising. Our aim was to better understand the transmission dynamics of TB in this remote region of Canada using whole-genome sequencing. METHODS: Isolates from patients who had culture-positive pulmonary TB in Iqaluit, Nunavut, between 2009 and 2015 underwent whole-genome sequencing (WGS). The number of transmission events between cases within clusters was calculated using a threshold of a ≤3 single nucleotide polymorphism (SNP) difference between isolates and then combined with detailed epidemiological data using a reproducible novel algorithm. Social network analysis of epidemiological data was used to support the WGS data analysis. RESULTS: During the study period, 140 Mycobacterium tuberculosis isolates from 135 cases were sequenced. Four clusters were identified, all from Euro-American lineage. One cluster represented 62% of all cases that were sequenced over the entire study period. In this cluster, 2 large chains of transmission were associated with 3 superspreading events in a homeless shelter. One of the superspreading events was linked to a nonsanctioned gambling house that resulted in further transmission. Shelter to nonshelter transmission was also confirmed. An algorithm developed for the determination of transmission events demonstrated very good reproducibility (κ score .98, 95% confidence interval, .97-1.0). CONCLUSIONS: Our study suggests that socioeconomic factors, namely residing in a homeless shelter and spending time in a gambling house, combined with the superspreading event effect may have been significant factors explaining the rise in cases in this predominantly Inuit Arctic community.

The latent tuberculosis infection cascade of care in Iqaluit, Nunavut, 2012-2016.

BACKGROUND: A remote arctic region of Canada predominantly populated by Inuit with the country's highest incidence of tuberculosis. METHODS: The study was undertaken to describe the latent tuberculosis infection (LTBI) cascade of care and identify factors associated with non-initiation and non-completion of LTBI treatment. Data were extracted retrospectively from medical records for all patients with a tuberculin skin test (TST) implanted in Iqaluit, Nunavut between January 2012 and March 2016. Associations between demographic and clinical factors and both treatment non-initiation among and treatment non-completion were identified using log binomial regression models where convergence could be obtained and Poisson models with robust error variance where convergence was not obtained. RESULTS: Of 2303 patients tested, 439 (19.1%) were diagnosed with LTBI. Treatment was offered to 328 patients, was initiated by 246 (75.0% of those offered) and was completed by 186 (75.6% of initiators). In multivariable analysis, older age (adjust risk ratio [aRR] 1.17 per 5-year increase, 95%CI:1.09-1.26) and undergoing TST due to employment screening (aRR 1.63, 95%CI:1.00-2.65, compared to following tuberculosis exposure) were associated with increased non-initiation of treatment. Older age (aRR 1.13, 95%CI: 1.03-1.17, per 5-year increase) was associated with increased non-completion of treatment. CONCLUSIONS: A similar rate of treatment initiation and higher rate of treatment completion were found compared to previous North American studies. Interventions targeting older individuals and those identified via employment screening may be considered to help to address the largest losses in the cascade of care.

Weather, environmental conditions, and waterborne Giardia and Cryptosporidium in Iqaluit, Nunavut.

Indigenous communities in the Arctic often face unique drinking water quality challenges related to inadequate infrastructure and environmental contamination; however, limited research exists on waterborne parasites in these communities. This study examined Giardia and Cryptosporidium in untreated surface water used for drinking in Iqaluit, Canada. Water samples (n = 55) were collected weekly from June to September 2016 and tested for the presence of Giardia and Cryptosporidium using microscopy and polymerase chain reaction (PCR). Exact logistic regressions were used to examine associations between parasite presence and environmental exposure variables. Using microscopy, 20.0% of samples tested positive for Giardia (n = 11) and 1.8% of samples tested positive for Cryptosporidium (n = 1). Low water temperatures (1.1 to 6.7 °C) and low air temperatures (-0.1 to 4.5 °C) were significantly associated with an increased odds of parasite presence (p = 0.047, p = 0.041, respectively). These results suggest that surface water contamination with Giardia and Cryptosporidium may be lower in Iqaluit than in other Canadian regions; however, further research should examine the molecular characterization of waterborne parasites to evaluate the potential human health implications in Northern Canada.

Single mutation to a sex pheromone receptor provides adaptive specificity between closely related moth species.

Sex pheromone communication, acting as a prezygotic barrier to mating, is believed to have contributed to the speciation of moths and butterflies in the order Lepidoptera. Five decades after the discovery of the first moth sex pheromone, little is known about the molecular mechanisms that underlie the evolution of pheromone communication between closely related species. Although Asian and European corn borers (ACB and ECB) can be interbred in the laboratory, they are behaviorally isolated from mating naturally by their responses to subtly different sex pheromone isomers, (E)-12- and (Z)-12-tetradecenyl acetate and (E)-11- and (Z)-11-tetradecenyl acetate (ACB: E12, Z12; ECB; E11, Z11). Male moth olfactory systems respond specifically to the pheromone blend produced by their conspecific females. In vitro, ECB(Z) odorant receptor 3 (OR3), a sex pheromone receptor expressed in male antennae, responds strongly to E11 but also generally to the Z11, E12, and Z12 pheromones. In contrast, we show that ACB OR3, a gene that has been subjected to positive selection (ω = 2.9), responds preferentially to the ACB E12 and Z12 pheromones. In Ostrinia species the amino acid residue corresponding to position 148 in transmembrane domain 3 of OR3 is alanine (A), except for ACB OR3 that has a threonine (T) in this position. Mutation of this residue from A to T alters the pheromone recognition pattern by selectively reducing the E11 response ∼14-fold. These results suggest that discrete mutations that narrow the specificity of more broadly responsive sex pheromone receptors may provide a mechanism that contributes to speciation.

Asian corn borer pheromone binding protein 3, a candidate for evolving specificity to the 12-tetradecenyl acetate sex pheromone.

Most moth species in the genus Ostrinia use varying ratios of (Z)-11- and (E)-11-tetradecenyl acetate as their main sex pheromone components. The Asian corn borer is unique within the genus having evolved to use pheromone components with a shift in the location of the double bond, (Z)-12- and (E)-12-tetradecenyl acetate. We identified cDNAs representing five pheromone binding proteins (PBPs) and two sensory neuron membrane protein genes from an antennal transcriptome. The coding regions of the orthologous genes were cloned from the Asian corn borer and the (E) and (Z) sex pheromone races of the European corn borer. Their nucleotide sequences and transcript expression levels were analyzed to identify candidate genes from the Asian corn borer that may have evolved specificity to the 12-tetradecenyl acetate ligand. PBP2 and PBP3 transcripts were expressed at high male-biased levels. PBP3 had the most nonsynonymous nucleotide substitutions resulting in ten amino acid changes. Based on the predicted three-dimensional structure of PBP3, six of these ten amino acid changes occur in domains that may interact with the pheromone ligand. Future studies will determine whether PBP3 has evolved specificity to the Asian corn borer sex pheromone.

Sex pheromone receptor specificity in the European corn borer moth, Ostrinia nubilalis.

BACKGROUND: The European corn borer (ECB), Ostrinia nubilalis (Hubner), exists as two separate sex pheromone races. ECB(Z) females produce a 97ratio3 blend of Z11- and E11-tetradecenyl acetate whereas ECB(E) females produce an opposite 1ratio99 ratio of the Z and E isomers. Males of each race respond specifically to their conspecific female's blend. A closely related species, the Asian corn borer (ACB), O. furnacalis, uses a 3ratio2 blend of Z12- and E12-tetradecenyl acetate, and is believed to have evolved from an ECB-like ancestor. To further knowledge of the molecular mechanisms of pheromone detection and its evolution among closely related species we identified and characterized sex pheromone receptors from ECB(Z). METHODOLOGY: Homology-dependent (degenerate PCR primers designed to conserved amino acid motifs) and homology-independent (pyrophosphate sequencing of antennal cDNA) approaches were used to identify candidate sex pheromone transcripts. Expression in male and female antennae was assayed by quantitative real-time PCR. Two-electrode voltage clamp electrophysiology was used to functionally characterize candidate receptors expressed in Xenopus oocytes. CONCLUSION: We characterized five sex pheromone receptors, OnOrs1 and 3-6. Their transcripts were 14-100 times more abundant in male compared to female antennae. OnOr6 was highly selective for Z11-tetradecenyl acetate (EC(50) = 0.86+/-0.27 microM) and was at least three orders of magnitude less responsive to E11-tetradecenyl acetate. Surprisingly, OnOr1, 3 and 5 responded to all four pheromones tested (Z11- and E11-tetradecenyl acetate, and Z12- and E12-tetradecenyl acetate) and to Z9-tetradecenyl acetate, a behavioral antagonist. OnOr1 was selective for E12-tetradecenyl acetate based on an efficacy that was at least 5-fold greater compared to the other four components. This combination of specifically- and broadly-responsive pheromone receptors corresponds to published results of sensory neuron activity in vivo. Receptors broadly-responsive to a class of pheromone components may provide a mechanism for variation in the male moth response that enables population level shifts in pheromone blend use.

Novel single-nucleotide change in GYP*A in a person who made an alloantibody to a new high-prevalence MNS antigen called ENEV.

BACKGROUND: Alloantibodies that define some high-prevalence MNS antigens are made by people with glycophorin A (GPA) altered by a single-amino-acid change or replacement of amino acids from part of the Pseudoexon 3 of GYP*B. The finding of a patient whose plasma contained a novel alloanti-En(a)FR prompted this study. RESULTS: The patient's serum contained an alloantibody to a high-prevalence antigen, resistant to papain, ficin, trypsin, alpha-chymotrypsin, or dithiothreitol. The antibody was strongly reactive with all panel red blood cells (RBCs) tested, showed reduced reactivity with ENEP- and ENAV- RBCs, and was nonreactive with M(k)M(k), En(a-), GP.Hil/GP.Hil, and GP.JL/M(k) RBCs. The patient's RBCs typed M+N-S+s-, Wr(a-b+(w)), ENEP-, and ENAV-. These results indicated that the antibody recognized a new high-prevalence antigen in the MNS system. Sequencing of DNA prepared from the patient's white blood cells revealed a GYP*A nucleotide substitution of 242T>G (predicted to change Val62 of GPA to Gly). This change ablates an RsaI restriction enzyme site and polymerase chain reaction-restriction fragment length polymorphism confirmed that the proband was homozygous for Nucleotide 242G. CONCLUSIONS: We describe a novel high-prevalence MNS antigen, characterized by Val62 in GPA and named ENEV. The absence of the antigen is associated with Gly62. The change explains the weakened reactivity of the patient's serum with ENEP- and ENAV- RBCs and nonreactivity with anti-ENEP and anti-ENAV against her RBCs. The ENEV antigen has been assigned the ISBT number MNS45.

MDCT evaluation of central airway and vascular complications of lung transplantation.

OBJECTIVE: The purpose of this article is to illustrate the spectrum of central airway and vascular complications in lung transplantation using MDCT, with an emphasis on the usefulness of advanced postprocessing techniques. CONCLUSION: MDCT is an invaluable tool in the diagnosis, evaluation, and posttreatment assessment of central airway and vascular complications in lung transplant recipients. Advanced postprocessing techniques provide complementary information that is visually accessible and anatomically meaningful for the clinician.

Rapid prenatal testing for human beta-glucuronidase deficiency (MPS VII).

Prenatal diagnosis for the lysosomal storage disorders is typically achieved by enzymatic analysis of the relevant lysosomal enzyme in cultured amniocytes or chorionic villi. While prenatal diagnosis of some genetic diseases can be done by analysis of pertinent metabolites in amniotic fluid, there are few data regarding prenatal diagnosis of lysosomal disorders by enzyme analysis of amniotic fluid. Prenatal diagnosis by enzyme analysis of amniotic fluid has the potential advantage of providing a more rapid prenatal test result. In this study we describe an assay for the prenatal diagnosis of the mucopolysaccharidosis beta-glucuronidase deficiency (MPS VII; MIM #253220) using amniotic fluid and we confirm its reliability in detecting an affected fetus in an at-risk pregnancy by enzyme analysis of cultured amniocytes and fetal fibroblasts. Because MPS VII is rare and few instances of prenatal diagnosis for this and nearly all other lysosomal disorders have been accomplished by enzyme analysis of amniotic fluid, confirmation of results obtained from enzyme analysis of amniotic fluid should be carried out by enzyme or mutation analysis using cultured amniocytes or chorionic villus specimens.

Multislice CT angiography.

The introduction of multislice CT into clinical radiology constitutes a quantum leap that significantly widens the scope of vascular CT imaging. The advances over conventional spiral CT have been quantitative, mainly in terms of increased image acquisition speed which provides unprecedented volume coverage and spatial resolution. Moreover, significant technical innovations, such as cardiac scanning capabilities, have brought about a qualitative shift towards applications that were thought to be beyond the scope of CT imaging. This way multislice CT offers a wealth of new opportunities for quickly and accurately diagnosing suspected vascular disease in all organ systems; however, as we move towards faster and faster image acquisition techniques, we are also facing new challenges that require development of novel strategies in order to take full advantage of the increased capabilities of multislice CT in its current form and future generations of CT scanners.