The gut microbiome is shaped through infancy and impacts the maturation of the immune system, thus protecting against chronic disease later in life. Phages, or viruses that infect bacteria, modulate bacterial growth by lysis and lysogeny, with the latter being especially prominent in the infant gut. Viral metagenomes (viromes) are difficult to analyse because they span uncharted viral diversity, lacking marker genes and standardized detection methods. Here we systematically resolved the viral diversity in faecal viromes from 647 1-year-olds belonging to Copenhagen Prospective Studies on Asthma in Childhood 2010, an unselected Danish cohort of healthy mother–child pairs. By assembly and curation we uncovered 10,000 viral species from 248 virus family-level clades (VFCs). Most (232 VFCs) were previously unknown, belonging to theCaudoviricetesviral class. Hosts were determined for 79% of phage using clustered regularly interspaced short palindromic repeat spacers within bacterial metagenomes from the same children. TypicalBacteroides-infecting crAssphages were outnumbered by undescribed phage families infectingClostridialesandBifidobacterium. Phage lifestyles were conserved at the viral family level, with 33 virulent and 118 temperate phage families. Virulent phages were more abundant, while temperate ones were more prevalent and diverse. Together, the viral families found in this study expand existing phage taxonomy and provide a resource aiding future infant gut virome research.

Early diagnosis of severe infections requires of a rapid and reliable diagnosis to initiate appropriate treatment, while avoiding unnecessary antimicrobial use and reducing associated morbidities and healthcare costs. It is a fact that conventional methods usually require more than 24–48 h to culture and profile bacterial species. Mass spectrometry (MS) is an analytical technique that has emerged as a powerful tool in clinical microbiology for identifying peptides and proteins, which makes it a promising tool for microbial identification. Matrix assisted laser desorption ionization–time of flight MS (MALDI–TOF MS) offers a cost- and time-effective alternative to conventional methods, such as bacterial culture and even 16S rRNA gene sequencing, for identifying viruses, bacteria and fungi and detecting virulence factors and mechanisms of resistance. This review provides an overview of the potential applications and perspectives of MS in clinical microbiology laboratories and proposes its use as a first-line method for microbial identification and diagnosis.

Culture techniques have associated colonization with pathogenic bacteria in the airways of neonates with later risk of childhood asthma, whereas more recent studies utilizing sequencing techniques have shown the same phenomenon with specific anaerobic taxa. Here, we analyze nasopharyngeal swabs from 1 month neonates in the COPSAC₂₀₀₀prospective birth cohort by 16S rRNA gene sequencing of the V3-V4 region in relation to asthma risk throughout childhood. Results are compared with previous culture results from hypopharyngeal aspirates from the same cohort and with hypopharyngeal sequencing data from the later COPSAC₂₀₁₀cohort. Nasopharyngeal relative abundance values ofStreptococcus pneumoniae, Haemophilus influenzae, andMoraxella catarrhalisare associated with the same species in the hypopharyngeal cultures. A combined pathogen score of these bacteria’s abundance values is associated with persistent wheeze/asthma by age 7. No other taxa are associated. Compared to the hypopharyngeal aspirates from the COPSAC₂₀₁₀cohort, the anaerobesVeillonellaandPrevotella, which have previously been implicated in asthma development, are less commonly detected in the COPSAC₂₀₀₀nasopharyngeal samples, but correlate with the pathogen score, hinting at latent community structures that bridge current and previous results. These findings have implications for future asthma prevention efforts.

Purpose: While the beneficial effects of medications are numerous, drug–drug interactions may lead to adverse drug reactions that are preventable causes of morbidity and mortality. Our goal was to quantify the prevalence of potential drug–drug interactions in drug prescriptions at Danish hospitals, estimate the risk of adverse outcomes associated with discouraged drug combinations, and highlight the patient types (defined by the primary diagnosis of the admission) that appear to be more affected.Methods: This cross‐sectional (descriptive part) and cohort study (adverse outcomes part) used hospital electronic health records from two Danish regions (~2.5 million people) from January 2008 through June 2016. We included all inpatients receiving two or more medications during their admission and considered concomitant prescriptions of potentially interacting drugs as per the Danish Drug Interaction Database. We measured the prevalence of potential drug–drug interactions in general and discouraged drug pairs in particular during admissions and associations with adverse outcomes: post‐discharge all‐cause mortality rate, readmission rate and length‐of‐stay.Results: Among 2 886 227 hospital admissions (945 475 patients; median age 62 years [IQR: 41–74]; 54% female; median number of drugs 7 [IQR: 4–11]), patients in 1 836 170 admissions were exposed to at least one potential drug–drug interaction (659 525 patients; median age 65 years [IQR: 49–77]; 54% female; median number of drugs 9 [IQR: 6–13]) and in 27 605 admissions to a discouraged drug pair (18 192 patients; median age 68 years [IQR: 58–77]; female 46%; median number of drugs 16 [IQR: 11–22]). Meropenem‐valproic acid (HR: 1.5, 95% CI: 1.1–1.9), domperidone‐fluconazole (HR: 2.5, 95% CI: 2.1–3.1), imipramine‐terbinafine (HR: 3.8, 95% CI: 1.2–12), agomelatine‐ciprofloxacin (HR: 2.6, 95% CI: 1.3–5.5), clarithromycin‐quetiapine (HR: 1.7, 95% CI: 1.1–2.7) and piroxicam‐warfarin (HR: 3.4, 95% CI: 1–11.4) were associated with elevated mortality. Confidence interval bounds of pairs associated with readmission were close to 1; length‐of‐stay results were inconclusive.Conclusions: Well‐described potential drug–drug interactions are still missed and alerts at point of prescription may reduce the risk of harming patients; prescribing clinicians should be alert when using strong inhibitor/inducer drugs (i.e. clarithromycin, valproic acid, terbinafine) and prevalent anticoagulants (i.e. warfarin and non‐steroidal anti‐inflammatory drugs ‐ NSAIDs) due to their great potential for dangerous interactions. The most prominent CYP isoenzyme involved in mortality and readmission rates was 3A4.

Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, treatment outcomes, and complications. We address these issues through deep, fine-grained phenotypic stratification of a diabetes cohort. Text mining the electronic health records of 14,017 patients, we matched two controlled vocabularies (ICD-10 and a custom vocabulary developed at the clinical center Steno Diabetes Center Copenhagen) to clinical narratives spanning a 19 year period. The two matched vocabularies comprise over 20,000 medical terms describing symptoms, other diagnoses, and lifestyle factors. The cohort is genetically homogeneous (Caucasian diabetes patients from Denmark) so the resulting stratification is not driven by ethnic differences, but rather by inherently dissimilar progression patterns and lifestyle related risk factors. Using unsupervised Markov clustering, we defined 71 clusters of at least 50 individuals within the diabetes spectrum. The clusters display both distinct and shared longitudinal glycemic dysregulation patterns, temporal co-occurrences of comorbidities, and associations to single nucleotide polymorphisms in or near genes relevant for diabetes comorbidities.