Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases

Urinary tract disease is a common reason for use (and likely misuse, improper use, and overuse) of antimicrobials in dogs and cats. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, guidelines for diagnosis and management of urinary tract infections were created by a Working Group of the International Society for Companion Animal Infectious Diseases. While objective data are currently limited, these guidelines provide information to assist in the diagnosis and management of upper and lower urinary tract infections in dogs and cats

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20–365 from study allocation and (ii) days alive and without exacerbation within days 20–365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142. Registered on August 25, 2017. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06720-z

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

DNA methylation and body mass index from birth to adolescence : meta-analyses of epigenome-wide association studies

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P <1.06 x 10(-7), with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth P-enrichment = 1; childhood P-enrichment = 2.00 x 10(-4); adolescence P-enrichment = 2.10 x 10(-7)). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.Peer reviewe

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

Abdominal Aortic Aneurysm Repair in Patients with Concomitant Cancer: A Literature Review

ObjectivesAbdominal aortic aneurysmal (AAA) repair in patients with concomitant cancer is controversial due to increased comorbidity and reduced life expectancy in this specific patient group. This literature review aims to investigate the evidence supporting one treatment modality over another (endovascular aortic repair (EVAR) or open repair (OR)), as well as treatment strategy (staged AAA-, cancer first or simultaneous procedures) in patients with AAA and concomitant cancer.MethodsLiterature review, including studies published from 2000 to 2021 on surgical treatment in patients with AAA and concomitant cancer and related outcomes (30-day morbidity/complications as well as 30-day and 3-year mortality).Results24 studies comprising 560 patients undergoing surgical treatment of AAA and concomitant cancer were included. Of these, 220 cases were treated with EVAR and 340 with OR. Simultaneous procedures were performed in 190 cases, 370 received staged procedures. The 30-day mortality for EVAR versus OR was 1% and 8%, corresponding to a relative risk (RR) of 0.11 (95% CI: 0.03–0.46, p = 0.002). No difference in mortality was observed between staged versus simultaneous procedure nor between AAA-first versus cancer-first strategy, RR 0.59 (95% CI: 0.29–1.1, p = 0.13) and 0.88 (95% CI 0.34–2.31, p = 0.80), respectively. Overall, 3-year mortality was 21% for EVAR and 39% for OR from 2000–2021, while the mortality up to 3 years after EVAR within recent years (2015–2021) was 16%.ConclusionThis review supports EVAR treatment as first choice if suitable. No consensus was established on treating either the aneurysm or the cancer first or simultaneously. Long-term mortality after EVAR was comparable to non-cancer patients within recent years

47. Increased risk of death in patients with double positive serology of anti-GBM antibodies and ANCA

Background and Aims: Double positivity of anti-GBM and ANCA serology is uncommon but may represent a distinct disease entity of small vessel vasculitis. Previous research has been challenged by low disease incidence, and conflicting results pertaining to risk of death and ESRD. Accordingly, we examined incidence and outcomes based on data from multiple Danish nationwide healthcare registries. Method: All patients with incident positive anti-GBM serology between 2013 and 2018 were identified from 4 of 5 administrative regions in Denmark. Serological positivity was defined as serum concentrations exceeding the upper reference level. Double positivity was defined by either presence of PR3-ANCA or MPO-ANCA within a margin of 30 days from inclusion. Baseline information and clinical diagnoses defined by administrative diagnoses were subsequently ascertained by cross-referencing of data from the Danish nationwide administrative registries. Risks of death or ESRD were compared based on adjusted absolute risk ratios (ARR) and cumulative incidences assessed based on the Aalen-Johansen estimator. Results: A total of 118 patients with positive anti-GBM serology (4.4 cases/million/year) were identified. Concomitant ANCA serology was tested in 104 (88.1%), with 39 patients (37.5%) demonstrating double positivity (20 and 13 patients positive for PR3-ANCA (51.3%) and MPO-ANCA (33.3%), respectively, and 6 patients positive for all autoantibodies (5.8%)). Mean follow-up for the total study population was 1.9 (SD ±1.6) years. Compared with patients positive for anti-GBM alone, double positivity was associated with female gender (61.5%, P=0.02), and more frequent employment of plasma exchange (53.8%, P=0.04). No difference was observed with regard to age (63.2 years [SD 18.5], P=0.60), and mean anti-GBM concentration (125.5 [SD 182.4] IU/L vs. 108.9 [SD 212.7] IU/L, P=0.30). One-year mortality was 17.7% (n=14) in patients positive for anti-GBM alone, and 28.2% (n=11) in patients positive for both anti-GBM and ANCA. Double positive serology was associated with increased risk of death (ARR 2.10 [CI 1.20-3.65], P=0.009) (figure); however, there was no difference in risk of ESRD (ARR 1.28 [0.66-2.50], P=0.46). Of all identified patients, only 32 (27%) were diagnosed with anti-GBM disease according to ICD10 code (1.2 cases/million/year). In patients with confirmatory serology and ICD-10 code, 13 (40%) had double positive serology (46.2% PR3-ANCA and 53.8% MPO-ANCA). In the subset of patients with confirmatory ICD-10 code, double positivity was associated with male gender (63.2%, P=0.07), numerical lower mean age (56.1 [SD 25.2], P=0.50), and increased mean anti-GBM concentration (333.3 [SD 278.7] vs 150.7 [SD 146.5] P= 0.026). There was no difference in risk of death or ESRD between the two groups. Conclusion: Double positivity of anti-GBM and ANCA serology plausibly defines a distinct group of patients and is associated with a higher risk of death. While the association between an ICD10-confirmed diagnosis of anti-GBM disease and anti-GBM serology is well established, the significance of serology alone remains uncertain. Disclosures: None Figure. Mortality in patients with single anti-GBM antibodies and double positive serolog

Supplementary Material for: The Association between Physical Morbidity and Subtypes of Severe Depression

Background: Physical illness and depression are related, but the association between specific physical diseases and diagnostic subtypes of depression remains poorly understood. This study aimed to clarify the relationship between a number of physical diseases and the nonpsychotic and psychotic subtype of severe depression. Methods: This is a historical prospective cohort study. The study population consisted of all patients diagnosed with ICD-10 severe depression, either nonpsychotic or psychotic subtype, in Danish psychiatric hospitals between 1994 and 2008. The patients’ history of physical disease was assessed using the Danish National Patient Register. Using logistic regression it was investigated whether specific physical diseases were associated with relative increased risk for subsequent development of either the nonpsychotic or psychotic depressive subtype. Results: A total of 24,173 patients with severe depression were included in the study. Of those, 8,260 (34%) were of the psychotic subtype. A history of the following physical diseases, as opposed to their absence, increased the relative risk for subsequent development of the nonpsychotic compared to the psychotic depressive subtype [adjusted incidence odds ratio (AIOR) nonpsychotic vs. psychotic]: ischemic heart disease (AIOR = 1.3, p &lt; 0.001), hypertension (AIOR = 1.2, p = 0.008), stroke (AIOR = 1.2, p = 0.042) and chronic lower pulmonary disease (AIOR = 1.2, p = 0.005). The total load of physical disease also increased the relative risk of nonpsychotic depression [AIOR = 1.05 (per disease), p = 0.001]. Conclusions: This study revealed that, in severe depression, a history of physical disease increased the relative risk of the nonpsychotic rather than the psychotic subtype

Psychosocial health in pregnancy and postpartum among women living with - and without HIV and non-pregnant women living with HIV living in Nordic countries – Results from a longitudinal survey study

Abstract Background The success of antiretroviral therapy has normalized pregnancy among women living with HIV (WWH) with a very low risk of perinatal transmission of HIV. Despite these advances, WWH still face complex medical and psychosocial issues during pregnancy and postpartum. The aim of this study was to assess differences in psychosocial health outcomes between pregnant WWH, non-pregnant WWH, and pregnant women without HIV, and further identify factors associated with probable depression in the third trimester and postpartum. Methods In a longitudinal survey study, participants were included from sites in Denmark, Finland, and Sweden during 2019–2020. Data was collected in the 3rd trimester, 3 and 6 months postpartum using standardized questionnaires assessing depression, perceived stress, loneliness, and social support. Mixed regression models were used to assess changes over time within and between groups. Logistic regression models were used to identify factors associated with depression in pregnancy and postpartum. Results A total of 47 pregnant WWH, 75 non-pregnant WWH, and 147 pregnant women without HIV were included. The prevalence of depression was high among both pregnant and non-pregnant WWH. There was no significant difference between pregnant and non-pregnant WWH in depression scores, perceived stress scores, or social support scores at any time point. Compared to pregnant women without HIV, pregnant WWH reported worse outcomes on all psychosocial scales. Social support and loneliness were associated with an increased odds of depressive symptoms in the adjusted analysis. Conclusions A high burden of adverse psychosocial outcomes was observed in both pregnant and non-pregnant women living with HIV compared to pregnant women without HIV. Loneliness and inadequate social support were associated with increased odds of depression in pregnancy and should be a focus in future support interventions