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Introduction The optimal duration of antibiotic therapy for community-acquired pneumonia (CAP) is unsettled. Short-course therapy has proved successful in clinical trials but is not yet implemented in everyday clinical practice. Validation of results from randomised controlled trials is crucial to evaluate existing evidence and provide clinicians with assurance of using new treatment strategies. In a pragmatic framework, we aim to assess the use of short-course antibiotic therapy guided by the onset of clinical stability in patients hospitalised with CAP.Methods and analysis This study is a randomised controlled trial with a non-inferiority design that will examine the efficacy of short-course antibiotic therapy in patients hospitalised with CAP. From six hospitals across Denmark, we plan to enrol 564 patients between 2019 and 2024. Within 3–5 days after initiating antibiotic therapy, participants will be randomised 1:1 to parallel treatment arms: (1) short-course antibiotic therapy of 5 days or (2) antibiotic therapy of at least 7 days. The primary outcome will be 90-day readmission-free survival and will be estimated as an absolute risk difference with a predefined non-inferiority margin of −6%. Secondary outcomes will comprise other safety measures including new antibiotics, adverse events, length of hospital stay and postdischarge outpatient visits. Both intention-to-treat and per-protocol analyses will be performed.Ethics and dissemination This study has been approved by the Health Research Ethics Committee of the Capital Region of Denmark (identifier number: H-19014479). Trial data will be made available in anonymous form when the trial has ended.Trial registration number NCT04089787, ClinicalTrials.Gov.

Introduction Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.Methods and analysis Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.Ethics and dissemination The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.Trial registration number ClinicalTrials.Gov:NCT04291768.

Purpose The ENFORCE cohort is a national Danish prospective cohort of adults who received a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine as part of the Danish National SARS-CoV-2 vaccination programme. It was designed to investigate the long-term effectiveness, safety and durability of SARS-CoV-2 vaccines used in Denmark.Participants A total of 6943 adults scheduled to receive a SARS-CoV-2 vaccine in the Danish COVID-19 vaccination programme were enrolled in the study prior to their first vaccination. Participants will be followed for a total of 2 years with five predetermined follow-up visits and additional visits in relation to any booster vaccination. Serology measurements are performed after each study visit. T-cell immunity is evaluated at each study visit for a subgroup of 699 participants. Safety information is collected from participants at visits following each vaccination. Data on hospital admissions, diagnoses, deaths and SARS-CoV-2 PCR results are collected from national registries throughout the study period. The median age of participants was 64 years (IQR 53–75), 56.6% were women and 23% were individuals with an increased risk of a serious course of COVID-19. A total of 340 (4.9%) participants tested positive for SARS-CoV-2 spike IgG at baseline.Findings to date Results have been published on risk factors for humoral hyporesponsiveness and non-durable response to SARS-CoV-2 vaccination, the risk of breakthrough infections at different levels of SARS-CoV-2 spike IgG by viral variant and on the antibody neutralising capacity against different SARS-CoV-2 variants following primary and booster vaccinations.Future plans The ENFORCE cohort will continuously generate studies investigating immunological response, effectiveness, safety and durability of the SARS-CoV-2 vaccines.Trial registration number NCT04760132.

Objective: The success of antiretroviral therapy has resulted in the normalization of pregnancy among women living with HIV and a very low risk of perinatal transmission of HIV. Despite these advances, women living with HIV still face complex medical and psychosocial issues during pregnancy. The purpose of this study is to describe experiences of pregnancy and the relevance of social support among women living with HIV in Nordic countries. Methods: This qualitative study examined data from pregnant women living with HIV from sites in Denmark, Sweden and Finland from 2019 to 2020. Data were collected in the third trimester via individual interviews using a hybrid, narrative/semistructured format. The transcribed interviews were analyzed using narrative thematic analysis. Results: In total, 31 women living with HIV were enrolled, of whom 61% originated from an African country and 29% from a Nordic country. The analysis generated four primary narrative themes: just a normal pregnancy, unique considerations and concerns, interactions with healthcare, and social support. Women living with HIV have a strong desire to have normal pregnancies and to be treated like any other pregnant woman. However, this normality is fragile, and being pregnant and living with HIV does come with unique considerations and concerns, such as fear of transmission, antiretroviral therapy, and the need for specialized care, which are fundamental to the women’s experiences. Interactions with healthcare providers and social support influence their experiences in both positive and negative ways. Conclusion: The findings emphasize a sense of normality in pregnancy among women living with HIV. However, pregnancy does come with unique considerations and concerns, which highly influence the women’s experience of pregnancy. Healthcare providers should focus on person-centered care, ensuring continuity and that women living with HIV do not feel discriminated against throughout their pregnancy.

Purpose The purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark and their children, in the era of antiretroviral therapy and other interventions for treatment and prophylaxis.Participants All WLWH giving birth to one or more children in Denmark after 31 December 1999 are included, with consecutive ongoing enrolment, if they are living with HIV and pregnant, or if they are diagnosed with HIV in relation to pregnancy, delivery or shortly after delivery.Findings to date DHBC has been used to describe trends in the management of pregnancies in WLWH and their outcomes on a nationwide basis, mode of delivery and predictors of emergency caesarean section as well as risk factors during pregnancy in WLWH for birth-related complications compared with women from the general population (WGP). We have found that HIV-exposed, but uninfected (HEU) children born to WLWH had a lower median birth weight and gestational age and were at higher risk of intrauterine growth retardation than children born to WGP. We have investigated risk of in-hospital admission and use of antibiotics during the first 4 years of life among HEU children and showed that HEU children had an increased risk of overall hospital admission compared with a matched control group of unexposed children.Further, we compared anthropometric outcomes in children with a matched control group of children not exposed to HIV.Future plans To continuously investigate the significance of HIV infection and antiretroviral therapy in pregnancy and after delivery in WLWH in Denmark and their HEU children and compare these findings with children born to WGP.

BackgroundTuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.Methods and findingsAdult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30-43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%-80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%-50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%-74.6%), and that of LF-LAM 31.4% (95% CI 19.1%-43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%-93.6%), compared to 56.0% (95% CI 43.9%-64.9%) for LF-LAM. In patients with CD4 count 101-200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%-71.9%), compared to 25.3% (95% CI 15.8%-34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%-53.9%), compared to 10.9% (95% CI 5.2%-18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%-93.7%), and that of LF-LAM 95.3% (95% CI 92.2%-97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.ConclusionsIn this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.

OBJECTIVES:Mortality from tuberculosis (TB) has been declining since 2000, nevertheless there is still a significant number of patients who die before or during TB treatment. The aims were to examine and describe predictors associated with TB related mortality. METHODS:Patients notified with TB from 2009 though 2014 in Denmark were included. Data were extracted from national registers and patient records were examined for clinical information and treatment outcome. Cox proportional hazards regression was used to examine TB related mortality. RESULTS:A total of 2131 cases were identified, 141 (6.6%) patients died before or during TB treatment. TB related mortality accounted for 104 cases (73.8%) and decreased significantly from 6.7% to 3.2% (p = .04) during the study period. Within 1 months of diagnosis, 49% of TB related deaths had occurred. The strongest risk factors present at time of diagnosis, associated with TB related mortality, were: age > 70 years, Charlson comorbidity index > 1, alcohol abuse, weight loss, anemia, and C-reactive protein > 100 mg/L (p < .05). CONCLUSION:The majority of TB related deaths occurred soon after diagnosis, emphasizing that TB patients identified to have a high risk of mortality should be closely monitored before and during the intensive treatment period to improve their outcomes.

Introduction The success of combination antiretroviral therapy has decreased the risk of perinatal HIV transmission and normalised pregnancy in women living with HIV (WLWH). Despite these advances, WLWH still face complex medical and psychosocial issues during pregnancy and postpartum, and there is a gap of knowledge on the experiences of becoming and being a mother living with HIV in today’s context. The overall aim of this study is to investigate psychosocial outcomes and experiences of WLWH in Scandinavia during pregnancy and early motherhood.Methods and analysis This is a multicentre longitudinal convergent mixed methods study consisting of a quantitative survey study, a qualitative interview study and a mixed methods analysis. The survey study aims to examine psychosocial outcomes of WLWH across the pregnancy – postpartum trajectory. Participants are pregnant WLWH living in Scandinavia. Two control groups of HIV-negative pregnant women and non-pregnant WLWH are also included. Data is collected in the third trimester, 3 and 6 months postpartum using standardised questionnaires. Statistical analysis will assess changes over time and identify predictors of adverse outcomes. The interview study seeks to understand experiences of pregnancy and becoming a mother while living with HIV. Pregnant WLWH who are enrolled in the survey study will be asked to participate in individual interviews in the third trimester and 6 months postpartum. Data will be analysed using narrative analysis. The survey and interview results will be merged in a mixed methods analysis to assess confirmation, expansion or discordance between the data sets.Ethics and dissemination Approval from the Danish Data Protection Agency (VD-2018–253), and the Finnish and Swedish Ethics Committees have been obtained (HUS/1330/2019 and Dnr: 2019–04451, respectively). Study results will be disseminated to patient organisations, through publications in peer-reviewed journals and at scientific conferences.

Evidence on mortality rates and causes of death associated with extrapulmonary nontuberculous mycobacteria (NTM) infection is limited. This nationwide register-based study in Denmark used diagnostic codes to match adult patients with extrapulmonary NTM infection 1:4 to controls. During 2000–2017, we identified 485 patients, who had significantly more comorbidities than controls. The 5-year mortality rate for patients was 26.8% (95% CI 23.1%–31.0%) and for controls, 10.9% (95% CI 9.6%–12.4%). The median age at death was 76 (interquartile range 63–85) years for patients and 84 (interquartile range 73–90) years for controls. The adjusted hazard rate of death for patients was 1.34 (95% CI 1.10–1.63; p = 0.004). Patients and controls mainly died of cardiovascular disease and solid malignant neoplasms. Hematologic malignancies and HIV were more frequently causes of death in patients. Mortality rates are substantial among patients with extrapulmonary NTM infection, predominantly caused by underlying conditions.

Abstract Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72–2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46–1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.

Worldwide, millions of persons have received multiple COVID-19 vaccinations and subsequently recovered from SARS-CoV-2 Omicron breakthrough infections. In 2 small, matched cohorts (n = 12, n = 24) in Denmark, we found Omicron BA.1/BA.2 breakthrough infection after 3-dose BNT162b2 vaccination provided improved Omicron BA.5 neutralization over 3-dose vaccination alone.

The SARS-CoV-2 Omicron variant BA.2 sublineage is rapidly replacing earlier Omicron lineages, suggesting BA.2 has increased vaccine evasion properties. We measured neutralization titers of authentic BA.1 and BA.2 isolates in serum samples from persons who received the BNT162b2 booster vaccine. All samples neutralized BA.1 and BA.2 at equal median values.