Prognosis after Intensive Care for COPD Exacerbation in Relation to Long-Term Oxygen Therapy: A Nationwide Cohort Study.

Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p < 0.001) and one-year mortality (70% vs. 43%; p < 0.001). Multivariable logistic and Cox regression models adjusted for age, sex and SAPS3 score confirmed higher mortality in LTOT, odds ratio for 30-day mortality was 1.8 ([95% confidence interval] 1.5-2.3) and hazard ratio for one-year mortality was 1.8 (1.6-2.0). In summary, although need for LTOT is a negative prognostic marker for survival after AECOPD requiring intensive care, a majority of patients with LTOT survived the AECOPD and 30% were alive after one year.

Oral Fluoroquinolone Use and the Risk of Acute Liver Injury: A Nationwide Cohort Study.

BACKGROUND: Antibiotics are considered to be among the most frequent causes of drug-related acute liver injury (ALI). Although many ALIs have mild and reversible clinical outcomes, there is substantial risk of severe reactions leading to acute liver failure, need for liver transplant, and death. Recent studies have raised concerns of hepatotoxic potential related to the use of fluoroquinolones. METHODS: This study examined the risk of ALI associated with oral fluoroquinolone treatment compared with amoxicillin (419 930 courses, propensity score matched 1:1). The information on drug use was collected from a national, registry-based cohort derived from all Swedish adults aged 40-85 years. RESULTS: During a follow-up period of 60 days, users of oral fluoroquinolones had a >2-fold risk of ALI compared to users of amoxicillin (hazard ratio, 2.32 [95% confidence interval {CI}, 1.01-5.35). The adjusted absolute risk difference for use of fluoroquinolones as compared to amoxicillin was 4.94 (95% CI, .04-16.3) per 1 million episodes. CONCLUSIONS: In this propensity score-matched study, fluoroquinolone treatment was associated with an increased risk of ALI in the first 2 months after starting treatment.

Prevalence and factors associated with faecal carriage of extended-spectrum ß-lactamase-producing Enterobacterales among peripartum women in the community in Cambodia.

BACKGROUND: In Southeast-Asia, where many conditions associated with dissemination of ESBL-producing Enterobacterales (ESBL-E) in the community are met, data from the community are scarce but show high ESBL-E carriage prevalence. Maternal ESBL-E colonization is considered a risk factor for neonatal colonization, which is the first step towards developing neonatal sepsis. Despite this, ESBL-E carriage prevalence and its risk factors during pregnancy or postpartum remain undefined in Southeast-Asia. OBJECTIVES: To estimate the prevalence of ESBL-E faecal colonization among peripartum women in the community of an urban and a rural area in Cambodia, to investigate ESBL-E genomic characteristics and to identify associated risk factors. METHODS: Epidemiological data and faecal samples from 423 peripartum women were collected in an urban and rural areas in Cambodia (2015-16). Bacterial cultures, antibiotic susceptibility tests and ESBL gene sequencing were performed. Risk factor analysis was conducted using logistic regression. RESULTS: The prevalence of ESBL-E faecal carriage was 79.2% (95% CI 75.0%-82.8%) among which Escherichia coli (n = 315/335, 94.0%) were most frequent. All isolates were multidrug resistant. Among 318 ESBL-E, the genes most frequently detected were blaCTX-M-15 (41.5%), blaCTX-M-55 (24.8%), and blaCTX-M-27 (15.1%). Low income, undernutrition, multiparity, regular consumption of pork, dried meat, and raw vegetables, were associated with ESBL-E faecal carriage. CONCLUSIONS: The high prevalence of ESBL-E carriage observed among peripartum women in Southeast-Asia and the identified associated factors underline the urgent need for public health measures to address antimicrobial resistance, including a 'One Health' approach.

A retrospective cohort study of the effect of SARS-CoV-2 point of care rapid RT-PCR at the Emergency Department on targeted admission.

BACKGROUND: To prevent nosocomial transmission of SARS-CoV-2, infection prevention control (IPC) measures are implemented for patients with symptoms compatible with COVID-19 until reliable test results are available. This delays admission to the most appropriate ward based on the medical condition. SARS-CoV-2 rapid antigen detection (RAD) tests and point-of-care (POC) rapid RT-PCR (VitaPCR) were introduced at emergency department (ED) at Skåne University Hospital, Sweden in late 2020, but the consequence on patient flow and targeted admission is unknown. METHODS: Patients presenting at the emergency department of a referral hospital (N = 2940) between 13-Nov-2020 and 12-Jan-2021 were included. The study period was delimited into three periods by the introduction of RAD tests and the VitaPCR. Participant data was collected from hospital records, and outcome variables were Length-of-Stay (LoS), intrahospital transfers and targeted admission to COVID-19 ward. RESULTS: Compared to baseline (RT-PCR only), RAD tests reduced ED Length-of-Stay (LoS) for participants with positive tests. Negative VitaPCR results reduced mean hospital LoS by 1.5 (95% CI 0.3-2.7) days and admissions to COVID-19 wards from 34.5 (95% CI 28.9-40.5) to 14.7 (95% CI 11.1-19.1) per 100 admissions and reduced transfers between hospital wards in the first 5 days from 50.0 (95% CI 45.0-55.0) to 34.0 (95% CI 30.3-37.9) per 100 admissions. CONCLUSION: RAD tests enabled prompt detection of SARS-CoV-2 infection which had pronounced effects on LoS at the ED. Negative VitaPCR enabled cessation of IPC measures and a negative test was associated with increased targeted admissions, reduced intrahospital transfers and shorter LoS at the hospital.

Persistent Aspergillus fumigatus infection in cystic fibrosis: impact on lung function and role of treatment of asymptomatic colonization-a registry-based case-control study.

BACKGROUND: Aspergillus fumigatus is the most common filamentous fungus isolated from the airways of people with cystic fibrosis (CF). The aim of this study was to investigate how chronic A. fumigatus colonization affects lung function in people with CF, to identify risk factors for colonization, and to evaluate antifungal treatment of asymptomatic Aspergillus colonization. METHODS: Data from 2014-2018 was collected from the Swedish CF registry and medical records. Baseline data before the start of A. fumigatus colonization was compared with the two succeeding years to evaluate how colonization and treatment affected lung function and other clinical aspects. RESULTS: A total of 437 patients were included, of which 64 (14.6%) became colonized with A. fumigatus during the study period. Inhaled antibiotics was associated with A. fumigatus colonization (adjusted OR 3.1, 95% CI 1.6-5.9, p < 0.05). Fungal colonization was not associated with a more rapid lung function decline or increased use of IV-antibiotics compared to the non-colonized group, but patients with A. fumigatus had more hospital days, a higher increase of total IgE, and higher eosinophil counts. In the Aspergillus group, 42 patients were considered to be asymptomatic. Of these, 19 patients received antifungal treatment. Over the follow up period, the treated group had a more pronounced decrease in percent predicted Forced Expiratory Volume in one second (ppFEV1) compared to untreated patients (- 8.7 vs - 1.4 percentage points, p < 0.05). CONCLUSION: Inhaled antibiotics was associated with A. fumigatus colonization, but no association was found between persistent A. fumigatus and subsequent lung function decline. No obvious benefits of treating asymptomatic A. fumigatus colonization were demonstrated.

A regression discontinuity analysis of the social distancing recommendations for older adults in Sweden during COVID-19.

BACKGROUND: This article investigates the impact of a non-mandatory and age-specific social distancing recommendation on isolation behaviours and disease outcomes in Sweden during the first wave of the coronavirus disease 2019 (COVID-19) pandemic (March to July 2020). The policy stated that people aged 70 years or older should avoid crowded places and contact with people outside the household. METHODS: We used a regression discontinuity design-in combination with self-reported isolation data from COVID Symptom Study Sweden (n = 96 053; age range: 39-79 years) and national register data (age range: 39-100+ years) on severe COVID-19 disease (hospitalization or death, n = 21 804) and confirmed cases (n = 48 984)-to estimate the effects of the policy. RESULTS: Our primary analyses showed a sharp drop in the weekly number of visits to crowded places (-13%) and severe COVID-19 cases (-16%) at the 70-year threshold. These results imply that the age-specific recommendations prevented approximately 1800-2700 severe COVID-19 cases, depending on model specification. CONCLUSIONS: It seems that the non-mandatory, age-specific recommendations helped control COVID-19 disease during the first wave of the pandemic in Sweden, as opposed to not implementing a social distancing policy aimed at older adults. Our study provides empirical data on how populations may react to non-mandatory, age-specific social distancing policies in the face of a novel virus.

COVID-19 vaccine effectiveness against severe disease from SARS-CoV-2 Omicron BA.1 and BA.2 subvariants - surveillance results from southern Sweden, December 2021 to March 2022.

We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.

Risk of severe COVID-19 from the Delta and Omicron variants in relation to vaccination status, sex, age and comorbidities - surveillance results from southern Sweden, July 2021 to January 2022.

We compared the risk of severe COVID-19 during two periods 2021 and 2022 when Delta and Omicron, respectively, were the dominating virus variants in Scania county, Sweden. We adjusted for differences in sex, age, comorbidities, prior infection and vaccination. Risk of severe disease from Omicron was markedly lower among vaccinated cases. It was also lower among the unvaccinated but remained high (> 5%) for older people and middle-aged men with two or more comorbidities. Efforts to increase vaccination uptake should continue.

Proton-Pump Inhibitor Use and the Risk of Community-Associated Clostridium difficile Infection.

BACKGROUND: Proton-pump inhibitors (PPIs) have been reported to increase the risk of community-associated Clostridium difficile infection (CDI), but the association remains disputed. METHODS: A nationwide cohort study among adults in Denmark, 2010-2013, linking register data on C. difficile testing, filled prescriptions, and patient characteristics. All incident episodes of community-associated CDI (ie, positive culture, molecular assay, or toxin test in individuals without previous hospitalization in the prior 12 weeks and without a positive test for C. difficile in the prior 8 weeks) were identified in the Danish National Microbiological Database. Self-controlled case-series analyses were used to estimate incidence rate ratios (IRRs) for community-associated CDI, comparing periods with and without exposure to PPIs. By design, models took fixed confounders such as chronic disease, genetics, and socioeconomic status into account; further, time-varying confounders, including hospital stay and antibiotic and corticosteroid use were adjusted for. RESULTS: 3583 episodes of community-associated CDI were identified, of which 964 occurred during current use of PPIs, 324 occurred 0-6 months after treatment cessation, 123 occurred 6-12 months after treatment cessation, and 2172 occurred during time periods without use of PPIs. The adjusted IRR was 2.03 (95% confidence interval, 1.74-2.36), comparing use of PPI with nonuse. The increased risk remained elevated in later time periods: 1.54 (1.31-1.80) for 0-6 months, 1.24 (1.00-1.53) for 6-12 months after current use. CONCLUSIONS: Use of PPIs was associated with moderately increased risk of community-associated CDI. The risk remained elevated up to 1 year after PPI treatment had ended.

Short time to blood culture positivity in Enterococcus faecalis infective endocarditis.

Time to blood culture positivity (TTP) is an indirect measure of bacterial concentration in blood. A short TTP has been linked to the presence of infective endocarditis (IE) and to poor prognosis in Staphylococcus aureus bacteremia. We analyze factors influencing TTP in bacteremia with Enterococcus faecalis. This retrospective observational study of medical records included adults diagnosed with monomicrobial E. faecalis bacteremia between 2015 and 2018 in the Skåne region (Sweden). For each episode, the shortest TTP was recorded. Median TTP was compared between patients grouped based on age, sex, comorbidity, site of acquisition, and focus of infection. Using a dichotomized TTP (shorter or longer than 12 h), a multivariable logistic regression for factors associated to TTP was performed. The association between TTP and IE or mortality was evaluated. Three hundred sixty-seven episodes with monomicrobial E. faecalis bacteremia with the corresponding TTP were identified. Median TTP for the entire cohort was 11.6 (IQR 9.9-14.1) h and a significantly shorter TTP was noted for episodes which represented IE (n = 55, 9.4 (IQR 6.4-10.6) h). Only IE remained associated with a short TTP (≤ 12 h) in binary logistic regression analysis. Factors associated with IE were investigated and TTP was associated with IE also when adjusted for age, gender, comorbidity, and nosocomial acquisition. There was no association between TTP and mortality. A low TTP is associated with IE in E. faecalis bacteremia and could be used as a help in determining the need for echocardiography in patients with this condition.

Streptococcus bovis-bacteremia: subspecies distribution and association with colorectal cancer: a retrospective cohort study.

This study aimed to describe the incidence of Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteremia, distribution of the SBSEC subspecies, and their respective association with colorectal cancer (CRC). A population-based retrospective cohort study of all episodes of SBSEC-bacteremia from 2003 to 2018 in Skåne Region, Sweden. Subspecies was determined by whole-genome sequencing. Medical charts were reviewed. The association between subspecies and CRC were analysed using logistic regression. In total 266 episodes of SBSEC-bacteremia were identified and the average annual incidence was 2.0 per 100 000 inhabitants. Of the 236 isolates available for typing, the most common subspecies was S. gallolyticus subsp. pasteurianus 88/236 (37%) followed by S. gallolyticus subsp. gallolyticus 58/236 (25%). In order to determine the risk of cancer following bacteremia, an incidence cohort of 174 episodes without a prior diagnosis of CRC or metastasised cancer was followed for 560 person-years. CRC was found in 13/174 (7%), of which 9 (69%) had S. gallolyticus subsp. gallolyticus-bacteremia. In contrast to other European studies, S. gallolyticus subsp. pasteurianus was the most common cause of SBSEC-bacteremia. CRC diagnosis after bacteremia was strongly associated with S. gallolyticus subsp. gallolyticus-bacteremia. Identification of SBSEC subspecies can guide clinical decision-making regarding CRC work-up following bacteremia.

Isolation of Nontuberculous Mycobacteria in Southeast Asian and African Human Immunodeficiency Virus-infected Children With Suspected Tuberculosis.

We enrolled 427 human immunodeficiency virus-infected children (median age, 7.3 years), 59.2% severely immunodeficient, with suspected tuberculosis in Southeast Asian and African settings. Nontuberculous mycobacteria were isolated in 46 children (10.8%); 45.7% of isolates were Mycobacterium avium complex. Southeast Asian origin, age 5-9 years, and severe immunodeficiency were independently associated with nontuberculous mycobacteria isolation. CLINICAL TRIALS REGISTRATION: NCT01331811.

Long-Term Risk of Cardiovascular Death With Use of Clarithromycin and Roxithromycin: A Nationwide Cohort Study.

Recent studies have raised concern that macrolide antibiotics may be associated with an increased long-term risk of cardiovascular death. We examined the 1-year risk associated with treatment with clarithromycin (n = 187,887) or roxithromycin (n = 698,899) compared with penicillin V (n = 3,473,081), matched 1:4 on propensity score, in a nationwide, registry-based cohort study in Danish outpatients, 1997-2011. Among clarithromycin courses, the rate ratio for cardiovascular death was 1.24 (95% confidence interval (CI): 0.96, 1.59). Among roxithromycin courses, the rate ratio was 0.99 (95% CI: 0.86, 1.16). In analyses by time after treatment start, the rate ratio associated with clarithromycin was 1.66 (95% CI: 0.98, 2.79) during days 0-7. This was attenuated in later time periods (days 8-89, rate ratio = 1.30, 95% CI: 0.88, 1.94; and days 90-364, rate ratio = 0.96, 95% CI: 0.63, 1.47). For roxithromycin, the rate ratios were 0.88 (95% CI: 0.59, 1.32) during days 0-7, 1.17 (95% CI: 0.92, 1.48) during days 8-89, and 0.88 (95% CI: 0.70, 1.10) during days 90-364. We found no increased risk of cardiovascular death in a general outpatient population. With clarithromycin, we observed a transient increased risk during days 0-7 after treatment start, which corresponds to the period of active treatment. This association was absent in later time periods, which is consistent with no long-term toxicity resulting in cardiovascular death.

Heparin-binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients.

Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1ß, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in bronchoalveolar lavage fluid (BALF) as potential biomarkers for pulmonary infection in lung-transplanted patients. One hundred thirteen BALF samples from 29 lung transplant recipients were collected at routine scheduled bronchoscopies at 3 and 6 months, or on clinical indication. Samples were classified into no, possible, probable, or definite infection at the time of sampling. Rejection was defined by biopsy results. HBP, lysozyme, and cytokines were analyzed in BALF and correlated to likelihood of infection and rejection. All biomarkers were significantly increased in BALF during infection, whereas patients with rejection presented low levels that were comparable to noninfection samples. HBP, IL-1ß, and IL-8 were the best diagnostic markers of infection with area under the receiver-operating characteristic curve values of 0.88, 0.91, and 0.90, respectively. In conclusion, HBP, IL-1ß, and IL-8 could be useful diagnostic markers of pulmonary infection in lung-transplanted patients.

Microbiological findings in bronchoalveolar lavage fluid from lung transplant patients in Sweden.

BACKGROUND: Lung transplant patients experience a high risk of airway infections and microbial colonization of the lung due to constant exposure to the environment through inhaled microorganisms, denervation, reduced ciliary transport, and decreased cough. METHODS: In this nationwide prospective study on Swedish lung transplant patients, we evaluated the microbiological panorama of bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained the first year after lung transplantation (LTx). Differences in microbiological findings depending of concomitant signs of infection and background factors were assessed. RESULTS: A total of 470 bronchoscopies from 126 patients were evaluated. Sixty-two percent (n = 293) of BALF samples had positive microbiological finding(s). Forty-six percent (n = 217) had bacterial growth, 29% (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of BALF samples (n = 181), a single microbe was found, whereas a combination of bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most common microbiological findings were Candida albicans, Pseudomonas aeruginosa and coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients, respectively). Microbiological findings were similar in BALF from patients with and without signs of lung infection and the frequency of multidrug resistant (MDR) bacteria was low. No significant association was found between background factors and time to first lung infection. CONCLUSION: This study gives important epidemiologic insights and reinforces that microbiological findings have to be evaluated in the light of clinical symptoms and endobronchial appearance in the assessment of lung infections in lung transplant patients.

Fever in the Emergency Department Predicts Survival of Patients With Severe Sepsis and Septic Shock Admitted to the ICU.

OBJECTIVES: To study the prognostic value of fever in the emergency department in septic patients subsequently admitted to the ICU. DESIGN: Observational cohort study from the Swedish national quality register for sepsis. SETTING: Thirty ICU's in Sweden. PATIENTS: Two thousand two hundred twenty-five adults who were admitted to an ICU within 24 hours of hospital arrival with a diagnosis of severe sepsis or septic shock were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Body temperature was measured and classified according to four categories (< 37°C, 37-38.29°C, 38.3-39.5°C, ≥ 39.5°C). The main outcome was in-hospital mortality. Odds ratios for mortality according to body temperature were estimated using multivariable logistic regression. Subgroup analyses were conducted according to age, sex, underlying comorbidity, and time to given antibiotics. Overall mortality was 25%. More than half of patients had a body temperature below 38.3°C. Mortality was inversely correlated with temperature and decreased, on average, more than 5% points per °C increase, from 50% in those with the lowest temperatures to 9% in those with the highest. Increased body temperature in survivors was also associated with shorter hospital stays. Patients with fever received better quality of care, but the inverse association between body temperature and mortality was robust and remained consistent after adjustment for quality of care measures and other factors that could have confounded the association. Among vital signs, body temperature was best at predicting mortality. CONCLUSIONS: Contrary to common perceptions and current guidelines for care of critically ill septic patients, increased body temperature in the emergency department was strongly associated with lower mortality and shorter hospital stays in patients with severe sepsis or septic shock subsequently admitted to the ICU.

Incidence of stroke and stroke subtypes in chronic obstructive pulmonary disease.

It is uncertain whether the incidence of stroke is increased in patients with chronic obstructive pulmonary disease (COPD), and whether COPD is associated with all subtypes of stroke (i.e. ischemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage). We evaluated the association between COPD and incidence of stroke in a nation-wide cohort study. All individuals between 40 and 84 years of age, hospitalised for COPD between 1987 and 2003 in Sweden were identified in the Swedish hospital discharge register. For each COPD patient (n = 103,419), one reference individual was randomly selected from the general population matched for year of birth, sex and county of residence. After excluding subjects with prior stroke, incidence rates during 10 years follow-up were calculated. Hazard ratios (HR) for stroke comparing COPD patients with reference subjects were estimated using Cox regression adjusting for demographics and comorbidities. Incidence of all-cause stroke (n events = 17,402) was significantly increased in COPD patients compared to reference individuals (HR 1.24, 95 % CI 1.19-1.28), especially during the first 2 years after COPD diagnosis (HR 1.46, 1.37-1.55). Incidences of ischemic stroke (HR 1.20, 1.15-1.25), intracerebral haemorrhage (HR 1.29, 1.16-1.43) and subarachnoid haemorrhage (HR 1.46, 1.16-1.85) were all increased in COPD patients. Incidences of all stroke subtypes are increased in COPD, especially during the first years after COPD diagnosis. The association was independent of several comorbidities, although residual confounding from smoking and hypertension cannot be excluded. A global evaluation of stroke risk factors seems warranted in patients with COPD.

Recurrent erysipelas--risk factors and clinical presentation.

BACKGROUND: Erysipelas is a common infection that often recurs, but the impact of specific risk factors for reoccurrence remains elusive. In the present study we aimed at clarifying predisposing conditions for reoccurrence. METHODS: Medical records were reviewed from all patients ≥18 years of age diagnosed with erysipelas at the Department of Infectious Diseases at Skåne University Hospital, Sweden, from January 2007 to February 2011. 502 patients were included, of which 357 were single episode erysipelas and 145 had recurrent erysipelas. These two groups were compared regarding underlying conditions and clinical presentation. RESULTS: Erysipelas in the lower limbs had the greatest propensity of recurrence. The associations between underlying conditions and recurrence were largely depending on the site of erysipelas. Overall, the most prominent risk factor for recurrence was lymphedema and other conditions causing a chronic impairment of the defence against microbes. Conditions temporarily disrupting the skin barrier (e.g. a local wound or toe web intertrigo), although likely being risk factors for erysipelas per se, did not seem to predispose to repeated episodes. Individuals with recurrent erysipelas tended to seek medical attention earlier, and were less likely to be hospitalized or receive intravenous antibiotics, but there was no evidence of any difference in inflammatory reaction when taking confounding factors into account. CONCLUSIONS: In this large cross-sectional study of over 500 patients with erysipelas, lymphedema was the most prominent risk factors for recurrence although the distribution of predisposing conditions varies depending on the site of erysipelas.