A genome-wide association study of susceptibility to upper urinary tract infections.

BACKGROUND: Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). METHODS: We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. RESULTS: One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1-AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively). CONCLUSIONS: We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.

Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trøndelag Health Study in Norway.

PURPOSE: Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. METHODS: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. RESULTS: Participants with eGFR < 30 ml/min/1.732 had HR 3.35 for BSI (95% confidence intervals (CI) 2.12-5.3) and HR 2.94 for sepsis (95% CI 1.82-4.8) compared to normal eGFR (≥ 90 ml/min/1.732). HRs of death from BSI and sepsis were 4.2 (95% CI 1.71-10.4) and 4.1 (95% CI 1.88-8.9), respectively. Participants with severely increased albuminuria (ACR > 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30-5.6) and 3.14 for sepsis (95% CI 1.94-5.1) compared to normal albumin excretion (ACR < 3 mg/mmol). HRs of death were 2.67 (95% CI 0.82-8.7) and 2.16 (95% CI 0.78-6.0), respectively. CONCLUSION: In this large population-based cohort study, CKD was clearly associated with an increased risk of BSI and sepsis and related death.

Circulating levels of micronutrients and risk of infections: a Mendelian randomization study.

BACKGROUND: Micronutrients play an essential role at every stage of the immune response, and deficiencies can therefore lead to increased susceptibility to infections. Previous observational studies and randomized controlled trials of micronutrients and infections are limited. We performed Mendelian randomization (MR) analyses to evaluate the effect of blood levels of eight micronutrients (copper, iron, selenium, zinc, beta-carotene, vitamin B12, vitamin C, and vitamin D) on the risk of three infections (gastrointestinal infections, pneumonia, and urinary tract infections). METHODS: Two-sample MR was conducted using publicly available summary statistics from independent cohorts of European ancestry. For the three infections, we used data from UK Biobank and FinnGen. Inverse variance-weighted MR analyses were performed, together with a range of sensitivity analyses. The threshold for statistical significance was set at P < 2.08E-03. RESULTS: We found a significant association between circulating levels of copper and risk of gastrointestinal infections, where a one standard deviation increase in blood levels of copper was associated with an odds ratio of gastrointestinal infections of 0.91 (95% confidence interval 0.87 to 0.97, P = 1.38E-03). This finding was robust in extensive sensitivity analyses. There was no clear association between the other micronutrients and the risk of infection. CONCLUSIONS: Our results strongly support a role of copper in the susceptibility to gastrointestinal infections.

Insomnia symptoms and risk of bloodstream infections: prospective data from the prospective population-based Nord-Trøndelag Health Study (HUNT), Norway.

Previous research suggests decreased immune function and increased risk of infections in individuals with insomnia. We examined the effect of insomnia symptoms on risk of bloodstream infections (BSIs) and BSI-related mortality in a population-based prospective study. A total of 53,536 participants in the second Norwegian Nord-Trøndelag Health Study (HUNT2) (1995-97) were linked to prospective data on clinically relevant BSIs until 2011. In Cox regression, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for a first-time BSI and for BSI-related mortality (BSI registered ≤30 days prior to death) associated with insomnia symptoms. Compared with participants who reported "no symptoms", participants reporting having "difficulty initiating sleep" (DIS) often/almost every night had a HR for a first-time BSI of 1.14 (95% CI 0.96-1.34). Participants reporting "difficulties maintaining sleep" (DMS) often/almost every night had a HR of 1.19 (95% CI 1.01-1.40), whereas those having a feeling of "non-restorative sleep" once a week or more had a HR of 1.23 (95% CI 1.04-1.46). Participants frequently experiencing all three of the above symptoms had a HR of 1.39 (1.04-1.87), whilst those who had both DIS and DMS had a HR of 1.15 (0.93-1.41) and being troubled by insomnia symptoms to a degree that affected work performance was associated with a HR of 1.41 (95% CI 1.08-1.84). The HRs for BSI-related mortality suggest an increased risk with increasing insomnia symptoms, but the CIs are wide and inconclusive. We found that frequent insomnia symptoms and insomnia symptoms that affected work performance were associated with a weak positive increased risk of BSI.

Trends in mortality after a sepsis hospitalization: a nationwide prospective registry study from 2008 to 2021.

BACKGROUND: Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis. METHODS: Patients ≥ 18 years admitted to all Norwegian hospitals (2008-2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression. RESULTS: The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI - 0.39 to - 0.19), 0.43 (95% CI - 0.56 to - 0.29), 0.61 (95% CI - 0.73 to - 0.49) and 0.66 (95% CI - 0.84 to - 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction. CONCLUSION: Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality.

Thyroid function and risk of bloodstream infections: Results from the Norwegian prospective population-based HUNT Study.

OBJECTIVE: Previous studies on thyroid function and risk of infection is conflicting and often stem from intensive care cohorts were nonthyroidal illness syndrome (NTIS) may be present. The objective of this study was to identify the risk of bloodstream infections (BSI) and BSI-related mortality with thyroid-stimulating hormone (TSH) levels within the reference range in a general population. DESIGN: Prospective follow-up. PARTICIPANTS: The HUNT2 (1995-97) included 34,619 participants with information on TSH levels. MEASUREMENTS: Hazard ratios (HRs) with 95% confidence interval (CI) confirmed BSIs and BSI-related mortality until 2011. RESULTS: During a median follow-up of 14.5 years, 1179 experienced at least one episode of BSI and 208 died within 30 days after a BSI. TSH levels within the reference range of 0.5-4.5 mU/L were not associated with the risk of first-time BSI, with an HR of 0.97 (95% CI: 0.90-1.04) per mU/L. Stratified by baseline age < or ≥65 years, TSH was inversely associated with the risk of BSI (HR: 0.88; 95% CI: 0.78-1.00 per mU/L) in the youngest age group only. Persons with any baseline thyroid disease had a 30% risk and the hyperthyroid subgroup a 57%, and hypothyroidism a 20% increased risk of BSI. TSH levels were not clearly associated with BSI mortality, but the HRs were imprecise due to few BSI-related deaths. CONCLUSION: There was some evidence of a weak inverse association between TSH levels and the risk of BSI in persons below 65 years of age. The increased risk seen in persons with thyroid illness is probably explained by confounding by concurrent ill health.

The Role of FER rs4957796 in the Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-up of the Population-based Nord-Trøndelag Health Study.

BACKGROUND: Bloodstream infection and sepsis are major causes of health loss worldwide, and it is important to identify patients at risk of developing and dying from these conditions. The single-nucleotide polymorphism most strongly associated with sepsis mortality is FER rs4957796. However, it is not known how this variant is associated with bloodstream infection incidence and mortality. METHODS: We used prospective data from 1995-2017 from the population-based HUNT Study. Genotypes were ascertained from blood samples, and additional genotypes were imputed. Information on bloodstream infection and diagnosis codes at hospitalization were collected through record linkage with all hospitals in the area. RESULTS: A total of 69 294 patients were included. Patients with the rs4957796 CC genotype had an increased risk of developing a bloodstream infection compared with the TT genotype (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00-1.43). However, there was a protective additive effect of the C allele in terms of mortality in the total study population (HR, 0.77; 95% CI, .64-.92 per copy of the C allele) and among bloodstream infection patients (odds ratio, 0.70; 95% CI, .58-.85 per copy of the C allele). The results did not appear to be affected by selection bias. CONCLUSIONS: The rs4957796 CC genotype was associated with an increased risk of contracting a bloodstream infection but with a reduced risk of dying from one. The latter finding is in line with studies of sepsis case fatality, while the former expands our understanding of the immunoregulatory role of this polymorphism.

The promise and pitfalls of composite endpoints in sepsis and COVID-19 clinical trials.

Composite endpoints reveal the tendency for statistical convention to arise locally within subfields. Composites are familiar in cardiovascular trials, yet almost unknown in sepsis. However, the VITAMINS trial in patients with septic shock adopted a composite of mortality and vasopressor-free days, and an ordinal scale describing patient status rapidly became standard in COVID studies. Aware that recent use could incite interest in such endpoints, we are motivated to flag their potential value and pitfalls for sepsis research and COVID studies.

Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study.

BACKGROUND: In observational studies of the general population, higher body mass index (BMI) has been associated with increased incidence of and mortality from bloodstream infection (BSI) and sepsis. On the other hand, higher BMI has been observed to be apparently protective among patients with infection and sepsis. We aimed to evaluate the causal association of BMI with risk of and mortality from BSI. METHODS AND FINDINGS: We used a population-based cohort in Norway followed from 1995 to 2017 (the Trøndelag Health Study [HUNT]), and carried out linear and nonlinear Mendelian randomization analyses. Among 55,908 participants, the mean age at enrollment was 48.3 years, 26,324 (47.1%) were men, and mean BMI was 26.3 kg/m2. During a median 21 years of follow-up, 2,547 (4.6%) participants experienced a BSI, and 451 (0.8%) died from BSI. Compared with a genetically predicted BMI of 25 kg/m2, a genetically predicted BMI of 30 kg/m2 was associated with a hazard ratio for BSI incidence of 1.78 (95% CI: 1.40 to 2.27; p < 0.001) and for BSI mortality of 2.56 (95% CI: 1.31 to 4.99; p = 0.006) in the general population, and a hazard ratio for BSI mortality of 2.34 (95% CI: 1.11 to 4.94; p = 0.025) in an inverse-probability-weighted analysis of patients with BSI. Limitations of this study include a risk of pleiotropic effects that may affect causal inference, and that only participants of European ancestry were considered. CONCLUSIONS: Supportive of a causal relationship, genetically predicted BMI was positively associated with BSI incidence and mortality in this cohort. Our findings contradict the "obesity paradox," where previous traditional epidemiological studies have found increased BMI to be apparently protective in terms of mortality for patients with BSI or sepsis.

Genome-Wide Linkage Analysis of the Risk of Contracting a Bloodstream Infection in 47 Pedigrees Followed for 23 Years Assembled From a Population-Based Cohort (the HUNT Study).

OBJECTIVES: Bloodstream infection is an important cause of death worldwide. The main objective of this study was to identify genetic loci linked to risk of contracting a bloodstream infection. DESIGN: Genome-wide linkage analysis. SETTING: Population-based, Norwegian cohort, followed between 1995 and 2017. SUBJECTS: Among 69,423 genotyped subjects, there were 47 families with two or more second-degree relatives with bloodstream infection in the follow-up period. There were 365 subjects in these families, of which 110 were affected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort was genotyped using Illumina HumanCoreExome (Illumina, San Diego, CA) arrays. Before linkage analysis, single-nucleotide polymorphisms were pruned and clumped. In nonparametric linkage analysis using an exponential model, we found three loci with a suggestive linkage to bloodstream infection, all on chromosome 4, at 46.6 centimorgan (logarithm of odds, 2.3), 57.7 centimorgan (logarithm of odds, 3.2), and 70.0 centimorgan (logarithm of odds, 2.1). At the peak of the lead region are three genes: TLR10, TLR1, and TLR6. CONCLUSIONS: Variations in the TLR10/1/6 locus appear to be linked with the risk of contracting a bloodstream infection.

Correction to: Monitoring quality of care for peripheral intravenous catheters; feasibility and reliability of the peripheral intravenous catheters mini questionnaire (PIVC-miniQ).

An amendment to this paper has been published and can be accessed via the original article.

Use of peripheral venous catheters in two Norwegian hospitals. / Bruk av perifere venekatetre ved to norske sykehus.

BACKGROUND: Most patients in Norwegian hospitals are routinely given one or more peripheral venous catheters. A peripheral venous catheter is considered to be a benign device but may entail a risk of local infection with resulting bloodstream infection and sepsis. Good practice in the insertion and care of these catheters is essential to prevent infection. MATERIAL AND METHOD: This study presents Norwegian data from the 'One Million Global Catheters Study', which evaluated practice in relation to peripheral venous catheters in 419 hospitals in 51 countries. Two Norwegian hospitals collected data from medical and surgical wards on a single day in November 2014 (Levanger Hospital) and a single day in February 2015 (St Olavs Hospital). Professional development nursing specialists recorded observations of peripheral venous catheters such as insertion site, dressing, documentation and indication. RESULTS: We evaluated 136 peripheral venous catheters in a total of 121 patients. We found 44 (32.4 %) catheters associated with various clinical problems such as pain, redness or swelling around the insertion site, catheter dislocation, or blood in the infusion set. Altogether 50 peripheral venous catheters (36.8 %) were not in use for either medications or fluid on the day in question. In 93 of 131 cases (71.0 %), there was no documentation of venous catheter assessment in the previous 24 hours. INTERPRETATION: Care and monitoring of venous catheters could be significantly improved. There was considerable incidence of unused peripheral venous catheters, and lack of documentation was widespread.

Monitoring quality of care for peripheral intravenous catheters; feasibility and reliability of the peripheral intravenous catheters mini questionnaire (PIVC-miniQ).

BACKGROUND: Peripheral intravenous catheters (PIVCs) account for a mean of 38% of catheter associated bloodstream infections (CABSI) with Staphylococcus aureus, which are preventable if deficiencies in best practice are addressed. There exists no feasible and reliable quality surveillance tool assessing all important areas related to PIVC quality. Thus, we aimed to develop and test feasibility and reliability for an efficient quality assessment tool of overall PIVC quality. METHODS: The Peripheral Intravenous Catheter- mini Questionnaire, PIVC-miniQ, consists of 16 items calculated as a sum score of problems regarding the insertion site, condition of dressing and equipment, documentation, and indication for use. In addition, it contains background variables like PIVC site, size and insertion environment. Two hospitals tested the PIVC-miniQ for feasibility and inter-rater agreement. Each PIVC was assessed twice, 2-5 min apart by two independent raters. We calculated the intraclass correlation coefficient (ICC) for each hospital and overall. For each of the 16 items, we calculated negative agreement, positive agreement, absolute agreement, and Scott's pi. RESULTS: Sixty-three raters evaluated 205 PIVCs in 177 patients, each PIVC was assessed twice by independent raters, in total 410 PIVC observations. ICC between raters was 0.678 for hospital A, 0.577 for hospital B, and 0.604 for the pooled data. Mean time for the bedside assessment of each PIVC was 1.40 (SD 0.0007) minutes. The most frequent insertion site symptom was "pain and tenderness" (14.4%), whereas the most prevalent overall problem was lack of documentation of the PIVC (26.8%). Up to 50% of PIVCs were placed near joints (wrist or antecubital fossae) or were inserted under suboptimal conditions, i.e. emergency department or ambulance. CONCLUSIONS: Our study highlights the need for PIVC quality surveillance on ward and hospital level and reports the PIVC-miniQ to be a reliable and time efficient tool suitable for frequent point-prevalence audits.

Anxiety and Depression Symptoms in a General Population and Future Risk of Bloodstream Infection: The HUNT Study.

OBJECTIVE: We examined whether anxiety and depression symptoms constitute increased risk of bloodstream infection (BSI), as a proxy for sepsis. METHODS: A general population with self-reported anxiety and depression symptoms was followed prospectively for hospital-verified BSI. Using multivariable Cox regression analysis, we estimated hazard ratios (HR) with 95% confidence intervals (CI) of BSI and BSI mortality, with and without statistical adjustment for comorbidities, BMI, and life-style factors that may confound or mediate the associations. RESULTS: During 14.8 years median follow-up of 59,301 individuals, 1578 (2.7%) experienced BSI and 328 (0.55%) participants died within 30 days after a BSI. Severe depression symptoms were associated with a 38% increased risk of BSI, adjusted for age, sex, and education (HR = 1.38, 95% CI = 1.10-1.73). The HR was attenuated to 1.23 (0.96-1.59) after adjustment for comorbidities and to 1.15 (0.86-1.53) after additional adjustment for BMI and life-style factors. For severe anxiety symptoms, the corresponding HRs were 1.48 (1.20-1.83), 1.35 (1.07-1.70), and 1.28 (0.99-1.64). Moderate symptoms of depression and anxiety were not associated with increased BSI risk. The analysis of BSI mortality yielded imprecise results but suggested an increased risk of BSI mortality in participants with moderate depression symptoms. CONCLUSIONS: Severe depression and anxiety symptoms were associated with a moderately increased risk of BSI. The association may, at least in part, be confounded or mediated by comorbidities, BMI, and life-style. Future research should investigate whether interventions targeting improved BMI and life-style may reduce the risk of BSI and sepsis in people with depression and anxiety symptoms.

Burden of bloodstream infection in an area of Mid-Norway 2002-2013: a prospective population-based observational study.

BACKGROUND: Studies from several countries indicate that the incidence and mortality of bloodstream infection (BSI) have been increasing over time. METHODS: We studied the burden of disease and death related to BSI in a defined geographical area of Mid-Norway, where BSI episodes were prospectively recorded by the same microbiological department during 12 consecutive years. Death from BSI was defined as death within 30 days of BSI detection. Age and sex standardized incidence and mortality rates and case fatality rates were calculated. RESULTS: Between 2002 and 2013, 1995 episodes of BSI in 1719 patients aged 16 to 99 years were included. The overall incidence of BSI was 215 per 100,000 person-years. The incidence increased exponentially with age, particularly in males. The incidence increased from 205 to 223 per 100,000 person-years from 2002-07 to 2008-13. Escherichia coli was the most frequently isolated infective agent, followed by Streptococcus pneumoniae and Staphylococcus aureus. The rate of S. pneumoniae BSI decreased over time in males (on average by 9.2% annually), but not in females. The total rate of BSI microbes with acquired resistance increased slightly over time, but did not exceed 2 episodes per 100,000 person-years. The mortality of BSI was 32 per 100,000 person-years, higher in males than in females (36 vs. 28 per 100,000 person-years) and was significantly higher in old age, particularly in males. The total BSI mortality was similar in the first and second halves of the study period, but the mortality of S. pneumoniae BSI decreased in males (15.0% annually). The crude case fatality decreased from the first to the second half of the study period (17.2% to 13.1%; p = 0.014). The rate of blood culture sampling increased more than twofold during the study period. CONCLUSIONS: The mortality of BSI remained stable during 2002-2013. At the same time, BSI incidence increased and case fatality rate decreased, perhaps because an increased rate of blood culture sampling may have led to improved detection of milder BSI episodes. Very low, yet slightly increasing rates of microbes with acquired resistance were observed.

Trends in antimicrobial resistance and empiric antibiotic therapy of bloodstream infections at a general hospital in Mid-Norway: a prospective observational study.

BACKGROUND: The occurrence of bloodstream infection (BSI) and antimicrobial resistance have been increasing in many countries. We studied trends in antimicrobial resistance and empiric antibiotic therapy at a medium-sized general hospital in Mid-Norway. METHODS: Between 2002 and 2013, 1995 prospectively recorded episodes of BSI in 1719 patients aged 16-99 years were included. We analyzed the antimicrobial non-susceptibility according to place of acquisition, site of infection, microbe group, and time period. RESULTS: There were 934 community-acquired (CA), 787 health care-associated (HCA) and 274 hospital-acquired (HA) BSIs. The urinary tract was the most common site of infection. Escherichia coli was the most frequently isolated infective agent in all three places of acquisition. Second in frequency was Streptococcus pneumoniae in CA and Staphylococcus aureus in both HCA and HA. Of the BSI microbes, 3.5% were non-susceptible to the antimicrobial regimen recommended by the National Professional Guidelines for Use of Antibiotics in Hospitals, consisting of penicillin, gentamicin, and metronidazole (PGM). In contrast, 17.8% of the BSI microbes were non-susceptible to cefotaxime and 27.8% were non-susceptible to ceftazidime. Antimicrobial non-susceptibility differed by place of acquisition. For the PGM regimen, the proportions of non-susceptibility were 1.4% in CA, 4.8% in HCA, and 6.9% in HA-BSI (p < 0.001), and increasing proportions of non-susceptibility over time were observed in HA-BSI, 2.2% in 2002-2005, 6.2% in 2006-2009, and 11.7% in 2010-2013 (p = 0.026), mainly caused by inherently resistant microbes. We also observed increasing numbers of bacteria with acquired resistance, particularly E. coli producing ESBL or possessing gentamicin resistance, and these occurred predominantly in CA- and HCA-BSI. CONCLUSIONS: Generally, antimicrobial resistance was a far smaller problem in our BSI cohort than is reported from countries outside Scandinavia. In our cohort, appropriate empiric antibiotic therapy could be achieved to a larger extent by replacing second- and third-generation cephalosporins with penicillin-gentamicin or piperacillin-tazobactam.

Epidemiology and outcome of sepsis in adult patients with Streptococcus pneumoniae infection in a Norwegian county 1993-2011: an observational study.

BACKGROUND: Invasive pneumococcal disease (IPD) is responsible for significant mortality and morbidity worldwide. There are however few longitudinal studies on the changes in case fatality rate of IPD in recent years. We carried out a prospective observational study of patients with IPD in Nord Trøndelag county in Norway from 1993 to 2011 to study the clinical variables and disease outcome. The main outcome was all-cause mortality after 30 and 90 days. METHODS: Patients with positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were registered retrospectively from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between mortality and predictive factors was studied using a logistic regression model. RESULTS: The total number of patients was 414 with mean age of 67 years and 53 % were male. Comorbidity was assessed by the Charlson Comorbidity Index (CCI). A CCI-score of 0 was registered in 144 patients (34.8 %), whereas 190 had a score of 1-2 (45.9 %) and 80 (19.3 %) had a score ≥3. 68.8 % of the patients received appropriate antibiotics within the first 6 h. The 30-day mortality risk increased by age and was 3-fold higher for patients aged ≥80 years (24.9, 95 % CI 16.4-33.4 %) compared to patients aged <70 (8.0, 95 % CI 3.5-12.4 %). 110 patients, (26.6 %) had severe sepsis and 37 (8.9 %) had septic shock. The 30 day all-cause mortality risk for those with sepsis without organ failure was 5.4 % (95 % CI 2.7-8.0 %), 20.2 % (95 % CI 13.5-27.4 %) for those with severe sepsis and 35.0 % (95 % CI 21.6-49.0 %) for those with septic shock. The mortality risk did not differ between the first and the second halves of the study period with a 30-day mortality risk of 13.5 % (95 % CI 7.9-19.2 %) for 1993-2002 versus 11.8 % (95 % CI 8.2-15.3 %) for 2003-2011. CONCLUSION: IPD carries a high mortality despite early and appropriate antibiotics in most cases. We found no substantial decrease in case fatality rate during the study period of 18 years. Older age and higher severity of disease were important risk factors for death in IPD.

Early identification of sepsis in hospital inpatients by ward nurses increases 30-day survival.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis are now frequently identified by observations of vital signs and detection of organ failure during triage in the emergency room. However, there is less focus on the effect on patient outcome with better observation and treatment at the ward level. METHODS: This was a before-and-after intervention study in one emergency and community hospital within the Mid-Norway Sepsis Study catchment area. All patients with confirmed bloodstream infection have been prospectively registered continuously since 1994. Severity of sepsis, observation frequency of vital signs, treatment data, length of stay (LOS) in high dependency and intensive care units, and mortality were retrospectively registered from the patients' medical journals. RESULTS: The post-intervention group (n = 409) were observed better and had higher odds of surviving 30 days (OR 2.7, 95 % CI 1.6, 4.6), lower probability of developing severe organ failure (0.7, 95 % CI 0.4, 0.9), and on average, 3.7 days (95 % CI 1.5, 5.9 days) shorter LOS than the pre-intervention group (n = 472). CONCLUSIONS: In a cohort with stable mortality rates, early sepsis recognition by ward nurses may have reduced progression of disease and improved survival for patients in hospital with sepsis.