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.

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.

Infectious tenosynovitis with bloodstream infection caused by Erysipelothrix rhusiopathiae, a case report on an occupational pathogen.

BACKGROUND: Erysipelothrix rhusiopathiae is an established animal pathogen, which may cause infections in humans. It is a gram-positive rod and found in the tonsils or the digestive tracts of animals. The bacterium is occupationally related, as usually only people with frequent animal contacts are infected. We report a case of a patient who was admitted with an infectious tenosynovitis with bloodstream infection due to E. rhusiopathiae, and to our knowledge, this is the first report of a tenosynovitis with systemic manifestation associated with this bacterium. CASE PRESENTATION: A 52-year old Norwegian man, who worked with transportation of swine cadavers, was admitted to the local hospital with sepsis and unknown focus of infection. A few days earlier he had an injury to the skin of one of his fingers that later proved to be infected with E. rhusiopathiae. There were no other causes for his symptoms than the infectious tenosynovitis with systemic manifestation. The infection resolved on treatment with antibiotics and surgery. A transoesophageal echocardiogram was performed to exclude endocarditis, which may be associated with this pathogen. CONCLUSIONS: This case report highlights the importance of clinicians being aware of this bacterium, and we describe risk factors for infection, differences in the clinical manifestations of the disease, challenges with diagnosing the bacterium and adverse effects of immunosuppressive drugs. Recommended treatment is appropriate antibiotic therapy and adequate debridement and surgical drainage of the tendon sheath.

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.

Impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, and quality of life.

PURPOSE: Inflammatory bowel disease has been associated with neurological symptoms including restless legs syndrome. Here, we investigated the impact of restless legs syndrome in patients with inflammatory bowel disease on sleep, fatigue, mood, cognition, and quality of life. METHODS: Two groups of inflammatory bowel disease patients, with and without restless legs syndrome, were prospectively evaluated for sleep disorders, fatigue, daytime sleepiness, depression, anxiety, and health-related quality of life. Furthermore, global cognitive function, executive function, attention, and concentration were assessed in both groups. Disease activity and duration of inflammatory bowel disease as well as current medication were assessed by interview. Inflammatory bowel disease patients with and without restless legs syndrome were matched for age, education, severity, and duration of their inflammatory bowel disease. RESULTS: Patients with inflammatory bowel disease and clinically relevant restless leg syndrome suffered significantly more frequent from sleep disturbances including sleep latency and duration, more fatigue, and worse health-related quality of life as compared to inflammatory bowel disease patients without restless legs syndrome. Affect and cognitive function including cognitive flexibility, attention, and concentration showed no significant differences among groups, indicating to be not related to restless legs syndrome. CONCLUSIONS: Sleep disorders including longer sleep latency, shorter sleep duration, and fatigue are characteristic symptoms of restless legs syndrome in inflammatory bowel disease patients, resulting in worse health-related quality of life. Therefore, clinicians treating patients with inflammatory bowel disease should be alert for restless legs syndrome.

The single intake of levodopa modulates implicit learning in drug naïve, de novo patients with idiopathic Parkinson's disease.

Although dopamine is known to aggravate implicit learning, the exact impact on behaviour when feedback is unavailable remains unclear. Previous studies revealed that non-rewarded learning habits are affected in long-term dopaminergic treated patients with Parkinson's disease (PD). We studied the influence of a onetime levodopa intake on implicit learning in de novo, untreated PD patients. De novo PD patients (n = 22) before and after the single intake of levodopa and control subjects (n = 23) took part in a Go/NoGo paradigm. One stimulus was defined as target, which was first consistently preceded by one of three non-target stimuli (conditioning). This coupling was dissolved thereafter (deconditioning). In the 'Go version' subjects were asked to respond to the target by pressing a key, whereas in the 'NoGo version' response had to be inhibited. PD patients and controls (n = 14/n = 19) with an initial learning effect due to the target were included for further statistical analysis. Within the subgroup incorrect responses upon NoGo stimuli increased during the deconditioning phase. In contrast, the same patients failed to show any change after receiving 200 mg of levodopa. During the Go version, no change of the overall error rate between conditioning and deconditioning was detectable over all groups. Learning behaviour in untreated PD patients and healthy controls was indistinguishable. In contrast, the same patients varied in their implicit learning after one-time intake of levodopa, when actions had to be inhibited. Hence, the single intake of levodopa appears to modulate implicit learning behaviour in de novo PD patients.

Somatosensory symptoms in unmedicated de novo patients with idiopathic Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative condition presenting with motor and non-motor symptoms including somatosensory disturbances. As neuropathic syndromes in advanced PD patients are supposed to be due to antiparkinsonian medication, we studied the presence of somatosensory symptoms and peripheral nerve function in drug naïve patients with PD as well as age-matched healthy controls. Somatosensory symptoms and signs were investigated in 39 de novo PD patients and 32 age-matched healthy controls using the modified Toronto Clinical Neuropathy Scale. To elucidate potential underlying mechanisms, peripheral nerve function was analyzed with sensory and motor neurography. About two thirds of de novo diagnosed levodopa naïve PD patients (66.7 %) reported somatosensory symptoms in comparison to one third of the control group (31.2 %) (p = 0.003). The presence of PD (p = 0.017) was a predictive factor for the occurrence of somatosensory symptoms among all participants. In contrast to the significantly higher frequency of somatosensory symptoms in patients with PD compared to controls, neurographically based peripheral nerve function did not differ between the groups. Our results indicate that somatosensory symptoms are a PD feature, which can be found when diagnosed first and independently of dopaminergic treatment. As the electrophysiologically determined peripheral nerve function was not different from that obtained in the control group, somatosensory symptoms are inherent in early PD and may be, at least partially, of central origin.

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.

Epidemiology and outcome of Staphylococcus aureus bloodstream infection and sepsis in a Norwegian county 1996-2011: an observational study.

BACKGROUND: Staphylococcus aureus is one of the most common and lethal causes of bloodstream infection and the incidence is increasing. We carried out a prospective observational study of patients with Staphylococcus aureus bloodstream infection and sepsis in Nord-Trøndelag county in Norway from 1996-2011. The main outcome of interest was all-cause mortality within 30 and 90 days. METHODS: Positive blood cultures were registered prospectively by the microbiology laboratory and clinical variables were retrospectively registered from patients' hospital records. The severity of sepsis was assigned according to the 2001 International Sepsis Definition Conference criteria. The association between clinical characteristics and mortality was studied using logistic regression analysis, and adjusted 30- and 90-day mortality risks were estimated. RESULTS: Among 373 patients, the median age was 74 years and 60.3% were male. 0.8% of the patients were diagnosed with MRSA. 29.8% of the patients developed severe sepsis and 12.9% developed septic shock. The all-cause mortality was 14.5%, 27.3% and 36.2% at 7, 30 and 90 days, respectively. Compared to patients with sepsis without organ failure (Mortality risk 13.3%, 95% CI 7.5-16.3%), the 30-day mortality risk was 3-fold higher among those with severe sepsis (39.9%, 95% CI 29.5-48.5%) and more than 4-fold higher for those with septic shock (57.3%, 95% CI 42.5-72.2%). The 30-day all-cause mortality varied by focus of infection, with the highest 30-day mortality risk among those with a pulmonary focus (42.4%, 95% CI 26.0-58.5%) and unknown focus of infection (38.7%, 95% CI 27.5-48.2%). The mortality risk did not differ between the first and second halves of the study period with a 30-day mortality risk of 27.3%, (95% CI 18.1-33.1%) for 1996-2003 versus 27.4% (95% CI 19.4-31.4%) for 2004-2011. The same pattern was seen for 90-day mortality risk. CONCLUSION: Staphylococcus aureus bloodstream infection carries a high case fatality rate, especially among those with severe sepsis and septic shock and among those with a pulmonary or unknown focus of infection. There was no decrease in 30- or 90-day mortality risk during the study period. This underscores the importance of continuing surveillance and efforts to improve the outcome of this serious disease.

Association of iron status with the risk of bloodstream infections: results from the prospective population-based HUNT Study in Norway.

PURPOSE: As iron is essential for both immune function and microbial growth, alterations in iron status could influence the risk of infections. We assessed the associations of iron status with risk of bloodstream infections (BSIs) and BSI mortality. METHODS: We measured serum iron, transferrin saturation (Tsat) and total iron-binding capacity (TIBC) in 61,852 participants in the population-based HUNT2 study (1995-97). Incident BSIs (1995-2011) were identified through linkage with the Mid-Norway Sepsis Register, which includes prospectively registered information on BSI from local and regional hospitals. We assessed the risk of a first-time BSI and BSI mortality with the iron indices using Cox proportional hazards regression analysis. RESULTS: During a median follow-up of 14.8 years, 1738 individuals experienced at least one episode of BSI, and 370 died within 30 days after a BSI. In age- and sex-adjusted analyses, BSI risk was increased among participants with indices of iron deficiency, serum iron ≤ 2.5th percentile (HR 1.72, 95% CI 1.34-2.21), Tsat ≤ 2.5th percentile (HR 1.48, 95% CI 1.12-1.96) or TIBC ≥ 97.5th percentile (HR 1.46, 95% CI 1.06-2.01). The associations remained similar after adjusting for comorbidities and exclusion of BSI related to cancer, rheumatic illnesses and inflammatory bowel disease. BSI mortality showed similar associations. CONCLUSION: Indices of severe iron deficiency are associated with an increased risk of a future BSI.

Associations of obesity and lifestyle with the risk and mortality of bloodstream infection in a general population: a 15-year follow-up of 64 027 individuals in the HUNT Study.

Background: Bloodstream infections (BSI) cause considerable morbidity and mortality, and primary prevention should be a priority. Lifestyle factors are of particular interest since they represent a modifiable target. Methods: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT2 Survey, where 64 027 participants were followed from 1995-97 through 2011 by linkage to prospectively recorded information on BSI at local and regional hospitals. The exposures were: baseline body mass index (BMI) measurements; and self-reported smoking habits, leisure time physical activity and alcohol intake. The outcomes were hazard ratios (HR) of BSI and BSI mortality. Results: During 810 453 person-years and median follow-up of 14.8 years, 1844 (2.9%) participants experienced at least one BSI and 396 (0.62%) died from BSI. Compared with normal weight participants (BMI 18.5-24.9 kg/m2), the age- and sex-adjusted risk of a first-time BSI was 31% [95% confidence interval (CI) 14-51%] higher at BMI 30.0-34.9 kg/m2, 87% (95% CI 50-135%) higher at BMI 35.0-39.9 kg/m2 and 210% (95% CI 117-341%) higher at BMI ≥ 40.0 kg/m2. The risk of BSI mortality was similarly increased. Compared with never-smokers, current smokers had 51% (95% CI 34-70%) and 75% (95% CI 34-129%) higher risks of BSI and BSI mortality, respectively. Physically inactive participants had 71% (95% CI 42-107%) and 108% (95% CI 37-216%) higher risks of BSI and BSI mortality, respectively, compared with the most physically active. Conclusions: Obesity, smoking and physical inactivity carry increased risk of BSI and BSI mortality.