Bloodstream infections following different types of surgery in a Finnish tertiary care hospital, 2009-2014

The risk and outcome of bloodstream infections (BSIs) were evaluated following surgery. BSIs were identified in Helsinki University Hospital during 2009-2014 as part of the national surveillance. Of 711 BSIs identified, 51% were secondary and 49% primary. The rate was highest after cardiovascular surgery (8.7 per 1000 procedures) and lowest after gynaecologic (1.0 per 1000). Surgical site infection was the most frequent source of secondary BSIs (34%) and 45% of primary BSIs were central-line-associated. The 28-day case fatality ranged from zero in gynaecology/obstetrics to 21% in cardiovascular surgery. Besides BSIs related to surgical site infections, half of BSIs were primary, providing additional foci for prevention. (C) 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Population-Based Study of Bloodstream Infection Incidence and Mortality Rates, Finland, 2004-2018

We evaluated the incidence, outcomes, and causative agents of bloodstream infections (BSI) in Finland during 2004-2018 by using data from the national registries. We identified a total of 173,715 BSIs; annual incidence increased from 150 to 309 cases/100,000 population. BSI incidence rose most sharply among persons >= 80 years of age. The 1-month case-fatality rate decreased from 13.0% to 12.6%, but the 1-month all-cause mortality rate rose from 20 to 39 deaths/100,000 population. BSIs caused by Escherichia coli increased from 26% to 30% of all BSIs. BSIs caused by multidrug-resistant microbes rose from 0.4% to 2.8%, mostly caused by extended-spectrum beta-lactamase-producing E. coli. We observed an increase in community-acquired BSIs, from 67% to 78%. The proportion of patients with severe underlying conditions rose from 14% to 23%. Additional public health and healthcare prevention efforts are needed to curb the increasing trend in community-acquired BSIs and antimicrobial drug-resistant E. coli.Peer reviewe

The outcome and timing of death of 17,767 nosocomial bloodstream infections in acute care hospitals in Finland during 1999-2014

Few studies covering all patient groups and specialties are available regarding the outcome of nosocomial bloodstream infections (BSI). We analyzed the role of patient characteristics and causative pathogens of nosocomial BSIs reported by the hospitals participating in national surveillance in Finland during 1999-2014, in terms of outcome, with particular interest in those leading to death within 2 days (i.e. early death). National nosocomial BSI surveillance was laboratory-based and hospital-wide. Data on nosocomial BSIs was collected by infection control nurses, and dates of death were obtained from the national population registry with linkage to national identity codes. A total of 17,767 nosocomial BSIs were identified; 557 BSIs (3%) were fatal within 2 days and 1150 (6%) within 1 week. The 1-month case fatality was 14% (2460 BSIs), and 23% of the deaths occurred within 2 days and 47% within 1 week. The patients who died early were older than those who survived > 28 days, and their BSIs were more often related to intensive care. Gram-positive bacteria caused over half of the BSIs of patients who survived, whereas gram-negative bacteria, especially Pseudomonas aeruginosa, caused more often BSIs of patients who died early, and fungi BSIs of patients who died within 1 week. A significant portion of patients with nosocomial BSIs died early, which underlines the importance of rapid recognition of BSI. Hospital-wide surveillance data of causative pathogens can be utilized when composing recommendations for empiric antimicrobial treatment in collaboration with clinicians, as well as when promoting infection prevention.Peer reviewe

Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension

Objective In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured > 600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. Methods Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings. Results Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10(-5)) and losartan (P values down to 2 x 10(-4)) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium-and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10(-4)) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation. Conclusions Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension.Peer reviewe

Effect of hydrochlorothiazide on serum uric acid concentration : a genome-wide association study

Aim: To recognize genetic associations of hydrochlorothiazide-induced change in serum uric acid (SUA) concentration. Patients & methods: We conducted a genome-wide association study on hydrochlorothiazide-induced change in SUA in 214 Finnish men from the GENRES study. Replication analyses were performed in 465 Finns from the LIFE study. Results: In GENRES, we identified 31 loci associated with hydrochlorothiazide-induced change in SUA at p <5 x 10(-5). rs1002976 near VEGFC associated with the change in GENRES and in LIFE. rs950569 near BRINP3 associated with the change in SUA in GENRES and LIFE. The analysis of previously reported SNPs and candidate genes provided some proof for PADI4 and ABCC4. Conclusion: We report genetic markers that may predict the increase in SUA concentration during thiazide treatment.Peer reviewe

Strategies for the introduction of human papillomavirus vaccination: modelling the optimum age- and sex-specific pattern of vaccination in Finland

Phase III trials have demonstrated the efficacy of human papillomavirus (HPV) vaccines in preventing transient and persistent high-risk (hr) HPV infection and precancerous lesions. A mathematical model of HPV type 16 infection and progression to cervical cancer, parameterised to represent the infection in Finland, was used to explore the optimal age at vaccination and pattern of vaccine introduction. In the long term, the annual proportion of cervical cancer cases prevented is much higher when early adolescents are targeted. Vaccinating against hr HPV generates greater long-term benefits if vaccine is delivered before the age at first sexual intercourse. However, vaccinating 12 year olds delays the predicted decrease in cervical cancer, compared to vaccinating older adolescents or young adults. Vaccinating males as well as females has more impact on the proportion of cases prevented when vaccinating at younger ages. Implementing catch-up vaccination at the start of a vaccination programme would increase the speed with which a decrease in HPV and cervical cancer incidence is observed

Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism

As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA-1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner.Peer reviewe

Pharmacoepigenetics of hypertension : genome-wide methylation analysis of responsiveness to four classes of antihypertensive drugs using a double-blind crossover study design

Essential hypertension remains the leading risk factor of global disease burden, but its treatment goals are often not met. We investigated whether DNA methylation is associated with antihypertensive responses to a diuretic, a beta-blocker, a calcium channel blocker or an angiotensin receptor antagonist. In addition, since we previously showed an SNP at the transcription start site (TSS) of the catecholamine biosynthesis-related ACY3 gene to associate with blood pressure (BP) response to beta-blockers, we specifically analysed the association of methylation sites close to the ACY3 TSS with BP responses to beta-blockers. We conducted an epigenome-wide association study between leukocyte DNA methylation and BP responses to antihypertensive monotherapies in two hypertensive Finnish cohorts: the GENRES (; amlodipine 5 mg, bisoprolol 5 mg, hydrochlorothiazide 25 mg, or losartan 50 mg daily) and the LIFE-Fin studies (; atenolol 50 mg or losartan 50 mg daily). The monotherapy groups consisted of approximately 200 individuals each. We identified 64 methylation sites to suggestively associate (P < 1E-5) with either systolic or diastolic BP responses to a particular study drug in GENRES. These associations did not replicate in LIFE-Fin . Three methylation sites close to the ACY3 TSS were associated with systolic BP responses to bisoprolol in GENRES but not genome-wide significantly (P < 0.05). No robust associations between DNA methylation and BP responses to four different antihypertensive drugs were identified. However, the findings on the methylation sites close to the ACY3 TSS may support the role of ACY3 genetic and epigenetic variation in BP response to bisoprolol.Peer reviewe