A Primary Care Emergency Service Reduction Did Not Increase Office-Hour Service Use : A Longitudinal Follow-up Study

This study, conducted in a Finnish city, examined whether decreasing emergency department (ED) services in an overcrowded primary care ED and corresponding direction to office-hour primary care would guide patients to office-hour visits to general practitioners (GP). This was an observational retrospective study based on a before-and-after design carried out by gradually decreasing ED services in primary care. The interventions were (a) application of ABCDE-triage combined with public guidance on the proper use of EDs, (b) cessation of a minor supplementary ED, and finally (c) application of "reverse triage" with enhanced direction of the public to office-hour services from the remaining ED. The numbers of visits to office-hour primary care GPs in a month were recorded before applying the interventions fully (preintervention period) and in the postintervention period. The putative effect of the interventions on the development rate of mortality in different age groups was also studied as a measure of safety. The total number of monthly visits to office-hour GPs decreased slowly over the whole study period without difference in this rate between pre- and postintervention periods. The numbers of office-hour GP visits per 1000 inhabitants decreased similarly. The rate of monthly visits to office-hour GP/per GP did not change in the preintervention period but decreased in the postintervention period. There was no increase in the mortality in any of the studied age groups (0-19, 20-64, 65+ years) after application of the ED interventions. There is no guarantee that decreasing activity in a primary care ED and consecutive enhanced redirecting of patients to the office-hour primary care systems would shift patients to office-hour GPs. On the other hand, this decrease in the ED activity does not seem to increase mortality either.Peer reviewe

Home-Applied Dual-Light Photodynamic Therapy in the Treatment of Stable Chronic Periodontitis (HOPE-CP)—Three-Month Interim Results

A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients were randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination was conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BOP) was lower in the NSPT + Lumoral®-group than in the NSPT group (p = 0.045), and more patients in the NSPT + Lumoral®-group had their BOP below 10% (54% vs. 22%, respectively, p = 0.008). In addition, patients in the NSPT + Lumoral®-group improved their oral hygiene by visible-plaque-index (p = 0.0003), while the NSPT group showed no statistical improvement compared to the baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT + Lumoral® group (92% vs. 63%, p = 0.02). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT + Lumoral®-group (71% vs. 33%, p = 0.01). Patients with initially less than ten deep pockets had fewer deep pockets at the three-month follow-up in the Lumoral® group (p = 0.01). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy

Developing a spatially explicit modelling and evaluation framework for integrated carbon sequestration and biodiversity conservation: application in southern Finland

The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27 024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a-1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilised for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits.The challenges posed by climate change and biodiversity loss are deeply interconnected. Successful co-managing of these tangled drivers requires innovative methods that can prioritize and target management actions against multiple criteria, while also enabling cost-effective land use planning and impact scenario assessment. This paper synthesises the development and application of an integrated multidisciplinary modelling and evaluation framework for carbon and biodiversity in forest systems. By analysing and spatio-temporally modelling carbon processes and biodiversity elements, we determine an optimal solution for their co-management in the study landscape. We also describe how advanced Earth Observation measurements can be used to enhance mapping and monitoring of biodiversity and ecosystem processes. The scenarios used for the dynamic models were based on official Finnish policy goals for forest management and climate change mitigation. The development and testing of the system were executed in a large region in southern Finland (Kokemäenjoki basin, 27,024 km2) containing highly instrumented LTER (Long-Term Ecosystem Research) stations; these LTER data sources were complemented by fieldwork, remote sensing and national data bases. In the study area, estimated total net emissions were currently 4.2 TgCO2eq a−1, but modelling of forestry measures and anthropogenic emission reductions demonstrated that it would be possible to achieve the stated policy goal of carbon neutrality by low forest harvest intensity. We show how this policy-relevant information can be further utilized for optimal allocation of set-aside forest areas for nature conservation, which would significantly contribute to preserving both biodiversity and carbon values in the region. Biodiversity gain in the area could be increased without a loss of carbon-related benefits.Peer reviewe

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (PPeer reviewe

Common breast cancer susceptibility alleles are associated with tumor subtypes in BRCA1 and BRCA2 mutation carriers : results from the Consortium of Investigators of Modifiers of BRCA1/2.

Abstract Introduction Previous studies have demonstrated that common breast cancer susceptibility alleles are differentially associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers. It is currently unknown how these alleles are associated with different breast cancer subtypes in BRCA1 and BRCA2 mutation carriers defined by estrogen (ER) or progesterone receptor (PR) status of the tumour. Methods We used genotype data on up to 11,421 BRCA1 and 7,080 BRCA2 carriers, of whom 4,310 had been affected with breast cancer and had information on either ER or PR status of the tumour, to assess the associations of 12 loci with breast cancer tumour characteristics. Associations were evaluated using a retrospective cohort approach. Results The results suggested stronger associations with ER-positive breast cancer than ER-negative for 11 loci in both BRCA1 and BRCA2 carriers. Among BRCA1 carriers, single nucleotide polymorphism (SNP) rs2981582 (FGFR2) exhibited the biggest difference based on ER status (per-allele hazard ratio (HR) for ER-positive = 1.35, 95% CI: 1.17 to 1.56 vs HR = 0.91, 95% CI: 0.85 to 0.98 for ER-negative, P-heterogeneity = 6.5 &#215; 10-6). In contrast, SNP rs2046210 at 6q25.1 near ESR1 was primarily associated with ER-negative breast cancer risk for both BRCA1 and BRCA2 carriers. In BRCA2 carriers, SNPs in FGFR2, TOX3, LSP1, SLC4A7/NEK10, 5p12, 2q35, and 1p11.2 were significantly associated with ER-positive but not ER-negative disease. Similar results were observed when differentiating breast cancer cases by PR status. Conclusions The associations of the 12 SNPs with risk for BRCA1 and BRCA2 carriers differ by ER-positive or ER-negative breast cancer status. The apparent differences in SNP associations between BRCA1 and BRCA2 carriers, and non-carriers, may be explicable by differences in the prevalence of tumour subtypes. As more risk modifying variants are identified, incorporating these associations into breast cancer subtype-specific risk models may improve clinical management for mutation carriers

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat