Tukeva diabeetikko - tapauksen ratkaisu

Terveyskeskuslääkärin vastaanotolle diabetestarkastukseen tulleella 49-vuotiaalla naisella verensokerit olivat lääkityksestä huolimatta huonolla mallilla

Weight Loss Trajectories in Healthy Weight Coaching : Cohort Study

Background: As global obesity prevalence continues to increase, there is a need for accessible and affordable weight management interventions, such as web-based programs. Objective: This paper aims to assess the outcomes of healthy weight coaching (HWC), a web-based obesity management program integrated into standard Finnish clinical care. Methods: HWC is an ongoing, structured digital 12-month program based on acceptance and commitment therapy. It includes weekly training sessions focused on lifestyle, general health, and psychological factors. Participants received remote one-on-one support from a personal coach. In this real-life, single-arm, prospective cohort study, we examined the total weight loss, weight loss profiles, and variables associated with weight loss success and program retention in 1189 adults (963 women) with a BMI >25 kg/m(2) among participants of the program between October 2016 and March 2019. Absolute (kg) and relative (%) weight loss from the baseline were the primary outcomes. We also examined the weight loss profiles, clustered based on the dynamic time-warping distance, and the possible variables associated with greater weight loss success and program retention. We compared different groups using the Mann-Whitney test or Kruskal-Wallis test for continuous variables and the chi-squared test for categorical variables. We analyzed changes in medication using the McNemar test. Results: Among those having reached the 12-month time point (n=173), the mean weight loss was 4.6% (SE 0.5%), with 43% (n=75) achieving clinically relevant weight loss (>= 5%). Baseline BMI >= 40 kg/m(2) was associated with a greater weight loss than a lower BMI (mean 6.6%, SE 0.9%, vs mean 3.2%, SE 0.6%; P=.02). In addition, more frequent weight reporting was associated with greater weight loss. No significant differences in weight loss were observed according to sex, age, baseline disease, or medication use. The total dropout rate was 29.1%. Dropouts were slightly younger than continuers (47.2, SE 0.6 years vs 49.2, SE 0.4 years; P=.01) and reported their weight less frequently (3.0, SE 0.1 entries per month vs 3.3, SE 0.1 entries per month; P Conclusions: A comprehensive web-based program such as HWC is a potential addition to the repertoire of obesity management in a clinical setting. Heavier patients lost more weight, but weight loss success was otherwise independent of baseline characteristics.Peer reviewe

Weight Loss Trajectories in Healthy Weight Coaching: Cohort Study

BACKGROUNDAs global obesity prevalence continues to increase, there is a need for accessible and affordable weight management interventions, such as web-based programs.OBJECTIVEThis paper aims to assess the outcomes of healthy weight coaching (HWC), a web-based obesity management program integrated into standard Finnish clinical care.METHODSHWC is an ongoing, structured digital 12-month program based on acceptance and commitment therapy. It includes weekly training sessions focused on lifestyle, general health, and psychological factors. Participants received remote one-on-one support from a personal coach. In this real-life, single-arm, prospective cohort study, we examined the total weight loss, weight loss profiles, and variables associated with weight loss success and program retention in 1189 adults (963 women) with a BMI >25 kg/m² among participants of the program between October 2016 and March 2019. Absolute (kg) and relative (%) weight loss from the baseline were the primary outcomes. We also examined the weight loss profiles, clustered based on the dynamic time-warping distance, and the possible variables associated with greater weight loss success and program retention. We compared different groups using the Mann-Whitney test or Kruskal-Wallis test for continuous variables and the chi-squared test for categorical variables. We analyzed changes in medication using the McNemar test.RESULTSAmong those having reached the 12-month time point (n=173), the mean weight loss was 4.6% (SE 0.5%), with 43% (n=75) achieving clinically relevant weight loss (≥5%). Baseline BMI ≥40 kg/m² was associated with a greater weight loss than a lower BMI (mean 6.6%, SE 0.9%, vs mean 3.2%, SE 0.6%; P=.02). In addition, more frequent weight reporting was associated with greater weight loss. No significant differences in weight loss were observed according to sex, age, baseline disease, or medication use. The total dropout rate was 29.1%. Dropouts were slightly younger than continuers (47.2, SE 0.6 years vs 49.2, SE 0.4 years; P=.01) and reported their weight less frequently (3.0, SE 0.1 entries per month vs 3.3, SE 0.1 entries per month; PCONCLUSIONA comprehensive web-based program such as HWC is a potential addition to the repertoire of obesity management in a clinical setting. Heavier patients lost more weight, but weight loss success was otherwise independent of baseline characteristics.</p

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe

Resilience trinity: Safeguarding ecosystem functioning and services across three different time horizons and decision contexts

Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi‐faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time‐horizons: 1) reactive, when there is an imminent threat to ES resilience and a high pressure to act, 2) adjustive, when the threat is known in general but there is still time to adapt management and 3) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology and engineering are often implicitly focussing on provident, adjustive or reactive resilience, respectively, but these different notions of resilience and their corresponding social, ecological and economic tradeoffs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer‐term management actions are not missed while urgent threats to ES are given priority

Resilience trinity: safeguarding ecosystem functioning and services across three different time horizons and decision contexts

Ensuring ecosystem resilience is an intuitive approach to safeguard the functioning of ecosystems and hence the future provisioning of ecosystem services (ES). However, resilience is a multi-faceted concept that is difficult to operationalize. Focusing on resilience mechanisms, such as diversity, network architectures or adaptive capacity, has recently been suggested as means to operationalize resilience. Still, the focus on mechanisms is not specific enough. We suggest a conceptual framework, resilience trinity, to facilitate management based on resilience mechanisms in three distinctive decision contexts and time-horizons: i) reactive, when there is an imminent threat to ES resilience and a high pressure to act, ii) adjustive, when the threat is known in general but there is still time to adapt management, and iii) provident, when time horizons are very long and the nature of the threats is uncertain, leading to a low willingness to act. Resilience has different interpretations and implications at these different time horizons, which also prevail in different disciplines. Social ecology, ecology, and engineering are often implicitly focussing on provident, adjustive, or reactive resilience, respectively, but these different notions and of resilience and their corresponding social, ecological, and economic trade-offs need to be reconciled. Otherwise, we keep risking unintended consequences of reactive actions, or shying away from provident action because of uncertainties that cannot be reduced. The suggested trinity of time horizons and their decision contexts could help ensuring that longer-term management actions are not missed while urgent threats to ES are given priority

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study

Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabinerelated cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n ¼ 170), continuous infusion 5-FU (n ¼ 22), or bolus 5-FU (n ¼ 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n ¼ 228/200) included chest pain (n ¼ 125), coronary syndrome/ infarction (n ¼ 69), arrhythmia (n ¼ 22), heart failure/cardiomyopathy (n ¼ 7), cardiac arrest (n ¼ 4), and malignant hypertension (n ¼ 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.</p

Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples

<p>Abstract</p> <p>Background</p> <p>Readthrough fusions across adjacent genes in the genome, or transcription-induced chimeras (TICs), have been estimated using expressed sequence tag (EST) libraries to involve 4-6% of all genes. Deep transcriptional sequencing (RNA-Seq) now makes it possible to study the occurrence and expression levels of TICs in individual samples across the genome.</p> <p>Methods</p> <p>We performed single-end RNA-Seq on three human prostate adenocarcinoma samples and their corresponding normal tissues, as well as brain and universal reference samples. We developed two bioinformatics methods to specifically identify TIC events: a targeted alignment method using artificial exon-exon junctions within 200,000 bp from adjacent genes, and genomic alignment allowing splicing within individual reads. We performed further experimental verification and characterization of selected TIC and fusion events using quantitative RT-PCR and comparative genomic hybridization microarrays.</p> <p>Results</p> <p>Targeted alignment against artificial exon-exon junctions yielded 339 distinct TIC events, including 32 gene pairs with multiple isoforms. The false discovery rate was estimated to be 1.5%. Spliced alignment to the genome was less sensitive, finding only 18% of those found by targeted alignment in 33-nt reads and 59% of those in 50-nt reads. However, spliced alignment revealed 30 cases of TICs with intervening exons, in addition to distant inversions, scrambled genes, and translocations. Our findings increase the catalog of observed TIC gene pairs by 66%.</p> <p>We verified 6 of 6 predicted TICs in all prostate samples, and 2 of 5 predicted novel distant gene fusions, both private events among 54 prostate tumor samples tested. Expression of TICs correlates with that of the upstream gene, which can explain the prostate-specific pattern of some TIC events and the restriction of the <it>SLC45A3-ELK4 </it>e4-e2 TIC to <it>ERG</it>-negative prostate samples, as confirmed in 20 matched prostate tumor and normal samples and 9 lung cancer cell lines.</p> <p>Conclusions</p> <p>Deep transcriptional sequencing and analysis with targeted and spliced alignment methods can effectively identify TIC events across the genome in individual tissues. Prostate and reference samples exhibit a wide range of TIC events, involving more genes than estimated previously using ESTs. Tissue specificity of TIC events is correlated with expression patterns of the upstream gene. Some TIC events, such as <it>MSMB-NCOA4</it>, may play functional roles in cancer.</p

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe